UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
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FORM 10-K
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(Mark One)
| ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 | |||||
For the fiscal year ended November 30 , 2023
OR
| TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE TRANSITION PERIOD FROM TO | |||||
Commission File Number 001-39398
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(Exact name of Registrant as specified in its Charter)
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(State or other jurisdiction of incorporation or organization) | (I.R.S. Employer Identification No.) | ||||
| (Address of principal executive offices) | (Zip Code) | ||||
Registrant’s telephone number, including area code: (415 ) 660-5320
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Securities registered pursuant to Section 12(b) of the Act:
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Securities registered pursuant to Section 12(g) of the Act: None
Indicate by check mark if the Registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes o No x
Indicate by check mark if the Registrant is not required to file reports pursuant to Section 13 or 15(d) of the Act. Yes o No x
Indicate by check mark whether the Registrant: (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the Registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes x No o
Indicate by check mark whether the Registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the Registrant was required to submit such files). Yes x No o
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.
| Large accelerated filer | o | Accelerated filer | o | ||||||||
| x | Smaller reporting company | ||||||||||
| Emerging growth company | |||||||||||
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. o
If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously issued financial statements. o
Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). o
Indicate by check mark whether the Registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes o No x
Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. o
The aggregate market value of the common stock held by non-affiliates of the Registrant, based on the closing price of the Registrant’s common stock on May 31, 2023 (the last business day of the Registrant’s most recently completed second fiscal quarter) as reported by the Nasdaq Global Market on such date was approximately $470.8 million. This calculation does not reflect a determination that certain persons are affiliates of the Registrant for any other purpose.
As of February 5, 2024, the Registrant had 48,894,084 shares of common stock, $0.001 par value per share, outstanding.
DOCUMENTS INCORPORATED BY REFERENCE
Certain sections of the Registrant’s definitive Proxy Statement to be filed in connection with the Registrant’s 2024 Annual Meeting of Stockholders are incorporated by reference into Part III of this Annual Report on Form 10-K where indicated. Such definitive Proxy Statement will be filed with the Securities and Exchange Commission pursuant to Regulation 14A within 120 days of the Registrant’s fiscal year ended November 30, 2023.
TABLE OF CONTENTS
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| Item 1C. | ||||||||
SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS
This Annual Report on Form 10-K contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this Annual Report on Form 10-K other than statements of historical fact, including statements concerning our business strategy and plans, future operating results and financial position, as well as our objectives and expectations for our future operations, are forward-looking statements.
In some cases, you can identify forward-looking statements by such terminology as “believe,” “may,” “will,” “potentially,” “estimate,” “continue,” “anticipate,” “intend,” “could,” “would,” “project,” “plan,” “expect” and similar expressions that convey uncertainty of future events or outcomes, although not all forward-looking statements contain these words. Forward-looking statements include, but are not limited to, statements about:
•the timing and conduct of our clinical trial programs for our lead drug candidates NX-5948, NX-2127 and NX-1607 and other drug candidates, including statements regarding the timing of data and anticipated announcements, the selection of new development candidates and the initiation of clinical trials;
•the timing of, and our ability to obtain, marketing approvals for our lead drug candidates NX-5948, NX-2127 and NX-1607 and other drug candidates;
•our plans to pursue research and development of other drug candidates;
•the timing of investigational new drug application (IND) submissions for our drug candidates;
•the potential advantages of our DELigase platform, our drug candidates and Degrader-Antibody Conjugates (DACs);
•the extent to which our scientific approach, our DELigase platform, protein degradation, antibody-drug conjugation, and DACs may potentially address a broad range of diseases;
•the potential benefits of our arrangements with Gilead Sciences, Inc., Sanofi S.A. and Seagen Inc. (now a part of Pfizer Inc.);
•the timing of and our ability to obtain and maintain regulatory approvals for our drug candidates;
•the potential receipt of revenue from future sales of our drug candidates;
•the rate and degree of market acceptance and clinical utility of our drug candidates;
•our estimates regarding the potential market opportunity for our drug candidates;
•our sales, marketing and distribution capabilities and strategy;
•our ability to establish and maintain arrangements for the manufacturing of our drug candidates;
•the expected impact of global business, political and macroeconomic conditions, including inflation, increasing interest rates and volatile market conditions, uncertainty with respect to the federal budget and debt ceiling and potential government shutdowns related thereto, cybersecurity events, instability in the global banking system, and global events, including regional conflicts around the world, on our business, clinical trials, financial condition, liquidity and results of operations;
•the potential achievement of milestones and receipt of royalty payments under our collaborations;
•our ability to enter into additional collaborations with third parties;
•our intellectual property position;
•our estimates regarding expenses, future revenues, capital requirements and needs for additional financing;
•the impact of government laws and regulations; and
•our competitive position.
We have based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our business, financial condition, results of operations, prospects and financial needs. These forward-looking statements speak only as of the date of this Annual Report on Form 10‑K and are subject to a number of risks, uncertainties and assumptions described in the section titled “Risk Factors” and elsewhere in this Annual Report on Form 10-K. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. We disclaim any intention or obligation to update publicly or revise any forward-looking statements for any reason or to conform such statements to actual results or revised expectations, except as required by law.
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Risk Factors Summary
Our business is subject to a number of risks and uncertainties, including those risks discussed at-length below. These risks include, among others, the following:
•We have incurred significant losses since our inception. We expect to incur losses over at least the next several years and may never achieve or maintain profitability.
•We have never generated revenue from product sales and may never be profitable.
•We will need substantial additional funding. If we are unable to raise capital when needed, we may be required to delay, limit, reduce or terminate our research or product development programs or future commercialization efforts.
•Current and future legislation may increase the difficulty and cost for us, and any collaborators, to obtain marketing approval of and commercialize our drug candidates and affect the prices we, or they, may obtain.
•We are early in our development efforts. Our lead drug candidates, NX-5948, NX-2127 and NX-1607, are in the early stages of clinical development. If we are unable to advance our drug candidates through clinical development, develop, obtain regulatory approval for and commercialize our drug candidates or experience significant delays in doing so, our business may be materially harmed.
•Our limited operating history may make it difficult to evaluate the success of our business to date and to assess our future viability.
•If serious adverse events, undesirable side effects or unexpected characteristics are identified during the development of any drug candidates we may develop, we may need to abandon or limit our further clinical development of those drug candidates.
•The results of preclinical studies and early-stage clinical trials may not be predictive of future results. Initial success in clinical trials may not be indicative of results obtained when these trials are completed or in later-stage trials.
•If we decide to seek Orphan Drug Designation or other designations from regulators for any of our current or future drug candidates, we may be unsuccessful or may be unable to maintain the benefits associated with these designations, including the potential for supplemental market exclusivity associated with an Orphan Drug Designation.
•If any of our drug candidates are not considered to be a new active substance or are deemed to fall within the “global marketing authorization” of an existing medicinal product or if pediatric studies are not adequately completed, this may result in lack of regulatory data protection or failure to obtain an extension to existing regulatory data protection.
•We face substantial competition in an environment of rapid technological change, which may result in others discovering, developing or commercializing products before or more successfully than we do.
•We expect to depend on collaborations with third parties for the research, development and commercialization of certain of the drug candidates we may develop. If any such collaborations are not successful, we may not be able to capitalize on the market potential of those drug candidates.
•We rely on third-party contract manufacturing organizations (CMOs) for the manufacture of both drug substance and finished drug product for our drug candidates for preclinical and clinical testing and expect to continue to do so for any future clinical trials and commercialization. This reliance on third parties may increase the risk that we will not have sufficient quantities of our drug candidates or products or such quantities at an acceptable cost or quality, which could delay, prevent or impair our development or commercialization efforts.
•If we are unable to obtain and maintain patent protection for our technology, our current drug candidates and any future drug candidates that we may develop, or if the scope of the patent protection obtained is not sufficiently broad, our competitors and other third parties could develop and commercialize technology and drug candidates similar or identical to ours, and our ability to successfully commercialize our technology and drug candidates may be impaired, and we may not be able to compete effectively in our market.
•We may not identify relevant third-party patents or may incorrectly interpret the relevance, scope or expiration of a third-party patent, and third parties may initiate legal proceedings alleging that we are infringing, misappropriating or otherwise violating their intellectual property rights, the outcome of which would be uncertain and could have a material adverse effect on our business.
•Unfavorable global economic conditions could adversely affect our business, financial condition, stock price and results of operations.
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•If we fail to attract and retain management and other key personnel, we may be unable to continue to successfully develop our current and any future drug candidates, commercialize our drug candidates or otherwise implement our business plan.
•Even if we are able to commercialize any drug candidates, the products may become subject to unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, which would harm our business.
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PART I
Item 1. Business
When used in this report, unless otherwise indicated, “Nurix,” “Company,” “we,” “us” and “our” refers to Nurix Therapeutics, Inc. and its wholly owned subsidiaries.
Overview
We are a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of innovative small molecules and antibody therapies based on the modulation of cellular protein levels as a novel treatment approach for cancer, inflammatory conditions and other challenging diseases. Leveraging our extensive expertise in E3 ligases together with our proprietary DNA-encoded libraries, we have built DELigase, an integrated discovery platform to identify and advance novel drug candidates targeting E3 ligases, a broad class of enzymes that can modulate proteins within the cell. Our drug discovery approach is to either harness or inhibit the natural function of E3 ligases within the ubiquitin-proteasome system to selectively decrease or increase cellular protein levels. Our wholly owned, clinical stage pipeline includes targeted protein degraders of Bruton’s tyrosine kinase (BTK), a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene B (CBL-B), an E3 ligase that regulates activation of multiple immune cell types including T cells and NK cells. Our partnered drug discovery pipeline consists of multiple programs under collaboration agreements with Gilead Sciences, Inc. (Gilead), Sanofi S.A. (Sanofi) and Seagen Inc. (now a part of Pfizer Inc.) (Pfizer), within which we retain certain options for co-development, co-commercialization and profit sharing in the United States for multiple drug candidates.
Our Clinical Development Pipeline
Our wholly owned pipeline of Targeted Protein Modulation (TPM) drug candidates comprises three clinical stage programs in our Targeted Protein Degradation (TPD) and Targeted Protein Elevation (TPE) portfolios. These two portfolios demonstrate our ability to either decrease or increase protein levels in cells through the modulation of E3 ligases. The following chart summarizes our clinical pipeline and ongoing clinical studies:
MOA, mechanism of action; IND, investigational new drug; DAC, degrader-antibody conjugates; I&I, inflammation and immunology
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Targeted Protein Degradation
Our portfolio of targeted protein degraders of BTK, a B‑cell signaling protein, comprises NX‑5948, an orally bioavailable BTK degrader for the treatment of relapsed or refractory B-cell malignancies and potentially autoimmune diseases, and NX‑2127, an orally bioavailable BTK degrader that also degrades cereblon neosubstrates IKZF1 (Ikaros) and IKZF3 (Aiolos) for the treatment of relapsed or refractory B‑cell malignancies.
NX-5948: We are currently treating patients in a Phase 1a/1b dose-escalation and cohort expansion study in patients with relapsed or refractory B-cell malignancies. In January 2024, the U.S. Food and Drug Administration (FDA) granted Fast Track designation for NX-5948 for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two lines of therapy, including a BTK inhibitor (BTKi) and a B-cell lymphoma 2 (BCL2) inhibitor.
NX‑2127: We are currently treating patients in a Phase 1a/1b dose-escalation and cohort expansion study of NX-2127 in patients with relapsed or refractory B-cell malignancies. We have initiated Phase 1b expansion cohorts for patients with relapsed CLL, diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). Enrollment of new patients in this clinical trial is paused pending resolution of a partial clinical hold, which was implemented by the FDA in late October 2023. Patients already enrolled who are receiving clinical benefit may continue treatment.
Targeted Protein Elevation
Our targeted protein elevation program includes NX-1607, an orally bioavailable an inhibitor of CBL-B, an E3 ligase that regulates the activation of multiple immune cell types including T cells and NK cells. NX-1607 is targeted for immuno-oncology indications.
We are currently treating patients in a Phase 1a/1b dose-escalation and cohort expansion study of NX-1607 in patients with a range of oncology indications. This study also includes a cohort within the Phase 1a dose escalation study testing NX-1607 in combination with paclitaxel, a taxane chemotherapy commonly used across a range of relapsed and refractory solid tumor indications. NX-1607 was awarded an Innovative Passport from the UK Medicines and Healthcare products Regulatory Agency to accelerate time to market and facilitate patient access to novel drugs to treat serious and life-threatening diseases.
Drug Discovery Pipeline
In addition to our clinical stage drug candidates, we are extending our protein modulation portfolio, both on our own and with partners by developing new targeted protein degraders and ligase inhibitors for a number of targets for which we believe the protein modulation modality can be clinically advantageous over existing therapies. These existing and future programs may have the potential to address diseases with significant unmet need, including cancer, autoimmunity, inflammation, and other challenging diseases.
We have entered into several revenue generating collaborations with large biopharmaceutical companies, including with Gilead, Sanofi and Seagen (now a part of Pfizer), to leverage our DELigase platform for drug discovery. These collaborations allow us to further advance our future pipeline with multiple currently identified targets included in these collaborations. In aggregate, we have received $413.0 million in non-dilutive financing from our collaborators to date, and as of November 30, 2023, we are eligible to receive up to $8.1 billion in potential future fees and milestone payments, as well as royalties on future product sales. We retain certain options for co-development, co-commercialization and profit sharing in the United States for multiple drug candidates pursuant to these collaborations.
Corporate Strategy
Our strategy is to leverage our DELigase platform to discover breakthrough therapies to not only improve upon existing drugs, but also address targets that are thought to be undruggable with current modalities. The key elements of our strategy are to:
•Advance our lead programs through clinical development. We have three drug candidates in Phase 1 clinical development and anticipate the following advancements in 2024.
•NX-5948. Enrollment is ongoing in our Phase 1a/1b clinical trial of NX-5948 in adults with relapsed or refractory B-cell malignancies, including CLL. In 2024, we seek to define doses for Phase 1b cohort expansion in CLL and NHL and accelerate Phase 1 clinical trial enrollment to enable pivotal trials. We plan to present additional clinical data with higher dose levels and longer treatment duration in mid-2024.
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•NX-2127. Screening and enrollment of new patients in our Phase 1a/1b clinical trial of NX-2127 in adults with relapsed or refractory B-cell malignancies have been paused due to a partial clinical hold placed on the study by the FDA. Patients currently enrolled in the clinical study who are deriving clinical benefit may continue to receive treatment in accordance with the ongoing study protocol. In 2024, we expect to resolve the partial clinical hold to enable the introduction of newly manufactured drug product into the ongoing Phase 1 clinical trial.
•NX-1607. Enrollment is ongoing in our Phase 1 trial for NX-1607 in adults with a range of oncology indications. In 2024, we expect to present data from the Phase 1a dose escalation portion of the trial of NX-1607 and to define dose(s) to enable Phase 1b cohort expansion.
•Advance our portfolio of preclinical programs to generate development candidates for our partners and our proprietary pipeline. Our research efforts are largely focused on the advancement of multiple programs for our partners Gilead, Sanofi, and Pfizer and for our proprietary pipeline. These partnered and wholly owned programs are at various stages of DNA-encoded library (DEL) screening, lead optimization and preclinical research. We aim to advance at least one program to the development candidate stage in 2024.
•Enhance and refine our DELigase platform. Targeted Protein Modulation is a rapidly emerging therapeutic modality that can provide significant advantages over existing modalities. Our proprietary DELigase platform enables us to advance an industry-leading approach to either selectively decrease or increase protein levels. We intend to continue to invest resources in our research and development activities to enhance our DELigase platform both in terms of the number of ligases available for drug discovery and the scale of our DEL collection. We plan to continue to leverage our platform capabilities to further enhance our position as a leader in the promising field of protein modulation.
•Explore additional strategic collaborations to maximize the commercial potential of our DELigase platform and our drug candidates. We have received $413.0 million in non-dilutive funding to date from our collaborations to support our research and development activities and to create new targeted protein modulation drugs with our partners. Under our Gilead, Sanofi and Pfizer collaborations, as of November 30, 2023, we have the opportunity to receive up to $8.1 billion in potential future fees and milestone payments, as well as royalties on future sales while retaining certain commercialization options. We currently retain worldwide development and commercialization rights to our BTK and CBL-B portfolios. While we intend to become a fully integrated biopharmaceutical company and build a targeted sales force in the United States to support the commercialization of our drug candidates, if approved, we intend to selectively evaluate technology collaborations and commercialization partnerships for our drug candidates with partners whose capabilities complement our own while retaining meaningful commercial rights in key geographic territories.
Targeted Protein Modulation
In disease settings where currently available treatments are limited by suboptimal efficacy or safety, or where relevant protein targets are not druggable by conventional means, we believe targeted protein modulation represents a novel treatment paradigm with the potential to improve upon or become the standard of care. Recent advances in the field have highlighted the significant therapeutic potential of harnessing E3 ligases to promote targeted protein degradation. In addition, we believe the largely unexplored area of inhibiting E3 ligases directly to increase protein levels represents an equally promising approach. Using our powerful DELigase platform, we have demonstrated our ability to discover and advance small molecule drug candidates to decrease or increase protein levels by either harnessing or inhibiting the activity of the appropriate E3 ligase, depending on the desired therapeutic effect. We have carefully selected and are advancing over 90 E3 ligases in our DELigase platform, expanding the universe of E3 ligases that can be modulated beyond cereblon and von Hippel-Lindau (VHL), the two predominantly used in the field of targeted protein degradation today. Our DEL collection consists of billions of small molecule compounds used to identify potential binders to ligases and protein targets as critical starting points in our drug discovery process. The differentiation of our protein modulation platform is in its breadth and versatility, enabling us to alter protein levels either upward or downward for both clinically validated targets, such as BTK, and for targets previously thought to be “undruggable;” that is, proteins that could not be addressed by conventional pharmacological means, such as CBL-B.
Proteins as targets in treating disease
Each cell type within the body is comprised of proteins that define its biochemistry and biological function. When proteins are expressed and regulated correctly, the health of each individual cell as well as the body as a whole is maintained. However, disease can occur when normal cellular processes are dysregulated as a result of changes in protein structure, function, expression levels or pathway regulation. Factors such as genetic mutations, infection, exposure to toxins, diet and behavior can lead to dysregulation of cellular processes and, if unchecked, a disease process.
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The traditional approach to discovering treatments for disease has involved the development of small molecule drugs that bind to a protein’s surface and modulate its activity. These “druggable” proteins contain distinct structural features that mediate protein function called active sites which can be exploited when identifying and optimizing compounds that disrupt protein activity. However, the vast majority of the body’s proteins do not have distinct active sites that can be targeted using traditional discovery methods. Because dysregulation and disease are not restricted to these “druggable” proteins, a significant number of therapeutically relevant proteins have not been addressed by traditional small molecule drugs. Other modalities, including antibody and protein-based therapies, genetic medicines and cell therapies, have emerged to address these issues but are still limited by their modes of delivery, their scalability and their therapeutic applications.
Leveraging E3 ligases and the ubiquitin proteasome system as a new treatment modality
Normal cellular physiology requires highly orchestrated and regulated processes that operate at the level of individual proteins. The ability of proteins to respond to stimuli quickly and in a coordinated fashion requires protein function to be readily controllable. One of the most exquisitely ordered cellular systems governing cellular proteins is the ubiquitin proteasome system (UPS).
As depicted above, the UPS is responsible for regulating and maintaining normal protein levels in the cell. An important class of enzymes called E3 ligases mediate this process with a high degree of specificity by recognizing individual proteins and catalyzing the attachment of ubiquitin protein tags to their surface. Proteins marked with chains of ubiquitin are then shuttled to the proteasome for degradation and removal from the cell. In addition to protein degradation, E3 ligases also mediate other functions such as protein localization, receptor internalization, protein signaling and protein quality control. There are over 600 E3 ligases encoded within the human genome, representing more than 5% of genes. The prevalence of the E3 ligase class of enzymes reflects the diversity of their physiological roles and biological significance and may allow for the creation of a wide spectrum of ligase-targeted therapeutics.
Modulating protein levels through small molecule therapeutics targeting E3 ligases
Advances in our understanding of the UPS suggest broad potential for the development of new therapies that modulate E3 ligases in the context of diseases such as cancer and autoimmune disorders. An example are the so-called immunomodulatory drugs, Revlimid (lenalidomide) and Pomalyst (pomalidomide), which are approved cancer drugs. These drugs exert their therapeutic effects by targeting the E3 ligase cereblon and redirecting its activity toward proteins it would not normally degrade such as Ikaros and Aiolos (also known as IKZF1 and IKZF3), transcription factors regulating immune cell function. Elucidation of this mechanism led to the recognition that pharmacological control of E3 ligase activity could more generally represent a promising new paradigm for small molecule drug action. This idea has since translated into the development of targeted protein degraders, which we believe have significant therapeutic potential. In addition, the largely unexplored area of inhibiting E3 ligases directly to increase cellular protein levels, which we call Targeted Protein Elevation, may represent an equally promising approach.
Targeted Protein Modulation is the term we use to describe our ability to either decrease target protein levels by harnessing E3 ligases for targeted protein degradation or increase protein levels through the inhibition of E3 ligases for targeted protein elevation.
•Targeted Protein Degradation (Harnessing E3 ligases). Targeted protein degradation harnesses the natural activity of ligases to remove specific proteins from the cell. Targeted protein degradation is accomplished by using bifunctional small molecules, which are composed of an E3 ligase binding element, or harness, linked to a target protein binding element. Unlike traditional small molecule inhibition, targeted protein degradation is catalytic whereby one molecule can induce the degradation of multiple copies of the protein target, enabling the efficient elimination of cellular proteins. In addition, since the effect is mediated through the binding of a small molecule drug rather than through functional inhibition, proteins lacking active sites are potentially targetable, greatly expanding the spectrum of both proteins and diseases amenable to small molecule therapeutic intervention.
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•Targeted Protein Elevation (Inhibiting E3 ligases). By inhibiting the function of E3 ligases in targeted protein elevation, it is possible to rapidly increase specific protein levels to control biological pathways. Increasing the levels of distinct sets of proteins could be a powerful approach to blocking pathological processes and restoring normal physiology. While there is enthusiasm in the scientific community around the therapeutic potential of E3 ligase inhibition, the discovery of such inhibitors has been impeded by the limited understanding of this biochemically and structurally complex class of proteins.
Targeted Protein Modulation
We believe that targeting E3 ligases to modulate protein levels represents a new therapeutic frontier that retains the favorable attributes of small molecule treatment modalities while addressing some major limitations. In addition to the points above, we believe other key differentiating attributes of our treatment modality include:
•Expansive therapeutic potential. The UPS and its associated E3 ligases function across the majority of cell types and organ systems, making it possible to modulate virtually any protein of interest for a wide range of diseases.
•Deliverable and tunable. Oral delivery of small molecule compounds lends itself to broad medical applicability in a range of patient populations with delivery that may be readily calibrated through dosing schedule and quantity.
•Ease of manufacturing. Development and manufacturing of small molecules utilizes established, cost-efficient processes that are readily scalable.
Our Programs
Our targeted protein degradation portfolio includes two clinical stage drug candidates that catalyze potent degradation of BTK, a well validated target for B-cell malignancies. Our two BTK degrader drug candidates, NX-5948 and NX-2127, are oral drug candidates being evaluated for the treatment of relapsed or refractory B-cell malignancies including CLL and non-Hodgkin’s lymphoma (NHL). NX-5948 is designed to solely degrade BTK, and NX-2127 is designed to degrade BTK and the immunomodulatory substrates of Ikaros and Aiolos. NX-5948 has the potential to address B-cell mediated autoimmune indications due to its specificity for BTK, and neurologic autoimmune indications due to its ability to cross the blood brain barrier.
In preclinical studies and in patient-derived samples, we have demonstrated the ability of both NX-5948 and NX-2127 to degrade BTK in cells harboring either wild type BTK or a variety of clinically relevant mutant forms of BTK that are known to confer resistance to both currently marketed BTK inhibitors and next-generation BTK inhibitors in late-stage development. Based on our preclinical and clinical data, we believe that both NX-5948 and NX-2127 have the potential to demonstrate unique and improved clinical benefit over the current standard-of-care in multiple oncology indications.
Our targeted protein elevation portfolio includes our lead ligase inhibitor NX-1607, an oral, clinical stage small molecule drug candidate that inhibits CBL-B, an intracellular orchestrator of the activation of T cells, B cells and NK cells. In preclinical studies, primary human T cells exposed to NX-1607 demonstrated increased T-cell activation in the absence of co-stimulation with CD3 and CD28, a potential advantage in an immune suppressive tumor microenvironment. In addition, NX-1607 has been shown in preclinical models to increase T‑cell proliferation and result in increased secretion of interleukin-2 (IL-2), a key cytokine involved in immune activation. We believe that oral delivery of a CBL-B inhibitor has the potential to drive immune cell activation and stimulation of localized IL-2 secretion, leading to enhanced anti-tumor response across a wide range of oncology indications.
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Targeted protein degradation portfolio in clinical trials
We have developed two targeted protein degrader drug candidates that are potent degraders of the BTK protein, a clinically validated signaling factor that drives B-cell activation and proliferation. Both of our BTK degraders harness the E3 ligase cereblon. NX-5948 is designed to selectively degrade BTK and has demonstrated the ability to cross the blood brain barrier in animal models and degrade BTK in both brain-resident tumor cells and normal microglia in the brain. NX-2127 was engineered to degrade both BTK and cereblon neosubstrates Ikaros and Aiolos for the treatment of relapsed or refractory B-cell malignancies. In several B-cell malignancy indications, and in particular in certain NHL subtypes, we believe dual activity may provide therapeutic advantages not addressable by pure BTK degraders or inhibitors, that could in turn result in improved outcomes for patients. We are currently treating patients with relapsed or refractory B-cell malignancies in Phase 1 trials for NX-5948 and NX-2127.
BTK’s role in B-cell malignancy
BTK is a key component of the B-cell receptor signaling pathway and has been clinically validated as a target in the treatment of B-cell malignancies, most notably in CLL but also in NHL. In 2022, it was estimated that over 20 thousand patients were diagnosed with CLL and over 80 thousand patients were diagnosed with NHLs in the United States. Approximately 85% of NHLs are a result of B-cell malignancies. The natural progression of NHL varies widely and takes multiple forms, ranging from aggressive subtypes such as DLBCL, to more indolent forms such as follicular lymphoma (FL).
Background on BTK inhibitors and immunomodulatory drugs for B-cell malignancies
The first generation BTK inhibitor Imbruvica, or ibrutinib, is approved for the treatment of CLL, Waldenstrom’s macroglobulinemia (WM), and chronic graft versus host disease (GVHD). Second generation BTK inhibitors include Calquence, or acalabrutinib, which is approved for use in CLL and MCL, and Brukinsa, or zanubrutinib, which is approved for use in CLL, MCL, WM and marginal zone lymphoma (MZL). Based on reported sales to date, we estimate that 2023 BTK sales were approximately $8.7 billion. These BTK inhibitors bind covalently to cysteine C481 of the BTK protein and irreversibly inhibit BTK; however, all have some off-target binding to other kinases, which leads to unwanted side effects. In addition, acquired resistance, most commonly through mutations in C481, may limit long term efficacy of these first and second generation BTK inhibitors. A number of noncovalent BTK inhibitors are currently being investigated in clinical trials as potential therapies for patients with relapsed and refractory disease, including Jaypirca, or pirtobrutinib, which was recently approved for use in CLL and MCL. However, the noncovalent inhibitors are also subject to acquired resistance, and treatment with these agents has led to the discovery of a broad range of new resistance mutations.
BTK degraders possess several unique properties that offer potential advantages over inhibitors:
•Addresses scaffold function of BTK. Removal of the BTK protein rather than just inactivating the kinase domain addresses the scaffolding activity of BTK, more completely blocking the signaling activity of both wild type and mutant forms of BTK.
•Event-driven pharmacology. BTK degraders do not require strong and prolonged binding to BTK to trigger degradation, which increases the ability our degraders to act on mutated BTK and may decrease the probability of forming new resistance mutations.
•Catalytic activity. A single degrader molecule is able to affect multiple target BTK molecules sequentially without the need to be constantly bound to the target.
We believe that targeted protein degradation of BTK may be a superior approach to existing covalent or noncovalent BTK inhibitors, particularly in the relapsed and refractory setting, and in the setting of resistance mutations to both covalent and noncovalent inhibitors.
The immunomodulatory drugs including Revlimid, or lenalidomide, and Pomalyst, or pomalidomide, are analogs of Thalomid, or thalidomide. These drugs possess several anti-tumor properties, including anti-angiogenic and anti-proliferative effects. They also have multiple effects on the immune system, including enhancement of T-cell mediated and NK-cell mediated immunity. Revlimid, the market leader in this class by global sales, was first approved in 2006 for the treatment of multiple myeloma. In May of 2019, Revlimid in combination with Rituxan received a supplemental indication approval for previously treated FL, MZL and MCL, and in August of 2020, Revlimid in combination with Monjuvi received a supplemental indication in DLBCL, thus validating the importance of this drug class in these indications. In 2022, global sales of this drug class including Revlimid and Pomalyst were approximately $13.5 billion. Subsequent to their approval and successful commercialization, studies demonstrated that these immunomodulatory drugs exert their therapeutic effect by triggering the degradation of specific proteins including Aiolos and Ikaros through the E3 ligase activity of cereblon and hence were identified retrospectively as the first approved drugs to target an E3 ligase.
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Published studies have recently reported early clinical data showing that combining a BTK inhibitor with an immunomodulatory drug may have the potential to augment clinical activity of certain standard of care agents in some hematologic malignancies such as non-germinal center B-cell like (non-GCB) DLBCL. Further, scientific publications have previously described synthetic lethality in a DLBCL cell line treated with both ibrutinib and lenalidomide. By targeting both BTK and cereblon-mediated immunomodulatory pathways simultaneously, it is believed that the survival mechanisms driven by accumulated mutations within certain cancers can be overcome, thereby preventing escape and disease relapse. This may be especially effective if each pathway has not only different functions but also if they share certain critical components. One possible intersection pathway is the suppression of interferon regulatory factor 4 (IRF4), a member of a family of transcription factors leading to a cell lethal increase in interferon production. The early clinical study cited above was particularly noteworthy since few combinations have previously produced promising results in DLBCL. This may suggest that simultaneous degradation of BTK combined with cereblon-mediated immunomodulatory activity by a single agent could produce an additive or synergistic effect in certain B-cell malignancies.
Potential advantages of BTK degraders
We have conducted extensive preclinical studies of our two clinical stage BTK degraders. We have demonstrated that both NX-5948 and NX-2127 can induce BTK degradation and inhibit tumor growth with oral administration in xenograft mouse models implanted with both wild type and ibrutinib-resistant lymphoma cell lines. We have also demonstrated the ability of both NX-5948 and NX-2127 to degrade BTK in circulating B-cells of non-human primates and in B-cell lymphoma patients following once daily oral dosing in ongoing Phase 1 trials. We have specifically designed NX-5948 to degrade BTK with limited or no degradation of cereblon neosubstrates, and we have designed NX-2127 as a dual degrader of BTK as well as the cereblon neosubstrates Aiolos and Ikaros, for potential applications in indications where adding immunomodulatory activity may be beneficial.
We have optimized NX-5948 and NX-2127 to be able to degrade both wild type BTK and the C481S variant of BTK that has been identified as the most common mutation in patients who have become resistant to ibrutinib therapy over time. Both agents have subsequently demonstrated the ability to degrade additional mutant variants of BTK associated with resistance to BTK inhibitors including L528W, T474I, M437R and V416L.
In our model of DLBCL cell line (TM8) harboring the most common resistance mutations, both NX-5948 and NX-2127 retained activity while all tested inhibitors demonstrated a major decrease in activity against at least one resistance mutation. The figure below shows a heat map of the relative activity of NX-5948 compared to a panel of first and second generation covalent BTK inhibitors and non-covalent BTK inhibitors.
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Potent tumor growth inhibition was achieved at varying doses of orally administered NX-2127 in mouse xenograft tumor models with a wild type BTK protein, as shown in the figure below on the top right. In this same model, NX-2127 demonstrated potent degradation of BTK in both circulating B cells (below on the top left) and in lymphoma tumors (below top middle). In this model system, 80% BTK degradation in circulating B cells correlated with 74% tumor growth inhibition, and 90% BTK degradation in circulating B cells correlated with 100% tumor growth inhibition. These target levels of inhibition suggest a potential therapeutic range correlating BTK degradation to tumor growth inhibition.
In addition to BTK degradation, we have also demonstrated the ability of NX-2127 to degrade both Aiolos (as shown in the figure below) and Ikaros (not shown), proteins targeted by immunomodulatory drugs Revlimid (lenalidomide) and Pomalyst (pomalidomide). Studies in human T cells comparing NX-2127 to lenalidomide and pomalidomide have shown comparable Aiolos degradation and resultant T-cell activation, as shown in the figure below. Based on the clinical data of both ibrutinib and the immunomodulatory drug in B-cell malignancies, we believe that this strategy of targeting both BTK and Aiolos/Ikaros in a single oral treatment may improve anti-tumor activity.
Clinical development studies for NX-5948
We are studying the pharmacology, safety, and clinical activity of NX-5948 in multiple subtypes of relapsed and refractory B-cell malignancies, including those in which ibrutinib has shown only modest effects or is ineffective, as in the case of CLL patients with BTK inhibitor resistance mutations.
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As illustrated in the diagram below, we are conducting a Phase 1a/1b dose-escalation and cohort expansion study of NX-5948 in patients with relapsed or refractory CLL and NHL. The Phase 1a portion is designed as a monotherapy dose escalation trial to investigate the safety and tolerability of NX-5948 and to identify a biologically active dose for cohort expansion and potentially a maximum tolerated dose. The Phase 1b portion of the trial is designed as a monotherapy expansion trial in up to five potential cohorts. The patients in the study represent a heavily pre-treated population with a variety of previous treatment options. Some patients also have resistance mutations and other high risk molecular features. The study is currently enrolling in the United States, the United Kingdom (UK) and the Netherlands.
aSubtypes include: transformed indolent lymphoma (e.g., grade 3b/transformed FL), Richter-transformed DLBCL, high-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangements, high-grade B-cell lymphomas NOS; bIncludes patients with secondary CNS involvement; cAdditional lines of therapy include anthracycline for non-GCB DLBCL and BTKi for MCL
Abbreviations: BCL-2i, B-cell lymphoma-2 inhibitor; BTKi, Bruton’s tyrosine kinase inhibitor; CIT, chemo-immunotherapy; CLL, chronic lymphocytic leukemia; CNS, central nervous system; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; GCB, germinal center B-cell; L, level; MCL, mantle cell lymphoma; LoT, line of therapy; MZL, marginal zone lymphoma; NOS, not otherwise specified; PCNSL, primary central nervous system lymphoma; SLL, small lymphocytic lymphoma; WM, Waldenströms macroglobulinemia
Initial clinical findings
Initial clinical findings from the NX-5948 clinical trial were presented at the 65th American Society of Hematology (ASH) annual meeting in December 2023. Pharmacokinetics (PK) and pharmacodynamics data from the ongoing Phase 1a trial shown below demonstrate dose-dependent PK and rapid, robust, and sustained BTK degradation in all patients with once daily oral dosing of NX-5948, confirming the findings and projections from previous preclinical research.
| NX-5948 C1D1 pharmacokinetics | BTK degradation in patients receiving NX-5948 | ||||
 |  | ||||
BTK, Bruton’s tyrosine kinase; MFI, mean fluorescence intensity; SEM, standard error of the mean
Source: Searle et al., ASH 2023, Poster #4473
Results from the first data disclosure of the NX-5948 Phase 1a trial showed that NX-5948 is well tolerated and demonstrates clinical benefit.
Out of 26 patients dosed, there were no dose limiting toxicities and no treatment emergent adverse events (TEAEs) resulting in drug discontinuation. There were four NX-5948-related grade ≥3 TEAEs and no related serious adverse events (SAEs).
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As of the October 17, 2023 data cutoff, in the CLL patient population six out of seven dosed patients showed clinical benefit, including three partial responses (one ongoing over nine months) and three stable disease outcomes (two still on treatment). In the NHL patient population (19 dosed), durable responses were noted across indications, with eight patients, or almost half of the patient population, continuing treatment. An expanded data set from a larger number of patients treated at higher doses and for a longer duration of time is expected in 2024.
NX-5948 CLL efficacy
CI, confidence interval; CLL, chronic lymphocytic leukemia; CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease
NX-5948 NHL efficacy
CR, complete response; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma; NHL, non-Hodgkin’s lymphoma; PCNSL, primary CNS lymphoma; PD, progressive disease; PR, partial response; SD, stable disease; WM, Waldenstrom’s macroglobulinemia
Source: Searle et al., ASH 2023, Poster #4473
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Clinical development of NX-2127
We are studying the pharmacology, safety and clinical activity of NX-2127 in multiple subtypes of relapsed and refractory B‑cell malignancies, including CLL, DLBCL, MCL, MZL and FL. We plan to focus development in indications where NX-2127 shows evidence of compelling clinical activity and where there is high unmet need.
As illustrated in the diagram below, the Phase 1a/1b dose-escalation and cohort expansion trial is evaluating doses ranging from 50 mg to 300 mg, and currently includes expansion cohorts for patients with CLL, DLBCL and MCL. The Phase 1a portion is designed as a monotherapy dose escalation trial to investigate the safety and tolerability of NX‑2127 and to identify a maximum tolerated dose for further evaluation. The Phase 1b portion of the trial is designed as a monotherapy expansion trial in defined cohorts. We selected a 100 mg dose for a Phase 1b expansion in CLL patients and selected a 300 mg dose for Phase 1b expansion in MCL and DLBCL patients. The patient population in the trial was heavily pre-treated and included a sizeable proportion of patients with resistance mutations. Enrollment of new patients in this clinical trial is currently paused pending resolution of a partial clinical hold.
aPlanned number of evaluable patients (i.e., meeting DLT evaluability criteria); bPlanned number of evaluable patients (i.e., meeting efficacy evaluability criteria)
CLL, chronic lymphocytic leukemia; DLBCL, diffuse large B-cell lymphoma; DLT, dose-limiting toxicity; FL, follicular lymphoma; MCL, mantle cell lymphoma; MTD, maximum tolerated dose; MZL, marginal zone lymphoma; PD, pharmacodynamics; PK, pharmacokinetics; PCNSL, primary central nervous system lymphoma; SLL, small lymphocytic lymphoma; WM, Waldenstrom's macroglobulinemia
Clinical findings
Updated data from the NX-2127 clinical study presented at the 65th ASH annual meeting in December 2023 described positive data for NX-2127 in patients with NHL and CLL, confirming a manageable safety profile that is consistent with previous reports for BTK-targeted and immunomodulatory therapies.
BTK and Ikaros degradation was demonstrated at all dose levels in patient samples, as shown in the figure below.
Source: Danilov et al., ASH 2023, Poster #4463
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The safety findings from the study confirmed the manageable and predictable safety profile. The most common TEAEs (any grade) were fatigue, neutropenia, hypertension, bruising/contusion, and diarrhea. The most common grade ≥3 TEAEs were neutropenia, hypertension and anemia. Atrial fibrillation was observed in six patients (11.1%; down from 17% reported previously), with three patients (5.6%) having grade ≥3 events. Twenty-one patients (38.9%) had serious TEAEs, of whom eight (14.8%) had SAEs considered related to NX-2127 treatment. Two patients experienced dose limiting toxicities (cognitive disturbance, neutropenia; both at the 300 mg dose).
Efficacy findings showed promising clinical activity: For patients with NHL encouraging and durable responses were observed, including two complete responses at week eight and two partial responses at week eight. For patients with CLL despite a median of five prior lines of treatment and BTK mutations present in 36% of patients, NX-2127 treatment resulted in an objective overall response rate of 40.7%, including partial responses in 11 patients, with treatment ongoing in 13 patients. Tumor shrinkage and clinical responses were observed in patients regardless of prior lines of therapy or baseline BTK mutations.
NX-2127 NHL efficacy
NX-2127 CLL efficacy
Source: Danilov et al., ASH 2023, Poster #4463
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Targeted protein elevation portfolio in clinical trials
Background on CBL-B
T cells play a key role in cell-mediated adaptive immune response. Activation, expansion and function of antigen-specific T cells is a multistep process and its outcome depends on the balance of positive and negative feedback mechanisms controlling each step. Many factors can hamper the development of an efficient anti-tumor immune response, such as insufficient expression of tumor antigens, defective antigen presentation, inhibitory molecular interactions including those effected by immune checkpoints, immune suppressive factors or suppressor cells and T-cell exhaustion.
CBL-B, an E3 ligase expressed in immune cell lineages, functions as an intracellular orchestrator of the immune response by negatively regulating T-cell activation, as illustrated above. CBL-B also limits function and survival of NK cells, B cells and dendritic cells as well as promotes T-cell exhaustion, anergy, and cell death. As such CBL-B represents a pivotal pathway negatively regulating immunity. CBL-B deficient animal models demonstrate enhanced signal dependent T-cell activation and robust T-cell dependent anti-tumor immunity.
CBL-B is highly expressed in human CD4+ and CD8+ T cells, with expression tightly regulated by CD28 and CTLA-4 and other co-stimulatory and inhibitory signals. T cells typically require two signals for activation, the first provided by interaction of the T-cell receptor (TCR) with a peptide presented by an MHC molecule, and the second through co-stimulatory molecules on antigen-presenting cells. CBL-B plays an essential role in the negative regulation of T-cell activation by regulating the activity of the TCR through substrate proteins that require a costimulatory signal to mount a productive immune response upon TCR engagement. Studies have found that CBL-B deficient T cells display lower thresholds for activation by antigen recognition receptors and co-stimulatory molecules such as CD28. For example, loss of CBL-B in T cells results in T cells that can be activated upon TCR engagement without co-stimulation by CD28. Importantly, our CBL-B inhibitors do not appear to activate T cells in the absence of TCR engagement. Such CBL-B deficient T cells are resistant to T-cell anergy, a tolerance mechanism in which T cells are functionally inactivated and T-cell proliferation is greatly impaired. Notably, CBL-B deficient T cells show increased rates of proliferation as well as elevated cytokine secretion including IL-2. The increased secretion of IL-2 is of particular importance in the optimization and development of our CBL-B inhibitors, serves as a key cellular biomarker for measuring successful T-cell activation and is a known therapeutic cytokine in oncology.
We believe that our oral, small molecule CBL-B inhibitor, NX-1607, has several potential immunotherapy applications through enhancing T-cell mediated anti-tumor activity by lowering the activation threshold of T cells in a suppressive tumor microenvironment where CBL-B plays a key role in the downregulation of T cells. Importantly, NX-1607 does not appear to activate T cells in the absence of TCR engagement. We are studying NX-1607 in a Phase 1a dose escalation trial in multiple solid tumors and lymphoma. Solid tumors represent the vast majority of human cancers. Various immunotherapy strategies have been developed in order to increase the efficiency of anti-tumor immune response, including the use of antibody checkpoint inhibitors such as anti-PD-1, anti-PD-L1 and anti-CTLA-4, which block the “brakes” of immune response. These immune-stimulating antibodies have a more favorable clinical outcome than traditional treatment modalities on a growing list of tumor types. However, most patients fail to respond or experience only transient responses.
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Preclinical development of CBL-B inhibitors
We have developed a series of potent small molecule inhibitors of CBL-B activity that have demonstrated biochemical activity and effects in vitro on human immune cells as well as in mouse tumor models. Consistent with studies cited above, CBL-B inhibitors enhanced ex vivo T-cell activation as measured by induction of IL-2, a key cytokine required for immune cell activation and proliferation. Induction of IL-2 secretion occurs at low nanomolar concentrations in primary human and mouse T cells stimulated with anti-CD3/anti-CD28 antibodies or anti-CD3 antibodies alone. As illustrated below, we demonstrated several fold increases in IL-2 production in tandem with increasing biochemical activity of our CBL-B inhibitors. In addition, certain of our CBL-B inhibitors reduced anergy and exhaustion in an ex vivo model of T-cell exhaustion using human donor T cells and further, this effect was additive to that achieved with an anti-PD-1 antibody. Based on our findings to date, we believe that CBL-B inhibitors may induce an immune cell localized IL-2 secretion that in combination with other immune activation effects will enhance anti-tumor responses. The precursor compounds shown in the graphs below led to the optimization and selection of NX-1607 as a development candidate.
NX-1607, an oral CBL-B inhibitor for immuno-oncology
NX-1607 is an investigational, orally bioavailable, potent inhibitor of CBL-B. In vitro studies demonstrated that NX-1607 treatment resulted in a dose-dependent increase in T cell activation in TCR stimulated primary human T cells in the presence and, to a lesser extent, in the absence of CD28 co-stimulation, a potential advantage in a suppressive tumor microenvironment. In vitro, NX-1607 has been demonstrated to increase T-cell activation in primary human T cells in the absence of co-stimulation with CD3 and CD28, a potential advantage in a suppressive tumor microenvironment. In vivo, oral administration of NX-1607 in mice has demonstrated notable tumor growth inhibition in a tumor model as illustrated in the figure below on the left. The tumor growth inhibition with oral administration of NX-1607 recapitulates the genetic experiment in mice with a ligase-inactive version of CBL-B which also shows tumor growth inhibition as illustrated in the figure below on the right.
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The in vivo effects of orally administered NX-1607 were further evaluated as a single agent in several mouse models of cancer. In the experiments shown in the figure below on the left, oral treatment with NX-1607 at a dose of 30 mg/kg (blue circles) significantly reduced the size of tumors measured at day 25 compared to vehicle treated animals (black squares) in this colorectal cancer model. In the figure below in the middle, oral treatment with NX-1607 significantly increased survival in this neoadjuvant model of metastatic triple-negative breast cancer in which treatment was initiated just prior to surgical primary tumor resection. Without further treatment, all mice in the vehicle group (black line) died by day 60 as a result of disseminated tumor metastases in the lung, liver and brain. By contrast, animals treated with NX-1607 (blue line) administered as a daily oral dose starting at day seven and continuing through day 46 demonstrated a highly significant prolongation of survival. In the figure below on the right, oral treatment with NX-1607 (blue squares) significantly reduced the size of tumors and the rate of tumor growth compared to the vehicle group (black circles) in a B-cell lymphoma model.
The in vivo effects of orally administered NX-1607 were evaluated in combination with an antibody to PD-1 in several mouse models of cancer as shown in the figure below. In the left and middle panels, the combination of oral NX-1607 plus anti-PD-1 (light blue lines) demonstrated increased survival in two separate colorectal cancer models compared with animals treated with either NX-1607 alone (blue line), anti-PD-1 alone (red line) or vehicle (black line). In the panel on the right, the activity of oral NX-1607, anti-PD-1 and the combination of NX-1607 and anti-PD-1 were tested in a model of metastatic triple-negative breast cancer. Both single agent NX-1607 (blue triangles) and single agent anti-PD-1 (red circles) reduced the number of lung metastases at day 28 compared with the vehicle group (black squares), but the combination of NX-1607 and anti-PD-1 (light blue diamonds) was superior to either single agent.
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Clinical development of NX-1607
We are studying the pharmacology, safety and clinical activity of single-agent NX-1607 and the combination of NX-1607 with taxane chemotherapy in multiple solid tumor indications and lymphoma. The solid tumors selected for this initial assessment include three different immune phenotypes: checkpoint-resistant tumors, tumors with an immunosuppressive microenvironment and tumors that are poorly immunogenic. We believe that there is a scientific rationale for the role of CBL-B inhibition in each of these immune phenotypes.
As illustrated in the diagram below, we are conducting a Phase 1a/1b dose-escalation and cohort expansion study of NX-1607 in patients with relapsed or refractory solid tumors and lymphoma. We are currently enrolling patients in the Phase 1a dose escalation portion of the monotherapy trial.
Our DELigase platform
Our approach leverages the specificity of E3 ligases and the natural function of the UPS to regulate the cellular proteome for therapeutic effect. Development of therapies that modulate E3 ligases has been historically limited by the inherent difficulties in building biochemical and cellular assays relevant for measuring E3 ligase function, as well as by the relative lack of mechanistic understanding of this critical class of proteins. Through our focused efforts and investment over the past several years, we have developed proprietary tools, in-depth knowledge and expertise relating to E3 ligases as targets for drug discovery. In addition, we have assembled a team that has extensive experience applying DEL discovery technologies to a wide variety of proteins including targets previously considered undruggable. Together, these capabilities and insights have allowed us to develop a powerful platform technology called DELigase to identify and advance novel drug candidates that either selectively increase or decrease protein levels within the cell.
Our DELigase platform combines our proprietary DELs and E3 ligase expertise to empower efficient drug discovery. DEL technology is well suited to finding new binders for targets thought to be undruggable, which include the vast majority of proteins encoded in the human genome including E3 ligases.
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DEL technology taps enormous chemical space to overcome “druggability” limits
Our DEL collection comprises several billion compounds whereas typical screening collections contain less than a few million. This increased scale provides the necessary chemical diversity to identify chemical starting points for more challenging protein targets that have been considered undruggable by other approaches. DEL technology evaluates each library compound simultaneously in a single experiment, enabling a more accurate assessment of compound function. In addition, because DEL drug discovery is performed by measuring compound binding rather than biochemical activity it allows inclusion of proteins for which biochemical assays are lacking or not feasible. Further, the relative ease with which binding screens can be performed and interpreted provides sufficient flexibility to allow evaluation of structurally complicated proteins like E3 ligases, which display distinct conformations and activity states and are often part of large multi-protein complexes. Lastly, a chemical linker attaches each DEL compound to a strand of DNA, which functions as a structure barcode allowing screening hits to be easily identified. DEL’s built in chemical linker is also an advantage in the context of identifying bifunctional degraders, as it allows the discovery of compounds that can effectively bind proteins when linked to a partner molecule.
Our DELigase platform was designed for E3 ligase discovery
Our integrated DELigase platform relies on proprietary DELs we have specifically engineered to identify and select binders against a diverse group of target protein classes, including some considered to be undruggable, as well as binders to E3 ligases. Key features of our DELigase platform include:
•Custom-synthesized DELs. Our custom-synthesized chemical scaffolds impart desirable, drug-like chemical properties, like solubility, into each library compound in a manner that cannot be achieved when building DEL collections solely from commercial inputs. The three-dimensional design of the proprietary scaffolds allows our library compounds to complement the surface of the target proteins, making them ideal for binding targets classically considered undruggable, such as E3 ligases. For 75% of the undruggable targets screened by us, the scaffold libraries have been the sole source of hits from our collection. Our collection of over 5 billion compounds also enables us to find diverse hits for classical targets and contains a sizable subset of covalent compounds, which have been shown as another effective way to bind E3 ligases. Covalent compounds have begun to show promise in augmenting performance of targeted protein degraders, suggesting that our covalent DELs may have additional utility for Targeted Protein Modulation.
Design of the Nurix DEL Collection
•Proprietary data analysis and hit confirmation technologies. We have built a suite of custom analytical tools for interpretation and prioritization of our DEL binder outputs, which routinely contain thousands of productive hits. By leveraging data collected from hundreds of DEL screens, we are able to rapidly eliminate background signal and reveal the most promising target-specific ligands. We have also developed machine learning and high throughput methods for nanoscale hit resynthesis and affinity selection mass spectroscopy that allow a more comprehensive and industrialized process for finding the best chemical starting points for future pipeline programs.
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Leveraging the Nurix DEL Database for clear classification of enriched DEL ligands
•Many screens, one protein target. E3 ligases can exist in multiple potential conformation states. Our approach uses comprehensive parallel screening campaigns to interrogate numerous states and surfaces of the target protein. An illustration of how we probe the surface of an E3 ligase by DEL screening is depicted in the graphic below.
DELs allow access to a spectrum of binders across the protein surface, some of which inhibit protein function.
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•Rapid automated chemistry. Our state-of-the-art automated chemistry robotic suite allows for rapid synthesis of both binders and fully assembled degrader molecules. This automation enables us to sample unprecedented chemical space and allows for faster design test cycles which accelerates drug discovery projects.
•Harnessing our data generation pipelines with Machine Learning. Our investment in scalable science has created large data streams stemming from our DEL, automated chemistry, and high-throughput experimental platforms. Our internal machine learning team leverages these data in developing models to enable property prediction of our targeted degraders, to support small molecule and TPD lead optimization efforts and to enhance the data analysis and lead ID workflows of our DEL platform.
Our DELigase discovery platform enables us to address multiple therapeutic applications
We have expanded the universe of E3 ligases available for therapeutic manipulation from the two predominantly used in the field, cereblon and VHL, by screening over 60 additional E3 ligases to date. We have carefully selected these E3 ligases for use in drug discovery across our three core areas of therapeutic expertise: oncology, immuno-oncology and immune disorders. We consider the unique biological function of each ligase and the therapeutic requirements of the disease state for inhibitor programs. For ligases that direct targeted protein degradation, we take into account the biochemical specificity of the E3 ligase as well as tissue specificity of action and cellular localization of the target protein. E3 ligases that are required for cancer cell survival are also of high interest for cancer indications to reduce the risk of intrinsic resistance to degrader action. We are growing our set of E3 ligases for use in our DELigase platform tailored to our core therapeutic areas.
DELigase for E3 ligase harnesses
We apply our platform to utilize the ubiquitination function of E3 ligases for targeted protein degradation. Our DELigase platform enables us to identify binders to E3 ligases, which we refer to as harnesses, as well as binders to degradation targets. We use these molecular starting points to design compounds using a modular approach that connects an E3 ligase harness to a target protein binder with a linker. We refer to these bifunctional molecules as targeted protein degraders, which function by bringing the E3 ligase into proximity of the target protein to catalyzing its ubiquitination and degradation.
DELigase for E3 ligase inhibitors
By inhibiting the function of E3 ligases, it is possible to rapidly increase specific protein levels to control biological pathways. Increasing the levels of distinct sets of proteins could be a powerful approach to blocking pathological processes and restoring normal physiology. Our DELigase platform enables the identification of inhibitors through parallel screening of distinct E3 ligase activity states using chemical matter tailored specifically for binding to E3 ligases. Our substantial expertise in E3 ligase biochemistry and biology has allowed us to identify and develop potent inhibitors of E3 ligases that play pivotal roles in T-cell signaling and immune cell function.
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Drug candidate identification and selection process
We employ a series of processes and studies from target validation to preclinical development for selection of the appropriate candidate for further development. We have invested in an integrated drug development infrastructure that enables us to perform every step of the drug discovery and early preclinical development process within our research facility. Each of our primary areas of core expertise and technology are highlighted in the below illustration.
Our integrated drug discovery and development system and core technical expertise
Collaborations and License Agreements
Gilead
In June 2019, we entered into a global strategic collaboration agreement with Gilead (as subsequently amended, the Gilead Agreement) to discover, develop and commercialize a pipeline of targeted protein degradation drugs for patients with cancer and other challenging diseases using our DELigase platform to identify novel agents that utilize E3 ligases to induce degradation of five specified drug targets. In August 2019 and September 2022, we entered into the First Amendment and the Second Amendment, respectively, to the Gilead Agreement to clarify certain language of the Gilead Agreement.
Under the Gilead Agreement, Gilead has the option to license drug candidates directed to up to five targets resulting from the collaboration and is responsible for the clinical development and commercialization of drug candidates resulting from the collaboration. We retain the option to co-develop and co-promote, under a profit share structure, up to two drug candidates in the United States, provided that we may only exercise such option once per licensed product and Gilead retains the right to veto our option selection for any one drug candidate of its choice. The collaboration excludes our current internal protein degradation programs for which we retain all rights, and also excludes our future internal programs, provided that we have distinguished future programs as excluded from the scope of the collaboration. In March 2023, Gilead exercised the option to exclusively license one target (Gilead License Option Exercise), the first development candidate resulting from the Gilead Agreement. Pursuant to the Gilead Agreement, we received a license option exercise payment of $20.0 million in April 2023 for the Gilead License Option Exercise.
Over time, Gilead may elect to replace the initial drug targets with other drug targets. For drug targets that are subject to the collaboration, we are obligated to use commercially reasonable efforts to undertake a research program in accordance with a research plan agreed to by the parties and established on a target-by-target basis. We have primary responsibility under the Gilead Agreement for performing preclinical research activities (including target validation, drug discovery, identification or synthesis) pursuant to a research plan. Each party will bear its own costs in the conduct of research activities. Gilead will be responsible for any development, commercialization and manufacturing activities, unless we exercise our co-development and co-promotion option. For those programs that we exercise our option to co-develop and co-promote, we and Gilead will split U.S. development costs as well as U.S. profits and losses evenly, and we will be eligible to receive royalties on net ex-U.S. sales and reduced milestone payments.
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Upon signing the Gilead Agreement, Gilead paid us an upfront payment of $45.0 million, plus $3.0 million in additional fees. In addition, from the signing of the Gilead Agreement to November 30, 2023, we received payments of $47.0 million for research milestones and additional payments and $20.0 million for a license option exercise payment. As of November 30, 2023, we are eligible to receive up to approximately $2.3 billion in total additional payments based on certain additional fees, payments and the successful completion of certain preclinical, clinical, development and sales milestones. We also are eligible to receive mid-single digit to low tens percentage tiered royalties on annual net sales from any commercial products directed to the optioned collaboration targets, subject to certain reductions and excluding sales in the United States of any products for which we exercise our option to co-develop and co-promote, for which the parties share profits and losses evenly.
Subject to earlier expiration in certain circumstances, the Gilead Agreement expires on a licensed product-by-licensed product and country-by-country basis upon the later of (1) the expiration of the last to expire patent with a valid claim covering the applicable licensed product in the applicable country, (2) the expiration of any regulatory exclusivity for the applicable licensed product in the applicable country or (3) ten years after the first commercial sale of the applicable licensed product in the applicable country covered by the Gilead Agreement, provided that the term for any profit-shared licensed product in the United States will expire upon the expiration or termination of the applicable profit-share term as set forth in an applicable profit-share agreement to be negotiated upon our exercise of our option to co-develop and co-promote such licensed product. If Gilead does not exercise an option to license a drug candidate, then the Gilead Agreement will terminate at the end of the last to expire option period.
Sanofi
In December 2019, we entered into a strategic collaboration with Genzyme Corporation, a subsidiary of Sanofi, which became effective in January 2020 (as subsequently expanded and amended, the Sanofi Agreement), to discover, develop and commercialize a pipeline of targeted protein degradation drugs for patients with challenging diseases in multiple therapeutic areas using our DELigase platform to identify small molecules designed to induce degradation of three specified initial drug targets. In January 2021, as part of the existing Sanofi Agreement, Sanofi paid us $22.0 million to exercise its option to expand the number of targets in the Sanofi Agreement from three to a total of five targets.
In January 2021, we entered into the First Amendment to the Sanofi Agreement to modify the research term on all targets. In December 2021, we entered into the Second Amendment to the Sanofi Agreement to extend the substitution deadline on certain targets. In July 2022, we entered into the Third Amendment to the Sanofi Agreement to further extend the substitution deadline on certain targets. Also in July 2022, Sanofi elected to replace certain drug targets, and the substitution extended the research term of those targets by one year to 5.25 years. In August 2022 and November 2023, we entered into the Fourth Amendment and Fifth Amendment, respectively, to the Sanofi Agreement to modify the research plan for certain targets.
Under the Sanofi Agreement, Sanofi has exclusive rights and is responsible for the clinical development, commercialization and manufacture of drug candidates resulting from the collaboration while we retain the option to co-develop, co-promote and co-commercialize all drug candidates in the United States directed to up to two targets, one of which must be selected from a list of targets designated at the execution of the Sanofi Agreement or any replacement of such targets, and one of which must be selected from targets identified by Sanofi as part of their January 2021 expansion. Our right to exercise our option to co-develop, co-promote and co-commercialize a given target is dependent on our ability to demonstrate, within a given timeframe, that we have sufficient cash resources and personnel to commercialize the product. The collaboration excludes our current internal protein degradation programs for which we retain all rights, and also excludes our future internal programs, provided that we distinguished future programs as excluded from the scope of the collaboration.
For drug targets that are subject to the collaboration, we have primary responsibility for conducting preclinical research activities (including target validation, drug discovery, identification or synthesis) in accordance with the applicable research plan agreed to by the parties and established on a target-by-target basis. We are obligated to use commercially reasonable efforts to identify relevant target binders and targeted protein degraders in order to identify development candidates. Subject to certain exceptions, each party will bear its own costs in the conduct of such research. Sanofi will be responsible for any development and commercialization activities unless we exercise our co-development and co-promotion option. For those programs that we exercise our option to co-develop, co-promote and co-commercialize, we will be responsible for a portion of the U.S. development costs, and the parties will split U.S. profits and losses evenly, and we will be eligible to receive royalties on ex-U.S. net sales and reduced milestone payments on such optioned products.
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Upon signing the Sanofi Agreement, Sanofi paid us an upfront payment of $55.0 million. Subsequently in January 2021, Sanofi paid us an additional $22.0 million to exercise its option to expand the number of targets beyond the initial targets included in the collaboration. In addition, from the signing of the Sanofi Agreement to November 30, 2023, we received payments of $7.0 million for research milestones. Additionally, we achieved two research milestones in November 2023 and received payments totaling $4.0 million in January 2024 as a result. As of November 30, 2023, we are eligible to receive up to approximately $2.5 billion in total additional payments based on certain additional fees, payments and the successful completion of certain research development, regulatory and sales milestones, as well as mid-single digit to low teen percentage tiered royalties on annual net sales of any commercial products that may result from the collaboration, subject to certain reductions and excluding sales in the United States of any products for which we exercise our option to co-develop and co-promote, for which the parties share profits and losses evenly.
Subject to earlier expiration in certain circumstances, the Sanofi Agreement expires on a licensed product-by-licensed product or profit-shared licensed product-by-profit-shared licensed product basis and country-by-country basis upon on the later of (1) the expiration of the last-to-expire patent with a valid claim covering the applicable licensed product in the applicable country, (2) the expiration of any regulatory exclusivity for the applicable licensed product in the applicable country or (3) ten years after the first commercial sale of the applicable licensed product in the applicable country covered by the Sanofi Agreement.
Pfizer
In September 2023, we entered into a strategic collaboration with Seagen Inc. (now a part of Pfizer Inc.) (the Pfizer Agreement) to develop a suite of targeted protein degraders against multiple targets nominated by Pfizer that are suitable for antibody conjugation. Pfizer will be responsible for conjugating these degraders to antibodies to make Degrader-Antibody Conjugates (DACs), a new class of medicines for use in cancer treatment, and advancing these DAC drug candidates through preclinical and clinical development and commercialization.
Under the Pfizer Agreement, Pfizer has the option to obtain exclusive licenses to develop and commercialize certain degraders, while we retain an option for U.S. profit sharing and co-promotion on two products arising from the collaboration. The collaboration excludes our current internal protein degradation programs for which we retain all rights, and also excludes our future internal programs, provided that we have distinguished future programs as excluded from the scope of the collaboration.
For the targets nominated by Pfizer under the collaboration, we shall use commercially reasonable efforts to identify, synthesize, characterize and deliver targeted protein degraders that selectively bind to and degrade such targets. Development of licensed degraders, with the exception of licensed products for which we exercised our profit-share options, will be at Pfizer’s sole cost and expense. For the profit-share products, the parties will share net profits and net losses and global development costs, and we will be eligible to receive royalty and milestone payments on such optioned products.
Under the terms of the Pfizer Agreement, we received an upfront payment of $60.0 million. We are eligible to receive up to approximately $3.4 billion in contingent payments based on specified research, development, regulatory and commercial milestones across multiple programs, and are eligible for mid-single to low double digit percentage tiered royalties on future sales.
Subject to the exceptions described in the Pfizer Agreement, the Pfizer Agreement expires upon the first to occur of (1) the expiration of the last-to-expire option exercise period under the Pfizer Agreement if no such option has been exercised prior to such expiration and (2) the expiration of the last-to-expire royalty term under the Pfizer Agreement.
Manufacturing and Supply
We do not own or operate, and currently have no plans to establish, any facilities for product manufacturing, packaging, storage and distribution, or testing. We rely on and expect to continue to rely on contract manufacturing organizations (CMOs) for both drug substance and finished drug product. We have personnel or engaged consultants with extensive technical, manufacturing, analytical and quality experience and good project management to oversee contract manufacturing and testing activities. We have engaged third-party manufacturers to supply the drug substances for NX-5948, NX-2127 and NX-1607 and to develop and manufacture finished drug products for use in our clinical trials. Should any of these manufacturers become unavailable to us for any reason, we believe that there are a number of potential replacements, although we may incur some delay in identifying and qualifying such replacements.
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All of our drug candidates are organic compounds of low molecular weight, generally called small molecules, but which are larger than traditional small molecule therapeutics. We have selected these compounds not only on the basis that they could have potentially favorable efficacy and safety profiles, but also for their ease of synthesis and the reasonable cost of their starting materials. In particular, our lead drug candidates are manufactured using reliable and reproducible synthetic processes from readily available starting materials. The chemistry is amenable to scale up and does not require unusual equipment in the manufacturing process. We expect to continue to develop drug candidates that can be produced cost-effectively at contract manufacturing facilities.
Competition
The biotechnology and biopharmaceutical industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis on intellectual property and proprietary products. While we believe that our technology, development experience, scientific knowledge and intellectual property portfolio provide us with competitive advantages, we face potential competition from many different sources, including major pharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions, governmental agencies and public and private research institutions that conduct research, seek patent protection and establish collaborative arrangements for research, development, manufacturing, and commercialization. Not only must we compete with other companies that are focused on protein modulation, but any drug candidates that we successfully develop and commercialize will compete with existing therapies and new therapies that may become available in the future. Moreover, our industry is characterized by the existence of large numbers of patents and frequent allegations of patent infringement.
Our focus is the discovery and development of innovative small molecules and antibody therapies designed to modulate protein levels, including targeted protein degraders. Other companies that primarily focus on developing small molecules that degrade target proteins include, but are not limited to, Arvinas, Inc., BioTheryX, Inc., C4 Therapeutics, Inc., Cullgen Inc., Foghorn Therapeutics Inc., Kymera Therapeutics, Inc. and Monte Rosa Therapeutics. Drug candidates from our BTK degrader and CBL-B inhibitor programs may face competition from drugs with similar mechanisms of action. We are aware of clinical-staged BTK degraders currently in development by AbbVie Inc., Accutar Biotechnology, Inc., BeiGene, Ltd, Haisco Pharmaceutical Group Co., Ltd. and Ubix Therapeutics, Inc. In addition, we are aware of a clinical-staged CBL-B inhibitor currently in development by HotSpot Therapeutics, Inc.
Our lead drug candidates target hematologic cancers and immune-mediated diseases. The most common methods of treating patients in oncologic indications are surgery, radiation and drug therapy, including chemotherapy, hormone therapy and targeted drug therapy. There are a variety of available drug therapies marketed for cancer, including hematologic cancers. In many cases, these drugs are administered in combination to enhance efficacy. Some of the currently approved drug therapies are branded and subject to patent protection, and others are available on a generic basis. Many of these approved drugs are well established therapies and are widely accepted by physicians, patients and third-party payors. In general, although there has been considerable progress over the past few decades in the treatment of cancer and the currently marketed therapies provide benefits to many patients, these therapies all are limited to some extent in their efficacy and frequency of adverse events, and none of them are successful in treating all patients. As a result, the level of morbidity and mortality from cancer remains high.
In addition to currently marketed drugs, there are also several drug candidates in late-stage clinical development for the treatment of oncologic indications and immune-mediated diseases. These products in development may provide efficacy, safety, convenience and other benefits that are not provided by currently marketed therapies. As a result, they may provide significant competition for any of our drug candidates for which we obtain market approval.
If any of our drug candidates are approved for the indications for which we currently are conducting clinical trials or for which we expect to conduct clinical trials, they will compete with the foregoing therapies and the currently marketed drugs and potentially any drugs in development. It is also possible that we will face competition from other biologic or pharmaceutical approaches as well as from other types of therapies.
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Many of our current or potential competitors, either alone or with strategic partners, have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that we may develop. Our competitors also may obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market. In addition, our ability to compete may be affected in many cases by insurers or other third-party payors seeking to encourage the use of generic products. There are generic products currently on the market for certain of the indications that we are pursuing, and additional products are expected to become available on a generic basis over the coming years. If our drug candidates are approved, we expect that they will be priced at a significant premium over competitive generic products.
The key competitive factors affecting the success of all our programs, if approved, are likely to be their efficacy, safety, convenience, price, level of generic competition and availability of reimbursement.
Intellectual Property
We strive to protect and enhance the proprietary technology, inventions, platforms, drug candidates and improvements thereof that are commercially important to our business, including obtaining, maintaining and defending patent rights, whether developed internally or licensed from third parties. Our policy is to seek to protect our proprietary position by, among, other methods, pursuing patent protection in the United States and in jurisdictions outside of the United States related to our proprietary technology, inventions, improvements, platforms and drug candidates that are important to the development and implementation of our business. Our patent portfolio is intended to cover, but is not limited to, our technology platforms, drug candidates and components thereof and their methods of use, and any other inventions that are commercially important to our business.
We also rely on trade secret protection of our confidential information and know-how relating to our proprietary technology, platforms and drug candidates and continuing innovation to develop, strengthen and maintain our position in our DELigase platform and drug candidates. Trade secrets are difficult to protect and provide us with only limited protection. Our commercial success may depend in part on our ability to obtain and maintain patent and other proprietary protection for our technology, inventions and improvements; to preserve the confidentiality of our trade secrets; to maintain our licenses to use intellectual property owned or controlled by third parties; to defend and enforce our proprietary rights, including our patent applications; to defend against challenges and assertions by third parties of their purported intellectual property rights; and to operate without infringement of valid and enforceable patents and other proprietary rights of third parties. For risks related to our intellectual property, please see “Risk Factors—Risks Related to Our Intellectual Property.”
We believe that we have a strong global intellectual property position and substantial know how and trade secrets relating to our DELigase platform and drug candidates. As of December 31, 2023, we have five U.S. patents, 22 U.S. patent applications, one foreign patent and 103 foreign applications that we own, and one U.S. patent, four pending U.S. patent applications and 26 foreign patent applications that we co-own with Gilead. The expected expirations for issued patents and patents that may issue from pending applications covering our clinical candidates are between the years 2039 and 2042 for NX-5948 and NX-2127; and between 2040 and 2043 for NX-1607.
The term of individual patents depends upon the laws of the countries in which they are obtained. In most countries in which we file, including the United States, the patent term is 20 years from the earliest date of filing of a non-provisional patent application in the applicable country. However, the patent term of U.S. patents may, in certain cases, be adjusted for administrative delays by the United States Patent and Trademark Office (USPTO) in examining and granting a patent or may be shortened if a patent is terminally disclaimed over an earlier filed patent. In addition, the term of a patent may be extended as compensation for the patent term lost during the FDA regulatory review process. For example, for drugs that are regulated by the FDA under the Hatch-Waxman Act, it is permitted to extend the term of a patent that covers such drug for up to five years beyond the normal expiration date of the patent. For more information on patent term extensions, see “Business—Government Regulation—The Hatch-Waxman Act—Patent term extension.” In the future, if and when our pharmaceutical drug candidates receive FDA approval, we expect to apply for patent term extensions on patents, if issued, covering those drug candidates. We intend to seek patent term extensions to any of our patents, if issued, in any jurisdiction where these are available; however, there is no guarantee that the applicable authorities, including the USPTO and FDA, will agree with our assessment of whether such extensions should be granted, and even if granted, the length of such extensions.
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The actual protection afforded by a patent varies on a product-by-product basis, from country-to-country, and depends upon many factors, including the type of patent, the scope of its coverage, the availability of regulatory-related extensions, the availability of legal remedies in a particular country and the validity and enforceability of the patent.
We also rely on trade secret protection for our know-how, confidential and proprietary information and continuing technological innovation to develop and maintain our competitive position. We seek to protect and maintain the confidentiality of proprietary information to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection. Although we take steps to protect our confidential and proprietary information as trade secrets, including through contractual means with our employees, consultants, outside scientific collaborators, sponsored researchers and other advisors, competitors or other third parties may independently develop substantially equivalent proprietary information and techniques or otherwise gain access to our trade secrets or disclose our technology. Thus, we may not be able to meaningfully protect our trade secrets. It is our policy to require our employees, consultants, outside scientific collaborators, sponsored researchers and other advisors to execute confidentiality agreements under the commencement of employment or consulting relationships with us. Despite these efforts, we cannot provide any assurances that all such agreements have been duly executed, and any of these parties may breach the agreements and disclose our proprietary information, and we may not be able to obtain adequate remedies for such breaches. We also seek to preserve the integrity and confidentiality of our proprietary technology and processes by maintaining physical security of our premises and physical and electronic security of our information technology systems. Although we have confidence in these individuals, organizations and systems, agreements or security measures may be breached, and we may not have adequate remedies for any breach. To the extent that our employees, contractors, consultants, collaborators and advisors use intellectual property owned by others in their work for us, disputes may arise as to the rights in relation to the resulting know-how or inventions. For more information, please see the sections titled “Risk Factors—Risks Related to Our Intellectual Property” and “Risk Factors—Risks Related to Regulatory Approval and Marketing of Our Drug Candidates.”
Government Regulation
The processes for obtaining regulatory approvals in the United States and in foreign countries and jurisdictions, along with subsequent compliance with applicable statutes and regulations and other regulatory authorities, require the expenditure of substantial time and financial resources.
FDA approval process
In the United States, biological and pharmaceutical products are subject to extensive regulation by the FDA. The Federal Food, Drug, and Cosmetic Act (FDCA), Public Health Service Act (PHSA), and other federal and state statutes and regulations govern, among other things, the research, development, testing, manufacture, quality control, packaging, storage, recordkeeping, approval, labeling, promotion, advertising and marketing, distribution, post-approval monitoring and reporting, sampling, tracking and tracing and import and export of biological and pharmaceutical products. Failure to comply with applicable U.S. requirements may subject a company to a variety of administrative or judicial sanctions, such as FDA refusal to approve pending new drug applications (NDAs) or biologics licensure applications (BLAs), withdrawal of an approval, imposition of a clinical hold, warning or untitled letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement of profits or civil or criminal investigations and penalties brought by the FDA and the Department of Justice (DOJ) or other governmental entities.
Biological or pharmaceutical product development for a new product or certain changes to an approved or licensed product in the United States typically involves preclinical laboratory and animal tests, the submission to the FDA of an investigational new drug application (IND) which must become effective before clinical testing may commence, and adequate and well-controlled clinical trials to establish the safety and effectiveness of a drug, or the safety, purity, or potency of a biological product, for each indication for which FDA approval is sought. Satisfaction of FDA pre-market approval and licensure requirements typically takes many years and the actual time required may vary substantially based upon the type, complexity and novelty of the product or disease.
Preclinical tests include laboratory evaluation of product chemistry, formulation and toxicity, as well as in vitro and animal trials to assess the characteristics and potential safety and efficacy of the product for initial testing in humans and to establish a rationale for therapeutic use. The conduct of the preclinical tests must comply with federal regulations and requirements, including Good Laboratory Practices (GLPs). The results of preclinical testing are submitted to the FDA as part of an IND along with other information, including information about product chemistry, manufacturing and controls, and a proposed clinical trial protocol. Long-term preclinical tests, such as animal tests of reproductive toxicity and carcinogenicity, may continue after the IND is submitted.
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An IND is an exemption from the FDCA that allows an unapproved new drug or biological product to be shipped in interstate commerce for use in an investigational clinical trial and a request for FDA authorization to administer an investigational drug or biological product to humans. Such authorization must be secured prior to interstate shipment and administration of any new drug or biological product that is not the subject of an approved NDA or BLA. In support of a request for an IND, a sponsor must submit a protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part of the IND. The sponsor may be a company seeking to develop the drug or biological product or, as in the case of an investigator-initiated trial, the sponsor may be an investigator who is conducting the trial. In addition, the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature and plans for clinical trials, among other things, are submitted to the FDA as part of an IND.
A 30-day waiting period after the submission of each IND is required prior to the commencement of clinical testing in humans. This waiting period is designed to allow the FDA to review the IND to determine whether human research subjects will be exposed to unreasonable health risks. At any time during this 30-day period, the FDA may raise concerns or questions about the conduct of the trials as outlined in the IND and impose a clinical hold. In this case, the IND sponsor and the FDA must resolve any outstanding concerns before clinical trials can begin. If the FDA has neither commented on nor questioned the IND within this 30-day period, the clinical trial proposed in the IND may begin.
Clinical trials involve the administration of the investigational new drug or biological product to healthy volunteers or patients under the supervision of a qualified investigator. Clinical trials must be conducted: (i) in compliance with federal regulations; (ii) in compliance with good clinical practice (GCP), which is an international standard meant to protect the rights and health of patients and to define the roles of clinical trial sponsors, administrators and monitors; as well as (iii) under protocols detailing the objectives of the trial, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. Each protocol involving testing on U.S. patients and subsequent protocol amendments must be submitted to the FDA as part of the IND.
The FDA may order the temporary or permanent discontinuation of a clinical trial at any time, as a clinical hold or partial clinical hold, or impose other sanctions, if it believes that the clinical trial either is not being conducted in accordance with FDA requirements or presents an unacceptable risk to the clinical trial patients. A clinical hold is an order issued by the FDA to the sponsor to delay a proposed clinical investigation or to suspend an ongoing investigation. A partial clinical hold is a delay or suspension of only part of the clinical work requested under the IND. For example, a specific protocol, or part of a protocol, is not allowed to proceed, while other protocols may do so. No more than 30 days after imposition of a clinical hold or partial clinical hold, the FDA will provide the sponsor a written explanation of the basis for the hold. Following issuance of a clinical hold or partial clinical hold, an investigation may only resume after the FDA has notified the sponsor that the investigation may proceed. The FDA will base that determination on information provided by the sponsor correcting the deficiencies previously cited or otherwise satisfying the FDA that the investigation can proceed.
A sponsor may choose, but is not required, to conduct a foreign clinical study under an IND. When a foreign clinical study is conducted under an IND, all IND requirements must be met unless waived. When the foreign clinical study is not conducted under an IND, the sponsor must ensure that the study complies with certain FDA regulatory requirements in order to use the study as support for an IND or application for marketing approval or licensure. Specifically, the FDA has promulgated regulations governing the acceptance of data from foreign clinical trials not conducted under an IND, establishing that such data from studies will be accepted as support for an IND or application for marketing approval if the study was conducted in accordance with GCP, including review and approval by an independent ethics committee and use of proper procedures for obtaining informed consent from subjects, and the FDA is able to validate the data from the study through an onsite inspection if the FDA deems such inspection necessary. The GCP requirements encompass both ethical and data integrity standards for clinical studies. The FDA’s regulations are intended to help ensure the protection of human subjects enrolled in non-IND foreign clinical trials, as well as the quality and integrity of the resulting data. They further help ensure that non-IND foreign studies are conducted in a manner comparable to that required for IND studies. If a marketing application is based solely on foreign clinical data, the FDA requires that the foreign data be applicable to the U.S. population and U.S. medical practice; the studies must have been performed by clinical investigators of recognized competence; and the FDA must be able to validate the data through an onsite inspection or other appropriate means, if the FDA deems such an inspection to be necessary.
The study protocol and informed consent information for patients in clinical trials must also be submitted to an institutional review board (IRB) representing each institution participating in the clinical trial. The IRB must review and approve the plan for any clinical trial before it commences at that institution, and the IRB must conduct continuing review and reapprove the study at least annually. The IRB must review and approve, among other things, the study protocol and informed consent information to be provided to study subjects. An IRB must operate in compliance with FDA regulations. An IRB may also require the clinical trial at the site to be halted, either temporarily or permanently, for failure to comply with the IRB’s requirements, or may impose other conditions.
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Additionally, some trials are overseen by an independent group of qualified experts organized by the trial sponsor, known as a data safety monitoring board or committee. This group provides authorization for whether or not a trial may move forward at designated check points based on access that only the group maintains to available data from the study. Suspension or termination of development during any phase of clinical trials can occur if it is determined that the participants or patients are being exposed to an unacceptable health risk. Other reasons for suspension or termination may be made by us based on evolving business objectives and/or competitive climate.
Information about certain clinical trials must be submitted within specific timeframes to the National Institutes of Health (NIH) for public dissemination on its ClinicalTrials.gov website. Sponsors are also obligated to disclose the results of their clinical trials after completion. Disclosure of the results of these trials can be delayed in certain circumstances for up to two years after the date of completion of the trial.
Clinical trials to support NDAs or BLAs for marketing approval or licensure are typically conducted in three sequential phases, but the phases may overlap. In Phase 1, the drug or biological product is introduced into healthy human subjects or in certain indications such as cancer, into patients with the target disease or condition. The drug is tested in Phase 1 to assess metabolism, pharmacokinetics, pharmacological actions, side effects associated with increasing doses, and, if possible, early evidence of effectiveness. Phase 2 usually involves trials in a limited patient population to determine the effectiveness or potency of the drug or biological product for a particular indication, dosage tolerance and optimum dosage, and to identify common adverse effects and safety risks. If a product candidate demonstrates evidence of effectiveness and an acceptable safety profile in Phase 2 evaluations, Phase 3 trials are conducted. In a Phase 3 trial, the drug or biological product is administered to an expanded patient population, generally at geographically dispersed clinical trial sites, in well-controlled clinical trials to generate enough data to statistically evaluate the efficacy or potency and purity, and safety, of the product for approval or licensure, to establish the overall risk benefit profile of the product, and to provide adequate information for the labeling of the product.
In most cases the FDA requires at least two adequate and well-controlled Phase 3 clinical trials to demonstrate the efficacy or potency of the drug. A single Phase 3 trial with other confirmatory evidence may be sufficient in rare instances, such as where the study is a large multicenter trial demonstrating internal consistency and a statistically very persuasive finding of a clinically meaningful effect on mortality, irreversible morbidity or prevention of a disease with a potentially serious outcome and confirmation of the result in a second trial would be practically or ethically impossible. Post-approval studies, or Phase 4 trials, are often required following initial approval and are intended to gain additional experience and data from treatment of patients in the intended therapeutic indication.
Progress reports detailing the results of the clinical trials conducted under an IND must be submitted at least annually to the FDA and more frequently if serious adverse effects occur. In addition, IND safety reports must be submitted to the FDA for any of the following: serious and unexpected suspected adverse reactions; findings from other studies or animal or in vitro testing that suggest a significant risk in humans exposed to the drug or biological product; and any clinically important increase in the case of a serious suspected adverse reaction over that listed in the protocol or investigator brochure. Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, or at all. Furthermore, the FDA or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects are being exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution, or an institution it represents, if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug or biological product has been associated with unexpected serious harm to patients. The FDA will typically inspect one or more clinical sites to assure compliance with GCP and the integrity of the clinical data submitted in an NDA or BLA.
Concurrent with clinical trials, companies often complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the drug or biological product as well as finalize a process for manufacturing the product in commercial quantities in accordance with current good manufacturing practices (cGMP) requirements. The manufacturing process must be capable of consistently producing quality batches of the drug or biological product candidate and, among other things, must develop methods for testing the identity, strength, quality and purity of the final drug. Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the drug or biological product candidate does not undergo unacceptable deterioration over its shelf life.
After completion of the required clinical testing, an NDA or BLA is prepared and submitted to the FDA. FDA approval of the NDA or BLA is required before marketing of the product may begin in the United States. The application must include the results of all preclinical, clinical and other testing and a compilation of data relating to the product’s pharmacology, chemistry, manufacture and controls. The cost of preparing and submitting an application is substantial. The submission of most NDAs or BLAs is additionally subject to a substantial application user fee, currently set for fiscal year 2023 at $3,242,026 for applications requiring clinical data, and $1,621,013 for applications not requiring clinical data, and the manufacturer and sponsor under an approved NDA or BLA are also subject to annual program fees, currently set for fiscal year 2023 at $393,933 for each prescription product. These fees are typically increased annually. Sponsors of applications for drugs granted Orphan Drug Designation are exempt from these user fees.
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The FDA has 60 days from its receipt of an NDA or BLA to determine whether the application will be accepted for filing based on the agency’s threshold determination that it is sufficiently complete to permit substantive review. The FDA may request additional information rather than accept an NDA or BLA for filing. In this event, the application must be resubmitted with the additional information. The resubmitted application is also subject to review before the FDA accepts it for filing. Once the submission is accepted for filing, the FDA begins an in-depth review. The FDA has agreed to certain performance goals in the review of NDAs and BLAs to encourage timeliness. The FDA intends to review applications for standard review product candidates within ten months of the 60-day filing date; and applications for priority review product candidates within six months. Priority review can be applied to drugs or biological products that the FDA determines treat a serious condition, and if approved, would offer a significant improvement in safety or effectiveness. The FDA determines, on a case-by-case basis, whether the proposed product represents a significant improvement when compared with other available therapies. Significant improvement may be illustrated by evidence of increased effectiveness in the treatment of a condition, elimination or substantial reduction of a treatment limiting product reaction, documented enhancement of patient compliance that may lead to improvement in serious outcomes, and evidence of safety and effectiveness in a new subpopulation. The review process for both standard and priority review may be extended by the FDA for three additional months to consider certain late-submitted information, or information intended to clarify information already provided in the submission.
The FDA is required to refer an application for a novel drug or biological product to an advisory committee for review, evaluation and a recommendation as to whether the application should be approved, or otherwise explain why such referral was not made. An advisory committee is typically a panel that includes clinicians and other experts. The FDA is not bound by the recommendation of an advisory committee, but it generally follows such recommendations.
Before approving an NDA or BLA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP. Additionally, the FDA will inspect the facility or the facilities at which the drug or biological product is manufactured. The FDA will not approve the application unless compliance with cGMPs is satisfactory and the application contains data that provide substantial evidence that the drug is safe and effective, or the biological product is safe, pure and potent, in the indication studied.
After the FDA evaluates the NDA or BLA and accompanying information and the manufacturing facilities, it issues either an approval letter or a complete response letter. An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications. A complete response letter generally outlines the deficiencies in the submission and may require substantial additional testing, or information, in order for the FDA to reconsider the application. If, or when, those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the NDA or BLA, the FDA will issue an approval letter. The FDA intends to review such resubmissions in two or six months depending on the type of information included. Even with submission of this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval or licensure.
An approval letter authorizes commercial marketing of the drug or biological product with specific prescribing information for specific indications. As a condition of approval or licensure, the FDA may require a risk evaluation and mitigation strategy (REMS) to help ensure that the benefits of the drug or biological product outweigh the potential risks. REMS can include medication guides, communication plans for healthcare professionals and elements to assure safe use (ETASU). ETASU can include, but are not limited to, special training or certification for prescribing or dispensing, dispensing only under certain circumstances, special monitoring and the use of patient registries. The requirement for a REMS can materially affect the potential market and profitability of the drug or biological product. Moreover, product approval may require substantial post-approval testing and surveillance to monitor the drug’s safety or efficacy. Once granted, product approvals may be withdrawn if compliance with regulatory standards is not maintained or problems are identified following initial marketing.
If the FDA approves or licenses a drug or biological product, it may limit the approved indications for use of the product; require that contraindications, warnings or precautions be included in the product labeling; require that post-approval studies, including Phase 4 clinical trials, be conducted to further assess the drug’s safety after approval or licensure; require testing and surveillance programs to monitor the product after commercialization; or impose other conditions, including distribution restrictions or other risk management mechanisms, including REMS, which can materially affect the potential market and profitability of the product. The FDA may prevent or limit further marketing of a product based on the results of post-market studies or surveillance programs. Changes to some of the conditions established in an approved application, including changes in indications, labeling, or manufacturing processes or facilities, require submission and FDA approval of a new NDA or BLA, or an NDA or BLA supplement before the change can be implemented. An NDA or BLA supplement for a new indication typically requires clinical data similar to that in the original application, and the FDA uses the same procedures and actions in reviewing NDA and BLA supplements as it does in reviewing NDAs and BLAs.
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Approval of medicines in the European Union (EU)
In the EU, companies can apply for marketing authorizations under the centralized procedure to the European Medicines Agency (EMA) or they can submit their application to the competent authorities in the European Economic Area (EEA) Member States via the decentralized procedure, the national procedure, or the mutual recognition procedure. The centralized procedure is mandatory for certain medicines, such as those produced by biotechnology, orphan medicinal products, advanced therapy medicinal products and those containing a new active substance indicated for the treatment of HIV, AIDS, cancer, neurodegenerative disorders, autoimmune and other immune dysfunctions, viral diseases, or diabetes. The centralized procedure remains optional for medicines containing a new active substance, or which are a significant therapeutic, scientific, or technical innovation or whose authorization would be in the interest of public health. Therefore the centralized procedure remains mandatory for the majority of biological medicinal products.
The marketing authorization granted under the centralized procedure by the EMA will be valid in all EEA Member States. The maximum timeframe for the evaluation of a marketing authorization application by the EMA is 210 days but can be extended should additional information be required by the EMA’s Committee for Medicinal Products for Human Use (CHMP). The European Commission makes the final decision to grant a marketing authorization, which is issued within 67 days of receipt of the EMA’s positive opinion. An accelerated assessment procedure of 150 days may be implemented for drugs considered to be of major public health interest.
Under the mutual recognition procedure, the national marketing authorization holder may submit an application to other EEA Member States. The Member States involved must decide whether to recognize the approval within 90 days of receiving the application. If a Member State does not recognize the marketing authorization, the disputed points are eventually referred to the European Commission, whose decision is binding.
Since the UK has left the EU, Great Britain is no longer covered by centralized marketing authorizations. This is not the case for Northern Ireland as under the Northern Ireland Protocol, centralized marketing authorizations continue to be recognized in Northern Ireland. Medicines with existing centralized marketing authorizations were automatically converted to Great Britain marketing authorizations on January 1, 2021. For a period of two years from January 1, 2021, the Medicines and Healthcare Products Regulatory Agency (MHRA), the UK medicines regulator, can rely on a decision taken by the European Commission on the approval of a new marketing authorization in the centralized procedure, in order to more quickly grant a new Great Britain marketing authorization. A separate application is, however, still required. The UK government reached a new agreement with the EU, the “Windsor Framework,” which aims to replace the Northern Ireland protocol. According to the Windsor Framework, medicinal products intended for the UK market including Northern Ireland will be authorized by the MHRA and will bear a “UK only” label. This means that medicinal products placed on the market in Northern Ireland will no longer need to be compliant with EU law. These new measures will be implemented beginning January 1, 2025. The MHRA has ceased to participate in the assessment of any centralized procedures since January 1, 2021. Since then, the MHRA has launched the Innovative Licensing and Access Pathway (ILAP), a new accelerated assessment procedure for marketing authorization applications that enables companies to enter the UK market faster. On January 1, 2024, the MHRA launched an International Recognition Procedure for Great Britain (England, Scotland and Wales) marketing authorization applications whereby the MHRA will, when considering such applications, recognize the approval of medicines by trusted reference regulators in Australia, Canada, Switzerland, Singapore, Japan, United States and EU following its own abbreviated assessment.
Clinical trials regulation and data sharing in the EU
In the EU, a Clinical Trial Application (CTA) must be submitted for each clinical trial to each Member State’s national competent authority (NCA) and ethics approval must be sought from an independent Ethics Committee. Once the CTA is approved in accordance with a particular Member State’s requirements, the clinical trial may proceed. Under the EU Clinical Trials Regulation 536/2014, which has been in effect since January 31, 2022 replacing the EU Clinical Trials Directive 2001/20/EC, suspected unexpected serious adverse reactions to the drug being trialed occurring during the clinical trial must be reported to the NCA and the Ethics Committee of the Member State where they occurred.
In the EU, Transparency Regulation No 1049/ 2001, EMA Policy 0043, EMA Policy 0070, as well as the Clinical Trials Regulation No 536/2014 set out the obligation for sponsors to make publicly available certain information stemming from clinical studies, whether proactively or in response to third party requests. Interested parties based in the EU may submit a request to the EMA to access information included in the marketing authorization application for authorized medicinal products. Commercially confidential information and protected personal data, however, may not be accessed.
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On May 3, 2022, the European Commission published a proposal for a regulation on the European Health Data Space (EHDS), which aims to further enable exchange of electronic health data both for primary use (among national EU healthcare systems for patient care) and secondary use (among private companies and regulators to enable scientific research). Whilst the regulation is currently under discussions among the EU legislators, the text is expected to be finalized by the end of 2023 and for the EHDS to become reality in 2025. This will impose new obligations, but also create opportunities, for entities engaged in health-related research to share and access health data on a scale much larger than what is foreseen under current applicable transparency provisions.
Regulatory framework in the UK following Brexit
The UK officially left the EU on January 31, 2020. A transition period during which EU law remained applicable to the UK began on February 1, 2020 and ended on December 31, 2020. The EU regulatory framework for medicinal products in place before the end of the transition period has been preserved in UK domestic legislation as “retained EU law” but the UK may diverge from EU law in the future should it wish to do so. Pursuant to the Northern Ireland Protocol, the EU pharmaceutical legal framework acquis continues to apply in Northern Ireland and medicines can only be placed in the Northern Ireland market if they comply with EU law. The UK government reached a new agreement with the EU, the “Windsor Framework,” which aims to replace the Northern Ireland protocol. According to the Windsor Framework, medicinal products intended for the UK market including Northern Ireland will be authorized by the MHRA and will bear a “UK only” label. This means that medicinal products placed on the market in Northern Ireland will no longer need to be compliant with EU law. These new measures will be implemented beginning January 1, 2025.
Expedited approval pathways
The FDA is authorized to designate certain products for expedited review if they are intended to address an unmet medical need in the treatment of a serious or life-threatening disease or condition. These programs are referred to as Fast Track designation, Breakthrough Therapy designation and Priority Review designation. In addition, Accelerated Approval offers the potential for approval based on a surrogate or intermediate clinical endpoint. In May 2014, the FDA published a final Guidance for Industry titled “Expedited Programs for Serious Conditions Drugs and Biologics,” which provides guidance on the FDA programs that are intended to facilitate and expedite development and review of new drug or biological product candidates as well as threshold criteria generally applicable to concluding that a product candidate is a candidate for these expedited development and review programs.
The FDA may designate a product for Fast Track review if it is intended, whether alone or in combination with one or more other products, for the treatment of a serious or life threatening disease or condition, and nonclinical or clinical data demonstrate the potential to address unmet medical needs for such a disease or condition. For Fast Track products, sponsors may have greater interactions with the FDA and the FDA may initiate review of sections of a Fast Track product’s application before the application is complete. This rolling review may be available if the FDA determines, after preliminary evaluation of clinical data submitted by the sponsor, that a Fast Track product may be effective. The sponsor must also provide, and the FDA must approve, a schedule for the submission of the remaining information and the sponsor must pay applicable user fees. However, the FDA’s review clock for a Fast Track application does not begin until the last section of the application is submitted. In addition, the Fast Track designation may be withdrawn by the FDA if the FDA believes that the designation is no longer supported by data emerging in the clinical trial process.
A product may be designated as a Breakthrough Therapy if it is intended, either alone or in combination with one or more other products, to treat a serious or life threatening disease or condition and preliminary clinical evidence indicates that the product may demonstrate substantial improvement over existing available therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. The FDA may take certain actions with respect to Breakthrough Therapies, including holding meetings with the sponsor throughout the development process; providing timely advice to the product sponsor regarding development and approval; involving more senior staff in the review process; assigning a cross disciplinary project lead for the review team; rolling review; and taking other steps to design the clinical trials in an efficient manner.
Accelerated Approval Pathway
The FDA may grant Accelerated Approval to a drug or biological product for a serious or life threatening condition that provides meaningful therapeutic advantage to patients over available treatments based upon a determination that the drug or biological product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit. The FDA may also grant Accelerated Approval for such drug or biological product for such a condition when the product has an effect on an intermediate clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality (IMM) and that is reasonably likely to predict an effect on IMM or other clinical benefit, taking into account the severity, rarity or prevalence of the condition and the availability or lack of alternative treatments. Drugs and biological products granted Accelerated Approval must meet the same statutory standards for safety and effectiveness as those granted traditional approval.
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For the purposes of Accelerated Approval, a surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit but is not itself a measure of clinical benefit. Surrogate endpoints can often be measured more easily or more rapidly than clinical endpoints. An intermediate clinical endpoint is a measurement of a therapeutic effect that is considered reasonably likely to predict the clinical benefit of a drug or biological product, such as an effect on IMM. The FDA has limited experience with Accelerated Approvals based on intermediate clinical endpoints, but has indicated that such endpoints generally may support Accelerated Approval where the therapeutic effect measured by the endpoint is not itself a clinical benefit and basis for traditional approval, if there is a basis for concluding that the therapeutic effect is reasonably likely to predict the ultimate clinical benefit of a drug or biological product.
The Accelerated Approval Pathway is most often used in settings in which the course of a disease is long and an extended period of time is required to measure the intended clinical benefit of a drug or biological product, even if the effect on the surrogate or intermediate clinical endpoint occurs rapidly. Thus, Accelerated Approval has been used extensively in the development and approval of drugs and biological products for treatment of a variety of cancers in which the goal of therapy is generally to improve survival or decrease morbidity and the duration of the typical disease course requires lengthy and sometimes large trials to demonstrate a clinical or survival benefit.
The Accelerated Approval Pathway is contingent on a sponsor’s agreement to conduct, in a diligent manner, additional post-approval confirmatory studies to verify and describe the product’s clinical benefit. As a result, a drug or biological product candidate approved on this basis is subject to rigorous post-marketing compliance requirements, including the completion of Phase 4 or post-approval clinical trials to confirm the effect on the clinical endpoint. Failure to conduct required post-approval studies, or confirm a clinical benefit during post-marketing studies, would allow the FDA to withdraw the drug or biological product from the market on an expedited basis. In addition, all promotional materials for drugs and biological products approved under accelerated regulations are subject to prior review by the FDA.
The EU and UK operate accelerated evaluation and assessment schemes, which include, at EU level, PRIME (PRIority MEdicines) scheme and, at UK level, the Early Access to Medicines Scheme (EAMS), which may be granted in exceptional cases, often when there is unmet medical need for a life-threatening or serious debilitating condition and existing data show a positive benefit/risk balance that means the medicinal product is of a major public health interest. The CHMP of the EMA or the MHRA (or other national competent authority) will make this determination on a case-by-case basis and subject to meeting eligibility criteria. Accelerated assessment takes place within 150 days. Other regulatory facilitations for these pathways include additional scientific advice at key development milestones and frequent guidance and discussions throughout the approval process. In the UK, the MHRA has launched the Innovative Licensing and Access Pathway (ILAP), a new accelerated assessment procedure for marketing authorization applications that enables companies to enter the UK market faster, available since January 1, 2021. On January 1, 2024, the MHRA launched an International Recognition Procedure for Great Britain (England, Scotland and Wales) marketing authorization applications whereby the MHRA will, when considering such applications, recognize the approval of medicines by trusted reference regulators in Australia, Canada, Switzerland, Singapore, Japan, United States and EU following its own abbreviated assessment.
Orphan drugs
Under the Orphan Drug Act, the FDA may grant Orphan Drug Designation to drugs or biological products intended to treat a rare disease or condition—generally a disease or condition that affects fewer than 200,000 individuals in the United States. Orphan Drug Designation must be requested before submitting an NDA. After the FDA grants Orphan Drug Designation, the name of the drug or biological product and its potential orphan-designated use are disclosed publicly by the FDA. Orphan Drug Designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.
The first NDA or BLA applicant to receive FDA approval for a particular drug or biological product to treat a particular disease with FDA Orphan Drug Designation is entitled to a seven-year exclusive marketing period in the United States for that product, for that indication. During the seven-year exclusivity period, the FDA may not approve any other applications to market the same drug or biological product for the same disease, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity. Orphan drug exclusivity does not prevent the FDA from approving a different drug or biological product for the same disease or condition, or the same drug or biological product for a different disease or condition. Among the other benefits of Orphan Drug Designation are tax credits for certain research and an exemption from the NDA or BLA application user fee.
A designated orphan drug or biological product may not receive orphan drug exclusivity if it is licensed for a use that is broader than the indication for which it received orphan designation. In addition, exclusive marketing rights in the United States may be rescinded if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.
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In the EU and UK, under Regulation (EC) 141/2000 and the UK Human Medicines Regulations 2012 SI 2012 No. 1916 (as amended), respectively, medicinal products may be granted an orphan drug designation if they are used to treat or prevent life-threatening or chronically debilitating conditions that affect no more than five in 10,000 people in the EU/UK and for which there is no satisfactory method of diagnosis, prevention or treatment when the application is made, or when the medicinal product is of significant benefit to those affected by the condition. In addition, orphan drug designation can be granted to drugs used to treat or prevent life-threatening or chronically debilitating conditions which, for economic reasons, would be unlikely to be developed without incentives.
The application for orphan designation must be submitted to and approved by the EMA in respect of the EU or to the MHRA for Great Britain before an application is made for marketing authorization for the product. Medicinal products which benefit from orphan status, which they successfully maintain post-grant of the marketing authorization, can benefit from up to ten years of market exclusivity in respect of the approved indication. This prevents regulatory authorities in the EU or Great Britain, as the case may be, from granting marketing authorizations for similar medicinal products for the same therapeutic indication, unless another applicant can show that the similar medicinal product in question is safer, more effective or clinically superior to the orphan-designated product or if the marketing authorization holder consents to the second orphan medicinal product application, or where the marketing authorization holder cannot supply the needs of the market.
The ten-year market exclusivity may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for orphan designation, for example, if the product is sufficiently profitable not to justify the maintenance of market exclusivity. Conversely, the 10-year exclusivity period can be further extended by two years, when pediatric studies are conducted in accordance with an agreed pediatric investigation plan (PIP) and in completion of all the legal requirements.
It is noted that the general pharmaceutical legislative framework, as well as the framework applicable to orphan and pediatric medicinal products in the EU, is under review. On April 26, 2023, the European Commission adopted a proposal for a new Regulation set to replace Regulation (EC) No 726/2004 and a new Directive to replace Directive 2001/83 on the Community Code relating to medicinal products for human use. If made into law, this proposal will revise the existing general pharmaceutical legislation and may reduce applicable regulatory exclusivities which will significantly affect all medicinal products that will be authorized after the legislative changes have taken effect.
Post-approval requirements
Drugs and biological products manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to recordkeeping, periodic reporting, product sampling and distribution, advertising and promotion and reporting of adverse experiences with the product. After approval, most changes to the approved product, such as adding new indications or other labeling claims, are subject to prior FDA review, through the applicant’s submission of a supplemental application, and approval. There also are continuing, annual user fee requirements for any marketed products and the establishments at which such products are manufactured, as well as new application fees for supplemental applications with clinical data.
In addition, drug and biological product manufacturers and other entities involved in the manufacture and distribution of approved products are required to register their establishments with the FDA and state agencies, and are subject to periodic unannounced inspections by the FDA and these state agencies for compliance with cGMP requirements. Changes to the manufacturing process are strictly regulated and often require prior FDA approval before being implemented. FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting and documentation requirements upon the sponsor and any third-party manufacturers that the sponsor may decide to use. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain cGMP compliance.
Once an approval is granted, the FDA may withdraw the approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical trials to assess new safety risks; or imposition of distribution or other restrictions under a REMS program. Other potential consequences include, among other things:
•Restrictions on the marketing or manufacturing of the product, including total or partial suspension of production, complete withdrawal of the product from the market or product recalls;
•Fines, untitled or warning letters or holds on post-approval clinical trials;
•Refusal of the FDA to approve pending NDAs, BLAs or supplements to approved NDAs or BLAs, or suspension or revocation of product license approvals;
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•Product seizure or detention, or refusal to permit the import or export of products; or
•Injunctions or the imposition of civil or criminal penalties.
The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market. Drugs and biological products may be promoted only for the approved indications and consistently with the provisions of the approved labeling. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off label uses, and a company that is found to have improperly promoted off label uses may be subject to significant liability.
In addition, the distribution of prescription drug and biological products is subject to the Prescription Drug Marketing Act (PDMA) which regulates the distribution of drugs, biological products and drug or biological product samples at the federal level, and sets minimum standards for the registration and regulation of drug and biological product distributors by the states. Both the PDMA and state laws limit the distribution of prescription drug and biological product samples and impose requirements to ensure accountability in distribution.
Many jurisdictions, including the EU and the UK, require each marketing authorization holder, national competent authority and the EMA to operate a pharmacovigilance system to ensure that the safety of all medicines is monitored throughout the lifetime of a medicinal product. The overall EU pharmacovigilance system operates through cooperation between the EU Member States, EMA and the European Commission. Applicable obligations extend to all activities consisting of procuring, holding, supplying or exporting medicinal products to the public and may therefore be incumbent upon importers, distributors and other economic operators in the supply chain.
Abbreviated new drug applications for generic drugs
In 1984, with passage of the Hatch-Waxman Amendments to the FDCA, Congress established an abbreviated regulatory scheme allowing the FDA to approve generic drugs that are shown to contain the same active ingredients as, and to be bioequivalent to, drugs previously approved by the FDA pursuant to NDAs. To obtain approval of a generic drug, an applicant must submit an abbreviated new drug application (ANDA) to the agency. An ANDA is a comprehensive submission that contains, among other things, data and information pertaining to the active pharmaceutical ingredient, bioequivalence, drug product formulation, specifications and stability of the generic drug, as well as analytical methods, manufacturing process validation data and quality control procedures. ANDAs are “abbreviated” because they generally do not include preclinical and clinical data to demonstrate safety and effectiveness. Instead, in support of such applications, a generic manufacturer may rely on the preclinical and clinical testing previously conducted for a drug product previously approved under an NDA, known as the reference listed drug (RLD).
Specifically, in order for an ANDA to be approved, the FDA must find that the generic version is identical to the RLD with respect to the active ingredients, the route of administration, the dosage form and the strength of the drug. An applicant may submit an ANDA suitability petition to request the FDA’s prior permission to submit an abbreviated application for a drug that differs from the RLD in route of administration, dosage form, or strength, or for a drug that has one different active ingredient in a fixed combination drug product (i.e., a drug product with multiple active ingredients). At the same time, the FDA must also determine that the generic drug is “bioequivalent” to the innovator drug. Under the statute, a generic drug is bioequivalent to a RLD if “the rate and extent of absorption of the drug do not show a significant difference from the rate and extent of absorption of the listed drug.” Upon approval of an ANDA, the FDA indicates whether the generic product is “therapeutically equivalent” to the RLD in its publication “Approved Drug Products with Therapeutic Equivalence Evaluations,” also referred to as the “Orange Book.” Physicians and pharmacists may consider a therapeutic equivalent generic drug to be fully substitutable for the RLD. In addition, by operation of certain state laws and numerous health insurance programs, the FDA’s designation of therapeutic equivalence often results in substitution of the generic drug without the knowledge or consent of either the prescribing physician or patient.
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Abridged marketing authorization applications for generic and biosimilar drugs in the EU and the UK
Generic and hybrid medicinal products of reference medicinal products authorized via the centralized procedure have automatic access to the centralized procedure. Generic and hybrid products can refer to the complete dossier (i.e., the quality, preclinical and clinical data) of the reference medicinal product in their marketing authorization application, by demonstration of bioequivalence, usually through the submission of the appropriate bioavailability studies after the period of regulatory data protection (also called “data exclusivity”) has expired, namely eight years after the grant of the marketing authorization of the reference medicinal product. Applicants will be able to cross-refer to the dossier of the reference medicinal product, as long as the data protection period has expired. This abridged application procedure avoids the requirement to repeat trials and allows generic applicants a faster entry to the market. If a biosimilar of a reference biological product does not meet the conditions in the definition of generic medicinal products, owing to, in particular, differences relating to raw materials or differences in manufacturing processes of the biological medicinal product and the reference biological medicinal product, the results of appropriate preclinical studies or clinical trials relating to these conditions must be provided. The type and quantity of supplementary data to be provided must comply with the relevant criteria stated in Annex I of Directive 2001/83 as amended and the related detailed guidelines. The results of other tests and trials from the reference medicinal product’s dossier do not need to be provided.
505(b)(2) New Drug Applications
As an alternative path to FDA approval for modifications to formulations or uses of products previously approved by the FDA pursuant to an NDA, an applicant may submit an NDA under Section 505(b)(2) of the FDCA. Section 505(b)(2) was enacted as part of the Hatch-Waxman Amendments and permits the filing of an NDA where at least some of the information required for approval comes from studies not conducted by, or for, the applicant, and for which the applicant has not obtained a right of reference. If the 505(b)(2) applicant can establish that reliance on the FDA’s previous findings of safety and effectiveness is scientifically and legally appropriate, it may eliminate the need to conduct certain preclinical studies or clinical trials of the new product. The FDA may also require companies to perform additional bridging studies or measurements, including clinical trials, to support the change from the previously approved reference drug. The FDA may then approve the new drug candidate for all, or some, of the label indications for which the reference drug has been approved, as well as for any new indication sought by the 505(b)(2) applicant.
Hatch-Waxman patent certification and the 30-month stay
In seeking approval for a drug through an NDA, applicants are required to list with the FDA each patent whose claims cover the applicant’s product. Upon approval of a drug, each of the patents listed in the application for the drug is then published in the FDA’s Orange Book.
When an ANDA applicant files its application with the FDA, the applicant is required to certify to the FDA concerning any patents listed for the reference product in the Orange Book, except for patents covering methods of use for which the ANDA applicant is not seeking approval. To the extent that the Section 505(b)(2) applicant is relying on studies conducted for an already approved product, the applicant is required to certify to the FDA concerning any patents listed for the approved product in the Orange Book to the same extent that would be required of an ANDA applicant. Specifically, the applicant must certify that (i) the required patent information has not been filed; (ii) the listed patent has expired; (iii) the listed patent has not expired but will expire on a particular date and approval is sought after patent expiration; or (iv) the listed patent is invalid or will not be infringed by the new product. The ANDA applicant may also elect to submit a statement certifying that its proposed ANDA label does not contain (or carve out) any language regarding the patented method-of-use rather than certify to a listed method-of-use patent, known as a Section VIII statement. If the applicant does not challenge the listed patents, the ANDA application will not be approved until all the listed patents claiming the referenced product have expired. A certification that the new product will not infringe the already approved product’s listed patents, or that such patents are invalid, is called a Paragraph IV certification. If the ANDA applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification to the NDA and patent holders once the ANDA has been accepted for filing by the FDA. The NDA and patent holders may then initiate a patent infringement lawsuit in response to the notice of the Paragraph IV certification. The filing of a patent infringement lawsuit within 45 days of the receipt of a Paragraph IV certification automatically prevents the FDA from approving the ANDA until the earlier of 30 months, expiration of the patent, settlement of the lawsuit or a decision in the infringement case that is favorable to the ANDA applicant.
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Exclusivity under the Hatch-Waxman Amendments
In addition, under the Hatch-Waxman Amendments, the FDA may not approve an ANDA or 505(b)(2) NDA referencing a particular drug until any applicable period of non-patent exclusivity for the RLD has expired. The FDCA provides a period of five years of non-patent data exclusivity for a new drug containing a new chemical entity (NCE). For the purposes of this provision, an NCE is a drug that contains no active moiety that has previously been approved by the FDA in any other NDA. An active moiety is the molecule or ion responsible for the physiological or pharmacological action of the drug substance. In cases where such NCE exclusivity has been granted, an ANDA or 505(b)(2) NDA may not be submitted to the FDA until the expiration of five years from the date the NDA is approved, unless the submission is accompanied by a Paragraph IV certification, in which case the applicant may submit its application four years following the original product approval.
The FDCA also provides for a period of three years of exclusivity if the NDA includes reports of one or more new clinical investigations, other than bioavailability or bioequivalence studies, that were conducted by or for the applicant and are essential to the approval of the application. This three-year exclusivity period often protects changes to a previously approved drug product, such as a new dosage form, route of administration, combination or indication. Three-year exclusivity would be available for a drug product that contains a previously approved active moiety, provided the statutory requirement for a new clinical investigation is satisfied. Unlike five-year NCE exclusivity, an award of three-year exclusivity does not block the FDA from accepting ANDAs or 505(b)(2) NDAs seeking approval for generic versions of the drug as of the date of approval of the original drug product; it does, however, block the FDA from approving ANDAs or 505(b)(2) NDAs during the period of exclusivity. The FDA typically makes decisions about awards of data exclusivity shortly before a product is approved.
Biosimilars and reference product exclusivity
The Biologics Price Competition and Innovation Act of 2009 (BPCIA) created an abbreviated approval pathway for biological product candidates shown to be highly similar, or “biosimilar,” to or interchangeable with an FDA licensed reference biological product. Biosimilarity, which requires that a product is highly similar to the reference product notwithstanding minor differences in clinically inactive components, and that there be no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency, can generally be shown through analytical studies, animal studies, and a clinical study or studies. Interchangeability requires that a product is biosimilar to the reference product and the product must demonstrate that it can be expected to produce the same clinical results as the reference product in any given patient and, for products that are administered multiple times to an individual, the interchangeable biosimilar and the reference biological product may be alternated or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biological product. A product shown to be biosimilar or interchangeable with an FDA-approved reference biological product may rely in part on the FDA’s previous determination of safety and effectiveness for the reference product for approval, which can potentially reduce the cost and time required to obtain approval to market the product. Complexities associated with the larger, and often more complex, structures of biological products, as well as the processes by which such products are manufactured, pose significant hurdles and have slowed implementation of the BPCIA by the FDA.
Under the BPCIA, an application for a biosimilar product may not be submitted to the FDA until four years following the date that the reference product was first licensed by the FDA. In addition, the approval of a biosimilar product may not be made effective by the FDA until 12 years from the date on which the reference product was first licensed. During this 12-year period of reference product exclusivity, another company may obtain FDA licensure and market a competing version of the reference product if the FDA approves a full BLA for the competing product containing that applicant’s own preclinical data and data from adequate and well-controlled clinical trials to demonstrate the safety, purity and potency of its product. The BPCIA also created certain exclusivity periods for biosimilars approved as interchangeable products. At this juncture, it is unclear whether products deemed “interchangeable” by the FDA will, in fact, be readily substituted by pharmacies, which are governed by state pharmacy law.
The BPCIA is complex and continues to be interpreted and implemented by the FDA. In addition, there has been discussion of whether Congress should reduce the 12-year reference product exclusivity period. Other aspects of the BPCIA, some of which may impact the BPCIA exclusivity provisions, have also been the subject of recent litigation. As a result, the ultimate implementation of the BPCIA is subject to significant uncertainty.
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In the EU and the UK, an abridged procedure is available for the regulatory approval of biosimilars, on the basis of comparability studies to the reference biological medicine to substantiate the safety and efficacy profile of the biosimilar product. This comparability with the reference biological medicinal product is only available after the period of regulatory data protection has expired namely eight years after the grant of the marketing authorization of the reference biological medicinal product has expired. Recently, the MHRA and the EMA have stated that comparative data may not be required across all therapeutic indications and may be extrapolated to other indications already approved for the reference medicinal product. The interchangeability of biosimilars remains subject to national determination, on a case-by-case basis; however a recent scientific recommendation by the EMA may lead to a default assumption of interchangeability across all biosimilars in the EU and in the UK.
Pediatric studies and exclusivity
Under the Pediatric Research Equity Act of 2003, an NDA, BLA or supplement thereto must contain data that are adequate to assess the safety and effectiveness of the drug or biological product for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective. With enactment of the Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA), sponsors must also submit pediatric study plans prior to the assessment data.
Those plans must contain an outline of the proposed pediatric study or studies the applicant plans to conduct, including study objectives and design, any deferral or waiver requests, and other information required by regulation. The applicant, the FDA and the FDA’s internal review committee must then review the information submitted, consult with each other and agree upon a final plan. The FDA or the applicant may request an amendment to the plan at any time.
The FDA may, on its own initiative or at the request of the applicant, grant deferrals for submission of some or all pediatric data until after approval of the product for use in adults, or full or partial waivers from the pediatric data requirements. Additional requirements and procedures relating to deferral requests and requests for extension of deferrals are contained in the FDASIA. Unless otherwise required by regulation, the pediatric data requirements do not apply to products with Orphan Drug Designation.
Pediatric exclusivity is another type of non-patent marketing exclusivity in the United States and, if granted, provides for the attachment of an additional six months of marketing protection to the term of any existing regulatory exclusivity, including the non-patent and orphan exclusivity. This six-month exclusivity may be granted if an NDA sponsor submits pediatric data that fairly respond to a written request from the FDA for such data. The data do not need to show the product to be effective in the pediatric population studied; rather, if the clinical trial is deemed to fairly respond to the FDA’s request, the additional protection is granted. If reports of requested pediatric studies are submitted to and accepted by the FDA within the statutory time limits, whatever statutory or regulatory periods of exclusivity or patent protection cover the product are extended by six months. This is not a patent term extension, but it effectively extends the regulatory period during which the FDA cannot approve another application.
Under the European Pediatric Regulation (Regulation (EC) No 1901/2006), which has also been reflected in and retained by UK law, applicants must submit to the national competent authority or the EMA data from pediatric studies in compliance with an agreed PIP for the validation or acceptance of a marketing authorization application, unless the medicine is exempt because of a deferral or waiver. The conduct of the pediatric studies in accordance with the agreed PIP will result in the grant of a reward (period of protection) which will depend on the type of product (i.e., orphan medicinal product will benefit from an extension of the orphan exclusivity by two years, bringing it to 12 years of marketing exclusivity; or an extension of the supplementary protection certificate by six months).
Patent term extension
After NDA approval, owners of relevant drug or biological product patents may apply for up to a five-year patent extension, which permits patent term restoration as compensation for the patent term lost during the FDA regulatory process. The allowable patent term extension is typically calculated as one-half the time between the effective date of an IND application and the submission date of a NDA or BLA, plus the time between submission date and the approval date of the NDA or BLA, up to a maximum of five years. The time can be shortened if the FDA determines that the applicant did not pursue approval with due diligence. The total patent term after the extension may not exceed 14 years from the date of product approval. Only one patent applicable to an approved drug or biological product is eligible for extension and only those claims covering the approved drug or biological product, a method for using it or a method for manufacturing it may be extended and the application for the extension must be submitted prior to the expiration of the patent in question. However, we may not be granted an extension because of, for example, failing to exercise due diligence during the testing phase or regulatory review process, failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements.
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In the EU and the UK, a patent may be extended by up to a maximum of five years and the protection conferred by the certificate shall extend only to the product covered by the authorization to place the corresponding medicinal product on the market (in the EU and UK) and for any use of the product as a medicinal product that has been authorized before the expiry of the certificate. The aim is to compensate for the erosion of patent term between the filing of a patent and the grant of an MA for a medicinal product incorporating the relevant invention. The term of a supplementary protection certification may be extended by a further six months if the pediatric studies have been conducted in accordance with an agreed PIP within the applicable timeframe.
Foreign regulation
In addition to regulations in the United States, we will be subject to a variety of foreign regulations governing clinical trials and commercial sales and distribution of our drug candidates to the extent we choose to sell any products outside of the United States. Whether or not we obtain FDA approval for a product, we must obtain approval of a product by regulatory authorities of foreign countries before we can commence clinical trials or marketing of the product in those countries. The approval process varies from country to country and the time may be longer or shorter than that required for FDA approval. The requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from country to country. As in the United States, post-approval regulatory requirements, such as those regarding product manufacture, marketing or distribution would apply to any product that is approved outside the United States.
We will also be subject to certain ex-U.S. privacy laws in connection with our clinical trial activities outside the United States such as the EU General Data Protection Regulation (EU GDPR), non-compliance with which could result in administrative fines of up to the greater of €20.0 million or 4% of global annual revenues. The EU GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies and obtain compensation for damages resulting from violations of the EU GDPR.
Reimbursement of medicines in Europe
In the EU, pricing and reimbursement methods can differ in each Member State. Some Member States and the UK may require that health technology assessments (HTA) be completed for the product to be recommended for funding under the NHS. The outcome of HTAs is decided on a national basis and some Member States may decide not to reimburse the use of medicines or may reduce the rate of reimbursement. In December 2021, the EU adopted a new Regulation on Health Technology Assessment which allows Member States to carry out joint clinical assessments and operate joint clinical consultations. It is expected that the new Regulation will come into effect in 2025. In the UK, NICE is the body in England and Wales, which conducts HTAs and issues guidance on whether a product is considered to be “cost-effective” and therefore recommended for use and reimbursement under the national health service. This means that if a positive recommendation has been obtained, then the medicinal product will be widely available to patients in England and Wales. For avoidance of doubt, Scotland and Northern Ireland have their own HTA bodies which will conduct their own assessment.
Other healthcare laws
Although we do not currently have any products on the market, in addition to FDA restrictions on marketing of pharmaceutical and biological products, we are also subject to healthcare statutory and regulatory requirements and enforcement by the U.S. federal and state governments. Even though we are not in a position to make patient referrals and do not bill Medicare, Medicaid or other government or commercial third-party payers, our relationships with healthcare providers, physicians and third-party payors will subject us to healthcare statutory and regulatory requirements and enforcement by federal and state governments. These laws include anti-kickback statutes, false claims statutes and other healthcare laws and regulations.
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The federal Anti-Kickback Statute prohibits, among other things, knowingly and willfully offering, paying, soliciting or receiving any remuneration, directly or indirectly, in cash or in kind, to induce, or in return for, purchasing, leasing, ordering or arranging for, referring, or recommending the purchase, lease or order of any healthcare item or service that may be reimbursable, in whole or in part, under Medicare, Medicaid, or other federal health care program. The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act (collectively, the ACA) amended the intent element of the federal Anti-Kickback Statute to clarify that a person or entity need not have actual knowledge of the statute or specific intent to violate it in order to commit a violation. Among others, this statute applies to arrangements between pharmaceutical and biological product manufacturers on the one hand and prescribers, pharmacies, purchasers and formulary managers on the other, including, for example, consulting/speaking arrangements, discount and rebate offers, grants, charitable contributions and patient support offerings. A conviction for violation of the federal Anti-Kickback Statute can result in criminal fines and/or imprisonment and requires mandatory exclusion from participation in federal health care programs. Exclusion from the federal healthcare programs may also be imposed if the government determines that an entity has committed acts that are prohibited by the federal Anti-Kickback Statute. Although there are a number of statutory exceptions and regulatory safe harbors protecting certain common activities from prosecution or other regulatory sanctions under the law, the exceptions and safe harbors are drawn narrowly and practices that involve remuneration intended to induce prescribing, purchases or recommendations may be subject to scrutiny if they do not qualify for an exception or safe harbor.
The federal civil False Claims Act prohibits, among other things, any person or entity from knowingly presenting, or causing to be presented, a false claim for payment to the federal government, or knowingly making, or causing to be made, a false record or statement material to a false claim. The False Claims Act covers claims made to programs where the federal government reimburses (directly or indirectly) individuals and entities, such as under the Medicare and Medicaid programs, as well as programs where the federal government is a direct purchaser, such as when it purchases off of the Federal Supply Schedule. The law also prohibits avoiding, decreasing or concealing an obligation to pay money to the federal government. The government can bring claims directly or through a civil whistleblower or qui tam action, and potential liability includes mandatory treble damages and significant per claim penalties currently set at $13,946 up to $27,894 per false claim or statement for penalties assessed after January 15, 2024. Numerous pharmaceutical and other healthcare companies have been prosecuted under these laws for allegedly inflating drug or biological product prices they report to pricing services, which in turn were used by the government to set Medicare and Medicaid reimbursement rates, and for allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product. In addition, certain marketing practices, including off-label promotion, may also violate false claims laws. Additionally, the ACA amended the federal Anti-Kickback Statute such that a violation of that statute can serve as a basis for liability under the federal False Claims Act. Most states also have statutes or regulations similar to the federal Anti-Kickback Statute and False Claims Act, which apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply to commercially reimbursed items or services or regardless of whether reimbursement from a federal or state healthcare program is available for the item or service. There is also the Federal Criminal False Claims Act, which is similar to the Federal Civil False Claims Act and imposes criminal liability on those that make or present a false, fictitious or fraudulent claim to the federal government.
Other federal statutes pertaining to healthcare fraud and abuse include the civil monetary penalties statute, which prohibits, among other things, the offer or payment of remuneration to a Medicaid or Medicare beneficiary that the offeror or payor knows or should know is likely to influence the beneficiary to order or receive a reimbursable item or service from a particular provider, practitioner or supplier (although pharmaceutical and biological product manufacturers are not considered providers, practitioners or suppliers for purposes of this law), and contracting with an individual or entity that the person knows or should know is excluded from participation in a federal health care program. In addition, federal criminal statutes created by the Health Insurance Portability and Accountability Act of 1996 (HIPAA) prohibit, among other things, knowingly and willfully executing or attempting to execute a scheme to defraud any healthcare benefit program or obtain by means of false or fraudulent pretenses, representations or promises any money or property owned by or under the control of any healthcare benefit program in connection with the delivery of or payment for healthcare benefits, items or services.
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In addition, HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act (HITECH) and their respective implementing regulations, including the Final Omnibus Rule published on January 25, 2013, imposes obligations on certain healthcare providers, health plans and healthcare clearinghouses, known as covered entities, as well as their business associates that perform certain services involving the storage, use or disclosure of individually identifiable health information, including mandatory contractual terms, requirements to facilitate certain patient rights, requirements to safeguard the privacy, security, and transmission of individually identifiable health information, and requirements to provide notice to affected individuals and regulatory authorities of certain breaches of security of individually identifiable health information. HITECH increased the civil and criminal penalties that may be imposed against covered entities, business associates and possibly other persons, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions. On December 10, 2020, the Office of Civil Rights within the Department of Health and Human Services (HHS) issued proposed revisions to the HIPAA Privacy Rule aimed at reducing regulatory burdens that may exist in discouraging coordination of care and patient access to their health information, among other changes. While a final rule has not yet been issued, if adopted, these proposed changes may require us to update our policies and procedures to comply with the new requirements. In addition, many state laws govern the privacy and security of health information and other personal information in certain circumstances (such as the California Consumer Privacy Act of 2018, the Virginia Consumer Data Protection Act, and similar state privacy laws in Colorado, Connecticut and Utah, along with health privacy focused laws such as the Washington My Health My Data Act), and these state laws may differ from each other in significant ways and may not have the same effect. These laws are rapidly evolving and may impose additional regulatory compliance burden and legal risks on our operations.
Further, pursuant to the ACA, the Centers for Medicare & Medicaid Services (CMS) has promulgated regulations to implement what is commonly known as the federal Physician Payment Sunshine Act, which, among other things, requires manufacturers of prescription drugs and biological products, among others, to collect and report information on certain payments or transfers of value they make to U.S.-licensed physicians, teaching hospitals, physician assistants, nurse practitioners or clinical nurse specialists, certified registered nurse anesthetists, anesthesiologist assistants and certified nurse-midwives, as well as investment interests in the manufacturer held by physicians and their immediate family members. The reports must be submitted on an annual basis, and the reported data is made available in searchable form on a public website. Failure to submit required information may result in civil monetary penalties.
In addition, several states require prescription drug and biological product companies to report certain expenses relating to the marketing and promotion of drug and biological products and to report gifts and payments to individual healthcare practitioners in these states. Other states prohibit various marketing-related activities, such as the provision of certain kinds of gifts or meals. Still other states require the posting of information relating to clinical studies and their outcomes. Some states require the reporting of certain pricing information, including information pertaining to and justifying price increases, or prohibit prescription drug price gouging. In addition, states such as California, Connecticut, Nevada and Massachusetts require pharmaceutical companies to implement compliance programs and/or marketing codes. Several additional states are considering similar proposals. Certain states and local jurisdictions also require the registration of pharmaceutical sales representatives. Compliance with these laws is difficult and time consuming, and companies that do not comply with these state laws face civil penalties.
Efforts to ensure that business arrangements with third parties comply with applicable healthcare laws and regulations involve substantial costs. If a company’s operations are found to be in violation of any such requirements, it may be subject to significant penalties, including civil, criminal and administrative penalties, damages, fines, disgorgement, imprisonment, the curtailment or restructuring of its operations, loss of eligibility to obtain approvals from the FDA, exclusion from participation in government contracting, healthcare reimbursement or other federal or state government healthcare programs, including Medicare and Medicaid, integrity oversight and reporting obligations, imprisonment, and reputational harm. Although effective compliance programs can mitigate the risk of investigation and prosecution for violations of these laws, these risks cannot be entirely eliminated. Any action for an alleged or suspected violation can cause a company to incur significant legal expenses and divert management’s attention from the operation of the business, even if such action is successfully defended.
In the EU and the UK companies must comply with national general anti-bribery legislation, including the UK Bribery Act 2010, as well as medicines legislation which prohibits the supply, offer or promise of certain gifts and benefits in connection with the promotion of medicinal products to any person qualified to prescribe, recommend, use, procure or supply them. Companies that breach these laws may incur substantial fines and imprisonment.
In the EU and the UK, payments made to healthcare professionals must be publicly disclosed under applicable transparency provisions and agreements with healthcare professionals must be the subject of prior notification and approval by the healthcare professional’s employer. Such requirements are set out in national laws, industry codes or professional codes of conduct, applicable in the EU Member States and in the UK. Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment.
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U.S. healthcare reform
In the United States there have been, and continue to be, proposals by the federal government, state governments, regulators and third-party payors to control or manage the costs of health care and, more generally, to reform the U.S. healthcare system. The pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives. For example, in March 2010, the ACA was enacted, which was intended to substantially change the way healthcare is financed by both governmental and private insurers, and significantly impacts the U.S. pharmaceutical industry. The ACA, among other things, (i) proscribed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs and therapeutic biologics that are inhaled, infused, instilled, implanted or injected, (ii) increased the minimum Medicaid rebates owed by manufacturers under the Medicaid Drug Rebate Program and extended the rebate program to individuals enrolled in Medicaid managed care organizations, (iii) established annual nondeductible fees and taxes on manufacturers of certain branded prescription drugs and therapeutic biologics, apportioned among these entities according to their market share in certain government healthcare programs, (iv) expanded eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to additional individuals and by adding new mandatory eligibility categories for individuals with income at or below 138% of the federal poverty level, thereby potentially increasing manufacturers’ Medicaid rebate liability, (v) expanded the entities eligible for discounts under the 340B Public Health program, (vi) required annual reporting of certain information regarding drug samples that manufacturers and distributors provide to licensed practitioners, (vii) created a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in and conduct comparative clinical effectiveness research, along with funding for such research, and (viii) established a Center for Medicare Innovation at CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending. Some of these cost-savings pilots and projects, such as the Enhancing Oncology Model, are directed specifically at oncology.
The ACA and certain of its provisions have been subject to judicial challenges as well as legislative and regulatory efforts to repeal or replace them or to alter their interpretation or implementation. For example, the Tax Cuts and Jobs Act (TCJA), among other things, included a provision repealing, effective January 1, 2019, the tax-based shared responsibility payment, or penalty, imposed by the ACA on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate.” Further, the Bipartisan Budget Act of 2018, among other things, amended the ACA, effective January 1, 2019, to increase from 50% to 70% the point-of-sale discount that is owed by pharmaceutical manufacturers who participate in Medicare Part D and to close the coverage gap in most Medicare drug plans, commonly referred to as the “donut hole.” Additionally, the Further Consolidated Appropriations Act of 2020, signed into law December 20, 2019, fully repealed the ACA’s “Cadillac Tax” on certain high-cost employer-sponsored insurance plans (for tax years beginning after December 31, 2019), the annual fee imposed on certain health insurance providers based on market share (for calendar year 2021) and the medical device excise tax on non-exempt medical devices. On June 17, 2021, the U.S. Supreme Court dismissed the most recent judicial challenge to the ACA brought by several states who argued that, without the individual mandate, the entire ACA was unconstitutional. The Supreme Court’s dismissal of the lawsuit did not specifically rule on the constitutionality of the ACA.
On March 11, 2021, Congress enacted the American Rescue Plan Act of 2021, which included among its provisions a sunset of the ACA’s cap on pharmaceutical manufacturers’ rebate liability under the Medicaid Drug Rebate Program. Under the ACA, manufacturers’ rebate liability was capped at 100% of the average manufacturer price for a covered outpatient drug. Effective January 1, 2024, manufacturers’ MDRP rebate liability is no longer capped, potentially resulting in a manufacturer paying more in MDRP rebates than it receives on the sale of certain covered outpatient drugs. The American Rescue Plan Act also temporarily increased premium tax credit assistance for individuals eligible for subsidies under the ACA for 2021 and 2022 and removed the 400% federal poverty level limit that otherwise applies for purposes of eligibility to receive premium tax credits. Most recently, the Inflation Reduction Act of 2022 extended this increased tax credit assistance and removal of the 400% federal poverty limit through 2025. In the future, there may be additional challenges and/or amendments to the ACA. It remains to be seen precisely what any new legislation will provide, when or if it will be enacted, and what impact it will have on the availability and cost of healthcare items and services, including drug and biological products.
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Other legislative changes have been proposed and adopted in the United States since the ACA was enacted to reduce healthcare expenditures. These changes include the Budget Control Act of 2011, which, among other things, led to aggregate reductions of Medicare payments to providers of up to 2% per fiscal year that started in 2013 and, due to subsequent statutory amendments, will remain in effect through the first six months of the FY 2032 sequestration order unless additional Congressional action is taken, with the exception of a temporary suspension from May 1, 2020 through July 1, 2022 due to the COVID-19 pandemic. The American Taxpayer Relief Act of 2012 made other changes, including the reduction of Medicare payments to several types of providers and an increase in the statute of limitations period for the government to recover overpayments to providers from three to five years. More recently, in August 2022, President Biden signed into law the Inflation Reduction Act of 2022, which implements substantial changes to the Medicare program, including drug pricing reforms and changes to the Medicare Part D benefit design. Among other reforms, the Inflation Reduction Act of 2022 imposes inflation rebates on drug and biological product manufacturers for products reimbursed under Medicare Parts B and D if the prices of those products increase faster than inflation beginning in 2023; implements changes to the Medicare Part D benefit that, beginning in 2025, will cap benefit annual out-of-pocket spending at $2,000, with new discount obligations for pharmaceutical manufacturers; and, beginning in 2026, establishes a “maximum fair price” for a fixed number of pharmaceutical and biological products covered under Medicare Parts B and D following a price negotiation process with the CMS. CMS has also taken steps to implement the IRA, including: on June 30, 2023, issuing guidance detailing the requirements and parameters of the first round of price negotiations, to take place during 2023 and 2024, for products subject to the “maximum fair price” provision that would become effective in 2026; on August 29, 2023, releasing the initial list of ten drugs subject to price negotiations; on November 17, 2023, releasing guidance outlining the methodology for identifying certain manufacturers eligible to participate in a phase-in period where discounts on applicable products will be lower than those required by the Medicare Part D Manufacturer Discount Program; and on December 14, 2023, releasing a list of 48 Medicare Part B products that had an adjusted coinsurance rate based on the inflationary rebate provisions of the IRA for the time period of January 1, 2024 to March 31, 2024. If federal spending is further reduced, anticipated budgetary shortfalls may also impact the ability of relevant agencies, such as the FDA or the NIH to continue to function at current levels. Amounts allocated to federal grants and contracts may be reduced or eliminated. These reductions may also impact the ability of relevant agencies to timely review and approve research and development, manufacturing, and marketing activities which may delay our ability to develop, market and sell any products we may develop.
Additionally, the cost of prescription pharmaceuticals and biological products has recently been the subject of considerable discussion in the United States. For example, in response to an Executive Order dated July 9, 2021, on September 9, 2021, the HHS issued a Comprehensive Plan for Addressing High Drug Prices that identified potential legislative policies and administrative tools that Congress and the agency can pursue in order to make drug prices more affordable and equitable, improve and promote competition throughout the prescription drug industry, and foster scientific innovation. In addition, on February 2, 2022, the Biden administration signaled its continued commitment to the Cancer Moonshot initiative, which was initially launched in 2016. In its announcement, the administration noted that its new goals under the initiative include addressing inequities in order to ensure broader access to cutting-edge cancer therapeutics and investing in a robust pipeline for new treatments. In alignment with President Biden’s Cancer Moonshot initiative, on June 27, 2023, the Center for Medicare Innovation at CMS announced a new model, the Enhancing Oncology Model, that is designed to make high-quality cancer care more affordable to both patients and Medicare. On September 12, 2022, President Biden issued an Executive Order to promote biotechnology and biomanufacturing innovation. The Order noted several methods through which the Biden administration would support the advancement of biotechnology and biomanufacturing in healthcare, and instructed the HHS to submit, within 180 days of the Order, a report assessing how to use biotechnology and biomanufacturing to achieve medical breakthroughs, reduce the overall burden of disease, and improve health outcomes. Additionally, on October 14, 2022 President Biden issued an Executive Order on Lowering Prescription Drug Costs for Americans, which instructed the Secretary of the HHS to consider whether to select for testing by the CMS Innovation Center new health care payment and delivery models that would lower drug costs and promote access to innovative drug therapies for beneficiaries enrolled in the Medicare and Medicaid programs. The Executive Order further directed the Secretary of the HHS to submit, within 90 days after the date of the Executive Order, a report regarding any models that may lead to lower cost-sharing for commonly used drugs and support value-based payment that promotes high-quality care. Moreover, there have been several recent U.S. Congressional inquiries and proposed federal legislation designed to, among other things, bring more transparency to drug and biological product pricing, review the relationship between pricing and manufacturer patient support programs, reduce the cost of prescription drugs and biological products under Medicare and reform government program reimbursement methodologies for drug and biological products. While several proposed reform measures will require Congress to pass legislation to become effective, Congress and the Biden administration have each indicated that it will continue to seek new legislative and/or administrative measures to address prescription drug and biological product costs, as discussed in greater detail in the section titled “Risk Factors.”
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At the state level, legislatures are increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures and, in some cases, to encourage importation from other countries and bulk purchasing. Most recently, on January 5, 2024, the FDA approved Florida’s importation plan to allow pharmacists and wholesalers in the state to import certain medications from Canada. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability, or commercialize any product that is ultimately approved, if approved. In addition, several recently passed state laws require disclosures related to state agencies and/or commercial purchasers with respect to certain price increases that exceed a certain level as identified in the relevant statutes. Some of these laws and regulations contain ambiguous requirements that government officials have not yet clarified. Given the lack of clarity in the laws and their implementation, our future reporting actions could be subject to the penalty provisions of the pertinent federal and state laws and regulations.
Additionally, on May 30, 2018, the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017 was signed into law. The law, among other things, provides a federal framework for certain patients to access certain investigational new drug or biological products that have completed a Phase 1 clinical trial and that are undergoing investigation for FDA approval. Under certain circumstances, eligible patients can seek treatment without enrolling in clinical trials and without obtaining FDA authorization under an FDA expanded access program; however, manufacturers are not obligated to provide investigational new drug or biological products under the current federal right to try law.
Human Capital
As of November 30, 2023, we had 284 full-time or part-time employees, of which approximately 40% have earned an M.D. or a Ph.D. As of November 30, 2023, 249 of our full-time or part-time employees are engaged in research and development. From time to time, we retain independent contractors to support our organization. None of our employees are represented by a labor union or covered by collective bargaining agreements, and we believe our relationship with our employees is good.
We consider the intellectual capital of our employees to be an essential driver of our business. We continually evaluate our business needs and opportunities and strive to balance in-house expertise and capacity with outsourced expertise and capacity. Currently, we outsource substantially all clinical trial work to clinical research organizations and drug substance and finished drug product manufacturing to contract manufacturers.
Competitive pay and benefits
Drug development is a complex endeavor which requires deep expertise and experience across a broad array of disciplines. Biotechnology and pharmaceutical companies both large and small compete for a limited number of qualified applicants to fill specialized positions. We monitor our compensation programs closely and provide what we consider to be a very competitive mix of compensation, insurance and wellness benefits for all our employees, as well as participation in our equity and other enhanced benefit programs. To attract qualified applicants, we offer a total rewards package consisting of a base salary and cash target bonus, a comprehensive benefits package and equity compensation for all full-time and part-time employees. Bonus opportunity and equity compensation increase as a percentage of total compensation based on level of responsibility. Actual bonus payout is based on company and individual performance.
Diversity and inclusion
We are committed to creating and maintaining a workplace free from discrimination or harassment on the basis of color, race, sex, national origin, ethnicity, religion, age, disability, sexual orientation, gender identification or expression or any other status protected by applicable law. Our management team and employees are expected to exhibit and promote honest, ethical and respectful conduct in the workplace. All of our employees must adhere to a code of conduct that sets standards for appropriate behavior and are required to attend biennial training to help prevent, identify, report and stop any type of discrimination and harassment. Recruitment, hiring, development, training, compensation and advancement at our company is based on qualifications, performance, skills and experience without regard to gender, race and ethnicity.
As of November 30, 2023, approximately 52% of our full-time and part-time employees were self-reported as female. Of our vice president-level and above employees, approximately 42% were self-reported as female.
In addition, as of November 30, 2023, approximately 57% of our full-time employees were self-reported as ethnic or racial minorities in the United States, with 42% Asian, 2% Black or African American, 8% Hispanic or Latino and 6% of other minority groups or two or more races. Of our vice president-level and above employees, 25% were self-reported as ethnic or racial minorities in the United States, with 17% Asian and 8% Black or African American.
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Employee development and training
We focus on attracting, retaining and cultivating talented individuals. We emphasize employee development and training by providing access to a wide range of online and instructor led development and continual learning programs. Employees are encouraged to attend scientific, clinical and technological meetings and conferences and have access to broad resources they need to be successful.
Board of Directors oversight
Our Board of Directors (Board) recognizes the critical importance of our team and the necessity to ensure a diverse, inclusive, and innovative work environment that is centered around a values-based culture. Our Board meets regularly with management to discuss issues impacting our employees, and to focus on ways to support our workforce. Our focus on culture comes from our Board and flows throughout our company. In evaluating our Chief Executive Officer and management team, significant emphasis is place on their contributions to our overall culture.
Our Board’s Compensation Committee is responsible for reviewing with management our human resources activities, which include, among other things, matters relating to employee development, management and engagement, pay equity, and our demographics, diversity and inclusion.
Our Board’s Nominating and Corporate Governance Committee is responsible for developing and recommending to the Board any company program relating to corporate responsibility and sustainability, including environmental, social and governance matters.
Corporate Information
We were incorporated under the laws of the State of Delaware in August 2009 under the name Kura Therapeutics, Inc. We subsequently changed our name to Nurix, Inc. in February 2012 and then to Nurix Therapeutics, Inc. in October 2018. Our principal executive offices are located at 1700 Owens Street, Suite 205, San Francisco, California 94158, and our telephone number is (415) 660-5320.
The mark “Nurix” is our registered trademark in Canada, France, Germany, Italy, Japan, Mexico, Spain, the United Kingdom and the United States. The mark “DELigase” is our registered trademarks in the United States. The Nurix logo is our common law trademark. All other service marks, trademarks and trade names appearing in this Annual Report on Form 10-K are the property of their respective owners. Solely for convenience, the trademarks and trade names referred to in this Annual Report on Form 10-K appear without the ® and ™ symbols, but those references are not intended to indicate, in any way, that we will not assert, to the fullest extent under applicable law, our rights, or the right of the applicable licensor to these trademarks and trade names.
Additional Information
Nurix’s Internet website address is http://www.nurixtx.com. On our website, we make available, free of charge, our annual, quarterly and current reports, including amendments to such reports, as soon as reasonably practicable after we electronically file such material with, or furnish such material to, the Securities and Exchange Commission (SEC). The SEC maintains a website at www.sec.gov that contains reports as well as other information regarding us and other companies that file materials with the SEC electronically.
Also available on our website is information relating to corporate governance at Nurix and our Board, including our Corporate Governance Guidelines; our Code of Business Conduct and Ethics (for our directors, officers and employees); and our Board Committee Charters. We will provide any of the foregoing information without charge upon written request to our Corporate Secretary, Nurix Therapeutics, Inc., 1700 Owens Street, Suite 205, San Francisco, California 94158.
We use our Investor Relations website (http://ir.nurixtx.com) as a means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD promulgated by the SEC. These disclosures are included in the “News” and “Events and Presentations” sections of our website. Accordingly, investors should monitor these portions of our website, in addition to following our press releases, SEC filings and public conference calls and webcasts.
The information contained on our website does not constitute, and shall not be deemed to constitute, a part of this Annual Report on Form 10-K, or any other report we file with, or furnish to, the SEC. Our references to the URLs for websites are intended to be inactive textual references only.
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Item 1A. Risk Factors
Investing in our common stock involves a high degree of risk. You should carefully consider the risks and uncertainties described below, together with all of the other information in this Annual Report on Form 10-K, including the section titled “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and our consolidated financial statements and the accompanying notes and the information contained in our other public filings before deciding whether to invest in shares of our common stock. We cannot assure you that any of the events described below will not occur. The risks and uncertainties described below are not the only ones we face. Additional risks and uncertainties that we are unaware of or that we deem immaterial may also become important factors that adversely affect our business. If any of the following risks occur, our business, financial condition, results of operations, and future prospects could be materially and adversely affected. In that event, the trading price of our common stock could decline, and you could lose part or all of your investment.
Risks Related to Our Financial Position and Need for Additional Capital
We have incurred significant losses since our inception. We expect to incur losses over at least the next several years and may never achieve or maintain profitability.
Our net loss was $143.9 million and $180.4 million for the fiscal years ended November 30, 2023 and 2022, respectively. As of November 30, 2023, we had an accumulated deficit of $545.2 million. To date, we have not generated any revenue from product sales and have financed our operations primarily through our collaborations and sales of our equity interests. We are in the early stages of development of our drug candidates. Our lead drug candidates, NX-5948, NX-2127 and NX-1607, are in the early stages of clinical development. We expect to continue to incur significant expenses and increasing operating losses for at least the next several years. We anticipate that our operating expenses and capital expenditure requirements will increase substantially if and as we:
•increase enrollment in and further development of our Phase 1 clinical trials of our drug candidates NX-5948, NX-2127 and NX-1607;
•submit investigational new drug applications (INDs) and initiate clinical trials of our other drug candidates;
•enter advanced clinical development and scale up external manufacturing capabilities to supply clinical trials;
•expand the capabilities of our DELigase platform and apply our DELigase platform to advance additional drug candidates into preclinical and clinical development;
•conduct process development for manufacturing of our drug candidates;
•seek marketing approvals for any drug candidates that successfully complete clinical trials;
•prepare for negotiations with the pricing authorities and submission to the health technology appraisal (HTA) bodies;
•ultimately establish a sales, marketing and distribution infrastructure and scale up external manufacturing capabilities to commercialize any drug candidates for which we may obtain marketing approval;
•expand, maintain and protect our intellectual property portfolio;
•hire additional clinical, regulatory, manufacturing, quality assurance and scientific personnel; and
•add operational, financial and management information systems and personnel to support our research, product development and future commercialization efforts and support our operations as a public company.
Our expenses could increase beyond our expectations if we are required by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) or other regulatory authorities to perform trials in addition to those we currently expect, or if there are any delays in establishing appropriate manufacturing arrangements for or in completing our planned clinical trials or the development of any of our drug candidates.
Because of the numerous risks and uncertainties associated with pharmaceutical product development, we are unable to accurately predict the timing or amount of increased expenses we will incur or when, if ever, we will be able to achieve profitability. Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. Our failure to become and remain profitable would depress the value of our company and could impair our ability to raise capital, expand our business, maintain our research and development efforts, diversify our product offerings or even continue our operations. A decline in the value of our company could also cause you to lose all or part of your investment.
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We have never generated revenue from product sales and may never be profitable.
We are in the early stages of clinical development of our drug candidates NX-5948, NX-2127 and NX-1607. We expect that it will be many years, if ever, before we have a drug candidate ready for commercialization. We may never succeed in these activities and, even if we do, may never generate revenues that are significant enough to achieve profitability. To become and remain profitable, we must succeed in developing, obtaining marketing approval for and commercializing products that generate significant revenue. This will require us to be successful in a range of challenging activities, including completing preclinical testing and clinical trials of our drug candidates, discovering additional drug candidates, establishing and maintaining arrangements with third parties for the manufacture of clinical supplies of our drug candidates, obtaining marketing approval for our drug candidates and manufacturing, marketing, selling and obtaining reimbursement for any products for which we may obtain marketing approval.
If one or more of the drug candidates that we develop is approved for commercial sale, we anticipate incurring significant costs associated with commercializing any approved drug candidate. Even if we are able to generate revenues from the sale of any approved products, we may not become profitable and may need to obtain additional funding to continue operations.
We will need substantial additional funding. If we are unable to raise capital when needed, we may be required to delay, limit, reduce or terminate our research or product development programs or future commercialization efforts.
We expect our expenses to increase substantially in connection with our ongoing activities, particularly as we conduct our Phase 1 clinical trials of NX-5948, NX-2127 and NX-1607, grow our pipeline of drug candidates, expand the breadth of our DELigase platform, continue research and development and initiate additional clinical trials of and potentially seek marketing approval for our lead programs and other drug candidates. In addition, if we obtain marketing approval for any of our drug candidates, we expect to incur significant commercialization expenses related to product manufacturing, marketing, reimbursement and sales and distribution. Furthermore, we expect to incur additional costs associated with operating as a public company. Accordingly, we will need to obtain substantial additional funding in connection with our continuing operations. If we are unable to raise capital when needed or on attractive terms, we may be required to delay, limit, reduce or terminate our research, product development programs or any future commercialization efforts or grant rights to develop and market drug candidates that we otherwise would prefer to develop and market ourselves.
We had cash, cash equivalents and marketable securities of $295.3 million as of November 30, 2023. We believe that our existing cash, cash equivalents and marketable securities will be sufficient to fund our operating expenses and capital expenditure requirements through at least the next 12 months. However, our future capital requirements and the period for which we expect our existing resources to support our operations may vary significantly from what we expect, and we may need to seek additional funds sooner than planned. In addition, we may seek additional capital due to favorable market conditions or strategic considerations, even if we believe we have sufficient funds for our current or future operating plans. Our future capital requirements will depend on many factors, including:
•the progress, costs and results of our Phase 1 clinical trials for NX-5948, NX-2127 and NX-1607 and any future clinical development of such drug candidates;
•the scope, progress, costs and results of preclinical and clinical development for our other drug candidates and development programs;
•the number and development requirements of other drug candidates that we pursue;
•the scope of, and costs associated with, future advancements to our DELigase platform;
•the success of our collaborations with Gilead Sciences, Inc. (Gilead), Sanofi S.A. (Sanofi) and Seagen Inc. (now a part of Pfizer Inc. (Pfizer)) and any other collaborations we may establish;
•the costs, timing and outcome of regulatory review of our drug candidates;
•the costs and timing of future commercialization activities, including product manufacturing, marketing, sales and distribution, for any of our drug candidates for which we receive marketing approval;
•the revenue, if any, received from commercial sales of our drug candidates for which we receive marketing approval;
•the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims; and
•our ability to establish additional collaboration arrangements with other biotechnology or pharmaceutical companies on favorable terms, if at all, for the development or commercialization of our drug candidates.
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We will need to raise substantial additional capital to complete the development and commercialization of our drug candidates. In addition, our drug candidates, if approved, may not achieve commercial success. Our commercial revenues, if any, will be derived from sales of products that we do not expect to be commercially available for many years, if at all. Accordingly, we will need to obtain substantial additional funds to achieve our business objectives. Adequate additional funds may not be available to us on acceptable terms, or at all.
Raising additional capital may cause dilution to our stockholders, restrict our operations or require us to relinquish rights to our technologies or drug candidates.
Until such time, if ever, as we can generate substantial revenue from product sales, we expect to finance our cash needs through a combination of equity offerings, debt financings, collaborations, strategic alliances and marketing, distribution or licensing arrangements. Although we may receive potential future milestone payments under our collaborations with Gilead, Sanofi and Pfizer, we do not currently have any committed external source of funds. To the extent that we raise additional capital through the sale of equity or convertible debt securities, your ownership interest will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect your rights as a holder of common stock. Debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making acquisitions or capital expenditures or declaring dividends.
If we raise additional funds through collaborations, strategic alliances or marketing, distribution or licensing arrangements with third parties, we may have to relinquish valuable rights to our intellectual property, technologies, future revenue streams, research programs or drug candidates or grant licenses on terms that may not be favorable to us.
Our limited operating history may make it difficult to evaluate the success of our business to date and to assess our future viability.
We commenced operations in 2009, and our operations to date have been limited to organizing and staffing our company, business planning, raising capital, conducting discovery and research activities, filing patent applications, identifying potential drug candidates, undertaking preclinical studies, establishing arrangements with third parties for the manufacture of initial quantities of our drug candidates and conducting early-stage clinical trials. Our lead drug candidates are in the early stages of clinical development and their risk of failure is high. We have not yet demonstrated our ability to successfully: complete any clinical trials, including large-scale, pivotal clinical trials; obtain marketing approvals; manufacture a commercial-scale product or arrange for a third party to do so on our behalf; or conduct market access, sales, marketing and distribution activities necessary for successful product commercialization. Consequently, any predictions you make about our future success or viability may not be as accurate as they could be if we had a longer operating history.
In addition, as an early-stage business, we may encounter unforeseen expenses, difficulties, complications, delays and other known and unknown factors. We will need to transition at some point from a company with a research and development focus to a company capable of supporting commercial activities. We may not be successful in such a transition.
We expect our financial condition and results of operations to continue to fluctuate significantly from quarter to quarter and year to year due to a variety of factors, many of which are beyond our control. Accordingly, you should not rely upon the results of any quarterly or annual periods as indications of future operating performance.
Risks Related to the Discovery and Development of Our Drug Candidates
We are early in our development efforts. Our lead drug candidates, NX-5948, NX-2127 and NX-1607, are in the early stages of clinical development. If we are unable to advance our drug candidates through clinical development, develop, obtain regulatory approval for and commercialize our drug candidates or experience significant delays in doing so, our business may be materially harmed.
We are early in our development efforts. Our lead drug candidates, NX-5948, NX-2127 and NX-1607, are in the early stages of clinical development and their risk of failure is high. We have invested substantially all of our efforts and financial resources in building our DELigase platform, in the identification and preclinical development of our current drug candidates and in the preparation for and initiation of Phase 1 clinical trials for our lead drug candidates. Our ability to generate revenue from product sales, which we do not expect will occur for many years, if ever, will depend heavily on the successful development and eventual commercialization of one or more of our drug candidates. The success of our drug candidates will depend on several factors, including the following:
•sufficiency of our financial and other resources;
•successful completion of preclinical studies;
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•successful submission of INDs or Clinical Trial Applications and initiation of clinical trials;
•successful patient enrollment in, and completion of, clinical trials;
•receipt and related terms of marketing approvals from applicable regulatory authorities;
•obtaining and maintaining patent and trade secret protection and regulatory exclusivity for our drug candidates as well as obtaining relevant exclusivity extensions (due to the conduct of pediatric studies);
•making arrangements with third-party manufacturers, or establishing manufacturing capabilities, for both clinical and commercial supplies of our drug candidates;
•achieving desirable therapeutic properties for our drug candidates’ intended indications;
•establishing sales, marketing and distribution capabilities and launching commercial sales of our products, if and when approved, whether alone or in collaboration with others;
•acceptance of our products, if and when approved, by patients, the medical community and third-party payors;
•obtaining and maintaining third-party coverage and adequate reimbursement;
•establishing a continued acceptable safety profile of our drug candidates and maintaining such a profile following approval; and
•effectively competing with other therapies.
If we do not successfully achieve one or more of these factors in a timely manner, or at all, we could experience significant delays or an inability to successfully commercialize our drug candidates, which could materially harm our business. Moreover, if we do not receive regulatory approvals, we may not be able to continue our operations.
In addition, we filed for and received an Innovation Passport designation for NX-1607 in the United Kingdom (UK) in February 2022. The Innovation Passport is the mandated entry point to the Innovative Licensing and Access Pathway (ILAP) in the UK to facilitate approval of and market access to an innovative medicine. Grant of the Innovation Passport paves the way for enhanced engagement with key stakeholders such as the Medicines and Healthcare products Regulatory Agency (MHRA), health technology agencies in the UK such as the National Institute for Health and Care Excellence (NICE) or the Scottish Medicines Consortium (SMC) and NHS England. However, although the goal of ILAP and the Innovation Passport is to reduce the time to market and enable earlier patient access, they do not accelerate conduct of clinical trials or mean that the regulatory requirements are less stringent, nor do they ensure that any NX-1607 marketing authorization application (MAA) will be approved or that any approval will be granted within any particular timeframe. Despite receiving an Innovation Passport designation, we may decide to delay or forego the commercialization of NX-1607 in the UK or the development may otherwise not proceed.
One of our approaches to the discovery and development of drug candidates based on our targeted protein degradation platform is unproven, which makes it difficult to predict the time, cost of development and likelihood of successfully developing any products.
Treating diseases using targeted protein degradation is a new treatment modality. Our future success depends on the successful development of this novel therapeutic approach. Very few small molecule drug candidates designed to control cellular protein levels, such as our BTK degraders, have been tested in humans, none have been approved in the United States or Europe, and the data underlying the feasibility of developing these therapeutic products is both preliminary and limited. Discovery and development of targeted protein degraders that harness ligases to degrade protein targets have been impeded largely by the complexities and limited understanding of the functions, biochemistry and structural biology of E3 ligases as well as by challenges of engineering compounds that promote protein-protein interactions.
We believe that our targeted protein degrader drug candidates may offer an improved therapeutic approach by removing the disease-causing proteins instead of simply inhibiting their activities. However, the scientific research that forms the basis of our efforts to develop our targeted protein degrader drug candidates is ongoing and the scientific evidence to support the feasibility of developing targeted protein degrader-based therapeutic treatments is both preliminary and limited. Further, certain patients have shown inherent (primary) resistance to approved BTK inhibitors and other patients have developed acquired (secondary) resistance to these inhibitors. Both NX-5948 and NX-2127 degrade BTK with mutations that confer resistance to currently marketed BTK inhibitors, and we believe that preliminary data from our ongoing Phase 1 trials of NX-5948 and NX-2127 may provide evidence of clinical benefit to patients with such resistance mutations. However, any inherent primary or acquired secondary resistance to our BTK degraders in patients would prevent or diminish their clinical benefit.
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We are in the early stages of clinical development of NX-5948 and NX-2127 and we currently have limited safety data of NX-5948 and NX-2127 in humans. Although some of our drug candidates have produced observable results in animal studies, these drug candidates may not demonstrate the same chemical and pharmacological properties in humans, and may interact with human biological systems in unforeseen, ineffective or harmful ways. As such, there may be adverse effects from treatment with any of our current or future drug candidates that we cannot predict at this time.
Additionally, the regulatory approval process for novel drug candidates such as ours can be more expensive and take longer than for other, better-known or extensively-studied drug candidates. Although other companies are also developing therapeutics based on targeted protein degradation, no regulatory authority has granted approval for any such therapeutic. As a result of these factors, it is more difficult for us to predict the time and cost of targeted protein degrader drug candidate development, and we cannot predict whether targeted protein degradation will result in the development and marketing approval of any products. Any development problems we experience in the future related to any of our targeted protein degrader research programs may cause significant delays or unanticipated costs or may prevent the development of a commercially viable product. Advancing our targeted protein degrader drug candidates creates significant challenges for us, including:
•educating medical personnel regarding the potential efficacy and safety benefits, as well as the challenges, of incorporating our drug candidates, if approved, into treatment regimens; and
•establishing the sales and marketing capabilities to gain market acceptance, if approved.
Any of these factors may prevent us from completing our preclinical studies or any clinical trials that we may initiate, or from commercializing any targeted protein degrader drug candidates we may develop on a timely or profitable basis, if at all.
Drug development is a lengthy and expensive process, with an uncertain outcome. We may incur unexpected costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of our drug candidates.
Our lead drug candidates are in the early stages of clinical development and their risk of failure is high. We are unable to predict when or if any of our drug candidates will prove effective or safe in humans or will receive marketing approval. Before obtaining marketing approval from regulatory authorities for the sale of any drug candidate, we must conduct extensive clinical trials to demonstrate the safety and efficacy of our drug candidates in humans. Before we can commence clinical trials for a drug candidate, we must complete extensive preclinical testing and studies that support our planned INDs in the United States or similar applications in other jurisdictions. We cannot be certain of the timely completion or outcome of our preclinical testing and studies and cannot predict if the FDA or similar regulatory authorities outside the United States will accept our proposed clinical programs or if the outcome of our preclinical testing and studies ultimately will support the further development of our programs.
Clinical testing is expensive, difficult to design and implement, can take many years to complete and is uncertain as to the outcome. A failure of one or more clinical trials can occur at any stage of testing. Clinical trials may produce negative or inconclusive results, and we or any future collaborators may decide, or regulators may require us, to conduct additional clinical trials or preclinical studies. We will be required to demonstrate with substantial evidence through adequate and well-controlled clinical trials that our drug candidates are safe and effective for use in treating specific conditions in order to obtain marketing approvals for their commercial sale. Success in preclinical studies and early-stage clinical trials does not mean that any future larger registration clinical trials will be successful because drug candidates in later-stage clinical trials may fail to demonstrate safety and efficacy to the satisfaction of the FDA and non-U.S. regulatory authorities despite having progressed through preclinical studies and early-stage clinical trials. Drug candidates that have shown promising results in preclinical studies and early-stage clinical trials may still suffer significant setbacks in subsequent larger registration clinical trials. Additionally, the outcome of preclinical studies and early-stage clinical trials may not be predictive of the success of later-stage clinical trials.
We may experience numerous unforeseen events during, or as a result of, clinical trials, that could delay or prevent our ability to receive marketing approval or commercialize our drug candidates, including:
•we may experience delays in reaching, or may fail to reach, a consensus with regulators on trial design;
•the supply or quality of our drug candidates or other materials necessary to conduct clinical trials of our drug candidates may be insufficient or inadequate, including as a result of delays in the testing, validation, manufacturing and delivery of drug candidates to the clinical sites by us or by third parties with whom we have contracted to perform certain of those functions;
•we may experience delays in reaching, or may fail to reach, agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites;
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•regulators or institutional review boards (IRBs) may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site;
•we may receive feedback from regulatory authorities that requires us to modify the design of our clinical trials;
•we may face delays under human tissue act legislation and restrictions across various jurisdictions;
•we may experience difficulty in designing clinical trials and in selecting endpoints for diseases that have not been well-studied and for which the natural history and course of the disease is poorly understood;
•the selection of certain clinical endpoints may require prolonged periods of clinical observation or analysis of the resulting data;
•the number of patients required for clinical trials of our drug candidates may be larger than we anticipate, enrollment in these clinical trials may be slower than we anticipate or participants may drop out of these clinical trials at a higher rate than we anticipate;
•our drug candidates may have undesirable side effects or other unexpected characteristics, causing us or our investigators, regulators or IRBs to suspend or terminate the trials;
•we may have to suspend or terminate clinical trials of our drug candidates for various reasons, including a partial or full clinical hold based on a finding that our drug candidates have undesirable side effects or other unexpected characteristics, or that the participants are being exposed to unacceptable health risks;
•our third-party contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all;
•regulators or IRBs may require that we or our investigators suspend or terminate clinical trials for various reasons, including noncompliance with regulatory requirements;
•clinical trials of our drug candidates may produce negative or inconclusive results, and we may decide, or regulators may require us, to conduct additional clinical trials or abandon product development programs;
•the cost of clinical trials of our drug candidates may be greater than we anticipate;
•the supply or quality of our drug candidates or other materials necessary to conduct clinical trials of our drug candidates may be insufficient or inadequate;
•regulators may revise the requirements for approving our drug candidates, or such requirements may not be as we anticipate;
•any future collaborators that conduct clinical trials may face any of the above issues and may also conduct clinical trials in ways they view as advantageous to them but that are suboptimal for us; and
•disruptions caused by macroeconomic, political and market conditions, including supply chain disruptions, may increase the likelihood that we encounter such difficulties or delays in initiating, enrolling, conducting or completing our planned and ongoing clinical trials.
In some instances, there can be significant variability in safety and efficacy results between different clinical trials of the same drug candidate due to numerous factors, including changes in trial protocols, differences in size and type of the patient populations, differences in and adherence to the dosing regimen and other trial protocols and the rate of dropout among clinical trial participants. We do not know whether any clinical trials we may conduct will demonstrate consistent or adequate safety and efficacy sufficient to obtain marketing approval for our drug candidates.
If we are required to conduct additional clinical trials or other testing of our drug candidates beyond those that we currently contemplate, if we are unable to successfully complete clinical trials of our drug candidates or other testing, if the results of these trials or tests are not positive or are only modestly positive or if there are safety concerns, we may:
•be delayed in obtaining marketing approval for our drug candidates;
•not obtain marketing approval at all;
•obtain approval for indications or patient populations that are not as broad as intended or desired;
•obtain approval with labeling that includes significant use or distribution restrictions or safety warnings;
•be subject to additional post-marketing testing requirements or changes in the way the product is administered; or
•have the product removed from the market after obtaining marketing approval.
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Our product development costs also will increase if we experience delays in preclinical studies or clinical trials or in obtaining marketing approvals. We do not know whether any of our preclinical studies or clinical trials will begin as planned, will need to be restructured or will be completed on schedule, or at all. Significant preclinical study or clinical trial delays also could shorten any periods during which we may have the exclusive right to commercialize our drug candidates, or could allow our competitors to bring products to market before we do and impair our ability to successfully commercialize our drug candidates, which may harm our business, results of operations, financial condition and prospects.
Further, cancer therapies sometimes are characterized as first-line, second-line or third-line, and the FDA often approves new therapies initially only for third-line or later use, meaning for use after two or more other treatments have failed. When cancer is detected early enough, first-line therapy, usually chemotherapy, hormone therapy, immunotherapy, radiation therapy, surgery, targeted therapy or a combination of these, is sometimes adequate to cure the cancer or prolong life without a cure. Second- and third-line therapies are administered to patients when prior therapy was ineffective. Our current and planned clinical trials for our drug candidates NX-5948, NX-2127 and NX-1607 are and will be with patients who have received one or more prior treatments. Subsequently, for those drug candidates that prove to be sufficiently beneficial, if any, we may seek approval potentially as a first-line therapy, but any drug candidates we develop, even if approved, may not be approved for first-line therapy, and, prior to any such approvals, we may have to conduct additional clinical trials.
If serious adverse events, undesirable side effects or unexpected characteristics are identified during the development of any drug candidates we may develop, we may need to abandon or limit our further clinical development of those drug candidates.
We have recently begun to evaluate our lead drug candidates in human clinical trials, and there have been very few clinical trials to date involving small molecule drug candidates designed to control cellular protein levels through targeted protein degradation. It is impossible to predict when or if any drug candidates we may develop will prove safe in humans. There is a limited safety data set for the effects of NX-5948, NX-2127 and NX-1607 in animals and we only recently have begun to test the safety of our drug candidates in humans. There can be no assurance that our current drug candidates or any future drug candidate will not cause undesirable side effects. Unforeseen side effects from our drug candidates could arise at any time during preclinical or clinical development.
A potential risk in any protein modulation product is that healthy proteins or proteins not targeted for modulation will be modulated or that the modulation of the targeted protein in itself could cause adverse events, undesirable side effects or unexpected characteristics. It is possible that healthy proteins or proteins not targeted for modulation could be modulated by our drug candidates in any of our current or future preclinical studies or clinical trials. There also is the potential risk of delayed adverse events following treatment with our drug candidates.
If any drug candidates we develop are associated with serious adverse events or undesirable side effects, or have characteristics that are unexpected, including in preclinical studies, we may need to abandon their development or limit development to certain uses or subpopulations in which the adverse events, undesirable side effects or other characteristics are less prevalent, less severe or more acceptable from a risk-benefit perspective, any of which would have a material adverse effect on our business, financial condition, results of operations and prospects. For example, increased bleeding risk and cardiac arrhythmia such as atrial fibrillation have been reported side effects of approved BTK inhibitors. Furthermore, NX-1607 could activate the immune response to unsafe levels and may have the potential to induce hypercytokinemia, or cytokine storm, which is the overstimulation of immune cells and subsequent overproduction of their activating compounds. Many drug candidates that initially showed promise in early-stage testing for treating cancer or other diseases later have been found to cause side effects that prevented further clinical development of the drug candidates or limited their competitiveness in the market.
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The results of preclinical studies and early-stage clinical trials may not be predictive of future results. Initial success in clinical trials may not be indicative of results obtained when these trials are completed or in later-stage trials.
The results of preclinical studies may not be predictive of the results of clinical trials, and the results of any early-stage clinical trials we commence may not be predictive of the results of the later-stage clinical trials. In addition, initial success in clinical trials may not be indicative of results obtained when such trials are completed. In particular, the small number of patients in our planned early clinical trials may make the results of these trials less predictive of the outcomes of later clinical trials. For example, even if successful, the results of our initial clinical trials for NX-5948, NX-2127 and NX-1607 may not be predictive of the results of further clinical trials of these drug candidates or any of our other drug candidates. Moreover, preclinical and clinical data often are susceptible to varying interpretations and analyses, and many companies that have believed their drug candidates performed satisfactorily in preclinical studies and clinical trials nonetheless have failed to obtain marketing approval of their products. Our future clinical trials may not ultimately be successful or support further clinical development of any of our drug candidates. There is a high failure rate for drug candidates proceeding through clinical trials. A number of companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in clinical development even after achieving encouraging results in earlier studies and clinical trials. Any such setbacks in our clinical development could materially harm our business, results of operations, financial condition and prospects.
Interim top-line and preliminary data from our planned clinical trials that we announce or publish from time to time may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data.
From time to time, we may publish interim top-line or preliminary data from our planned clinical trials. Interim data from clinical trials that we may complete are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available. Preliminary or top-line data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published. As a result, interim and preliminary data should be viewed with caution until the final data are available. Adverse differences between preliminary or interim data and final data could significantly harm our reputation, business, results of operations, financial condition and prospects.
If we experience delays or difficulties in enrolling patients in clinical trials, our receipt of necessary marketing approvals could be delayed or prevented.
We may not be able to initiate or continue clinical trials for our drug candidates if we are unable to locate and enroll a sufficient number of eligible patients to participate in these trials as required by the FDA or similar regulatory authorities outside of the United States. In particular, we are currently conducting Phase 1 clinical trials for each of our lead drug candidates: NX-5948, NX-2127 and NX-1607. We cannot predict how difficult it will be to enroll patients for these trials. Therefore, our ability to identify and enroll eligible patients for our NX-5948, NX-2127 and NX-1607 clinical trials may be limited or may result in slower enrollment than we anticipate. In addition, some of our competitors have ongoing clinical trials for drug candidates that treat the same indications as our drug candidates, and patients who otherwise would be eligible for our planned clinical trials instead may enroll in clinical trials of our competitors’ drug candidates. Moreover, the size of the relevant patient populations for the diseases that our lead drug candidates target is small, and as more companies begin to focus attention and resources on drug candidates to treat the same indications as our drug candidates, we may experience delays or be unable to successfully recruit and enroll a sufficient number of eligible patients in our clinical trials. Patient enrollment is affected by other factors including:
•the severity of the disease under investigation;
•the size of the patient population and process for identifying patients;
•the availability and efficacy of approved medications for the disease under investigation;
•the eligibility criteria for the trial in question;
•the perceived risks and benefits of the drug candidates under study;
•the efforts to facilitate timely enrollment in clinical trials;
•physicians’ attitudes and practices with respect to clinical trial enrollment;
•the burden on patients due to inconvenient procedures;
•the ability to monitor patients adequately during and after treatment; and
•the proximity and availability of clinical trial sites for prospective patients.
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Our inability to enroll a sufficient number of patients for our current or planned clinical trials would result in significant delays and could require us to abandon one or more clinical trials altogether. Enrollment delays in our current or planned clinical trials may result in increased development costs for our drug candidates, which would cause the value of our company to decline and limit our ability to obtain additional financing.
We may expend our limited resources to pursue a particular drug candidate or indication and fail to capitalize on drug candidates or indications that may be more profitable or for which there is a greater likelihood of success.
Because we have limited financial and managerial resources, we focus on research programs and drug candidates that we identify for specific indications. As a result, we may forego or delay pursuit of opportunities with other drug candidates or for other indications that later prove to have greater commercial potential. Our resource allocation decisions may cause us to fail to capitalize on viable commercial products or profitable market opportunities. Our spending on current and future research and development programs and drug candidates for specific indications may not yield any commercially viable products. If we do not accurately evaluate the commercial potential or target market for a particular drug candidate, we may relinquish valuable rights to that drug candidate through collaboration, licensing or other royalty arrangements in cases in which it would have been more advantageous for us to retain sole development and commercialization rights to such drug candidate.
The manufacture of drugs is complex, and we and our third-party manufacturers are early in our manufacturing efforts.
We have established manufacturing relationships with a limited number of suppliers to manufacture raw materials and the drug substance of any drug candidate for which we are currently pursuing, or may in the future pursue, preclinical or clinical development. Our systems for complying with current good manufacturing practices (cGMPs), manufacturing process development with our third-party manufacturers and scale-up are at an early stage. The actual cost to manufacture and process our drug candidates could be greater than we expect and could materially and adversely affect the commercial viability of our drug candidates. We or any of our third-party manufacturers may encounter difficulties in production, including contamination, equipment failure, improper installation or operation of equipment, vendor or operator error, inconsistency in yields, variability in product characteristics and difficulties in scaling the production process. Even minor deviations from normal manufacturing processes could result in reduced production yields, product defects and other supply disruptions. If we or any of our third-party manufacturers encounter such difficulties, our ability to provide supply of our current or future drug candidates for clinical trials, our ability to obtain marketing approval or our ability to provide supply of our drug candidates for patients, if approved, could be delayed or stopped. For example, in October 2023, following our communication to the FDA of our intention to transition to an improved manufacturing process for NX-2127, the FDA placed a partial clinical hold on our ongoing Phase 1 clinical trial evaluating NX-2127. Currently-enrolled patients who are deriving clinical benefit may continue to receive treatment in accordance with the ongoing study protocol, but no additional patients may be enrolled until the partial clinical hold is resolved. We remain actively engaged in discussions with FDA as part of our efforts to lift the partial clinical hold. However, there can be no assurance that we can address the issues resulting in the partial clinical hold in a timely manner or at all, and we may incur additional expenses in connection with our efforts to advance our NX-2127 program.
We may not be successful in our efforts to identify or discover additional potential drug candidates.
A key element of our strategy is to apply our DELigase platform to address a broad array of targets and new therapeutic areas. The therapeutic discovery activities we are conducting may not be successful in identifying drug candidates that are useful in treating hematologic cancers, immune-mediated diseases or any other diseases. Our research programs initially may show promise in identifying potential drug candidates, yet fail to yield drug candidates for clinical development for a number of reasons, including:
•the research methodology used may not be successful in identifying potential drug candidates;
•potential drug candidates may, on further study, be shown to have harmful side effects or other characteristics that indicate that they are unlikely to be drugs that will receive marketing approval or achieve market acceptance; or
•potential drug candidates may not be effective in treating their targeted diseases.
Research programs to identify new drug candidates require substantial technical, financial and human resources. We may choose to focus our efforts and resources on a potential drug candidate that ultimately proves to be unsuccessful. If we are unable to identify suitable drug candidates for preclinical and clinical development, we will not be able to obtain revenues from the sale of products in future periods, which likely would result in significant harm to our financial position and adversely impact our stock price.
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We may not be successful in our efforts to expand the breadth of our DELigase platform.
A key element of our strategy is to expand the capabilities of our DELigase platform and leverage our platform to discover, develop and potentially commercialize additional drug candidates beyond our current portfolio to target diseases in a wide range of organ systems and tissues and treat various disease states. These enhancements require substantial technical, financial and human resources, and may not result in the discovery or development of additional drug candidates or therapies. We may pursue what we believe is a promising opportunity to leverage our platform only to discover that certain of our risk or resource allocation decisions were incorrect or insufficient, or that individual products or our science in general has technology or biology risks that were previously unknown or underappreciated. Our strategy of pursuing the value of our DELigase platform over a long time horizon and across a broad array of human diseases may not be effective. In the event material decisions in any of these areas turn out to be incorrect or sub-optimal, we may experience a material adverse impact on our business and ability to fund our operations and we may never realize what we believe is the potential of our DELigase platform.
We face substantial competition in an environment of rapid technological change, which may result in others discovering, developing or commercializing products before or more successfully than we do.
The development and commercialization of new drug products is highly competitive. Moreover, the biotechnology and pharmaceutical industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary products. We face and will continue to face competition from third parties that use protein modulation, antibody therapy, adoptive cell therapy, inhibitory nucleic acid, gene editing or gene therapy development platforms and from companies focused on more traditional therapeutic modalities, such as small molecule inhibitors. The competition is likely to come from multiple sources, including major pharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions, government agencies and other public and private research institutions that conduct research, seek patent protection and establish collaborative arrangements for research, development, manufacturing and commercialization.
We are aware of a number of biotechnology companies focused on developing small molecules that degrade target proteins or inhibit E3 ligases, including, but not limited to, Accutar Biotechnology Inc., Arvinas, Inc., BeiGene, Ltd., BioTheryX, Inc., C4 Therapeutics, Inc., Cullgen Inc., Foghorn Therapeutics Inc., HotSpot Therapeutics, Inc., Kymera Therapeutics, Inc. and Monte Rosa Therapeutics, all of which currently are in preclinical or clinical development. In addition, certain large pharmaceutical companies have disclosed investments in this field, including AbbVie Inc., Amgen Inc., AstraZeneca plc, Bayer AG, Bristol-Myers Squibb Company, Genentech, Inc., GlaxoSmithKline plc and Novartis International AG. Furthermore, we are aware of multiple other BTK degrader programs in clinical development, including programs from AbbVie Inc., Accutar Biotechnology, Inc., BeiGene, Ltd, Haisco Pharmaceutical Group Co., Ltd. and Ubix Therapeutics, Inc.
Many of our current or potential competitors, either alone or with their collaboration partners, have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. Further, mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies also may prove to be significant competitors, particularly through collaborative arrangements with large and established companies. All of these competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products we may develop. Our competitors also may obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval for ours, which could prevent us from obtaining the orphan designation in the European Union (EU) and/or in the UK and result in our competitors establishing a strong market position before we are able to enter the market. In addition, our ability to compete may be affected in many cases by insurers or other third-party payors seeking to encourage the use of generic products. There are generic products currently on the market for certain of the indications that we are pursuing, and additional products are expected to become available on a generic basis over the coming years. If our drug candidates are approved, we expect that they will be priced at a significant premium over competitive generic products.
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If we do not achieve our projected development goals in the time frames we expect and announce, the commercialization of our products may be delayed and, as a result, our stock price may decline.
From time to time, we estimate the timing of the anticipated accomplishment of various scientific, clinical, regulatory and other product development goals, which we sometimes refer to as milestones. These milestones may include the commencement or completion of scientific studies and clinical trials and the submission of regulatory filings and may be associated with payments from third-party collaborators such as Gilead, Sanofi or Pfizer. From time to time, we may publicly announce the expected timing of some of these milestones. All of these milestones are and will be based on numerous assumptions. The actual timing of these milestones can vary dramatically compared to our estimates, in some cases for reasons beyond our control. If we do not meet these milestones as publicly announced, or at all, our revenue may be lower than expected, the commercialization of our products may be delayed or never achieved and, as a result, our stock price may decline.
Our estimated market opportunities for our drug candidates are subject to numerous uncertainties and may prove to be inaccurate. If we have overestimated the size of our market opportunities, our future growth may be limited.
Our estimated addressable markets and market opportunities for our drug candidates are based on a variety of inputs, including data published by third parties, our own market insights and internal market intelligence and internally generated data and assumptions. We have not independently verified any third-party information and cannot be assured of its accuracy or completeness. Market opportunity estimates, whether obtained or derived from third-party sources or developed internally, are subject to significant uncertainty and are based on assumptions and estimates that may prove inaccurate. Although we believe our market opportunity estimates are reasonable, such information is inherently imprecise. In addition, our assumptions and estimates of market opportunities are necessarily subject to a high degree of uncertainty and risk due to a variety of factors, including but not limited to those described in this Annual Report on Form 10-K. If this third-party or internally generated data prove to be inaccurate or if we make errors in our assumptions based on that data, our actual market may be more limited than we estimate it to be. In addition, these inaccuracies or errors may cause us to misallocate capital and other critical business resources, which could harm our business.
Risks Related to Dependence on Third Parties
We expect to depend on collaborations with third parties for the research, development and commercialization of certain of the drug candidates we may develop. If any such collaborations are not successful, we may not be able to capitalize on the market potential of those drug candidates.
We have sought third-party collaborators for the research, development and commercialization of some of our targeted protein degrader programs. For example, in June 2019 we entered into a collaboration with Gilead; in December 2019 we entered into a collaboration with Sanofi, which was subsequently expanded and amended in January 2021; and in September 2023 we entered into a collaboration with Seagen Inc. (now a part of Pfizer). Each of the foregoing collaborations requires us to conduct certain research activities. Our likely collaborators for any other collaboration arrangements include large and mid-size pharmaceutical companies, biotechnology companies and universities. These and any future arrangements with third parties limit our control over the amount and timing of resources that our collaborators dedicate to the development or commercialization of any drug candidates we may seek to develop with them. Our ability to generate revenues from these arrangements will depend on our collaborators’ abilities to successfully perform the functions assigned to them in these arrangements. We cannot predict the success of any collaboration that we enter into.
Collaborations involving our research programs or any drug candidates we may develop, including our collaborations with Gilead, Sanofi and Pfizer, pose risks to us, including:
•Collaborators have significant discretion in determining the efforts and resources that they will apply to collaborations with us.
•Collaborators may not pursue development and commercialization of any drug candidates we may develop or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborator’s strategic focus or available funding or external factors such as an acquisition or business combination that diverts resources or creates competing priorities.
•Gilead and Sanofi have broad option rights to select up to five targets each, and Pfizer has option rights to multiple targets, for exclusive targeted protein degrader development, so long as not excluded by us under the terms of each collaboration, and may select targets we are considering but have not taken sufficient action to exclude under each collaboration.
•Collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a drug candidate, repeat or conduct new clinical trials or require a new formulation of a drug candidate for clinical testing.
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•Collaborators could develop independently, or develop with third parties, products that compete directly or indirectly with our products or drug candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours.
•Collaborators with marketing and distribution rights to one or more products may not commit sufficient resources to the marketing and distribution of such product or products.
•Collaborators may not properly obtain, maintain, enforce or defend our intellectual property or proprietary rights or may use our proprietary information in such a way that could jeopardize or invalidate our proprietary information or expose us to potential litigation. For example, Gilead, Sanofi and Pfizer have the first right to enforce or defend certain intellectual property rights under the applicable collaboration arrangement with respect to particular licensed programs, and although we may have the right to assume the enforcement and defense of such intellectual property rights if the collaborator does not, our ability to do so may be compromised by their actions.
•Disputes may arise between the collaborators and us that result in the delay or termination of the research, development or commercialization of our products or drug candidates or that result in costly litigation or arbitration that diverts management attention and resources.
•We may lose certain valuable rights under circumstances identified in our collaborations, including if we undergo a change of control. For example, Sanofi may terminate its agreement with us if we undergo a change of control.
•Collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable drug candidates. For example, each of Gilead, Sanofi and Pfizer can terminate its agreement with us in its entirety or with respect to a specific target for convenience upon written notice or in connection with a material breach of the agreement by us that remains uncured for a specified period of time.
•Collaboration agreements may not lead to development or commercialization of drug candidates in the most efficient manner, or at all. For instance, if a present or future collaborator of ours were to be involved in a business combination, the continued pursuit and emphasis on our product development or commercialization program under such collaboration could be delayed, diminished or terminated.
If our collaborations do not result in the successful development and commercialization of products, or if one of our collaborators terminates its agreement with us, we may not receive any future research funding or milestone or royalty payments under the collaboration. If we do not receive the funding we expect under these agreements, our development of drug candidates could be delayed, and we may need additional resources to develop drug candidates. In addition, if one of our collaborators terminates its agreement with us, we may find it more difficult to find a suitable replacement collaborator or attract new collaborators, and our development programs may be delayed or the perception of us in the business and financial communities could be adversely affected. Moreover, all of the risks relating to product development, marketing approval and commercialization described in this Annual Report on Form 10-K apply to the activities of our collaborators.
We may in the future decide to collaborate with pharmaceutical and biotechnology companies for the development and potential commercialization of any drug candidates we may develop. These relationships may require us to incur non-recurring and other charges, increase our near- and long-term expenditures, issue securities that dilute the ownership interest of our existing stockholders, or disrupt our management and business. In addition, we could face significant competition in seeking appropriate collaborators, and the negotiation process is time-consuming and complex. Our ability to reach a definitive collaboration agreement will depend upon, among other things, our assessment of the proposed collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed collaborator’s evaluation of several factors. If we license rights to any drug candidates we or our collaborators may develop, we may not be able to realize the benefit of such transactions if we are unable to successfully integrate them with our existing operations and company culture.
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We may seek to establish additional collaborations. If we are not able to establish collaborations on commercially reasonable terms, we may have to alter our development and commercialization plans.
We plan to continue to selectively pursue collaborations with leading biopharmaceutical and biotechnology companies with development and commercial expertise and capabilities. We face significant competition in attracting appropriate collaborators to advance the development of any drug candidates for which we may seek a collaboration. Whether we reach a definitive agreement for a collaboration will depend upon, among other things, our assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed collaborator’s evaluation of a number of factors. Those factors may include the design or results of preclinical studies and clinical trials, the likelihood of approval by the FDA or other regulatory authorities, the potential market for the subject drug candidate, the costs and complexities of manufacturing and delivering such drug candidate to patients, the potential of competing products, uncertainty with respect to our ownership of technology (which can exist if there is a challenge to such ownership without regard to the merits of the challenge), the terms of any existing collaboration agreements and industry and market conditions generally. The collaborator also may have the opportunity to collaborate on other drug candidates or technologies for similar indications and will have to evaluate whether such a collaboration could be more attractive than one with us.
Collaborations are complex and time-consuming to negotiate, document and execute. In addition, consolidation among large pharmaceutical companies has reduced the number of potential future collaborators, and we may not be able to locate a suitable collaborator. Any collaboration we enter into may limit our ability to enter into future agreements on particular terms or covering similar target indications with other potential collaborators.
We may not be able to negotiate collaborations on a timely basis, on acceptable terms, or at all. If we are unable to do so, we may have to curtail the development of the drug candidate for which we are seeking to collaborate, reduce or delay its development program or one or more of our other development programs, delay its potential commercialization or reduce the scope of any sales or marketing activities or increase our expenditures and undertake development or commercialization activities at our own expense. If we elect to increase our expenditures to fund development or commercialization activities on our own, we may need to obtain additional capital, which may not be available to us on acceptable terms, or at all. If we do not have sufficient funds, we may not be able to further develop our drug candidates or bring them to market and generate revenue from product sales, which could have an adverse effect on our business, financial condition, results of operations and prospects.
We rely on third parties to conduct our clinical trials, and those third parties may not perform satisfactorily, including failing to meet deadlines for completing such trials.
We rely on third-party contract research organizations (CROs) to conduct our Phase 1 clinical trial programs for NX-5948, NX-2127 and NX-1607 and we will rely on third-party CROs to conduct any clinical trials for other drug candidates. Agreements with these CROs might terminate for a variety of reasons, including for such CRO’s failure to perform. Entry into alternative arrangements, if necessary, could significantly delay our product development activities.
Our reliance on these CROs for research and development activities will reduce our control over these activities but will not relieve us of our responsibilities. For example, we will remain responsible for ensuring that each of our clinical trials is conducted in accordance with the general investigational plan and protocols in the applicable IND. Moreover, the FDA and other foreign regulators such as the EMA and the MHRA require compliance with good clinical practice standards, commonly referred to as GCPs, for conducting, recording and reporting the results of clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity and confidentiality of trial participants are protected.
If these CROs do not successfully carry out their contractual duties, meet expected deadlines or conduct our clinical trials in accordance with regulatory requirements or our stated protocols, we will not be able to obtain, or may be delayed in obtaining, marketing approvals for our drug candidates and will not be able to, or may be delayed in our efforts to, successfully commercialize our drug candidates.
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We rely on third-party contract manufacturing organizations (CMOs) for the manufacture of both drug substance and finished drug product for our drug candidates for preclinical and clinical testing and expect to continue to do so for any future clinical trials and commercialization. This reliance on third parties may increase the risk that we will not have sufficient quantities of our drug candidates or products or such quantities at an acceptable cost or quality, which could delay, prevent or impair our development or commercialization efforts.
We do not own or operate, and currently have no plans to establish, any manufacturing facilities. We rely on and expect to continue to rely on third-party contract manufacturing organizations (CMOs) for both drug substance and finished drug product. This reliance on CMOs, particularly where one CMO is the sole source of the drug substance or finished drug product, may increase the risk that we will not have sufficient quantities of our drug candidates or products or such quantities at an acceptable cost or quality, which could delay, prevent or impair our development or commercialization efforts.
We may be unable to establish agreements with CMOs or to do so on acceptable terms. Even if we are able to establish agreements with CMOs, reliance on them entails additional risks, including:
•reliance on the CMO for regulatory, compliance and quality assurance;
•the possible breach of the manufacturing agreement by the CMO;
•the possible misappropriation of our proprietary information, including our trade secrets and know-how; and
•the possible termination or nonrenewal of the agreement by the CMO at a time that is costly or inconvenient for us.
We have only limited technology transfer agreements in place with respect to our drug candidates, and these arrangements do not extend to commercial supply. We acquire many key materials on a purchase order basis. As a result, we do not have long-term committed arrangements with respect to our drug candidates and other materials. If we receive marketing approval for any of our drug candidates, we will need to establish an agreement for commercial manufacture with a third party.
The CMOs we retain may not be able to comply with cGMP regulations or similar regulatory requirements outside of the United States. Our failure, or the failure of our CMOs, to comply with applicable regulations could result in sanctions or other adverse regulatory actions, including untitled or warning letters, clinical holds, fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, failure to approve pending applications, license revocation, seizures or recalls of drug candidates or products, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our products.
The facilities used by our contract manufacturers to manufacture our drug candidates must be approved by the FDA or the EMA or other national or international regulatory agencies pursuant to inspections that will be conducted after we submit our new drug application (NDA) to the FDA or our MAA to the EMA or other regulatory authority. We do not have complete control over all aspects of the manufacturing process of, and are dependent on, our contract manufacturing partners for compliance with cGMP regulations for manufacturing both active drug substances and finished drug products. Third-party manufacturers may not be able to comply with cGMP regulations or similar regulatory requirements outside of the United States. If our contract manufacturers cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA, the EMA or comparable foreign regulatory bodies, they will not be able to secure and/or maintain approval for their manufacturing facilities. In addition, we do not have complete control over the ability of our contract manufacturers to maintain adequate quality control, quality assurance and qualified personnel. If the FDA, the EMA or a comparable foreign regulatory authority does not approve these facilities for the manufacture of our drug candidates or if such regulatory authority withdraws any such approval in the future, we may need to find alternative manufacturing facilities, which would significantly impact our ability to develop, obtain marketing approval for or market our drug candidates, if approved.
Our drug candidates and any products that we may develop may compete with other drug candidates and products for access to suitable manufacturing facilities. As a result, we may not obtain access to these facilities on a priority basis or at all. There are a limited number of manufacturers that operate under cGMP regulations and that might be capable of manufacturing for us.
Any performance failure on the part of our existing or future manufacturers could delay clinical development or marketing approval or could result in withdrawal of marketing approval. We do not currently have arrangements in place for redundant supply or a second source for bulk drug substance. If our current CMOs cannot perform as agreed, we may be required to replace such manufacturers. Although we believe that there are several potential alternative manufacturers who could manufacture our drug candidates, we may incur added costs and delays in identifying and qualifying any such replacement manufacturer or may not be able to reach agreement with any alternative manufacturer.
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Our current and anticipated future dependence upon others for the manufacture of our drug candidates or products may adversely affect our future profit margins and our ability to commercialize any products that receive marketing approval on a timely and competitive basis.
Some of our suppliers may experience disruption to their respective supply chain due to the effects of macroeconomic conditions, which could delay, prevent or impair our development or commercialization efforts.
We obtain certain chemical or biological intermediates in the synthesis of our drug candidates and natural health products (NHPs) for toxicology testing in countries affected by macroeconomic events and conditions, including inflation, increasing interest rates, uncertainty with respect to the federal budget and debt ceiling and potential government shutdowns related thereto, increasing financial market volatility and uncertainty, the impact of war or military conflict, including regional conflicts around the world, and public health pandemics. If we are unable to obtain these chemical or biological intermediates or NHPs in sufficient quantity and in a timely manner due to disruptions in the global supply chain caused by macroeconomic events and conditions, the development, testing and clinical trials of that drug candidate may be delayed or infeasible, and regulatory approval or commercial launch of any resulting product may be delayed or not obtained, which could significantly harm our business.
Our CMOs may be unable to successfully scale-up manufacturing of our drug candidates in sufficient quality and quantity, which would delay or prevent us from developing our drug candidates and commercializing approved products, if any.
In order to conduct clinical trials of our drug candidates, we will need to manufacture our drug candidates in large quantities. Quality issues may arise during scale-up activities. Our reliance on a limited number of CMOs, the complexity of drug manufacturing and the difficulty of scaling up a manufacturing process could cause the delay of clinical trials, regulatory submissions, required approvals or commercialization of our drug candidates, cause us to incur higher costs and prevent us from commercializing our drug candidates successfully. Furthermore, if our CMOs fail to deliver the required commercial quality and quantities of materials on a timely basis and at commercially reasonable prices, and we are unable to secure one or more replacement CMOs capable of production in a timely manner at a substantially equivalent cost, then testing and clinical trials of that drug candidate may be delayed or infeasible, and regulatory approval or commercial launch of any resulting product may be delayed or not obtained, which could significantly harm our business.
Risks Related to the Commercialization of Our Drug Candidates
Even if any of our drug candidates receive marketing approval, a drug candidate may fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial success.
If any of our drug candidates receive marketing approval, they may nonetheless fail to gain sufficient market acceptance by physicians, patients, third-party payors and others in the medical community. For example, ibrutinib is a well-established current treatment for chronic lymphocytic leukemia (CLL), and doctors may continue to rely on this and other treatments. If our drug candidates do not achieve an adequate level of acceptance, we may not generate sufficient revenue from product sales and we may not become profitable. The degree of market acceptance of our drug candidates, if approved for commercial sale, will depend on a number of factors, including:
•the efficacy and potential advantages compared to alternative treatments;
•the prevalence and severity of any side effects, in particular compared to alternative treatments;
•our ability to offer our products for sale at competitive prices;
•the convenience and ease of administration compared to alternative treatments;
•the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies;
•the strength of our marketing, sales and distribution support;
•the availability of third-party payor coverage and adequate reimbursement;
•the ability to secure a positive HTA recommendation for the product to be prescribed and reimbursed under the national health system;
•the timing of any marketing approval in relation to other product approvals; and
•any restrictions on the use of our products together with other medications.
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If we are unable to establish sales and marketing capabilities, we may not be successful in commercializing our drug candidates if and when they are approved.
We do not have a sales or marketing infrastructure and have no experience in the sale, marketing or distribution of biopharmaceutical products. To achieve commercial success for any product for which we obtain marketing approval, we will need to establish sales, marketing and distribution capabilities, either by ourselves or through collaboration or other arrangements with third parties.
We currently expect that we may build our own focused, specialized sales and marketing organization to support the commercialization in the United States of drug candidates for which we receive marketing approval and which can be commercialized with such capabilities. There are risks involved with establishing our own sales and marketing capabilities. For example, recruiting and training a sales force is expensive and time-consuming and could delay any product launch. If the commercial launch of a drug candidate for which we recruit a sales force and establish marketing capabilities is delayed or does not occur for any reason, we would have incurred these commercialization expenses prematurely or unnecessarily. These efforts may be costly, and our investment would be lost if we cannot retain or reposition our sales and marketing personnel.
Factors that may inhibit our efforts to commercialize our products on our own include:
•our inability to recruit, train and retain adequate numbers of effective sales, marketing, reimbursement, customer service, medical affairs and other support personnel;
•the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines; and
•unforeseen costs and expenses associated with creating an independent sales and marketing organization.
If we are unable to establish our own sales and marketing capabilities or enter into arrangements with third parties to perform these services, our revenue from product sales and our profitability, if any, are likely to be lower than if we ourselves were to market and sell any products that we develop. In addition, we may not be successful in entering into arrangements with third parties to market and sell our drug candidates or may be unable to do so on terms that are acceptable to us. Any of these third parties may fail to devote the necessary resources and attention to sell and market our products effectively. If we do not establish sales and marketing capabilities successfully, either on our own or in collaboration with third parties, we will not be successful in commercializing our drug candidates.
Even if we are able to commercialize any drug candidates, the products may become subject to unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, which would harm our business.
The regulations that govern marketing approvals, pricing, coverage and reimbursement for new drug products vary widely from country to country. Current and future legislation may significantly change the approval requirements in ways that could involve additional costs and cause delays in obtaining approvals. Some countries require approval of the sale price of a drug before it can be marketed. In many countries, the pricing review period begins after marketing or product licensing approval is granted. To obtain reimbursement or pricing approval in some countries, we may be required to conduct a clinical trial that compares the cost-effectiveness of our drug candidate to other available therapies. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmental control even after initial approval is granted. As a result, we might obtain marketing approval for a drug candidate in a particular country, but then be subject to price regulations that delay our commercial launch of the product, possibly for lengthy time periods, and negatively impact the revenues, if any, we are able to generate from the sale of the product in that country. Adverse pricing limitations may hinder our ability to recoup our investment in one or more drug candidates, even if our drug candidates obtain marketing approval.
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Our ability to commercialize any drug candidates successfully also will depend in part on the extent to which coverage and adequate reimbursement for these products and related treatments will be available from government healthcare programs, private health insurers, national health technology assessment authorities in Europe and other organizations, and if reimbursement and coverage is available, the level of reimbursement and coverage. Government authorities and third-party payors, such as private health insurers and health maintenance organizations, decide which medications they will pay for and establish reimbursement levels. A key focus in the U.S. healthcare industry and elsewhere is cost containment. Government authorities and third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications, as well as mandating a system of manufacturer rebates to government payors. Increasingly, government authorities and third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for medical products. Coverage and reimbursement may not be available for any product that we commercialize and, even if these are available, the level of reimbursement may not be sufficient to cover our costs. Reimbursement may affect the demand for, or the price of, any drug candidate for which we obtain marketing approval. Obtaining and maintaining adequate reimbursement for our products may be difficult. We may be required to conduct expensive pharmacoeconomic studies to justify coverage and reimbursement or the level of reimbursement relative to other therapies. If coverage and adequate reimbursement are not available or reimbursement is available only to limited levels, we may not be able to successfully commercialize any drug candidate for which we obtain marketing approval.
There may be significant delays in obtaining coverage and reimbursement for newly approved drugs, and coverage may be more limited than the purposes for which the drug is approved by the FDA or similar regulatory authorities outside of the United States. Moreover, eligibility for coverage and reimbursement does not imply that a drug will be paid for in all cases, across the entire eligible patient population, as a first-line treatment or at a rate that covers our costs, including research, development, intellectual property, manufacture, sale and distribution expenses. Interim reimbursement levels for new drugs, if applicable, also may not be sufficient to cover our costs and may not be made permanent. Reimbursement rates may vary according to the use of the drug and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost drugs, may take into account comparative cost-effectiveness, particularly in European jurisdictions, and may be incorporated into existing payments for other services. Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the United States. Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement policies. Our inability to promptly obtain coverage and adequate reimbursement rates from both government-funded and private payors for any approved products that we develop could have a material adverse effect on our results of operations, our ability to raise capital needed to commercialize products and our overall financial condition.
Product liability lawsuits against us could cause us to incur substantial liabilities and to limit commercialization of any products that we may develop.
We face an inherent risk of product liability exposure related to the testing of our drug candidates in human clinical trials and will face an even greater risk if we commercially sell any products that we may develop. If we cannot successfully defend ourselves against claims that our drug candidates or products caused injuries, we will incur substantial liabilities. Regardless of merit or eventual outcome, liability claims may result in:
•decreased demand for any drug candidates or products that we may develop;
•termination of clinical trials;
•withdrawal of marketing approval, recall, restriction on the approval or a “black box” warning or contraindication for an approved drug;
•withdrawal of clinical trial participants;
•significant costs to defend the related litigation;
•substantial monetary awards to trial participants or patients;
•loss of revenue;
•injury to our reputation and significant negative media attention;
•reduced resources of our management to pursue our business strategy; and
•the inability to commercialize any products that we may develop.
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Although we maintain product liability insurance coverage, it may not be adequate to cover all liabilities that we may incur. We anticipate that we will need to increase our product liability insurance coverage as we initiate our clinical trials, as we expand our clinical trials and if we commence commercialization of our drug candidates. Insurance coverage is increasingly expensive. We may not be able to maintain or increase our insurance coverage at a reasonable cost or in an amount adequate to satisfy any liability that may arise.
Risks Related to Our Intellectual Property
If we are unable to obtain and maintain patent protection for our technology, our current drug candidates and any future drug candidates that we may develop, or if the scope of the patent protection obtained is not sufficiently broad, our competitors and other third parties could develop and commercialize technology and drug candidates similar or identical to ours, and our ability to successfully commercialize our technology and drug candidates may be impaired, and we may not be able to compete effectively in our market.
Our commercial success depends, in large part, on our ability to obtain and maintain patent and other intellectual property and proprietary protection in the United States and other countries with respect to our current drug candidates, future drug candidates that we may develop and proprietary technology. We seek to protect our proprietary position by filing patent applications in the United States and abroad related to our novel technologies and drug candidates. If we are unable to obtain or maintain patent protection with respect to our proprietary drug candidates and technology or do not otherwise adequately protect our intellectual property, competitors and other third parties may be able to use our drug candidates and technologies and erode or negate any competitive advantage that we may have, which could have a material adverse effect on our business. Any disclosure to or misappropriation by third parties of our confidential proprietary information could enable competitors and other third parties to quickly duplicate or surpass our technological achievements, thus eroding our competitive position in our market. Moreover, the patent applications we own, co-own or license may fail to result in issued patents that cover our current and future drug candidates in the United States or in other foreign countries. Our patent applications cannot be enforced against third parties practicing the technology claimed in such applications unless, and until, a patent issues from such applications, and then only to the extent the issued claims cover the technology. If the patent applications we hold with respect to our development programs and drug candidates fail to issue, if their breadth or strength of protection is threatened or if they fail to provide meaningful exclusivity for our current and future drug candidates, it could have a material adverse effect on our ability to commercialize our drug candidates and our business.
To protect our proprietary positions, we file patent applications in the United States and other countries related to our novel technologies and drug candidates that are important to our business. The patent application and prosecution process is expensive, complex and time-consuming, and we may not be able to file and prosecute all necessary or desirable patent applications in all potential jurisdictions at a reasonable cost or in a timely manner. It is also possible that we will fail to identify patentable aspects of our research and development output before it is too late to obtain patent protection. It is possible that defects of form in the preparation or filing of our patents or patent applications may exist, or may arise in the future, such as with respect to proper priority claims, inventorship, claim scope or patent term adjustments, and it is possible that we may be unable to correct such defects. If any current or future licensors or licensees are not fully cooperative or disagree with us as to the prosecution, maintenance or enforcement of any patent rights, such patent rights could be compromised and we might not be able to prevent third parties from making, using and selling competing products. If there are material defects in the form or preparation of our patents or patent applications, such patents or applications may be invalid and unenforceable. Moreover, our competitors and other third parties may independently develop equivalent knowledge, methods and know-how, or design around our claimed subject matter. Any of these outcomes could impair our ability to prevent competition from third parties.
Method of use patents protect the use of a product for the specified method. This type of patent does not prevent a competitor from making and marketing a product that is identical to our therapeutics for an indication that is outside the scope of the patented method. Moreover, even if competitors do not actively promote their product for our targeted indications, clinicians may prescribe these products “off-label.” Although off-label prescriptions may infringe or contribute to the infringement of method of use patents, the practice is common and such infringement is difficult to prevent or prosecute. Consequently, the types of claims in issued patents of our patent portfolio may fail to afford strong protection against third-party infringement.
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The patent position of biotechnology and pharmaceutical companies generally is highly uncertain, involves complex legal and factual questions and has in recent years been the subject of much litigation, resulting in court decisions, including U.S. Supreme Court decisions, which have increased uncertainties as to the ability to enforce patent rights in the future. In addition, the protections offered by laws of different countries vary and the laws of foreign countries may not protect our rights to the same extent as the laws of the United States. For example, European patent law and jurisprudence restricts the patentability of methods of treatment of the human body more than U.S. patent law does. No consistent policy regarding the breadth of claims allowed in biotechnology and pharmaceutical patents has emerged to date in the United States or in many foreign jurisdictions. In addition, the determination of patent rights with respect to pharmaceutical compounds and technologies commonly involves complex legal and factual questions, which have in recent years been the subject of much litigation. As a result, the issuance, scope, validity, enforceability and commercial value of our patent rights, whether owned or in-licensed, are highly uncertain.
We may not be aware of all third-party intellectual property rights potentially relating to our current and future drug candidates or their intended uses, and as a result the impact of such third-party intellectual property rights upon the patentability of our own patents and patent applications, as well as the impact of such third-party intellectual property upon our freedom to operate, is highly uncertain. Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions typically are not published until 18 months after filing, or in some cases not at all. Therefore, we cannot know with certainty whether we or our licensors were the first to make the inventions claimed in our patents or pending patent applications, or that we or our licensors were the first inventors to file for patent protection of such inventions. As a result, the issuance, scope, validity, enforceability and commercial value of our patent rights are highly uncertain. Our pending and future patent applications, whether owned or in-licensed, may not result in patents being issued that protect our technology or drug candidates, in whole or in part, or that effectively prevent others from commercializing competitive technologies and products. Changes in either the patent laws or interpretation of the patent laws in the United States and other countries may diminish the value of our patents or narrow the scope of our patent protection. Moreover, we may be subject to third-party challenges in patent offices in the United States and abroad. Even issued patents may later be found invalid or unenforceable or may be modified or revoked in proceedings instituted by third parties before various patent offices or in courts. For example, our pending patent applications may be subject to third-party submissions of prior art to the United States Patent and Trademark Office (USPTO) challenging the validity of one or more claims of our owned or licensed pending patent applications, precluding the granting of a patent based on one of our owned or licensed pending patent applications or we may become involved in opposition, derivation, reexamination, inter partes review, post-grant review or other post-grant proceedings, in the United States or elsewhere, challenging our or our licensors’ patent rights or the patent rights of others. An adverse determination in any such challenge could reduce the scope of, or invalidate, our patent rights, allow third parties to commercialize our technology or drug candidates and compete directly with us, without payment to us, or result in our inability to manufacture or commercialize products without infringing third-party patent rights, which could significantly harm our business and results of operations. Such challenges may result in loss of patent rights or exclusivity, or in patent claims being narrowed, invalidated or held unenforceable, in whole or in part, which could limit our ability to stop others from using or commercializing similar or identical technology and drug candidates, or limit the duration of the patent protection of our technology and drug candidates. Such proceedings also may result in substantial cost and require significant time from our scientific personnel and management, even if the eventual outcome is favorable to us. In addition, any threat to the breadth or strength of protection provided by our patents and patent applications could dissuade companies from collaborating with us to license, develop or commercialize current or future drug candidates.
Even if our patent applications issue as patents and are unchallenged, they may not issue in a form that will provide us with any meaningful protection against competing products or processes sufficient to achieve our business objectives, prevent competitors and other third parties from competing with us or otherwise provide us with any competitive advantage. Our competitors and other third parties may be able to design around or circumvent our patents, should they issue, by developing similar or alternative technologies or products in a non-infringing manner. Our competitors and other third parties may seek approval to market their own products similar to or otherwise competitive with our products. In these circumstances, we may need to defend and/or assert our patents, including by filing lawsuits alleging patent infringement. In any of these types of proceedings, a court or other agency with jurisdiction may find our patents invalid and/or unenforceable. If the patent protection provided by the patents and patent applications we own or license is not sufficiently broad and strong to impede such competition, our ability to successfully commercialize our drug candidates could be negatively affected and companies may be dissuaded from collaborating with us, which could have a material adverse effect on our business, financial condition, results of operations and prospects.
Given the amount of time required for the development, testing and regulatory review of new drug candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. As a result, our patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours. The degree of future protection for our proprietary rights is uncertain. Only limited protection may be available and may not adequately protect our rights or permit us to gain or keep any competitive advantage. Any of the foregoing could have a material adverse effect on our business, financial condition, results of operations and prospects.
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Changes in patent law in the United States and in non-U.S. jurisdictions could diminish the value of patents in general, thereby impairing our ability to protect our drug candidates.
As is the case with other biopharmaceutical companies, our success is heavily dependent on intellectual property, particularly patents. Obtaining and enforcing patents in the biopharmaceutical industry involves both technological and legal complexity, and therefore is costly, time-consuming and inherently uncertain. Past or future patent reform legislation in the United States and other countries could increase the uncertainties and costs surrounding the prosecution of patent applications and the enforcement or defense of issued patents, may diminish the value of our patents or narrow the scope of our patent protection and may affect the scope, strength and enforceability of our patent rights or the nature of proceedings that may be brought by or against us related to our patent rights.
Additionally, recent U.S. Supreme Court rulings have narrowed the scope of patent protection available in certain circumstances and weakened the rights of patent owners in certain situations. In addition to increasing uncertainty with regard to our ability to obtain patents in the future, this combination of events has created uncertainty with respect to the value of patents once obtained. Depending on decisions and actions by the U.S. Congress, the U.S. Supreme Court, the U.S. courts, the USPTO and the relevant law-making bodies in other countries, the laws and regulations governing patents could change in unpredictable ways that would weaken our ability to obtain new patents or to enforce our existing patents and patents that we might obtain in the future. Any of the foregoing, including any similar adverse changes in the patent laws of other jurisdictions, could also have a material adverse effect on our business, financial condition, results of operations and prospects.
Even if we are able to obtain patent protection for our drug candidates, the life of such protection is limited, and third parties could develop and commercialize products and technologies similar or identical to ours and compete directly against us after the expiration of our patent rights and our ability to successfully commercialize any product or technology would be materially adversely affected.
The life of a patent and the protection it affords is limited. For example, in the United States, if all maintenance fees are timely paid, the natural expiration of a patent is generally 20 years from its earliest U.S. non-provisional filing date. Even if we successfully obtain patent protection for an approved drug candidate, it may face competition from generic or biosimilar medications. Manufacturers of generic or biosimilar drugs may challenge the scope, validity or enforceability of our patents in court or before a patent office, and we may not be successful in enforcing or defending those intellectual property rights and, as a result, may not be able to develop or market the relevant product exclusively, which would materially adversely affect any potential sales of that product.
Given the amount of time required for the development, testing and regulatory review of new drug candidates, patents protecting such drug candidates might expire before or shortly after such drug candidates are commercialized. As a result, our patents and patent applications may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours. Upon issuance in the United States, the term of a patent can be increased by patent term adjustment based on certain delays caused by the USPTO, but this increase can be reduced or eliminated based on certain delays caused by the patent applicant during patent prosecution. The term of a U.S. patent may also be shortened if the patent is terminally disclaimed over an earlier-filed patent. A patent term extension (“PTE”) based on regulatory delay may be available in the United States. However, only a single patent can be extended for each marketing approval, and any patent can be extended only once, for a single product. Laws governing extensions analogous to PTEs in foreign jurisdictions vary widely, as do laws governing the ability to obtain multiple patents from a single patent family. Additionally, we may not receive an extension if we fail to exercise due diligence during the testing phase or regulatory review process, apply within applicable deadlines, fail to apply prior to expiration of relevant patents or otherwise fail to satisfy applicable requirements. If we are unable to obtain PTE or restoration, or the term of any such extension is less than we request, the period during which we will have the right to exclusively market our therapeutic will be shorter and our competitors may obtain approval of competing products following our patent expiration and may take advantage of our investment in development and clinical trials by referencing our clinical and preclinical data to launch their product earlier than might otherwise be the case, and our revenue could be reduced, possibly materially. Upon the expiration of patents that may issue from our pending patent applications, we will not be able to assert such patent rights against potential competitors and other third parties, which would materially adversely affect our business, financial condition, results of operations and prospects.
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We may need to license intellectual property from third parties, such licenses may not be available or may not be available on commercially reasonable terms and we may not be successful in obtaining or maintaining necessary rights to our drug candidates through acquisitions and in-licenses.
A third party may hold intellectual property, including patent rights, that are important or necessary to the development of our drug candidates. It may be necessary for us to use the patented or proprietary technology of a third party to commercialize our own technology or drug candidates, in which case we would be required to obtain a license from such third party. Because our development programs may in the future require the use of proprietary rights held by third parties, the growth of our business may depend in part on our ability to acquire, in-license, or use these third-party proprietary rights. A license to such intellectual property may not be available or may not be available on commercially reasonable terms, which could have a material adverse effect on our business, financial condition, results of operations and prospects. We may be unable to acquire or in-license any compositions, methods of use, processes or other third-party intellectual property rights from third parties that we identify as necessary for our drug candidates.
The licensing and acquisition of third-party intellectual property rights is a competitive practice, and companies that may be more established, or have greater resources than we do, also may be pursuing strategies to license or acquire third-party intellectual property rights that we may consider necessary or attractive in order to commercialize our drug candidates. More established companies may have a competitive advantage over us due to their larger size and cash resources or greater clinical development and commercialization capabilities. In addition, companies that perceive us to be a competitor may be unwilling to assign or license rights to us. We also may be unable to license or acquire third-party intellectual property rights on terms that would allow us to make an appropriate return on our investment or at all. We may not be able to successfully complete such negotiations and ultimately acquire the rights to the intellectual property surrounding the additional drug candidates we may seek to acquire. If we are unable to successfully obtain rights to required third-party intellectual property rights or maintain the existing intellectual property rights we have, we may have to abandon development of the relevant program or drug candidate, which could have a material adverse effect on our business, financial condition, results of operations, and prospects.
We may not identify relevant third-party patents or may incorrectly interpret the relevance, scope or expiration of a third-party patent, and third parties may initiate legal proceedings alleging that we are infringing, misappropriating or otherwise violating their intellectual property rights, the outcome of which would be uncertain and could have a material adverse effect on our business.
Our commercial success depends, in part, upon our ability, and the ability of our collaborators to develop, manufacture, market and sell our drug candidates and future drug candidates and use our proprietary technologies without infringing, misappropriating or otherwise violating the intellectual property and other proprietary rights of third parties.
Numerous third-party U.S. and non-U.S. issued patents exist in the area of biotechnology, including in the area of targeted protein degraders and including patents owned or controlled by our competitors. There is considerable and complex intellectual property litigation in the biotechnology and pharmaceutical industries, as well as administrative proceedings for challenging patents, including interference, reexamination and inter partes review proceedings before the USPTO and oppositions and other comparable proceedings in foreign jurisdictions. We may in the future become party to, or be threatened with, adversarial proceedings or litigation regarding intellectual property rights with respect to our drug candidates, future drug candidates and technology, including interference, derivation, reexamination or inter partes review proceedings before the USPTO. Our competitors or other third parties may assert infringement claims against us based on existing patents or patents that may be granted in the future and claims may also come from competitors or other third parties against whom our own patent portfolio may have no deterrent effect. The outcome of intellectual property litigation is subject to uncertainties that cannot be adequately quantified in advance. Other parties may allege that our drug candidates or the use of our technologies infringe patent claims or other intellectual property rights held by them or that we are employing their proprietary technology without authorization.
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As we continue to develop and, if approved, commercialize our current and future drug candidates, competitors or other third parties may claim that our technology infringes, misappropriates or otherwise violates their intellectual property rights. There are and may in the future be additional U.S. and foreign-issued patents and pending patent applications owned by third parties in the fields in which we are pursuing drug candidates. For example, we are aware of a patent owned by a third party with a claim that covers many potential targeted protein degraders. This patent may be alleged to cover one or more of our targeted protein degrader drug candidates, including our NX-5948 and NX-2127 drug candidates. While we believe that we have valid defenses against any assertion of such patent against us, such defenses may be unsuccessful. If we are unsuccessful and any of our targeted protein degrader drug candidates is found to infringe this patent, we could be required to obtain a license to such patent or forced to permanently cease developing, manufacturing, marketing and commercializing the infringing targeted protein degrader drug candidate. We may not be able to obtain any required license on commercially reasonable terms or at all, and even if we were able to obtain a license, it could be non-exclusive, thereby giving the licensor and other third parties the right to use the same technologies licensed to us, and it could require us to make substantial licensing, royalty and other payments. We also could be forced, including by court order, to permanently cease developing, manufacturing, marketing and commercializing the drug candidate. In addition, we could be found liable for significant monetary damages, including treble damages and attorneys’ fees, if we are found to have willingly infringed any such patent. Even if we were ultimately to prevail, any litigation could require us to divert substantial financial and management resources that we would otherwise be able to devote to our business.
Moreover, as the biotechnology and pharmaceutical industries expand and more patents are issued, the risk increases that our drug candidates may give rise to claims of infringement of the patent rights of others. There may be third-party patents of which we are currently unaware with claims to materials, formulations, methods of manufacture or methods for treatment related to the use or manufacture of our drug candidates or we may incorrectly conclude that a third-party patent is invalid, unenforceable or not infringed by our activities. Because patent applications can take many years to issue, there may be currently pending patent applications that may later result in issued patents that our drug candidates may infringe. In addition, third parties may obtain patents in the future and claim that use of our technologies infringes upon these patents.
Patent and other types of the intellectual property litigation can involve complex factual and legal questions, and their outcome is uncertain. If we are found, or believe there is a risk we may be found, by a court of competent jurisdiction to infringe, misappropriate or otherwise violate a third party’s intellectual property rights, we could be required or may choose to obtain a license from such third party to continue developing and marketing our products and technology. In addition, we could be found liable for monetary damages, which could be significant, including treble damages and attorneys’ fees if we are found to have willfully infringed a patent or other intellectual property right. A finding of infringement could prevent us from producing or commercializing our drug candidates or future drug candidates or force us to cease some of our business operations, which could materially harm our business. Alternatively, we may need to redesign our infringing products, which may be impossible or require substantial time and monetary expenditure, including due to any additional or separate regulatory approval to which the redesigned products may be subject by regulatory authorities, and any redesigned products may be of inferior quality or performance. If we lose a foreign patent lawsuit alleging our infringement of a competitor’s patents, we could be prevented from marketing our therapeutics in one or more foreign countries and/or be required to pay monetary damages for infringement or royalties in order to continue marketing. Claims that we have misappropriated the confidential information, trade secrets or other intellectual property of third parties could have a similar negative impact on our business. Any of these outcomes would have a material adverse effect on our business.
Further, we do not know which processes we will use for commercial manufacture of our future products, or which technologies owned or controlled by third parties may prove important or essential to those processes. Many companies have filed, and continue to file, patent applications related to novel protein modulation therapies that target disease-causing proteins and many companies have filed and continue to file patent applications related to ACT. Some of these patent applications have already been allowed or issued and others may issue in the future. Because this area is competitive and of strong interest to pharmaceutical and biotechnology companies, there likely will be additional patent applications filed and additional patents granted in the future, as well as additional research and development programs expected in the future. If a patent holder believes the manufacture, use, sale, offer for sale or importation of one of our drug candidates or future products infringes its patent, the patent holder may sue us even if we have licensed other patent protection for our technology. Moreover, we may face patent infringement claims from non-practicing entities that have no relevant product revenue and against whom our licensed patent portfolio may therefore have no deterrent effect.
It is also possible that we have failed to identify all relevant third-party patents or applications. Patent searching is imperfect due to differences in terminology among patents, incomplete databases and the difficulty in assessing the meaning of patent claims. We may fail to identify relevant patents or patent applications or may identify pending patent applications of potential interest but incorrectly predict the likelihood that such patent applications may issue with claims of relevance to our technology. For example, we may incorrectly determine that our drug candidates are not covered by a third-party patent or may incorrectly predict whether a third-party’s pending application will issue with claims of relevant scope.
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In addition, we may be unaware of one or more issued patents that would be infringed by the manufacture, sale, importation or use of a current or future drug candidate, or we may incorrectly conclude that a third-party patent is invalid, unenforceable or not infringed by our activities. Our competitors in both the United States and abroad, many of which have substantially greater resources and have made substantial investments in patent portfolios and competing technologies, may have applied for or obtained or may in the future apply for and obtain, patents that will prevent, limit or otherwise interfere with our ability to make, use and sell our therapeutics. We do not always conduct independent reviews of pending patent applications of and patents issued to third parties.
Furthermore, because patent applications can take many years to issue, may be confidential for 18 months or more after filing and can be revised before issuance, there may be applications now pending that we are not aware of that may later result in issued patents that may be infringed by the manufacture, use, sale or importation of our drug candidates or future products. Additionally, pending patent applications that have been published can, subject to certain limitations, later be amended in a manner that could cover our technologies, our future products or the manufacture or use of our future products. As such, there may be applications of others now pending or recently revived patents of which we are unaware. These patent applications may later result in issued patents, or the revival of previously abandoned patents, that will prevent, limit or otherwise interfere with our ability to make, use or sell our products.
Third parties may assert infringement claims against us based on existing intellectual property rights and intellectual property rights that may be granted in the future. If we were to challenge the validity of an issued U.S. patent in court, such as an issued U.S. patent of potential relevance to some of our drug candidates or future drug candidates or manufacture or methods of use, we would need to overcome a statutory presumption of validity that attaches to every U.S. patent. This burden is a high one and in order to prevail, we would have to present clear and convincing evidence as to the invalidity of the patent’s claims. Even if we believe third-party intellectual property claims are without merit, there is no assurance that a court would find in our favor on questions of infringement, validity or enforceability by invalidating the claims of any such U.S. patent or finding that our drug candidates or technology did not infringe any such claims.
We may choose to challenge the enforceability or validity of claims in a third party’s U.S. patent by requesting that the USPTO review the patent claims in an ex-parte re-exam, inter partes review or post-grant review proceedings. These proceedings are expensive and may consume our time or other resources. We may choose to challenge a third party’s patent in patent opposition proceedings in the European Patent Office (EPO) or other foreign patent office. The costs of these opposition proceedings could be substantial and may consume our time or other resources. If we fail to obtain a favorable result at the USPTO, EPO or other patent office then we may be exposed to litigation by a third party alleging that the patent may be infringed by our drug candidates or proprietary technologies.
Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may be time-consuming, cause us to incur significant expenses and could distract our technical and management personnel from their normal responsibilities and ongoing business operations. If we are unable to avoid infringing the patent rights of others, we may be required to seek a license, defend an infringement action or challenge the validity of the patents in court, or redesign our future products or processes. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments. If securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock. Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development activities or any future sales, marketing or distribution activities. Unlike some of our larger competitors and other third parties, we may not have sufficient financial or other resources to conduct such litigation or proceedings adequately. Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation or administrative proceedings, there is a risk that some of our confidential information could be compromised by disclosure. Uncertainties resulting from the litigation of patent litigation and other proceedings could delay our research and development efforts, adversely affect our ability to raise additional funds and could limit our ability to continue our operations. Any of the foregoing could have a material adverse effect on our business.
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We may be subject to claims by third parties asserting that we or our employees, consultants, contractors or advisors have misappropriated, wrongfully used or disclosed alleged trade secrets or other intellectual property, or claiming ownership of what we regard as our own intellectual property.
We may hire and employ individuals who were previously employed at, or may have previously provided or may be currently providing consulting services to, universities as well as other biotechnology or pharmaceutical companies, including our competitors or potential competitors. We have received confidential and proprietary information from collaborators, prospective licensees and other third parties. Although we try to ensure that our employees, consultants and advisors do not improperly use the proprietary information or know-how of others in their work for us, we may be subject to claims that these individuals or we have inadvertently or otherwise improperly used or disclosed intellectual property, including trade secrets or other proprietary information, of any such individual’s former employer. We also may in the future be subject to claims that we have caused such individual to breach the terms of his or her non-competition or non-solicitation agreement or from former employers or other third parties claiming to have an ownership interest in our patents or other intellectual property. Litigation may be necessary to defend against these claims. We may not be successful in defending these claims, and if we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights, such as exclusive ownership of, or right to use, valuable intellectual property. In addition, we may lose personnel as a result of such claims and any such litigation or the threat thereof may adversely affect our ability to hire employees or contract with independent contractors. A loss of key personnel or their work product could hamper or prevent our ability to commercialize our drug candidates, which would have a material adverse effect on our business, results of operations, financial condition and prospects. Even if we are successful, litigation could result in substantial cost and reputational loss and distract our management and other employees from their regular responsibilities.
In addition, although it is our policy to require our employees, consultants and contractors who may be involved in the development of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who in fact develops intellectual property that we regard as our own. Moreover, even when we obtain agreements assigning intellectual property to us, such assignment agreements may not be self-executing or may be breached, and we may be forced to bring claims against third parties, or defend claims they may bring against us, to determine the ownership of what we regard as our intellectual property. Furthermore, individuals executing agreements with us may have preexisting or competing obligations to a third party, such as an academic institution, and thus an agreement with us may be ineffective in perfecting ownership of inventions developed by that individual. In addition, we or our licensors may in the future be subject to claims by former employees, consultants or other third parties asserting an ownership right in our owned or licensed patents or patent applications. An adverse determination in any such litigation or proceeding may result in loss of exclusivity or freedom to operate or in patent claims being narrowed, invalidated or held unenforceable, in whole or in part, which could limit our ability to stop others from using or commercializing similar technology and therapeutics, without payment to us, or could limit the duration of the patent protection covering our technology and drug candidates. Such challenges may also result in our inability to develop, manufacture or commercialize our drug candidates without infringing third-party patent rights. In addition, if the breadth or strength of protection provided by our owned or licensed patents and patent applications is threatened, it could dissuade companies from collaborating with us to license, develop or commercialize current or future drug candidates. Any of the foregoing could have a material adverse effect on our business, financial condition, results of operations and prospects.
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We may become involved in lawsuits to protect or enforce our patents, the patents of our licensors, or other intellectual property, which could be expensive, time-consuming and unsuccessful.
Competitors or other third parties may infringe our patents, the patents of our licensors or other intellectual property. To counter infringement or unauthorized use, we may be required to file infringement claims, which, regardless of merit, can be expensive, time-consuming, unpredictable and divert the time and attention of our management and scientific personnel. Any claims we assert against perceived infringers could provoke those parties to assert counterclaims against us alleging that we infringe their patents or other intellectual property. In addition, in a patent infringement proceeding, a court may decide that a patent of ours or our licensors is invalid or unenforceable, in whole or in part, construe the patent’s claims narrowly or refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the technology in question. Grounds for a validity challenge could include an alleged failure to meet any of several statutory requirements, including lack of novelty, obviousness, written description, non-enablement or failure to claim patent-eligible subject matter. Grounds for an unenforceability assertion could include an allegation that someone connected with prosecution of the patent withheld information material to patentability from the USPTO, or made a misleading statement, during prosecution. Third parties also may raise similar claims before administrative bodies in the United States or abroad, even outside the context of litigation. Such mechanisms include reexamination, post-grant review, inter partes review, interference proceedings, derivation proceedings and equivalent proceedings in foreign jurisdictions. Such proceedings could result in the revocation or cancellation of or amendment to our patents in such a way that they no longer cover our drug candidates or prevent third parties from competing with our drug candidates. The outcome following legal assertions of invalidity and unenforceability is unpredictable. With respect to the validity question, for example, we cannot be certain that there is no invalidating prior art, of which the patent examiner and we or our licensing partners were unaware during prosecution. In any patent infringement proceeding, there is a risk that a court will decide that a patent of ours is invalid or unenforceable, in whole or in part. If a third party were to prevail on a legal assertion of invalidity or unenforceability, we could lose at least part, and perhaps all, of the patent protection on our drug candidates. There is also a risk that, even if the validity of such patents is upheld, the court will construe the patent’s claims narrowly or decide that we do not have the right to stop the other party from using the invention at issue on the grounds that our patent claims do not cover the invention, or decide that the other party’s use of our future patented technology falls under the safe harbor to patent infringement under 35 U.S.C. §271(e)(1). An adverse result in any litigation or proceeding involving our patents or patent applications may put one or more of our patents at risk of being invalidated, held unenforceable or interpreted narrowly. An adverse outcome in a litigation or proceeding involving our patents could limit our ability to assert our patents against those parties or other competitors and may curtail or preclude our ability to exclude third parties from making and selling similar or competitive products. Any of these occurrences could adversely affect our competitive business position, business prospects and financial condition. Similarly, if we assert trademark infringement claims, a court may determine that the marks we have asserted are invalid or unenforceable, or that the party against whom we have asserted trademark infringement has superior rights to the marks in question. In this case, we could ultimately be forced to cease use of such trademarks.
Even if we successfully assert our patents or other intellectual property rights, a court may not award remedies that sufficiently compensate us for our losses. For example, the court may decide not to grant an injunction against further infringing activity and instead award only monetary damages, which may or may not be an adequate remedy. Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during litigation. The impact of public announcements of the results of hearings related to such awards on the price of our common stock may be uncertain. If securities analysts or investors perceive such results to be negative, it could have a substantial adverse effect on the price of our common stock. Moreover, there can be no assurance that we will have sufficient financial or other resources to file and pursue such infringement claims, which typically last for years before they are concluded. Some of our competitors or other third parties may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their greater financial resources and more mature and developed intellectual property portfolios. Even if we ultimately prevail in such claims, the monetary cost of such litigation and the diversion of the attention of our management and scientific personnel for significant periods of time during such litigation could outweigh any benefit we receive as a result of the proceedings. In addition, the uncertainties associated with litigation could compromise our ability to raise the funds necessary to continue our clinical trials, continue our internal research programs, in-license needed technology or other drug candidates, or enter into development partnerships that would help us bring our drug candidates to market. Accordingly, despite our efforts, we may not be able to prevent third parties from infringing, misappropriating or successfully challenging our intellectual property rights. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could have a material adverse effect on our business, financial condition, results of operations and prospects.
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We may not be able to pursue or guarantee protection of our intellectual property rights in jurisdictions outside the United States.
Patents are of national or regional effect. Filing, prosecuting and defending patents on drug candidates, research programs and technology in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States could be less extensive than those in the United States. In some cases, we may not be able to obtain patent protection for certain technology and drug candidates outside the United States. In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States, even in jurisdictions where we do pursue patent protection. Consequently, we may not be able to prevent third parties from practicing our inventions in all countries outside the United States, even in jurisdictions where we do pursue patent protection, or from selling or importing products made using our inventions in and into the United States or other jurisdictions. Competitors or other third parties may use our technologies in jurisdictions where we have not pursued and obtained patent protection to develop their own products and, further, may export otherwise infringing products to territories where we have patent protection, but enforcement is not as strong as that in the United States. These products may compete with our drug candidates and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing.
Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions. The legal systems of certain countries, particularly certain developing countries, may not favor the enforcement of patents, trade secrets and other intellectual property protection, particularly those relating to biotechnology products, which could make it difficult for us to stop the infringement of our patents, if pursued and obtained, or marketing of competing products in violation of our proprietary rights generally. Proceedings to enforce our patent rights in foreign jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly and our patent applications at risk of not issuing and could provoke third parties to assert claims against us. We may not prevail in any lawsuits that we initiate and the damages or other remedies awarded, if any, may not be commercially meaningful. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.
Many countries have compulsory licensing laws under which a patent owner may be compelled to grant licenses to third parties. In addition, many countries limit the enforceability of patents against government agencies or government contractors. In these countries, the patent owner may have limited remedies, which could materially diminish the value of such patent. If we or any of our licensors is forced to grant a license to third parties with respect to any patents relevant to our business, our business, financial condition, results of operations and prospects could be materially and adversely affected. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.
In Europe, beginning June 1, 2023, European applications and patents may be subject to the jurisdiction of the Unified Patent Court (UPC). Also, European applications will have the option, upon grant of a patent, of becoming a Unitary Patent which will be subject to the jurisdiction of the UPC. This will be a significant change in European patent practice. As the UPC is a new court system, there is no precedent for the court, increasing the uncertainty of any litigation. As a single court system can invalidate a European patent, we, where applicable, may opt out of the UPC, and as such, each European patent would need to be challenged in each individual country.
Obtaining and maintaining patent protection depends on compliance with various procedural, documentary, fee payment and other requirements imposed by governmental patent offices, and our patent protection could be reduced or eliminated for non-compliance with these requirements.
Periodic maintenance, renewal and annuity fees and various other government fees on any issued patent and/or patent application are due to be paid to the USPTO and patent offices in foreign countries in several stages over the lifetime of the patent and/or patent application. The USPTO and patent offices in various foreign countries require compliance with a number of procedural, documentary, fee payment and other similar requirements during the patent application process and throughout the life of a granted patent. Although an inadvertent lapse can in many cases be cured by payment of a late fee or by other means in accordance with the applicable rules, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of a patent or patent rights in the relevant jurisdiction. Non-compliance events that could result in abandonment or lapse of a patent or patent application include, but are not limited to, failure to respond to official actions within prescribed time limits, non-payment of fees and failure to properly legalize and submit formal documents. In such an event, our competitors or other third parties might be able to enter the market, which could have a material adverse effect on our business and competitive position.
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We may become subject to claims challenging the inventorship or ownership of our patents and other intellectual property.
We may be subject to claims that former employees, collaborators or other third parties have an interest in our patents or other intellectual property as an inventor or co-inventor. The failure to name the proper inventors on a patent application can result in the patents issuing thereon being unenforceable. Inventorship disputes may arise from conflicting views regarding the contributions of different individuals named as inventors, the effects of foreign laws where foreign nationals are involved in the development of the subject matter of the patent, conflicting obligations of third parties involved in developing our drug candidates or as a result of questions regarding co-ownership of potential joint inventions. Litigation may be necessary to resolve these and other claims challenging inventorship or ownership. Alternatively, or additionally, we may enter into agreements to clarify the scope of our rights in such intellectual property. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights, such as exclusive ownership of, or right to use, valuable intellectual property. Such an outcome could have a material adverse effect on our business. Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management and other employees.
In addition, while it is our policy to require our employees and contractors who may be involved in the conception or development of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who, in fact, conceives or develops intellectual property that we regard as our own. The assignment of intellectual property rights may not be self-executing, or the assignment agreements may be breached, and we may be forced to bring claims against third parties, or defend claims that they may bring against us, to determine the ownership of what we regard as our intellectual property. Such claims could have a material adverse effect on our business, financial condition, results of operations, and prospects.
If we are unable to protect the confidentiality of our trade secrets, our business and competitive position would be harmed.
In addition to seeking patents for some of our technology and drug candidates, we also rely on trade secrets, including unpatented know-how, technology and other proprietary information, and confidentiality agreements to maintain our competitive position. Any disclosure, either intentional or unintentional, by our employees, the employees of third parties with whom we share our facilities or third-party consultants and vendors that we engage to perform research, clinical trials or manufacturing activities, or misappropriation by third parties (such as through a cybersecurity breach) of our trade secrets or proprietary information could enable competitors to duplicate or surpass our technological achievements, thus eroding our competitive position in our market.
Trade secrets can be difficult to protect. We seek to protect our trade secrets, proprietary technology and processes, in part, by entering into non-disclosure and confidentiality agreements with parties who have access to them, such as our employees, corporate collaborators, outside scientific collaborators, CROs, contract manufacturers, consultants, advisors and other third parties. We also enter into confidentiality and invention or patent assignment agreements with our employees and consultants. We also seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining physical security of our premises and physical and electronic security of our information technology systems; however, such systems and security measures may be breached, and we may not have adequate remedies for any breach. We cannot guarantee that we have entered into such agreements with each party that may have or had access to our trade secrets or proprietary technology and processes and even in cases we have, we cannot be certain that our trade secrets and other confidential proprietary information will not be disclosed or used in an unauthorized manner by third parties. Monitoring unauthorized uses and disclosures of our intellectual property is difficult, and we do not know whether the steps we have taken to protect our intellectual property will be effective. Furthermore, despite these efforts, any of these parties may breach the agreements and disclose our proprietary information, including our trade secrets, and we may not be able to obtain adequate remedies for such breaches. Enforcing a claim that a party illegally disclosed or misappropriated a trade secret is expensive, time-consuming and difficult to prove and the outcome is unpredictable. In addition, some courts inside and outside of the United States may be less willing or unwilling to protect trade secrets. As a result, we could lose our trade secrets and third parties could use our trade secrets to compete with our drug candidates and technology.
Moreover, our competitors or other third parties may independently develop knowledge, methods and know-how equivalent to our trade secrets. If any of our trade secrets were to be lawfully obtained or independently developed by a competitor or other third parties, we would have no right to prevent them, or those to whom they communicate it, from using that technology or information to compete with us. If any of our trade secrets were to be disclosed to or independently developed by a competitor or other third parties, our competitive position would be harmed.
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Intellectual property rights do not necessarily address all potential threats.
The degree of future protection afforded by our intellectual property rights is uncertain because intellectual property rights have limitations and may not adequately protect our business or permit us to maintain our competitive advantage. For example:
•others may be able to make products that are similar to any drug candidates we may develop or utilize similar technology but that are not covered by the claims of the patents that we own or license now or in the future, or may develop drug candidates for the diseases our drug candidates seek to treat that do not infringe on our intellectual property rights, but which perform better or are more successful than our drug candidates;
•drug candidates utilizing issued patents and other intellectual property that we hold may prove to be ineffective for their intended treatment or we may not obtain regulatory approval for such drug candidates;
•we, or our current or future license partners or collaborators, might not have been the first to make the inventions covered by the issued patent or pending patent application that we own or license now or in the future;
•we, or our current or future license partners or collaborators, might not have been the first to file patent applications covering certain of our or their inventions;
•others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our owned or licensed intellectual property rights;
•it is possible that our pending owned patent applications or those that we may own or license in the future will not lead to issued patents;
•we cannot predict the scope of protection of any patent issuing based on our patent applications, including whether the patent applications that we own will result in issued patents with claims directed to our drug candidates or uses thereof in the United States or in other foreign countries;
•the claims of any current patents or patent issuing based on patent applications that we own may not provide protection against competitors or any competitive advantages or may be challenged by third parties;
•issued patents that we may hold rights to in the future may be held invalid or unenforceable, including as a result of legal challenges by our competitors;
•our competitors might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets;
•we may not develop additional proprietary technologies that are patentable;
•there may be significant pressure on the U.S. government and international governmental bodies to limit the scope of patent protection both inside and outside the United States for disease treatments that prove successful, as a matter of public policy regarding worldwide health concerns;
•countries other than the United States may have patent laws less favorable to patentees than those upheld by U.S. courts, allowing foreign competitors a better opportunity to create, develop and market competing drug candidates;
•we may need to initiate litigation or administrative proceedings to enforce and/or defend our patent rights which will be costly whether we win or lose;
•if we enforce and/or defend our patent rights, a court may not hold that our patents are valid, enforceable and infringed;
•we may choose not to file a patent application in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent application covering such intellectual property;
•we may fail to adequately protect and police our trademarks and trade secrets; and
• the patents of others may have an adverse effect on our business, including if others obtain patents claiming subject matter similar to or improving subject matter that is covered by our patent applications.
Should any of these events occur, they could have a material adverse effect on our business, financial condition, results of operations and prospects.
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Risks Related to Regulatory Approval and Marketing of Our Drug Candidates
The regulatory approval process of the FDA and other national or European regulators is lengthy, time-consuming and inherently unpredictable, and if we are ultimately unable to obtain marketing approval for our drug candidates, our business will be substantially harmed.
The time required to obtain approval by the FDA and other national or European regulators is unpredictable but typically takes many years following the commencement of clinical trials and depends upon numerous factors, including the substantial discretion of the regulatory authorities. In addition, approval policies, regulations or the type and amount of clinical data necessary to gain approval may change during the course of a drug candidate’s clinical development and may vary among jurisdictions. We have not obtained marketing approval for any drug candidate, and it is possible that none of our existing drug candidates, or any drug candidates we may seek to develop in the future, will ever obtain marketing approval.
Our drug candidates could be delayed or fail to receive marketing approval for many reasons, including the following:
•the FDA may disagree with our interpretation of data from preclinical studies or clinical trials;
•the FDA may disagree with the design or implementation of our planned clinical trials;
•data collected from clinical trials of our drug candidates may not be sufficient to support the submission of an NDA to the FDA or other submissions necessary to obtain marketing approval in the United States;
•we may be unable to demonstrate to the satisfaction of the FDA that a drug candidate is safe and effective for its proposed indication;
•the results of clinical trials may not meet the level of statistical significance required by the FDA for approval;
•we may be unable to demonstrate that our drug candidates’ clinical and other benefits outweigh their safety risks;
•the FDA may find deficiencies with or fail to approve the manufacturing processes or facilities of third-party manufacturers with which we contract for clinical and commercial supplies; and
•the approval policies or regulations of the FDA may significantly change in a manner rendering our clinical data insufficient for approval.
This lengthy approval process, as well as the unpredictability of future clinical trial results, may result in our failing to obtain regulatory approval to market any of our drug candidates, which would significantly harm our business, results of operations, financial condition and prospects. The FDA has substantial discretion in the approval process, and in determining when or whether regulatory approval will be obtained for any of our drug candidates. Even if we believe the data collected from clinical trials of our drug candidates are promising, such data may not be sufficient to support approval by the FDA.
In addition, even if we were to obtain approval, regulatory authorities may approve any of our drug candidates for fewer or more limited indications than we request, or they may impose significant limitations in the form of narrow indications, warnings or a risk evaluation and mitigation strategy (REMS). In addition, regulatory authorities may not approve the price we intend to charge for our products, may require precautions or contra-indications with respect to conditions of use, may grant approval contingent on the performance of costly post-marketing clinical trials, or may approve a drug candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization of that drug candidate. Any of the foregoing scenarios could materially harm the commercial prospects for our drug candidates.
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We have received Fast Track designation for NX-5948 and may seek Fast Track designation for other drug candidates in the future. Fast Track designation may not lead to faster development or regulatory review or approval process, and it does not increase the likelihood that our drug candidates will receive marketing approval.
In January 2024, the FDA granted Fast Track designation for NX-5948 in the United States for the treatment of adult patients with relapsed or refractory CLL or small lymphocytic lymphoma after at least two lines of therapy, including a BTK inhibitory and a B-cell lymphoma 2 inhibitor. As part of our business strategy, we may also seek Fast Track designation for other of our drug candidates. Programs with Fast Track designation may be eligible for more frequent interactions with the FDA, and, if relevant criteria are met, eligibility for Accelerated Approval and Priority Review. Fast Track designation applies to the drug candidate and the specific indication for which it is being studied. The FDA has broad discretion whether or not to grant this designation, so even if we believe a particular drug candidate is eligible for this designation, we cannot guarantee that the FDA would decide to grant it. If a drug candidate receives Fast Track designation but does not continue to meet the criteria for Fast Track designation, or if our clinical trials are delayed, suspended or terminated, or put on clinical hold due to unexpected adverse events or issues with clinical supply, we will not receive the benefits associated with the Fast Track program.
Furthermore, Fast Track designation does not change the standards for approval. The receipt of Fast Track designation for a drug candidate may not result in a faster development, regulatory review or approval process compared to drug candidates considered for approval under conventional FDA procedures and does not assure ultimate approval by the FDA. In addition, even if any drug candidate qualifies for FastTrack designation, the FDA may later decide that the drug candidate no longer meets the conditions for qualification or that the time period for FDA review or approval will not be shortened. Fast Track designation alone does not guarantee qualification for FDA Priority Review.
Under FDA policies, a drug candidate is eligible for Priority Review, or review within a six-month time frame from the time a complete NDA is accepted for filing, if the drug candidate provides a significant improvement compared to marketed drugs in the treatment, diagnosis or prevention of a disease. The FDA determines whether a drug qualifies for Priority Review after an NDA for such drug is submitted to the FDA. Therefore, until we submit NDAs for our drug candidates, we cannot be assured that they will be granted Priority Review. Even if Priority Review is granted for one of our drug candidates, the FDA does not always meet its six-month goal date for Priority Review, and the review process may be extended if the FDA requests additional information or clarification.
We may submit an NDA for our drug candidates under the Accelerated Approval pathway. If we are unable to obtain approval of our drug candidates through the Accelerated Approval Program in the United States, we may be required to conduct additional nonclinical and clinical studies and trials beyond those that we currently contemplate, which could increase the expense of obtaining, reduce the likelihood of obtaining and/or delay the timing of obtaining, necessary marketing approval. Even if we receive approval from the FDA through the Accelerated Approval Program, if our confirmatory postmarketing trial does not verify clinical benefit, or if we do not comply with rigorous postmarketing requirements, the FDA may seek to withdraw the approval.
We may submit an NDA for one or more of our drug candidates seeking approval through the Accelerated Approval Pathway. For any approval to market a drug product, we must provide the FDA and foreign regulatory agencies with clinical data that adequately demonstrate the safety and efficacy of the product for the indication applied for in the NDA or other respective regulatory filings. The Accelerated Approval Program is one of several approaches used by the FDA to make prescription drugs more rapidly available for the treatment of serious or life-threatening diseases. Section 506(c) of the Federal Food, Drug and Cosmetic Act (FDCA) provides that the FDA may grant Accelerated Approval to “a product for a serious or life-threatening condition upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.” Approval through the Accelerated Approval Program is subject, however, to the requirement that the applicant conduct additional postmarketing clinical trials to verify and describe the drug’s clinical benefit, where there is uncertainty as to the relationship of the surrogate endpoint to the clinical benefit, or of the observed clinical endpoint to ultimate outcome. Typically, clinical benefit is verified when postmarketing clinical trials show that the drug provides a clinically meaningful positive therapeutic effect, that is, an effect on how a patient feels, functions, or survives. The FDA may require that these studies be underway prior to Accelerated Approval pursuant to the Food and Drug Omnibus Reform Act of 2022. If such confirmatory trials fail to confirm the drug’s clinical profile or risks and benefits, the FDA may withdraw its approval of the drug.
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The FDA has broad discretion with regard to approval through the Accelerated Approval Program, and even if we believe that the Accelerated Approval Program is appropriate for one of our drug candidates, we cannot assure you that the FDA will ultimately agree. The FDA may also change its policies with respect to Accelerated Approval over time. For example, in March 2023, the FDA announced the availability of draft guidance on “Clinical Trial Considerations to Support Accelerated Approval of Oncology Therapeutics,” in which the agency outlined, and invited public comment on, its “preferred approach” of randomized controlled trials, including those that provide for longer term follow-up that could fulfill a postmarketing requirement to verify clinical benefit. In that draft guidance, the FDA acknowledged that historically, single-arm trial designs and response endpoints have most commonly been used in oncology but noted that such trials have limitations. Furthermore, even if we do obtain approval through the Accelerated Approval Program, we may not experience a faster development process, review or approval compared to conventional FDA procedures.
Even if the FDA reviews an NDA seeking Accelerated Approval, there can be no assurance that approval will be granted on a timely basis, or at all. The FDA may disagree that the design of, or results from, our studies support Accelerated Approval. Additionally, the FDA could require us to conduct further studies or trials prior to granting approval of any type, including by determining that approval through the Accelerated Approval Program is not appropriate and that our clinical trials may not be used to support approval through the conventional pathway. We might not be able to fulfill the FDA’s requirements in a timely manner, which would cause delays, or approval might not be granted because our submission is deemed incomplete by the FDA. There also can be no assurance that after subsequent FDA feedback we will continue to pursue approval through the Accelerated Approval Program. A failure to obtain approval through the Accelerated Approval Program could result in a longer time period to obtain approval of our drug candidates, could increase the cost of their development, could delay our ability to commercialize our products and could significantly harm our financial position and competitive position in the marketplace.
Even if we receive approval for one or more of our drug candidates through the Accelerated Approval Program, we will be subject to rigorous postmarketing requirements, including the completion of one or more confirmatory postmarketing trials as the FDA may require, to verify the clinical benefit of the product, and submission to the FDA of all promotional materials prior to their dissemination. The FDA could seek to withdraw the approval for multiple reasons, including if we fail to conduct any required confirmatory postmarketing trial with due diligence, our confirmatory postmarketing trial does not confirm the predicted clinical benefit, other evidence shows that the product is not safe or effective under the conditions of use, or we disseminate promotional materials that are found by the FDA to be false and misleading.
Moreover, Congress is considering potential changes to the Accelerated Approval Program that could impact our ability to obtain Accelerated Approval, or increase the burdens associated with postmarketing requirements in the event we do obtain Accelerated Approval. In particular, the FDA must specify certain conditions for required postapproval studies for products that receive Accelerated Approval, which may include enrollment targets and milestones, including the target date for study completion, by the time the drug is approved. The FDA may also require postapproval studies to be underway at the time of Accelerated Approval or within a specified time period following Accelerated Approval for such drugs, and must explain any instances where it does not require such studies.
Any delay in obtaining, or inability to obtain, approval through the Accelerated Approval Program, or any issues in maintaining approval granted under the Accelerated Approval Program, would delay or prevent commercialization of our products, and would materially adversely affect our business, financial condition, results of operations and prospects.
We, as a company, have limited experience in filing for and obtaining regulatory approval to initiate a clinical trial, and we do not have experience completing any clinical trials, including large-scale, pivotal clinical trials or in manufacturing or in quality assurance in order to market a new drug in the United States or in any other jurisdiction.
As a company, we have limited experience in filing for or obtaining regulatory approval to initiate clinical trials, we do not have experience completing any clinical trials, including large-scale, pivotal clinical trials and we rely on third parties to conduct our clinical trials. We also do not have experience in manufacturing or in quality assurance in order to market a new drug and expect to rely on CROs or other third-party consultants or vendors to assist us in this process. Our inexperience may result in failure to or delays in obtaining the required regulatory approvals to initiate clinical trials, to successfully complete clinical trials and to obtain marketing approval for our drug candidates. If we are unable to obtain regulatory and marketing approval for our drug candidates or experience significant delays in our efforts to do so, our business could be substantially harmed.
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Failure to obtain marketing approval in foreign jurisdictions would prevent our drug candidates from being marketed abroad and may limit our ability to generate revenue from product sales.
To market and sell our drug candidates in jurisdictions outside the United States, we must obtain separate marketing approvals and comply with numerous and varying regulatory requirements. The approval procedure varies among countries and can involve additional testing. The time required to obtain approvals from foreign regulatory authorities may differ substantially from that required to obtain FDA approval. The regulatory approval process outside the United States generally includes all of the risks associated with obtaining FDA approval. In addition, in many countries outside the United States, we must secure product reimbursement approvals before regulatory authorities will approve the product for sale in that country. Failure to obtain foreign regulatory approvals on a timely basis or non-compliance with foreign regulatory requirements could result in significant delays, difficulties and costs for us and could delay or prevent the introduction of our drug candidates in certain countries. Approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions, and approval by one regulatory authority outside the United States does not ensure approval by regulatory authorities in other countries or jurisdictions or by the FDA. We may not be able to file for marketing approvals and may not receive necessary approvals to commercialize our products in any jurisdiction, which would materially impair our ability to generate revenue.
The UK’s exit from the EU continues to create political and economic uncertainty, particularly in the UK and the EU. The UK is now being treated as a “third country” by the EU. Although UK legislation has retained existing EU law, new UK legislation is being drafted and the UK has not retained new EU law, including the Clinical Trials Regulation (EU) No 536/2014. This means that some regulatory activities, such as batch testing and Qualified Person certification, conducted in the UK are no longer recognized in the EU; although the UK accepts the batch testing data carried out in many third countries with recognized equivalent high standards to avoid delays and supply disruption due to re-testing. However, the UK and EU have concluded a Trade and Cooperation Agreement (TCA), which has been approved by the UK Parliament, European Council and European Parliament and has limited the disruption to the supply of medicines, particularly by enabling tariff and quota-free trade between the UK and the EU (provided that the rules of origin requirements are met), and has streamlined some issues, for example by enabling mutual recognition of cGMP inspections and certificates. The regulatory framework for medicines that existed before the end of the transition period has also effectively been preserved in UK domestic legislation as “retained EU law.” By retaining a snapshot of EU legislation at its core, the UK has prevented substantial divergence in the regulation of medicines (although divergence has appeared in some areas). However, some changes to the UK legislation have been immediately necessary, including the implementation of the Northern Ireland Protocol (NIP), pursuant to which, the EU pharmaceutical legal framework acquis continues to apply in Northern Ireland (subject to periodic consent of the Northern Ireland Legislative Assembly), and only products compliant with EU law can be placed in the Northern Ireland market—adding an extra layer of regulatory complexity. As a result, companies now need to comply with a separate UK regulatory legal framework in order to commercialize medicinal products in Great Britain (namely, England, Wales and Scotland, as EU law continues to apply in Northern Ireland). The UK government has attempted to renegotiate fundamental aspects of the NIP so this is an unpredictable area for companies in the near future. Failed attempts to renegotiate the NIP have led to media reports of the UK potentially triggering Article 16 of the NIP, a safeguarding measure, that may be engaged unilaterally if the application of the NIP leads to serious economic, societal or environmental difficulties that are liable to persist, or to diversion of trade. The UK government has introduced the Northern Ireland Protocol Bill which, if enacted into law, would enable the government to unilaterally disapply parts of the NIP which may lead to changes to the regulatory environment in Northern Ireland, and may trigger retaliatory measures against the UK by the EU. The UK government reached a new agreement with the EU, the “Windsor Framework,” which aims to replace the NIP. According to the Windsor Framework, medicinal products intended for the UK market including Northern Ireland will be authorized by the MHRA and will bear a “UK only” label. This means that medicinal products placed on the market in Northern Ireland will no longer need to be compliant with EU law. These new measures will be implemented beginning January 1, 2025. The TCA allows for future deviation from the current regulatory framework, and it is not known if and/or when any deviations may occur, which may have an impact on development, manufacture, marketing authorization, commercial sales and distribution of pharmaceutical products. It is also important to note that obtaining a marketing authorization is not sufficient to gain effective access to the market in the EU and in the UK; companies still need to agree to a reimbursement price for the products and in some jurisdictions, such as the UK and Germany, a further positive recommendation from health technology on cost-effectiveness is required for the products to be actually prescribed and reimbursed by the respective national health systems (see “—Governments outside of the United States tend to impose strict price controls, which may adversely affect our revenues from the sales of drugs, if any” below). If we fail to comply with the regulatory requirements in international markets and thus do not receive applicable marketing approvals, our target market will be reduced, our ability to realize the full market potential of our drug candidates will be harmed and our business will be adversely affected. We may not obtain foreign regulatory approvals on a timely basis, or at all. Our failure to obtain approval of any of our drug candidates by regulatory authorities in another country may significantly diminish the commercial prospects of that drug candidate and our business prospects could decline.
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Even if we, or any collaborators, obtain marketing approvals for our drug candidates, the terms of approvals and ongoing regulation of our products may limit how we, or they, manufacture and market our products, which could materially impair our ability to generate revenue.
Once marketing approval has been granted, an approved product and its manufacturer and marketer are subject to ongoing review and extensive regulation. We, and any collaborators, must therefore comply with requirements concerning advertising and promotion for any of our drug candidates for which we or they obtain marketing approval. Promotional communications with respect to prescription drugs are subject to a variety of legal and regulatory restrictions and must be consistent with the information in the product’s approved labeling. Thus, we, and any collaborators, will not be able to promote any products we develop for indications or uses for which they are not approved.
In addition, manufacturers of approved products and those manufacturers’ facilities are required to comply with extensive FDA, EMA, MHRA and other regulatory requirements, including ensuring that quality control and manufacturing procedures conform to cGMPs, which include requirements relating to quality control and quality assurance, as well as the corresponding maintenance of records and documentation and reporting requirements. We, our third-party manufacturers, and any collaborators and their third-party manufacturers could be subject to periodic unannounced inspections by the FDA and other regulatory agencies to monitor and ensure compliance with cGMPs.
Accordingly, assuming we, or any collaborators, receive marketing approval for one or more of our drug candidates, we, any collaborators, and our respective third-party manufacturers will continue to expend time, money and effort in all areas of regulatory compliance, including manufacturing, production, product surveillance and quality control.
If we, and any collaborators, are not able to comply with post-approval regulatory requirements, we, and any collaborators, could have the marketing approvals for our products withdrawn by regulatory authorities and our, or any collaborators’, ability to market any future products could be limited, which could adversely affect our ability to achieve or sustain profitability. Further, the cost of compliance with post-approval regulations may have a negative effect on our business, results of operations, financial condition and prospects.
Any drug candidate for which we, or any collaborators, obtain marketing approval could be subject to post-marketing restrictions or withdrawal from the market and we, or any collaborators, may be subject to substantial penalties if we, or they, fail to comply with regulatory requirements or if we, or they, experience unanticipated problems with our products when and if any of them are approved.
Any drug candidate for which we, or any collaborators, obtain marketing approval, as well as the manufacturing processes, post-approval clinical data, labeling, advertising and promotional activities for such product, will be subject to continual requirements of and review by the FDA, EMA, the MHRA and other regulatory authorities. These requirements include submissions of safety and other post-marketing information and reports, registration and listing requirements, cGMP requirements relating to manufacturing, quality control, quality assurance and corresponding maintenance of records and documents, requirements regarding the distribution of samples to physicians, tracking and tracing, serialization, postmarket adverse event reporting and recordkeeping. Even if marketing approval of a drug candidate is granted, the approval may be subject to limitations on the indicated uses for which the product may be marketed or to the conditions of approval, including the requirement to implement REMS. New cancer drugs frequently are indicated only for patient populations that have not responded to an existing therapy or have relapsed. If any of our drug candidates receive marketing approval, the accompanying label may limit the approved use of our drug in this way, which could limit sales of the product.
Clinical trials of our drug candidates must be conducted in carefully defined subsets of patients who have agreed to enter into clinical trials. Consequently, it is possible that our clinical trials, or those of any future collaborator, may indicate an apparent positive effect of a drug candidate that is greater than the actual positive effect, if any, or alternatively fail to identify undesirable side effects. If one or more of our drug candidates receives marketing approval and we, or others, discover that the drug is less effective than previously believed or causes undesirable side effects that were not previously identified, a number of potentially significant negative consequences could result, including:
•regulatory authorities may withdraw their approval of the drug or seize the drug;
•we, or any future collaborators, may be required to recall the drug, change the way the drug is administered or conduct additional clinical trials;
•additional restrictions may be imposed on the marketing of, or the manufacturing processes for, the particular drug;
•we may be subject to fines, injunctions or the imposition of civil or criminal penalties;
•regulatory authorities may require the addition of labeling statements, such as a “black box” warning or a contraindication;
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•we, or any future collaborators, may be required to create a Medication Guide outlining the risks of the previously unidentified side effects for distribution to patients;
•we, or any future collaborators, could be sued and held liable for harm caused to patients;
•the drug may become less competitive in the marketplace; and
•our reputation may suffer.
Any of these events could have a material and adverse effect on our operations and business and could adversely impact our stock price.
The FDA also may impose requirements for costly post-marketing studies or clinical trials and surveillance to monitor the safety or efficacy of the product, including the adoption and implementation of REMS. The FDA and other agencies, including the U.S. Department of Justice (DOJ), closely regulate and monitor the post-approval marketing and promotion of drugs to ensure they are marketed and distributed only for the approved indications and in accordance with the provisions of the approved labeling. The FDA and DOJ impose stringent restrictions on manufacturers’ communications regarding off-label use, and if we do not market our products only for their approved indications, we may be subject to enforcement action for off-label marketing. Violations of the FDCA and other statutes, including the False Claims Act, relating to the promotion and advertising of prescription drugs may lead to investigations and enforcement actions alleging violations of federal and state healthcare fraud and abuse laws, as well as state consumer protection laws. Other jurisdictions, including European countries, have similar provisions which may lead to investigations and enforcement actions by national authorities.
In addition, later discovery of previously unknown side effects or other problems with our products or their manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may yield various results, including:
•restrictions on such products, manufacturers or manufacturing processes;
•restrictions and warnings on the labeling or marketing of a product;
•restrictions on product distribution or use;
•requirements to conduct post-marketing studies or clinical trials;
•warning letters or untitled letters;
•withdrawal of the products from the market;
•refusal to approve pending applications or supplements to approved applications that we submit;
•recall of products;
•fines, restitution or disgorgement of profits or revenues;
•suspension or withdrawal of marketing approvals;
•suspension of any ongoing clinical trials;
•damage to relationships with any potential collaborators;
•unfavorable press coverage and damage to our reputation;
•refusal to permit the import or export of our products;
•product seizure;
•injunctions or the imposition of civil or criminal penalties; or
•litigation involving patients using our products.
Non-compliance with EU and UK requirements regarding safety monitoring or pharmacovigilance, and with requirements related to the development of products for the pediatric population (as explained further under “—If any of our drug candidates are not considered to be a new active substance or are deemed to fall within the “global marketing authorization” of an existing medicinal product or if pediatric studies are not adequately completed, this may result in lack of regulatory data protection or failure to obtain an extension to existing regulatory data protection,” below), also can result in significant financial penalties, and non-compliance with pediatric requirements may prevent regulatory approvals from being granted. Similarly, failure to comply with the EU and UK’s requirements regarding the protection of personal information can lead to significant penalties and sanctions.
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In addition, manufacturers of approved products and those manufacturers’ facilities are required to comply with extensive FDA requirements, including ensuring that quality control and manufacturing procedures conform to cGMPs applicable to drug manufacturers which include requirements relating to quality control and quality assurance, as well as the corresponding maintenance of records and documentation and reporting requirements. We, any contract manufacturers we may engage in the future, our collaborators and their contract manufacturers also will be subject to other regulatory requirements, including submissions of safety and other post-marketing information and reports, registration and listing requirements, requirements regarding the distribution of samples to clinicians, recordkeeping, and costly post-marketing studies or clinical trials and surveillance to monitor the safety or efficacy of the product, such as the requirement to implement a REMS.
If we decide to seek Orphan Drug Designation or other designations from regulators for any of our current or future drug candidates, we may be unsuccessful or may be unable to maintain the benefits associated with these designations, including the potential for supplemental market exclusivity associated with an Orphan Drug Designation.
We may seek Orphan Drug Designation or other designations from regulators for one or more of our current or future drug candidates. Regulatory authorities in some jurisdictions, including the United States, EU and European Economic Area (EEA), Switzerland and the UK, may designate drugs or biological products for relatively small patient populations as orphan drugs. Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biological product intended to treat a rare disease or condition, defined as a disease or condition with a patient population of fewer than 200,000 in the United States, or a patient population greater than 200,000 in the United States when there is no reasonable expectation that the cost of developing and making available the drug in the United States will be recovered from sales in the United States for that drug or biological product. In the United States, Orphan Drug Designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers. After the FDA grants Orphan Drug Designation, the identity of the drug or biological product and its potential orphan use are disclosed publicly by the FDA. Orphan Drug Designation does not convey any advantage in, or shorten the duration of, the regulatory review process.
If a product that has Orphan Drug Designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications, including an NDA or BLA, to market the same drug or biological product for the same indication for seven years, except in limited circumstances such as a showing of clinical superiority to the product with orphan drug exclusivity or if the FDA finds that the holder of the orphan drug exclusivity has not shown that it can assure the availability of sufficient quantities of the orphan drug to meet the needs of patients with the disease or condition for which the biological product was designated. As a result, even if one of our drug candidates receives orphan exclusivity, the FDA can still approve or license other drugs or biological products for use in treating the same indication or disease. Further, the FDA can waive orphan exclusivity if we are unable to manufacture sufficient supply of our product.
In addition, Congress is considering updates to the orphan drug provisions of the FDCA in response to a recent decision by the U.S. Court of Appeals for the Eleventh Circuit. Any changes to the orphan drug provisions could change our opportunities for, or likelihood of success in obtaining, orphan drug exclusivity and would materially adversely affect our business, results of operations, financial condition and prospects.
We may seek Orphan Drug Designation for our drug candidates in additional orphan indications in which there is a medically plausible basis for the use of these drug candidates. Even when we obtain Orphan Drug Designation, exclusive marketing rights in the United States may be limited if we seek licensure for an indication broader than the orphan designated indication and may be lost if the FDA later determines that the request for designation was materially defective or if we, through our manufacturer, are unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition. In addition, although we may seek Orphan Drug Designation for other drug candidates, we may never receive these designations.
In order to obtain orphan designation in the EEA (the UK has a similar legislation), the product must fulfill certain criteria. Under Article 3 of Regulation (EC) 141/2000, a medicinal product may be designated as an orphan medicinal product if it meets the following criteria: (1) it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition; (2) either the prevalence of such condition must not be more than five in 10,000 persons in the EU when the application is made, or without the benefits derived from orphan status, it must be unlikely that the marketing of the medicine would generate sufficient return in the EU to justify the investment needed for its development; and (3) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing in the EU or if such a method exists, the product will be of significant benefit to those affected by the condition, as defined in Regulation (EC) 847/2000.
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Products receiving orphan designation in the EU may receive 10 years of orphan market exclusivity (which can be further extended by two years if pediatric studies have been conducted in accordance with an agreed pediatric investigational plan). Applications must first satisfy the orphan designation criteria and apply for orphan designation before making the application for marketing authorization. The applicant must then successfully maintain the orphan designation at the time of the MAA in order to qualify for 10 years of orphan market exclusivity. During this 10-year period, the competent authorities of the EU Member States and European Commission may not accept applications or grant marketing authorization for other similar medicinal products for the same orphan therapeutic indication. The protection afforded by orphan market exclusivity in the EU may, in some circumstances, be circumvented by competitor products which are demonstrated not to be “similar” or which are authorized for different therapeutic indications. There may be a risk that products may be prescribed “off-label” for the orphan therapeutic indication by healthcare professions in some EU Member States.
There are also three exceptions to the orphan market exclusivity principle. Marketing authorization may be granted to a similar medicinal product for the same orphan therapeutic indication if:
•the second applicant can establish in its application that its medicinal product, although similar to the orphan medicinal product already authorized, is safer, more effective or otherwise clinically superior;
•the holder of the marketing authorization for the original orphan medicinal product consents to a second orphan medicinal product application; or
•the holder of the marketing authorization for the original orphan medicinal product cannot supply sufficient quantities of orphan medicinal product.
An orphan product can also obtain an additional two years of orphan market exclusivity in the EU if the MAA contains the results of all pediatric studies conducted in accordance with and agreed pediatric investigation plan. The 10-year market exclusivity may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for orphan designation; for example, if the product is sufficiently profitable not to justify maintenance of market exclusivity.
The UK’s regulatory legal framework provides for similar periods of protection (namely regulatory data protection, marketing protection and market exclusivity).
It is important to note that the regulatory protection afforded to medicinal products such as data exclusivity, marketing protection, market exclusivity for orphan indications and pediatric extension are currently under review at the EU level. It is expected that the protection currently afforded in the EU will be reduced in the years to come. On April 26, 2023, the European Commission adopted a proposal for a new Directive and a new Regulation. If enacted into law, this proposal will revise and replace the existing general pharmaceutical legislation and will affect the existing period of regulatory protections afforded to medicinal products.
If the FDA or comparable foreign regulatory authorities approve generic versions of any of our drug candidates that receive marketing approval, or such authorities do not grant our drug candidates appropriate periods of data or market exclusivity before approving generic versions of our drug candidates, the sales of our drug candidates could be adversely affected.
Once an NDA is approved, the drug covered thereby becomes a “reference-listed drug” in the FDA’s publication, “Approved Drug Products with Therapeutic Equivalence Evaluations.” Manufacturers may seek marketing approval of generic versions of reference-listed drugs through submission of abbreviated new drug applications (ANDAs) in the United States. In support of an ANDA, a generic manufacturer need not conduct clinical trials demonstrating safety and efficacy. Rather, the applicant generally must show that its drug is pharmaceutically equivalent to the reference listed drug, in that it has the same active ingredient(s), dosage form, strength, route of administration and conditions of use or labeling as the reference-listed drug, and that the generic version is bioequivalent to the reference-listed drug, meaning it is absorbed in the body at the same rate and to the same extent. Generic drugs may be significantly less costly to bring to market than the reference-listed drug and companies that produce generic drugs are generally able to offer them at lower prices. Thus, following the introduction of a generic drug, a significant percentage of the sales of any branded product or reference-listed drug is typically lost to the generic drug.
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The FDA may not approve an ANDA for a generic drug until any applicable period of non-patent exclusivity for the reference-listed drug has expired. The FDCA provides a period of five years of non-patent exclusivity for a new drug containing a new chemical entity. During the exclusivity period, the FDA may not accept for review an ANDA or a 505(b)(2) NDA submitted by another company for another version of such drug candidate where the applicant does not own or have a legal right of reference to all the data required for approval. However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement. The FDCA also provides three years of marketing exclusivity for an NDA, 505(b)(2) NDA or supplement to an approved NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example, for new indications, dosages or strengths of an existing drug candidate. This three-year exclusivity covers only the conditions associated with the new clinical investigations and does not prohibit the FDA from approving ANDAs for drug candidates containing the original active agent for other conditions of use. Five-year and three-year exclusivity will not delay the submission or approval of a full NDA. However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the nonclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness. Manufacturers may seek to launch these generic drugs following the expiration of the marketing exclusivity period, even if we still have patent protection for our drug.
Competition that our drug candidates may face from generic versions of our drug candidates could materially and adversely impact our future revenue, profitability and cash flows and substantially limit our ability to obtain a return on the investments we have made in those drug candidates. Our future revenues, profitability and cash flows could also be materially and adversely affected and our ability to obtain a return on the investments we have made in those drug candidates may be substantially limited if our drug candidates, if and when approved, are not afforded the appropriate periods of non-patent exclusivity.
If any of our drug candidates are not considered to be a new active substance or are deemed to fall within the “global marketing authorization” of an existing medicinal product or if pediatric studies are not adequately completed, this may result in lack of regulatory data protection or failure to obtain an extension to existing regulatory data protection.
Where an applicant for a marketing authorization submits a full dossier containing its own pharmaceutical, preclinical tests and clinical trials data, and where the application does not fall within the “global marketing authorization” of an existing medicinal product, the applicant is entitled to eight years of regulatory data protection upon grant of the marketing authorization (the period starts to run from the first marketing authorization in the EU and EEA). During this period, applicants for approval of generics or biosimilars cannot rely on data contained in the marketing authorization dossier submitted for the already authorized, or reference, medicinal product to support their application. After the expiration of the eight-year period of regulatory data protection, the reference medicinal product benefits from a further two-year period of marketing protection. During these two years of marketing protection, no generic or biosimilar medicinal product that relies upon the reference medicinal product’s dossier may be placed on the EU market, but a generic or biosimilar MAA can be submitted to the competent regulatory authorities in the EU Member States during this time. The two-year period of marketing protection can further be extended by one year if, during the first eight years of the grant of the first marketing authorization, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies. However, even if a compound is considered to be a new active substance and the innovator is able to gain the period of regulatory data protection and marketing protection, provided that no other IP or regulatory exclusivities applied, another unrelated company could also apply for a marketing authorization and market another competing medicinal product for the same therapeutic indication if such company obtained its own marketing authorization based on a separate MAA based on a full self-standing scientific data package supporting the application. The period of regulatory data protection and marketing protection applies in the UK (running from the date of the first authorization in Great Britain).
In the EU, pursuant to Regulation 1901/2006, and in the UK pursuant to the Human Medicines Regulations 2012 (as amended), MAAs must include pediatric data based on pediatric investigation plans agreed with the EMA if the MAA concerns (i) a new active substance, or (ii) a new indication, pharmacological form, or route of administration (where the product is protected by a supplementary protection certificate or a patent qualifying for a supplementary certificate). Applicants may obtain waivers or deferrals to these requirements in certain circumstances (for example a waiver may be obtained if the condition only occurs in adult populations). Where required, pediatric studies must cover all sub-sets of the pediatric population for both existing and new indications, pharmacological forms and route of administrations. Limited further exclusions apply, including in relation to generic or biosimilar applications. Certain rewards may be available for completion of pediatric studies. For example, where MAAs include the results of all studies conducted in compliance with an agreed pediatric investigation plan, the holder of the patent or supplementary protection certificate may be entitled to a six-month extension to the supplementary protection certificate. Additionally, the European Commission’s new proposed legislation, if implemented, will also affect the current EU legal framework of pediatric medicines.
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Our operations and relationships with actual and potential customers, providers and third-party payors will be subject to applicable anti-kickback, fraud and abuse and other healthcare laws and regulations, which could expose us to penalties including criminal sanctions, civil penalties, exclusions from government programs, contractual damages and reputational harm, and could diminish our future profits and earnings.
Our arrangements with third-party payors, physicians, and other potential customers will subject us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we market, sell and distribute any drug candidates for which we obtain marketing approval.
Applicable U.S. federal and state and non-U.S. healthcare laws and regulations include the following:
•the federal Anti-Kickback Statute, a criminal law, which prohibits, among other things, persons and entities from knowingly and willfully offering, paying, soliciting or receiving any remuneration, directly or indirectly, in cash or in kind, to induce or reward purchasing, leasing, ordering, or arranging for, referring, or recommending the purchase, lease or order of any good or service for which payment may be made, in whole or in part, under federal healthcare programs such as Medicare and Medicaid. A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation. Violations of the federal Anti-Kickback Statute can result in significant civil monetary penalties and criminal fines, as well as imprisonment and exclusion from participation in federal healthcare programs;
•the federal Civil False Claims Act, which may be enforced through civil whistleblower or qui tam actions and imposes significant civil penalties, treble damages and potential exclusion from federal healthcare programs against individuals or entities for, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or for making a false record or statement material to an obligation to pay the federal government or for knowingly and improperly avoiding, decreasing or concealing an obligation to pay money to the federal government. Further, a violation of the federal Anti-Kickback Statute can serve as a basis for liability under the federal Civil False Claims Act. There is also the federal Criminal False Claims Act, which is similar to the federal Civil False Claims Act and imposes criminal liability on those that make or present a false, fictitious or fraudulent claim to the federal government;
•the federal Civil Monetary Penalties Law, which authorizes the imposition of substantial civil monetary penalties against an entity that engages in activities including, among others (1) knowingly presenting, or causing to be presented, a claim for services not provided as claimed or that is otherwise false or fraudulent in any way; (2) arranging for or contracting with an individual or entity that is excluded from participation in federal health care programs to provide items or services reimbursable by a federal health care program; (3) violations of the federal Anti-Kickback Statute; or (4) failing to report and return a known overpayment;
•federal criminal statutes created by the Health Insurance Portability and Accountability Act (HIPAA), which impose criminal liability for, among other things, knowingly and willfully executing or attempting to execute a scheme to defraud any healthcare benefit program, including private insurance plans, or, in any matter involving a healthcare benefit program, for knowingly and willfully making materially false, fictitious or fraudulent statements in connection with the delivery of or payment for health care benefits;
•HIPAA, as amended by the Health Information Technology for Economic Clinical Health Act, and its implementing regulations, which also imposes obligations, including mandatory contractual terms, on certain types of people and entities with respect to safeguarding the privacy, security and transmission of individually identifiable health information;
•the federal Food, Drug, and Cosmetic Act and Public Health Service Act which among other things, strictly regulates drug marketing, prohibits manufacturers from marketing such products for off-label use or misbranding or adulterating their products, and regulates the distribution of samples;
•the federal and state laws that require pharmaceutical manufacturers to report certain calculated product pricing metrics to the government or provide certain discounts or rebates to government authorities or private entities, often as a condition of product coverage and reimbursement under federal healthcare programs;
•the federal Physician Payment Sunshine Act, which requires applicable manufacturers of covered drugs, devices, biologics, and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, among others, to annually track and report payments and other transfers of value provided to U.S.-licensed physicians, teaching hospitals, physician assistants, nurse practitioners, clinical nurse specialists, certified nurse anesthetists, anesthesiologist assistants and certified nurse-midwives, as well as certain ownership and investment interests held in the manufacturer by physicians and their immediate families;
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•analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, that may apply to our business practices, including sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers;
•state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and relevant compliance guidance promulgated by the federal government;
•state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures;
•state and local laws that prohibit various marketing-related activities, such as the provision of certain kinds of gifts or meals; require the reporting of certain pricing information, including information pertaining to and justifying price increases, or prohibit prescription drug price gouging; impose payment caps on certain pharmaceutical products deemed by the state to be “high cost”; and require the registration of pharmaceutical sales representatives; and
•state and foreign laws that govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
Efforts to ensure that our business arrangements with third parties will comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, imprisonment, exclusion of drug candidates from government-funded healthcare programs, such as Medicare and Medicaid, disgorgement, contractual damages, reputational harm, diminished profits and future earnings, and the curtailment or restructuring of our operations. If any physicians or other healthcare providers or entities with whom we expect to do business are found not to be in compliance with applicable laws, they may also be subject to criminal, civil or administrative sanctions, including exclusions from government-funded healthcare programs. Although effective compliance programs can mitigate the risk of investigation and prosecution for violations of these laws, these risks cannot be entirely eliminated. Any action for an alleged or suspected violation can cause us to incur significant legal expenses and divert management’s attention from the operation of the business, even if such action is successfully defended.
Providing benefits or advantages to induce or reward improper performance generally to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order or use of medicinal products is prohibited in the EU and the UK. The provision of benefits or advantages to induce or reward improper performance is governed by the national anti-bribery laws of EU Member States, and in respect of the UK, the UK Bribery Act 2010 (Bribery Act). Infringement of these laws may result in substantial fines and imprisonment. EU Directive 2001/83/EC, which is the EU Directive governing medicinal products for human use, provides that, where medicinal products are being promoted to healthcare professionals, no gifts, pecuniary advantages or benefits in kind may be supplied, offered or promised to such individuals unless they are inexpensive and relevant to the practice of medicine or pharmacy. This provision was transposed into the Human Medicines Regulations 2012 and as such remains applicable in the UK.
Payments made to physicians in certain EU Member States must be publicly disclosed. In addition, agreements with healthcare professionals must often be the subject of prior notification and approval by the healthcare professional’s employer, his or her competent professional organization and/or the regulatory authorities of individual EU Member States. These requirements are set out in national laws, industry codes or professional codes of conduct, applicable in the EU Member States and in the UK. Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment.
The FDA’s and other regulatory authorities’ policies may change, and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our drug candidates.
The FDA’s and other regulatory authorities’ policies may change, and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our drug candidates. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained, and we may not achieve or sustain profitability. We also cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative or executive action, either in the United States or abroad.
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Current and future legislation may increase the difficulty and cost for us, and any collaborators, to obtain marketing approval of and commercialize our drug candidates and affect the prices we, or they, may obtain.
In the United States and some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing approval of our drug candidates, restrict or regulate post-approval activities and affect our ability to profitably sell any drug candidates for which we obtain marketing approval. The biopharmaceutical industry has been a particular focus of these efforts and has been significantly affected by legislative initiatives. Current laws, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price that we receive for any FDA-approved product.
Healthcare reform measures that may be adopted in the future may result in reductions in Medicare and other healthcare funding, more rigorous coverage criteria, new payment methodologies and additional downward pressure on the price that we receive for any approved product and/or the level of reimbursement physicians receive for administering any approved product we might bring to market. Reductions in reimbursement levels may negatively impact the prices we receive or the frequency with which our products are prescribed or administered. Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors.
To date, there have been several U.S. congressional inquiries and proposed and enacted state and federal legislation and regulations designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient support programs, reduce the costs of drugs under Medicare and reform government program reimbursement methodologies for drug products. Most notably, the Inflation Reduction Act (IRA), which was signed into law on August 16, 2022, allows Medicare to: beginning in 2026, establish a “maximum fair price” for a fixed number of pharmaceutical and biological products covered under Medicare Parts B and D following a price negotiation process with the Centers for Medicare and Medicaid Services (CMS); and, beginning in 2023, penalize drug companies that raise prices for products covered under Medicare Parts B and D faster than inflation, among other reforms. CMS has recently taken steps to implement the IRA, including:
•On June 30, 2023, issuing guidance detailing the requirements and parameters of the first round of price negotiations, to take place during 2023 and 2024, for products subject to the “maximum fair price” provision that would become effective in 2026;
•On August 29, 2023, releasing the initial list of 10 drugs subject to price negotiations;
• On November 17, 2023, releasing guidance outlining the methodology for identifying certain manufacturers eligible to participate in a phase-in period where discounts on applicable products will be lower than those required by the Medicare Part D Manufacturer Discount Program; and
•On December 14, 2023, releasing a list of 48 Medicare Part B products that had adjusted coinsurance rates based on the inflationary rebate provisions of the IRA for the time period of January 1, 2024 to March 31, 2024 as well as issuing revised guidance for manufacturers in the Medicare Part B and D drug discount programs.
It is unclear how future regulatory actions to implement the IRA, as well as the outcome of pending litigation against the IRA, may affect our products and future profitability.
On October 14, 2022, President Biden issued an Executive Order on Lowering Prescription Drug Costs for Americans, which instructed the Secretary of the Department of Health and Human Services (HHS) to consider whether to select for testing by the CMS Innovation Center new health care payment and delivery models that would lower drug costs and promote access to innovative drug therapies for beneficiaries enrolled in the Medicare and Medicaid programs. The Executive Order further directed the Secretary of HHS to submit, within 90 days after the date of the Executive Order, a report regarding any models that may lead to lower cost-sharing for commonly used drugs and support value-based payment that promotes high-quality care. On February 14, 2023, the HHS issued a report in response to the October 14, 2022 Executive Order, which, among other things, selects three potential drug affordability and accessibility models to be tested by the CMS Innovation Center. Specifically, the report addresses: (1) a model that would allow Part D Sponsors to establish a “high-value drug list” setting the maximum co-payment amount for certain common generic drugs at $2; (2) a Medicaid-focused model that would establish a partnership between CMS, manufacturers, and state Medicaid agencies that would result in multi-state outcomes-based agreements or certain cell and gene therapy drugs; and (3) a model that would adjust Medicare Part B payment amounts for Accelerated Approval Program drugs to advance the developments of novel treatments.
We cannot be sure what impact, if any, the foregoing changes will have on the profitability of any of our drug candidates, if approved for commercial use, in the future.
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At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing. These include legislation and regulations regarding price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, legislative action designed to encourage importation from other countries and bulk purchasing. For example, on January 5, 2024, the FDA approved Florida’s importation plan, which allows pharmacists and wholesalers to import certain products from Canada. In addition, regional health care authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other health care programs. These measures could reduce the ultimate demand for our products, once approved, or put pressure on our product pricing.
Legislative and regulatory proposals have also been made to expand post-approval requirements and restrict sales and promotional activities for pharmaceutical products. We cannot be sure whether additional legislative changes will be enacted, or whether the FDA regulations, guidance or interpretations will be changed, or what the impact of such changes on the marketing approvals of our drug candidates, if any, may be. Increased scrutiny by the U.S. Congress of the FDA’s approval process may significantly delay or prevent marketing approval, as well as subject us to more stringent product labeling and post-marketing testing and other requirements.
Governments outside of the United States tend to impose strict price controls, which may adversely affect our revenues from the sales of drugs, if any.
In some countries, particularly the countries of the EU and the UK, the pricing of prescription pharmaceuticals is subject to governmental control. In these countries, pricing negotiations with governmental authorities can take considerable time after the receipt of marketing approval for a drug. To obtain reimbursement or pricing approval in some countries, we, or our collaborators, may be required to conduct a clinical trial that compares the cost-effectiveness of our drug to other available therapies. Furthermore, in some European countries, the authorities conduct an HTA to assess the cost-effectiveness of the product (in the UK that HTA assessment is conducted by the National Institute for Health and Care Excellence), which may significantly impact effective access to the market. If reimbursement of our drugs is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, our business could be materially harmed.
Risks Related to Employees, Managing our Growth and Other Legal Matters
If we fail to attract and retain management and other key personnel, we may be unable to continue to successfully develop our current and any future drug candidates, commercialize our drug candidates or otherwise implement our business plan.
Our ability to compete in the highly competitive biopharmaceuticals industry depends upon our ability to attract and retain highly qualified managerial, scientific, medical, sales and marketing and other personnel. We are highly dependent on our management and scientific personnel, including our President and Chief Executive Officer, Arthur T. Sands, M.D., Ph.D., and Chief Scientific Officer, Gwenn Hansen, Ph.D. The loss of the services of Dr. Sands, Dr. Hansen or other members of our senior leadership team could impede, delay or prevent the successful development of our product pipeline, completion of our current and planned clinical trials, commercialization of our products or in-licensing or acquisition of new assets, and could negatively impact our ability to successfully implement our business plan. If we lose the services of such individuals, we might not be able to find suitable replacements on a timely basis or at all, and our business could be harmed as a result. We do not maintain “key man” insurance policies on the lives of these individuals or the lives of any of our other employees.
We employ all of our executive officers and key personnel on an at-will basis and their employment can be terminated by us or them at any time, for any reason and without notice. In order to retain valuable employees at our company, in addition to salary and cash incentives, we provide stock options and restricted stock units (RSUs) that vest over time. The value to employees of stock options and RSUs that vest over time will be significantly affected by movements in our stock price that are beyond our control and may at any time be insufficient to counteract offers from other companies.
Moreover, we might not be able to attract or retain qualified management and other key personnel in the future due to the intense competition for qualified personnel among biotechnology, pharmaceutical and other businesses, particularly in the San Francisco Bay Area where we are headquartered. We could have difficulty attracting experienced personnel to our company and may be required to expend significant financial resources in our employee recruitment and retention efforts. Many pharmaceutical companies with whom we compete for qualified personnel have greater financial and other resources, different risk profiles and longer histories in the industry than we do. They also may provide more diverse opportunities and better chances for career advancement. If we are unable to attract and retain the necessary personnel to accomplish our business objectives, we may experience constraints that will harm our ability to implement our business strategy and achieve our business objectives.
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In addition, we have scientific and clinical advisors who assist us in formulating our development and clinical strategies. These advisors are not our employees and may have commitments to, or consulting or advisory contracts with, other entities that may limit their availability to us. In addition, our advisors may have arrangements with other companies to assist those companies in developing products or technologies that may compete with ours.
We will need to grow our organization, and we may experience difficulties in managing this growth, which could disrupt our operations.
As our development and commercialization plans and strategies develop, and as we continue our transition into operating as a public company, we expect to expand our employee base for managerial, operational, financial and other resources. In addition, we have limited experience in product development. We filed our first IND in December 2020 and currently have three drug candidates in ongoing Phase 1 trials. As our drug candidates enter and advance through preclinical studies and clinical trials, we will need to expand our development, regulatory and manufacturing capabilities or contract with other organizations to provide these capabilities for us. In the future, we expect to have to manage additional relationships with collaborators or partners, suppliers and other organizations. Our ability to manage our operations and future growth will require us to continue to improve our operational, financial and management controls, reporting systems and procedures. We may not be able to implement improvements to our management information and control systems in an efficient or timely manner and may discover deficiencies in existing systems and controls. Our inability to successfully manage our growth and expand our operations could have a material and adverse effect on our business, financial condition, results of operations and prospects.
Our employees, independent contractors, vendors, principal investigators, CROs and consultants may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements and insider trading laws.
We are exposed to the risk that our employees, independent contractors, vendors, principal investigators, CROs and consultants may engage in fraudulent conduct or other illegal activity. Misconduct by these parties could include:
•intentional, reckless or negligent conduct or disclosure to us of unauthorized activities that violate the regulations of the FDA or similar foreign regulatory authorities;
•healthcare fraud and abuse in violation of U.S. and foreign laws and regulations;
•violations of U.S. federal securities laws relating to trading in our common stock; and
•failures to report financial information or data accurately.
In particular, sales, marketing and business arrangements in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, misconduct, kickbacks, self-dealing and other abusive practices. These laws and regulations regulate a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements. While we have adopted a code of conduct and implemented other internal controls applicable to all of our employees, it is not always possible to identify and deter misconduct by employees and other third parties, and the precautions we take to detect and prevent this activity may not be effective. Additionally, we are subject to the risk that a person could allege fraud or other misconduct, even if none occurred. If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business, including the imposition of civil, criminal and administrative penalties, damages, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs and diminished profits and future earnings, any of which could adversely affect our ability to operate our business or cause reputational harm.
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We depend on our information technology systems, and any failure of these systems, or those of our CROs, third-party vendors, collaborators or other contractors or consultants we may utilize, could harm our business. Security breaches, cyber-attacks, loss of data and other disruptions could compromise sensitive information related to our business or other personal information, prevent us from accessing critical information and expose us to liability, which could adversely affect our business, reputation, results of operations, financial condition and prospects.
We collect and maintain information in digital form that is necessary to conduct our business, and we are increasingly dependent on information technology systems, infrastructure and data to operate our business. In the ordinary course of our business, we collect, store and transmit large amounts of confidential information, including but not limited to intellectual property, proprietary business information and personal information. It is critical that we do so in a secure manner to maintain the confidentiality, integrity and availability of such confidential information. We have established physical, electronic and organizational measures to safeguard and secure our systems which are designed to prevent data compromise, and rely on commercially available systems, software, tools and monitoring to provide security for our information technology systems and the processing, transmission and storage of digital information. We have also outsourced elements of our information technology infrastructure, resulting in a number of third-party vendors that may or could have access to our confidential information.
Despite the implementation of security measures, our internal information technology systems and infrastructure, and those of our current and any future CROs, collaborators, contractors and consultants and other third parties on which we rely, are vulnerable to breach, breakdown or other damage or interruption from service interruptions, system malfunction, computer viruses, malware, natural disasters, terrorism, war, telecommunication and electrical failures, cyber-attacks or cyber-intrusions over the Internet (including harmful attachments to emails, ransomware, denial-of-service attacks, social engineering, and other means to affect service reliability and threaten the confidentiality, integrity, and availability of information), persons inside our organization, or persons with access to systems inside our organization. Any of the foregoing may compromise or lead to data leakage of our system infrastructure, or that of our CROs, third-party vendors and other contractors and consultants.
The risk of a security breach or disruption, particularly through cyber-attacks or cyber-intrusion, including by computer hackers, foreign governments and cyber terrorists, has generally increased as the number, intensity and sophistication of attempted attacks and intrusions from around the world have increased. We may not be able to anticipate all types of security threats, and we may not be able to implement preventive measures effective against all such security threats. The techniques used by cyber criminals change frequently, may not be recognized until launched and can originate from a wide variety of sources. In addition, the prevalent use of mobile devices and remote work applications that access confidential information increases the risk of data security breaches, which could lead to the loss of confidential information or other intellectual property or unauthorized access to personal information. To the extent that any disruption or security breach were to result in a loss of, or damage to, our data or applications, or those of our third-party vendors, CROs and other contractors and consultants, or inappropriate disclosure of confidential, personal or proprietary information, we could incur liability and reputational damage and the further development and commercialization of our drug candidates could be delayed. The costs to us to mitigate network security problems, bugs, viruses, worms, malicious software programs and security vulnerabilities could be material, and although we have and continue to invest in and implement security measures designed to protect our data security and information technology systems, our efforts to address these problems may not be successful, and these problems could result in unexpected interruptions, delays, cessation of service and other harm to our business and our competitive position. If the information technology systems of our third-party vendors, CROs and other contractors and consultants become subject to disruptions or security breaches, we may have insufficient recourse against such third parties and we may have to expend significant resources to mitigate the impact of such an event, and to develop and implement protections to prevent future events of this nature from occurring.
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We and our third-party service providers regularly defend against and respond to data security incidents, and we cannot assure you that our data protection efforts and our investment in information technology will prevent significant breakdowns, data leakages, breaches in our systems, or those of our third-party vendors, CROs and other contractors and consultants, or other cyber incidents that could have a material adverse effect upon our reputation, business, operations, or financial condition. If such an event were to occur that causes interruptions in our operations, or those of our third-party vendors, CROs and other contractors and consultants, it could result in a material disruption or delay of our product development programs. For example, the loss of clinical trial data from completed, ongoing or planned clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. Furthermore, significant disruptions of our internal information technology systems or those of our third-party vendors and other contractors and consultants, or security breaches could result in the loss, misappropriation, and/or unauthorized access, use, or disclosure of, or the prevention of access to, confidential information (including trade secrets or other intellectual property, proprietary business information, and personal information), which could result in financial, legal, business, and reputational harm to us. If any such event, including a computer security breach, results in the unauthorized access, use or release of personal information, our reputation could be materially damaged. In addition, such a breach may require notification to governmental agencies, the media or individuals pursuant to various federal and state data privacy and security laws (and other similar non-U.S. laws), subject us to mandatory corrective action, and otherwise subject us to liability under laws and regulations that protect the privacy and security of personal information. For example, data breaches frequently result in regulatory actions and commercial and class action litigation based on a variety of laws and legal duties, such as the California Consumer Privacy Act (CCPA), which provides for a private right of action in the event of certain data security breaches. Additionally, the SEC also adopted a new cybersecurity rule requiring companies subject to SEC reporting requirements to formally report material cybersecurity incidents, where failure to report may result in regulatory investigations leading to consent orders that may require additional compliance obligations and/or injunctions, fines and other penalties. Such actions could result in significant legal and financial exposure and reputational damages that could have a material adverse effect on our business, financial condition, results of operations and prospects.
Currently, we carry business interruption coverage and cybersecurity insurance to mitigate certain potential losses, but this insurance is limited in amount and may not be sufficient in type or amount to cover us against claims related to a cybersecurity breach and related business and system disruptions. We cannot be certain that such potential losses will not exceed our policy limits, insurance will continue to be available to us on economically reasonable terms, or at all, or any insurer will not deny coverage as to any future claim. In addition, we may be subject to changes in our insurance policies, including premium increases or the imposition of large deductible or co-insurance requirements.
We are or may become subject to a variety of stringent privacy and data security laws, regulations, policies and contractual obligations related to data privacy and security, and changes in such laws, regulations, policies and contractual obligations and our failure, or any failure by our third-party vendors, collaborators, contractors or consultants, to comply with them could harm our business and result in enforcement action by regulators and claims from affected individuals.
We maintain and process, and our third-party vendors, collaborators, contractors and consultants maintain and process on our behalf, a large quantity of proprietary and sensitive information, including confidential business information, personal and patient health information in connection with our preclinical studies and clinical trials and personal information of our employees. We are subject to global privacy and data protection laws and regulations that apply to the collection, transmission, storage and use of personal information, which among other things, impose certain requirements relating to the privacy, security and transmission of personal information. Failure by us or our third-party vendors, collaborators, contractors and consultants to comply with any of these laws and regulations could result in enforcement actions by data protection authorities against us, including fines or penalties, claims for damages by affected individuals, damage to our reputation and loss of goodwill, any of which could have a material adverse effect on our business, financial condition, results of operations or prospects.
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In the United States, there are numerous federal and state privacy and data security laws and regulations governing the collection, use, disclosure and protection of personal information, including federal and state health information privacy laws, federal and state security breach notification laws, and federal and state consumer protection laws. Each of these laws is subject to varying interpretations and the legislative landscape is constantly evolving. In particular, laws and regulations governing the privacy of health information, such as HIPAA, establish privacy and security standards that limit the use and disclosure of individually identifiable health information, or protected health information, and require the implementation of administrative, physical and technological safeguards to protect the privacy of protected health information and ensure the confidentiality, integrity and availability of electronic protected health information. Determining how protected health information may be used, shared or processed in compliance with applicable privacy standards and our contractual obligations can be complex and may be subject to changing interpretation. Further, if we fail to comply with applicable privacy laws, we could face civil and criminal penalties, or claims for breach of contract. The HHS has enforcement discretion for HIPAA, and any enforcement activity can result in financial liability and reputational harm, and responses to such enforcement activity can consume significant internal resources. In addition, states have shown an increased interest in protecting the privacy of health data. Washington state passed the My Health My Data Act, which will take effect on March 31, 2024, and is focused on the collection of consumer health data. The My Health My Data Act has a broader scope than HIPAA and includes a private right of action—depending on whether this law applies to us, there may be substantial regulatory action and litigation associated with this act. Following Washington, Nevada enacted Senate Bill 370, which will take effect on March 31, 2024, and is similar to the My Health My Data Act and requires in-scope entities to comply with certain requirements regarding consumer health data. Notably, Senate Bill 370 does not include a private right of action nor does it apply to entities that are subject to HIPAA. Connecticut also amended its comprehensive privacy law in 2023, the Connecticut Data Privacy Act, to impose obligations aimed at “consumer health data.” Furthermore, state attorneys general are authorized to bring civil actions seeking either injunctions or damages in response to violations that threaten the privacy of state residents pursuant to local state laws. We cannot be sure how these regulations will be interpreted, enforced or applied to our operations. In addition to the risks associated with enforcement activities and potential contractual liabilities, our ongoing efforts to comply with evolving laws and regulations at the federal and state level may be costly and require ongoing modifications to our policies, procedures and systems.
Personal data privacy remains an evolving landscape at both the U.S. state and international level, with new regulations coming into effect. For example, the CCPA, which came into effect on January 1, 2020, and was amended and expanded by the California Privacy Rights Act (CPRA) as of January 1, 2023, provides California residents expanded privacy rights, including the right to request correction, access, and deletion of their personal information, the right to opt out of certain personal information sharing, and the right to receive detailed information about how their personal information is processed, including by California residents’ employers. Additionally, the CCPA, as amended, requires companies that process personal information of California residents to make disclosures to consumers about their data collection, use and sharing practices, allow consumers to opt out of certain data sharing with third parties, complete certain audits and assessments when processing higher risk data and provide a private right of action for data breaches, as described above. Although the CCPA includes limited exceptions—including exceptions for personal health information collected by covered entities or business associates subject to HIPAA among others, the CCPA may regulate or impact our processing of personal information depending on the context. Failure to comply with the CCPA may result in significant civil penalties, injunctive relief, or statutory or actual damages as determined by the California Privacy Protection Agency, the newly created state agency from the CPRA legislation that is charged with creating new rules and enforcing the CCPA, and the California Attorney General, who also still maintains some CCPA enforcement powers. Notably, following California’s lead, several other states enacted privacy laws that took effect in 2023: the Colorado Privacy Act, the Connecticut Personal Data Privacy and Online Monitoring Act, the Utah Consumer Privacy Act, and the Virginia Consumer Data Protection Act. Additional state privacy laws are set to take effect in 2024: the Florida Digital Bill of Rights (July 1, 2024), Montana’s Consumer Data Privacy Act (October 1, 2024), Oregon’s protections for the personal data of consumer enacted through SB 619 (July 1, 2024), and the Texas Data Privacy and Security Act (July 1, 2024). Compliance with this new privacy legislation adds complexity and may require investment in additional resources for compliance programs, thus potentially result in additional costs and expense of resources to maintain compliance.
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In the EU, the EU GDPR governs the collection, use, disclosure, transfer, or other processing of personal data. The UK has implemented the EU GDPR as the UK GDPR which sits alongside the UK Data Protection Act 2018 (the UK GDPR, and together with the EU GDPR, the GDPR). The GDPR imposes compliance obligations on controllers, including (among others) mandating burdensome documentation requirements, granting certain privacy rights to individuals to control how companies collect, use, disclose, retain and otherwise process information about them as well as specific requirements for obtaining valid consent where consent is the legal basis for processing, requirements around accountability and transparency, the obligation to consider data protection when any new products or services are developed, the obligation to appoint data protection officers in certain circumstances, the obligation to notify relevant data supervisory authorities of notifiable personal data breaches without undue delay (and no later than 72 hours) after becoming aware of the personal data breach, and the requirement for more detailed notices for clinical trial subjects and investigators. In addition, the EU GDPR prohibits the international transfer of personal data from clinical trial sites and other third parties (e.g., CROs) located in the EEA to jurisdictions that the European Commission does not recognize as having ‘adequate’ data protection laws, unless a data transfer mechanism has been put in place or a derogation under the EU GDPR can be relied upon. After years of uncertainty following the July 16, 2020 decision of the Court of Justice of the European Union invalidating the EU-U.S. Privacy Shield Framework for purposes of international transfers and imposing further restrictions on the use of standard contractual clauses (EU SCCs), including a requirement for companies to carry out a transfer privacy impact assessment (TIA), on July 10, 2023, the European Commission adopted its Final Implementing Decision granting the U.S. adequacy (Adequacy Decision) for EU-U.S. transfers of personal data for entities self-certified to the EU-U.S. Data Privacy Framework (DPF). Entities relying on EU SCCs for transfers to the United States are also able to rely on the analysis in the Adequacy Decision as support for their TIA regarding the equivalence of U.S. national security safeguards and redress.
Under the UK GDPR, companies not established in the UK but who process personal data in relation to the offering of goods or services to individuals in the UK, or to the monitoring of their behavior will be subject to the UK GDPR—the requirements of which at this time are largely aligned with those under the EU GDPR. The European Commission has adopted an adequacy decision in favor of the UK, enabling data transfers from EU Member States to the UK without additional safeguards. However, the UK adequacy decision will automatically expire in June 2025 unless the European Commission reassesses and renews/extends that decision, and remains under review by the European Commission during this period.
The UK GDPR also imposes similar restrictions on transfers of personal data from the UK to jurisdictions that the UK Government does not consider adequate, including the U.S.. The UK’s Information Commissioner’s Office (ICO) published: (i) its own form of EU SCCs, known as the International Data Transfer Agreement to replace the old Standard Contractual Clauses for transfers to outside the UK; (ii) a “UK addendum” to the new EU SCCs which amends the relevant provisions of such clauses to work in a UK context; and (iii) its own version of the TIA and guidance on international transfers (although entities may choose to adopt either the EU or UK-style TIA). Further, on September 21, 2023, the UK Secretary of State for Science, Innovation and Technology established a UK-U.S. data bridge (i.e., a UK equivalent of the Adequacy Decision) and adopted UK regulations to implement the UK-U.S. data bridge (“UK Adequacy Regulations”). Personal data may now be transferred from the UK under the UK-U.S. data bridge through the UK extension to the DPF to organizations self-certified under the UK extension to the DPF.
As a company, we have invested, and expect to continue to invest, significant time and resources in our GDPR compliance program. This is necessary to ensure we can initiate and maintain GDPR-compliant clinical trials in the EU or UK (as applicable). Any failure or perceived failure by us with respect to GDPR compliance could mean we either cannot initiate additional GDPR-compliant clinical trials in the EU or UK (as applicable) or we may face regulatory investigations, significant fines and penalties, reputational damage or be required to change our business practices, all of which could adversely affect our business, financial condition and results of operations. There is a risk that we could be impacted by a cybersecurity incident that results in loss or unauthorized disclosure of personal data, potentially resulting in us facing harms similar to those described above.
Some countries also are considering or have passed legislation requiring local storage and processing of data, or similar requirements, which could increase the cost and complexity for conducting preclinical testing and clinical trials or delivering our future products, if any. Additionally, other countries (e.g., Australia and Japan) have adopted certain legal requirements for cross-border transfers of personal information. These obligations may be interpreted and applied in a manner that is inconsistent from one jurisdiction to another and may conflict with other requirements or our practices.
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It is possible that these laws may be interpreted and applied in a manner that is inconsistent with our practices, and our efforts to comply with the evolving data protection rules may be unsuccessful. In addition to the possibility of fines, lawsuits, regulatory investigations, public censure, other claims and penalties, and significant costs for remediation and damage to our reputation, we could be materially and adversely affected if legislation or regulations are expanded to require changes in our data processing practices and policies or if governing jurisdictions interpret or implement their legislation or regulations in ways that negatively impact our business. Compliance with these and any other applicable privacy and data security laws and regulations is a rigorous and time-intensive process, and we may be required to put in place additional mechanisms for ensuring compliance with the new data protection rules. In addition to government regulation, privacy advocates and industry groups have and may in the future propose self-regulatory standards from time to time. These and other industry standards may legally or contractually apply to us, or we may elect to comply with such standards. It is possible that if our practices are not consistent or viewed as not consistent with legal and regulatory requirements, including changes in laws, regulations and standards or new interpretations or applications of existing laws, regulations and standards, we may become subject to audits, inquiries, whistleblower complaints, adverse media coverage, investigations, loss of export privileges, or severe criminal or civil sanctions, all of which may have a material and adverse impact on our business, results of operations, reputation, and financial condition. Even if we are not determined to have violated these laws, government investigations into these issues typically require the expenditure of significant resources and generate negative publicity, which could harm our business, financial condition, results of operations or prospects.
Any such liability, litigation, investigations and proceedings may or may not be covered by our liability insurance and may subject us to significant penalties and negative publicity, require us to change our business practices, increase our costs, severely disrupt our business, and may result in significant reputational harm and have a material and adverse impact on our business, financial condition, results of operations or prospects.
U.S. federal income tax reform and changes in other tax laws could adversely affect us.
In December 2017, U.S. federal tax legislation commonly referred to as the TCJA was signed into law, significantly reforming the Internal Revenue Code of 1986, as amended (Code). The TCJA, among other things, changed the U.S. federal tax treatment of research and experimental (R&E) expenses. For tax years beginning on or after January 1, 2022, taxpayers are required to capitalize and amortize, rather than deduct, R&E expenses. R&E expenses are amortizable over five years for research performed in the United States and 15 years for research performed outside the United States. Although there are legislative proposals to repeal or defer the capitalization requirement to later years, there can be no assurance that the provision will be repealed or otherwise modified.
Effective for transactions occurring on or after January 1, 2023, the IRA imposed a new one percent excise tax on certain repurchases of stock by publicly traded U.S. domestic corporations. The excise tax is imposed on the repurchasing corporation itself, not its shareholders from which shares are repurchased. For purposes of calculating the base excise tax, repurchasing corporations are permitted to net the fair market value of certain new stock issuances against the fair market value of stock repurchases during the same taxable year. Certain repurchases are not counted in the base of the excise tax.
In addition, new legislation or regulations that could affect our tax burden could be enacted by any governmental authority. We cannot predict the timing or extent of such tax-related developments that could negatively impact our financial results. We use our best judgment in attempting to quantify and reserve for these tax obligations. However, a challenge by a taxing authority, our ability to utilize tax benefits such as carryforwards or tax credits, or a deviation from other tax-related assumptions could have a material adverse effect on our business, results of operations, or financial condition.
Our ability to utilize our net operating loss carryforwards may be subject to limitations.
We have incurred substantial losses during our history, do not expect to become profitable in the near future and may never achieve profitability. As of November 30, 2023, we had federal and state net operating loss (NOL) carryforwards of approximately $269.3 million and $410.9 million, respectively. To the extent we continue to generate taxable losses, unused losses will carry forward to offset future taxable income, if any, subject to the restrictions and exceptions described below. Federal NOLs generated in tax years beginning on or before December 31, 2017, may be carried forward 20 tax years and expire on various dates beginning in 2029. Under current law, NOLs arising in tax years beginning after December 31, 2017, may be carried forward indefinitely, but are limited to no more than 80% of the excess, if any, of current year taxable income (without regard to certain deductions). Our state NOLs can be carried forward 20 years and begin expiring in 2029.
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Under Sections 382 and 383 of the Code, if a corporation undergoes an “ownership change” (generally defined as a greater than 50% change (by value) in its equity ownership over a three-year period), the corporation’s ability to use its pre-change NOLs and other pre-change tax attributes (such as research tax credits) to offset its post-change income or post-change income tax may be limited. We have identified two ownership changes since our inception that have triggered a limitation on pre-change NOLs under Section 382. A majority of our pre-change NOLs remain available within the carryforward period provided by the Code, subject to availability of taxable income. We may have experienced additional ownership changes that have not yet been identified that could result in the expiration of our NOL and credit carryforwards before utilization and we may experience additional ownership changes in the future as a result of subsequent shifts in our stock ownership, some of which are outside our control. As a result, if we earn net taxable income, our ability to use our pre-change NOLs and tax credit carryovers to offset U.S. federal taxable income and tax liability may be subject to limitations that potentially could result in increased future tax liability to us. In addition, at the state level, there may be periods during which the use of NOLs is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed.
Future acquisitions, joint ventures, spin outs or strategic alliances or transactions could disrupt our business and harm our financial condition and results of operations.
We may acquire additional businesses or drugs, form strategic alliances or create joint ventures with third parties that we believe will complement or augment our existing business. If we acquire businesses with promising markets or technologies, we may not be able to realize the benefit of acquiring such businesses if we are unable to successfully integrate them with our existing operations and company culture. We may encounter numerous difficulties in developing, manufacturing and marketing any new drugs resulting from a strategic alliance or acquisition that delay or prevent us from realizing their expected benefits or enhancing our business. We cannot be certain that, following any such acquisition, we will achieve the expected synergies to justify the transaction. The risks we face in connection with acquisitions include:
•diversion of management time and focus from operating our business to addressing acquisition integration challenges;
•coordination of research and development efforts;
•retention of key employees from the acquired company;
•changes in relationships with strategic partners as a result of product acquisitions or strategic positioning resulting from the acquisition;
•cultural challenges associated with integrating employees from the acquired company into our organization;
•the need to implement or improve controls, procedures and policies at a business that prior to the acquisition may have lacked sufficiently effective controls, procedures and policies;
•liability for activities of the acquired company before the acquisition, including intellectual property infringement claims, violation of laws, commercial disputes, tax liabilities and other known liabilities;
•unanticipated write-offs or charges; and
•litigation or other claims in connection with the acquired company, including claims from terminated employees, customers, former stockholders or other third parties.
Our failure to address these risks or other problems encountered in connection with our past or future acquisitions or strategic alliances could cause us to fail to realize the anticipated benefits of these transactions or cause us to incur unanticipated liabilities and harm the business generally. There also is a risk that future acquisitions will result in our incurring debt, contingent liabilities, amortization expenses or incremental operating expenses, any of which could harm our financial condition or results of operations. Additionally, we may not realize the expected value of out-licensing, joint ventures, spin outs or other strategic transactions.
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We are subject to anti-corruption laws, as well as export control laws, customs laws, sanctions laws and other laws governing our operations. If we fail to comply with these laws, we could be subject to civil or criminal penalties, or other remedial measures and legal expenses, any of which could adversely affect our business, results of operations and financial condition.
Our operations are subject to anti-corruption laws, including the Foreign Corrupt Practices Act (FCPA), the Bribery Act and other anticorruption laws that apply in countries where we do business and may do business in the future. The FCPA, the Bribery Act and other anti-corruption or similar laws generally prohibit us, our officers and our employees and intermediaries from bribing, being bribed or making other prohibited payments to government officials or other persons to obtain or retain business or gain some other business advantage. We may in the future operate in jurisdictions that pose a high risk of potential FCPA or Bribery Act violations, and we may participate in collaborations and relationships with third parties whose actions could potentially subject us to liability under the FCPA, the Bribery Act or local anti-corruption laws. In addition, we cannot predict the nature, scope or effect of future regulatory requirements to which our international operations might be subject or the manner in which existing laws might be administered or interpreted.
We also are subject to other laws and regulations governing our international operations, including regulations administered by the governments of the United States, UK and authorities in the EU, including applicable export control regulations, economic sanctions on countries and persons, customs requirements and currency exchange regulations, which we collectively refer to as Trade Control Laws.
There is no assurance that we will be completely effective in ensuring our compliance with all applicable anti-corruption laws, including the FCPA, the Bribery Act, or other legal requirements including Trade Control Laws. If we are not in compliance with the FCPA, the Bribery Act, and other anti-corruption laws or Trade Control Laws, we may be subject to criminal and civil penalties, legal expenses, and disgorgement and other sanctions and remedial measures, which could have an adverse impact on our business, financial condition, results of operations and liquidity. The Securities and Exchange Commission (SEC) also may suspend or bar issuers from trading securities on U.S. exchanges for violations of the FCPA’s accounting provisions. Likewise, any investigation of any potential violations of the FCPA, the Bribery Act, other anti-corruption laws or Trade Control Laws by U.S., UK or other authorities also could have an adverse impact on our reputation, our business, results of operations and financial condition.
If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could significantly harm our business.
We are subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. From time to time and in the future, our operations may involve the use of hazardous and flammable materials, including chemicals and biological materials, and may produce hazardous waste products. Although we contract with third parties for the disposal of these materials and waste products, we cannot completely eliminate the risk of contamination or injury resulting from these materials. In the event of contamination or injury resulting from the use or disposal of our hazardous materials, we could be held liable for any resulting damages, and any liability could exceed our resources. We also could incur significant costs associated with civil or criminal fines and penalties for failure to comply with such laws and regulations.
We maintain workers’ compensation insurance to cover costs and expenses we may incur due to injuries to our employees resulting from the use of hazardous materials, but this insurance may not provide adequate coverage against potential liabilities. We do not maintain insurance for environmental liability or toxic tort claims that may be asserted against us. In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations. Current or future environmental laws and regulations may impair our research, development or production efforts, which could adversely affect our business, financial condition, results of operations or prospects. In addition, failure to comply with these laws and regulations may result in substantial fines, penalties or other sanctions.
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Unfavorable global economic conditions could adversely affect our business, financial condition, stock price and results of operations.
Our results of operations could be adversely affected by general conditions in the global economy and in the global financial markets. For example, the global financial crisis of 2007-2008 caused extreme volatility and disruptions in the capital and credit markets. Similarly, the volatility associated with the COVID-19 pandemic caused significant instability and disruptions in the capital and credit markets and, more recently, the global economy has been impacted by increasing interest rates and inflation, uncertainty with respect to the federal budget and debt ceiling and potential government shutdowns related thereto, as well as the possibility of a recession or further economic downturn. Moreover, there have been recent concerns with respect to the stability of the global banking system. For example, on March 10, 2023, Silicon Valley Bank (SVB), which was one of our banking partners, was closed by the California Department of Financial Protection and Innovation, which appointed the Federal Deposit Insurance Corporation (FDIC) as receiver. Similarly, on March 12, 2023, Silvergate Capital Corp. and Signature Bank were each swept into receivership. While we only had a minimal amount of our cash directly at SVB and the FDIC took steps to make depositors of SVB whole such that we regained access to this cash, there is no assurance that similar guarantees will be made in the event of further bank closures and continued instability in the global banking system. Our ongoing cash management strategy is to maintain diversity in our deposit accounts across financial institutions, but deposits in these institutions may exceed the amount of insurance provided on such deposits and there can be no assurance that this strategy will be successful. If other banks and financial institutions enter receivership or become insolvent in the future in response to financial conditions affecting the banking system and financial markets, then our ability to access our cash, cash equivalents and marketable securities may be threatened, which could have a material adverse effect on our business and financial condition. Furthermore, the capital and credit markets may be adversely affected by regional conflicts around the world and the possibility of a wider global conflict, global sanctions imposed in response to regional conflicts or an energy crisis. A severe or prolonged economic downturn, such as the global financial crisis, could result in a variety of risks to our business, including weakened demand for our drug candidates and in our ability to raise additional capital when needed on acceptable terms, if at all. A weak or declining economy also could strain our suppliers, possibly resulting in supply disruption. We cannot anticipate all of the ways in which the foregoing, and the current economic climate and financial market conditions generally, could adversely impact our business. Furthermore, our stock price may decline due in part to the volatility of the stock market and any general economic downturn.
Our current operations are in the San Francisco Bay Area, and we or the third parties upon whom we depend may be adversely affected by earthquakes or other natural disasters as to which our business continuity and disaster recovery plans may not be adequate to protect us.
Our current operations are located in our facilities in San Francisco, California. Any unplanned event, such as earthquake, flood, fire, explosion, extreme weather condition, medical epidemic, power shortage, telecommunication failure or other natural or man-made accident or incident that results in our being unable to fully utilize our facilities, or the manufacturing facilities of our third-party contract manufacturers, may have a material and adverse effect on our ability to operate our business, particularly on a daily basis, and have significant negative consequences on our financial and operating conditions. Loss of access to these facilities may result in increased costs, delays in the development of our drug candidates or interruption of our business operations, and have a material adverse effect on our business, financial condition, results of operations and prospects. If a natural disaster, power outage or other event occurred that prevented us from using all or a significant portion of our headquarters, that damaged critical infrastructure such as our research facilities or the manufacturing facilities of our third-party contract manufacturers, or that otherwise disrupted operations, it may be difficult or, in certain cases, impossible, for us to continue our business for a substantial period of time. The disaster recovery and business continuity plans we have in place may prove inadequate in the event of a serious disaster or similar event. We may incur substantial expenses as a result of the limited nature of our disaster recovery and business continuity plans, which could have a material adverse effect on our business. As part of our risk management policy, we maintain insurance coverage at levels that we believe are appropriate for our business. However, in the event of an accident or incident at these facilities, we cannot assure you that the amounts of insurance will be sufficient to satisfy any damages and losses. If our facilities, or the manufacturing facilities of our third-party contract manufacturers, are unable to operate because of an accident or incident or for any other reason, even for a short period of time, any or all of our research and development programs may be harmed. Any business interruption could have a material and adverse effect on our business, financial condition, results of operations and prospects.
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Risks Related to Our Common Stock
Our quarterly results of operations may fluctuate significantly or may fall below the expectations of investors or securities analysts, each of which may cause our stock price to fluctuate or decline.
We expect our results of operations to be subject to quarterly fluctuations. Our net loss and other results of operations will be affected by numerous factors, including:
•variations in the level of expense related to the ongoing development of our drug candidates, DELigase platform, or future development programs;
•results of preclinical studies and clinical trials, or the addition or termination of clinical trials or funding support by us or by existing or future collaborators or licensing partners;
•our execution of any additional collaboration, licensing or similar arrangements, and the timing of payments we may make or receive under existing or future arrangements or the termination or modification of any such existing or future arrangements;
•any intellectual property infringement lawsuit or opposition, interference or cancellation proceeding in which we may become involved;
•additions and departures of key personnel;
•strategic decisions by us or our competitors, such as acquisitions, divestitures, spin-offs, joint ventures, strategic investments or changes in business strategy;
•if any of our drug candidates receives regulatory approval, the terms of such approval and market acceptance and demand for such drug candidates;
•regulatory developments affecting our drug candidates or those of our competitors; and
•changes in general market and economic conditions, including increasing interest rates, inflation, uncertainty with respect to the federal budget and debt ceiling and potential government shutdowns related thereto, instability in the global banking system and the possibility of a recession or further economic downturn.
If our quarterly results of operations fall below the expectations of investors or securities analysts, the price of our common stock could decline substantially. Furthermore, any quarterly fluctuations in our results of operations may, in turn, cause the price of our common stock to fluctuate substantially. We believe that quarterly comparisons of our financial results are not necessarily meaningful and should not be relied upon as an indication of our future performance.
Our stock price may be volatile and you could lose all or part of your investment.
The trading price of our common stock may be highly volatile and subject to wide fluctuations in response to various factors, some of which we cannot control. As a result of this volatility, investors may not be able to sell their common stock at or above the purchase price. The market price for our common stock may be influenced by many factors, including the other risks described in this “Risk Factors” section and the following:
•results of preclinical studies and clinical trials of our drug candidates, or those of our competitors or our existing or future collaborators;
•regulatory or legal developments in the United States and other countries, especially changes in laws or regulations applicable to our drug candidates;
•the success of competitive products or technologies;
•introductions and announcements of new products by us, our collaboration partners, or our competitors, and the timing of these introductions or announcements;
•actions taken by regulatory agencies with respect to our drug candidates, clinical trials, manufacturing process or sales and marketing terms;
•actual or anticipated variations in our financial results or in those of companies that are perceived to be similar to us;
•the success of our efforts to acquire or in-license additional technologies, products or drug candidates;
•developments concerning our current or future collaborations, including but not limited to those with our sources of manufacturing supply and our commercialization partners;
•market conditions in the pharmaceutical and biotechnology sectors;
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•announcements by us or our competitors of significant acquisitions, strategic collaborations, joint ventures or capital commitments;
•developments or disputes concerning patents or other proprietary rights, including patents, litigation matters and our ability to obtain patent protection for our drug candidates and products;
•our ability or inability to raise additional capital and the terms on which any additional capital is raised;
•the recruitment or departure of key personnel;
•changes in the structure of healthcare payment systems;
•actual or anticipated changes in earnings estimates or changes in stock market analyst recommendations regarding our common stock, other comparable companies or our industry generally;
•our failure or the failure of our competitors to meet analysts’ projections or guidance that we or our competitors may provide to the market;
•fluctuations in the valuation of companies perceived by investors to be comparable to us;
•announcement and expectation of additional financing efforts;
•speculation in the press or investment community;
•trading volume of our common stock;
•sales of our common stock by us or our stockholders;
•the concentrated ownership of our common stock;
•changes in accounting principles;
•cybersecurity events;
•terrorist acts, acts of war or periods of widespread civil unrest, including the increasingly volatile global economic conditions resulting from regional conflicts around the world;
•effects of public health crises, pandemics and epidemics;
•natural disasters and other calamities; and
•general economic, industry and market conditions, including increasing interest rates, inflation, uncertainty with respect to the federal budget and debt ceiling and potential government shutdowns related thereto, instability in the global banking system and the possibility of a recession or further economic downturn.
In addition, the stock market in general, and the markets for pharmaceutical, biopharmaceutical and biotechnology stocks in particular, have experienced extreme price and volume fluctuations that often have been unrelated or disproportionate to the operating performance of the issuer. These broad market and industry factors may seriously harm the market price of our common stock, regardless of our actual operating performance. The realization of any of the above risks or any of a broad range of other risks, including those described in this “Risk Factors” section, could have a dramatic and adverse impact on the market price of our common stock.
A sale of a substantial number of shares of our common stock may cause the price of our common stock to decline.
Sales of a substantial number of shares of our common stock in the public market could occur at any time. If our stockholders sell, or the market perceives that our stockholders intend to sell, substantial amounts of our common stock in the public market, the market price of our common stock could decline significantly.
We cannot predict what effect, if any, sales of our shares in the public market or the availability of shares for sale will have on the market price of our common stock. However, future sales of substantial amounts of our common stock in the public market, including shares issued upon exercise of outstanding options or vesting and settlement of outstanding restricted stock units, or the perception that such sales may occur, could adversely affect the market price of our common stock.
We also expect that significant additional capital may be needed in the future to continue our planned operations. To raise capital, we may sell common stock, convertible securities or other equity securities in one or more transactions at prices and in a manner we determine from time to time. These sales, or the perception in the market that the holders of a large number of shares intend to sell shares, could reduce the market price of our common stock.
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If securities or industry analysts do not publish research or reports about our business, or if they issue an adverse or misleading opinion regarding our stock, our stock price and trading volume could decline.
The trading market for our common stock is and will be influenced by the research and reports that industry or securities analysts publish about us or our business. We do not have any control over the analysts or the content and opinions included in their reports. If any of the analysts who cover us issue an adverse or misleading opinion regarding us, our business model, our intellectual property or our stock performance, or if our preclinical studies and clinical trials and results of operations fail to meet the expectations of analysts, our stock price would likely decline. If one or more of such analysts cease coverage of us or fail to publish reports on us regularly, we could lose visibility in the financial markets, which in turn could cause a decline in our stock price or trading volume.
The future sale and issuance of equity or of debt securities that are convertible into equity will dilute our share capital.
We may choose to raise additional capital in the future, depending on market conditions, strategic considerations and operational requirements. For example, in March 2021, we sold an additional 5,175,000 shares of our common stock in a follow-on public offering. In addition, we currently have on file with the SEC a shelf registration statement on Form S-3 which allows us to offer and sell up to $450.0 million of our registered common stock, preferred stock, debt securities, warrants, subscriptions rights and or units from time to time pursuant to one or more offerings at prices and terms to be determined at the time of sale. In August 2021, we entered into an Equity Distribution Agreement with Piper Sandler & Co. (Piper Sandler) pursuant to which, from time to time, we may offer and sell through Piper Sandler up to $150.0 million of the common stock registered under the shelf registration statement pursuant to one or more “at the market” offerings. In June 2022, we issued and sold 2,000,000 shares of common stock under the Equity Distribution Agreement to Piper Sandler for net proceeds of approximately $19.3 million, after deducting offering commissions and expenses paid by us. As of November 30, 2023, we had $130.0 million of common stock remaining available for sale pursuant to the Equity Distribution Agreement. Sales of our common stock under the Equity Distribution Agreement with Piper Sandler could be subject to business, economic or competitive uncertainties and contingencies, many of which may be beyond our control, and which could cause actual results from the sale of our common stock to differ materially from expectations. In addition, in July 2022, we entered into separate Securities Purchase Agreements with certain purchasers to issue and sell pre-funded warrants to purchase an aggregate of 6,814,920 shares of our common stock in registered direct offerings for gross proceeds to us of $95.0 million before deducting offering expenses. Such pre-funded warrants are immediately exercisable, have an exercise price of $0.001 and may be exercised at any time after the date of issuance. To the extent additional capital is raised through the sale and issuance of shares or other securities convertible into shares, the ownership interest of our stockholders will be diluted. Future issuances of our common stock or other equity securities, or the perception that such sales may occur, could adversely affect the trading price of our common stock and impair our ability to raise capital through future offerings of shares or equity securities. No prediction can be made as to the effect, if any, that future sales of common stock or the availability of common stock for future sales will have on the trading price of our common stock.
We will not receive a significant amount, or potentially any, additional funds upon the exercise of our pre-funded warrants; however, any exercise would increase the number of shares eligible for future resale in the public market and result in substantial dilution to our stockholders.
As of November 30, 2023, we have issued pre-funded warrants to purchase a total of 6,814,920 shares of our common stock, of which 6,097,560 were outstanding as of November 30, 2023. Each pre-funded warrant is exercisable for $0.001 per share of common stock underlying such pre-funded warrant, which may be paid by way of a cashless exercise, meaning that the holder may not pay a cash purchase price upon exercise, but instead would receive upon such exercise the net number of shares of common stock determined according to the formula set forth in the pre-funded warrant. Accordingly, we will not receive a significant amount, or potentially any, additional funds upon the exercise of the pre-funded warrants. To the extent such pre-funded warrants are exercised, additional shares of common stock will be issued for nominal or no additional consideration, which will result in substantial dilution to the then existing holders of our common stock and will increase the number of shares eligible for resale in the public market. Sales of substantial numbers of such shares in the public market could adversely affect the market price of the common stock, causing our stock price to decline.
There is no public market for our pre-funded warrants.
There is no public trading market for our pre-funded warrants issued, and we do not expect a market to develop. In addition, we do not intend to apply to list the pre-funded warrants on any securities exchange or nationally recognized trading system, including the Nasdaq Global Market (Nasdaq). Without an active market, the liquidity of the pre-funded warrants will be limited, and the value of the pre-funded warrants may be adversely impacted.
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Additionally, each holder of pre-funded warrants will not be entitled to exercise any portion of any pre-funded warrant, which, upon giving effect to such exercise, would cause (i) the aggregate number of shares of our common stock beneficially owned by the holder (together with its affiliates) to exceed 9.99% of the number of shares of our common stock outstanding immediately after giving effect to the exercise, or (ii) the combined voting power of our securities beneficially owned by the holder (together with its affiliates) to exceed 9.99% of the combined voting power of all of our securities then outstanding immediately after giving effect to the exercise. However, any holder may increase or decrease such percentage to any other percentage (not in excess of 19.99%) upon at least 61 days’ prior notice from the holder to us.
Anti-takeover provisions in our charter documents and under Delaware law could make an acquisition of us, which may be beneficial to our stockholders, more difficult and may prevent attempts by our stockholders to replace or remove our current management.
Our restated certificate of incorporation and our amended and restated bylaws contain provisions that could delay or prevent a change in control of our company. These provisions also could make it difficult for stockholders to elect directors who are not nominated by current members of our board of directors or to take other corporate actions, including effecting changes in our management. These provisions:
•establish a classified board of directors so that not all members of our board are elected at one time;
•permit only our board of directors to establish the number of directors and fill vacancies on our board;
•provide that directors may be removed only “for cause” and only with the approval of two-thirds of our stockholders;
•require super-majority voting to amend some provisions in our restated certificate of incorporation and amended and restated bylaws, unless such amendments are approved by two-thirds of our board of directors, in which case stockholders can approve by a simple majority;
•authorize the issuance of “blank check” preferred stock that our board could use to implement a stockholder rights plan;
•eliminate the ability of our stockholders to call special meetings of stockholders;
•prohibit stockholder action by written consent, which requires all stockholder actions to be taken at a meeting of our stockholders;
•prohibit cumulative voting; and
•establish advance notice requirements for nominations for election to our board or for proposing matters that can be acted upon by stockholders at annual stockholder meetings.
In addition, Section 203 of the Delaware General Corporation Law (DGCL) may discourage, delay or prevent a change in control of our company. Section 203 imposes certain restrictions on mergers, business combinations and other transactions between us and holders of 15% or more of our common stock.
Our restated certificate of incorporation and our amended and restated bylaws contain exclusive forum provisions for certain claims, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers or employees.
Our restated certificate of incorporation, to the fullest extent permitted by law, provides that the Court of Chancery of the State of Delaware will be the exclusive forum for any derivative action or proceeding brought on our behalf; any action asserting a breach of fiduciary duty; any action asserting a claim against us arising pursuant to the DGCL, our restated certificate of incorporation, or our amended and restated bylaws; or any action asserting a claim against us that is governed by the internal affairs doctrine.
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Moreover, Section 22 of the Securities Act of 1933, as amended (the Securities Act) creates concurrent jurisdiction for federal and state courts over all claims brought to enforce any duty or liability created by the Securities Act or the rules and regulations thereunder and our amended and restated bylaws provide that the federal district courts of the United States of America will, to the fullest extent permitted by law, be the exclusive forum for resolving any complaint asserting a cause of action arising under the Securities Act (a Federal Forum Provision). Our decision to adopt a Federal Forum Provision followed a decision by the Supreme Court of the State of Delaware holding that such provisions are facially valid under Delaware law. While there can be no assurance that federal or state courts will follow the holding of the Delaware Supreme Court or determine that the Federal Forum Provision should be enforced in a particular case, application of the Federal Forum Provision means that suits brought by our stockholders to enforce any duty or liability created by the Securities Act must be brought in federal court and cannot be brought in state court. Section 27 of the Exchange Act creates exclusive federal jurisdiction over all claims brought to enforce any duty or liability created by the Exchange Act or the rules and regulations thereunder and neither the exclusive forum provision nor the Federal Forum Provision applies to suits brought to enforce any duty or liability created by the Exchange Act. Accordingly, actions by our stockholders to enforce any duty or liability created by the Exchange Act or the rules and regulations thereunder must be brought in federal court. Our stockholders will not be deemed to have waived our compliance with the federal securities laws and the regulations promulgated thereunder.
Any person or entity purchasing or otherwise acquiring or holding any interest in any of our securities shall be deemed to have notice of and consented to our exclusive forum provisions, including the Federal Forum Provision. These provisions may limit our stockholders’ ability to bring a claim in a judicial forum they find favorable for disputes with us or our directors, officers, or other employees, which may discourage lawsuits against us and our directors, officers, and other employees. Alternatively, if a court were to find the choice of forum provision contained in our restated certificate of incorporation and/or amended and restated bylaws to be inapplicable or unenforceable in an action, we may incur additional costs associated with resolving such action in other jurisdictions, which could harm our business, results of operations and financial condition.
We will continue to incur increased costs as a result of operating as a public company, and our management will be required to devote substantial time to new compliance initiatives and corporate governance practices.
As a public company, we incur significant legal, accounting and other expenses. We are subject to the reporting requirements of the Exchange Act, the Sarbanes-Oxley Act, the Dodd-Frank Wall Street Reform and Consumer Protection Act, the listing requirements of Nasdaq and other applicable securities rules and regulations which impose various requirements on public companies, including establishment and maintenance of effective disclosure and financial controls and corporate governance practices. Compliance with these rules and regulations may strain our financial and management systems, internal controls, and employees. For example, the Exchange Act requires, among other things, that we file annual, quarterly, and current reports with respect to our business and results of operations and the disclosure requirements under the Exchange Act are subject to change from time to time. For example, in 2023 the SEC adopted rules requiring disclosure of material cybersecurity incidents suffered by public companies, as well as annual disclosure regarding cybersecurity governance and risk management. Complying with these new disclosure obligations once applicable to our company, or any or any additional new disclosure requirements that may apply to us in the future, could cause us to incur substantial costs and could increase negative publicity surrounding any incident that we are required to disclose. Any failure or perceived failure by us to comply with these obligations may also subject us to enforcement action or litigation, any of which could harm our business.
Therefore, as a result of being a public company, our management and other personnel are required to devote a substantial amount of time to these compliance initiatives. Moreover, these rules and regulations have increased our legal and financial compliance costs and have made some activities more time-consuming and costly. We cannot predict or estimate the amount or timing of additional costs we may incur to respond to these requirements. The impact of these requirements also could make it more difficult for us to attract and retain qualified persons to serve on our board of directors, our board committees or as executive officers. Moreover, these rules and regulations often are subject to varying interpretations, in many cases due to their lack of specificity, and, as a result, their application in practice may evolve over time as new guidance is provided by regulatory and governing bodies. This could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing revisions to disclosure and governance practices.
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If we fail to maintain effective internal control over financial reporting, our ability to produce accurate and timely financial statements could be impaired, which could harm our results of operations, investors’ views of us and, as a result, the value of our common stock.
Pursuant to the rules and regulations of the SEC, we are required to furnish a report by our management on, among other things, our internal control over financial reporting. To achieve compliance with these rules and regulations, we engage in a process to document and evaluate our internal control over financial reporting, which is both costly and time-consuming. Effective internal control over financial reporting is necessary for us to provide reliable financial reporting and, together with adequate disclosure controls and procedures, are designed to prevent material misstatements due to fraud or error. Any failure to design new or improved internal controls necessary to address risks of material misstatement in our interim or annual financial statements, or difficulties encountered in their implementation or operation, could cause us to fail to meet our reporting obligations. Ineffective internal control over financial reporting could also cause investors to lose confidence in our reported financial information, which could have a negative effect on the trading price of our common stock.
The reporting on our assessment of the effectiveness of our internal control over financial reporting needs to include disclosure of any material weaknesses identified in our internal control over financial reporting. Moreover, in the event that we qualify as a large accelerated filer or accelerated filer under SEC rules in future years, our independent registered public accounting firm will be required to audit the effectiveness of our internal control over financial reporting pursuant to Section 404(b) of the Sarbanes-Oxley Act (Section 404(b)). Any mandatory or voluntary compliance with Section 404(b) will result in increased costs, expenses, and management resources. Undetected material weaknesses in our internal control over financial reporting could lead to financial statement restatements and require us to incur the expense of remediation. For example, we previously identified material weaknesses in our internal control over financial reporting for the fiscal year ended November 30, 2021, related to controls over segregation of duties in our journal entry and account reconciliation processes, and certain information technology general controls. The material weaknesses identified did not result in any misstatement of our financial statements and during the year ended November 30, 2022, the material weaknesses was remediated. However, we cannot assure you that the measures we have taken to date, and actions we may take in the future, will prevent or avoid potential future material weaknesses.
We are also required to disclose changes made in our internal control over financial reporting that have materially affected, or are reasonably likely to materially affect, internal control over financial reporting on a quarterly basis. To comply with the requirements of being a public company, we have undertaken, and may need to further undertake in the future, various actions, such as implementing new internal controls and procedures and hiring additional accounting staff.
Moreover, our current controls and any new controls that we develop may become inadequate because of changes in conditions in our business. Further, material weaknesses in our disclosure controls and procedures and internal control over financial reporting may be discovered in the future. Any failure to develop or maintain effective internal control over financial reporting or any difficulties encountered in their implementation or improvement could harm our results of operations or cause us to fail to meet our reporting obligations and may result in a restatement of our financial statements for prior periods, which could cause the price of our common stock to decline. In addition, if we are not able to continue to meet these requirements, we may not be able to remain listed on Nasdaq.
We are a “smaller reporting company” and the reduced disclosure requirements applicable to smaller reporting companies may make our common stock less attractive to investors.
We became a “smaller reporting company” as of May 31, 2022. We will continue to be a smaller reporting company so long as either (i) the market value of our stock held by non-affiliates is less than $250.0 million as of the prior May 31 or (ii) our annual revenue is less than $100.0 million during the most recently completed fiscal year and the market value of our stock held by non-affiliates is less than $700.0 million as of the prior May 31. As a smaller reporting company, we may take advantage of many of the same exemptions from disclosure requirements as an emerging growth company, including reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements. We cannot predict if investors will find our common stock less attractive because we may rely on these exemptions. If some investors find our common stock less attractive as a result, there may be a less active trading market for our common stock and our stock price may be more volatile.
Because we do not anticipate paying any cash dividends on our capital stock in the foreseeable future, capital appreciation, if any, will be your sole source of gain.
We have never declared or paid cash dividends on our capital stock. We currently intend to retain all of our future earnings, if any, to finance the growth and development of our business. As a result, capital appreciation, if any, of our common stock will be your sole source of gain for the foreseeable future.
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We may be subject to securities litigation, which is expensive and could divert management attention.
The market price of our common stock may be volatile. In the past, companies that have experienced volatility in the market price of their stock have been subject to securities class action litigation. We may be the target of this type of litigation in the future. Securities litigation against us could result in substantial costs and divert our management’s attention from other business concerns, which could seriously harm our business.
Item 1B. Unresolved Staff Comments
None.
Item 1C. Cybersecurity
Not applicable.
Item 2. Properties and Facilities
Our principal executive office is located in San Francisco, California, where we lease a total of 77,222 square feet of office and laboratory spaces that we use for our administrative, research and development and other activities. The lease for 19,320 square feet of space expires in June 2024, and the lease for 57,902 square feet of space expires in April 2025. Additionally, we lease a total of 50,094 square feet of office and laboratory space in The Woodlands, Texas that expires in February 2035. We believe that our existing facilities are suitable and adequate for our current requirements and operations.
Item 3. Legal Proceedings
From time to time, we may be involved in legal proceedings arising in the ordinary course of our business. We are not presently a party to any legal proceedings that, in the opinion of management, would have a material adverse effect on our business or consolidated financial statements. Regardless of outcome, litigation can have an adverse impact on us due to defense and settlement costs, diversion of management resources, negative publicity and reputational harm and other factors.
Item 4. Mine Safety Disclosures
Not applicable.
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PART II
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities
Market Information for Common Stock
Our common stock has been listed on the Nasdaq Global Market under the symbol “NRIX” since July 24, 2020. Prior to that date, there was no public trading market for our common stock.
Holders of Record
As of close of business on February 5, 2024, there were 16 holders of record of our common stock. The actual number of stockholders is greater than this number of record holders, and includes stockholders who are beneficial owners, but whose shares are held in street name by brokers and other nominees. This number of holders of record also does not include stockholders whose shares may be held in trust by other entities.
Dividend Policy
We have never declared or paid cash dividends on our capital stock. We currently intend to retain all available funds and future earnings, if any, to finance the growth and development of our business, and we do not anticipate paying any cash dividends in the foreseeable future. Any future determination regarding the declaration and payment of dividends will fall within the discretion of our Board of Directors, and will depend on various factors, including our operating results, financial condition, and capital requirements, restrictions that may be imposed by applicable law, and other factors deemed relevant by our Board of Directors.
Stock Price Performance Graph
As a “smaller reporting company” as defined by Item 10 of Regulation S-K, we are not required to provide this information.
Use of Proceeds from Registered Securities
None.
Securities Authorized for Issuance under Equity Compensation Plans
Information regarding our equity compensation plans and the securities authorized for issuance thereunder is set forth in Part III, Item 12 of this Annual Report on Form 10-K.
Unregistered Sales of Equity Securities
None.
Purchases of Equity Securities by Issuers and Affiliated Purchasers
None.
Item 6. [Reserved]
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Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations
The following discussion and analysis of our financial condition and results of operations should be read in conjunction with our financial statements and related notes appearing elsewhere in this Annual Report on Form 10‑K. As discussed in the section titled “Special Note Regarding Forward Looking Statements,” the following discussion and analysis contains forward looking statements that involve risks and uncertainties, as well as assumptions that, if they never materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward looking statements. Factors that could cause or contribute to these differences include, but are not limited to, those identified below and those discussed in the section titled “Risk Factors” in Part I, Item 1A of this Annual Report on Form 10-K.
Overview
We are a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of innovative small molecules and antibody therapies based on the modulation of cellular protein levels as a novel treatment approach for cancer, inflammatory conditions and other challenging diseases. Leveraging our extensive expertise in E3 ligases together with our proprietary DNA-encoded libraries, we have built DELigase, an integrated discovery platform to identify and advance novel drug candidates targeting E3 ligases, a broad class of enzymes that can modulate proteins within the cell. Our drug discovery approach is to either harness or inhibit the natural function of E3 ligases within the ubiquitin-proteasome system to selectively decrease or increase cellular protein levels. Our wholly owned, clinical stage pipeline includes targeted protein degraders of Bruton’s tyrosine kinase (BTK), a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene B (CBL-B), an E3 ligase that regulates activation of multiple immune cell types including T cells and NK cells. Our partnered drug discovery pipeline consists of multiple programs under collaboration agreements with Gilead Sciences, Inc. (Gilead), Sanofi S.A. (Sanofi) and Seagen Inc. (now a part of Pfizer Inc. (Pfizer)), within which we retain certain options for co-development, co-commercialization and profit sharing in the United States for multiple drug candidates.
Targeted Protein Degradation
Our portfolio of targeted protein degraders of BTK, a B‑cell signaling protein, comprises NX‑5948, an orally bioavailable BTK degrader for the treatment of relapsed or refractory B-cell malignancies and potentially autoimmune diseases, and NX‑2127, an orally bioavailable BTK degrader that also degrades cereblon neosubstrates IKZF1 (Ikaros) and IKZF3 (Aiolos) for the treatment of relapsed or refractory B‑cell malignancies.
NX-5948: We are currently treating patients in a Phase 1a/1b dose-escalation and cohort expansion study in patients with relapsed or refractory B-cell malignancies. In January 2024, the U.S. Food and Drug Administration (FDA) granted Fast Track designation for NX-5948 for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two lines of therapy, including a BTK inhibitor (BTKi) and a B-cell lymphoma 2 (BCL2) inhibitor.
NX‑2127: We are currently treating patients in a Phase 1a/1b dose-escalation and cohort expansion study of NX-2127 in patients with relapsed or refractory B-cell malignancies. We have initiated Phase 1b expansion cohorts for patients with relapsed CLL, diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). Enrollment of new patients in this clinical trial is paused pending resolution of a partial clinical hold, which followed our communication to the FDA of our intention to transition to an improved manufacturing process. Patients already enrolled who are receiving clinical benefit may continue treatment.
Targeted Protein Elevation
Our targeted protein elevation program includes NX-1607, an orally bioavailable inhibitor of CBL-B, an E3 ligase that regulates the activation of multiple immune cell types including T cells and NK cells. NX-1607 is targeted for immuno-oncology indications.
We are currently treating patients in a Phase 1a/1b dose-escalation and cohort expansion study of NX-1607 in patients with a range of oncology indications. This study also includes a cohort within the Phase 1a dose escalation study testing NX-1607 in combination with paclitaxel, a taxane chemotherapy commonly used across a range of relapsed and refractory solid tumor indications. NX-1607 was awarded an Innovative Passport from the UK Medicines and Healthcare products Regulatory Agency to accelerate time to market and facilitate patient access to novel drugs to treat serious and life-threatening diseases.
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Drug Discovery Pipeline
In addition to our clinical stage drug candidates, we are extending our protein modulation portfolio, both on our own and with partners by developing new targeted protein degraders and ligase inhibitors for a number of targets for which we believe the protein modulation modality can be clinically advantageous over existing therapies. These existing and future programs may have the potential to address diseases with significant unmet need, including cancer, autoimmunity, inflammation, and other challenging diseases.
We have entered into several revenue generating collaborations with large biopharmaceutical companies, including with Gilead, Sanofi and Seagen (now a part of Pfizer), to leverage our DELigase platform for drug discovery. These collaborations allow us to further advance our future pipeline with multiple currently identified targets included in these collaborations. In aggregate, we have received $413.0 million in non-dilutive financing from our collaborators to date, and as of November 30, 2023, we are eligible to receive up to $8.1 billion in potential future fees and milestone payments, as well as royalties on future product sales. We retain certain options for co-development, co-commercialization and profit sharing in the United States for multiple drug candidates, pursuant to these collaborations.
Collaborations and License Agreements
Gilead
In June 2019, we entered into a global strategic collaboration agreement with Gilead (as subsequently amended, the Gilead Agreement) to discover, develop and commercialize a pipeline of targeted protein degradation drugs for patients with cancer and other challenging diseases using our DELigase platform to identify novel agents that utilize E3 ligases to induce degradation of five specified drug targets. In August 2019 and September 2022, we entered into the First Amendment and the Second Amendment, respectively, to the Gilead Agreement to clarify certain language of the Gilead Agreement. These amendments had no impact on revenue recognition.
Under the Gilead Agreement, Gilead has the option to license drug candidates directed to up to five targets resulting from the collaboration and is responsible for the clinical development and commercialization of drug candidates resulting from the collaboration. We retain the option to co-develop and co-promote, under a profit share structure, up to two drug candidates in the United States, provided that we may only exercise such option once per licensed product and Gilead retains the right to veto our option selection for any one drug candidate of its choice. The collaboration excludes our current internal protein degradation programs for which we retain all rights, and also excludes our future internal programs, provided that we have distinguished future programs as excluded from the scope of the collaboration. In March 2023, Gilead exercised the option, which did not represent a material right at contract inception, since it was not offered for free or at a discount, to exclusively license one target (Gilead License Option Exercise), the first development candidate resulting from the Gilead Agreement. Pursuant to the Gilead Agreement, we received a license option exercise payment of $20.0 million in April 2023 for the Gilead License Option Exercise. The license to the functional intellectual property and all goods and services related to the Gilead License Option Exercise were transferred during the second quarter of fiscal year 2023.
Over time, Gilead may elect to replace the initial drug targets with other drug targets. For drug targets that are subject to the collaboration, we are obligated to use commercially reasonable efforts to undertake a research program in accordance with a research plan agreed to by the parties and established on a target-by-target basis. We have primary responsibility under the Gilead Agreement for performing preclinical research activities (including target validation, drug discovery, identification or synthesis) pursuant to a research plan. Each party will bear its own costs in the conduct of research activities. Gilead will be responsible for any development, commercialization and manufacturing activities, unless we exercise our co-development and co-promotion option. For those programs that we exercise our option to co-develop and co-promote, we and Gilead will split U.S. development costs as well as U.S. profits and losses evenly, and we will be eligible to receive royalties on net ex-U.S. sales and reduced milestone payments.
Upon signing the Gilead Agreement, Gilead paid us an upfront payment of $45.0 million, plus $3.0 million in additional fees. In addition, from the signing of the Gilead Agreement to November 30, 2023, we received payments of $47.0 million for research milestones and additional payments and $20.0 million for a license option exercise payment. As of November 30, 2023, we are eligible to receive up to approximately $2.3 billion in total additional payments based on certain additional fees, payments and the successful completion of certain preclinical, clinical, development and sales milestones. We also are eligible to receive mid-single digit to low tens percentage tiered royalties on annual net sales from any commercial products directed to the optioned collaboration targets, subject to certain reductions and excluding sales in the United States of any products for which we exercise our option to co-develop and co-promote, for which the parties share profits and losses evenly.
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Subject to earlier expiration in certain circumstances, the Gilead Agreement expires on a licensed product-by-licensed product and country-by-country basis upon the later of (1) the expiration of the last to expire patent with a valid claim covering the applicable licensed product in the applicable country, (2) the expiration of any regulatory exclusivity for the applicable licensed product in the applicable country or (3) ten years after the first commercial sale of the applicable licensed product in the applicable country covered by the Gilead Agreement, provided that the term for any profit-shared licensed product in the United States will expire upon the expiration or termination of the applicable profit-share term as set forth in an applicable profit-share agreement to be negotiated upon our exercise of our option to co-develop and co-promote such licensed product. If Gilead does not exercise an option to license a drug candidate, then the Gilead Agreement will terminate at the end of the last to expire option period.
We recognized collaboration revenue from the Gilead Agreement of $29.9 million and $23.7 million during the years ended November 30, 2023 and 2022, respectively. As of November 30, 2023 and 2022, there was $10.0 million and $27.4 million, respectively, of deferred revenue related to payments received by us under the Gilead Agreement.
Sanofi
In December 2019, we entered into a strategic collaboration with Genzyme Corporation, a subsidiary of Sanofi, which became effective in January 2020 (as subsequently expanded and amended, the Sanofi Agreement), to discover, develop and commercialize a pipeline of targeted protein degradation drugs for patients with challenging diseases in multiple therapeutic areas using our DELigase platform to identify small molecules designed to induce degradation of three specified initial drug targets. In January 2021, as part of the existing Sanofi Agreement, Sanofi paid us $22.0 million to exercise its option to expand the number of targets in the Sanofi Agreement from three to a total of five targets.
In January 2021, we entered into the First Amendment to the Sanofi Agreement to modify the research term on all targets. In December 2021, we entered into the Second Amendment to the Sanofi Agreement to extend the substitution deadline on certain targets. In July 2022, we entered into the Third Amendment to the Sanofi Agreement to further extend the substitution deadline on certain targets. The extensions of the substitution deadline had no impact on revenue recognition. Also in July 2022, Sanofi elected to replace certain drug targets, and the substitution extended the research term of those targets by one year to 5.25 years and increased overall forecasted costs, which had an immaterial impact on revenue recognition. In August 2022 and November 2023, we entered into the Fourth Amendment and Fifth Amendment, respectively, to the Sanofi Agreement to modify the research plan for certain targets, which had no impact on revenue recognition.
Under the Sanofi Agreement, Sanofi has exclusive rights and is responsible for the clinical development, commercialization and manufacture of drug candidates resulting from the collaboration while we retain the option to co-develop, co-promote and co-commercialize all drug candidates in the United States directed to up to two targets, one of which must be selected from a list of targets designated at the execution of the Sanofi Agreement or any replacement of such targets, and one of which must be selected from targets identified by Sanofi as part of their January 2021 expansion. Our right to exercise our option to co-develop, co-promote and co-commercialize a given target is dependent on our ability to demonstrate, within a given timeframe, that we have sufficient cash resources and personnel to commercialize the product. The collaboration excludes our current internal protein degradation programs for which we retain all rights, and also excludes our future internal programs, provided that we distinguished future programs as excluded from the scope of the collaboration.
For drug targets that are subject to the collaboration, we have primary responsibility for conducting preclinical research activities (including target validation, drug discovery, identification or synthesis) in accordance with the applicable research plan agreed to by the parties and established on a target-by-target basis. We are obligated to use commercially reasonable efforts to identify relevant target binders and targeted protein degraders in order to identify development candidates. Subject to certain exceptions, each party will bear its own costs in the conduct of such research. Sanofi will be responsible for any development and commercialization activities unless we exercise our co-development and co-promotion option. For those programs that we exercise our option to co-develop, co-promote and co-commercialize, we will be responsible for a portion of the U.S. development costs, and the parties will split U.S. profits and losses evenly, and we will be eligible to receive royalties on ex-U.S. net sales and reduced milestone payments on such optioned products.
Upon signing the Sanofi Agreement, Sanofi paid us an upfront payment of $55.0 million. Subsequently, in January 2021, Sanofi paid us an additional $22.0 million to exercise its option to expand the number of targets beyond the initial targets included in the collaboration. In addition, from the signing of the Sanofi Agreement to November 30, 2023, we received payments of $7.0 million for research milestones. Additionally, we achieved two research milestones in November 2023 and received payments totaling $4.0 million in January 2024 as a result. As of November 30, 2023, we are eligible to receive up to approximately $2.5 billion in total additional payments based on certain additional fees, payments and the successful completion of certain research development, regulatory and sales milestones, as well as mid-single digit to low teen percentage tiered royalties on annual net sales of any commercial products that may result from the collaboration, subject to certain reductions and excluding sales in the United States of any products for which we exercise our option to co-develop and co-promote, for which the parties share profits and losses evenly.
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Subject to earlier expiration in certain circumstances, the Sanofi Agreement expires on a licensed product-by-licensed product or profit-shared licensed product-by-profit-shared licensed product basis and country-by-country basis upon on the later of (1) the expiration of the last-to-expire patent with a valid claim covering the applicable licensed product in the applicable country, (2) the expiration of any regulatory exclusivity for the applicable licensed product in the applicable country or (3) ten years after the first commercial sale of the applicable licensed product in the applicable country covered by the Sanofi Agreement.
We recognized collaboration revenue from the Sanofi Agreement of $25.4 million and $15.0 million during the years ended November 30, 2023 and 2022, respectively. As of November 30, 2023 and 2022, there was $24.9 million and $46.2 million, respectively, of deferred revenue related to payments received by us under the Sanofi Agreement.
Pfizer
In September 2023, we entered into a strategic collaboration with Seagen Inc. (now a part of Pfizer Inc.) (the Pfizer Agreement) to develop a suite of targeted protein degraders against multiple targets nominated by Pfizer that are suitable for antibody conjugation. Pfizer will be responsible for conjugating these degraders to antibodies to make Degrader-Antibody Conjugates (DACs), a new class of medicines for use in cancer treatment, and advancing these DAC drug candidates through preclinical and clinical development and commercialization.
Under the Pfizer Agreement, Pfizer has the option to obtain exclusive licenses to develop and commercialize certain degraders, while we retain an option for U.S. profit sharing and co-promotion on two products arising from the collaboration. The collaboration excludes our current internal protein degradation programs for which we retain all rights, and also excludes our future internal programs, provided that we have distinguished future programs as excluded from the scope of the collaboration.
For the targets nominated by Pfizer under the collaboration, we shall use commercially reasonable efforts to identify, synthesize, characterize and deliver targeted protein degraders that selectively bind to and degrade such targets. Development of licensed degraders, with the exception of licensed products for which we exercised our profit-share options, will be at Pfizer’s sole cost and expense. For the profit-share products, the parties will share net profits and net losses and global development costs, and we will be eligible to receive royalty and milestone payments on such optioned products.
Under the terms of the Pfizer Agreement, we received an upfront payment of $60.0 million. We are eligible to receive up to approximately $3.4 billion in contingent payments based on specified research, development, regulatory and commercial milestones across multiple programs, and are eligible for mid-single to low double digit percentage tiered royalties on future sales.
Subject to the exceptions described in the Pfizer Agreement, the Pfizer Agreement expires upon the first to occur of (1) the expiration of the last-to-expire option exercise period under the Pfizer Agreement if no such option has been exercised prior to such expiration and (2) the expiration of the last-to-expire royalty term under the Pfizer Agreement.
We recognized collaboration revenue from the Pfizer Agreement of $1.7 million during the year ended November 30, 2023. As of November 30, 2023, there was $58.3 million of deferred revenue related to payments received by us under the Pfizer Agreement.
Financial Overview
Since the commencement of our operations, we have devoted substantially all of our resources to conducting research and development activities, establishing and maintaining our intellectual property portfolio, establishing our corporate infrastructure, raising capital and providing general and administrative support for these operations. We have funded our operations to date primarily from proceeds received under collaboration and license agreements with Celgene Corporation, Gilead, Sanofi and Pfizer and the issuance and sale of common stock, redeemable convertible preferred stock and pre-funded warrants. We do not expect to generate product revenue unless and until we successfully develop and obtain approval for the commercialization of a drug candidate, and we cannot assure you that we will ever generate significant revenue or profits.
Since inception, we have generally incurred significant losses and negative cash flows from operations. During the years ended November 30, 2023 and 2022, we incurred net losses of $143.9 million and $180.4 million, respectively. As of November 30, 2023, we had an accumulated deficit of $545.2 million. These losses have resulted primarily from costs incurred in connection with research and development activities and general and administrative costs associated with our operations.
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We do not expect to generate any revenue from commercial product sales unless and until we successfully complete development and obtain regulatory approval for one or more of our drug candidates, which we expect will take a number of years, if ever. We expect our expenses will increase substantially as we advance our drug candidates through preclinical and clinical development; enter advanced clinical development and scale up external manufacturing capabilities to supply clinical trials; apply our DELigase platform to advance additional drug candidates and expand the capabilities of our platform; seek marketing approvals for any drug candidates that successfully complete clinical trials; ultimately establish a sales, marketing and distribution infrastructure and scale up external manufacturing capabilities to commercialize any products for which we may obtain marketing approval; expand, maintain and protect our intellectual property portfolio; and hire additional clinical, regulatory, manufacturing, quality assurance and scientific personnel. Furthermore, we expect to continue incurring costs associated with operating as a public company, including significant legal, accounting, insurance, investor relations and other administrative and professional services expenses.
Our net losses and cash flows may fluctuate significantly from period to period, depending on, among other things, variations in the level of expense related to the ongoing development of our drug candidates, our DELigase platform or future development programs; the delay, addition or termination of clinical trials; and the execution of any additional collaboration, licensing or similar arrangements, and the timing of payments we may make or receive under such arrangements.
As of November 30, 2023, we had $295.3 million in cash, cash equivalents and marketable securities. We expect that our existing cash, cash equivalents and marketable securities are sufficient to fund our operations for at least the next 12 months. See the section titled “—Liquidity and Capital Resources” for more information. To finance our operations beyond that point, we will need to raise substantial additional capital to complete the development and commercialization of our drug candidates. Until such time as we can generate significant revenue from product sales, if ever, we expect to finance our operations through a combination of public or private equity offerings, debt financings, collaborations, strategic alliances, licensing arrangements and other marketing and distribution arrangements. In addition, we may seek additional capital due to favorable market conditions or strategic considerations, even if we believe we have sufficient funds for our current or future operating plans.
Impact of Current Global Business, Political and Macroeconomic Conditions
Uncertainty in the global business, political and macroeconomic environments present significant risks to our business. We are subject to continuing risks and uncertainties, including increasing financial market volatility and uncertainty, inflation, increasing interest rates, uncertainty with respect to the federal budget and debt ceiling and potential government shutdowns related thereto, instability in the global banking system, cybersecurity events, the impact of war or military conflict, including regional conflicts around the world, and public health pandemics. We are closely monitoring the impact of these factors on all aspects of our business, including the impacts on our clinical trial patients, employees, partner, suppliers, and vendors.
The ultimate extent of the impact of global economic conditions on our business remains highly uncertain and will depend on future developments and factors that continue to evolve. Most of these developments and factors are outside of our control and could exist for an extended period of time. As a result, we are subject to continuing risks and uncertainties and continue to closely monitor the impact of the current conditions on our business. For more information regarding these risks and uncertainties, see the section titled “Risk Factors” in this Annual Report on Form 10-K.
Components of Results of Operations
Collaboration Revenue
We have no products approved for commercial sale and to date have not generated any revenue from the sale of products and do not expect to generate any revenue from the sale of products in the near future.
Our revenue to date has been generated from payments received pursuant to collaboration and license arrangements with strategic partners. Collaboration revenue consists of revenue received from upfront, milestone and contingent payments received from our collaborators. We recognize revenue from upfront payments over the contract term using the cost-based input method. The material right to the two additional targets under the Sanofi Agreement was accounted for using the practical alternative and the expected consideration to be received on the options was included for revenue allocation. We expect to continue recognizing revenue from upfront payments related to our collaboration agreements using the cost-based input method in the foreseeable future.
In addition to receiving upfront payments, we may also be entitled to milestones and other contingent payments upon achieving predefined objectives. If a milestone is considered probable of being reached, and if it is probable that a significant revenue reversal would not occur, the associated milestone amount would also be included in the transaction price.
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We expect that any collaboration revenue we generate from our current collaboration and license agreements, and from any future collaboration partners, will fluctuate in the future as a result of the timing and amount of upfront, milestones and other collaboration agreement payments and other factors.
License Revenue
Our license revenue consists of a payment received from the Gilead License Option Exercise that was fully recognized during the second quarter of fiscal year 2023.
Research and Development Expenses
Research and development expenses consist primarily of costs incurred for the discovery and development of our drug candidates. We expense both internal and external research and development expenses to operations in the periods in which they are incurred. Nonrefundable advance payments for goods or services to be received in future periods for use in research and development activities are deferred and capitalized. The capitalized amounts are then expensed as the related goods are delivered and as services are performed. We track the external research and development costs incurred for each of our drug candidates.
Internal research and development costs include:
•payroll and personnel expenses, including benefits, stock-based compensation and travel expenses, for our research and development functions; and
•depreciation of research and development equipment, allocated overhead and facilities-related expenses.
External research and development expenses consist primarily of costs incurred for the development of our drug candidates and may include:
•fees paid to third parties such as consultants, contractors and contract research organizations to conduct our clinical trials, discovery programs and preclinical studies;
•costs to acquire, develop and manufacture supplies for clinical trials and preclinical studies, including fees paid to third parties such as contract manufacturing organizations; and
•expenses related to laboratory supplies and services.
We expect our research and development expenses to increase substantially for the foreseeable future as we conduct clinical trials for our drug candidates, continue to invest in research and development activities for discovery programs and preclinical studies, pursue regulatory approval of our drug candidates and expand our drug candidate pipeline. The process of conducting the necessary preclinical and clinical research to obtain regulatory approval is costly and time-consuming. To the extent that our drug candidates advance to and continue to advance through clinical trials, our expenses will continue increasing substantially and may become more variable. The actual probability of success for our drug candidates may be affected by a variety of factors, including the safety and efficacy of our drug candidates, investment in our clinical programs, the ability of collaborators to successfully develop our licensed drug candidates, manufacturing capability, competition with other products and commercial viability. As a result of these variables, we are unable to determine when and to what extent we will generate revenue from the commercialization and sale of our drug candidates. We may never succeed in achieving regulatory approval for any of our drug candidates.
General and Administrative Expenses
General and administrative expenses consist primarily of payroll and personnel expenses, including benefits and stock-based compensation, facilities-related expenses and professional fees for legal, consulting and audit and tax services. We expect our general and administrative expenses to increase for the foreseeable future as we continue to improve our infrastructure and operate as a public company. This may include expenses related to compliance with the rules and regulations of the Securities and Exchange Commission and listing standards applicable to companies listed on a national securities exchange, additional insurance, investor relations activities and other administrative and professional services. We also expect our intellectual property expenses to increase as we expand our intellectual property portfolio.
Interest and Other Income, Net
Interest and other income, net primarily consists of interest earned on our cash, cash equivalents and marketable securities. We expect interest income to vary each reporting period depending on our average bank deposit, money market fund and marketable securities balances during the period and market interest rates.
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Critical Accounting Policies and Estimates
Our accounting policies are more fully described in Note 2 of the consolidated financial statements to this Annual Report on Form 10-K. As disclosed in Note 2, the preparation of financial statements in conformity with generally accepted accounting principles requires management to make estimates and assumptions about future events that affect the amounts reported in the financial statements and accompanying notes. We base our estimates on historical experience, known trends and events and various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. We evaluate our estimates and assumptions on an ongoing basis. Actual results could differ significantly from those estimates. We believe that the following discussion addresses our most critical accounting policies and estimates, which are those that are most important to the portrayal of our financial condition and results of operations and require management’s most difficult, subjective and complex judgments.
Leases
We determine if an arrangement contains a lease and the classification of the lease at inception. An arrangement contains a lease if there is an identified asset and if we control the use of the identified asset throughout the period of use. The evaluation of whether the lease is an operating or a finance lease requires judgments in determining the fair value of the leased asset. Lease right-of-use (ROU) assets and lease liabilities are recognized at the lease commencement date based on the present value of the future minimum lease payments over the lease term at the commencement date. We use our incremental borrowing rate, if an implicit rate is not readily available, and the information available at the date of lease commencement in determining our lease liabilities. Our incremental borrowing rate is based on the rate of interest that we would have to pay to borrow on a collateralized basis over a similar term for an amount equal to the lease payments in a similar economic environment, and the determination of the rate requires us to make certain assumptions and judgements, including on our synthetic credit rating. Leases may include options to extend or early terminate the lease term. If we, using judgement, are reasonably certain that an option will be exercised, then the option will be included in the calculation of the lease term. The determination of the lease liabilities is sensitive to the incremental borrowing rate and the expected lease term. Lease expense for operating leases is recognized on a straight-line basis over the lease term. We do not have any finance leases.
Revenue Recognition
We recognize revenue when our customer obtains control of promised goods or services, in an amount that reflects the consideration which we expect to receive in exchange for those goods or services. At contract inception, we assess the goods or services promised within each contract, whether each promised good or service is distinct, and determine those that are performance obligations. We then recognize as revenue the amount of the transaction price that is allocated to the respective performance obligation when or as the performance obligation is satisfied.
We enter into collaboration agreements under which we may obtain upfront payments, milestone payments, royalty payments and other fees. Promises under these arrangements may include research licenses, research services, including selection campaign research services for certain replacement targets, the obligation to share information during the research term and the participation of alliance managers and in joint research committees, joint patent committees and joint steering committees. We assess these promises within the context of the agreements to determine the performance obligations.
Exclusive license rights: If a license to our intellectual property is determined to be distinct from the other promises identified in the arrangement, we recognize revenue from nonrefundable, upfront payments allocated to the license when the license is transferred to the customer and the customer is able to use and benefit from the license and the underlying intellectual property. If the license is the predominant promise, and it is determined that the license represents functional intellectual property, revenue is recognized at the point in time when control of the license is transferred. If it is determined that the license does not represent functional intellectual property, revenue is recognized over time using an appropriate method of measuring progress.
Research and collaboration licenses: Collaboration agreements may include research licenses and research and development services to be performed by us. For research licenses that are bundled with other promises, we utilize judgment to assess the nature of the combined performance obligation to determine whether the combined performance obligation is satisfied over time or at a point in time and, if over time, the appropriate method of measuring proportional performance for purposes of recognizing revenue from non-refundable, upfront payments. We evaluate the measure of proportional performance each reporting period and, if necessary, adjust the measure of performance and related revenue recognition.
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Milestone payments: At the inception of each arrangement that includes research, development or regulatory milestone payments, we evaluate whether the milestones are considered probable of being reached and estimate the amount to be included in the transaction price. We use the most likely amount method for research, development and regulatory milestone payments. Under the most likely amount method, an entity considers the single most likely amount in a range of possible consideration amounts. If it is probable that a significant revenue reversal would not occur, the associated milestone amount is included in the transaction price.
Customer options: Customer options, such as options granted to allow a licensee to extend a license or research term, to select additional research targets or to choose to research, develop and commercialize licensed compounds, are evaluated at contract inception to determine whether those options provide a material right (i.e., an optional good or service offered for free or at a discount) to the customer. If the customer options represent a material right, the material right is treated as a separate performance obligation at the outset of the arrangement. We allocate the transaction price to material rights based on the standalone selling price. As a practical alternative to estimating the standalone selling price of a material right when the underlying goods or services are both (i) similar to the original goods or services in the contract and (ii) provided in accordance with the terms of the original contract, we allocate the total amount of consideration expected to be received from the customer to the total goods or services expected to be provided to the customer. Amounts allocated to any material right are recognized as revenue when or as the related future goods or services are transferred or when the option expires.
For performance obligations satisfied over time, we recognize revenue using the cost-based input method and evaluate the measure of proportional performance each reporting period and, if necessary, adjust the measure of performance and related revenue recognition. To measure the proportional performance, we are required to make our best estimates of forecasted expenditures and development timelines, which are subject to uncertainties, including the timing of replacement targets, if any, associated with pharmaceutical product development. Forecasted total expenditures are driven primarily by the number of full-time employees, and the assumptions over the number of full-time employees require significant management judgement. The number of full-time employees may change based on the progress and timing of our product development, and may be influenced by resource allocation decisions on internal programs and overall constraint on resources. The model is highly sensitive to changes in resources assigned over the research term. Forecasted total expenditures also include other direct costs related to product development, including third-party contract costs, and may also require management’s estimate of costs and market conditions that may impact costs.
Results of Operations
Comparison of the years ended November 30, 2023 and 2022
Our results of operations for the years ended November 30, 2023 and 2022 are summarized as follows (in thousands):
| Year ended November 30, | |||||||||||||||||
| 2023 | 2022 | Change | |||||||||||||||
| Revenue: | |||||||||||||||||
| Collaboration revenue | $ | 56,987 | $ | 38,627 | $ | 18,360 | |||||||||||
| License revenue | 20,000 | — | 20,000 | ||||||||||||||
| Total revenue | 76,987 | 38,627 | 38,360 | ||||||||||||||
| Operating expenses: | |||||||||||||||||
| Research and development | 189,148 | 184,497 | 4,651 | ||||||||||||||
| General and administrative | 42,902 | 37,997 | 4,905 | ||||||||||||||
| Total operating expenses | 232,050 | 222,494 | 9,556 | ||||||||||||||
| Loss from operations | (155,063) | (183,867) | 28,804 | ||||||||||||||
| Interest and other income, net | 11,115 | 3,507 | 7,608 | ||||||||||||||
| Net loss | $ | (143,948) | $ | (180,360) | $ | 36,412 | |||||||||||
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Collaboration Revenue
Our collaboration revenue for the years ended November 30, 2023 and 2022 is summarized as follows (in thousands):
| Year ended November 30, | |||||||||||||||||
| 2023 | 2022 | Change | |||||||||||||||
| Gilead | $ | 29,947 | $ | 23,674 | $ | 6,273 | |||||||||||
| Sanofi | 25,350 | 14,953 | 10,397 | ||||||||||||||
| Pfizer | 1,690 | — | 1,690 | ||||||||||||||
| Total collaboration revenue | $ | 56,987 | $ | 38,627 | $ | 18,360 | |||||||||||
Our collaboration revenue increased by $18.4 million during the year ended November 30, 2023, compared to the year ended November 30, 2022, primarily due to increased effort resulting in a higher percentage of completion of performance obligations under our collaborations with Gilead and Sanofi in the current period. The increase was also due to higher achievement of research milestones that resulted in higher revenue recognized in each period and impacted the cumulative catch up in revenue for activities satisfied in previous periods. In addition, we recognized revenue of $1.7 million related to activities performed during the fourth fiscal quarter ended November 30, 2023 pursuant to the Pfizer Agreement.
License Revenue
Our license revenue was $20.0 million for the year ended November 30, 2023, and is related to the Gilead License Option Exercise. There was no license revenue for the year ended November 30, 2022.
Research and Development Expenses
Our research and development expenses for the years ended November 30, 2023 and 2022 are summarized as follows (in thousands):
| Year ended November 30, | |||||||||||||||||
| 2023 | 2022 | Change | |||||||||||||||
| Compensation and related personnel costs | $ | 72,876 | $ | 65,336 | $ | 7,540 | |||||||||||
| Stock-based compensation | 18,709 | 16,878 | 1,831 | ||||||||||||||
| Supplies and contract research | 43,943 | 47,814 | (3,871) | ||||||||||||||
| Preclinical activities | 1,652 | 5,912 | (4,260) | ||||||||||||||
| Contract manufacturing | 7,770 | 13,562 | (5,792) | ||||||||||||||
| Clinical costs | 17,500 | 13,887 | 3,613 | ||||||||||||||
| Facility and other costs | 26,698 | 21,108 | 5,590 | ||||||||||||||
| Total research and development expenses | $ | 189,148 | $ | 184,497 | $ | 4,651 | |||||||||||
Our research and development expense increased by $4.7 million during the year ended November 30, 2023, compared to the year ended November 30, 2022. There was an increase in compensation and related personnel costs and in non-cash stock-based compensation expense that were primarily attributable to higher headcount and the issuance of restricted stock units (RSUs) and incentive stock options. There was also an increase in clinical costs as we continued our clinical trial programs and ongoing patient enrollment and an increase in facility and other costs primarily driven by investments in equipment and expenses related to our leases of office and laboratory space, including the lease in The Woodlands, Texas. There was a decrease in research related costs as we concluded certain studies and sponsored research agreements and a decrease in contract manufacturing as we stabilized the supply needed for our clinical trials.
General and Administrative Expenses
Our general and administrative expenses increased by $4.9 million during the year ended November 30, 2023, compared to the year ended November 30, 2022. There was an increase in non-cash stock-based compensation expense primarily driven by the increased issuance of RSUs and incentive stock options and an increase in professional service costs related to the Pfizer Agreement, offset by a decrease in outside consulting costs.
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Interest and Other Income, Net
Our interest and other income, net increased by $7.6 million during the year ended November 30, 2023, compared to the year ended November 30, 2022, primarily attributable to higher interest rates earning higher interest income on our deposits, money market funds and marketable securities.
Liquidity and Capital Resources
Sources of Liquidity
In July 2020, we closed our initial public offering (IPO) and issued 12,550,000 shares of our common stock (including the exercise by the underwriters of their option to purchase an additional 1,550,000 shares of common stock in August 2020) at a price to the public of $19.00 per share for net proceeds of $218.1 million, after deducting underwriting discounts and commissions of $16.7 million and expenses of $3.6 million.
In March 2021, we completed a follow-on offering and issued 5,175,000 shares of our common stock (including the exercise by the underwriters of their option to purchase an additional 675,000 shares of common stock) at a price to the public of $31.00 per share for net proceeds of $150.2 million, after deducting underwriting discounts and commissions of $9.6 million and expenses of $0.6 million.
In August 2021, we entered into an Equity Distribution Agreement with Piper Sandler & Co. (Piper Sandler) pursuant to which, from time to time, we may offer and sell through Piper Sandler up to $150.0 million of the common stock registered under our shelf registration statement on Form S-3 pursuant to one or more “at the market” offerings. We are not required to sell any shares at any time during the term of the Equity Distribution Agreement. We agreed to pay Piper Sandler a commission of 3% of the gross sales price of any shares sold pursuant to the Equity Distribution Agreement. In June 2022, we issued and sold 2,000,000 shares of common stock under the Equity Distribution Agreement at a price of $10.0001 per share of common stock for net proceeds of approximately $19.3 million after deducting offering commissions and expenses paid by us (the June 2022 ATM Offering). As of November 30, 2023, we had $130.0 million of common stock remaining available for sale under the Equity Distribution Agreement.
In July 2022, we entered into separate securities purchase agreements with certain purchasers to issue and sell pre‑funded warrants to purchase an aggregate of 6,814,920 shares of our common stock in registered direct offerings (RDOs) at a price of $13.939 per pre-funded warrant. Net proceeds from the RDOs were approximately $94.8 million, after deducting offering expenses of $0.2 million. The pre-funded warrants were immediately exercisable, have an exercise price of $0.001 and may be exercised at any time after the date of issuance. A holder of the pre-funded warrants may not exercise the warrant if the holder, together with its affiliates, would beneficially own more than 9.99% of the number of shares of our common stock outstanding immediately after giving effect to such exercise. A holder of the pre-funded warrants may increase or decrease this percentage not in excess of 19.99% by providing us at least 61 days’ prior notice. As of November 30, 2023, a total of 6,097,560 pre-funded warrants remained available for exercise.
Funding Requirements
As of November 30, 2023, our operations have primarily been funded through the net proceeds from equity offerings of $650.5 million and proceeds from collaborations of $409.0 million. We do not have any products approved for sale, and we have not generated any revenue from product sales. As of November 30, 2023, we had $295.3 million in cash, cash equivalents and marketable securities.
We expect that our existing cash, cash equivalents and marketable securities are sufficient to meet our cash requirements and continue operating activities, including the clinical trials of our drug candidates NX-5948, NX-2127 and NX-1607 and the expansion of our intellectual property portfolio and infrastructure, for at least the next 12 months. We will need substantial additional funding to support our continuing operations and pursue our long-term business plan. We may seek to raise any necessary additional capital through a combination of public or private equity offerings, debt financings, collaborations, strategic alliances, licensing arrangements and other marketing and distribution arrangements. Because of the numerous risks and uncertainties associated with the development and commercialization of our drug candidates and the extent to which we may enter into additional collaborations with third parties to participate in their development and commercialization, we are unable to estimate the amounts of increased capital outlays and operating expenditures associated with our current and anticipated preclinical studies and clinical trials.
In the long term, our ability to support our working capital and capital expenditure requirements will depend on many factors, including the following:
•the progress, costs and results of our ongoing Phase 1 clinical trials for our lead drug candidates NX-5948, NX-2127 and NX-1607, and any future clinical development of such drug candidates;
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•the scope, progress, costs and results of preclinical and clinical development for our other drug candidates and development programs;
•the number and development requirements of other drug candidates that we pursue;
•the scope of, and costs associated with, future advancements to our DELigase platform;
•the success of our collaborations with Gilead, Sanofi, Pfizer and any other collaborations we may establish;
•the costs, timing and outcome of regulatory review of our drug candidates;
•the costs and timing of future commercialization activities, including product manufacturing, marketing, sales and distribution, for any of our drug candidates for which we receive marketing approval;
•the revenue, if any, received from commercial sales of our drug candidates for which we receive marketing approval;
•the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims; and
•our ability to establish additional collaboration arrangements with other biotechnology or pharmaceutical companies on favorable terms, if at all, for the development or commercialization of our drug candidates.
We considered whether there are conditions or events that raise substantial doubt about our ability to continue as a going concern and evaluated the funds necessary to maintain operations. If we are unable to obtain additional funding, we will be required to implement plans that are within our control, which may include the delay or scaling back of certain research and development programs, to maintain liquidity and operations. Additionally, we may be required to obtain funds through arrangements with others that may require us to relinquish rights to certain of our technologies or products that we would otherwise seek to develop or commercialize ourselves, or cease operations. If we do raise additional capital through public or private equity or convertible debt offerings, the ownership interest of our existing stockholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect our stockholders’ rights. If we raise additional capital through debt financing, we may be subject to covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends.
Our contractual obligations mostly consist of our operating lease obligations for our facilities in San Francisco, California and The Woodlands, Texas. Our total operating lease commitments as of November 30, 2023, were approximately $42.4 million, of which $7.6 million is expected to be paid within the next 12 months. In addition, we enter into agreements in the normal course of business with contract research organizations for clinical trials and with vendors for preclinical studies and other services and products for operating purposes, which are generally cancelable upon written notice.
We did not have during the periods presented, and we do not currently have, any commitments or obligations, including contingent obligations, arising from arrangements with unconsolidated entities or persons that have or are reasonably likely to have a material current or future effect on our financial condition, changes in financial condition, revenues or expenses, results of operations, liquidity, cash requirements or capital resources.
Cash flows
Our cash flows for the years ended November 30, 2023 and 2022 are summarized as follows (in thousands):
| Year ended November 30, | ||||||||||||||
| 2023 | 2022 | |||||||||||||
| Cash used in operating activities | $ | (81,365) | $ | (159,807) | ||||||||||
| Cash provided by investing activities | 68,301 | 27,198 | ||||||||||||
| Cash provided by financing activities | 3,217 | 117,192 | ||||||||||||
| Net decrease in cash, cash equivalents and restricted cash | $ | (9,847) | $ | (15,417) | ||||||||||
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Operating activities
Net cash used in operating activities was $81.4 million for the year ended November 30, 2023, and consisted of our net loss of $143.9 million, offset by non-cash adjustments of $42.5 million and a decrease in net assets of $20.1 million. Non-cash adjustments primarily consisted of stock-based compensation expenses of $33.7 million, depreciation and amortization expenses of $7.5 million and amortization of operating lease ROU assets of $6.1 million, offset by net accretion of discount on marketable securities of $5.4 million. The decrease in net assets consisted of an increase in deferred revenue of $19.5 million mainly from the upfront payment received pursuant to the Pfizer Agreement, an increase in accrued expenses and other liabilities of $3.1 million primarily related to the accrual of annual incentive compensation, a decrease in prepaid expenses and other assets of $2.1 million primarily due to the recognition of expenses for prepaid services and an increase in accounts payable of $1.6 million from outstanding payments to vendors, offset by a decrease in operating lease liabilities of $6.3 million due to payments made on operating leases.
Net cash used in operating activities was $159.8 million for the year ended November 30, 2022, and consisted of our net loss of $180.4 million and an increase in net assets of $19.0 million, offset by non-cash adjustments of $39.6 million. The increase in net assets consisted primarily of a decrease in deferred revenue of $26.6 million as we increased effort in our programs and recognized revenue, a decrease in operating lease liabilities of $4.9 million due to payments made on operating leases and an increase in prepaid expenses and other assets of $1.1 million primarily related to increased prepaid clinical and contract manufacturing costs and software license costs, offset by an increase in accrued expenses and other liabilities of $7.5 million primarily related to the accrual of contract research, laboratory supplies and annual incentive compensation and a decrease in accounts receivable of $6.0 million related to payments received under the Gilead Agreement. Non-cash adjustments primarily consisted of stock-based compensation expenses of $28.1 million, amortization of operating lease ROU assets of $5.5 million and depreciation and amortization expenses of $5.3 million.
Investing activities
Net cash provided by investing activities was $68.3 million for the year ended November 30, 2023, and consisted of the maturity of marketable securities of $323.0 million, offset by the purchase of marketable securities of $246.3 million and purchases of property and equipment of $8.4 million.
Net cash provided by investing activities was $27.2 million for the year ended November 30, 2022, and consisted of the maturity of marketable securities of $278.8 million, offset by the purchase of marketable securities of $239.4 million and purchases of property and equipment of $12.2 million.
Financing activities
Net cash provided by financing activities was $3.2 million for the year ended November 30, 2023, and consisted primarily of proceeds from the issuance of common stock under our Employee Stock Purchase Plan.
Net cash provided by financing activities was $117.2 million for the year ended November 30, 2022, and consisted primarily of net proceeds from the issuance of pre-funded warrants in the RDOs of $94.8 million and from the issuance of common stock in the June 2022 ATM Offering of $19.4 million.
Information About Segments
We currently operate in a single business segment. See additional information in our financial statements contained in Part II, Item 8 of this Annual Report on Form 10-K.
Item 7A. Quantitative and Qualitative Disclosures About Market Risk
As a “smaller reporting company” as defined by Item 10 of Regulation S-K, we are not required to provide this information.
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Item 8. Financial Statements and Supplementary Data
INDEX TO FINANCIAL STATEMENTS
Report of Independent Registered Public Accounting Firm (PCAOB ID | |||||
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REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM
To the Board of Directors and Stockholders of Nurix Therapeutics, Inc.
Opinion on the Financial Statements
We have audited the accompanying consolidated balance sheets of Nurix Therapeutics, Inc. and its subsidiaries (the “Company”) as of November 30, 2023 and 2022, and the related consolidated statements of operations, of comprehensive loss, of stockholders’ equity and of cash flows for the years then ended, including the related notes (collectively referred to as the “consolidated financial statements”). In our opinion, the consolidated financial statements present fairly, in all material respects, the financial position of the Company as of November 30, 2023 and 2022, and the results of its operations and its cash flows for the years then ended in conformity with accounting principles generally accepted in the United States of America.
Basis for Opinion
These consolidated financial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion on the Company’s consolidated financial statements based on our audits. We are a public accounting firm registered with the Public Company Accounting Oversight Board (United States) (PCAOB) and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.
We conducted our audits of these consolidated financial statements in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audits to obtain reasonable assurance about whether the consolidated financial statements are free of material misstatement, whether due to error or fraud. The Company is not required to have, nor were we engaged to perform, an audit of its internal control over financial reporting. As part of our audits we are required to obtain an understanding of internal control over financial reporting but not for the purpose of expressing an opinion on the effectiveness of the Company's internal control over financial reporting. Accordingly, we express no such opinion.
Our audits included performing procedures to assess the risks of material misstatement of the consolidated financial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the consolidated financial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the consolidated financial statements. We believe that our audits provide a reasonable basis for our opinion.
Emphasis of Matter
As discussed in Note 1 to the consolidated financial statements, the Company will need substantial additional funding to support its continuing operations and pursue its long-term business plan. Management’s plans in regard to this matter are described in Note 1.
Critical Audit Matters
The critical audit matter communicated below is a matter arising from the current period audit of the consolidated financial statements that was communicated or required to be communicated to the audit committee and that (i) relates to accounts or disclosures that are material to the consolidated financial statements and (ii) involved our especially challenging, subjective, or complex judgments. The communication of critical audit matters does not alter in any way our opinion on the consolidated financial statements, taken as a whole, and we are not, by communicating the critical audit matter below, providing a separate opinion on the critical audit matter or on the accounts or disclosures to which it relates.
Revenue Recognition - Estimated Costs of Internal Full-Time Employees (FTEs) - Sanofi
As described in Note 3 to the consolidated financial statements, the Company’s consolidated revenue was $76.9 million for the year ended November 30, 2023 of which there was revenue of $25.4 million generated from the Company’s collaboration agreement with Sanofi. During the contract term, management uses a cost-based input method, which the Company determined most faithfully depicts the transfer of its performance obligation to Sanofi, to recognize revenue based on the actual costs incurred as a percentage of total estimated costs as the Company completes its performance obligation under the contract. Costs consist primarily of internal FTE and third-party contract costs related to the Sanofi agreement. The cumulative effect of revisions to estimated costs to complete the Company’s performance obligation is recorded in the period in which changes are identified and amounts can be reasonably estimated. Total estimated costs are primarily driven by the number of estimated FTEs, which requires significant management judgment.
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The principal considerations for our determination that performing procedures relating to revenue recognition - estimated costs of internal FTEs is a critical audit matter are (i) the high degree of auditor judgment and subjectivity in performing procedures relating to the estimated costs of internal FTEs due to the significant judgment by management when determining the estimate and (ii) the significant audit effort in evaluating the significant assumption related to the number of estimated FTEs.
Addressing the matter involved performing procedures and evaluating audit evidence in connection with forming our overall opinion on the consolidated financial statements. These procedures included, among others, evaluating and testing management’s process for determining the estimated costs of internal FTEs, which included evaluating the reasonableness of the significant assumption related to the number of estimated FTEs, by (i) performing a comparison of management’s estimated costs of internal FTEs to the actual internal FTE costs driven by the number of estimated FTEs; (ii) testing the completeness and accuracy of the data used by management in the estimate; (iii) evaluating management’s timely identification of changes in estimated costs of internal FTEs driven by the number of estimated FTEs; and (iv) evaluating whether the estimate and assumption were consistent with evidence obtained in other areas of the audit.
/s/ PricewaterhouseCoopers LLP
February 15, 2024
We have served as the Company’s auditor since 2014.
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NURIX THERAPEUTICS, INC.
CONSOLIDATED BALANCE SHEETS
(in thousands, except share and per share amounts)
| November 30, | |||||||||||
| 2023 | 2022 | ||||||||||
| Assets | |||||||||||
| Current assets: | |||||||||||
| Cash and cash equivalents | $ | $ | |||||||||
| Marketable securities, current | |||||||||||
| Prepaid expenses and other current assets | |||||||||||
| Total current assets | |||||||||||
| Marketable securities, non-current | |||||||||||
| Operating lease right-of-use assets | |||||||||||
| Property and equipment, net | |||||||||||
| Restricted cash | |||||||||||
| Other assets | |||||||||||
| Total assets | $ | $ | |||||||||
| Liabilities and stockholdersʼ equity | |||||||||||
| Current liabilities: | |||||||||||
| Accounts payable | $ | $ | |||||||||
| Accrued expenses and other current liabilities | |||||||||||
| Operating lease liabilities, current | |||||||||||
| Deferred revenue, current | |||||||||||
| Total current liabilities | |||||||||||
| Operating lease liabilities, net of current portion | |||||||||||
| Deferred revenue, net of current portion | |||||||||||
| Total liabilities | |||||||||||
| Commitments and contingencies (Note 6) | |||||||||||
| Stockholders’ equity: | |||||||||||
Preferred stock, $ | |||||||||||
Common stock, $ | |||||||||||
| Additional paid-in capital | |||||||||||
| Accumulated other comprehensive loss | ( | ( | |||||||||
| Accumulated deficit | ( | ( | |||||||||
| Total stockholders’ equity | |||||||||||
| Total liabilities and stockholders’ equity | $ | $ | |||||||||
The accompanying notes are an integral part of these consolidated financial statements.
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NURIX THERAPEUTICS, INC.
CONSOLIDATED STATEMENTS OF OPERATIONS
(in thousands, except share and per share amounts)
| Year Ended November 30, | |||||||||||
| 2023 | 2022 | ||||||||||
| Revenue: | |||||||||||
| Collaboration revenue | $ | $ | |||||||||
| License revenue | |||||||||||
| Total revenue | |||||||||||
| Operating expenses: | |||||||||||
| Research and development | |||||||||||
| General and administrative | |||||||||||
| Total operating expenses | |||||||||||
| Loss from operations | ( | ( | |||||||||
| Interest and other income, net | |||||||||||
| Net loss | $ | ( | $ | ( | |||||||
| Net loss per share, basic and diluted | $ | ( | $ | ( | |||||||
| Weighted-average number of shares outstanding, basic and diluted | |||||||||||
The accompanying notes are an integral part of these consolidated financial statements.
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NURIX THERAPEUTICS, INC.
CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS
(in thousands)
| Year Ended November 30, | |||||||||||
| 2023 | 2022 | ||||||||||
| Net loss | $ | ( | $ | ( | |||||||
| Other comprehensive loss, net of tax: | |||||||||||
| Unrealized gain (loss) on available-for-sale marketable securities | ( | ||||||||||
| Total comprehensive loss | $ | ( | $ | ( | |||||||
The accompanying notes are an integral part of these consolidated financial statements.
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NURIX THERAPEUTICS, INC.
CONSOLIDATED STATEMENTS OF STOCKHOLDERS’ EQUITY
(in thousands, except share amounts)
| Common stock | Additional paid-in capital | Accumulated other comprehensive income (loss) | Accumulated deficit | Total stockholders’ equity | |||||||||||||||||||||||||||||||
| Shares | Amount | ||||||||||||||||||||||||||||||||||
| Balance as of November 30, 2021 | $ | $ | $ | ( | $ | ( | $ | ||||||||||||||||||||||||||||
Issuance of pre-funded warrants, net of issuance costs of $ | — | — | — | — | |||||||||||||||||||||||||||||||
Issuance of common stock in "at the market" financing, net of issuance costs of $ | — | — | |||||||||||||||||||||||||||||||||
| Exercise of stock options | — | — | — | ||||||||||||||||||||||||||||||||
| Vesting of restricted stock units | — | — | — | — | — | ||||||||||||||||||||||||||||||
| Vesting of early exercised stock options | — | — | — | — | |||||||||||||||||||||||||||||||
| Issuance under employee stock purchase plan | — | — | — | ||||||||||||||||||||||||||||||||
| Stock-based compensation | — | — | — | — | |||||||||||||||||||||||||||||||
| Unrealized loss on available-for-sale marketable securities | — | — | — | ( | — | ( | |||||||||||||||||||||||||||||
| Net loss | — | — | — | — | ( | ( | |||||||||||||||||||||||||||||
| Balance as of November 30, 2022 | ( | ( | |||||||||||||||||||||||||||||||||
| Exercise of pre-funded warrants | — | — | — | ||||||||||||||||||||||||||||||||
| Exercise of stock options | — | — | — | ||||||||||||||||||||||||||||||||
| Vesting of restricted stock units | — | — | — | — | — | ||||||||||||||||||||||||||||||
| Vesting of early exercised stock options | — | — | — | — | |||||||||||||||||||||||||||||||
| Issuance under employee stock purchase plan | — | — | — | ||||||||||||||||||||||||||||||||
| Stock-based compensation | — | — | — | — | |||||||||||||||||||||||||||||||
| Unrealized gain on available-for-sale marketable securities | — | — | — | — | |||||||||||||||||||||||||||||||
| Net loss | — | — | — | — | ( | ( | |||||||||||||||||||||||||||||
| Balance as of November 30, 2023 | $ | $ | $ | ( | $ | ( | $ | ||||||||||||||||||||||||||||
The accompanying notes are an integral part of these consolidated financial statements.
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NURIX THERAPEUTICS, INC.
CONSOLIDATED STATEMENTS OF CASH FLOWS
(in thousands)
| Year Ended November 30, | |||||||||||
| 2023 | 2022 | ||||||||||
| Cash flows from operating activities | |||||||||||
| Net loss | $ | ( | $ | ( | |||||||
| Adjustments to reconcile net loss to net cash used in operating activities: | |||||||||||
| Depreciation and amortization | |||||||||||
| Stock-based compensation | |||||||||||
| Net amortization (accretion) of premium (discount) on marketable securities | ( | ||||||||||
| Loss on disposal of property and equipment | |||||||||||
| Amortization of operating lease right-of-use assets | |||||||||||
| Other | |||||||||||
| Changes in operating assets and liabilities: | |||||||||||
| Accounts receivable | |||||||||||
| Prepaid expenses and other assets | ( | ||||||||||
| Accounts payable | |||||||||||
| Deferred revenue | ( | ||||||||||
| Operating lease liabilities | ( | ( | |||||||||
| Accrued expenses and other liabilities | |||||||||||
| Net cash used in operating activities | ( | ( | |||||||||
| Cash flows from investing activities | |||||||||||
| Purchases of marketable securities | ( | ( | |||||||||
| Maturities of marketable securities | |||||||||||
| Purchases of property and equipment | ( | ( | |||||||||
| Net cash provided by investing activities | |||||||||||
| Cash flows from financing activities | |||||||||||
| Proceeds from issuances of pre-funded warrants, net of issuance costs | |||||||||||
| Proceeds from issuances of common stock in equity financing, net of issuance costs | |||||||||||
| Proceeds from exercise of stock options and pre-funded warrants | |||||||||||
| Proceeds from issuance under employee stock purchase plan | |||||||||||
| Net cash provided by financing activities | |||||||||||
| Net decrease in cash, cash equivalents and restricted cash | ( | ( | |||||||||
| Cash, cash equivalents and restricted cash at beginning of period | |||||||||||
| Cash, cash equivalents and restricted cash at end of period | $ | $ | |||||||||
| Supplemental disclosures of non-cash investing and financing activities: | |||||||||||
| Additions to property and equipment included in accounts payable and accrued expenses and other liabilities | $ | $ | |||||||||
Capitalized stock-based compensation related to internal-use software development | $ | $ | |||||||||
| Right-of-use assets recognized in exchange for lease obligations | $ | $ | |||||||||
| Vesting of early exercised stock options | $ | $ | |||||||||
| Deferred issuance costs recognized related to equity financing | $ | $ | |||||||||
| As of November 30, | |||||||||||
| 2023 | 2022 | ||||||||||
| Reconciliation of cash, cash equivalents and restricted cash: | |||||||||||
| Cash and cash equivalents | $ | $ | |||||||||
| Restricted cash | |||||||||||
| Cash, cash equivalents and restricted cash | $ | $ | |||||||||
The accompanying notes are an integral part of these consolidated financial statements.
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NURIX THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
1. Organization
Description of Business
Nurix Therapeutics, Inc. (the Company) was incorporated in the state of Delaware on August 27, 2009, and is headquartered in San Francisco, California. The Company is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of innovative small molecules and antibody therapies based on the modulation of cellular protein levels as a novel treatment approach for cancer, inflammatory conditions and other challenging diseases. Leveraging the Company’s expertise in E3 ligases together with its proprietary DNA-encoded libraries, the Company has built DELigase, an integrated discovery platform to identify and advance novel drug candidates targeting E3 ligases, a broad class of enzymes that can modulate proteins within the cell. The Company’s drug discovery approach is to either harness or inhibit the natural function of E3 ligases within the ubiquitin-proteasome system to selectively decrease or increase cellular protein levels. The Company’s wholly owned, clinical stage pipeline includes targeted protein degraders of Bruton’s tyrosine kinase, a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene B, an E3 ligase that regulates activation of multiple immune cell types including T cells and NK cells. The Company’s partnered drug discovery pipeline consists of multiple programs under collaboration agreements with Gilead Sciences, Inc. (Gilead), Sanofi S.A. (Sanofi) and Seagen Inc. (now a part of Pfizer Inc. (Pfizer)), within which the Company retains certain options for co-development, co-commercialization and profit sharing in the United States for multiple drug candidates.
Equity Distribution Agreement
In August 2021, the Company filed a shelf registration statement on Form S-3 with the Securities and Exchange Commission, which was amended in February 2023. This shelf registration statement, which includes a base prospectus, allows the Company at any time to offer and sell up to $450.0 million of the Company’s registered common stock, preferred stock, debt securities, warrants, subscriptions rights and or units or any combination of securities described in the prospectus in one or more offerings. In addition, in August 2021, the Company entered into an Equity Distribution Agreement with Piper Sandler & Co. (Piper Sandler) pursuant to which, from time to time, the Company may offer and sell through Piper Sandler up to $150.0 million of the common stock registered under the shelf registration statement pursuant to one or more “at the market” offerings.
The Company is not required to sell any shares at any time during the term of the Equity Distribution Agreement. The Company agreed to pay Piper Sandler a commission of 3 % of the gross sales price of any shares sold pursuant to the Equity Distribution Agreement. In June 2022, the Company issued and sold 2,000,000 shares of common stock under the Equity Distribution Agreement at a price of $10.0001 per share of common stock for net proceeds of $19.3 million, after deducting offering commissions and expenses paid by the Company. As of November 30, 2023, the Company had $130.0 million of common stock remaining available for sale under the Equity Distribution Agreement.
Registered Direct Offerings
In July 2022, the Company entered into separate securities purchase agreements with certain purchasers to issue and sell pre‑funded warrants to purchase an aggregate of 6,814,920 shares of the Company’s common stock in registered direct offerings (RDOs) at a price of $13.939 per pre-funded warrant. Net proceeds from the RDOs were $94.8 million, after deducting offering expenses of $0.2 million. Refer to Note 7 for more information regarding the pre-funded warrants issued in the RDOs.
Liquidity and Management Plans
As of November 30, 2023, the Company had cash, cash equivalents and short-term marketable securities of $287.9 million, working capital of $208.5 million and an accumulated deficit of $545.2 million. The Company’s operations have historically been financed through the issuance of common stock, redeemable convertible preferred stock and pre-funded warrants and proceeds received under the Company’s collaboration and license agreements. Since inception, the Company has generally incurred significant losses and negative net cash flows from operations. The Company does not expect its existing cash, cash equivalents and marketable securities to be sufficient to fund the completion of its clinical trials through commercialization and will need substantial additional funding to support its continuing operations and pursue its long-term business plan. The Company anticipates incurring additional losses until such time, if ever, that it can generate significant sales of its drug candidates currently in development.
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2. Summary of Significant Accounting Policies
Basis of Presentation and Principles of Consolidation
Use of Estimates
The preparation of financial statements in conformity with U.S. GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and disclosures of contingent assets and liabilities at the date of the financial statements and reported amounts of revenues and expenses during the reporting period. On an ongoing basis, management evaluates its estimates, including those related to the useful lives of long-lived assets, the measurement of stock-based compensation, accruals for research and development activities, income taxes and revenue recognition. The Company also makes certain commencement date estimates for its leases, including the incremental borrowing rate, the expected lease term and the fair value of the leased asset. The Company bases its estimates on historical experience and on other relevant assumptions that are reasonable under the circumstances. Actual results could materially differ from those estimates. Refer to Note 3 for more information regarding the estimates related to revenue recognition.
Concentration of Credit Risk
Financial instruments that potentially subject the Company to concentration of credit risk consist of cash, cash equivalents and marketable securities. The Company’s marketable securities consist of debt securities issued by highly rated corporate entities, the U.S. federal government or state and local governments. The Company’s exposure to any individual corporate entity is limited by policy. Deposits may, at times, exceed federally insured limits. The Company invests its cash equivalents in highly rated money market funds. During the periods presented, the Company has not experienced any losses on its deposits of cash, cash equivalents or marketable securities.
Other Risks and Uncertainties
The Company is subject to a number of risks similar to other clinical stage biopharmaceutical companies, including, but not limited to, changes in any of the following areas that the Company believes could have a material adverse effect on its future financial position or results of operations: risks related to the successful discovery and development of its drug candidates, ability to raise additional capital, development of new technological innovations by its competitors and delay or inability to obtain drug substance and finished drug product from the Company’s third-party contract manufacturers necessary for the Company’s drug candidates, protection of intellectual property rights, litigation or claims against the Company based on intellectual property rights and regulatory clearance and market acceptance for any of the Company’s products candidates for which the Company receives marketing approval.
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Moreover, the Company is subject to risks and uncertainties as a result of global business, political and macroeconomic events and conditions, including increasing financial market volatility and uncertainty, inflation, increasing interest rates, uncertainty with respect to the federal budget and debt ceiling and potential government shutdowns related thereto, potential instability in the global banking system, cybersecurity events, the impact of war or military conflict, including regional conflicts around the world, and public health pandemics. The extent to which business, political and macroeconomic factors, including increasing financial market volatility and uncertainty, will impact the Company’s business will depend on future developments that are highly uncertain and cannot be predicted at this time.
The preparation of financial statements in conformity with generally accepted accounting principles requires management to make estimates and assumptions that affect the amounts reported in the financial statements and accompanying notes. The extent to which the increasing financial market volatility and uncertainty may directly or indirectly impact the Company’s financial statements is highly uncertain and subject to change.
Segments
Cash and Cash Equivalents
Restricted Cash
Fair Value of Financial Instruments
Marketable Securities
Marketable securities consist of money market funds, U.S. Treasuries, corporate debt securities, U.S. government agency securities, corporate commercial paper and foreign government securities. The Company’s marketable securities are classified as available-for-sale and carried at estimated fair values and reported in cash equivalents, short-term marketable securities or long-term marketable securities. Management determines the appropriate classification of the marketable securities at the time they are acquired and evaluates the appropriateness of such classifications at each consolidated balance sheet date. Marketable securities with contractual maturities greater than 12 months are considered long-term marketable securities.
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The Company regularly reviews its marketable securities for declines in estimated fair value below amortized cost. The factors considered in determining whether a credit loss exists include the creditworthiness of the security issuers, the number of marketable securities in an unrealized loss position, the severity and duration of the unrealized losses, and whether it is more likely than not that the Company will be required to sell the marketable securities before the recovery of their amortized cost basis. The cost of marketable securities sold is based on the specific identification method. In circumstances when an unrealized loss is determined to be credit-related, or when the Company intends to sell or is more likely than not required to sell a security before it recovers its amortized cost basis, the difference between the fair value and the amortized cost of the security is recognized as interest and other income, net in the consolidated statements of operations, and an allowance for credit loss is recorded on the consolidated balance sheet. In circumstances when the decline in fair value is non-credit related, the difference is reported in accumulated other comprehensive income (loss), net of tax as a separate component of stockholders’ equity.
The Company excludes accrued interest from both the fair value and the amortized cost basis of marketable securities for the purposes of identifying and measuring an impairment. The Company writes off accrued interest receivables that have become more than 90 days delinquent by reversing interest income. To date, the Company has not written off any accrued interest receivables associated with its marketable securities.
Property and Equipment
Leases
The Company determines if an arrangement contains a lease and the classification of the lease at inception. An arrangement contains a lease if there is an identified asset and if the Company controls the use of the identified asset throughout the period of use.The evaluation of whether the lease is an operating or a finance lease requires judgments in determining the fair value of the leased asset. Lease right-of-use (ROU) assets and lease liabilities are recognized at the lease commencement date based on the present value of the future minimum lease payments over the lease term at the commencement date. ROU assets also include any initial direct costs incurred and any lease payments made on or before the lease commencement date, less any lease incentives received. The Company uses its incremental borrowing rate, if an implicit rate is not readily available, and the information available at the date of lease commencement in determining its lease liabilities. The Company’s incremental borrowing rate is based on the rate of interest that the Company would have to pay to borrow on a collateralized basis over a similar term, an amount equal to the lease payments in a similar economic environment, and the determination of the rate requires the Company to make certain assumptions and judgements, including on its synthetic credit rating. Leases may include options to extend or early terminate the lease term. If the Company, using judgement, is reasonably certain that an option will be exercised, then the option will be included in the calculation of the lease term. The Company elected to combine lease and non-lease components for all underlying assets groups, and not recognize ROU assets or lease liabilities for short-term leases. A short-term lease is a lease that, at the commencement date, has a lease term of 12 months or less and does not include an option to purchase the underlying asset that the lessee is reasonably certain to exercise. Lease expense for operating leases is recognized on a straight-line basis over the lease term. The Company does not have any finance leases.
Internal-Use Software Development Costs
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Long-Lived Assets
Deferred Offering Costs
Revenue Recognition
The Company recognizes revenue when its customer obtains control of promised goods or services, in an amount that reflects the consideration which the Company expects to receive in exchange for those goods or services. To recognize revenue from a contract with a customer, the Company performs the following five steps:
(i)identify the contract(s) with a customer;
(ii)identify the performance obligations in the contract;
(iii)determine the transaction price;
(iv)allocate the transaction price to the performance obligations in the contract; and
(v)recognize revenue when (or as) the Company satisfies a performance obligation.
At contract inception, the Company assesses the goods or services promised within each contract, whether each promised good or service is distinct, and determines those that are performance obligations. The Company then recognizes as revenue the amount of the transaction price that is allocated to the respective performance obligation when or as the performance obligation is satisfied.
The Company enters into collaboration agreements under which it may obtain upfront payments, milestone payments, royalty payments and other fees. Promises under these arrangements may include research licenses, research services, including selection campaign research services for certain replacement targets, the obligation to share information during the research and the participation of alliance managers and in joint research committees, joint patent committees and joint steering committees. The Company assesses these promises within the context of the agreements to determine the performance obligations.
Exclusive license rights: If a license to the Company’s intellectual property is determined to be distinct from the other promises identified in the arrangement, the Company recognizes revenue from nonrefundable, upfront payments allocated to the license when the license is transferred to the customer and the customer is able to use and benefit from the license and the underlying intellectual property. If the license is the predominant promise, and it is determined that the license represents functional intellectual property, revenue is recognized at the point in time when control of the license is transferred. If it is determined that the license does not represent functional intellectual property, revenue is recognized over time using an appropriate method of measuring progress.
Research and collaboration licenses: Collaboration agreements may include research licenses and research and development services to be performed by the Company. For research licenses that are bundled with other promises, the Company utilizes judgment to assess the nature of the combined performance obligation to determine whether the combined performance obligation is satisfied over time or at a point in time and, if over time, the appropriate method of measuring proportional performance for purposes of recognizing revenue from non-refundable, upfront payments. The Company evaluates the measure of proportional performance each reporting period and, if necessary, adjusts the measure of performance and related revenue recognition.
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Milestone payments: At the inception of each arrangement that includes research, development or regulatory milestone payments, the Company evaluates whether the milestones are considered probable of being reached and estimates the amount to be included in the transaction price. The Company uses the most likely amount method for research, development and regulatory milestone payments. Under the most likely amount method, an entity considers the single most likely amount in a range of possible consideration amounts. If it is probable that a significant revenue reversal would not occur, the associated milestone amount is included in the transaction price.
Sales-based milestones and royalties: For arrangements that include sales-based milestone or royalty payments based on the level of sales, and in which the license is deemed to be the predominant item to which the sales-based milestone or royalties relate to, the Company recognizes revenue in the period in which the sales-based milestone is achieved and in the period in which the sales associated with the royalty occur. To date, the Company has not recognized any sales-based milestone or royalty revenue resulting from its collaboration arrangements.
Customer options: Customer options, such as options granted to allow a licensee to extend a license or research term, to select additional research targets or to choose to research, develop and commercialize licensed compounds are evaluated at contract inception to determine whether those options provide a material right (i.e., an optional good or service offered for free or at a discount) to the customer. If the customer options represent a material right, the material right is treated as a separate performance obligation at the outset of the arrangement. The Company allocates the transaction price to material rights based on the standalone selling price. As a practical alternative to estimating the standalone selling price of a material right when the underlying goods or services are both (i) similar to the original goods or services in the contract and (ii) provided in accordance with the terms of the original contract, the Company allocates the total amount of consideration expected to be received from the customer to the total goods or services expected to be provided to the customer. Amounts allocated to any material right are recognized as revenue when or as the related future goods or services are transferred or when the option expires.
Deferred revenue, which is a contract liability, represents net amounts received by the Company for which the related revenues have not been recognized because one or more of the revenue recognition criteria have not been met. The current portion of deferred revenue represents the amount to be recognized within one year from the consolidated balance sheet date based on the estimated performance period of the underlying performance obligation. The non-current portion of deferred revenue represents amounts to be recognized after one year through the end of the performance period of the performance obligation.
All revenue was derived from customers located in the United States during the years ended November 30, 2023 and 2022.
Research and Development Expenses
The Company expenses all research and development costs as incurred. Research and development costs include, but are not limited to, payroll and personnel expenses, laboratory supplies, preclinical study costs, clinical trial costs, compound manufacturing costs, consulting costs and allocated overhead, including rent, equipment, depreciation and utilities.
The Company records accrued expenses for estimated costs of research and development activities conducted by third-party service providers, which include preclinical studies and clinical trials and contract manufacturing activities. The Company records the estimated costs of research and development activities based upon the estimated amount of services provided but not yet invoiced and includes these costs in accrued expenses and other current liabilities on the consolidated balance sheet.
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Stock-Based Compensation
The Company accounts for stock-based compensation using a fair value-based method, which requires the recognition of compensation expense for costs related to all stock-based payments including stock options, restricted stock units (RSUs) and purchase rights under the Company’s 2020 Employee Stock Purchase Plan (ESPP). The Company estimates the fair value of stock options and purchase rights granted under the ESPP on the date of grant using the Black-Scholes option pricing model, which is impacted by the fair value of the Company’s common stock, as well as changes in assumptions regarding a number of highly complex and subjective variables. The model requires management to make a number of assumptions including expected volatility, expected term, risk-free interest rate and expected dividend yield. The Company determines the fair value of stock options, RSUs and purchase rights under the ESPP using the market closing price of the Company’s common stock on the date of grant.
For stock-based payments with service conditions only, the Company uses the straight-line method to allocate compensation cost to reporting periods over the requisite service period, which is generally the vesting period. Stock-based compensation expense for non-employee stock-based awards is also measured based on the grant date fair value with the estimated fair value expensed over the period for which the non-employee is required to provide service in exchange for the award. For stock-based payments with performance conditions, the Company evaluates the probability of achieving performance conditions at each reporting date. The Company begins to recognize compensation cost using an accelerated attribution method when it is deemed probable that the performance condition will be met. The Company accounts for forfeitures as they occur.
Income taxes
The Company accounts for income taxes under the asset and liability method. Under this method, deferred tax assets and liabilities are determined based on the difference between the financial statement and tax bases of assets and liabilities using enacted tax rates in effect for the year in which the differences are expected to affect taxable income. Valuation allowances are established when in management’s estimate, it is more likely than not, that the deferred tax assets will not be recovered.
Financial statement effects of uncertain tax positions are recognized when it is more likely than not, based on the technical merits of the position, that it will be sustained upon examination. It is the Company’s policy to include penalties and interest expense related to income taxes as a component of the provision for income taxes. Non-income-based taxes are expensed as incurred within operating expenses on the Company’s consolidated statements of operations.
Comprehensive loss
Net loss per share
Basic net loss per share is calculated by dividing the net loss by the weighted-average number of shares of common stock (including non-voting common stock and pre-funded warrants) outstanding during the period, without consideration for all other common stock equivalents. Shares of common stock into which the pre-funded warrants may be exercised are considered outstanding for the purposes of computing net loss per share because the shares may be issued for little or no consideration, are fully vested and are exercisable after the original issuance date. Diluted net loss is calculated by dividing the net loss by the weighted-average number of common stock and potentially dilutive securities outstanding for the period. For purposes of the diluted net loss per share calculation, options to purchase common stock, options early exercised subject to vesting, RSUs and shares expected to be purchased under the ESPP are considered to be potentially dilutive securities. Diluted net loss per share is the same as basic net loss per share, since the effects of potentially dilutive securities are antidilutive given the net loss for each period presented.
Recent Accounting Pronouncements Not Yet Adopted
In November 2023, the Financial Accounting Standards Board (FASB) issued Accounting Standard Update (ASU) No. 2023‑07, Segment Reporting (Topic 280)—Improvements to Reportable Segment Disclosures (ASU 2023-07), which is intended to improve reportable segment disclosure requirements, primarily through enhanced disclosures about significant segment expenses. ASU 2023-07 should be applied on a retrospective basis. ASU 2023-07 is effective for annual periods beginning after December 15, 2023, and interim periods within fiscal years beginning after December 15, 2024. Early adoption is permitted. The Company is in the process of evaluating the impact of this new guidance on its disclosures.
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In December 2023, the FASB issued ASU 2023-09—Income Taxes (Topic 740): Improvements to Income Tax Disclosures (ASU 2023-09), which is intended to enhance the transparency and decision usefulness of income tax disclosures, primarily by amending disclosure requirements for the effective tax rate reconciliation and income taxes paid. ASU 2023-09 should be applied on a prospective basis, and retrospective application is permitted. ASU 2023-09 is effective for annual periods beginning after December 15, 2024. Early adoption is permitted. The Company is in the process of evaluating the impact of this new guidance on its disclosures.
3. Collaboration Agreements
Gilead
In June 2019, the Company entered into a global strategic collaboration agreement with Gilead (as subsequently amended, the Gilead Agreement) to discover, develop and commercialize a pipeline of targeted protein degradation drugs for patients with cancer and other challenging diseases using the Company’s DELigase platform to identify novel agents that utilize E3 ligases to induce degradation of five specified drug targets. In August 2019 and September 2022, the Company entered into the First Amendment and the Second Amendment, respectively, to the Gilead Agreement to clarify certain language of the Gilead Agreement. These amendments had no impact on revenue recognition.
Under the Gilead Agreement, Gilead has the option to license drug candidates directed to up to five targets resulting from the collaboration and is responsible for the clinical development and commercialization of drug candidates resulting from the collaboration. The Company retains the option to co-develop and co-promote, under a profit share structure, up to two drug candidates in the United States, provided that the Company may only exercise such option once per licensed product and Gilead retains the right to veto the Company’s option selection for any one drug candidate of its choice. The collaboration excludes the Company’s current internal protein degradation programs for which the Company retains all rights, and also excludes the Company’s future internal programs, provided that the Company has distinguished future programs as excluded from the scope of the collaboration. In March 2023, Gilead exercised the option, which did not represent a material right at contract inception, since it was not offered for free or at a discount, to exclusively license one target (Gilead License Option Exercise), the first development candidate resulting from the Gilead Agreement. Pursuant to the Gilead Agreement, the Company received a license option exercise payment of $20.0 million in April 2023 for the Gilead License Option Exercise. The license to the functional intellectual property and all goods and services related to the Gilead License Option Exercise were transferred during the second quarter of fiscal year 2023.
Over time, Gilead may elect to replace the initial drug targets with other drug targets. For drug targets that are subject to the collaboration, the Company is obligated to use commercially reasonable efforts to undertake a research program in accordance with a research plan agreed to by the parties and established on a target-by-target basis. The Company has primary responsibility under the Gilead Agreement for performing preclinical research activities (including target validation, drug discovery, identification or synthesis) pursuant to a research plan. Each party will bear its own costs in the conduct of research activities. Gilead will be responsible for any development, commercialization and manufacturing activities, unless the Company exercises its co-development and co-promotion option. For those programs that the Company exercises its option to co-develop and co-promote, the Company and Gilead will split U.S. development costs as well as U.S. profits and losses evenly, and the Company will be eligible to receive royalties on net ex-U.S. sales and reduced milestone payments.
Upon signing the Gilead Agreement, Gilead paid the Company an upfront payment of $45.0 million plus $3.0 million in additional fees. In addition, from the signing of the Gilead Agreement to November 30, 2023, the Company has received payments of $47.0 million for research milestones and additional payments and $20.0 million for a license option exercise payment. As of November 30, 2023, the Company is eligible to receive up to approximately $2.3 billion in total additional payments based on certain additional fees, payments and the successful completion of certain preclinical, clinical, development and sales milestones. The Company also is eligible to receive mid-single digit to low tens percentage tiered royalties on annual net sales from any commercial products directed to the optioned collaboration targets, subject to certain reductions and excluding sales in the United States of any products for which the Company exercises its option to co-develop and co-promote, for which the parties share profits and losses evenly.
Subject to earlier expiration in certain circumstances, the Gilead Agreement expires on a licensed product-by-licensed product and country-by-country basis upon the later of (1) the expiration of the last to expire patent with a valid claim covering the applicable licensed product in the applicable country, (2) the expiration of any regulatory exclusivity for the applicable licensed product in the applicable country or (3) ten years after the first commercial sale of the applicable licensed product in the applicable country covered by the Gilead Agreement, provided that the term for any profit-shared licensed product in the United States will expire upon the expiration or termination of the applicable profit-share term as set forth in an applicable profit-share agreement to be negotiated upon the Company’s exercise of its option to co-develop and co-promote such licensed product. If Gilead does not exercise an option to license a drug candidate, then the Gilead Agreement will terminate at the end of the last to expire option period.
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The Company identified the following promises in the Gilead Agreement: (1) the research licenses, (2) the research services, including selection campaign research services for certain replacement targets, (3) the obligation to share information during the research term and (4) the participation in the joint research committee and joint steering committee. The Company determined that the research licenses, the obligation to share information and the participation in joint committees are not capable of being distinct from the research services due to the specialized nature of the research services to be provided by the Company, and, accordingly, the promises identified were combined as one single performance obligation. The Company also concluded that, at the inception of the Gilead Agreement, Gilead’s options to obtain an exclusive development, manufacturing and commercialization license for each collaboration target, to extend the five-year research term and to perform selection campaign research services for certain replacement targets do not represent material rights and are not considered performance obligations because they do not contain a significant and incremental discount. The Company concluded that Gilead’s target reservation right is not a performance obligation as it does not require any specific action from the Company and it is rather an exclusivity right and an attribute of other performance obligations in the Gilead Agreement, such as the research licenses.
In order to determine the transaction price, the Company evaluated all the payments to be received during the duration of the contract. Certain milestone payments and additional fees were considered variable consideration, which were not included in the transaction price based on the most likely amount method as of November 30, 2023. The Company re-evaluates the transaction price in each reporting period and as uncertain events are resolved or other changes in circumstances occur. The Company determined that the transaction price at the inception of the Gilead Agreement consisted of the upfront payment of $45.0 million and $3.0 million in additional fees. Upon the achievement of research milestones and additional fees related to target reservations, $47.0 million in variable consideration was added to the transaction price, and a cumulative effect was recorded as revenue in the period the transaction price increased. The transaction price is recognized as collaboration revenue using the cost-based input method over the estimated research term of five years . The contract term was determined to be the five-year initial research term which represents the estimated timing of completion of the identified deliverables. Additionally, the Company considered the impact of Gilead terminating the Gilead Agreement prior to the completion of the research services during the initial five-year research term and determined that there were significant economic costs to Gilead for doing so, and as such, did not adjust the contract term.
Using the cost-based input method, which the Company determined most faithfully depicts the transfer of its performance obligation to Gilead, the Company recognizes revenue based on actual costs incurred as a percentage of total estimated costs as the Company completes its performance obligation under the contract. Costs consist primarily of internal full-time employee (FTE) and third-party contract costs related to the Gilead Agreement. The cumulative effect of revisions to estimated costs to complete the Company’s performance obligation is recorded in the period in which changes are identified and amounts can be reasonably estimated. Total estimated costs are primarily driven by the number of estimated FTEs, which requires significant management judgment.
For the year ended November 30, 2023, the Company recognized collaboration revenue related to the Gilead Agreement of $29.9 million, of which $20.3 million was included in deferred revenue as of November 30, 2022, and $7.9 million was related to performance obligations satisfied in previous periods. For the year ended November 30, 2022, the Company recognized collaboration revenue related to the Gilead Agreement of $23.7 million, of which $18.4 million was included in deferred revenue as of November 30, 2021, and $4.0 million was related to performance obligations satisfied in previous periods. As of November 30, 2023, deferred revenue related to the Gilead Agreement was $10.0 million, all of which was current. As of November 30, 2022, deferred revenue related to the Gilead Agreement was $27.4 million, of which $18.2 million was current.
Sanofi
In December 2019, the Company entered into a strategic collaboration with Genzyme Corporation, a subsidiary of Sanofi, which became effective in January 2020 (as subsequently expanded and amended, the Sanofi Agreement), to discover, develop and commercialize a pipeline of targeted protein degradation drugs for patients with challenging diseases in multiple therapeutic areas using the Company’s DELigase platform to identify small molecules designed to induce degradation of three specified initial drug targets. In January 2021, as part of the existing Sanofi Agreement, Sanofi paid the Company $22.0 million to exercise its option to expand the number of targets in the Sanofi Agreement from three to a total of five targets.
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In January 2021, the Company entered into the First Amendment to the Sanofi Agreement to modify the research term on all targets (the First Sanofi Amendment). In December 2021, the Company entered into the Second Amendment to the Sanofi Agreement to extend the substitution deadline on certain targets. In July 2022, the Company entered into the Third Amendment to the Sanofi Agreement to further extend the substitution deadline on certain targets. The extensions of the substitution deadline had no impact on revenue recognition. Also in July 2022, Sanofi elected to replace certain drug targets, and the substitution extended the research term of those targets by one year to 5.25 years and increased overall forecasted costs, which had an immaterial impact on revenue recognition. In August 2022 and November 2023, the Company entered into the Fourth Amendment and Fifth Amendment, respectively, to the Sanofi Agreement to modify the research plan for certain targets, which had no impact on revenue recognition.
Under the Sanofi Agreement, Sanofi has exclusive rights and is responsible for the clinical development, commercialization and manufacture of drug candidates resulting from the collaboration while the Company retains the option to co-develop, co-promote and co-commercialize all drug candidates in the United States directed to up to two targets, one of which must be selected from a list of targets designated at the execution of the Sanofi Agreement or any replacement of such targets, and one of which must be selected from targets identified by Sanofi as part of their January 2021 expansion. The Company’s right to exercise its option to co-develop, co-promote and co-commercialize a given target is dependent on its ability to demonstrate, within a given timeframe, that it has sufficient cash resources and personnel to commercialize the product. The collaboration excludes the Company’s current internal protein degradation programs for which it retains all rights, and also excludes future internal programs, provided that the Company distinguished future programs as excluded from the scope of the collaboration.
For drug targets that are subject to the collaboration, the Company has primary responsibility for conducting preclinical research activities (including target validation, drug discovery, identification or synthesis) in accordance with the applicable research plan agreed to by the parties and established on a target-by-target basis. The Company is obligated to use commercially reasonable efforts to identify relevant target binders and targeted protein degraders in order to identify development candidates. Subject to certain exceptions, each party will bear its own costs in the conduct of such research. Sanofi will be responsible for any development and commercialization activities unless the Company exercises its co-development and co-promotion option. For those programs that the Company exercises its option to co-develop, co-promote and co-commercialize, the Company will be responsible for a portion of the U.S. development costs, and the parties will split U.S. profits and losses evenly and the Company will be eligible to receive royalties on ex-U.S. net sales and reduced milestone payments on such optioned products.
Upon signing the Sanofi Agreement, Sanofi paid the Company an upfront payment of $55.0 million. Subsequently, in January 2021, Sanofi paid the Company an additional $22.0 million to exercise its option to expand the number of targets beyond the initial targets included in the collaboration. In addition, from the signing of the Sanofi Agreement to November 30, 2023, the Company has received payments of $7.0 million for research milestones. Additionally, the Company achieved two research milestones in November 2023 and received payments totaling $4.0 million in January 2024 as a result. As of November 30, 2023, the Company is eligible to receive up to approximately $2.5 billion in total additional payments based on certain additional fees, payments and the successful completion of certain research development, regulatory and sales milestones, as well as mid-single digit to low teen percentage tiered royalties on annual net sales of any commercial products that may result from the collaboration, subject to certain reductions and excluding sales in the United States of any products for which the Company exercises its option to co-develop and co-promote, for which the parties share profits and losses evenly.
Subject to earlier expiration in certain circumstances, the Sanofi Agreement expires on a licensed product-by-licensed product or profit-shared licensed product-by-profit-shared licensed product basis and country-by-country basis upon on the later of (1) the expiration of the last-to-expire patent with a valid claim covering the applicable licensed product in the applicable country, (2) the expiration of any regulatory exclusivity for the applicable licensed product in the applicable country or (3) ten years after the first commercial sale of the applicable licensed product in the applicable country covered by the Sanofi Agreement.
The Company identified the following promises in the Sanofi Agreement: (1) the research licenses, (2) the research services, (3) the obligation to share information during the research term and (4) the participation of alliance managers in the joint research committee and joint patent committee. The Company determined that the research licenses, the obligation to share information and the participation in the joint committees are not capable of being distinct from the research services due to the specialized nature of the research services to be provided by the Company, and, accordingly, the promises identified were combined as one single performance obligation. The Company also determined that Sanofi’s exclusive right to add up to two additional targets constitutes a material right as it represents a significant and incremental discount that Sanofi would not have received without entering into the Sanofi Agreement. The option to extend the license term does not represent a material right because it does not contain a significant and incremental discount.
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In order to determine the transaction price, the Company evaluated all the payments to be received during the duration of the contract. Certain milestone payments and additional fees were considered variable consideration, which were not included in the transaction price based on the most likely amount method as of November 30, 2023. The Company re-evaluates the transaction price in each reporting period and as uncertain events are resolved or other changes in circumstances occur. At the inception of the Sanofi Agreement, the Company determined that the transaction price consisted of the upfront payment of $55.0 million for three initial drug targets and $22.0 million for two additional targets. Subsequently, upon the achievement of research milestones, $11.0 million in variable consideration was added to the transaction price, which includes $4.0 million added during the three months ended November 30, 2023, and a cumulative effect was recorded as revenue in the period the transaction price increased. Revenue is recognized using the cost-based input method over the research term of 4.25 years, the revised research period that was agreed to in January 2021 in the First Sanofi Amendment, for certain targets, and 5.25 years, the revised research period due to the target substitutions in July 2022, for certain other targets.
Using the cost-based input method, which the Company determined most faithfully depicts the transfer of its performance obligation to Sanofi, the Company recognizes revenue based on actual costs incurred as a percentage of total estimated costs as the Company completes its performance obligation under the contract. Costs consist primarily of internal FTE and third-party contract costs related to the Sanofi Agreement. The cumulative effect of revisions to estimated costs to complete the Company’s performance obligation is recorded in the period in which changes are identified and amounts can be reasonably estimated. Total estimated costs are primarily driven by the number of estimated FTEs, which requires significant management judgment.
For the year ended November 30, 2023, the Company recognized collaboration revenue related to the Sanofi Agreement of $25.4 million, of which $21.0 million was included in deferred revenue as of November 30, 2022, and $2.6 million was related to performance obligations satisfied in previous periods. For the year ended November 30, 2022, the Company recognized collaboration revenue related to the Sanofi Agreement of $15.0 million, of which $14.0 million was included in deferred revenue as of November 30, 2021, and $0.6 million was related to performance obligations satisfied in previous periods. As of November 30, 2023, deferred revenue related to the Sanofi Agreement was $24.9 million, of which $20.3 million was current and includes $4.0 million in contract assets representing the unbilled amount related to the research milestones recognized in November 2023. As of November 30, 2022, deferred revenue related to the Sanofi Agreement was $46.2 million, of which $19.4 million was current and includes $1.0 million in contract assets representing the unbilled amount related to the research milestone recognized in November 2022.
Pfizer
In September 2023, the Company entered into a strategic collaboration with Seagen Inc. (now a part of Pfizer Inc.) (the Pfizer Agreement) to develop a suite of targeted protein degraders against multiple targets nominated by Pfizer that are suitable for antibody conjugation. Pfizer will be responsible for conjugating these degraders to antibodies to make Degrader-Antibody Conjugates (DACs), a new class of medicines for use in cancer treatment, and advancing these DAC drug candidates through preclinical and clinical development and commercialization.
Under the Pfizer Agreement, Pfizer has the option to obtain exclusive licenses to develop and commercialize certain degraders, while the Company retains an option for U.S. profit sharing and co-promotion on two products arising from the collaboration. The collaboration excludes the Company’s current internal protein degradation programs for which the Company retains all rights, and also excludes the Company’s future internal programs, provided that the Company has distinguished future programs as excluded from the scope of the collaboration.
For the targets nominated by Pfizer under the collaboration, the Company shall use commercially reasonable efforts to identify, synthesize, characterize and deliver targeted protein degraders that selectively bind to and degrade such targets. Development of licensed degraders, with the exception of licensed products for which the Company exercises its profit-share options, will be at Pfizer’s sole cost and expense. For the profit-share products, the parties will share net profits and net losses and global development costs, and the Company will be eligible to receive royalty and milestone payments on such optioned products.
Under the terms of the Pfizer Agreement, the Company received an upfront payment of $60.0 million. The Company is eligible to receive up to approximately $3.4 billion in contingent payments based on specified research, development, regulatory and commercial milestones across multiple programs, and is eligible for mid-single to low double digit percentage tiered royalties on future sales.
Subject to the exceptions described in the Pfizer Agreement, the Pfizer Agreement expires upon the first to occur of (1) the expiration of the last-to-expire option exercise period under the Pfizer Agreement if no such option has been exercised prior to such expiration and (2) the expiration of the last-to-expire royalty term under the Pfizer Agreement.
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The Company identified the following promises in the Pfizer Agreement: (1) the research licenses, (2) the research services, (3) the participation of a gatekeeper and an alliance managers and the participation in various joint committees, and (4) the obligation to share information during the research term. The Company determined that the research licenses, the participation in the joint committees and the obligation to share information are not capable of being distinct from the research services, and, accordingly, the identified promises were combined as one single performance obligation. The Company also determined that, at the inception of the Pfizer Agreement, Pfizer’s options to obtain an exclusive development, manufacturing and commercialization license for each collaboration target and to extend the four-year research term do not represent material rights and are not considered performance obligations because they do not contain a significant and incremental discount. Additionally, Pfizer’s target reservation right is not a performance obligation as it is an exclusivity right and an attribute of other performance obligations in the Pfizer Agreement, such as the research licenses, and does not require any specific actions from the Company.
In order to determine the transaction price, the Company evaluated all the payments to be received during the duration of the contract. Milestone payments and additional fees were considered variable consideration, which were not included in the transaction price based on the most likely amount method as of November 30, 2023. The Company re-evaluates the transaction price in each reporting period and as uncertain events are resolved or other changes in circumstances occur. The Company determined that the transaction price at the inception of the Pfizer Agreement consisted of the upfront payment of $60.0 million. The Company has not yet achieved any research milestones and no variable consideration has been added to the transaction price. The transaction price is recognized as collaboration revenue using the cost-based input method over the estimated research term of four years , which represents the estimated period to complete the identified deliverables. Additionally, the Company considered the impact of Pfizer terminating the Pfizer Agreement prior to the completion of the research services during the initial four-year research term and determined that there were significant economic costs to Pfizer for doing so, and as such, did not adjust the contract term.
Using the cost-based input method, which the Company determined most faithfully depicts the transfer of its performance obligation to Pfizer, the Company recognizes revenue based on actual costs incurred as a percentage of total estimated costs as the Company completes its performance obligation under the contract. Costs consist primarily of internal FTE and third-party contract costs related to the Pfizer Agreement. The cumulative effect of revisions to estimated costs to complete the Company’s performance obligation is recorded in the period in which changes are identified and amounts can be reasonably estimated. Total estimated costs are primarily driven by the number of estimated FTEs, which requires significant management judgment.
4. Consolidated Balance Sheet Components
Property and Equipment, Net
Property and equipment, net, consisted of the following (in thousands):
| November 30, | |||||||||||
| 2023 | 2022 | ||||||||||
| Laboratory equipment | $ | $ | |||||||||
| Leasehold improvements | |||||||||||
| Computer equipment | |||||||||||
| Furniture and fixtures | |||||||||||
| Software | |||||||||||
| Software in progress | |||||||||||
| Total property and equipment, gross | |||||||||||
| Less: Accumulated depreciation and amortization | ( | ( | |||||||||
| Total property and equipment, net | $ | $ | |||||||||
For the years ended November 30, 2023 and 2022, depreciation and amortization expense was $7.5 million and $5.3 million, respectively, which includes amortization expense related to capitalized software of $1.4 million and $1.2 million, respectively. All long-lived assets are maintained in the United States.
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Accrued Expenses and Other Current Liabilities
Accrued expenses and other current liabilities consisted of the following (in thousands):
| November 30, | |||||||||||
| 2023 | 2022 | ||||||||||
| Accrued compensation | $ | $ | |||||||||
| Accrued contract research and lab supplies | |||||||||||
| Accrued professional services | |||||||||||
| Accrued taxes | |||||||||||
| Other | |||||||||||
| Total accrued expenses and other current liabilities | $ | $ | |||||||||
5. Fair Value Measurements
In accordance with the authoritative guidance on fair value measurements and disclosures under U.S. GAAP, the Company discloses and recognizes the fair value of its assets and liabilities using a hierarchy that prioritizes the inputs to valuation techniques used to measure fair value. The hierarchy gives the highest priority to valuations based upon unadjusted quoted prices in active markets for identical assets or liabilities (Level 1 measurements) and the lowest priority to valuations based upon unobservable inputs that are significant to the valuation (Level 3 measurements). The guidance establishes three levels of the fair value hierarchy as follows:
Level 1—Inputs that reflect unadjusted quoted prices in active markets for identical assets or liabilities that the Company has the ability to access at the measurement date;
Level 2—Inputs other than quoted prices included within Level 1 that are observable for the asset or liability either directly or indirectly, including inputs in markets that are not considered to be active; and
Level 3—Inputs that are unobservable.
Assets and liabilities measured at fair value are classified in their entirety based on the lowest level of input that is significant to the fair value measurement. The Company’s assessment of the significance of a particular input to the fair value measurement in its entirety requires management to make judgments and considers factors specific to the asset or liability.
The following tables present the Company’s investments, which consist of cash equivalents and available-for-sale marketable securities, that are measured at fair value on a recurring basis as of November 30, 2023 and 2022 (in thousands):
| November 30, 2023 | Level | Amortized cost | Unrealized gain | Unrealized loss | Estimated fair value | |||||||||||||||||||||||||||
| Money market funds | Level 1 | $ | $ | $ | $ | |||||||||||||||||||||||||||
| U.S. treasury securities | Level 1 | ( | ||||||||||||||||||||||||||||||
| Corporate debt securities | Level 2 | ( | ||||||||||||||||||||||||||||||
| U.S. government agency securities | Level 2 | ( | ||||||||||||||||||||||||||||||
| Long-term marketable securities: | ||||||||||||||||||||||||||||||||
| U.S. government agency securities | Level 2 | ( | ||||||||||||||||||||||||||||||
| Total | $ | $ | $ | ( | $ | |||||||||||||||||||||||||||
| Included in cash and cash equivalents | $ | $ | $ | $ | ||||||||||||||||||||||||||||
| Included in marketable securities, current | $ | $ | $ | ( | $ | |||||||||||||||||||||||||||
| Included in marketable securities, non-current | $ | $ | $ | ( | $ | |||||||||||||||||||||||||||
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| November 30, 2022 | Level | Amortized cost | Unrealized gain | Unrealized loss | Estimated fair value | |||||||||||||||||||||||||||
| Money market funds | Level 1 | $ | $ | $ | $ | |||||||||||||||||||||||||||
| U.S. treasury securities | Level 1 | ( | ||||||||||||||||||||||||||||||
| Corporate debt securities | Level 2 | ( | ||||||||||||||||||||||||||||||
| U.S. government agency securities | Level 2 | ( | ||||||||||||||||||||||||||||||
| Corporate commercial paper | Level 2 | |||||||||||||||||||||||||||||||
| Foreign government securities | Level 2 | ( | ||||||||||||||||||||||||||||||
| Long-term marketable securities: | ||||||||||||||||||||||||||||||||
| U.S. treasury securities | Level 1 | ( | ||||||||||||||||||||||||||||||
| Corporate debt securities | Level 2 | ( | ||||||||||||||||||||||||||||||
| U.S. government agency securities | Level 2 | ( | ||||||||||||||||||||||||||||||
| Total | $ | $ | $ | ( | $ | |||||||||||||||||||||||||||
| Included in cash and cash equivalents | $ | $ | $ | $ | ||||||||||||||||||||||||||||
| Included in marketable securities, current | $ | $ | $ | ( | $ | |||||||||||||||||||||||||||
| Included in marketable securities, non-current | $ | $ | $ | ( | $ | |||||||||||||||||||||||||||
The following table summarizes the available-for-sale marketable securities in an unrealized loss position for which an allowance for credit losses has not been recorded as of November 30, 2023 and 2022, aggregated by investment category and length of time in a continuous unrealized loss position (in thousands):
| Less than 12 months | Greater than 12 months | Total | ||||||||||||||||||||||||||||||||||||
| November 30, 2023 | Fair Value | Gross Unrealized Loss | Fair Value | Gross Unrealized Loss | Fair Value | Gross Unrealized Loss | ||||||||||||||||||||||||||||||||
| U.S. treasury securities | $ | $ | ( | $ | $ | ( | $ | $ | ( | |||||||||||||||||||||||||||||
| Corporate debt securities | ( | ( | ||||||||||||||||||||||||||||||||||||
| U.S. government agency securities | ( | ( | ( | |||||||||||||||||||||||||||||||||||
| Total | $ | $ | ( | $ | $ | ( | $ | $ | ( | |||||||||||||||||||||||||||||
| Less than 12 months | Greater than 12 months | Total | ||||||||||||||||||||||||||||||||||||
| November 30, 2022 | Fair Value | Gross Unrealized Loss | Fair Value | Gross Unrealized Loss | Fair Value | Gross Unrealized Loss | ||||||||||||||||||||||||||||||||
| U.S. treasury securities | $ | $ | ( | $ | $ | ( | $ | $ | ( | |||||||||||||||||||||||||||||
| Corporate debt securities | ( | ( | ( | |||||||||||||||||||||||||||||||||||
| U.S. government agency securities | ( | ( | ( | |||||||||||||||||||||||||||||||||||
| Foreign government securities | ( | ( | ||||||||||||||||||||||||||||||||||||
| Total | $ | $ | ( | $ | $ | ( | $ | $ | ( | |||||||||||||||||||||||||||||
The accrued interest receivable related to the Company’s marketable securities was $0.8 million and $1.1 million as of November 30, 2023 and 2022, respectively, and was included in and other current assets on the consolidated balance sheet. Long-term marketable securities held by the Company generally mature within two years from the balance sheet date.
The Company classifies its money market funds and U.S. treasury securities, which are valued based on quoted market prices in active markets with no valuation adjustment, as Level 1 assets within the fair value hierarchy.
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The Company classifies its marketable securities in corporate debt securities, U.S. government agency securities, corporate commercial paper and foreign government securities as Level 2 assets within the fair value hierarchy. The fair values of these marketable securities are estimated by taking into consideration valuations obtained from third-party pricing services. The pricing services utilize industry standard valuation models, including both income- and market-based approaches, for which all significant inputs are observable, either directly or indirectly, to estimate fair value. These inputs include reported trades of and broker/dealer quotes on the same or similar securities, issuer credit spreads, benchmark securities, prepayment/default projections based on historical data and other observable inputs. There were no
As of November 30, 2023 and 2022, the unrealized losses for available-for-sale marketable securities were non-credit related, and the Company does not intend to sell the securities that were in an unrealized loss position, nor will it be required to sell those securities before recovery of their amortized cost basis, which may be maturity. As of November 30, 2023 and 2022, no not
6. Commitments and Contingencies
Legal Proceedings
From time to time, the Company may be involved in legal proceedings in the ordinary course of business. The Company accrues a liability for such matters when it is probable that future expenditures will be made and that such expenditures can be reasonably estimated. Significant judgment is required to determine both probability and the estimated amount. Legal fees and other costs associated with such actions are expensed as incurred. As of November 30, 2023, the Company was not a party to any material legal proceedings.
Indemnifications
In the ordinary course of business, the Company often includes standard indemnification provisions in its arrangements with its partners, suppliers and vendors, among others. Pursuant to these provisions, the Company may be obligated to indemnify such parties for losses or claims suffered or incurred in connection with its service, breach of representations or covenants, intellectual property infringement or other claims made against such parties. These provisions may limit the time within which an indemnification claim can be made. It is not possible to determine the maximum potential amount under these indemnification obligations due to the limited history of prior indemnification claims and the unique facts and circumstances involved in each particular agreement. The Company has not incurred any material costs as a result of such indemnifications and has not accrued any liabilities related to such obligations in these consolidated financial statements as management believes such liability is immaterial.
In addition, the Company has entered into indemnification agreements with directors and certain officers and employees that will require the Company, among other things, to indemnify them against certain liabilities that may arise by reason of their status or service as directors, officers or employees. No demands have been made upon the Company to provide indemnification under such agreements, and thus, there are no claims that the Company is aware of that could have a material effect on the Company’s consolidated financial statements. The maximum potential amount of future payments the Company could be required to make under these indemnification agreements is not specified in the agreements. However, the Company currently has directors’ and officers’ insurance that reduces its exposure and may enable the Company to recover a portion of any future amounts paid.
Operating Leases
The Company leases office and laboratory facilities totaling approximately 57,902 square feet within the same building in San Francisco, California under several lease agreements. The terms of these lease agreements expire in April 2025. The Company has an option to renew these leases for an additional two years , and the renewal term has not been included in the lease term used to calculate the right-of-use asset and lease liability as it is not reasonably certain that the Company will exercise the option.
In July 2021, the Company entered into a lease agreement for the lease of approximately 19,320 square feet of office space in a different building in San Francisco, California. The lease commenced in December 2021 and will expire in June 2024, unless terminated earlier.
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In March 2022, the Company entered into a lease agreement for the lease of approximately 46,434 square feet of office space in The Woodlands, Texas. In August 2023, the lease agreement was amended to increase the square footage of the leased premise to 50,094 square feet. The amendment had no impact on the accounting for the lease. The Company has an option to renew for two additional terms of five years each, and the renewal terms have not been included in the lease term used to calculate the right-of-use asset and lease liability as it is not reasonably certain that the Company will exercise the option. The lease commenced in September 2023 when the underlying assets became available for use and will expire in March 2035.
The Company is required to pay base rent plus its proportionate share of operating expenses, as defined in the applicable lease agreement on all of its leases. Variable lease payments related to operating expenses including utilities, maintenance costs and real estate taxes were $6.2 million and $4.4 million for the years ended November 30, 2023 and 2022, respectively. Additionally, for the year ended November 30, 2022, certain leased premises were subject to additional variable lease payments related to landlord-owned improvements which were not estimable at lease inception. The right-of-use asset recognized in exchange for lease obligations for these additional variable lease payments was $1.2 million for the year ended November 30, 2022.
Operating lease expenses, excluding variable lease payments, were $6.8 million and $5.9 million for the years ended November 30, 2023 and 2022, respectively. Short-term lease expense was not material for the periods presented. As of November 30, 2023, the weighted average remaining lease term was 9.1 years and the weighted average discount rate was 6.45 %.
Other information related to leases were as follows (in thousands):
| Year Ended November 30, | |||||||||||
| 2023 | 2022 | ||||||||||
| Cash paid for amounts included in the measurement of lease liabilities: | |||||||||||
| Cash flows from operating leases | $ | $ | |||||||||
The undiscounted future non-cancellable lease payments under the Company’s lease agreements as of November 30, 2023 were as follows (in thousands):
| Year ending November 30, | Operating Leases | |||||||
| 2024 | $ | |||||||
| 2025 | ||||||||
| 2026 | ||||||||
| 2027 | ||||||||
| 2028 | ||||||||
| 2029 to 2035 | ||||||||
| Total undiscounted lease payments | ||||||||
| Less: imputed interest | ( | |||||||
| Total operating lease liabilities | $ | |||||||
| Operating lease liabilities, current | $ | |||||||
| Operating lease liabilities, net of current portion | ||||||||
| Total operating lease liabilities | $ | |||||||
7. Common Stock
The Company’s Restated Certificate of Incorporation authorizes the Company to issue up to 500,000,000 0.001 one vote. As of November 30, 2023, no dividends have been declared.
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In July 2022, the Company issued pre-funded warrants to purchase an aggregate of 6,814,920 shares of the Company’s common stock in RDOs at a price of $13.939 per pre-funded warrant. The pre-funded warrants were immediately exercisable, have an exercise price of $0.001 and may be exercised at any time after the date of issuance. A holder of pre-funded warrants may not exercise the warrant if the holder, together with its affiliates, would beneficially own more than 9.99 % of the number of shares of the Company’s common stock outstanding immediately after giving effect to such exercise. A holder of the pre-funded warrants may increase or decrease this percentage not in excess of 19.99 % by providing at least 61 days’ prior notice to the Company. As of November 30, 2023, there were pre-funded warrants to purchase an aggregate of 6,097,560 shares of the Company’s common stock that remained available for exercise.
The pre-funded warrants were classified as a component of permanent equity in the Company's consolidated balance sheet as they are freestanding financial instruments that are immediately exercisable, do not embody an obligation for the Company to repurchase its own shares and permit the holders to receive a fixed number of shares of common stock upon exercise. All of the shares underlying the pre-funded warrants have been included in the weighted-average number of shares of common stock used to calculate net loss per share attributable to common stockholders because the shares may be issued for little or no consideration, are fully vested and are exercisable after the original issuance date of the pre-funded warrants.
Common stock reserved for future issuance, on an as-if converted basis, as of November 30, 2023 and 2022, consists of the following:
| November 30, | |||||||||||
| 2023 | 2022 | ||||||||||
| Options to purchase common stock issued and outstanding | |||||||||||
| Shares available for future equity grants | |||||||||||
| Shares available for issuance under employee stock purchase plan | |||||||||||
| Restricted stock units issued and outstanding | |||||||||||
| Pre-funded warrants issued and outstanding | |||||||||||
| Total common stock reserved for future issuance | |||||||||||
8. Stock-Based Compensation
Equity Incentive Plans
The Company’s 2020 Equity Incentive Plan (the 2020 Plan) serves as the successor to the Company’s 2012 Equity Incentive Plan (together with the 2020 Plan, the Stock Plans) and provides for the granting of stock options, stock appreciation rights, restricted stock awards, RSUs, performance awards and stock bonus awards to employees, directors, consultants, independent contractors and advisors of the Company.
Under the Stock Plans, the Company generally grants stock-based awards with service-based vesting conditions only. Options granted typically vest under various different vesting terms over a four-year period and expire ten years from the date of grant. In the case of an incentive stock option granted to an employee who at the time of grant owns stock representing more than 10 % of the total combined voting power of all classes of stock, the exercise price shall be no less than 110 % of the fair value per share on the date of grant, and the award shall expire five years from the date of grant. In the case of all other stock options, the per share exercise price shall be no less than 100 % of the fair value per share on the date of grant. RSUs issued typically vest under various different vesting terms over a - to four-year period.
Following the effectiveness of the 2020 Plan on July 22, 2020, the Company ceased making grants under the 2012 Plan. However, the 2012 Plan continues to govern the terms and conditions of the outstanding awards granted under it. Shares of common stock subject to awards granted under the 2012 Plan that cease to be subject to such awards by forfeiture or otherwise will be available for issuance under the 2020 Plan.
As of November 30, 2023, there were 1,614,035 shares of common stock reserved for future issuance pursuant to the 2020 Plan.
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Stock options
Option activity under the Stock Plans is set forth below:
____________________________
| Number of options outstanding | Weighted- average exercise price | Weighted- average contractual life (in years) | Aggregate intrinsic value(1) (in thousands) | ||||||||||||||||||||
| Balances as of November 30, 2022 | $ | $ | |||||||||||||||||||||
| Options granted | |||||||||||||||||||||||
| Options exercised | ( | ||||||||||||||||||||||
| Options forfeited | ( | ||||||||||||||||||||||
| Balances as of November 30, 2023 | $ | $ | |||||||||||||||||||||
Options vested and expected to vest as of November 30, 2023(2) | $ | $ | |||||||||||||||||||||
| Options exercisable as of November 30, 2023 | $ | $ | |||||||||||||||||||||
(1) | The aggregate intrinsic values were calculated as the pre-tax difference between the exercise price of stock options and the quoted market price of the Company’s common stock on November 30, 2023 for all in‑the‑money stock options. The total intrinsic value of stock options exercised during the years ended November 30, 2023 and 2022 was $ | ||||
(2) | As of November 30, 2023, a total of | ||||
The fair value of options granted during the years ended November 30, 2023 and 2022 was estimated using the Black-Scholes option pricing model on the grant date using the following assumptions:
| November 30, | |||||||||||
| 2023 | 2022 | ||||||||||
| Expected term (years) | |||||||||||
| Expected volatility | |||||||||||
| Risk-free interest rate | |||||||||||
| Dividend yield | |||||||||||
The expected term represents the weighted-average period the stock-based payments are expected to remain outstanding. The expected term assumption for stock options was determined using the simplified method for “plain-vanilla” options. The expected stock price volatility assumption was determined by examining the historical volatilities for industry peers, as the Company does not have sufficient trading history for its common stock. The risk-free rate assumption is based on the U.S. Treasury instruments. The expected dividend assumption is based on the Company’s history and expectation of dividend payouts. The expected dividend yield is 0 % as the Company has not paid and does not anticipate paying dividends on its common stock.
During the years ended November 30, 2023 and 2022, the weighted-average grant date fair value of options granted was $7.22 and $11.80 per share, respectively.
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Restricted stock units
RSU activity under the Stock Plans is set forth below:
| Number of RSUs | Weighted-average grant date fair value | ||||||||||
| Balances as of November 30, 2022 | $ | ||||||||||
| RSUs granted | |||||||||||
| RSUs vested | ( | ||||||||||
| RSUs forfeited | ( | ||||||||||
| Balances as of November 30, 2023 | $ | ||||||||||
During the years ended November 30, 2023 and 2022, the weighted-average grant date fair value of RSUs granted was $10.53 and $19.11 per share, respectively, and the total fair value of RSUs vested was $7.9 million and $0.9 million, respectively.
Employee Stock Purchase Plan
Under the Company’s ESPP, eligible employees are entitled to purchase shares of common stock at a discount with accumulated payroll deductions. The purchase price for shares of common stock purchased under the ESPP will be 85 % of the lesser of the fair market value of the Company’s common stock on (i) the first trading day of the applicable offering period or (ii) the last trading day of each purchase period in the applicable offering period.
During the year ended November 30, 2023, the Company issued 266,964 shares pursuant to the ESPP at a weighted-average price of $8.35 per share. As of November 30, 2023, there were 1,530,281 shares of common stock reserved for issuance pursuant to the ESPP.
The fair value of ESPP granted during the years ended November 30, 2023 and 2022 was estimated using the Black-Scholes option pricing model on the grant date using the following assumptions:
| November 30, | |||||||||||
| 2023 | 2022 | ||||||||||
| Expected term (years) | |||||||||||
| Expected volatility | |||||||||||
| Risk-free interest rate | |||||||||||
| Dividend yield | |||||||||||
Stock-Based Compensation
Stock-based compensation expense related to the Stock Plans and the ESPP that is included in the Company’s consolidated statements of operations is as follows (in thousands):
| Year Ended November 30, | |||||||||||
| 2023 | 2022 | ||||||||||
| Research and development | $ | $ | |||||||||
| General and administrative | |||||||||||
| Total stock-based compensation | $ | $ | |||||||||
During the years ended November 30, 2023 and 2022, capitalized stock-based compensation related to internal-use software development was $74,000 and $69,000 , respectively. As of November 30, 2023, the total compensation cost related to stock-based awards not yet recognized was $53.1 million, which is expected to be amortized on a straight-line basis over the weighted-average remaining vesting period of approximately 2.09 years.
9. Defined Contribution Plan
The Company sponsors a defined-contribution savings plan under Section 401(k) of the Internal Revenue Code of 1986, as amended (the 401(k) Plan), which provides for the Company to make discretionary matching or discretionary annual contributions to the 401(k) Plan, for its employees. Substantially all of the Company’s employees are eligible to participate in the 401(k) Plan. Employees may contribute a percentage of their annual compensation to the plan, subject to statutory limitations. The Company has made contributions to the 401(k) Plan and recorded contribution expense of $1.0 million and $0.9 million during the years ended November 30, 2023 and 2022, respectively.
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10. Income Taxes
For the years ended November 30, 2023 and 2022, the Company did not record any current income tax benefit or provision. The Company has generated net operating losses (NOLs) since inception and has established a valuation allowance against its deferred tax assets due to the uncertainty surrounding the realization of such assets.
Loss before provision for income taxes includes the following component (in thousands):
| November 30, | |||||||||||
| 2023 | 2022 | ||||||||||
| Domestic | $ | ( | $ | ( | |||||||
| $ | ( | $ | ( | ||||||||
The effective tax rate differs from the federal statutory rate as follows:
| November 30, | |||||||||||
| 2023 | 2022 | ||||||||||
| Federal statutory income tax rate | % | % | |||||||||
| State income tax rate | |||||||||||
| Research and development tax credits | |||||||||||
| Stock-based compensation | ( | ( | |||||||||
| Change in valuation allowance | ( | ( | |||||||||
| Other | ( | ||||||||||
| Total | % | % | |||||||||
Deferred Tax Assets and Liabilities
Deferred income taxes reflect the net tax effects of loss and credit carryforwards and temporary differences between the carrying amounts of assets and liabilities for financial reporting purposes and the amounts used for income tax purposes. Significant components of the deferred tax assets for federal and state income taxes are as follows (in thousands):
| Year ended November 30, | |||||||||||
| 2023 | 2022 | ||||||||||
| Deferred tax assets: | |||||||||||
| Net operating loss carryforwards | $ | $ | |||||||||
| Research and development tax credits | |||||||||||
| Deferred revenue | |||||||||||
| Stock-based compensation | |||||||||||
| Accrued expenses and other liabilities | |||||||||||
| Operating lease liabilities | |||||||||||
| Capitalized research and experimental expenses | |||||||||||
| Gross deferred tax assets | |||||||||||
| Valuation allowance | ( | ( | |||||||||
| Total deferred tax assets | |||||||||||
| Deferred tax liabilities: | |||||||||||
| Operating lease right-of-use assets | ( | ( | |||||||||
| Total deferred tax liabilities | ( | ( | |||||||||
| Net deferred tax assets | $ | $ | |||||||||
Realization of the deferred tax assets is dependent upon future taxable income, the amount, if any, and timing of which are uncertain. The Company has established a valuation allowance to offset deferred tax assets as of November 30, 2023 and 2022 due to the uncertainty of realizing future tax benefits from its NOL carryforwards and other deferred tax assets. The valuation allowance increased by $55.4 million to $193.7 million during the year ended November 30, 2023, primarily related to an increase on the deferred tax asset for research and development (R&D) credits, NOL carryforwards and Section 174 research and development capitalization. The valuation allowance increased by $54.8 million to $138.4 million during the year ended November 30, 2022, primarily related to an increase on the deferred tax asset for R&D credits and NOL carryforwards.
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As of November 30, 2023, the Company had NOL carryforwards available to reduce future taxable income, if any, for federal and state income tax purposes of $269.3 million and $410.9 million, respectively. All outstanding federal NOL carryforwards were generated for tax years beginning after December 31, 2017, and carry forward indefinitely. State NOL carryforwards begin expiring in 2029 . As of November 30, 2023, the Company had federal and state research credit carryforwards of $32.3 million and $20.2 million, respectively. If not utilized, the federal credit carryforwards will begin expiring in 2032 and the state credits carry forward indefinitely .
Section 382 of the Internal Revenue Code of 1986, as amended (IRC) places a limitation on the utilization of NOL and tax credit carryforwards in the event of certain cumulative changes in the ownership interest of significant stockholders over a three-year period in excess of 50 percentage points. The Company has identified two ownership changes that have triggered a limitation on pre-change NOLs under Section 382. A majority of the Company’s pre-change NOLs remain available within the carryforward period provided by the IRC, subject to availability of taxable income. As a result of the ownership changes, the Company has determined that approximately $0.4 million of NOLs will expire unutilized, and as such, these NOLs are not reflected in the Company’s deferred tax asset balance.
Unrecognized Tax Benefits
The Company has recorded a liability related to uncertain tax positions in the financial statements. The Company has unrecognized tax benefits of $15.5 million as of November 30, 2023, all of which are offset by a full valuation allowance. There are no tax benefits included in the balance of unrecognized tax benefits that, if recognized, would affect the effective tax rate. There are no interest and penalties accrued as of November 30, 2023.
A reconciliation of the beginning and ending amounts of unrecognized income tax benefits during the years ended November 30, 2023 and 2022 is as follows (in thousands):
| Years ended November 30, | |||||||||||
| 2023 | 2022 | ||||||||||
| Balance at beginning of period | $ | $ | |||||||||
| Additions based on tax positions related to current period | |||||||||||
| Balance at end of period | $ | $ | |||||||||
The Company files income tax returns in the United States and in various states. In January 2019, the California Franchise Tax Board (FTB) initiated an examination of the Company’s California tax return for tax years ending in 2015, 2016, 2017 and 2018. During the year ended November 30, 2021, the FTB issued proposed audit assessments related to revenue sourcing and R&D credits. The Company did not agree with the FTB’s assessments and challenged the assessments. Pursuant to a measurement analysis, the Company has not recorded an unrecognized tax benefit related to the FTB’s sourcing position. The Company maintains an unrecognized tax benefit related to its California R&D credits for all years. All of the Company’s tax years will remain open for examination by the federal and state authorities for and four years , respectively, from the date of the utilization of any NOLs.
In August 2022, the U.S. Inflation Reduction Act (the Act) was enacted into law. The Act includes various tax provisions, including an excise tax on stock repurchases, expanded tax credits for clean energy incentives and a corporate alternative minimum tax that generally applies to U.S. corporations with adjusted financial statement income in excess of $1.0 billion. The Company does not expect the Act to have a material impact on its financial statements.
In December 2017, the Tax Cuts and Jobs Act (TCJA) was signed into law, significantly reforming the IRC. The TCJA contains a provision impacting Section 174 of the IRC whereby for tax years beginning on or after January 1, 2022, taxpayers are required to capitalize and amortize, rather than deduct, research and experimental (R&E) expenses. The R&E expenses under Section 174 must be amortized over five years for research performed in the United States and 15 years for research performed outside the United States. This rule became effective for the Company during the year ended November 30, 2023. For the year ended November 30, 2023, the Company recorded a deferred tax asset of $44.3 million pursuant to the provisions of Section 174 of the IRC.
145
11. Net Loss Per Share
The following table sets forth the computation of the Company’s basic and diluted net loss per share attributable to common stockholders, which excludes shares which are legally outstanding but subject to repurchase by the Company (in thousands, except share and per share data):
| Year Ended November 30, | |||||||||||
| 2023 | 2022 | ||||||||||
| Numerator: | |||||||||||
| Net loss | $ | ( | $ | ( | |||||||
| Denominator: | |||||||||||
Weighted-average number of shares outstanding, basic and diluted (1) | |||||||||||
| Net loss per share, basic and diluted | $ | ( | $ | ( | |||||||
(1) | The shares underlying the pre-funded warrants to purchase shares of the Company’s common stock have been included in the calculation of the weighted-average number of shares outstanding, basic and diluted, for the years ended November 30, 2023 and 2022. | ||||
The following potentially dilutive securities were excluded from the computation of the diluted net loss per share of common stock for the periods presented because their effect would have been anti-dilutive:
| Years ended November 30, | |||||||||||
| 2023 | 2022 | ||||||||||
| Options to purchase common stock issued and outstanding | |||||||||||
| Options early exercised subject to vesting | |||||||||||
| Restricted stock units issued and outstanding | |||||||||||
| Shares expected to be purchased under employee stock purchase plan | |||||||||||
| Total | |||||||||||
12. Related Party Transactions
The Company’s Chief Financial Officer is a trustee for the multiple employer welfare association that facilitates the acquisition and administration of the Company’s healthcare plans. Expenses related to the healthcare plan premiums were $4.4 million and $4.0 million for the years ended November 30, 2023 and 2022, respectively. As of November 30, 2023 and 2022, the amount recorded in accounts payable and accrued expenses and other current liabilities in connection with this healthcare plan provider was not material.
146
Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure
None.
Item 9A. Controls and Procedures
Evaluation of Disclosure Controls and Procedures
Our management, with the participation of our President and Chief Executive Officer (CEO) and our Chief Financial Officer (CFO), our principal executive officer and principal accounting and financial officer, respectively, have evaluated the effectiveness of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as amended (the Exchange Act) as of November 30, 2023.
Disclosure controls and procedures are controls and other procedures that are designed to ensure that information required to be disclosed in our reports filed or submitted under the Exchange Act is recorded, processed, summarized and reported within the time periods specified in the Securities and Exchange Commission’s rules and forms. Disclosure controls and procedures include controls and procedures designed to ensure that information required to be disclosed in our reports filed under the Exchange Act is accumulated and communicated to management, including our CEO and our CFO, to allow timely decisions regarding required disclosure. Based on their evaluation, the CEO and CFO have concluded that our disclosure controls and procedures were effective as of November 30, 2023.
Management’s Report on Internal Control over Financial Reporting
Our management is responsible for establishing and maintaining adequate internal control over financial reporting, as such term is defined in Exchange Act Rules 13a-15(f) and 15d-15(f). Internal control over financial reporting has inherent limitations. Internal control over financial reporting is a process that involves human diligence and compliance and is subject to lapses in judgment and breakdowns resulting from human failures. Internal control over financial reporting also can be circumvented by collusion or improper management override. Because of such limitations, there is a risk that material misstatements will not be prevented or detected on a timely basis by internal control over financial reporting. However, these inherent limitations are known features of the financial reporting process. Therefore, it is possible to design safeguards into the process to reduce, though not eliminate, this risk.
Under the supervision and with the participation of our management, including our CEO and CFO, we conducted an evaluation of the effectiveness of our internal control over financial reporting as of November 30, 2023 based on the framework in “Internal Control — Integrated Framework” (2013) issued by the Committee of Sponsoring Organizations of the Treadway Commission. Based on this evaluation, our management concluded that our internal control over financial reporting was effective as of November 30, 2023.
This Annual Report on Form 10-K does not include an attestation report of our registered public accounting firm regarding internal control over financial reporting. For as long as we remain a “smaller reporting company” as defined by Rule 12b-2 of the Exchange Act and report less than $100 million of annual revenues in our most recent fiscal year, we intend to take advantage of the exemption permitting us not to comply with the requirement that our independent registered public accounting firm provide an attestation on the effectiveness of our internal control over financial reporting.
Changes in Internal Control Over Financial Reporting
There were no changes in our internal control over financial reporting identified in connection with the evaluation required by Rule 13a-15(d) and 15d-15(d) of the Exchange Act that occurred during the quarter ended November 30, 2023, that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.
Item 9B. Other Information
None.
Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspection
Not applicable.
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PART III
Item 10. Directors, Executive Officers and Corporate Governance
The information required by this item will be set forth in our definitive proxy statement for our 2024 Annual Meeting of Stockholders (Proxy Statement) to be filed with the Securities and Exchange Commission (SEC) within 120 days after the end of the fiscal year covered by this Annual Report on Form 10-K, and is incorporated herein by reference.
We have adopted a code of business conduct and ethics that applies to all employees, including our principal executive officer, principal financial officer, principal accounting officer or controller, or persons performing similar functions. The code of business conduct and ethics is available on our website at www.nurixtx.com. Amendments to, and waivers from, the code of business conduct and ethics that apply to any director, executive officer or persons performing similar functions will be disclosed at the website address provided above and, to the extent required by applicable regulations, on a Current Report on Form 8-K filed with the SEC.
Item 11. Executive Compensation
The information required by this item will be set forth in the Proxy Statement to be filed with the SEC within 120 days after the end of the fiscal year covered by this Annual Report on Form 10-K, and is incorporated herein by reference.
Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
The information required by this item will be set forth in the Proxy Statement to be filed with the SEC within 120 days after the end of the fiscal year covered by this Annual Report on Form 10-K, and is incorporated herein by reference.
Item 13. Certain Relationships and Related Transactions, and Director Independence
The information required by this item will be set forth in the Proxy Statement to be filed with the SEC within 120 days after the end of the fiscal year covered by this Annual Report on Form 10-K, and is incorporated herein by reference.
Item 14. Principal Accounting Fees and Services
The information required by this item will be set forth in the Proxy Statement to be filed with the SEC within 120 days after the end of the fiscal year covered by this Annual Report on Form 10-K, and is incorporated herein by reference.
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PART IV
Item 15. Exhibits, Financial Statement Schedules
The following documents are filed as part of this Annual Report on Form 10-K:
(1)Financial Statements
The financial statements filed as part of this Annual Report on Form 10-K are listed in the “Index to Financial Statements” under Part II, Item 8 of this Annual Report on Form 10-K.
(2)Financial Statement Schedules
Financial statement schedules have been omitted in this Annual Report on Form 10-K because they are not applicable, not required under the instructions, or the information requested is set forth in the financial statements or related notes thereto.
(3)Exhibits
The following is a list of exhibits filed with this Annual Report on Form 10-K incorporated herein by reference (numbered in accordance with Item 601 of Regulation S-K):
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EXHIBIT INDEX
| Incorporated by Reference | Filed or Furnished Herewith | |||||||||||||||||||||||||||||||||||||
| Exhibit Number | Description | Form | File No. | Exhibit | Filing Date | |||||||||||||||||||||||||||||||||
| 3.1 | 10-Q | 001-39398 | 3.1 | October 14, 2020 | ||||||||||||||||||||||||||||||||||
| 3.2 | 8-K | 001-39398 | 3.1 | December 16, 2022 | ||||||||||||||||||||||||||||||||||
| 4.1 | S-1 | 333-239651 | 4.1 | July 2, 2020 | ||||||||||||||||||||||||||||||||||
| 4.2 | S-1 | 333-239651 | 4.2 | July 2, 2020 | ||||||||||||||||||||||||||||||||||
| 4.3 | 10-K | 001-39398 | 4.3 | February 9, 2023 | ||||||||||||||||||||||||||||||||||
| 4.4 | 8-K | 001-39398 | 4.1 | July 8, 2022 | ||||||||||||||||||||||||||||||||||
| 10.1 | S-1 | 333-239651 | 10.1 | July 2, 2020 | ||||||||||||||||||||||||||||||||||
| 10.2* | S-1 | 333-239651 | 10.2 | July 2, 2020 | ||||||||||||||||||||||||||||||||||
| 10.3* | S-1/A | 333-239651 | 10.3 | July 20, 2020 | ||||||||||||||||||||||||||||||||||
| 10.4* | S-1/A | 333-239651 | 10.4 | July 20, 2020 | ||||||||||||||||||||||||||||||||||
| 10.5* | S-1/A | 333-239651 | 10.5 | July 20, 2020 | ||||||||||||||||||||||||||||||||||
| 10.6* | S-1 | 333-239651 | 10.11 | July 2, 2020 | ||||||||||||||||||||||||||||||||||
| 10.7* | S-1/A | 333-239651 | 10.7 | July 20, 2020 | ||||||||||||||||||||||||||||||||||
| 10.8* | 10-K | 001-39398 | 10.7 | February 16, 2021 | ||||||||||||||||||||||||||||||||||
| 10.9* | 10-K | 001-39398 | 10.9 | January 28, 2022 | ||||||||||||||||||||||||||||||||||
| 10.10* | 10-K | 001-39398 | 10.11 | January 28, 2022 | ||||||||||||||||||||||||||||||||||
| 10.11 | S-1 | 333-239651 | 10.8 | July 2, 2020 | ||||||||||||||||||||||||||||||||||
| 10.12 | 10-Q | 001-39398 | 10.2 | October 14, 2021 | ||||||||||||||||||||||||||||||||||
150
| 10.13 | 10-Q | 001-39398 | 10.1 | October 12, 2023 | ||||||||||||||||||||||||||||||||||
| 10.14 | 10-Q | 001-39398 | 10.1 | April 8, 2022 | ||||||||||||||||||||||||||||||||||
| 10.15 | 10-Q | 001-39398 | 10.2 | October 12, 2023 | ||||||||||||||||||||||||||||||||||
| 10.16†‡ | S-1 | 333-239651 | 10.9 | July 2, 2020 | ||||||||||||||||||||||||||||||||||
| 10.17 | 10-Q | 001-39398 | 10.2 | October 6, 2022 | ||||||||||||||||||||||||||||||||||
| 10.18‡ | 10-Q | 001-39398 | 10.3 | October 6, 2022 | ||||||||||||||||||||||||||||||||||
| 10.19†‡ | S-1 | 333-239651 | 10.10 | July 2, 2020 | ||||||||||||||||||||||||||||||||||
| 10.20† | 10-K | 001-39398 | 10.11 | February 16, 2021 | ||||||||||||||||||||||||||||||||||
| 10.21† | 10-Q | 001-39398 | 10.4 | October 6, 2022 | ||||||||||||||||||||||||||||||||||
| 10.22† | 10-Q | 001-39398 | 10.5 | October 6, 2022 | ||||||||||||||||||||||||||||||||||
| 10.23†‡ | 10-Q | 001-39398 | 10.6 | October 6, 2022 | ||||||||||||||||||||||||||||||||||
| 10.24†‡ | X | |||||||||||||||||||||||||||||||||||||
| 10.25†‡ | X | |||||||||||||||||||||||||||||||||||||
151
| 10.26 | S-3 | 333-258448 | 1.2 | August 4, 2021 | ||||||||||||||||||||||||||||||||||
| 21.1 | 10-K | 001-39398 | 21.1 | January 28, 2022 | ||||||||||||||||||||||||||||||||||
| 23.1 | X | |||||||||||||||||||||||||||||||||||||
| 24.1 | X | |||||||||||||||||||||||||||||||||||||
| 31.1 | X | |||||||||||||||||||||||||||||||||||||
| 31.2 | X | |||||||||||||||||||||||||||||||||||||
| 32.1§ | X | |||||||||||||||||||||||||||||||||||||
| 97.1 | X | |||||||||||||||||||||||||||||||||||||
| 101.INS | Inline XBRL Instance Document - the Instance Document does not appear in the Interactive Data File because its XBRL tags are embedded within the Inline XBRL document | X | ||||||||||||||||||||||||||||||||||||
| 101.SCH | Inline XBRL Taxonomy Extension Schema Document | X | ||||||||||||||||||||||||||||||||||||
| 101.CAL | Inline XBRL Taxonomy Extension Calculation Linkbase Document | X | ||||||||||||||||||||||||||||||||||||
| 101.DEF | Inline XBRL Taxonomy Extension Definition Linkbase Document | X | ||||||||||||||||||||||||||||||||||||
| 101.LAB | Inline XBRL Taxonomy Extension Label Linkbase Document | X | ||||||||||||||||||||||||||||||||||||
| 101.PRE | Inline XBRL Taxonomy Extension Presentation Linkbase Document | X | ||||||||||||||||||||||||||||||||||||
| 104 | Cover Page Interactive Data File (formatted as Inline XBRL and included in Exhibit 101) | X | ||||||||||||||||||||||||||||||||||||
| * | Indicates a management or compensatory plan or arrangement in which directors or executive officers are eligible to participate. | |||||||||||||||||||||||||||||||||||||
| † | Registrant has omitted portions of the exhibit as permitted under Item 601(b)(10) of Regulation S-K. | |||||||||||||||||||||||||||||||||||||
| ‡ | Registrant has omitted certain schedules pursuant to Item 601(a)(5) of Regulation S-K. | |||||||||||||||||||||||||||||||||||||
152
| § | The certifications furnished in Exhibits 32.1 hereto are deemed to accompany this Annual Report on Form 10-K and are not deemed “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liability of that section, nor shall they be deemed incorporated by reference into any filing under the Securities Act of the Exchange Act. | |||||||||||||||||||||||||||||||||||||
Item 16. Form 10-K Summary
None.
153
SIGNATURES
Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, as amended, the Registrant has duly caused this Report to be signed on its behalf by the undersigned, thereunto duly authorized.
| NURIX THERAPEUTICS, INC. | ||||||||
Date: February 15, 2024 | By: | /s/ ARTHUR T. SANDS | ||||||
Arthur T. Sands, M.D., Ph.D. President, Chief Executive Officer and Director | ||||||||
POWER OF ATTORNEY
KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below hereby constitutes and appoints Arthur T. Sands and Hans van Houte, and each of them, as his or her true and lawful attorneys-in-fact, proxies, and agents, each with full power of substitution, for him or her in any and all capacities, to sign any and all amendments to this Annual Report on Form 10-K, and to file the same, with all exhibits thereto and other documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorneys-in-fact, proxies, and agents full power and authority to do and perform each and every act and thing requisite and necessary to be done in connection therewith, as fully for all intents and purposes as he might or could do in person, hereby ratifying and confirming all that said attorneys-in-fact, proxies, and agents, or their or his or her substitute or substitutes, may lawfully do or cause to be done by virtue hereof.
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, this Report has been signed below by the following persons on behalf of the Registrant in the capacities and on the dates indicated.
| Name | Title | Date | ||||||||||||
/s/ ARTHUR T. SANDS | President, Chief Executive Officer and Director (Principal Executive Officer) | February 15, 2024 | ||||||||||||
| Arthur T. Sands, M.D., Ph.D. | ||||||||||||||
/s/ HANS VAN HOUTE | Chief Financial Officer (Principal Financial and Accounting Officer) | February 15, 2024 | ||||||||||||
| Hans van Houte | ||||||||||||||
/s/ DAVID L. LACEY | Chairman and Director | February 15, 2024 | ||||||||||||
| David L. Lacey, M.D. | ||||||||||||||
/s/ JULIA P. GREGORY | Director | February 15, 2024 | ||||||||||||
| Julia P. Gregory | ||||||||||||||
/s/ LORI A. KUNKEL | Director | February 15, 2024 | ||||||||||||
| Lori A. Kunkel, M.D. | ||||||||||||||
/s/ JUDITH A. REINSDORF | Director | February 15, 2024 | ||||||||||||
| Judith A. Reinsdorf, J.D. | ||||||||||||||
/s/ EDWARD C. SALTZMAN | Director | February 15, 2024 | ||||||||||||
| Edward C. Saltzman | ||||||||||||||
/s/ PAUL M. SILVA | Director | February 15, 2024 | ||||||||||||
| Paul M. Silva | ||||||||||||||
154
Exhibit 10.24
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [*], HAS BEEN OMITTED BECAUSE IT IS NOT MATERIAL AND WOULD LIKELY CAUSE COMPETITIVE HARM TO THE COMPANY IF PUBLICLY DISCLOSED.
FIFTH AMENDMENT TO COLLABORATION AND LICENSE AGREEMENT
This Fifth Amendment to Collaboration and License Agreement (this “Amendment”) is entered into as of November 3, 2023 (the “Amendment Date”) by and between Genzyme Corporation, a Massachusetts corporation (“Sanofi”), and Nurix Therapeutics, Inc., a Delaware corporation (“Nurix”). Sanofi and Nurix are each referred to herein by name or, individually, as a “Party” or, collectively, as the “Parties.”
Recitals
WHEREAS the Parties entered into that certain Collaboration and License Agreement (as amended by the Amendments, the “Agreement”), dated December 19, 2019, that certain First Amendment to Collaboration and License Agreement, dated January 6, 2021 (the “First Amendment”), that certain Second Amendment to Collaboration and License Agreement, dated December 16, 2021 (the “Second Amendment”), that certain Third Amendment to Collaboration and License Agreement, dated July 7, 2022 (the “Third Amendment”), and that certain Fourth Amendment to Collaboration and License Agreement, dated August 11, 2022 (the “Fourth Amendment” and, together with the First Amendment, the Second Amendment, and the Third Amendment, the “Amendments”); and
WHEREAS the Parties wish to amend the Agreement to modify the Research Plan for Collaboration Target [*] under Exhibit A under which Sanofi will conduct Research relating to [*], and to modify certain terms and conditions of the Agreement with respect to such Research as further described herein.
Now Therefore, in consideration of the foregoing premises and the mutual promises, covenants and conditions contained in this Amendment, in accordance with Section 18.5 of the Agreement, the Parties agree as follows:
1.Defined Terms. As used in this Amendment, capitalized terms, whether used in the singular or plural form, that are capitalized but not defined herein shall have the meanings ascribed to such terms in the Agreement.
2.Amendments.
(a)An amended Research Plan for the [*] is attached hereto as Exhibit A. Such Research Plan shall be deemed approved by the JRC as of the Amendment Date. For clarity:
(i)all pre-clinical research activities under such amended Research Plan, including those activities conducted by Sanofi or its Affiliates, shall be deemed to be Research under the Agreement and part of the Research Program for the [*];
(ii)nothing in this Amendment is intended to modify the Research Term, including with respect to such amended Research Plan for the [*];
(iii)in accordance with, and subject to the terms and conditions of, Section 2.1.1 (General) of the Agreement, each Party shall bear its own costs and expenses incurred by or on behalf of it or its respective Affiliates in the performance of such Party’s respective Research activities under such amended Research Plan;
(iv)in accordance with, and subject to the terms and conditions of, Section 12.1.1 (Research License to Nurix), Nurix may use [*] in its activities under the Research Plan for the [*], including for purposes of [*].
(b)Section 1.127 of the Agreement is hereby deleted in its entirety and replaced with the following:
1.127 “Licensed Product” means any pharmaceutical preparation in final form containing (a) a CTM (including any Development Candidate) that has relevant pharmacological activity and is Directed To a Collaboration Target, or (b) a Selected Target Binder or Collaboration [*] that is Directed To a Collaboration Target and itself has relevant pharmacological activity (each, a “Standalone Target Binder”), in each case that was identified (except for [*]), synthesized and Researched by or on behalf of Nurix or its Affiliates and/or, solely in the case of Collaboration [*], Sanofi or its Affiliates, in each case pursuant to a Research Plan, prior to the expiration of the applicable Collaboration Target Research Term (whether alone or as part of a Combination Product, and in all presentations and formulations including manner of delivery and dosage).
(c)Section 1.198 of the Agreement is hereby deleted in its entirety and replaced with the following:
1.198 “Reverted Product” means all CTMs, Target Binders, Standalone Target Binders and Development Candidates (and backups thereto) that are Directed To a Reverted Target, but in each case excluding any [*] and any CTMs comprising a [*]; provided, however, for clarity, if the [*] becomes a Reverted Target, then Reverted Products shall include all Collaboration [*] that are: (a) derived by [*] from Target Binders [*]; or (b) identified or developed by [*] using (i) [*] or (ii) [*].
(d)A new Section 1.246 is hereby added to the Agreement which shall provide as follows:
1.246 “Amended [*] Research Plan” means the amended Research Plan for the [*], attached as Exhibit A to Amendment No. 5 to the Agreement, as such plan may be further amended from time to time in accordance with this Agreement.
(e)A new Section 1.247 is hereby added to the Agreement which shall provide as follows:
1.247 “Collaboration [*]” means [*].
(f)A new Section 1.248 is hereby added to the Agreement which shall provide as follows:
1.248 “Collaboration [*]” means each [*].
(g)A new Section 1.249 is hereby added to the Agreement which shall provide as follows:
1.249 “[*] Sanofi Background IP” means Background IP Controlled by Sanofi consisting solely of: (a) Patents covering inventions that (i) were conceived or reduced to practice on or before [*] for the [*] (even if such Patents were applied for or issued after such
2
date), (ii) are [*] into a Collaboration [*] or [*] pursuant to Section 2.9.1 (Information Sharing), and (iii) [*], pursuant to Section 17.7.2 (Reversion); and (b) Know-How that (i) was in existence on or before [*] for the [*], (ii) is [*] under Part 2 ([*]) of the [*] and that [*] pursuant to Section 2.9.1 (Information Sharing), and (iii) [*] to Research, Develop, Manufacture, or Commercialize a Reverted Product that is Directed To the [*]. [*].
(h)For clarity, Section 2.9.1 (Information Sharing) shall apply to all Research conducted by Sanofi under Part 2 ([*]) of the Amended [*] Research Plan. For further clarity, notwithstanding anything to the contrary in Section 2.9.2 (Development Candidate Data Package) or Section 2.9.3 (Nurix Key Data Report) of the Agreement, [*] results of Sanofi’s activities with respect to the Research under Part 2 ([*]) of the [*], as assigned to Sanofi under the [*].
(i)Section 2.10.3 of the Agreement is hereby deleted in its entirety and replaced with the following:
2.10.3 Research Results. All Research Results generated by or on behalf of (i) Nurix or (ii) solely in the case of Research Results related to Collaboration [*], either Party, in each case, under this Agreement or any Ancillary Agreement will be deemed the Confidential Information of both Parties, provided, however, that, if Sanofi fails to make a License Extension Fee for a Collaboration Target in accordance with Section 11.4 (License Extension Fee) prior to the expiration of the License Extension Fee Timeframe for such Collaboration License, then upon the expiration of the Target Exclusivity Period for such Target, all Research Results related to such Target that are generated by or on behalf of (i) Nurix or (ii) solely in the case of [*], either Party, in each case, in the performance of the Collaboration will be deemed the Confidential Information of Nurix, to the extent such Research Results do not include any data, results or other information pertaining to any CTM comprising a [*], any [*] or other Sanofi Materials, or, in the case of [*], any [*], in each case, which will be deemed the Confidential Information of Sanofi. For clarity: (a) this Section 2.10.3 (Research Results) shall not limit Sanofi’s ability to exercise the license set forth in Section 17.7.2(c), in accordance with the terms and conditions thereof; and (b) Sanofi’s ability to use and disclose such Nurix Confidential Information to Third Parties is governed by Article 14 (Confidentiality), including Sanofi’s right to make disclosures as further described in Section 14.3.1(e)(ii) under customary confidentiality and non-use obligations, to the extent necessary or reasonably useful for Sanofi to exercise its rights under the license set forth in Section 17.7.2(c).
(j)Section 7.1 of the Agreement is hereby deleted in its entirety and replaced with the following:
7.1 Manufacturing. Subject to the terms and conditions of this Agreement, (a) Nurix, at its sole cost and expense, will Manufacture, itself or through Third Parties, Research supplies (other than GLP tox supplies) for the Parties’ use of the respective CTMs, Target Binders and Development Candidates in the Field in the Territory under the Collaboration, provided that [*], provided, further, that Research supplies for Sanofi shall be limited to those specified in any Research Plan for Sanofi activities or otherwise as permitted under Section 2.7.4 (Activities to be Performed by Sanofi), and (b) Sanofi will have the sole and exclusive right to Manufacture (and will solely and exclusively control, at its discretion, the Manufacture of), itself or with or through its Affiliates, Sublicensees or other Third Parties, the GLP tox supplies, and supplies to support Development or Commercial activities for the respective Development Candidates, backups thereto and Licensed Products in the Field in the Territory. Subject to the Co-Development/Co-Commercialization Agreement and Profit/Loss Share Agreement (if executed), all such Manufacturing described in clause (b) will be at Sanofi’s sole cost and expense. Notwithstanding the foregoing, Sanofi shall have the right, but not the obligation, to Manufacture, itself or through Third Parties, Research supplies of [*] to enable Sanofi’s activities with respect to the Research of Collaboration [*],
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as assigned to Sanofi under the [*]. Upon request, Nurix shall provide Sanofi with [*] for Sanofi to be able to Manufacture such Research supplies (and Nurix shall [*]), including, without limitation, [*], for the relevant Collaboration [*].
(k)Notwithstanding anything in Article 8 (Nurix Options) to the contrary: (i) under Section 8.1 (Delivery of Profit/Loss Share Data Package to Nurix), if [*] is achieved for a Licensed Product that is [*] (a “[*]”) and/or a [*], then Sanofi will provide Nurix with a Profit/Loss Share Data Package for [*] Licensed Product Directed To the [*] that achieves [*]; and (ii) under Section 8.2 (Option Exercise), [*], Nurix may elect to exercise a Co-Development/Co-Promotion Option for [*], in each case, after receiving the Profit/Loss Share Data Package for [*]. If (a) Nurix elects to exercise the Co-Development/Co-Promotion Option for [*] after receiving such Profit/Loss Share Data Package and (b) [*], then Sanofi will [*] for the [*]; provided that, for clarity, [*], which [*]. [*].
(l)Section 9.4.1 of the Agreement is hereby deleted in its entirety and replaced with the following:
9.4.1 JRC Decisions. Each Party will have one vote at the JRC. The JRC will endeavor to make decisions by consensus. In the absence of consensus, any dispute will be escalated to the Executive Officers, and if the Executive Officers are unable to resolve such dispute within [*] Business Days after such matter has been referred to them then (a) for matters relating to [*], Nurix shall have final decision-making ability; provided that, Sanofi shall have final decision-making ability for matters relating to [*], and (b) for all other matters and any matter overseen by the JRC, Sanofi shall have final decision-making ability. For clarity, Nurix shall not use its final decision-making ability to (i) [*]; (ii) [*] or (iii) [*].
(m)The additions to Schedule 1.188 (Research Milestone Event Criteria) that were effected by Exhibit B to the Fourth Amendment are hereby deleted and replaced by the language in Exhibit B attached to this Amendment to the Agreement, solely with respect to [*]. For clarity, with respect to [*], Schedule 1.188 shall remain unchanged.
(n)For clarity: (1) all Inventions made or created solely by Sanofi’s or its Affiliates’ employees, independent contractors or consultants in the course of conducting activities under Part 2 ([*]) of the [*] and Part 2 ([*]) of the [*] will be Foreground IP [*] in accordance with Section 13.1.1 (General); and (2) such Foreground IP (A) is licensed to Nurix in accordance with Section 12.1.1 (Research License to Nurix), including for purposes of the Research to be conducted by Nurix or its Affiliates under Part 1 of the [*], and (B) would be [*].
(o)Section 17.7.2 of the Agreement is hereby deleted in its entirety and replaced with the following:
17.7.2 Reversion.
(a) Sanofi hereby grants to Nurix (i) [*] license, under [*] to Develop, Manufacture and Commercialize all Reverted Products in the Field in each applicable country in the Territory, subject to Nurix’s obligations under Section 2.10.1 (Target Exclusivity), (ii) solely in the case of [*], subject to Nurix’s obligations under Section 2.10.1 (Target Exclusivity), and (iii) solely in the case of [*], subject to Nurix’s obligations under Section 2.10.1 (Target Exclusivity). Nurix will only exercise its rights under the foregoing license in accordance with Section 12.2 (Expiration; License Term Extension), if Sanofi fails to make the License Extension Fee for the applicable Collaboration Target in accordance with Section 11.4 (License Extension Fee) prior to the expiration of the License Extension Fee Timeframe for such Collaboration License, and will only exercise its rights under the foregoing license with respect to Reverted Products in existence as of the expiration date of the applicable
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Collaboration License. For clarity, Sanofi shall retain the right to use [*], and all such other intellectual property rights, Patents or Know-How owned or Controlled by Sanofi for [*] other than with respect to a Reverted Product. Nurix shall have the right to terminate all or any portion of the rights granted to it under this Section 17.7.2 (Reversion), upon written notice to Sanofi. Subject to the previous sentence, Nurix shall pay to Sanofi royalties on Annual Net Sales (as such term is applied mutatis mutandis to Nurix and its Affiliates and sublicensees) of: (a) Reverted Products that [*] or, (b) solely with respect to [*], to the extent Covered by [*]. For clarity, with respect to [*], the license granted to Nurix in this Section 17.7.2 (Reversion) shall be [*].
(b) [*].
(c) Nurix hereby grants to Sanofi a [*] license, under the Research Results generated by Sanofi related to [*] that became the sole Confidential Information of Nurix upon the expiration of the Target Exclusivity Period for [*] in accordance with Section 2.10.3 (Research Results) to use for [*].
3.Miscellaneous.
(a)No Other Amendments. This Amendment shall be deemed to be a part of and incorporated into the Agreement. In the event of a conflict between this Amendment and the Agreement, this Amendment shall control. Except as expressly set forth in this Amendment, all of the terms and conditions of the Agreement, including without limitation [*], shall remain unchanged and are ratified and confirmed in all respects and remain in full force and effect.
(b)Entire Agreement. This Amendment, together with the Agreement and any exhibits or attachments thereto, contains the entire agreement by the Parties with respect to the subject matter hereof, and any reference to the Agreement shall refer to the Agreement, as amended by this Amendment.
(c)Counterparts. This Amendment may be executed in counterparts with the same effect as if both Parties had signed the same document. All such counterparts will be deemed an original, will be construed together and will constitute one and the same instrument. Any such counterpart, to the extent delivered by Electronic Delivery, will be treated in all manner and respects as an original executed counterpart and will be considered to have the same binding legal effect as if it were the original signed version thereof delivered in person. No Party will raise the use of Electronic Delivery to deliver a signature or the fact that any signature or agreement or instrument was transmitted or communicated through the use of Electronic Delivery as a defense to the formation of a contract, and each Party forever waives any such defense, except to the extent that such defense relates to lack of authenticity.
(d)Choice of Law. This Amendment and any Dispute arising from the performance or breach hereof will be governed by and interpreted in accordance with the laws of the State of New York, without giving effect to any choice of law rules.
[Signature Page Follows]
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In Witness Whereof, and intending to be legally bound hereby, the Parties have caused this Amendment to be executed by their respective duly authorized representatives as of the Amendment Date.
NURIX THERAPEUTICS, INC. By: /s/ Christine Ring Name: Christine Ring Title: Chief Legal Officer | GENZYME CORPORATION By: /s/ Matthew J. LaMarche Name: Matthew J. LaMarche Title: US Site Head, Integrated Drug Discovery | ||||
Exhibit 10.25
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [*], HAS BEEN OMITTED BECAUSE IT IS NOT MATERIAL AND WOULD LIKELY CAUSE COMPETITIVE HARM TO THE COMPANY IF PUBLICLY DISCLOSED.
COLLABORATION AND LICENSE AGREEMENT
by and between
NURIX THERAPEUTICS, INC.
and
SEAGEN INC.
dated as of September 6, 2023
TABLE OF CONTENTS
ARTICLE 1 DEFINITIONS | |||||
ARTICLE 2 DEGRADER TARGET SETS | |||||
2.1 Overview | |||||
2.2 Collaboration Degrader Target Sets | |||||
2.3 Reserved Degrader Target Sets | |||||
2.4 Addition of Degrader Targets | |||||
2.5 Removal of Collaboration Degrader Targets | |||||
2.6 Licensed Degrader Target Sets | |||||
2.7 [*] Licensed Degrader Target Set | |||||
2.8 Former Collaboration Degrader Target Sets | |||||
2.9 Former Licensed Degrader Target Sets | |||||
ARTICLE 3 GATEKEEPING | |||||
3.1 Proposed Degrader Target Sets | |||||
3.2 Gatekeeping | |||||
ARTICLE 4 RESEARCH | |||||
4.1 Joint Research Plans | |||||
4.2 Joint Research Activities | |||||
4.3 Joint Research Term Extension | |||||
4.4 Seagen Research Activities | |||||
4.5 Additional Conjugation Candidates | |||||
4.6 Seagen-Provided Property | |||||
4.7 Nurix-Provided Property | |||||
4.8 Information Sharing | |||||
4.9 Records Retention | |||||
4.10 Research Costs | |||||
ARTICLE 5 DEGRADER LICENSE OPTION | |||||
5.1 Degrader License Option | |||||
5.2 Degrader License Option Exercise | |||||
5.3 Degrader License Option Period Extension | |||||
5.4 Antitrust Filings | |||||
ARTICLE 6 DEVELOPMENT | |||||
6.1 Development | |||||
ARTICLE 7 REGULATORY | |||||
7.1 Regulatory Matters | |||||
7.2 Regulatory Materials | |||||
7.3 Right of Reference; Access to Data | |||||
ARTICLE 8 MANUFACTURING; PHARMACOVIGILANCE | |||||
8.1 General | |||||
ARTICLE 9 COMMERCIALIZATION | |||||
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9.1 Commercialization Responsibility | |||||
9.2 Commercialization Diligence | |||||
ARTICLE 10 GOVERNANCE | |||||
10.1 Joint Steering Committee | |||||
10.2 Joint Research Committee | |||||
10.3 Joint Research Teams | |||||
10.4 Joint Patent Committee | |||||
10.5 Alliance Manager | |||||
10.6 Committee Decisions | |||||
10.7 Scope of Committee Authority | |||||
10.8 Day-to-Day Responsibilities | |||||
10.9 No Services | |||||
ARTICLE 11 U.S. PROFIT-SHARE OPTION | |||||
11.1 U.S. Profit-Share Option | |||||
11.2 Exercise of Profit-Share Option | |||||
11.3 U.S. Profit-Share Opt-In Veto | |||||
11.4 Nurix Opt-Out | |||||
ARTICLE 12 ASSISTANCE; TRANSITION; UPSTREAM LICENSE AGREEMENTS | |||||
12.1 Assistance | |||||
12.2 Know-How Transfer | |||||
12.3 Upstream License Agreements | |||||
ARTICLE 13 FINANCIAL TERMS | |||||
13.1 Upfront Consideration | |||||
13.2 Joint Research Term Extension Fee | |||||
13.3 Degrader Target Set [*] Reservation Fee | |||||
13.4 Research Milestones | |||||
13.5 Degrader License Option Period Extension Fee | |||||
13.6 Degrader License Fee | |||||
13.7 Development and Regulatory Milestones | |||||
13.8 Sales-Based Milestones | |||||
13.9 Invoice and Payment of Milestone Payments | |||||
13.10 Royalties | |||||
13.11 Additional Payment Terms | |||||
ARTICLE 14 LICENSE GRANT; EXCLUSIVITY | |||||
14.1 Research Licenses | |||||
14.2 Licensed Degrader License | |||||
14.3 Reversion Licenses | |||||
14.4 Subcontracting | |||||
14.5 Sublicensing | |||||
14.6 Retained Rights | |||||
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14.7 Negative Covenant | |||||
14.8 Certain Uses of Foreground IP | |||||
14.9 Exclusivity | |||||
ARTICLE 15 INTELLECTUAL PROPERTY MATTERS | |||||
15.1 Ownership | |||||
15.2 Prosecution and Maintenance of Foreground IP | |||||
15.3 Enforcement or Defense | |||||
15.4 Defense of Third Party Infringement Claims | |||||
15.5 Recovery | |||||
ARTICLE 16 CONFIDENTIALITY | |||||
16.1 Nondisclosure and Non-Use | |||||
16.2 Exceptions | |||||
16.3 Authorized Disclosure | |||||
16.4 Residual Knowledge | |||||
16.5 Terms of this Agreement | |||||
16.6 Securities Filings; Disclosure under Applicable Law | |||||
16.7 Publicity | |||||
16.8 Publications | |||||
16.9 Use of Names | |||||
16.10 Clinical Trials Registry | |||||
ARTICLE 17 REPRESENTATIONS AND WARRANTIES; CLOSING CONDITIONS; COVENANTS | |||||
17.1 Representations and Warranties of Each Party | |||||
17.2 Representations and Warranties of Nurix | |||||
17.3 Representations and Warranties of Seagen | |||||
17.4 Covenants | |||||
17.5 Disclaimer | |||||
ARTICLE 18 INDEMNIFICATION; INSURANCE | |||||
18.1 Indemnification | |||||
18.2 Indemnification Procedure | |||||
18.3 Insurance | |||||
18.4 Limitation of Liability | |||||
ARTICLE 19 TERM AND TERMINATION | |||||
19.1 Term; Expiration | |||||
19.2 Termination | |||||
19.3 Effects of Expiration and Termination | |||||
19.4 Surviving Provisions | |||||
ARTICLE 20 MISCELLANEOUS | |||||
20.1 Severability | |||||
20.2 Notices | |||||
20.3 Force Majeure | |||||
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20.4 Assignment; Change of Control | |||||
20.5 Waivers, Amendments and Modifications | |||||
20.6 Choice of Law; Dispute Resolution; Jurisdiction | |||||
20.7 Relationship of the Parties | |||||
20.8 Fees and Expenses | |||||
20.9 Third Party Beneficiaries | |||||
20.10 Entire Agreement | |||||
20.11 Counterparts | |||||
20.12 Equitable Relief; Cumulative Remedies | |||||
20.13 Interpretation | |||||
20.14 Further Assurances | |||||
SCHEDULES
Schedule 2.2.1 Initial Degrader Target Sets
Schedule 4.6 Form of Material Transfer Agreement
Schedule 10.3.1 Initial Joint Research Team Membership
Schedule 11.1A Profit-Share Product Agreement Terms
Schedule 11.1B Co-Promotion Agreement Terms
Schedule 16.7.1 Nurix Press Release
Schedule 17.2(a) Nurix Patents
EXHIBITS
[*]
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COLLABORATION AND LICENSE AGREEMENT
This COLLABORATION AND LICENSE AGREEMENT (this “Agreement”) is entered into as of September 6, 2023 (the “Effective Date”) by and between Nurix Therapeutics, Inc., a Delaware corporation (“Nurix”), and Seagen Inc., a Delaware corporation (“Seagen”). Nurix and Seagen are each referred to herein by name or as a “Party” or, collectively, as the “Parties.”
RECITALS
WHEREAS, Nurix is a biotechnology company developing therapies that control ubiquitin E3 ligases, the key enzymes responsible for protein breakdown in human cells, which have applications in the treatment of various diseases.
WHEREAS, Seagen is a global biotechnology company with expertise in researching, developing and commercializing targeted therapies to treat cancer, and owns or controls proprietary technology relating to antibody drug conjugates.
WHEREAS, Seagen has identified, or will identify under the terms and conditions of this Agreement, [*] Collaboration Degrader Target Sets (as defined below), each containing [*] Degrader Targets (as defined below) that are homologues of each other.
WHEREAS, Nurix wishes to grant Seagen, and Seagen wishes to receive, an exclusive option (as further described herein) to obtain an exclusive license to develop and commercialize certain compounds created by Nurix during the Joint Research Term (as defined below) that are optimized (as construed in accordance with Section 20.13.2(n)) to bind to and cause the degradation of one (1) or more Collaboration Degrader Targets (as defined below) in an applicable Collaboration Degrader Target Set (as further described herein). Such Collaboration Degraders may be developed as stand-alone compounds or conjugated to antibodies thereby targeting such Collaboration Degraders to certain cell types via the binding of such antibodies to certain cell-surface proteins (as further described herein).
WHEREAS, the Parties may, to the extent permitted herein and during the Degrader License Option Period (as defined below) for a Collaboration Degrader Target Set, amend such Collaboration Degrader Target Set to remove Degrader Targets from or add one (1) or more available Degrader Targets to such Collaboration Degrader Target Set, including for the purposes of optimizing toxicity or efficacy.
WHEREAS, if Seagen exercises the Degrader License Option with respect to a Collaboration Degrader Target Set, then such Collaboration Degrader Target Set will be a Licensed Degrader Target Set, and Seagen will obtain an exclusive license to further research, develop, manufacture and commercialize pharmaceutical products containing the applicable Licensed Degraders created by Nurix and optimized to degrade only such Licensed Degrader Target Set (or Subsets of such Licensed Degrader Target Set) either as stand-alone compounds or as Degrader-Antibody Conjugates in the Field in the Territory (each as defined below), subject to the terms and conditions set forth herein.
NOW, THEREFORE, in consideration of the foregoing and the mutual agreements set forth below, and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties hereby agree as follows:
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ARTICLE 1
DEFINITIONS
Unless specifically set forth to the contrary herein, the following terms will have the respective meanings set forth below.
1.1“Accounting Standard” means, with respect to a Party or its Affiliate or Sublicensee, GAAP or IFRS, as such Party, Affiliate or Sublicensee uses for its financial reporting obligations, in each case, consistently applied.
1.2“Acquired Party Family” means, in the case of a Change of Control of a Party, such Party and all of its Affiliates that exist immediately prior to the Change of Control transaction and are subject to such Change of Control transaction, and any direct or indirect subsidiaries thereof created after such Change of Control transaction.
1.3“Acquiring Entity” means, in the case of a Change of Control of a Party, the successor in interest, resulting entity, assignee or purchaser, as applicable, of such Party and its Affiliates.
1.4“Acquiring Entity Family” means, in the case of a Change of Control of a Party, the Acquiring Entity and its Affiliates existing immediately prior to the closing of the Change of Control transaction together with any future Affiliates of such Party (but excluding the Acquired Party Family).
1.5“Action” means any claim, action, suit, arbitration, inquiry, audit, proceeding or investigation by or before any Governmental Authority, court, tribunal, arbitrator or arbitral body.
1.6“Additional Active” is defined in Section 1.41(a).
1.7“Additional Conjugation Candidate” is defined in Section 4.5 (Additional Conjugation Candidates).
1.8“Affiliate” means, with respect to a Party, any Person which, directly or indirectly through one (1) or more intermediaries, controls, is controlled by or is under common control with such Party for so long as such Person controls, is controlled by, or is under common control with such Party. For purposes of this Section 1.8 (“Affiliate”) and Section 1.30 (“Change of Control”) only, the term “control” (including, with correlative meanings, the terms “controlled by” and “under common control with”) as used with respect to a Person means: (a) direct or indirect ownership of fifty percent (50%) or more of the voting securities or other voting interest of any Person (including attribution from related parties); or (b) the possession, directly or indirectly, of the power to direct, or cause the direction of: the management and policies of such Person, whether through ownership of voting securities, by contract, as a general partner, as a manager or otherwise.
1.9“Agreement” is defined in the preamble to this Agreement.
1.10“Agreement Payments” means any and all payments paid or payable pursuant to this Agreement.
1.11“Alliance Manager” is defined in Section 10.5 (Alliance Manager).
1.12“Ancillary Agreements” means (a) each Nurix Opt-In Agreement (if and when executed); (b) each Reversion Product License Agreement (if and when executed); (c) each Other Reversion License Agreement (if and when executed); and (d) any other agreement entered into
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between the Parties (or their respective Affiliates) pursuant to this Agreement or an Ancillary Agreement.
1.13“Annual Ex-U.S. Net Sales” means, with respect to a Licensed Product, [*].
1.14“Annual Global Net Sales” means, on a Licensed Product-by-Licensed Product basis, [*], calculated in accordance with the Accounting Standard of Seagen, its Affiliate or Sublicensee, as applicable.
1.15“Antibody” means (a) any antibody (whether monospecific, bispecific or multi-specific, fully human, humanized or chimeric, monoclonal or polyclonal, multiple or single chain, recombinant, engineered or naturally occurring) that specifically binds to one (1) or more Cell-Surface Antigens or (b) any antigen binding domain, sequence, portion, derivative, variant or fragment of an antibody described in clause (a).
1.16“Antitrust Filing” is defined in Section 5.2 (Degrader License Option Exercise).
1.17“Antitrust Law” means any Applicable Law that is designed to prohibit, restrict or regulate actions having the purpose or effect of monopolization, lessening of competition or restraint of trade, including the HSR Act.
1.18“Applicable Law” means all applicable laws, statutes, rules, regulations, treaties (including tax treaties), orders, judgments or ordinances having the effect of law of any national, multinational, supranational, federal, state, provincial, county, city or other political subdivision, including, to the extent applicable, the FFDCA, GCP, GLP and GMP, as well as all applicable data protection and privacy laws, rules and regulations, including, to the extent applicable, the United States Department of Health and Human Services privacy rules under the Health Insurance Portability and Accountability Act and the Health Information Technology for Economic and Clinical Health Act and the EU Data Protection Directive (Council Directive 95/46/EC) and applicable laws implementing the EU Data Protection Directive and the General Data Protection Regulation (2016/679).
1.19“Arbitration Notice” is defined in Section 20.6.2(a).
1.20“Arbitrators” is defined in Section 20.6.3(a).
1.21“Auditor” is defined in Section 13.11.7(b) (Audit Rights).
1.22“Available Degrader Target” means each Degrader Target that, as of the time of such determination in accordance with Article 3 (Gatekeeping), is not (a) an Excluded Degrader Target, (b) a Collaboration Degrader Target, (c) a Licensed Degrader Target, or (d) in any Reserved Degrader Target Set.
1.23“Available Degrader Target Set” means a Degrader Target Set comprising only Available Degrader Targets.
1.24“Background IP” is defined in Section 15.1.1 (Background IP).
1.25“Bankruptcy Code” means Title 11 of the United States Code entitled “Bankruptcy,” as now and hereafter in effect, or any successor statute.
1.26“Business Day” means any day other than: (a) a Saturday or Sunday or any day on which commercial banks in San Francisco, California or New York, New York are authorized or required by Applicable Law to remain closed; or (b) December 26 through December 31.
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1.27“Calendar Quarter” means each of the three (3) month periods ending March 31, June 30, September 30 and December 31; provided, that the first Calendar Quarter of the Term extends from the Effective Date to the end of the then-current Calendar Quarter, and the last Calendar Quarter extends from the first day of the last Calendar Quarter during the Term until the effective date of the termination or expiration of this Agreement.
1.28“Calendar Year” means each period beginning on January 1 and ending on December 31; provided, that the first Calendar Year of the Term extends from the Effective Date to December 31 of the then-current Calendar Year, and the last Calendar Year extends from January 1 of the last Calendar Year during the Term until the effective date of the termination or expiration of this Agreement.
1.29“Cell-Surface Antigen” means the extracellular domain of any transmembrane cell-surface protein or other cell-surface molecule that is capable of binding to an Antibody.
1.30“Change of Control” means, with respect to a Party, from and after the Effective Date: (a) a merger or consolidation in which (i) such Party is a constituent party, or (ii) an Affiliate of such Party that directly or indirectly controls such Party is a constituent party, except in the case of either clause (i) or (ii) any such merger or consolidation involving such Party or such Affiliate in which the shares of capital stock of such entity outstanding immediately prior to such merger or consolidation continue to represent, or are converted into or are exchanged for shares of capital stock which represent, immediately following such merger or consolidation, fifty percent (50%) or more by voting power of the capital stock of (A) the surviving or resulting corporation or (B) a parent corporation of such surviving or resulting corporation, whether direct or indirect; (b) the sale, lease, transfer, exclusive license or other disposition, in a single transaction or series of related transactions, by such Party or an Affiliate of such Party of all or substantially all of the assets of such Party and its Affiliates taken as a whole and whether owned directly or indirectly through Affiliates (except where such sale, lease, transfer, exclusive license or other disposition is to an Affiliate of such Party existing immediately prior to such time); or (c) any “person” or “group,” as such terms are defined in Sections 13(d) and 14(d) of the U.S. Securities Exchange Act of 1934, in a single transaction or series of related transactions, becomes the beneficial owner as defined under the U.S. Securities Exchange Act of 1934, directly or indirectly, whether by purchase or acquisition or agreement to act in concert or otherwise, of fifty percent (50%) or more by voting power of the then-outstanding capital stock or other equity interests of such Party. Notwithstanding the foregoing, the following shall not constitute a Change of Control: (x) a sale of capital stock to underwriters in an underwritten public offering of a Party’s capital stock solely for the purpose of financing, or (y) the acquisition of securities of a Party or its Affiliate by any Person or group of Persons that acquires such securities in a transaction or series of related transactions the primary purpose of which is to obtain financing for such Party or Affiliate through the issuance of equity securities.
1.31“Clinical Trial” means any clinical investigation, as that term is defined in FDA regulations at 21 C.F.R. § 312.3, or a similar clinical investigation conducted on human subjects, as defined under Applicable Law outside the United States. Without limiting the foregoing, Clinical Trial includes any Phase 1 Clinical Trial, Phase 1/2 Clinical Trial, Phase 2 Clinical Trial, Phase 3 Clinical Trial or Pivotal Trial.
1.32“CMC” means chemistry manufacturing and controls.
1.33“Co-Promotion Agreement” is defined in Section 11.1 (U.S. Profit-Share Option).
1.34“Collaboration Degrader” means, with respect to a Collaboration Degrader Target Set, a Degrader that (a) is discovered, designed, synthesized, studied, characterized,
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optimized or validated under the applicable Research Program and during the applicable Joint Research Term with respect to such Collaboration Degrader Target Set under this Agreement; and (b) is Directed To such Collaboration Degrader Target Set. For clarity, (x) a Collaboration Degrader may or may not contain one (1) or more attachment moieties in its Proteasome Protein Binder, Degrader Spacer, or Degrader Target Binder that enable the conjugation of such Collaboration Degrader to a Degrader-Antibody Linker, and (y) a Collaboration Degrader Directed To a Collaboration Degrader Target Set that, as of the time of determination, is simultaneously both a Collaboration Degrader Target Set and a Licensed Degrader Target Set (as further described in Section 1.38 (“Collaboration Degrader Target Set”)) shall be a Collaboration Degrader Directed To such Collaboration Degrader Target Set and, simultaneously, a Licensed Degrader Directed To such Licensed Degrader Target Set, until the expiration of the Joint Research Term applicable to such Collaboration Degrader Target Set (subsequently, upon expiration of the applicable Joint Research Term, such Degrader shall be a Licensed Degrader and not a Collaboration Degrader).
1.35“Collaboration Degrader-Antibody Conjugate” means, with respect to a Collaboration Degrader Target Set, a Degrader-Antibody Conjugate that (a) contains a Collaboration Degrader Directed To such Collaboration Degrader Target Set, and (b) does not contain any Degrader that is not a Collaboration Degrader or a Licensed Degrader.
1.36“Collaboration Degrader Criteria” means, with respect to a Collaboration Degrader Target Set, the set of key properties (as described in the applicable Joint Research Plan) of Collaboration Degraders Directed To such Collaboration Degrader Target Set that must be demonstrated in order to achieve Research Milestone [*].
1.37“Collaboration Degrader Target” means each Degrader Target in a Collaboration Degrader Target Set from and after the applicable Degrader Target Set Selection Date (including, for clarity, each Initial Degrader Target Set and [*], and as each of the foregoing may be replaced by any applicable Replacement Degrader Target Set); provided, that such Degrader Target shall no longer be a Collaboration Degrader Target from and after the time that (a) such Degrader Target becomes a Former Collaboration Degrader Target, or (b) the applicable Collaboration Degrader Target Set becomes a Licensed Degrader Target Set and is no longer a Collaboration Degrader Target Set. For clarity, a Collaboration Degrader Target Set may become a Licensed Degrader Target Set and remain a Collaboration Degrader Target Set as further described in Section 1.38 (“Collaboration Degrader Target Set”).
1.38“Collaboration Degrader Target Set” means (a) each of the [*] Initial Degrader Target Sets, and (b) [*], in each case ((a) and (b)), as may be replaced with a Replacement Degrader Target Set in accordance with Section 2.2.3 (Collaboration Degrader Target Set Replacement Right) or revised in accordance with Section 2.4 (Addition of Degrader Targets), Section 2.5 (Removal of Collaboration Degrader Targets), or Section 2.6 (Licensed Degrader Target Sets), provided, that each such Collaboration Degrader Target Set described above shall no longer be considered a Collaboration Degrader Target Set upon the earlier of (i) such Collaboration Degrader Target Set becoming a Former Collaboration Degrader Target Set, or (ii) both expiration of the Joint Research Term applicable to such Collaboration Degrader Target Set and occurrence of the Degrader License Effective Date with respect to such Collaboration Degrader Target Set. For clarity, (x) there can be no more than [*]Collaboration Degrader Target Sets at any one time, and (y) if the Degrader License Effective Date with respect to a Collaboration Degrader Target Set occurs before the expiration of the Joint Research Term applicable to such Collaboration Degrader Target Set, such Collaboration Degrader Target Set shall be, simultaneously, both a Collaboration Degrader Target Set and a Licensed Degrader Target Set, until the expiration of such Joint Research Term (subsequently, upon expiration of the applicable Joint Research Term, such Degrader Target Set shall be a Licensed Degrader Target Set and not a Collaboration Degrader Target Set).
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1.39“Collaboration Degrader Target Set Replacement Right” is defined in Section 2.2.3 (Collaboration Degrader Target Set Replacement Right).
1.40“Collaboration Degrader Target Set Replacement Term” means:
(a)with respect to [*], the period of time beginning on the Effective Date and ending on the first to occur of (i) achievement of the [*] (i.e., Research Milestone [*]) with respect to such Initial Degrader Target Set, (ii) occurrence of the Degrader License Exercise Date with respect to such Initial Degrader Target Set, or (iii) the [*] of the Effective Date, and
(b)with respect to [*], the period of time beginning on the applicable Degrader Target Set Selection Date and ending on the first to occur of (i) achievement of the [*] (i.e., Research Milestone [*]) with respect to such [*], (ii) occurrence of the Degrader License Exercise Date with respect to such [*], or (iii) the later to occur of (A) the [*] of the Effective Date or (B) the [*] of the Degrader Target Set Selection Date for [*].
1.41“Combination Product” means:
(a)a Licensed Product that contains (i) a Licensed Degrader-Antibody Conjugate; and (ii) one (1) or more active pharmaceutical or biological ingredients for which no royalty would be due hereunder if such ingredients were sold separately (each, an “Additional Active”), sold as a single formulation for a single price;
(b)a Licensed Product that contains a Licensed Degrader-Antibody Conjugate that is sold for a single price but as separate formulations in a single package, or otherwise co-packaged, combined, or co-administered, with one (1) or more Additional Actives and, in each case, sold for a single price;
(c)a Licensed Product that does not contain a Licensed Degrader-Antibody Conjugate but contains (i) a Licensed Degrader; and (ii) one (1) or more Additional Actives, sold as a single dose for a single price; or
(d)a Licensed Product that does not contain a Licensed Degrader-Antibody Conjugate but contains a Licensed Degrader, that is sold for a single price but as separate formulations in a single package, or otherwise co-packaged, combined, or co-administered, with one (1) or more Additional Actives and, in each case, sold for a single price.
For clarity, under no circumstance shall the Antibody contained in a Licensed Degrader-Antibody Conjugate be considered an Additional Active of a Combination Product under this Agreement.
1.42“Commercialization” means any and all activities directed to the commercialization of a pharmaceutical or biological product, including marketing; detailing; promotion; market research; distributing; order processing; handling returns and recalls; booking sales; customer service; administering and commercially selling such product; and importing, exporting and transporting such product for commercial sale, as well all regulatory compliance with respect to the foregoing. For clarity, “Commercialization” (a) includes Manufacturing for Commercialization, and (b) does not include any Clinical Trials or other trials commenced after Regulatory Approval. When used as a verb, “Commercialize” means to engage in Commercialization. When used as an adjective, “Commercial” means pertaining to Commercialization.
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1.43“Commercially Reasonable Efforts” means (a) in general, except as provided in clauses (b) and (c) below, with respect to the efforts and resources to be expended by a Party in connection with such Party’s obligations under this Agreement, the [*] efforts and resources [*]; [*].
1.44“Committee” is defined in Section 10.1.1 (JSC Membership).
1.45“Competing Product” is defined in Section 14.9.5(c).
1.46“Confidential Information” means, with respect to a Party, all confidential and proprietary information Controlled by such Party, including chemical or biological materials, chemical structures, research plans, Commercialization plans, correspondence, customer lists, data, Development plans, Manufacturing plans, formulae, improvements, inventions, Know-How, processes, regulatory filings, reports, strategies, techniques or other proprietary information, in each case, that are disclosed or made available by or on behalf of such Party to the other Party or its representatives pursuant to this Agreement or any Ancillary Agreement, regardless of whether any of the foregoing are marked “confidential” or “proprietary” or communicated to the other Party by or on behalf of the Disclosing Party, and regardless of whether disclosed or made available in oral, written, visual, graphic, electronic, or any other form.
1.47“Control,” “Controls” or “Controlled” means, subject to Section 12.3 (Upstream License Agreements) and Section 20.4 (Assignment; Change of Control), with respect to any material, Patent, Know-How, other intellectual property right or Confidential Information, the ability of a Party or its Affiliates, as applicable (whether through ownership or license (other than a license granted in this Agreement or any Ancillary Agreement)) to grant to the other Party the licenses or sublicenses as provided herein, to otherwise disclose such Know-How, intellectual property right or Confidential Information to the other Party, or to grant access to such material to the extent not in violation of the terms of any then-existing agreement with any Third Party at the time such Party or its Affiliates, as applicable, would be required hereunder to grant the other Party such license or sublicenses as provided herein or to otherwise disclose such Know-How, intellectual property right or Confidential Information to the other Party. Notwithstanding the foregoing but subject to Section 12.3 (Upstream License Agreements), in the event of a Change of Control of a Party, then, whether or not this Agreement is assigned to the Acquiring Entity, any Know-How, Patent or other intellectual property rights or Regulatory Material owned or controlled by the Acquiring Entity Family shall not be deemed to be Controlled by such Party after the effective date of such Change of Control transaction for purposes of this Agreement.
1.48“Cover” means, with respect to a Valid Claim in a Patent and a given compound, formulation, process, method or product, that, but for ownership of or rights granted to a Person under such Patent, the developing, making, using, practice, offering for sale, promoting, selling, exporting or importing of such compound, formulation, process, method or product, as applicable, would infringe such Valid Claim, or in the case of a Patent right that is a patent application, would infringe a Valid Claim in such patent application if it were to issue as a Patent.
1.49“Cure Period” is defined in Section 19.2.1(a) (Material Breach).
1.50“Damages” means all losses, costs, claims, damages, judgments, liabilities and expenses (including reasonable attorneys’ fees and expenses and other documented and reasonable out-of-pocket costs in connection therewith).
1.51“Deemed Exercise” is defined in Section 5.2 (Degrader License Option Exercise).
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1.52“Degrader” means a compound that consists of a Proteasome Protein Binder, a Degrader Spacer, and a Degrader Target Binder.
1.53“Degrader-Antibody Conjugate” means a compound that consists of a Degrader linked via a Degrader-Antibody Linker to an Antibody.
1.54“Degrader-Antibody Linker” means any chemical composition used to conjugate a Degrader to an Antibody.
1.55“Degrader-Antibody Linker Technology” means any method (including method of manufacture) or technology used to conjugate a Degrader to an Antibody, in each case, excluding the chemical moiety itself that is on or part of a Degrader and used as an attachment point on the Degrader to enable the conjugation of such Degrader to a Degrader-Antibody Linker.
1.56“Degrader License” is defined in Section 14.2 (Licensed Degrader License).
1.57“Degrader License Effective Date” is defined in Section 5.4.2 (Effectiveness).
1.58“Degrader License Exercise Date” is defined in Section 5.4.1 (Filings).
1.59“Degrader License Fee” is defined in Section 13.6 (Degrader License Fee).
1.60“Degrader License Option” is defined in Section 5.1 (Degrader License Option).
1.61“Degrader License Option Exercise” is defined in Section 5.2 (Degrader License Option Exercise).
1.62“Degrader License Option Exercise Notice” is defined in Section 5.2 (Degrader License Option Exercise).
1.63“Degrader License Option Period” means, on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, the period beginning on the applicable Degrader Target Set Selection Date of such Collaboration Degrader Target Set and ending on the earlier of (a) the date on which the Degrader License Option for such Collaboration Degrader Target Set is (i) exercised or (ii) deemed exercised, in each case, as further described in Section 5.2 (Degrader License Option Exercise); and (b) [*] after the end of the applicable Joint Research Term for such Collaboration Degrader Target Set; provided, that the Degrader License Option Period may be extended by Seagen on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis by [*] by [*] in accordance with Section 5.3 (Degrader License Option Period Extension).
1.64“Degrader License Option Period Extension” is defined in Section 5.3 (Degrader License Option Period Extension).
1.65“Degrader License Option Period Extension Fee” is defined in Section 13.5 (Degrader License Option Period Extension Fee).
1.66“Degrader Spacer” means a chemical composition used for linking a Proteasome Protein Binder to a Degrader Target Binder under this Agreement.
1.67“Degrader Target” means an intracellular protein that is:
(a)identified by a GenBank protein accession number or by its amino acid sequence and coded by a genetic locus;
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(b)naturally occurring and encoded by (i) a mutant version of the genetic locus referred to in clause (a) or (ii) a splice variation of the RNA transcribed from the genetic locus referred to in clause (a) or clause (b)(i); or
(c)a naturally occurring post-translational modification to any protein referred to in clauses (a) or (b).
A protein falling under clause (a), together with proteins falling under clauses (b) or (c) by reference to such protein or the applicable genetic locus shall, collectively, be considered a single “Degrader Target” for purposes of this Agreement.
1.68“Degrader Target Binder” means any chemical moiety that selectively binds a Degrader Target (including (a) a portion of such moiety sufficient to convey such binding and (b) such moiety or portion thereof as incorporated in a Degrader).
1.69“Degrader Target Binder Patent” means any and all Patents included in the Foreground IP that Cover a Degrader Target Binder that selectively binds one (1) or more Degrader Targets in the applicable Licensed Degrader Target Set.
1.70“Degrader Target Screening Notice” is defined in Section 3.2.2 (Gatekeeper Responsibilities).
1.71“Degrader Target Set” means any set of one (1) or more Degrader Target(s); provided, that (a) all Degrader Targets in a Degrader Target Set must be Homologous Targets of each other, and (b) no Degrader Target Set may contain more than [*] Degrader Targets unless the Parties otherwise mutually agree in writing.
1.72“Degrader Target Set [*] Reservation Fee” is defined in Section 13.3 (Degrader Target Set [*] Reservation Fee).
1.73“Degrader Target Set Reservation Extension Notice” is defined in Section 2.3.3 (Designation and Payment for Reserved Degrader Target Sets).
1.74“Degrader Target Set Selection Date” means, (a) with respect to [*], the Effective Date, and (b) with respect to [*] and any Replacement Degrader Target Set, if applicable, the date that the Parties mutually agree on the initial Joint Research Plan for such Degrader Target Set as further described in Section 4.1 (Joint Research Plans).
1.75“DEL Library” means the DNA-encoded libraries Controlled by Nurix or its Affiliates and used by or on behalf of Nurix to identify Proteasome Protein Binders or Degrader Target Binders, as may be modified from time to time during the Term.
1.76“DEL Library Technology” means any Know-How Controlled by Nurix or its Affiliates and used by or on behalf of Nurix to (a) make the DEL Library, (b) screen the DEL Library against a biological target, (c) identify compounds in the DEL Library that bind to the target, or (d) develop a structure-binding relationship of the DEL Library compounds that bind to the biological target.
1.77“DEL Screen” means the screening of the DEL Library by Nurix in connection with the performance of its activities under a Joint Research Plan to discover Proteasome Protein Binders and/or Degrader Target Binders that may be used in Degraders under this Agreement.
1.78“Development” means clinical drug development activities and other non-clinical or preclinical development activities with respect to a pharmaceutical or biological product,
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including Clinical Trials (and other trials commenced after Regulatory Approval), test method development and stability testing; toxicology testing; formulation and Manufacturing process development, qualification, and validation; quality assurance and quality control for clinical supply; statistical analysis and report writing; preparation and submission of INDs and MAAs; medical and regulatory affairs with respect to the foregoing and all other activities necessary or useful or otherwise requested or required by a Regulatory Authority or as a condition or in support of obtaining or maintaining a Regulatory Approval or Pricing Approval; provided, however, that “Development” does not include “Research” (as defined herein). For clarity, “Development” includes Manufacturing for Development. When used as a verb, “Develop” means to engage in Development.
1.79“Development and Regulatory Milestone Event” is defined in Section 13.7 (Development and Regulatory Milestones).
1.80“Development and Regulatory Milestone Payment” is defined in Section 13.7 (Development and Regulatory Milestones).
1.81“Directed To” means:
(a)with respect to a Degrader and a single Degrader Target, that the Degrader at issue (i) [*]; (ii) [*] binds such Degrader Target, and (iii) degrades such Degrader Target of such Degrader Target;
(b)with respect to a Degrader and a Degrader Target Set that such Degrader is “Directed To” (as defined in clause (a) above) any one (1) or more Degrader Target(s) in such Degrader Target Set, and is not “Directed To” (as defined in clause (a) above) any Degrader Target(s) not in such Degrader Target Set; provided, that if the Degrader Target Set in question for purposes of this clause (b) is a Subset of another Degrader Target Set (such other Degrader Target Set, a “Parent Target Set”), the applicable Degrader may be (but is not necessarily) “Directed To” (as defined in clause (a) above) Degrader Target(s) in the Parent Target Set that are not in such Degrader Target Set (e.g., in the case of a Degrader that is “Directed To” (as defined in clause (a) above) both a Subset of a Parent Target Set and the Parent Target Set, itself); and
(c)with respect to an Antibody and a Cell-Surface Antigen, that such Antibody specifically binds to such Cell-Surface Antigen.
For clarity, (i) a Degrader may be “Directed To” (A) more than one Degrader Target and (B) both a Degrader Target Set and a Subset thereof, and (ii) an Antibody may be “Directed To” more than one Cell-Surface Antigen. A Degrader-Antibody Conjugate or Licensed Product will be deemed to be “Directed To” a Degrader Target or Degrader Target Set if such Degrader-Antibody Conjugate or Licensed Product contains a Degrader that is “Directed To” such Degrader Target or Degrader Target Set, as applicable.
1.82“Disclosing Party” is defined in Section 16.1 (Nondisclosure and Non-Use)
1.83“Dispute” is defined in Section 20.6.2(a).
1.84“DOJ” is defined in Section 5.4.1 (Filings).
1.85“Effective Date” is defined in the preamble to this Agreement.
1.86“Electronic Delivery” is defined in Section 20.11 (Counterparts).
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1.87“EMA” is defined in Section 1.227 (“Regulatory Authority”).
1.88“Enforcing Party” is defined in Section 15.3.3(d).
1.89[*].
1.90“Excluded Degrader Target” means any Degrader Target that is, as of the time of such determination in accordance with Section 3.1 (Proposed Degrader Target Sets), as applicable: (a) [*], (b) any Former Collaboration Degrader Target or Former Licensed Degrader Target, (c) [*], or (d) [*].
1.91“Exclusive Degrader Target Set” means each Degrader Target Set with respect to which Nurix has exclusivity obligations in accordance with Section 14.9.1 (Collaboration Degrader Target Set Exclusivity), Section 14.9.2 (Reserved Degrader Target Set Exclusivity), Section 14.9.3 (Licensed Degrader Target Set Exclusivity), or Section 14.9.4 ([*] Licensed Degrader Target Set Exclusivity).
1.92“Exclusivity Period” means,
(a)on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, the period of time beginning on the applicable Degrader Target Set Selection Date and ending upon (i) the termination or expiration of the applicable Degrader License Option Period (as may be extended in accordance with Section 5.3 (Degrader License Option Period Extension)) if the applicable Degrader License Option is not exercised prior to the expiration of the applicable Joint Research Term, or (ii) the expiration of the applicable Joint Research Term if the applicable Degrader License Option is exercised (including if deemed to be exercised under Section 5.2 (Degrader License Option Exercise)) prior to the expiration of the applicable Joint Research Term;
(b)on a Licensed Degrader Target Set-by-Licensed Degrader Target Set basis, the period of time beginning on the Degrader License Effective Date for such Licensed Degrader Target Set, and ending upon the earlier of (i) termination of the Degrader License with respect to such Licensed Degrader Target Set, or (ii) [*];
(c)on an [*] Licensed Degrader Target Set-by-[*] Licensed Degrader Target Set basis, the period of time beginning on [*] for a Licensed Product containing a Licensed Degrader (including any Licensed Degrader-Antibody Conjugate) that is Pan-Directed To such [*] Licensed Degrader Target Set until the earliest of (i) termination of the Degrader License with respect to such [*] Licensed Degrader Target Set, (ii) the date on which no further payments in or for [*] can be made under this Agreement with respect to Licensed Products containing Licensed Degraders (including any Licensed Degrader-Antibody Conjugate) that are Directed To the applicable Licensed Degrader Target Set (including, for Profit-Share Products, expiration of the relevant profit-sharing period as set forth in the applicable Profit-Share Product Agreement, subject to Section 11.4 (Nurix Opt-Out)), (iii) the [*] anniversary of the Degrader License Effective Date with respect to the applicable Licensed Degrader Target Set, or (iv) the occurrence of [*] for such applicable Licensed Degrader Target Set [*]; and
(d)on a Reserved Degrader Target Set-by-Reserved Degrader Target Set basis, the period beginning on the date a Degrader Target Set becomes a Reserved Degrader Target Set and ending on the date such Degrader Target Set ceases to be a Reserved Degrader Target Set, in each case, as described in Section 2.3 (Reserved Degrader Target Sets).
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1.93“Executive Officers” means: (a) with respect to Nurix, the Chief Executive Officer of Nurix or their designee or successor with appropriate decision-making authority; and (b) with respect to Seagen, Seagen’s [*] or their designee or successor with appropriate decision-making authority.
1.94“Existing Regulatory Materials” is defined in Section 7.2.1 (Existing Regulatory Materials).
1.95“Exploit” means to make, have made, import, use, sell, or offer for sale, including to research, Develop, Commercialize, register, Manufacture, have Manufactured, hold, or keep (whether for disposal or otherwise), have used, import, export, transport, distribute, promote, market, or have sold or otherwise dispose of.
1.96“FCPA” means the United States Foreign Corrupt Practices Act (15 U.S.C. § 78dd-1, et seq.) as amended.
1.97“FDA” is defined in Section 1.227 (“Regulatory Authority”).
1.98“FFDCA” means the United States Federal Food, Drug, and Cosmetic Act, 21 U.S.C. §§ 301 et seq., as it may be amended from time to time, and the rules, regulations, guidance, guidelines, and requirements promulgated or issued thereunder.
1.99“Field” means any and all uses.
1.100“First Commercial Sale” means, on a Licensed Product-by-Licensed Product and country-by-country basis, the first sale of such Licensed Product in such country for monetary value for use or consumption by the general public (following receipt of all Regulatory Approvals and, solely to the extent the marketing and sale of the relevant product without any Pricing Approvals is prohibited under Applicable Law, following receipt of any such Pricing Approvals, that are required in order to sell such Licensed Product in such country) and for which any of Seagen or its Affiliates or Sublicensees has invoiced sales of Licensed Products in the Territory; provided, however, that the following will not constitute a First Commercial Sale: (a) any sale to an Affiliate or Sublicensee, unless such Affiliate or Sublicensee is the last Person in the distribution chain of the Licensed Product; (b) any use of such Licensed Product in Clinical Trials or non-clinical research or Development activities with respect to such Licensed Product by or on behalf of a Party; or (c) any disposal or transfer of such Licensed Product for a bona fide charitable purpose, for compassionate use, as samples, and any similar use. For clarity, references herein to “First Commercial Sale” without reference to a specific country are to the First Commercial Sale in any country in the Territory.
1.101“First Indication” is defined in Section 13.7.1.
1.102“First Licensed Product” is defined in Section 13.7.2(b).
1.103“Floor” is defined in Section 13.10.2(d).
1.104“Foregone Milestones” is defined in Section 11.2.3 (Profit-Share Products).
1.105“Foreground Antibody/Conjugation IP” means any and all Foreground IP that is not Foreground DEL IP or Foreground Degrader IP and that primarily relates to any of the following: (a) one (1) or more Antibodies, (b) any modifications of an Antibody, (c) the conjugation of an Antibody to a Degrader, (d) a Degrader-Antibody Linker, or (e) Degrader-Antibody Linker Technology.
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1.106“Foreground Degrader IP” means any and all Foreground IP that primarily relates to the composition of matter of any Collaboration Degrader or Licensed Degrader, in each case, as a whole.
1.107“Foreground DEL IP” means any and all Foreground IP that primarily relates to any of the following: (a) the DEL Library; (b) DEL Library Technology; (c) Degrader Target Binders derived from DEL Screens (including any chemical moiety that serves as an attachment point thereon that enables the conjugation of a Degrader containing any such Degrader Target Binder to a Degrader-Antibody Linker, as and to the extent such chemical moiety is attached to such Degrader Target Binder); (d) any Proteasome Protein Binders (including any chemical moiety that serves as an attachment point thereon that enables the conjugation of a Degrader containing any such Proteasome Protein Binder to a Degrader-Antibody Linker, as and to the extent such chemical moiety is attached to such Proteasome Protein Binder); and (e) any Degrader Spacers (including any chemical moiety that serves as an attachment point thereon that enables the conjugation of a Degrader containing any such Degrader Spacer to a Degrader-Antibody Linker, as and to the extent such chemical moiety is attached to such Degrader Spacer), in each case (clauses (a)-(c)), that do not primarily relate to any of the following: (i) one (1) or more Antibodies, (ii) the conjugation of an Antibody to a Degrader, (iii) a Degrader-Antibody Linker, or (iv) Degrader-Antibody Linker Technology.
1.108“Foreground IP” is defined in Section 15.1.2 (Foreground IP).
1.109“Foreground Patent” means any and all Patents included in the Foreground IP.
1.110“Former Collaboration Degrader Target” means (a) each Degrader Target that is in a Former Collaboration Degrader Target Set, and (b) to the extent not included in clause (a), any other Removed Degrader Target.
1.111“Former Collaboration Degrader Target Set” is defined in Section 2.8 (Former Collaboration Degrader Target Sets).
1.112“Former Licensed Degrader Target” means each Degrader Target that is in a Former Licensed Degrader Target Set.
1.113“Former Licensed Degrader Target Set” is defined in Section 2.9 (Former Licensed Degrader Target Sets).
1.114“FTC” is defined in Section 5.4.1 (Filings).
1.115“FTE” is defined in Section 1.122 (“Global Development Costs”).
1.116“FTE Costs” is defined in Section 1.122 (“Global Development Costs”).
1.117“Gatekeeper” is defined in Section 3.2.1 (Appointment of Gatekeeper).
1.118“Gatekeeper Availability Notice” is defined in Section 3.2.2 (Gatekeeper Responsibilities).
1.119“GCP” means the applicable then-current ethical and scientific quality standards for designing, conducting, recording and reporting Clinical Trials as are required by applicable Regulatory Authorities or Applicable Law in the relevant jurisdiction, and as amended from time to time, including, in the United States, Good Clinical Practices established in FDA regulations set forth in 21 C.F.R. Parts 50, 54, 56, and 58 and analogous rules and regulations as promulgated or endorsed by applicable Regulatory Authorities outside the United States, including Guidelines for
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Good Clinical Practice – ICH Harmonized Tripartite Guideline (ICH E6), to the extent such standards are not less stringent than United States GCP.
1.120“Generic/Biosimilar Product” means, with respect to a given Licensed Product in a particular country in the Territory, a pharmaceutical or biological product that (a) is approved for use in such country pursuant to a Regulatory Approval process governing approval of a generic product or biosimilar product of such Licensed Product based on the then-current standards for Regulatory Approval in such country, based upon all or part of the clinical data generated by or on behalf of the Parties pursuant to this Agreement or obtained using an abbreviated, expedited or other process, and (b) is sold in the same country as such Licensed Product by any Third Party that (i) is not a Sublicensee (other than a Sublicensee that has been granted a sublicense to any Foreground Patent by Seagen solely in connection with any settlement) and (ii) did not purchase such pharmaceutical product in a chain of distribution that included any of Seagen, its Affiliates or its or their Sublicensees.
1.121“Global Development Cost Estimated Budget” is defined in Section 11.2.1 (Option Data Package).
1.122“Global Development Costs” means, with respect to a Profit-Share Product, the sum of the FTE Costs and Out-of-Pocket Development Costs incurred by or on behalf of Seagen and its Affiliates for the Development of the applicable Profit-Share Product that is necessary or reasonably useful for obtaining, maintaining, or supporting Regulatory Approval in [*] (including, for the avoidance of doubt, (a) to the extent obtaining, maintaining, or supporting such Regulatory Approval is necessary or reasonably useful for Development or Commercialization in [*], and (b) whether such activities are conducted before or after receipt of such Regulatory Approval), in each case, excluding those Development costs reasonably allocable to Clinical Trials conducted solely to obtain Regulatory Approval in a jurisdiction outside [*] (and not for purposes of obtaining Regulatory Approval in [*]). By way of example, the Development costs of a [*] study would not be included in “Global Development Costs.” The Parties shall mutually agree in each Profit-Share Product Agreement on the applicable FTE rate for determination of FTE Costs and a mechanism for adjustments thereto; provided, that such rate and mechanism shall be in accordance with then-current industry practice. For purposes of this Section 1.122 (“Global Development Costs”): (i) “FTE Costs” means [*]; provided, that the FTE Costs shall be calculated in accordance with accounting and reimbursement principles consistent with Seagen’s then-current Accounting Standard (such calculation methodology will be discussed and agreed by the applicable Committee in connection with Nurix’s exercise of the relevant Profit-Share Option); (ii) “FTE” means a full-time equivalent person year as further defined and mutually agreed by the Parties in good faith in the relevant Profit-Share Product Agreement (which definition shall be consistent with Seagen’s then-current policies and Accounting Standard); and (iii) “Out-of-Pocket Development Costs” means all costs incurred by or on behalf of Seagen and its Affiliates for payments made to Third Parties in the Development of the applicable Profit-Share Product (including CMC Development and the Manufacture of clinical material for Clinical Trials for such Profit-Share Product).
1.123“GLP” means the applicable then-current good laboratory practice standards as are required by applicable Regulatory Authorities or Applicable Law in the relevant jurisdiction, including, in the United States, those promulgated or endorsed by the FDA, including FDA regulations set forth in 21 C.F.R. Part 58, or the equivalent thereof as promulgated or endorsed by the applicable Regulatory Authorities outside of the United States, to the extent such standards are not less stringent than United States GLP.
1.124“[*]” is defined in Section 13.4 (Research Milestones).
1.125“GMP” means all applicable then-current good manufacturing practice standards relating to fine chemicals, intermediates, bulk products, components, or finished pharmaceutical or
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biological products, as are required by applicable Regulatory Authorities or Applicable Law in the relevant jurisdiction, including: (a) all applicable requirements detailed in the FDA’s current Good Manufacturing Practices regulations at 21 C.F.R. Parts 210 and 211 and 600-680; (b) all applicable requirements detailed in the EMA’s “The Rules Governing Medicinal Products in the European Community, Volume IV, Good Manufacturing Practice for Medicinal Products” and (c) all Applicable Law promulgated by any other Governmental Authority having jurisdiction over the Manufacture of the applicable compound or pharmaceutical or biological product.
1.126“Governmental Authority” means any: (a) federal, state, local, municipal, foreign, or other government; (b) governmental authority of any nature (including any agency, board, body, branch, bureau, commission, council, department, division, office, officer, official, organization, representative, subdivision, unit, and any court or other tribunal); (c) multinational or supranational governmental organization or body; or (d) entity or body exercising, or entitled to exercise, any executive, legislative, judicial, administrative, regulatory, police, military or taxing authority or power (including any arbiter) on behalf of a government or governmental authority.
1.127“Homologous Target” means, with respect to the Degrader Target at issue, any Degrader Target that is a paralog of such Degrader Target as reasonably agreed in good faith by the Parties in writing; provided, that neither Party shall unreasonably withhold, condition or delay such agreement.
1.128“HSR Act” means the Hart-Scott-Rodino Antitrust Improvements Act of 1976 (15 U.S.C. § 18a).
1.129“IFRS” means the International Financial Reporting Standards.
1.130“[*] Potency Benchmark” means, with respect to a Collaboration Degrader Target Set, the set of key [*] potency properties (to be described in the applicable Joint Research Plan) of Collaboration Degraders Directed To such Collaboration Degrader Target Set that must be demonstrated (for clarity, demonstrated with respect to such Collaboration Degrader [*], unless otherwise determined by Seagen in its sole discretion) in order to achieve Research Milestone [*].
1.131“IND” means an investigational new drug application (including any amendment or supplement thereto) submitted to the FDA pursuant to 21 C.F.R. Part 312, including any amendments thereto. References herein to IND will include, to the extent applicable, any foreign counterpart of the foregoing filed with a Regulatory Authority outside the U.S. for the investigation of a pharmaceutical or biological product in any other country or group of countries (such as a Clinical Trial Application in the EU) in conformance with the requirements of such Regulatory Authority.
1.132“[*] Licensed Degrader Target Set” is defined in Section 2.7 ([*] Licensed Degrader Target Set).
1.133“Indemnification Claim Notice” is defined in Section 18.2.1 (Indemnification Notice).
1.134“Indemnitee” is defined in Section 18.2.1 (Indemnification Notice).
1.135“Indemnitor” is defined in Section 18.2.1 (Indemnification Notice).
1.136“Indication” means a separate and distinct disease, medical condition or disorder in humans that [*]; provided, however, that (a) the broadening of use of a product for different stages of a particular disease, condition or disorder shall not be separate Indications; (b) moving from one line of therapy to another for a particular disease, condition or disorder will not be
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considered to be a new Indication, (e.g., moving from second line therapy to first line therapy); (c) an Indication for a product includes all uses (e.g., prophylactic and therapeutic uses) for the relevant disease, condition or disorder for all patient populations (e.g., pediatric and adult uses) irrespective of different formulation(s), dosage forms, dosage strengths, or delivery system(s) used; and (d) obtaining a label expansion for use of a product in combination with another product in the same disease, condition or disorder will not be considered to be a new Indication.
1.137“Infringement” is defined in Section 15.3.1 (Notification).
1.138“Initial Degrader Target Set” is defined in Section 2.2.1 (Initial Degrader Target Sets).
1.139“Initial Joint Research Plan” is defined in Section 4.1 (Joint Research Plans).
1.140“Initiation” means, with respect to a pharmaceutical or biological product and a Clinical Trial, the administration of the first dose of such product or placebo to the first (1st) patient dosed in such Clinical Trial.
1.141“Invention” means any process, method, composition of matter, article of manufacture, discovery or finding, in each case, that is first conceived or reduced to practice under this Agreement.
1.142[*]
1.143“Joint Foreground IP” is defined in Section 15.1.2 (Foreground IP).
1.144“Joint Foreground Patents” is defined in Section 15.1.2 (Foreground IP).
1.145“Joint Patent Committee” or “JPC” is defined in Section 10.4 (Joint Patent Committee).
1.146“Joint Research” is defined in Section 4.2 (Joint Research Activities).
1.147“Joint Research Plan” means each research plan for each Collaboration Degrader Target Set approved as further described in Section 4.1 (Joint Research Plans) (as such plan may be amended as permitted under this Agreement), which plan shall include the applicable Collaboration Degrader Criteria and the [*] validation criteria (including the applicable [*] Potency Benchmark) for advancement of Collaboration Degraders or Collaboration Degrader-Antibody Conjugates that are Directed To such Collaboration Degrader Target Set as further described in Section 4.1 (Joint Research Plans).
1.148“Joint Research Team” is defined in Section 10.3.1 (Joint Research Team Membership).
1.149“Joint Research Term” means, on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, the period beginning upon the applicable Degrader Target Set Selection Date and ending upon the earliest of (a) the completion of the applicable Joint Research Plan for such Collaboration Degrader Target Set, (b) the date that is [*] after the applicable [*], or (c) the date that is [*] after the Effective Date; provided, that (x) the Joint Research Term may be extended on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis for [*] by the payment of the Joint Research Term Extension Fee in accordance with Section 4.3 (Joint Research Term Extension), and (y) except as the Parties may otherwise mutually agree in writing, under no circumstances (including any such extension under Section 4.3 (Joint Research Term Extension)) will the Joint Research Term with respect to any
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Collaboration Degrader Target Set, including [*] or any Replacement Degrader Target Set, as applicable, extend beyond the date that is [*] after the Effective Date.
1.150“Joint Research Term Extension” is defined in Section 4.3 (Joint Research Term Extension).
1.151“Joint Research Term Extension Fee” is defined in Section 13.2 (Joint Research Term Extension Fee).
1.152“JRC” is defined in Section 10.2.1 (JRC Membership).
1.153“JRC Co-Chairs” is defined in Section 10.2.2 (JRC Co-Chairs).
1.154“JSC” is defined in Section 10.1.1 (JSC Membership).
1.155“JSC Co-Chairs” is defined in Section 10.1.1 (JSC Membership).
1.156“Know-How” means any and all proprietary or confidential algorithms, data, information, inventions, knowledge, methods (including methods of use or administration or dosing), practices, results, software, techniques, technology and trade secrets, including analytical and quality control data, analytical methods (including applicable reference standards), assays, biomarkers, batch records, chemical structures and formulations, compositions of matter, formulae, manufacturing data, pharmacological, toxicological and clinical test data and results, processes, reports, research data, research tools, sequences, standard operating procedures and techniques, in each case, whether patentable or not, and, in each case, tangible manifestations thereof.
1.157“Licensed Degrader” means, with respect to a Licensed Degrader Target Set, any Collaboration Degrader Directed To such Licensed Degrader Target Set (for clarity, or a Subset thereof). For clarity, (a) a Licensed Degrader may or may not contain one (1) or more attachment moieties in its Proteasome Protein Binder, Degrader Spacer, or Degrader Target Binder that enable the conjugation of such Licensed Degrader to a Degrader-Antibody Linker, and (b) a Licensed Degrader Directed To a Licensed Degrader Target Set that, as of the time of determination, is simultaneously both a Licensed Degrader Target Set and a Collaboration Degrader Target Set (as further described in Section 1.159 (“Licensed Degrader Target Set”)) shall be a Licensed Degrader Directed To such Licensed Degrader Target Set and, simultaneously, a Collaboration Degrader Directed To such Collaboration Degrader Target Set, until the expiration of the Joint Research Term applicable to such Collaboration Degrader Target Set (subsequently, upon expiration of the applicable Joint Research Term, such Degrader shall be a Licensed Degrader and not a Collaboration Degrader).
1.158“Licensed Degrader Target” means each Degrader Target in a Licensed Degrader Target Set from and after the applicable Degrader License Effective Date; provided, that such Degrader Target shall no longer be a Licensed Degrader Target from and after the time that such Degrader Target becomes a Former Licensed Degrader Target.
1.159“Licensed Degrader Target Set” means a Collaboration Degrader Target Set for which the Degrader License Effective Date has occurred in accordance with Section 5.2 (Degrader License Option Exercise). For clarity, (a) there can be no more than [*] Licensed Degrader Target Sets at any one time (provided that, unless the context otherwise requires, a Licensed Degrader Target Set and its Subsets, including any [*] Licensed Degrader Target Set, shall be considered a single Licensed Degrader Target Set hereunder), and (b) if the Degrader License Effective Date with respect to a Collaboration Degrader Target Set occurs before the expiration of the Joint Research Term applicable to such Collaboration Degrader Target Set, such Collaboration Degrader Target Set is considered, simultaneously, both a Licensed Degrader Target Set and a Collaboration
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Degrader Target Set, until the expiration of such applicable Joint Research Term (subsequently, upon expiration of the applicable Joint Research Term, such Degrader Target Set shall be a Licensed Degrader Target Set and not a Collaboration Degrader Target Set).
1.160“Licensed Degrader-Antibody Conjugate” means, with respect to a Licensed Degrader Target Set, a Degrader-Antibody Conjugate that (a) contains a Licensed Degrader that is Directed To such Licensed Degrader Target Set (for clarity, or a Subset thereof) and (b) does not contain any Degrader that is not a Licensed Degrader. For clarity, any Degrader-Antibody Conjugate that contains (x) a Licensed Degrader and (y) a Collaboration Degrader that is not a Licensed Degrader, shall not be considered a Licensed Degrader-Antibody Conjugate.
1.161“Licensed Product” means any pharmaceutical or biological preparation that is a Licensed Degrader or Licensed Degrader-Antibody Conjugate (in all presentations and formulations including all manners of delivery, strengths and dosages).
1.162“MAA” means a Marketing Authorization Application or similar application, as applicable, and all amendments and supplements thereto, submitted to the FDA, EMA or other Regulatory Authority to obtain marketing approval (but excluding Pricing Approval) for a pharmaceutical or biological product in the U.S., EU, or other country or group of countries. For clarity, an MAA includes an NDA.
1.163“Manufacture” means all activities related to the manufacturing of a pharmaceutical or biological product or any component or ingredient thereof, including the production, manufacture, having manufactured, processing, filling, finishing, packaging, labeling, assembling, shipping and holding (including storage) of product or any intermediate thereof, including process development, process qualification and validation, scale-up, commercial manufacture and analytic development, product characterization, stability testing, quality assurance and quality control and release. When used as a verb, “Manufacture” means to engage in Manufacture.
1.164“Material Transfer Agreement” is defined in Section 4.6 (Seagen-Provided Property).
1.165“Milestone Event” means any Research Milestone Event, Development and Regulatory Milestone Event, or Sales Milestone Event, as applicable.
1.166“Milestone Payment” means any Research Milestone Payment, Development and Regulatory Milestone Payment, or Sales Milestone Payment, as applicable.
1.167“NDA” means, with respect to a pharmaceutical product, a New Drug Application submitted to the FDA in accordance with the FFDCA, and with respect to a biological product, a Biologics License Application submitted to the FDA in accordance with the Public Health Service Act and the applicable regulations promulgated thereunder.
1.168“Net Sales” means, with respect to a Licensed Product for any period during the Term, the gross amount billed or invoiced by Seagen or any of its Affiliates or its or their Sublicensees for the sale of a Licensed Product to a Third Party commencing with the First Commercial Sale of such Licensed Product less the following deductions determined in accordance with the Accounting Standard of Seagen, its Affiliates or Sublicensees from such gross amounts which are actually incurred, allowed, accrued or specifically allocated:
1.168.1[*];
1.168.2[*];
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1.168.3[*];
1.168.4[*];
1.168.5[*];
1.168.6[*];
1.168.7[*];
1.168.8[*]; and
1.168.9[*].
Net Sales shall not include transfers or dispositions of such Licensed Product for pre-clinical or clinical purposes, compassionate use or as samples, in each case, without charge. Such Party’s, its Affiliates’ or its or their Sublicensees’ transfer of any Licensed Product to an Affiliate or Sublicensee shall not result in any Net Sales unless the transferee is an end user.
In the event that a Licensed Product is sold in any country in the form of a Combination Product, Net Sales of such Combination Product shall be adjusted by multiplying actual Net Sales of such Combination Product in such country calculated pursuant to the foregoing definition of “Net Sales” by the fraction [*]. If either such Licensed Product that contains the applicable Licensed Degrader or Licensed Degrader-Antibody Conjugate as its sole active ingredient or any such product that solely contains Additional Active(s) is not sold separately (including in the case of the sale of a combination therapy that contains the Licensed Degrader but it is not sold separately) in a particular country, then the adjustment to Net Sales shall be determined by [*]. In the event that a dispute arises regarding the allocation mechanism under this paragraph, the Dispute shall be resolved [*].
1.169“Non-Enforcing Party” is defined in Section 15.3.3(d).
1.170“Notice of Dispute” is defined in Section 20.6.2(a).
1.171“Nurix” is defined in the preamble to this Agreement.
1.172“Nurix Background In-Licensed IP” is defined in Section 12.3 (Upstream License Agreements).
1.173“Nurix Background IP” is defined in Section 15.1.1 (Background IP).
1.174“Nurix Co-Promotion Plan” is defined in Section 11.2.5 (Co-Promotion Criteria).
1.175“Nurix Foreground In-Licensed IP” is defined in Section 12.3 (Upstream License Agreements).
1.176“Nurix Foreground IP” is defined in Section 15.1.2 (Foreground IP).
1.177“Nurix Foreground Patents” is defined in Section 15.1.2 (Foreground IP).
1.178“Nurix Indemnitee” is defined in Section 18.1.1 (Indemnification by Seagen).
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1.179“Nurix IP” means the Nurix Patents and the Nurix Know-How (for clarity, excluding any Joint Foreground IP).
1.180“Nurix Know-How” means any and all Know-How that, as between the Parties, is solely Controlled by Nurix or any of its Affiliates as of the Effective Date or thereafter during the Term which is necessary or reasonably useful for the research, Development, Manufacture or Commercialization of any Collaboration Degrader or Collaboration Degrader-Antibody Conjugate, including any Licensed Product, in the Field in the Territory.
1.181“Nurix Materials” means any materials made, generated or developed by Nurix, and any information that is necessary to apprise Seagen of the stability, proper storage and safe handling requirements for such materials, in each case, Controlled by Nurix or its Affiliates that are necessary or reasonably useful to the Parties’ Research activities under this Agreement or are necessary or reasonably useful to the research, Development, Manufacture, or Commercialization of Collaboration Degraders, Collaboration Degrader-Antibody Conjugates or Licensed Products (as applicable), including all applicable assays, Know-How and tangible materials related to the foregoing and actually provided by Nurix to Seagen in accordance with Section 4.7 (Nurix-Provided Property) for use with respect to the Parties’ research activities under this Agreement.
1.182“Nurix Opt-In Agreement(s)” is defined in Section 11.1 (U.S. Profit-Share Option).
1.183“Nurix Opt-Out Date” is defined in Section 11.4.2 (Opt-Out Date and Wind-Down).
1.184“Nurix Opt-Out Notice” is defined in Section 11.4.1 (Opt-Out Notice).
1.185“Nurix Patent” means any Patent that, as between the Parties, is solely Controlled by Nurix or any of its Affiliates as of the Effective Date or thereafter during the Term that Covers the research, Development, Manufacture or Commercialization of any Collaboration Degrader or Collaboration Degrader-Antibody Conjugate, including any Licensed Product, in the Field in the Territory, including all such Patents that are Nurix Foreground Patents.
1.186“Nurix Research” is defined in Section 4.2 (Joint Research Activities).
1.187“Nurix Resources” is defined in Section 11.2.5 (Co-Promotion Criteria).
1.188“Opt-Out Wind-Down Period” is defined in Section 11.4.2 (Opt-Out Date and Wind-Down).
1.189“Option Data Package” is defined in Section 11.2.1 (Option Data Package).
1.190“Other Reversion License Agreement” is defined in Section 14.3.2 (Potential Reversion Products).
1.191“Out-of-Pocket Development Costs” is defined in Section 1.122 (“Global Development Costs”).
1.192“Outside Date” is defined in Section 5.4.3 (Outside Date).
1.193“[*]” is defined in Schedule 2.2.1 (Initial Degrader Target Sets).
1.194“[*]” is defined in Schedule 2.2.1 (Initial Degrader Target Sets).
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1.195“Pan-Directed To” means, with respect to any Degrader Target Set, that (a) the Degrader at issue (i) is Directed To all Degrader Targets in such Degrader Target Set and no other Degrader Target, (ii) selectively binds all of the Degrader Target(s) in such Degrader Target Set, (iii) degrades all of the Degrader Target(s) in such Degrader Target Set; and (iv) has been optimized to cause pharmacologically relevant activity as a result of such degradation of such Degrader Target(s) in such Degrader Target Set; or (b) the Degrader-Antibody Conjugate at issue contains a Degrader that is Pan-Directed To (as defined in clause (a) above) such Degrader Target Set. For clarity, if the applicable Degrader Target Set contains only one (1) Degrader Target, then a Degrader or Degrader-Antibody Conjugate that is Directed To such Degrader Target is also considered Pan-Directed To such Degrader Target Set. A Licensed Product will be deemed to be “Pan-Directed To” a Degrader Target Set if such Licensed Product contains a Licensed Degrader or Licensed Degrader-Antibody Conjugate that is “Pan-Directed To” such Degrader Target Set.
1.196“Parent Target Set” is defined in Section 1.81(b).
1.197“Party” is defined in the preamble to this Agreement.
1.198“Patent” means: (a) any patent or patent application in any country or supranational jurisdiction worldwide; (b) any substitution, divisional, continuation, continuation-in-part, reissue, renewal, registration, confirmation or the like of any such patent or patent application or (c) any extension or restoration by existing or future extension or restoration mechanism, including revalidation, reissue, re-examination or extension, including any supplementary protection certificate and extension thereto of any of the foregoing.
1.199“Patent Dispute” is defined in Section 20.6.1 (Choice of Law).
1.200“Permitted Subcontractors” is defined in Section 14.4 (Subcontracting).
1.201“Person” means any individual, partnership, joint venture, limited liability company, corporation, firm, trust, association, unincorporated organization, Governmental Authority or any other entity not specifically listed herein.
1.202“Phase 1 Clinical Trial” means a Clinical Trial which provides for the initial introduction into humans of a pharmaceutical or biological product, conducted in healthy volunteers or patients to obtain information on product safety, tolerability, pharmacological activity or pharmacokinetics, as defined in 21 C.F.R. § 312.21(a) or its foreign equivalents.
1.203“Phase 1/2 Clinical Trial” means a Clinical Trial that combines both a Phase 1 Clinical Trial and a Phase 2 Clinical Trial into a single protocol, where the Phase 1 Clinical Trial portion is performed first to (a) establish initial safety, tolerability, pharmacokinetic and pharmacodynamic information for a pharmaceutical or biological product as a monotherapy or in combination with another agent and (b) determine the maximum tolerable dose of such product, and the Phase 2 Clinical Trial portion is performed second to evaluate the safety and efficacy of such product as a monotherapy or in combination with another agent in subjects with a target disease or medical condition treated with a selected dose. For clarity, “Phase 1/2 Clinical Trial” shall include any Clinical Trial that includes any combination of the portions of a Phase 1 Clinical Trial and a Phase 2 Clinical Trial, including a Phase 1b/2a Clinical Trial or a Phase 1b/2 Clinical Trial.
1.204“Phase 2 Clinical Trial” means a controlled Clinical Trial, the principal purposes of which are the evaluation of the efficacy of a pharmaceutical or biological product in a target patient population and a determination of the common side-effects and risks associated with the product in the dosage range under evaluation, and to obtain sufficient additional information to permit the design of a Pivotal Trial, and is otherwise consistent with 21 C.F.R. §312.21(b) or its
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foreign equivalents. For clarity, “Phase 2 Clinical Trial” will exclude in all cases any combined Phase 1/2 Clinical Trial.
1.205“Phase 3 Clinical Trial” means a controlled Clinical Trial to evaluate the efficacy and safety of a pharmaceutical or biological product, which is prospectively designed to demonstrate with statistical rigor whether such product is effective and safe for use in a particular Indication in a manner sufficient to support a filing for an MAA, and is otherwise consistent with the requirements of 21 C.F.R. § 312.21(c) or its foreign equivalents.
1.206“Pivotal Trial” means an expanded Clinical Trial of a pharmaceutical or biological product that: (a) is prospectively designed to demonstrate that a product is safe and effective for use in a particular Indication in a manner sufficient to evaluate the overall risk-benefit relationship of the product and to provide an adequate basis for physician labeling; (b) is intended to provide sufficient efficacy data to support the filing of a MAA for such product without the need for any additional Clinical Trials; and (c) which, at the time of Initiation of such Clinical Trial, is expected to be the basis for European Union Regulatory Approval of such product or Regulatory Approval by the FDA of such product, in each case, based on discussions with the relevant Regulatory Authority. For clarity, (x) a Phase 3 Clinical Trial (as defined herein) is always a “Pivotal Trial,” and (y) a Phase 2 Clinical Trial, Phase 1/2 Clinical Trial, Phase 1 Clinical Trial, or other Clinical Trial (such as a “Phase 2b/3” Clinical Trial) (as such terms are defined herein) are only a “Pivotal Trial” if all conditions of this definition are met.
1.207“PMDA” is defined in Section 1.227 (“Regulatory Authority”).
1.208“Potential Reversion Product” is defined in Section 14.3.2 (Potential Reversion Products).
1.209“Pricing Approval” means all approvals, agreements, determinations or decisions establishing prices that can be charged to consumers or third-party payors for a pharmaceutical or biological product or that will be reimbursed by Governmental Authorities for a pharmaceutical or biological product, in each case, in a country where Governmental Authorities approve or determine pricing for pharmaceutical or biological products for reimbursement or otherwise.
1.210“Prior CDA” is defined in Section 20.10 (Entire Agreement).
1.211“Product Patent” means: (a) with respect to any Licensed Product containing a Licensed Degrader-Antibody Conjugate, any and all Foreground Patents that include at least one (1) claim that claims the entirety of such Licensed Product, the Licensed Degrader-Antibody Conjugate contained in such Licensed Product, or the Licensed Degrader contained in such Licensed Degrader-Antibody Conjugate; and (b) with respect to any Licensed Product containing a Licensed Degrader and not containing a Licensed Degrader-Antibody Conjugate, any and all Foreground Patents that include at least one (1) claim that claims the entirety of such Licensed Product or the Licensed Degrader contained in such Licensed Product. For clarity, no “Product Patents” exist with respect to a Licensed Product prior to the applicable Degrader License Effective Date, but Patents existing prior to the Degrader License Effective Date may become Product Patents upon the Degrader License Effective Date.
1.212“Profit-Share Option” is defined in Section 11.1 (U.S. Profit-Share Option).
1.213“Profit-Share Option Exercise Notice” is defined in Section 11.2.2 (Option Exercise).
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1.214“Profit-Share Option Exercise Period” is defined in Section 11.2.2 (Option Exercise).
1.215“Profit-Share Option Triggering Event” means, with respect to each Licensed Product for so long as Nurix may exercise a Profit-Share Option in accordance with Section 11.1 (U.S. Profit-Share Option) and Seagen has an obligation to deliver an Option Data Package with respect to the Licensed Product pursuant to Section 11.2.1 (Option Data Package), (a) [*], or (b) otherwise, the [*].
1.216“Profit-Share Product” is defined in Section 11.1 (U.S. Profit-Share Option).
1.217“Profit-Share Product Agreement” is defined in Section 11.1 (U.S. Profit-Share Option).
1.218“Proposed Degrader Target Set” is defined in Section 3.1.1 (Proposed Degrader Target Set Notice).
1.219“Proposed Degrader Target Set Notice” is defined in Section 3.1.1 (Proposed Degrader Target Set Notice).
1.220“Prosecution and Maintenance” or “Prosecute and Maintain” means, with regard to a Patent, the preparation, filing, prosecution and maintenance of such Patent, as well as re-examinations, reissues and appeals with respect to such Patent, together with the initiation or defense of interferences, oppositions, inter partes review, derivations, re-examinations, post-grant proceedings and other similar proceedings (or other defense proceedings with respect to such Patent, but excluding the defense of challenges to such Patent as a counterclaim in an infringement proceeding) with respect to the particular Patent, and any appeals therefrom, and actions to obtain patent term extensions and supplementary protection certificates with respect to such Patent and the like. For clarification, “Prosecution and Maintenance” or “Prosecute and Maintain” will not include any other enforcement actions taken with respect to a Patent.
1.221“Proteasome Protein” means any protein component of the Ubiquitin Proteasome System that is capable of initiating proteasome-dependent degradation of a Degrader Target when such protein component is bound to a Degrader, including, for clarity, any E3 ubiquitin ligase. For purposes of this Section 1.221 (“Proteasome Protein”), “Ubiquitin Proteasome System” means the eukaryotic intracellular ubiquitin-proteasome protein degradation system, including, for clarity, ubiquitin, any protein members of the proteasome, and any E3 ubiquitin ligase (but, for clarity, not including any Degrader Target).
1.222“Proteasome Protein Binder” means any chemical moiety that selectively binds a Proteasome Protein (including (a) a portion of such moiety sufficient to convey such binding and (b) such moiety or portion thereof as incorporated in a Degrader under this Agreement).
1.223“Publication” is defined in Section 16.8 (Publications).
1.224“Publishing Party” is defined in Section 16.8 (Publications).
1.225“Receiving Party” is defined in Section 16.1 (Nondisclosure and Non-Use).
1.226“Regulatory Approval” means all approvals, licenses or authorizations of the applicable Regulatory Authority necessary for the marketing and sale of a pharmaceutical or biological product in a country or region (but excluding separate Pricing Approvals), and any supplements or amendments thereto including approval by the applicable Regulatory Authority of any expansion or modification of the label for such product.
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1.227“Regulatory Authority” means any national, multinational, supranational, regional, state or local Governmental Authority, including the U.S. Food and Drug Administration (and any successor entity thereto) (the “FDA”) in the U.S., the European Medicines Agency (and any successor entity thereto) (the “EMA”) in the EU or any counterpart to the foregoing agencies, such as the Pharmaceutical and Medical Device Agency in Japan (“PMDA”), that in each case, holds responsibility for regulating Development, Manufacturing, and Commercialization activities, and the granting of Regulatory Approval for, a pharmaceutical or biological product in the applicable country or region.
1.228“Regulatory Exclusivity” means, with respect to a Licensed Product, any rights or protections which are recognized, afforded or granted by the FDA or any other Regulatory Authority in any country or region of the Territory, in association with the Regulatory Approval of the Licensed Product, providing the Licensed Product (a) a period of regulatory exclusivity during which a Regulatory Authority will refrain from accepting, reviewing, approving or extending an MAA or similar regulatory submission submitted by a Third Party seeking to market a Generic/Biosimilar Product of such Licensed Product, including any period of orphan drug exclusivity, or (b) a period of marketing protection during which a Generic/Biosimilar Product of such Licensed Product may obtain a Regulatory Approval but is not permitted to be placed on the market under Applicable Law.
1.229“Regulatory Materials” means the registrations, applications, authorizations and Regulatory Approvals (including approvals of MAAs, supplements and amendments, pre- and post-approvals, Pricing Approvals and labeling approvals) and other submissions made to or with any Regulatory Authority, including drug master files, for research, Development (including the conduct of Clinical Trials), Manufacture or Commercialization of a pharmaceutical or biological product in a regulatory jurisdiction, together with all related correspondence to or from any Regulatory Authority and all documents referenced in the complete regulatory chronology for each NDA, MAA, IND and foreign equivalents of any of the foregoing.
1.230“Removed Degrader Target” is defined in Section 2.5.1 (Amendment of Joint Research Plan).
1.231“Replacement Degrader Target Set” is defined in Section 2.2.3 (Collaboration Degrader Target Set Replacement Right).
1.232“Research” means any pre-clinical or non-clinical research or development activities, including any related manufacturing activities, including Collaboration Degrader Target Set validation, drug discovery, identification or synthesis, with respect to a Collaboration Degrader Target Set, Collaboration Degrader, or Collaboration Degrader-Antibody Conjugate. When used as a verb, “Research” means to engage in Research.
1.233“Research Milestone #2” is defined in Section 13.4 (Research Milestones).
1.234“Research Milestone #3” is defined in Section 13.4 (Research Milestones).
1.235“Research Milestone Event” is defined in Section 13.4 (Research Milestones).
1.236“Research Milestone Payment” is defined in Section 13.4 (Research Milestones).
1.237“Research Program” means, on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, all Joint Research activities undertaken under the Joint Research Plan for such Collaboration Degrader Target Set, to identify compounds that are
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Collaboration Degraders and Collaboration Degrader-Antibody Conjugates, in each case, that are Directed To such Collaboration Degrader Target Set.
1.238“Research Results” means any Research data, relevant compound structures (including structures of Degraders, Proteasome Protein Binders, Degrader Spacers and Degrader Target Binders), material, results or other information related to or otherwise arising under or out of any Joint Research activities or Seagen Research activities, to the extent in existence and in the Control of Nurix or Seagen, as applicable, at the time that such material, results or information is required to be disclosed to the other Party in accordance with Section 4.8 (Information Sharing).
1.239“Reservation Period” is defined in Section 2.3.1 (General).
1.240“Reserved Degrader Target Set” is defined in Section 2.3.1 (General).
1.241[*]
1.242“Reversion Product” means, upon any Licensed Degrader Target Set becoming a Former Licensed Degrader Target Set, (a) any Profit-Share Product containing a Licensed Degrader or Licensed Degrader-Antibody Conjugate, in each case, Directed To such Former Licensed Degrader Target Set, and (b) any Licensed Product for which [*] comprising a Licensed Degrader Directed To such Former Licensed Degrader Target Set that does not contain a Licensed Degrader-Antibody Conjugate (a Licensed Product satisfying clause (b), a “Reverted Standalone Degrader”).
1.243“Reversion Product License Agreement” is defined in Section 14.3.1 (Reversion Product License Agreement).
1.244“Reverted Standalone Degrader” is defined in Section 1.242 (“Reversion Product”).
1.245“Reviewing Party” is defined in Section 16.8 (Publications).
1.246“Royalty Patents” means, collectively, with respect to a Licensed Product, any and all (a) [*] Patents, in each case, claiming [*] and (b) [*]. For clarity, the “Royalty Patents” shall not include [*].
1.247“Royalty Term” means, on a Licensed Product-by-Licensed Product and country by country basis, the period of time commencing on the First Commercial Sale of such Licensed Product in such country and ending upon the last to occur of: (a) the expiration of the last-to-expire Royalty Patent having at least one Valid Claim that Covers such Licensed Product as it is sold in such country; (b) the expiration of all Regulatory Exclusivity for such Licensed Product in such country; and (c) [*] years after the First Commercial Sale of such Licensed Product in such country.
1.248“Rules” is defined in Section 20.6.3 (Arbitration)
1.249“Sales Milestone Event” is defined in Section 13.8 (Sales-Based Milestones).
1.250“Sales Milestone Payment” is defined in Section 13.8 (Sales-Based Milestones).
1.251“Seagen” is defined in the preamble to this Agreement.
1.252“Seagen Background IP” is defined in Section 15.1.1 (Background IP).
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1.253“Seagen Desired Degrader Targets” is defined in Section 3.2.2 (Gatekeeper Responsibilities).
1.254“Seagen Foreground IP” is defined in Section 15.1.2 (Foreground IP).
1.255“Seagen Foreground Patents” is defined in Section 15.1.2 (Foreground IP).
1.256“Seagen Inactive Period” means, with respect to a Licensed Degrader Target Set, any consecutive [*] period (a) beginning after the applicable Degrader License Effective Date and (b) during which Seagen has not, directly or indirectly (including with or through any Affiliate or Third Party), [*]. Notwithstanding the foregoing, a Seagen Inactive Period will not be deemed to have occurred unless and until (A) Nurix notifies Seagen in writing of its good faith belief that a Seagen Inactive Period has occurred with respect to a [*] (the “Seagen Inactive Period Notice”) and (B) the passage of [*] days following delivery of such notice; provided, that if Seagen disputes that a Seagen Inactive Period has occurred and so notifies Nurix within [*] of delivery to Seagen of Nurix’s written notice, a Seagen Inactive Period will not be deemed to have occurred unless and until (1) the Parties mutually agree in writing that a Seagen Inactive Period has occurred or (2) the conclusion of a dispute resolution process under Section 20.6 (Choice of Law; Dispute Resolution; Jurisdiction) resulting in a final determination that a Seagen Inactive Period has occurred. Notwithstanding anything to the contrary in this Agreement, any Seagen activities undertaken after receipt of the Seagen Inactive Period Notice will not be considered in determining whether or not a Seagen Inactive Period has occurred, and any exercise by Seagen of its final decision-making authority under in Section 10.6 (Committee Decisions) not to conduct the activities described in the foregoing clauses (b)(ii) or (b)(iii) shall not be considered in any determining whether or not a Seagen Inactive Period has occurred.
1.257“Seagen Inactive Period Notice” is defined in Section 1.256 (“Seagen Inactive Period”).
1.258“Seagen Indemnitee” is defined in Section 18.1.2 (Indemnification by Nurix).
1.259“Seagen IP” means the Seagen Patents and the Seagen Know-How (for clarity, excluding any Joint Foreground IP).
1.260“Seagen Know-How” means any and all Know-How that, as between the Parties, is solely Controlled by Seagen or any of its Affiliates as of the Effective Date or thereafter which is necessary or reasonably useful for the Research, Development, Manufacture or Commercialization of a Licensed Product in the Field in the Territory.
1.261“Seagen Materials” means any materials made, generated or developed by Seagen, and any information that is necessary to apprise Nurix of the stability, proper storage and safe handling requirements for such materials, in each case, Controlled by Seagen or its Affiliates and provided by Seagen to Nurix in accordance with Section 4.6 (Seagen-Provided Property) for use with respect to the Parties’ Research activities under this Agreement.
1.262“Seagen Patent” means any Patent that, as between the Parties, is solely Controlled by Seagen or any of its Affiliates (other than by operation of the licenses granted by Nurix to Seagen under this Agreement or any Ancillary Agreement) as of or after the Effective Date and that Covers the research, Development, Manufacture or Commercialization of a Licensed Product in the Field in the Territory, including all such Patents that are Seagen Foreground Patents.
1.263“Seagen Prosecution Step-In Patent” is defined in Section 15.2.2(c).
1.264“Seagen Research” is defined in Section 4.2 (Joint Research Activities).
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1.265“Seagen Research Term” is defined in Section 4.4 (Seagen Research Activities).
1.266“Seagen Safety Review Committee” means (a) Seagen’s global safety risk management committee responsible for reviewing Development or Commercialization activities with respect to safety matters for Seagen and its Affiliates’ entire portfolio established and conducted in accordance with Seagen’s internal policies governing the management of global safety risk for products Developed or Commercialized by or on behalf of Seagen, or (b) successor committee(s) that may be in effect following the Effective Date that satisfy the conditions described in clause (a) above.
1.267“Second Indication” is defined in Section 13.7.1.
1.268“Second Licensed Product” is defined in Section 13.7.2(b).
1.269“Securities Regulator” is defined in Section 16.3.1(a).
1.270“Segregate” means, with respect to a Competing Product and an applicable Exclusive Degrader Target Set, to segregate the research, Development, Manufacture and Commercialization activities relating to such Competing Product conducted by or on behalf of the applicable Party from the Research, Development, Manufacture and Commercialization activities conducted by or on behalf of the applicable Party with respect to the Exclusive Degrader Target Set and Collaboration Degraders (if any) Directed To such Exclusive Degrader Target Set, including ensuring that: (a) no personnel involved in performing the research, Development, Manufacture or Commercialization, as applicable, of such Competing Product have access to non-public plans or non-public information relating to the Research, Development, Manufacture or Commercialization of the Exclusive Degrader Target Set or Collaboration Degraders (if any) Directed To such Exclusive Degrader Target Set, including all applicable Research Results and any other relevant Confidential Information of the Parties under this Agreement; and (b) no personnel involved in performing the Research, Development, Manufacture or Commercialization of the Exclusive Degrader Target Set or Collaboration Degraders (if any) Directed To such Exclusive Degrader Target Set have access to non-public plans or information relating to the research, Development, Manufacture or Commercialization of such Competing Product; provided, that in either case ((a) or (b)), [*].
1.271“Subcommittee” is defined in Section 10.1.1 (JSC Membership).
1.272“Sublicensee” means, with respect to Seagen, a Third Party to whom Seagen has granted a sublicense or license in accordance with Section 14.5 (Sublicensing), either directly or indirectly, in each case, of the Degrader License rights licensed to Seagen by Nurix pursuant to this Agreement, but excluding: (a) any Third Party acting as a service provider, vendor or distributor for Seagen or its Affiliates, and (b) Nurix and any of its Affiliates.
1.273“Subset” means, with respect to any Degrader Target Set containing more than one (1) Degrader Target, any smaller Degrader Target Set comprising some (but not all), or any one, of the Degrader Targets included in such Degrader Target Set. By way of example and not limitation, [*]. For clarity, (w) a Subset of a Degrader Target Set is also considered a “Degrader Target Set” hereunder, (x) no Degrader Target Set is considered a Subset of itself, (y) each Degrader Target included in a Degrader Target Set containing more than one (1) Degrader Target is a Subset of such Degrader Target Set, and (z) with respect to any Degrader Target Set containing only one (1) Degrader Target, no Subsets exist for such Degrader Target Set.
1.274“Supplementary Option Data Package” is defined in Section 11.2.1 (Option Data Package).
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1.275“Taxes” is defined in Section 13.11.6(a) (Generally).
1.276“Term” is defined in Section 19.1 (Term; Expiration).
1.277“Territory” means worldwide.
1.278[*]
1.279[*]
1.280“Third Party” means any Person other than (a) Nurix or Seagen, or (b) an Affiliate of Nurix or of Seagen.
1.281“Third Party Claim” means any and all Actions brought by a Third Party.
1.282“Third Party Infringement Claim” is defined in Section 15.4.1 (Notification).
1.283“Ubiquitin Proteasome System” is defined in Section 1.221 (“Proteasome Protein”).
1.284“United States” or “U.S.” means the United States of America and all of its territories and possessions.
1.285“U.S. Tax Forms” is defined in Section 13.11.6(b) (Tax Withholding).
1.286“Unprotected Licensed Product” means, on a Licensed Degrader Target Set-by-Licensed Degrader Target Set and country-by-country basis, any Licensed Product: (a) that is not the first Licensed Product Directed To such Licensed Degrader Target Set to achieve First Commercial Sale in such country; and (b) with respect to which, upon such First Commercial Sale of such Licensed Product in such country, there are no Valid Claims within the Royalty Patents that Cover such Licensed Product in such country.
1.287“Upstream License Agreement” is defined in Section 12.3 (Upstream License Agreements).
1.288“Valid Claim” means any claim of an issued unexpired patent that (a) has not been finally cancelled, withdrawn, abandoned or rejected by any administrative agency or other body of competent jurisdiction; (b) has not been permanently revoked, or held invalid by a decision of a court or other body of competent jurisdiction that is unappealable or unappealed within the time allowed for appeal; (c) has not been rendered unenforceable through terminal disclaimer or otherwise; and (d) is not lost through an interference proceeding that is unappealable or unappealed within the time allowed for appeal.
1.289“Wire Instructions” means the wire transfer instructions for a bank account designated by Nurix for payments hereunder and may be updated from time to time by Nurix, by written notice to Seagen in accordance with Nurix’s internal procedures for providing such information.
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ARTICLE 2
DEGRADER TARGET SETS
2.1Overview.
2.1.1Overview of Collaboration. As further described herein, the Parties anticipate that the Parties will perform the activities described in the Joint Research Plan applicable to each Collaboration Degrader Target Set to discover Collaboration Degraders that are Pan-Directed To such Collaboration Degrader Target Set, and that Seagen will create and evaluate Collaboration Degrader-Antibody Conjugates using such Collaboration Degraders, in each case, as described in Article 4 (Research). During the applicable Degrader License Option Period for a Collaboration Degrader Target Set, Seagen shall have the right to exercise its Degrader License Option and, upon such exercise in accordance with Section 5.2 (Degrader License Option Exercise), Seagen will be granted the Degrader License described in Section 14.2 (Licensed Degrader License) with respect to the applicable Licensed Degrader Target Set (and Subsets thereof) and the applicable Licensed Degraders and Licensed Degrader-Antibody Conjugates.
2.1.2Overview of Target Sets. The Parties have mutually agreed, as of the Effective Date, to designate the [*] Initial Degrader Target Sets as described in Section 2.2.1 (Initial Degrader Target Sets) as Collaboration Degrader Target Sets. Seagen may select [*] to be the [*] as described in Section 2.2.2 ([*]) as the [*]. For illustration purposes only and subject to the provisions referred to below, which shall control over any contrary reading of this illustration: (a) Seagen may replace each Collaboration Degrader Target Set with an Available Degrader Target Set as described in Section 2.2.3 (Collaboration Degrader Target Set Replacement Right); (b) Seagen may reserve Available Degrader Target Sets as described in Section 2.3 (Reserved Degrader Target Sets); (c) determinations as to whether a Degrader Target Set is an Available Degrader Target Set shall be made in accordance with Article 3 (Gatekeeping); (d) each Collaboration Degrader Target Set may be amended in accordance with Section 2.4 (Addition of Degrader Targets), or in accordance with Section 2.5 (Removal of Collaboration Degrader Targets); and (e) Collaboration Degrader Target Sets and Licensed Degrader Target Sets may become Former Collaboration Degrader Target Sets and Former Licensed Degrader Target Sets, respectively, with the consequences described in Section 2.8 (Former Collaboration Degrader Target Sets) and Section 2.9 (Former Licensed Degrader Target Sets), as applicable, upon which Nurix shall have the rights described in Section 14.3 (Reversion Licenses) with respect to such Former Licensed Degrader Target Sets.
2.2Collaboration Degrader Target Sets.
2.2.1Initial Degrader Target Sets. As of the Effective Date, the [*] Degrader Target Sets listed in Schedule 2.2.1 are each Collaboration Degrader Target Sets (each, an “Initial Degrader Target Set”).
2.2.2[*]. For a period of [*] after the Effective Date and subject to Section 3.1 (Proposed Degrader Target Sets), Seagen shall have the right to select [*] (including any Reserved Degrader Target Set) as a Collaboration Degrader Target Set ([*]) by delivery of a Proposed Degrader Target Set Notice to Nurix in accordance with Section 3.1 (Proposed Degrader Target Sets) (“[*] Notice”). Notwithstanding anything to the contrary in this Agreement, there will in no event be more than [*] Collaboration Degrader Target Sets in total under this Agreement at any time.
2.2.3Collaboration Degrader Target Set Replacement Right. On a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, during the applicable Collaboration Degrader Target Set Replacement Term, Seagen shall have the right to
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substitute an Available Degrader Target Set (including any Reserved Degrader Target Set) for such Collaboration Degrader Target Set upon delivery of written notice to Nurix’s Alliance Manager subject to Section 3.1 (Proposed Degrader Target Sets) (collectively, the “Collaboration Degrader Target Set Replacement Right”) (each such Available Degrader Target Set, thereafter a “Replacement Degrader Target Set”); provided, that Seagen shall only have the right to exercise its Collaboration Degrader Target Set Replacement Right a maximum of [*] for each Collaboration Degrader Target Set (for a maximum of [*] times), after which Seagen shall no longer have the right to exercise its Collaboration Degrader Target Set Replacement Right. Upon Seagen’s exercise of the Collaboration Degrader Target Set Replacement Right with respect to a Collaboration Degrader Target Set (subject to Section 3.1 (Proposed Degrader Target Sets)), such replaced Collaboration Degrader Target Set shall, effective from and after such time, cease to be a Collaboration Degrader Target Set and shall automatically become a Former Collaboration Degrader Target Set.
2.3Reserved Degrader Target Sets.
2.3.1General. Subject to this Section 2.3 (Reserved Degrader Target Sets) and Section 3.1 (Proposed Degrader Target Sets), Seagen shall have the right to designate [*] Available Degrader Target Sets to be subject to the exclusivity obligations set forth in Section 14.9.2 (Reserved Degrader Target Set Exclusivity) for [*] periods of [*] each subject to Section 2.3.4 (End of Reservation) (each such Available Degrader Target Set, a “Reserved Degrader Target Set”; each such period, a “Reservation Period”); provided, that [*]. Notwithstanding anything to the contrary in this Agreement, there will in no event be more than [*] Reserved Degrader Target Sets in total under this Agreement at any time.
2.3.2Activities for Reserved Degrader Target Sets. Upon the establishment or selection of a Reserved Degrader Target Set in accordance with Section 2.3.1 (General), Nurix shall perform certain Research activities with respect to such Reserved Degrader Target Sets exclusively under this Agreement to enable such Reserved Degrader Target Sets to be selected by Seagen as a Collaboration Degrader Target Set.
2.3.3Designation and Payment for Reserved Degrader Target Sets. Seagen may designate one (1) or more Available Degrader Target Set(s) to be Reserved Degrader Target Set(s) by delivery of one (1) or more Proposed Degrader Target Set Notice(s) to Nurix in accordance with Section 3.1 (Proposed Degrader Target Sets). Upon such designation, Seagen shall pay Nurix the Degrader Target Set [*] Reservation Fee described in Section 13.3 (Degrader Target Set [*] Reservation Fee) to reserve Degrader Target Sets as Reserved Degrader Target Sets for each Reservation Period commencing upon designation of such Reserved Degrader Target Set. Each Reserved Degrader Target Set may be reserved in accordance with this Section 2.3 (Reserved Degrader Target Sets) for multiple Reservation Periods, each upon payment of the Degrader Target Set [*] Reservation Fee and in accordance with the following sentence, but subject to Section 2.3.4 (End of Reservation). Prior to the expiration of any Reservation Period, Seagen shall have the right, upon written notice to Nurix, to extend the reservation of such Reserved Degrader Target Set for an additional Reservation Period (a “Degrader Target Set Reservation Extension Notice”); provided, that Seagen pays the Degrader Target Set [*] Reservation Fee for each such Reserved Degrader Target Set for each such additional Reservation Period in accordance with Section 13.3 (Degrader Target Set [*] Reservation Fee) prior to the expiration of the then-current Reservation Period.
2.3.4End of Reservation. Without limiting the foregoing, each Reserved Degrader Target Set shall immediately cease to be a Reserved Degrader Target Set upon the earliest of the following: (a) upon the [*] of the Effective Date, (b) upon the expiration of the Collaboration Degrader Target Set Replacement Term for all applicable Collaboration Degrader Target Sets, (c) upon Seagen exercising the Collaboration Degrader Target Set Replacement
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Right for all applicable Collaboration Degrader Target Sets, (d) if Seagen names such Reserved Degrader Target Set as the [*] in accordance with Section 2.2.2 ([*]); or (e) upon Seagen naming such Reserved Degrader Target Set as the Replacement Degrader Target Set with respect to a Collaboration Degrader Target Set in accordance with Section 2.2.3 (Collaboration Degrader Target Set Replacement Right).
2.4Addition of Degrader Targets. On a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis during the applicable Joint Research Term, the Parties may, subject to Section 10.6.1 (JRC Decisions) and Section 10.6.3 (Escalation of Certain JRC Disputes), amend the applicable Joint Research Plan (as further described in Section 4.1 (Joint Research Plans)) to add to such Collaboration Degrader Target Set [*] Available Degrader Target(s) that are Homologous Targets of the Degrader Targets in such Collaboration Degrader Target Set. For clarity, no Collaboration Degrader Target Set may contain more than [*] Degrader Targets unless the Parties otherwise mutually agreeing writing.
2.5Removal of Collaboration Degrader Targets.
2.5.1Amendment of Joint Research Plan. On a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis during the applicable Joint Research Term and before the occurrence of any Degrader License Exercise Date with respect to such Collaboration Degrader Target Set, the Parties may, subject to Section 10.6.1 (JRC Decisions) and Section 10.6.3 (Escalation of Certain JRC Disputes), amend the applicable Joint Research Plan (as further described in Section 4.1 (Joint Research Plans)) so that Nurix is no longer required under such Joint Research Plan to identify, synthesize, and characterize Collaboration Degraders that are Directed To one (1) or more Degrader Target(s) in the applicable Collaboration Degrader Target Set (such Degrader Targets, “Removed Degrader Targets”) and the consequences described in Section 2.5.2 (Removed Degrader Target) shall apply. Notwithstanding the foregoing, if any such amendment removes all Degrader Targets in a Collaboration Degrader Target Set, Seagen shall be deemed to have exercised a Collaboration Degrader Target Set Replacement Right with respect to such Collaboration Degrader Target Set subject to the terms of Section 2.2.3 (Collaboration Degrader Target Set Replacement Right); provided, that if no Collaboration Degrader Target Set Replacement Right is available as of such proposed amendment, then such proposed amendment shall have no force or effect and the Collaboration Degrader Target Set shall remain a Collaboration Degrader Target Set or Seagen may determine, in its sole discretion, to terminate this Agreement with respect to such Collaboration Degrader Target Set in accordance with Section 19.2.2(a) (Termination at Will).
2.5.2Removed Degrader Target. Upon the occurrence of an amendment described in Section 2.5.1 (Amendment of Joint Research Plan) with respect to a Collaboration Degrader Target Set: (a) each applicable Removed Degrader Target shall no longer be part of such Collaboration Degrader Target Set and shall not be a Collaboration Degrader Target, and (b) to the extent such original Collaboration Degrader Target Set contained one (1) or more Collaboration Degrader Targets in addition to the Removed Degrader Target(s), the Subset of such original Collaboration Degrader Target Set consisting of all such additional Collaboration Degrader Targets (and not the Removed Degrader Target(s)) shall, following such amendment, be considered the Collaboration Degrader Target Set.
2.6Licensed Degrader Target Sets. On a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, upon Seagen’s exercise of the applicable Degrader License Option and the occurrence of the Degrader License Effective Date in accordance with Article 5 (Degrader License Option) with respect to such Collaboration Degrader Target Set, such Collaboration Degrader Target Set shall become a Licensed Degrader Target Set, and all Collaboration Degraders that are Directed To such Collaboration Degrader Target Set shall become Licensed Degraders that are Directed To such Licensed Degrader Target Set.
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2.7[*] Licensed Degrader Target Set. On a Licensed Degrader Target Set-by-Licensed Degrader Target Set basis, upon [*] of a Licensed Product containing a Licensed Degrader (including any Licensed Degrader-Antibody Conjugate) that is Pan-Directed To (a) such Licensed Degrader Target Set or (b) a Subset thereof, such Licensed Degrader Target Set or such Subset, as applicable, shall become an “[*] Licensed Degrader Target Set.” For clarity, following such [*] (i) the Licensed Degrader Target Set will continue to be a Licensed Degrader Target Set, and (ii) the [*] Licensed Degrader Target Set may be the same Degrader Target Set as the Licensed Degrader Target Set, or alternatively, one of its Subsets.
2.8Former Collaboration Degrader Target Sets. If, prior to the occurrence of the Degrader License Effective Date with respect to Seagen’s exercise of the Degrader License Option for a Collaboration Degrader Target Set, such Collaboration Degrader Target Set (or any Subset thereof) becomes a Former Collaboration Degrader Target Set, then (i) the license grant by Nurix to Seagen as further described in Section 14.1 (Research Licenses) with respect to such Former Collaboration Degrader Target Set shall immediately terminate, (ii) Nurix’s exclusivity obligations described in Section 14.9.1 (Collaboration Degrader Target Set Exclusivity) shall no longer apply to such Former Collaboration Degrader Target Set, (iii) the license grant by Seagen to Nurix as further described in Section 14.1 (Research Licenses) with respect to such Former Collaboration Degrader Target Set shall immediately terminate, (iv) Nurix will have no further obligations under the applicable Joint Research Plan or Research activities with respect to such Former Collaboration Degrader Target Set; (v) Seagen will have no further obligations under this Agreement to Research, Develop, Commercialize, Manufacture or otherwise Exploit such Former Collaboration Degrader Target Set or any Collaboration Degrader or Collaboration Degrader-Antibody Conjugate Directed To such Former Collaboration Degrader Target Set, and (vi) the applicable provisions of Section 14.3 (Reversion Licenses) and Section 19.3 (Effects of Expiration and Termination) shall apply to such Former Collaboration Degrader Target Set. “Former Collaboration Degrader Target Set” means any Degrader Target Set that:
(a)was a Collaboration Degrader Target Set with respect to which a Replacement Degrader Target Set has been named in accordance with Section 2.2.3 (Collaboration Degrader Target Set Replacement Right);
(b)was a Collaboration Degrader Target Set with respect to which the Degrader License Option Period expired without Seagen exercising the applicable Degrader License Option in accordance with Section 5.2 (Degrader License Option Exercise); or
(c)was a Collaboration Degrader Target Set with respect to which Seagen had not exercised the applicable Degrader License Option as of the effective date of the termination of this Agreement (in its entirety or with respect to such Collaboration Degrader Target Set): (i) by Seagen, in accordance with Section 19.2.2 (Termination at Will) or Section 19.2.3 (Termination for Outside Date); or (ii) by Nurix, in accordance with Section 19.2.1 (Termination for Material Breach), Section 19.2.3 (Termination for Outside Date), or Section 19.2.4 (Termination for Bankruptcy);
provided, that no Degrader Target Set that includes any one (1) or more Collaboration Degrader Target(s), Licensed Degrader Target(s) or Degrader Targets in a Reserved Degrader Target Set is a Former Collaboration Degrader Target Set hereunder.
2.9Former Licensed Degrader Target Sets. If, after the occurrence of the Degrader License Effective Date that results from Seagen’s exercise (including any Deemed Exercise) of the Degrader License Option for a Collaboration Degrader Target Set as further described in Section 5.2 (Degrader License Option Exercise), such Licensed Degrader Target Set becomes a Former Licensed Degrader Target Set, then (i) the license grant by Nurix to Seagen as
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further described in Section 14.2 (Licensed Degrader License) with respect to such Former Licensed Degrader Target Set and each Subset thereof shall immediately terminate, (ii) Nurix’s exclusivity obligations described in Section 14.9.3 (Licensed Degrader Target Set Exclusivity) and Section 14.9.4 ([*] Licensed Degrader Target Set Exclusivity) shall no longer apply to such Former Licensed Degrader Target Set; (iii) Seagen will have no further obligations under this Agreement, including Section 6.1.2 (Development Diligence) and Section 9.2 (Commercialization Diligence), to Research, Develop, Commercialize, Manufacture or otherwise Exploit such Former Licensed Degrader Target Set or Licensed Products Directed To such Former Licensed Degrader Target Set, and (iv) the applicable provisions of Section 14.3 (Reversion Licenses) and Section 19.3 (Effects of Expiration and Termination) shall apply to such Former Licensed Degrader Target Set. “Former Licensed Degrader Target Set” means any Licensed Degrader Target Set with respect to which the corresponding Degrader License to Seagen has been terminated (including any termination of this Agreement in its entirety or with respect to such Licensed Degrader Target Set): (i) by Seagen, in accordance with Section 19.2.2 (Termination at Will); or (ii) by Nurix, in accordance with Section 19.2.1 (Termination for Material Breach) or Section 19.2.4 (Termination for Bankruptcy); provided, that no Degrader Target Set that includes any one (1) or more Collaboration Degrader Target(s), Licensed Degrader Target(s) or Degrader Targets in a Reserved Degrader Target Set is a Former Licensed Degrader Target Set hereunder.
ARTICLE 3
GATEKEEPING
3.1Proposed Degrader Target Sets.
3.1.1Proposed Degrader Target Set Notice. In the event that Seagen wishes to nominate a Degrader Target Set (a “Proposed Degrader Target Set”) to be (a) a Reserved Degrader Target Set under Section 2.3 (Reserved Degrader Target Sets), (b) the [*] in accordance with Section 2.2.2 ([*]), or (c) the Replacement Degrader Target Set substituting a Collaboration Degrader Target Set under Section 2.2.3 (Collaboration Degrader Target Set Replacement Right), then, in each case (clauses (a)-(c)), Seagen shall provide email notice to Nurix’s Alliance Manager of the identity of such Proposed Degrader Target Set and which of the Seagen rights described in clauses (a)-(c) above Seagen is exercising (each such notice, a “Proposed Degrader Target Set Notice”); provided, that unless such Proposed Degrader Target Set is a Reserved Degrader Target Set as of the date of the Proposed Degrader Target Set Notice, Seagen shall first undertake the Gatekeeper process described in Section 3.2 (Gatekeeping) for each Degrader Target in such Proposed Degrader Target Set prior to providing such Proposed Degrader Target Set Notice. For clarity, each Proposed Degrader Target Set shall contain no more than [*] Degrader Targets unless the Parties otherwise mutually agree in writing as further described in Section 1.71 (“Degrader Target Set”).
3.1.2Exercise of Seagen Rights.
(a)Reserved Degrader Target Sets. If, at the time of delivery of such Proposed Degrader Target Set Notice to Nurix’s Alliance Manager, the Proposed Degrader Target Set is a Reserved Degrader Target Set, then Seagen will be deemed to have exercised its applicable right described in clauses (a)-(c) of Section 3.1.1 (Proposed Degrader Target Set Notice), as set forth in the applicable Proposed Degrader Target Set Notice, with respect to such Proposed Degrader Target Set upon delivery of such Proposed Degrader Target Set Notice.
(b)Other Proposed Degrader Target Sets. For any Proposed Degrader Target Set for which Seagen wishes to exercise the applicable rights described in Section 3.1.1 (Proposed Degrader Target Set Notice) that is not a Reserved Degrader Target Set, Seagen may, after Seagen receives the applicable Gatekeeper Availability
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Notice pursuant to Section 3.2.2 (Gatekeeper Responsibilities) stating that all Degrader Target(s) contained in such Degrader Target Set are Available Degrader Targets, provide to Nurix’s Alliance Manager a Proposed Degrader Target Set Notice identifying the relevant Proposed Degrader Target Set comprising solely such Available Degrader Target(s) (as indicated by the Gatekeeper Availability Notice). If, at the time of delivery of such Proposed Degrader Target Set Notice to Nurix’s Alliance Manager, the Proposed Degrader Target Set is an Available Degrader Target Set, then Seagen will be deemed to have exercised its applicable right described in clauses (a)-(c) of Section 3.1.1 (Proposed Degrader Target Set Notice), as set forth in the applicable Proposed Degrader Target Set Notice, with respect to such Proposed Degrader Target Set upon delivery of such Proposed Degrader Target Set Notice.
3.1.3Unavailable Targets. If, at the time of delivery of such Proposed Degrader Target Set Notice to Nurix’s Alliance Manager, any Degrader Target in such Proposed Degrader Target Set is not an Available Degrader Target, then Seagen shall not have the right to exercise its applicable right described in clauses (a)-(c) of Section 3.1.1 (Proposed Degrader Target Set Notice) with respect to such Proposed Degrader Target Set.
3.2Gatekeeping.
3.2.1Appointment of Gatekeeper. During the Joint Research Term applicable to any Collaboration Degrader Target Set and until expiration of the Collaboration Degrader Target Set Replacement Term of all applicable Collaboration Degrader Target Sets, there shall be a gatekeeper that has been mutually agreed to and appointed by the Parties to perform the responsibilities set forth in Section 3.2.2 (Gatekeeper Responsibilities) (“Gatekeeper”). The Gatekeeper may be changed from time to time during the Joint Research Term upon either Party’s request and mutual written agreement of the Parties; provided, that the initial Gatekeeper as of the Effective Date shall be [*].
3.2.2Gatekeeper Responsibilities. At any time during the Joint Research Term applicable to any Collaboration Degrader Target Set and until expiration of the Collaboration Degrader Target Set Replacement Term of all applicable Collaboration Degrader Target Sets, and subject to this Section 3.2.2 (Gatekeeper Responsibilities), Seagen shall have the right to notify the Gatekeeper in writing of Degrader Targets that Seagen desires to have reviewed against a list of Excluded Degrader Targets then in effect that shall be maintained by Nurix and made available to the Gatekeeper to determine if such desired Degrader Targets are Available Degrader Targets (such desired Degrader Targets, “Seagen Desired Degrader Targets,” and such notice, a “Degrader Target Screening Notice”) which Degrader Target Screening Notice shall be in form and substance reasonably acceptable to both Parties, including with respect to customary and reasonable confidentiality and non-use obligations. Promptly (but no later than [*] Business Days) after receiving a Degrader Target Screening Notice, the Gatekeeper shall review and compare the Seagen Desired Degrader Targets listed in the Degrader Target Screening Notice against the list of Excluded Degrader Targets then in effect, and shall notify Seagen in writing, no later than [*] Business Days after delivery of the applicable Degrader Target Screening Notice, which, if any, of the Seagen Desired Degrader Targets are Available Degrader Targets (the “Gatekeeper Availability Notice”). The Gatekeeper shall not disclose to any Person (including any employee, agent or representative of Nurix or its Affiliates) other than Seagen the identity of, or any other information with respect to, the Seagen Desired Degrader Targets, including that Seagen has submitted a Degrader Target Screening Notice with respect to any Seagen Desired Degrader Target(s). The Parties acknowledge that the Gatekeeper may be an employee of Nurix and the disclosure by Seagen to such Gatekeeper of the Seagen Desired Degrader Targets shall not be considered a disclosure to Nurix or any Nurix Affiliate under this Section 3.2.2 (Gatekeeper Responsibilities), and further, such Gatekeeper shall at all times be bound by the confidentiality, non-disclosure and non-use obligations hereunder (including this
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Section 3.2.2 (Gatekeeper Responsibilities)) and in any Degrader Target Screening Notice. For clarity, the Seagen Desired Degrader Targets do not become Collaboration Degrader Targets until the requirements of Section 3.1 (Proposed Degrader Target Sets) are met. Seagen shall have the right to deliver to the Gatekeeper up to a maximum of [*] Degrader Target Screening Notices per Calendar Quarter, with a maximum of [*] Seagen Desired Degrader Targets described in all Degrader Target Screening Notices for each such Calendar Quarter.
ARTICLE 4
RESEARCH
4.1Joint Research Plans. The initial Joint Research Plan for each of the Initial Degrader Target Sets are attached hereto as [*], respectively (each an “Initial Joint Research Plan”). Within [*] following receipt by Nurix’s Alliance Manager of a [*] Notice in accordance with Section 2.2.2 ([*]) or Seagen’s exercise of its Collaboration Degrader Target Set Replacement Right in accordance with Section 2.2.3 (Collaboration Degrader Target Set Replacement Right), as applicable, Seagen shall prepare, and shall submit to the JRC for review, an initial draft Joint Research Plan for the applicable [*] or Replacement Degrader Target Set, which initial draft shall be substantially consistent with the Joint Research Plans for the Initial Degrader Target Sets. Without limiting the foregoing or Section 1.147 (“Joint Research Plan”), each Joint Research Plan shall (a) set forth in reasonable detail the Research activities to be undertaken by each Party with respect to the applicable Collaboration Degrader Target Set; (b) provide for Seagen’s ability to perform internal research with respect to the applicable Collaboration Degrader Target Set and applicable Collaboration Degraders; and (c) provide that Nurix shall use Commercially Reasonable Efforts to identify and deliver [*] Collaboration Degraders that (i) selectively bind and degrade all of the Degrader Target(s) in the applicable Collaboration Degrader Target Set, and (ii) meet the applicable Collaboration Degrader Criteria. The JRC will have [*] days to review and approve such draft of the Joint Research Plan, upon completion of which the Joint Research Plan will become effective; provided, that Nurix shall not unreasonably withhold, condition or delay its consent to such draft. For the avoidance of doubt, Nurix (A) exercising its rights under Section 10.6.2(b) or (B) withholding its consent with respect to a proposed Joint Research Plan amendment proposed by Seagen requiring Nurix to create, modify or optimize any Degrader to be orally available, in each case (clause (A) and (B)), shall not be deemed unreasonable hereunder. From time to time (at least on an annual basis), the JRC will discuss, prepare and approve amendments, as appropriate, to each then-current Joint Research Plan, including with respect to the removal of any Removed Degrader Targets (as further described in Section 2.5.1 (Amendment of Joint Research Plan)) and with respect to the addition of Available Degrader Targets to a Collaboration Degrader Target Set (as further described in Section 2.4 (Addition of Degrader Targets)). Subject to Section 10.6 (Committee Decisions), each amended Joint Research Plan will become effective and supersede the previous Joint Research Plan as of the date of approval by the JRC.
4.2Joint Research Activities. Subject to the terms and conditions herein, during each applicable Joint Research Term, on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, (a) the Parties will each use Commercially Reasonable Efforts to conduct the Research activities allocated to such Party in the applicable Joint Research Plan, and (b) without limiting the foregoing, Nurix will use Commercially Reasonable Efforts to (i) identify, synthesize, and characterize and deliver to Seagen Degraders that selectively bind and degrade one (1) or more of the Degrader Target(s) in the applicable Collaboration Degrader Target Set (including by conducting one (1) or more DEL Screens with respect to such Collaboration Degrader Target Set; provided, that if Nurix conducts any such DEL Screen(s) without Seagen’s prior written request, Nurix shall provide written notice to Seagen through the JRC that such DEL Screen(s) have been conducted, which notice shall summarize the results of such DEL Screen(s) in reasonable detail), (ii) optimize one (1) or more of the Degraders identified or synthesized through clause (i) above to cause pharmacologically relevant activity as a result of degrading one (1) or more of the Degrader Target(s) in such Collaboration Degrader Target Set, for the purpose of
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creating Collaboration Degraders that are Directed To such Collaboration Degrader Target Set; and (iii) work with Seagen to evaluate such Collaboration Degraders that are Directed To such Collaboration Degrader Target Set, including until they satisfy the applicable Collaboration Degrader Criteria, in each case (clauses (i)-(iii)), in accordance with the applicable Joint Research Plan (“Nurix Research”), and (c) once a Collaboration Degrader that is Directed To the applicable Collaboration Degrader Target Set satisfies the applicable Collaboration Degrader Criteria, Seagen will use Commercially Reasonable Efforts to (1) conjugate such Collaboration Degrader to one (1) or more Antibodies selected by Seagen, and (2) test whether the resulting Collaboration Degrader-Antibody Conjugates satisfy the applicable [*] Potency Benchmark, in each case, in accordance with the applicable Joint Research Plan (“Seagen Research”). For clarity, evaluation and optimization of a Collaboration Degrader may, in accordance with the applicable Joint Research Plan, continue after such Collaboration Degrader has satisfied the applicable Collaboration Degrader Criteria. Each Research Program will be subject to the oversight of the JRC. The foregoing activities, along with any other activities conducted under a Joint Research Plan, will be the “Joint Research.” Notwithstanding anything to the contrary in this Agreement, upon expiration of the Joint Research Term applicable to a Collaboration Degrader Target Set, Nurix shall have no further obligation to conduct any Research activities with respect to such Collaboration Degrader Target Set or its Collaboration Degraders.
4.3Joint Research Term Extension. Prior to the expiration of the applicable Joint Research Term, on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, upon written notice by Seagen to Nurix, Seagen may extend such Joint Research Term for [*] (a “Joint Research Term Extension”); provided, that (a) Seagen pays the Joint Research Term Extension Fee for each such Joint Research Term Extension in accordance with Section 13.2 (Joint Research Term Extension Fee), and (b) except as the Parties may otherwise mutually agree in writing, under no circumstances will the Joint Research Term with respect to any Collaboration Degrader Target Set, including [*] or any Replacement Degrader Target Set, as applicable, extend beyond the date that is [*] after the Effective Date.
4.4Seagen Research Activities. On a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, Seagen may continue to conduct the Seagen Research activities after the expiration of the applicable Joint Research Term and during the Degrader License Option Period (including as extended in accordance with Section 5.3 (Degrader License Option Period Extension)) (each a “Seagen Research Term”) and, following the Degrader License Effective Date that occurs with respect to Seagen’s exercise of the Degrader License Option in accordance with Section 5.2 (Degrader License Option Exercise), during the remaining Term of this Agreement. Seagen shall provide Nurix with updates regarding Seagen Research activities conducted by Seagen during the Seagen Research Term via the JSC and JRC as described in Section 10.1 (Joint Steering Committee) and Section 10.2 (Joint Research Committee). For clarity, notwithstanding that Nurix shall not have any obligation to perform any Research activities with respect to any Collaboration Degrader Target Set after the expiration of the Joint Research Term of such Collaboration Degrader Target Set, Nurix, at its sole discretion, may conduct certain Research activities to support Seagen Research activities during the Seagen Research Term.
4.5Additional Conjugation Candidates. On a Licensed Degrader Target Set-by-Licensed Degrader Target Set basis, Seagen may, after the applicable Degrader License Effective Date, request to obtain the right from Nurix to (a) conjugate the applicable Licensed Degrader to one (1) or more additional non-Antibody compound(s) that selectively binds any cell-surface protein and causes pharmacologically relevant activity as a result of such binding (such compound, an “Additional Conjugation Candidate”), and to (b) further Research, Develop, Manufacture, Commercialize or otherwise Exploit any such resulting Licensed Degrader-Additional Conjugation Candidate molecule in the Field in the Territory. Seagen shall provide a written notice to Nurix describing in reasonable detail any such Additional Conjugation Candidate and the cell-surface
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protein(s) to which such Additional Conjugation Candidate(s) are directed to. If, as of the delivery of such written notice to Nurix, such cell-surface protein(s) are neither [*], nor [*], then the Parties shall promptly execute an amendment to this Agreement in form and substance negotiated in good faith and reasonably acceptable to both Parties which allows Seagen to obtain the rights described in clauses (a) and (b) above.
4.6Seagen-Provided Property. Seagen will provide Nurix with (a) the Seagen Materials set forth in the applicable Joint Research Plan, and (b) any additional Seagen Materials to the extent necessary or reasonably useful for Nurix to conduct the Research activities assigned to Nurix under such Joint Research Plan, in each case ((a) and (b)), at Seagen’s sole expense. Prior to Seagen initially transferring any Seagen Materials to Nurix, the Parties shall enter into a material transfer agreement in substantially the form attached hereto as Schedule 4.6 (a “Material Transfer Agreement”), which Material Transfer Agreement will include an exhibit setting forth a description in reasonable detail of such Seagen Materials to be provided and the purposes for which such Seagen Materials will be used. Nurix shall not use any Seagen Materials for any purposes except as otherwise permitted under the terms and conditions of this Agreement or the applicable Material Transfer Agreement. For clarity, upon any Collaboration Degrader Target Set or Licensed Degrader Target Set becoming a Former Collaboration Degrader Target Set or a Former Licensed Degrader Target Set, as applicable, Nurix shall, at Seagen’s reasonable request, either promptly destroy or return any remaining Seagen Materials provided by Seagen with respect to such Collaboration Degrader Target Set or Licensed Degrader Target Set (provided such Seagen Materials are not necessary or reasonably useful for Nurix’s activities under this Agreement with respect to any Degrader Target Set that remains a Collaboration Degrader Target Set or a Licensed Degrader Target Set).
4.7Nurix-Provided Property. Nurix will provide Seagen, on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis during the applicable Joint Research Term and Seagen Research Term, (a) any Nurix Materials solely to the extent set forth in the applicable Joint Research Plan, at no additional cost to Seagen, and (b) other than pursuant to the preceding clause (a), any additional Nurix Materials, upon Seagen’s reasonable written request and at Seagen’s expense. Prior to Nurix initially transferring any such Nurix Materials to Seagen, the Parties shall enter into a Material Transfer Agreement in substantially the form attached hereto as Schedule 4.6, which Material Transfer Agreement will include an exhibit setting forth a description in reasonable detail of such Nurix Materials to be provided and the purposes for which such Nurix Materials will be used. Seagen shall not use, and shall not permit any Affiliate of Seagen or any Sublicensee to use, any Nurix Materials for any purposes except as otherwise permitted under the terms and conditions of this Agreement or the applicable Material Transfer Agreement. For clarity, upon any Collaboration Degrader Target Set or Licensed Degrader Target Set becoming a Former Collaboration Degrader Target Set or a Former Licensed Degrader Target Set, as applicable, Seagen shall, at Nurix’s reasonable request, either promptly destroy or return any remaining Nurix Materials provided by Nurix with respect to such Collaboration Degrader Target Set or Licensed Degrader Target Set (provided such Nurix Materials are not necessary or reasonably useful for Seagen’s activities under this Agreement with respect to any Degrader Target Set that remains a Collaboration Degrader Target Set or a Licensed Degrader Target Set).
4.8Information Sharing.
4.8.1Initial Information Sharing. Promptly, and in any event within [*] following each of (i) the Effective Date (or, within [*] after establishing the JRC, if later), (ii) receipt by Nurix’s Alliance Manager of a [*] Notice in accordance with Section 2.2.2 ([*]), or (iii) Seagen’s exercise of a Collaboration Degrader Target Set Replacement Right in accordance with Section 2.2.3 (Collaboration Degrader Target Set Replacement Right), as applicable, each Party will provide or make available to the JRC all relevant data and information Controlled by such Party with respect to the applicable Collaboration Degrader Target Set (including with
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respect to any Collaboration Degraders then Controlled by Nurix that are Directed To [*] or more Collaboration Degrader Targets included in the applicable Collaboration Degrader Target Set).
4.8.2Ongoing Information Sharing. During the Joint Research Term and Seagen Research Term, at each meeting of the JRC or as otherwise agreed by the Parties, the JRC shall review written reports or presentations regarding each Party’s activities and Research Results (as applicable) with respect to the Joint Research and Seagen Research of respective Collaboration Degraders and Collaboration Degrader-Antibody Conjugates. Each report or presentation under this Section 4.8 (Information Sharing) will cover such activities and Research Results since the previous JRC meeting, including a summary of results, information, chemical structures, data with respect to such Collaboration Degraders and Collaboration Degrader-Antibody Conjugates, and, during the Seagen Research Term, if applicable, in accordance with Section 4.4 (Seagen Research Activities) and at Nurix’s sole discretion, any request by Seagen for Nurix Research support. Upon request by the JRC or by the other Party, a Party will provide the JRC with such other information and such additional access to records with respect to Collaboration Degraders and Collaboration Degrader-Antibody Conjugates as the JRC or such other Party may reasonably request for the conduct or evaluation of the respective Joint Research activities or Seagen Research activities, including the underlying information used to create the Research Results and other summaries provided by such Party, such as data listings, data sets and programs used for the analyses collected by a Party in the course of conducting its activities with respect to the respective Collaboration Degraders and Collaboration Degrader-Antibody Conjugates. Within [*] after the expiration of the Joint Research Term with respect to a Collaboration Degrader Target Set, Nurix shall provide Seagen with a report summarizing all available Research Results generated by or on behalf of Nurix with respect to Collaboration Degraders that are Directed To such Collaboration Degrader Target Set.
4.9Records Retention. On a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, each Party will retain, and cause its Affiliates and its and their permitted subcontractors to retain, all records, accounts, notes, reports, data and laboratory notebooks with respect to the Joint Research activities performed with respect to such Collaboration Degrader Target Set until the [*] anniversary of the expiration of the Joint Research Term for such Collaboration Degrader Target Set or such longer period as may be required by Applicable Law.
4.10Research Costs. As between the Parties, [*]. For clarity, as between the Parties, Seagen shall [*].
ARTICLE 5
DEGRADER LICENSE OPTION
5.1Degrader License Option. Subject to the terms and conditions of this Agreement, including the provisions of this Article 5 (Degrader License Option), Nurix hereby grants to Seagen an exclusive option, exercisable by Seagen on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, in Seagen’s sole discretion at any time during the applicable Degrader License Option Period, to obtain the exclusive license described in Section 14.2 (Licensed Degrader License) (each, a “Degrader License Option”).
5.2Degrader License Option Exercise. Seagen may exercise each Degrader License Option (each, a “Degrader License Option Exercise”) at any point during the applicable Degrader License Option Period by providing written notice thereof (each, a “Degrader License Option Exercise Notice”) to Nurix, which notice will (a) identify the Collaboration Degrader Target Set that is the subject of such Degrader License Option Exercise, as further described in Section 2.6 (Licensed Degrader Target Sets), and (b) include Seagen’s determination as to whether any filings, notices, applications or other submissions under Antitrust Law are necessary or
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advisable in connection with such Degrader License Option Exercise (each such filing, notice, application or other submission, an “Antitrust Filing”) as further described in this Section 5.2 (Degrader License Option Exercise). Notwithstanding the foregoing, upon achievement of [*], a Degrader License Option Exercise shall be deemed to have occurred with respect to such Collaboration Degrader Target Set (“Deemed Exercise”). Notwithstanding anything to the contrary in this Agreement, there will in no event be more than [*] Licensed Degrader Target Sets in total under this Agreement at any time.
5.3Degrader License Option Period Extension. On a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, prior to the expiration of the applicable Degrader License Option Period for such Collaboration Degrader Target Set and on [*] with respect to such Degrader License Option Period, Seagen may extend such Degrader License Option Period for [*] upon delivery of written notice by Seagen to Nurix (each, a “Degrader License Option Period Extension”) and payment of the Degrader License Option Period Extension Fee for such Degrader License Option Period Extension in accordance with Section 13.5 (Degrader License Option Period Extension Fee).
5.4Antitrust Filings.
5.4.1Filings. As soon as reasonably practicable following the date on which Seagen provides a Degrader License Option Exercise Notice to Nurix in accordance with Section 5.2 (Degrader License Option Exercise) (the “Degrader License Exercise Date”) and in any event within [*] Business Days following the applicable Degrader License Exercise Date, if required, each of Nurix and Seagen will prepare and submit any Antitrust Filings, including any such required filings under the HSR Act and the rules promulgated thereunder, with respect to the relevant Degrader License Option Exercise. In connection with any such Antitrust Filings, the Parties will furnish promptly to the United States Federal Trade Commission (the “FTC”), the Antitrust Division of the United States Department of Justice (the “DOJ”) and any other applicable Governmental Authority any additional information requested within their authority under the HSR Act or other Antitrust Law, use reasonable efforts to obtain antitrust clearance for the transactions contemplated hereunder as soon as practicable with respect to the applicable Degrader License Option Exercise and otherwise cooperate with each other in the governmental antitrust clearance process. Seagen will bear all fees in connection with any filings under this Section 5.4 (Antitrust Filings), and each Party will bear its respective attorneys’ fees and other expenses in connection therewith.
5.4.2Effectiveness. Following a Degrader License Option Exercise, Seagen’s rights and obligations hereunder in connection with such Degrader License Option Exercise (including the licenses to be granted in connection therewith) will not become effective unless and until: (a) the day on which the applicable waiting period provided by the HSR Act, if any, will have expired or been terminated and all other required antitrust clearances under Antitrust Law have been obtained (solely to the extent applicable in any antitrust filings), as determined by Seagen in accordance with Applicable Law; or (b) the day on which Seagen determines in accordance with Applicable Law that no Antitrust Filings are required under Antitrust Law and delivers written notice to Nurix of such determination (the earlier to occur of (a) or (b), with respect to such Degrader License Option Exercise, the “Degrader License Effective Date”).
5.4.3Outside Date. On a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, if (a) Seagen identifies any Antitrust Filings as being necessary or advisable in the applicable Degrader License Option Exercise Notice in accordance with Section 5.2 (Degrader License Option Exercise) and (b) the applicable Degrader License Effective Date does not occur on or before [*] after the applicable Degrader License Exercise Date (each, an “Outside Date”), then:
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(a)Seagen may, in its sole discretion and upon written notice to Nurix delivered on or prior to the applicable Outside Date, extend the applicable Outside Date for such Degrader License Option Exercise by [*];
(b)if on such Outside Date (as extended under Section 5.4.3(a)) [*], either Party may terminate this Agreement with respect to such Collaboration Degrader Target Set by delivery of written notice to the other Party; and
(c)if on such Outside Date (as extended under Section 5.4.3(a)), or at any time following the applicable Degrader License Option Exercise Notice as determined by Seagen, any applicable clearances under Antitrust Laws have not been obtained in any country other than [*], upon Seagen’s written request to Nurix delivered on or prior to the applicable Outside Date (as may be extended under Section 5.4.3(a)), the Parties shall promptly amend this Agreement to exclude such country or countries from the definition of “Territory” with respect to the applicable Licensed Degrader Target Set and the Degrader License Effective Date shall occur, subject to such amended “Territory” definition, on the effective date of such amendment, provided, that if any such clearances under Antitrust Laws in any such country other than [*], are subsequently obtained during the Term, upon Seagen’s written request to Nurix the Parties shall promptly amend this Agreement to restore such country in the definition of “Territory” with respect to the applicable Licensed Degrader Target Set.
ARTICLE 6
DEVELOPMENT
6.1Development.
6.1.1Development Responsibility. Subject to the terms and conditions of this Agreement, Seagen will have the sole and exclusive right to Develop (and will solely and exclusively control, at its discretion, the Development of), itself or with or through its Affiliates, Sublicensees or other Third Parties, the respective Licensed Degrader and Licensed Degrader-Antibody Conjugate, including all Licensed Products, in the Field in the Territory. Subject to an applicable Profit-Share Product Agreement (if executed), all such Development will be at Seagen’s sole cost and expense.
6.1.2Development Diligence. Subject to the terms and conditions of this Agreement, on a Licensed Degrader Target Set-by-Licensed Degrader Target Set basis commencing upon the applicable Degrader License Effective Date, Seagen will, itself or with or through its Affiliates or Sublicensees or other Third Parties, use Commercially Reasonable Efforts to obtain Regulatory Approval of at least one (1) Licensed Product that is Directed To such Licensed Degrader Target Set for [*] Indications in each [*]. For clarity, such requirement may be satisfied by [*].
6.1.3Nurix Support. Nurix will, upon Seagen’s reasonable written request and at Seagen’s expense, reasonably assist Seagen with respect to the Development of (including obtaining and maintaining Regulatory Approval for) the Licensed Products. Seagen will reimburse Nurix for the costs of its support at the rate of [*].
6.1.4Development Updates. With respect to any Licensed Degrader Target Set, commencing upon [*] and continuing until [*], Seagen will submit to Nurix, [*], a [*] of Seagen’s material Development activities with respect to Licensed Products that are Directed To such Licensed Degrader Target Set that have been conducted since Seagen’s delivery of the applicable prior report, and any material Development activities that Seagen then [*]. The first such report shall be provided to Nurix within [*] days of [*] for such Licensed Product in or for
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the [*]. Upon Nurix’s reasonable written request, the Parties shall meet (including by teleconference) to discuss such report(s) and activities.
ARTICLE 7
REGULATORY
7.1Regulatory Matters.
7.1.1Responsibility. Subject to the terms and conditions of this Agreement, Seagen will have the sole right (and will solely control, at its discretion), itself or with or through its Affiliates, Sublicensees or other Third Parties, to: (a) prepare and submit to applicable Regulatory Authorities all Regulatory Materials, including MAAs and Clinical Trial applications, for the respective Licensed Products and (b) obtain and maintain all Regulatory Approvals for the respective Licensed Products.
7.1.2Communications with Regulatory Authorities. For clarity and without limiting Section 7.1.1 (Responsibility), Seagen will have the exclusive right to correspond or communicate with Regulatory Authorities regarding the respective Licensed Products. Unless required by Applicable Law, Nurix, its Affiliates and its permitted subcontractors will not correspond or communicate with Regulatory Authorities regarding any respective Licensed Product without first obtaining Seagen’s prior written consent. If Nurix, its Affiliates or its permitted subcontractors receive any correspondence or other communication from a Regulatory Authority regarding a Licensed Product, Nurix will provide Seagen with access to or copies of all such material written or electronic correspondence promptly after its receipt.
7.1.3Nurix Support. Nurix will support Seagen as may be reasonably requested in writing by Seagen from time to time in connection with Seagen’s preparation, submission to Regulatory Authorities and maintenance of Regulatory Materials for respective Licensed Products, including, upon Seagen’s reasonable written request, attending meetings with Regulatory Authorities regarding any respective Licensed Product. Seagen will reimburse Nurix for the costs of its support at the rate of [*].
7.2Regulatory Materials.
7.2.1Existing Regulatory Materials. Except to the extent notified otherwise in writing by Seagen, on a Licensed Product-by-Licensed Product basis, Nurix will assign and transfer (and hereby does assign and transfer as of the applicable Degrader License Effective Date), to Seagen (or its designee), no later than ten (10) Business Days after the applicable Degrader License Effective Date all Regulatory Materials (if any) for the applicable Licensed Degraders Controlled by or on behalf of Nurix or its Affiliates as of the applicable Degrader License Effective Date (the “Existing Regulatory Materials”), including by providing true, accurate and complete hard and electronic copies thereof to Seagen. From and after such assignment and transfer, Seagen (or its designee) will have the sole right, in its sole discretion, to file, maintain and hold title to all such Existing Regulatory Materials.
7.2.2New Regulatory Materials. All Regulatory Materials generated or arising from or in connection with activities under this Agreement with respect to Licensed Products after the Degrader License Effective Date for such Licensed Product will be owned by and held in the name of Seagen or its designee, and, except for Existing Regulatory Materials (which are addressed in Section 7.2.1 (Existing Regulatory Materials)), any such Regulatory Materials issued in the name of Nurix, its Affiliates or contractors will, promptly following the applicable Degrader License Effective Date, be assigned by Nurix to Seagen or its designee to the extent permitted by Applicable Law or, in the event assignment is not permitted under Applicable Law, held in trust for, or for the sole benefit of, Seagen or its designee.
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7.3Right of Reference; Access to Data. In the event of failure to transfer and assign any Regulatory Materials to Seagen or its designee, as required by Section 7.2.1 (Existing Regulatory Materials) or Section 7.2.2 (New Regulatory Materials), Seagen and its designees will have, and Nurix (on behalf of itself and its Affiliates) hereby grants to Seagen and its designees, access (as described in Section 7.2.1 (Existing Regulatory Materials) or Section 7.2.2 (New Regulatory Materials)) and a right of reference (without any further action required on the part of Nurix, its Affiliates or contractors, whose authorization to file this consent with any Regulatory Authority is hereby granted) to all Existing Regulatory Materials and Regulatory Materials described in Section 7.2.2 (New Regulatory Materials) and all data contained or referenced therein for Seagen and its designees to exercise its rights and perform its obligations under this Agreement with respect to the applicable Licensed Products. In all cases, Seagen and its designees will have access to all data contained or referenced in all such Regulatory Materials described in Section 7.2.1 (Existing Regulatory Materials) or Section 7.2.2 (New Regulatory Materials), and Nurix will ensure that Seagen and its designees are afforded such access by fulfilling its obligations thereunder.
ARTICLE 8
MANUFACTURING; PHARMACOVIGILANCE
8.1General. From and after the applicable Degrader License Effective Date, and subject to the terms and conditions of this Agreement, Seagen will have the sole right to Manufacture (and will solely control, at its discretion, the Manufacture of), itself or with or through its Affiliates, Sublicensees or other Third Parties, the respective Collaboration Degraders, Collaboration Degrader-Antibody Conjugates, and Licensed Products in the Field in the Territory. Subject to an applicable Profit-Share Product Agreement (if executed), all such Manufacturing will be at Seagen’s sole cost and expense. Nurix will keep Seagen informed regarding any relevant pharmacovigilance information Controlled by Nurix regarding other Degraders that include the same Proteasome Protein Binder as any Licensed Product to the extent necessary for Seagen and its Affiliates and Sublicensees to comply with Applicable Law. Without limiting the foregoing, the Parties shall negotiate in good faith and enter into a pharmacovigilance agreement or quality agreement if required by Applicable Law.
ARTICLE 9
COMMERCIALIZATION
9.1Commercialization Responsibility. Subject to the terms and conditions of this Agreement and the applicable Nurix Opt-In Agreements (if executed), Seagen will have the sole and exclusive right to Commercialize (and will solely and exclusively control, at its discretion, the Commercialization of), itself or with or through its Affiliates, Sublicensees or other Third Parties, the applicable Licensed Products in the Field in the Territory. Subject to the applicable Nurix Opt-In Agreements (if executed), all such Commercialization will be at Seagen’s sole cost and expense.
9.2Commercialization Diligence. For each Licensed Degrader Target Set, following the first Regulatory Approval of a Licensed Product that is Directed To such Licensed Degrader Target Set for the applicable country, Seagen will use Commercially Reasonable Efforts to Commercialize at least one (1) Licensed Product that is Directed To such Licensed Degrader Target Set for [*] Indications in each of the [*] countries. For clarity, such requirement may be satisfied by [*].
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ARTICLE 10
GOVERNANCE
10.1Joint Steering Committee.
10.1.1JSC Membership. Promptly, and in any event within [*] days following the Effective Date, the Parties will establish a joint steering committee (the “JSC”) as a forum for communication between the Parties in connection with their activities under this Agreement, to resolve Disputes that are properly escalated to the JSC pursuant to this Article 10 (Governance) and, to the extent Nurix exercises its Profit-Share Option, to serve as a forum for communication regarding Development and U.S. Commercialization activities with respect to the relevant Profit-Share Product during the Term that are relevant to this Agreement or the relevant Nurix Opt-In Agreement(s). The JSC will comprise [*] employee representatives of Seagen and [*] employee representatives of Nurix (or such other equal number of representatives as the Parties may agree), and the Alliance Managers may also attend JSC meetings in a non-voting capacity. Subject to the foregoing, each Party will appoint its respective representatives to the JSC from time to time, and may change its representatives, in its sole discretion, effective upon notice to the other Party designating such change. The JSC shall have co-chairpersons (the “JSC Co-Chairs”), and each Party shall select from their representatives its respective JSC Co-Chair and may change its designated JSC Co-Chair in its sole discretion, effective upon notice to the other Party designating such change. The JSC Co-Chairs will be jointly responsible for calling meetings of the JSC, circulating agenda and performing administrative tasks required to assure efficient operation of the JSC. The JSC may from time to time establish one (1) or more committees, subcommittees, or other project teams or working groups (each, a “Subcommittee”) to perform certain duties and exercise certain powers of the JSC as expressly set forth in this Agreement or delegated by the JSC to such Subcommittee (e.g., in the event Nurix exercises a Profit-Share Option, one (1) or more Subcommittees to oversee and coordinate the Parties’ co-promotion activities and the sharing of profit/loss and development costs with respect to the applicable Profit-Share Product). The JSC and any Subcommittee, including the JRC, and each Joint Research Team, are each referred to herein as a “Committee.”
10.1.2JSC Meetings. The JSC will meet [*] or as otherwise mutually agreed by the Parties (provided, that following dissolution of the JRC, the JSC shall not meet unless (i) there is a Profit-Share Product, or (ii) to resolve a Dispute properly referred to the JSC for resolution by the Joint Patent Committee in accordance with Section 10.6.4 (JPC Decisions)). The location for in-person meetings will alternate between Nurix and Seagen facilities (or such other location as is determined by the JSC). Alternatively, the JSC may meet by means of teleconference, videoconference or other similar means. As appropriate, additional employees or consultants of each Party may from time to time attend the JSC meetings as nonvoting observers; provided, that any such consultant will agree in writing to comply with confidentiality and non-use obligations substantially similar to those under this Agreement; and provided, further, that no Third Party personnel may attend unless otherwise agreed by both Parties and such Third Party is bound by confidentiality and non-use obligations substantially similar to those under this Agreement. Each Party will bear its own expenses related to the attendance of the JSC meetings by its representatives. Each Party may also call for special meetings to resolve particular matters requested by such Party upon at least [*] Business Days’ prior written notice to the other Party. Each Party’s respective JSC Co-Chair or their designee will alternate responsibility for preparing reasonably detailed written minutes of each JSC meeting to record all decisions made, action items assigned or completed and other appropriate matters. The JSC Co-Chairs or their respective designees will send meeting minutes to all members of the JSC for review promptly after each meeting. Each member will have [*] Business Days from receipt to comment on and to approve or provide comments to the minutes (such approval not to be unreasonably withheld, conditioned or delayed). If a member, within such time period, does not notify the applicable JSC Co-Chair in writing that they do not approve the minutes, the minutes will be deemed to
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have been approved by such member. Each Party’s JSC Co-Chair may designate another staff member of such Party, which could be the Alliance Manager, to coordinate administrative work for the JSC, including sending the written notice of holding JSC meetings, creating the draft of minutes or distributing the minutes.
10.1.3JSC Functions. The JSC’s responsibilities are as follows:
(a)Serving as a forum for communication between the Parties regarding the performance of the Research Programs hereunder, as necessary;
(b)If Nurix has exercised a Profit-Share Option, serving as a forum for communication regarding Development and U.S. Commercialization activities with respect to the relevant Profit-Share Product during the Term that are relevant to this Agreement or the relevant Nurix Opt-In Agreement(s);
(c)Resolving matters properly escalated to it by any other Committee that are within the scope of responsibilities of the JSC, or delegated to such other Committee by the JSC, or otherwise pursuant to this Agreement; and
(d)Fulfilling such other responsibilities as may be allocated to the JSC under this Agreement or by mutual written agreement of the Parties.
10.1.4JSC Dissolution. The JSC shall automatically dissolve and have no further responsibilities or authority after the expiration of the Term.
10.2Joint Research Committee.
10.2.1JRC Membership. Promptly, and in any event within [*] days following the Effective Date, the Parties will establish a joint research committee (the “JRC”) to oversee and coordinate the activities of the Parties under this Agreement with respect to the Research Programs. The JRC will be comprised of [*] employee representatives of Seagen and [*] employee representatives of Nurix (or such other equal number of representatives as the JSC or JRC may determine) that have appropriate expertise, credentials and authority for the tasks to be undertaken by the JRC, and the Alliance Managers will also attend JRC meetings in a non-voting capacity. Subject to the foregoing, each Party will appoint its respective representatives to the JRC from time to time, and may change its representatives, in its sole discretion, effective upon written notice to the other Party designating such change. Representatives from each Party will have appropriate technical credentials, experience and knowledge pertaining to and ongoing familiarity with the Research activities under the Joint Research Plans.
10.2.2JRC Co-Chairs. The JRC shall have co-chairpersons (the “JRC Co-Chairs”). The JRC Co-Chairs will be responsible for calling meetings of the JRC, circulating agenda and performing administrative tasks required to assure efficient operation of the JRC. Each Party’s respective JRC Co-Chair or their designee will alternate responsibility for preparing reasonably detailed written minutes of each JRC meeting to record all decisions made, action items assigned or completed and other appropriate matters. The applicable JRC Co-Chair will send meeting minutes to all members of the JRC promptly after a meeting for review. Each member will have [*] Business Days from receipt in which to comment on and to approve or provide comments to the minutes (such approval not to be unreasonably withheld, conditioned or delayed). If a member, within such time period, does not notify the applicable JRC Co-Chair in writing that they do not approve of the minutes, the minutes will be deemed to have been approved by such member. Each Party’s JRC Co-Chair may designate another staff member of such Party, which could be the Alliance Manager, to coordinate administrative work for the JRC,
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including sending the written notice of holding JRC meetings, creating the draft of minutes or distributing the minutes.
10.2.3JRC Meetings. The JRC will meet by mutual written agreement of the Parties no less frequently than once every [*] months. The location for in-person meetings will alternate between Nurix and Seagen facilities (or such other location as is determined by the JRC). Alternatively, the JRC may meet by means of teleconference, videoconference or other similar means. Each Party may also call for special meetings to discuss particular matters requested by such Party upon at least [*] Business Days’ prior written notice to the other Party.
10.2.4Other Members; Expenses. As appropriate, additional employees or consultants of each Party may from time to time attend the JRC meetings as nonvoting observers; provided, that any such consultant will agree in writing to comply with confidentiality and non-use obligations substantially similar to those under this Agreement; and provided, further, that no Third Party personnel may attend unless otherwise agreed by both Parties and such Third Party is bound by confidentiality and non-use obligations substantially similar to those under this Agreement. Each Party will bear its own expenses related to the attendance of the JRC meetings by its representatives.
10.2.5JRC Functions. The purpose of the JRC will be to oversee and coordinate the conduct of the Research Programs. The JRC’s specific responsibilities are as follows:
(a)Overseeing and coordinating the activities of each Party (including those of any of its Affiliates and Third Parties acting under its authority) under each Research Program, including the performance of Research activities under this Agreement, including as set forth in the applicable Joint Research Plan;
(b)Preparing and approving the Joint Research Plan for the [*] or any Replacement Degrader Target Set;
(c)Receiving and reviewing Research Results;
(d)Determining that a Collaboration Degrader meets (or does not meet) the applicable Collaboration Degrader Criteria;
(e)Determining whether to remove any Degrader Target(s) from a Collaboration Degrader Target Set;
(f)Approving any proposed amendment to any Joint Research Plan;
(g)Fulfilling such other responsibilities as may be allocated to the JRC under this Agreement, by the JSC or by mutual written agreement of the Parties.
10.2.6JRC Dissolution. The JRC shall automatically dissolve and have no further responsibilities or authority after the expiration of the last-to-expire Seagen Research Term.
10.3Joint Research Teams.
10.3.1Joint Research Team Membership. Promptly, and in any event within [*] days following the applicable Degrader Target Set Selection Date, the JRC shall establish a joint research team as a working group of the JRC for each Collaboration Degrader Target Set (each a “Joint Research Team”); provided, that with respect to the Initial Degrader Target Sets, the applicable Joint Research Teams shall be formed on the Effective Date and shall comprised of
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the individuals set forth on Schedule 10.3.1. Each Joint Research Team shall include appropriate representation of each Party (which representation need not be equal), and each member of a Joint Research Team shall have appropriate technical expertise, credentials, experience and authority for the relevant Collaboration Degrader Target Set and the tasks to be undertaken by such Joint Research Team. Subject to the foregoing, each Party will appoint its respective representatives to each Joint Research Team from time to time, and may change its representatives, in its sole discretion, effective upon written notice to the other Party designating such change; provided, that each Party shall designate [*] from such Party to each Joint Research Team.
10.3.2Functions; No Decision-Making Authority. Each Joint Research Team shall serve as a forum for communication between the Parties with respect to the applicable Collaboration Degrader Target Set and the relevant Joint Research Plan, and shall monitor the implementation of such Joint Research Plan hereunder. The Joint Research Teams shall endeavor to agree and operate by consensus with respect to any matter before the Joint Research Team; provided, that the Joint Research Teams shall not have any decision-making authority under this Agreement. In the event the representatives of the Parties on a Joint Research Team are not able to reach agreement on a matter properly before the Joint Research Team within [*] days, then the matter shall be reported to the Alliance Managers for escalation to the JRC.
10.3.3Joint Research Team Dissolution. Each Joint Research Team shall automatically dissolve and have no further responsibilities or authority upon the expiration of the Seagen Research Term for the relevant Collaboration Degrader Target Set applicable to such Joint Research Team.
10.4Joint Patent Committee. Promptly after the first JSC meeting, the Parties will form a Joint Patent Committee (the “Joint Patent Committee” or “JPC”). The Joint Patent Committee shall comprise an equal number of representatives from each Party. The Joint Patent Committee will be responsible for the coordination of the Parties’ efforts in accordance with the provisions set forth in Article 15 (Intellectual Property Matters).
10.5Alliance Manager. Within [*] Business Days following the Effective Date, each Party will appoint an individual to act as the alliance manager for such Party (each, an “Alliance Manager”). Each Alliance Manager will thereafter be permitted to attend meetings of each Committee as a nonvoting observer. The Alliance Managers will be the primary point of contact for the Parties regarding the activities under this Agreement and will help facilitate all such activities hereunder. At any given time, the Alliance Managers will be responsible for keeping a then-current list of (a) each Collaboration Degrader Target Set, including any addition or removal thereto, (b) progress under the respective Joint Research Plan, (c) Research Milestone Events that have been achieved, (d) Collaboration Degraders and Collaboration Degrader-Antibody Conjugates under each applicable Research Program, and (e) Licensed Degrader Target Sets, Licensed Degraders and Licensed Degrader-Antibody Conjugates. The Alliance Managers will also keep the JRC reasonably informed of any changes to the items identified in the immediately previous sentence.
10.6Committee Decisions.
10.6.1JRC Decisions. The JRC will endeavor to make decisions by consensus with each Party having, collectively, a single vote on any matter before the JRC irrespective of the number of representatives of such Party in attendance at a meeting of the JRC. In the absence of consensus with respect to a matter that remains unresolved, each Party shall have the right to refer such matter to the JSC for resolution in accordance with and subject to Section 10.6.2 (JSC Decisions) and Section 10.6.3 (Escalation of Certain JRC Disputes).
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10.6.2JSC Decisions. Any decision by the JSC on any matter with respect to which it has authority must be made by consensus, with each Party having, collectively, a single vote on any such matter irrespective of the number of representatives of such Party in attendance at a meeting of the JSC; provided, that if, despite using reasonable efforts, the JSC cannot reach consensus on any such deadlocked matter within a period of [*] days (or such other period as the Parties may agree in writing) after it has met and attempted to reach such consensus, then either Party may, by written notice to the other Party, refer the deadlocked matter to the Executive Officers for resolution in the manner described in Section 20.6.2 (Dispute Escalation) (notwithstanding anything to the contrary contained in such Section); provided, however, that, if such Executive Officers do not reach agreement on such deadlocked matter within [*] days after such deadlocked matter is first referred to the Executive Officers, then, subject to Section 15.2.1(b), if applicable, on a Research Program-by-Research Program basis:
(a)Seagen will have final decision-making authority on the JSC with respect to any decision:
(i)involving the occurrence of a Research Milestone Event;
(ii)involving the day-to-day implementation of any Seagen Research activity that is set forth in a Joint Research Plan, including any amendments thereto;
(iii)involving the clinical Development and Commercialization of a Licensed Product;
(iv)primarily related to (A) the conjugation of a Collaboration Degrader to an Antibody, or (B) the advancement of a Collaboration Degrader-Antibody Conjugate to a subsequent stage of Research or Development (for clarity, the Collaboration Degrader Criteria may be used in connection with decisions as to whether to advance particular Collaboration Degraders that are Directed To such Collaboration Degrader Target Set); and
(v)to amend a Joint Research Plan (including amending a Joint Research Plan to remove any Degrader Target from a Collaboration Degrader Target Set, as described in Section 2.5 (Removal of Collaboration Degrader Targets), and any corresponding activity intended to optimize a Collaboration Degrader to cause pharmacologically relevant activity as a result of binding or degradation of the applicable Degrader Target); provided, that such amendment does not (A) add any Degrader Target to the applicable Collaboration Degrader Target Set (without limiting Seagen’s rights under Article 2 (Degrader Target Sets) or Article 3 (Gatekeeping)), or (B) require Nurix to (1) take any action that would or would reasonably be expected to result in a violation of Applicable Law, (2) breach or terminate any agreement between Nurix and a Third Party, (3) hire or engage additional employees or agents outside the ordinary course of business, (4) purchase any capital equipment solely for use in connection with such Joint Research Plan outside the ordinary course of business, or (5) acquire or expand any interest in real property.
(b)Nurix, subject to its obligations to use Commercially Reasonable Efforts as described in Article 4 (Research), will have final decision-making authority on the JSC with respect to any decision primarily related to:
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(i)the allocation and use of Nurix resources in the performance of the Research activities assigned to Nurix under any Joint Research Plan;
(ii)the day-to-day implementation of any Nurix Research activity that is set forth in the Joint Research Plan, including any amendments thereto;
(iii)the design or synthesis of Collaboration Degraders; provided, that Nurix will not, and will not use its final decision-making authority herein to, unreasonably withhold, condition, or delay consent to any Seagen-requested change to the chemical composition of a Collaboration Degrader; provided, that (A) such Seagen-requested change is reasonable, (B) such Seagen-requested change would not cause Nurix to violate any exclusivity obligations owed to a Third Party, and (C) the resulting Collaboration Degrader would continue to be Directed To the applicable Collaboration Degrader Target Set; and
(iv)the design and execution of Collaboration Degrader preclinical absorption, distribution, metabolism, and excretion (ADME) studies as contemplated by the applicable Joint Research Plan to be conducted by Nurix for the purposes of informing the activities in clause (ii) above; provided, that such design and execution are consistent with the applicable portions of such Joint Research Plan.
10.6.3Escalation of Certain JRC Disputes. Any decision by the JRC on any matter with respect to which it has express authority must be made by consensus, with each Party having, collectively, a single vote on any such matter irrespective of the number of representatives of such Party in attendance at a meeting of the JRC; provided, that if, despite using reasonable efforts, the JRC cannot reach consensus on any such deadlocked matter within a period of [*] days (or such other period as the Parties may agree in writing) after it has met and attempted to reach such consensus, then either Party may, by written notice to the other Party, refer the deadlocked matter to the JSC for resolution pursuant to Section 10.6.2 (JSC Decisions).
10.6.4JPC Decisions. Subject to Section 15.2.1(b), if applicable, in the event of a dispute or failure to reach unanimous agreement on any matter before the Joint Patent Committee, such dispute or failure to agree shall be submitted to the chief patent counsels of each Party for resolution, subject to the provisions of Article 15 (Intellectual Property Matters) that determine which Party has control and final decision-making authority with respect to certain matters related to the Prosecution and Maintenance and enforcement of Patents. Subject to Section 20.6.1 (Choice of Law) regarding Patent Disputes and Section 15.2.1(b), if applicable, any other such dispute or failure to agree not resolved by the chief patent counsels of the Parties may be referred to the JSC for resolution.
10.7Scope of Committee Authority. For clarity and notwithstanding the creation of any Committee, each Party will retain the rights, powers and discretion granted to it hereunder, and no Committee will be delegated or vested with such rights, powers or discretion unless such delegation or vesting is expressly provided herein, or the Parties expressly so agree in writing (including any decision to be made at Party’s sole discretion hereunder). No Committee, nor a Party via exercise of its final decision-making authority will have the power to (a) subject to Seagen’s final decision-making authority in Section 10.6.2(a)(i), resolve any Dispute regarding the amount of any payment owed under this Agreement, (b) amend, waive or modify any term of this Agreement, (c) determine whether or not a Party has met its diligence or other obligations under this Agreement, or (d) determine whether or not a Party has final decision-making authority with
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respect to a matter, and no decision of any Committee or exercise by a Party of its final decision-making authority will be in contravention of any express terms or conditions of this Agreement. It is understood and agreed that issues to be formally decided by the JRC are limited to those specific issues that are expressly provided in Section 10.2.5 (JRC Functions) of this Agreement and Disputes at the JRC which relate to subjects other than those expressly set forth in Section 10.2.5 (JRC Functions) will be handled according to Section 10.6.1 (JRC Decisions) and Section 20.6 (Choice of Law; Dispute Resolution; Jurisdiction), as applicable. Once a Committee is disbanded, such Committee will have no further obligations under this Agreement and, thereafter, each Party will designate a contact person for the exchange of information under this Agreement or such exchange of information will be made through the Alliance Managers. In the event a Committee is disbanded, any decisions that are designated under this Agreement as being subject to the review or approval of such Committee will be made by the Parties directly, subject to the other terms and conditions of this Agreement.
10.8Day-to-Day Responsibilities. Each Party will be responsible for day-to-day implementation and operations of the activities for which it has or is otherwise assigned responsibility under this Agreement; provided, that such implementation is not inconsistent with the express terms of this Agreement or the decisions of the JRC within the scope of its authority specified herein.
10.9No Services. The activities to be performed by the JRC and any Subcommittee shall solely relate to governance under this Agreement and are not intended to be or involve the delivery of services.
ARTICLE 11
U.S. PROFIT-SHARE OPTION
11.1U.S. Profit-Share Option. Subject to the terms set forth in this Article 11 (U.S. Profit-Share Option), Nurix will have two (2) options (each such option, a “Profit-Share Option”), each such Profit-Share Option exercisable with respect to one (1) Licensed Product (each such Licensed Product after Profit-Share Option exercise in accordance with this Article 11 (U.S. Profit-Share Option), including Section 11.2.3 (Profit-Share Products), a “Profit-Share Product”), to enter into the following agreements with Seagen or its Affiliate for each such Profit-Share Product: (a) a Profit-Share Product Co-Funding and Profit-Sharing Agreement providing for the sharing of the net profits and net losses of and Global Development Costs for such Profit-Share Product on a [*] basis ([*]) on the terms set forth in Schedule 11.1A (each such agreement, a “Profit-Share Product Agreement”), and (b) a Co-Promotion Agreement regarding the co-promotion of such Profit-Share Product in the U.S. on the terms set forth in Schedule 11.1B (each such agreement, a “Co-Promotion Agreement”). The Profit-Share Product Agreement and Co-Promotion Agreement for a particular Profit-Share Product, and any other agreement(s) entered into by the Parties or their Affiliates pursuant to such agreements, are referred to herein, together, as the “Nurix Opt-In Agreement(s).” Each of the Nurix Opt-In Agreements will contain the terms and conditions set forth in the respective Schedules referenced above for such Nurix Opt-In Agreement as well as other terms and conditions as are reasonable and customary for the applicable subject matter in the context of a similar arrangement between similarly situated biopharmaceutical or biotechnology companies involving a similar product, taking into account all relevant factors (including, for example, the experience of the Parties in Commercializing biopharmaceutical products and the relative roles of the Parties with respect to the promotion of and medical affairs related to the relevant Profit-Share Product). Such Nurix Opt-In Agreement terms shall be negotiated in good faith by the Parties promptly following exercise by Nurix of the applicable Profit-Share Option; provided, that the Parties shall use Commercially Reasonable Efforts to execute all Nurix Opt-In Agreements with respect to the applicable Profit-Share Product within [*] following Nurix’s delivery to Seagen of the Profit-Share Option Exercise Notice; provided, further, that if, at the end of such [*] period, the Parties are continuing to negotiate in
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good faith (i) with respect to the applicable Profit-Share Product Agreement, such period shall be extended to a date mutually agreed by the Parties to enable the Parties to finalize and execute such Profit-Share Product Agreement and (ii) with respect to the applicable Co-Promotion Agreement, such period shall be extended by [*] (it being agreed and acknowledged that in order for Nurix to exercise its co-promotion rights with respect to a Profit-Share Product, the Parties shall use Commercially Reasonable Efforts to mutually agree on a form of Co-Promotion Agreement as promptly as practicable and shall enter into the relevant Co-Promotion Agreement (A) if the Profit-Share Option Triggering Event was [*], and (B) for all other Profit-Share Option Triggering Events, at least [*] before the expected Commercial launch of the Profit-Share Product in the U.S.).
11.2Exercise of Profit-Share Option.
11.2.1Option Data Package. No later than [*] before the anticipated achievement by Seagen of a Profit-Share Option Triggering Event with respect to any Licensed Product, Seagen shall provide or make available to Nurix a data package for such Licensed Product including (a) to the extent available and in Seagen’s possession and Control (for clarity, without requiring Seagen to conduct any additional Research or Development activities): (i) [*], (ii) [*], and (iii) [*]; and (b) [*], in each case, for such Licensed Product (clauses (a) and (b), collectively, the “Option Data Package”); provided, that Seagen shall have no obligation to provide an Option Data Package to Nurix for a given Licensed Product and Nurix shall have no right to exercise its Profit-Share Option with respect to such Licensed Product, in each case, if Nurix has previously exercised two (2) Profit-Share Options and the Parties have entered into a Profit-Share Product Agreement for the Profit-Share Products that were the subject of such exercises. If the applicable Profit-Share Option Triggering Event has not occurred within [*] of Seagen’s delivery of the applicable Option Data Package or if the Profit-Share Option Triggering Event was [*], then Seagen shall, within [*] Business Days following the applicable Profit-Share Option Triggering Event, provide Nurix with a written summary of material updates to the information provided by Seagen for the applicable Option Data Package and provide or make available to Nurix updated copies of the documents and information described in clause (a) above, as applicable, including any [*] with respect to such Licensed Product to the extent applicable (such written summary and updates, the “Supplementary Option Data Package”). For the avoidance of doubt, Seagen may, upon notice to Nurix or through a Committee, update its anticipated date of obtaining Regulatory Approval and Commercial launch in the U.S. for a Licensed Product from time to time, and Seagen shall notify Nurix of its anticipated date of obtaining Regulatory Approval and Commercial launch in the U.S. for a Licensed Product from time to time upon Nurix’s reasonable request.
11.2.2Option Exercise. Seagen shall notify Nurix in writing promptly following the occurrence of a Profit-Share Option Triggering Event, which notice shall indicate the relevant event and date thereof. At any time during the applicable Profit-Share Option Exercise Period, Nurix may exercise one (1) of its Profit-Share Options with respect to the Licensed Product identified in such Option Data Package by providing a written notice to Seagen (such notice the “Profit-Share Option Exercise Notice”). For purposes of this Agreement, “Profit-Share Option Exercise Period” means, on a Licensed Product-by-Licensed Product basis, the period of time beginning on the occurrence of the Profit-Share Option Triggering Event for such Licensed Product, and ending on the later to occur of (a) [*] after delivery by Seagen of the Option Data Package for such Licensed Product, and (b) [*] after the later to occur of (i) delivery of written notice by Seagen to Nurix that the applicable the Profit-Share Option Triggering Event for such Licensed Product had occurred, and (ii) to the extent required under Section 11.2.1 (Option Data Package), delivery of the Supplementary Option Data Package.
11.2.3Profit-Share Products. If Nurix exercises a Profit-Share Option for a Licensed Product and Seagen does not veto such exercise to the extent permitted to do so and in
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accordance with Section 11.3 (U.S. Profit-Share Opt-In Veto), then: (a) upon execution of the applicable Profit-Share Product Agreement, such Licensed Product will be a Profit-Share Product; and (b) starting from such exercise and subject to Section 11.2.4 (Milestone Payments Related to the Profit-Share Triggering Events) and Section 11.4.2 (Opt-Out Date and Wind-Down), Nurix will forego the right to receive Development and Regulatory Milestone Payments for [*] Development and Regulatory Milestones Events achieved or deemed achieved by such Profit-Share Product (such Milestone Payments, the “Foregone Milestones”). For the avoidance of doubt, there shall be no more than two (2) Profit-Share Products under this Agreement.
11.2.4Milestone Payments Related to the Profit-Share Triggering Events.
(a)If (i) the Profit-Share Option Triggering Event is [*], (ii) Nurix exercises its Profit-Share Option in accordance with Section 11.2 (Exercise of Profit-Share Option), and (iii) Seagen does not veto such exercise pursuant to Section 11.3 (U.S. Profit-Share Opt-In Veto), then, in the case of (i), (ii) and (iii), notwithstanding anything to the contrary contained herein:
(A) such Profit-Share Option Triggering Event shall constitute achievement of Development and Regulatory Milestone Event [*], and Seagen shall pay Nurix the Development and Regulatory Milestone Payment for Development and Regulatory Milestone Event [*] in accordance with Section 13.7 (Development and Regulatory Milestones) (e.g., if the applicable Licensed Product is the First Licensed Product (as defined in Section 13.7.2(b)), then Seagen shall pay Nurix [*];
(B) in lieu of paying Development and Regulatory Milestone Payment [*] in accordance with Section 13.7 (Development and Regulatory Milestones), Seagen shall, upon achievement of Development and Regulatory Milestone Event [*], pay Nurix an amount equal to [*]; and
(C) for clarity, in the event that the applicable Licensed Product is not the First Licensed Product (as defined in Section 13.7.2(b)), then the principles set forth above shall apply to the applicable payment amounts as adjusted subject to [*].
(b)If (i) the Profit-Share Option Triggering Event is [*], (ii) Nurix exercises its Profit-Share Option in accordance with Section 11.2 (Exercise of Profit-Share Option), and (iii) Seagen does not veto such exercise pursuant to Section 11.3 (U.S. Profit-Share Opt-In Veto), then, in the case of (i), (ii) and (iii), notwithstanding anything to the contrary contained herein, such Profit-Share Option Triggering Event shall constitute achievement of Development and Regulatory Milestone Event [*]; provided that, in lieu of paying Development and Regulatory Milestone Payment [*] in accordance with Section 13.7 (Development and Regulatory Milestones), Seagen shall pay Nurix an amount equal to [*]. For clarity, in the event that the applicable Licensed Product is not the First Licensed Product (as defined in Section 13.7.2(b)), then the principles set forth above shall apply to the applicable payment amounts as adjusted subject to [*].
(c)If (i) the Profit-Share Option Triggering Event is [*], (ii) Nurix exercises its Profit-Share Option in accordance with Section 11.2 (Exercise of Profit-Share Option), and (iii) Seagen does not veto such exercise pursuant to Section 11.3 (U.S. Profit-Share Opt-In Veto), then, in the case of (i), (ii) and (iii), notwithstanding anything to the contrary contained herein:
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(A) such Profit-Share Option Triggering Event shall constitute achievement of Development and Regulatory Milestone Event [*]; provided that, in lieu of paying Development and Regulatory Milestone Payment [*] in accordance with Section 13.7 (Development and Regulatory Milestones), Seagen shall pay Nurix an amount equal to [*];
(B) such Profit-Share Option Triggering Event shall also constitute achievement of Development and Regulatory Milestone Event [*]; provided that, in lieu of paying Development and Regulatory Milestone Payment [*] in accordance with Section 13.7 (Development and Regulatory Milestones) upon [*], Seagen shall pay Nurix an amount equal to the Development and Regulatory Milestone Payment for Development and Regulatory Milestone Event [*]; and
(C) for clarity, in the event that the applicable Licensed Product is not the First Licensed Product (as defined in Section 13.7.2(b)), then the principles set forth above shall apply to the applicable payment amounts as adjusted subject to [*].
(d)Notwithstanding anything to the contrary contained herein (including in Section 13.9.1 (Research, Development and Regulatory Milestones)), in the event that any Development and Regulatory Milestone Event is achieved or deemed to be achieved pursuant to this Section 11.2.4 (Milestone Payments Related to the Profit-Share Triggering Events), Seagen shall notify Nurix thereof within [*] after Seagen’s receipt of the applicable Profit-Share Option Exercise Notice and request an invoice from Nurix for the applicable Milestone Payment, and Seagen, subject to any good faith Dispute regarding the applicable Milestone Event or Milestone Payment, shall pay the applicable Milestone Payment within [*] after receipt of such invoice. In the event of any conflict or inconsistency between the notice and payment provisions of Article 13 (Financial Terms) and this Section 11.2.4 (Milestone Payments Related to the Profit-Share Triggering Events) with respect to any Milestone Event or Milestone Payment that is or could be subject to this Section 11.2.4 (Milestone Payments Related to the Profit-Share Triggering Events), the terms of this Section 11.2.4 (Milestone Payments Related to the Profit-Share Triggering Events) shall control, and the notice and payment provisions of Article 13 (Financial Terms) shall be tolled until it is determined whether the terms and conditions of this Section 11.2.4 (Milestone Payments Related to the Profit-Share Triggering Events) apply to any such Milestone Event or Milestone Payment.
(e)[*].
11.2.5Co-Promotion Criteria. Notwithstanding anything to the contrary contained in this Agreement, on a Profit-Share Product-by-Profit-Share Product basis, as soon as practicable following Nurix’s delivery to Seagen of a Profit-Share Option Exercise Notice, Nurix shall provide to Seagen (a) a plan (supported with reasonable documentation) to phase in and hire an adequate sales force and sufficient medical affairs personnel to support Nurix’s co-promotion activities with respect to the Profit-Share Product consistent with the applicable Option Data Package and Global Development Cost Estimated Budget (“Nurix Co-Promotion Plan”) which plan shall be delivered to Seagen (i) if the Profit-Share Option Triggering Event was [*], at [*], and (ii) for all other Profit-Share Option Triggering Events, at least [*], and (b) reasonable documentation that Nurix has or shall have the Nurix Resources in place as of the anticipated date of entry of the applicable Co-Promotion Agreement. If Nurix does not provide to Seagen the Nurix Co-Promotion Plan, or have in place the Nurix Resources, in each case as of
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the date when required to be provided or satisfied (as applicable) under this Section 11.2.5 (Co-Promotion Criteria), then Nurix shall not have the right and Seagen shall not have the obligation to enter into a Co-Promotion Agreement with respect to such Profit-Share Product. Any Dispute regarding Nurix’s satisfaction of the requirements of this Section 11.2.5 (Co-Promotion Criteria) shall be resolved pursuant to Section 20.6.2 (Dispute Escalation). For the avoidance of doubt, failure by Nurix to satisfy the co-promotion criteria contemplated by this Section 11.2.5 (Co-Promotion Criteria) or the absence of a Co-Promotion Agreement as contemplated hereby will have no impact on the rights and obligations of the Parties with respect to a Profit-Share Product Agreement with respect to such Profit-Share Product. For purposes of this Agreement, “Nurix Resources” means with respect to the Profit-Share Product, Nurix has as of such time [*] in cash or a bona fide financing plan to raise such amount in cash in the timeframe required by the Global Development Cost Estimated Budget for such Profit-Share Product.
11.3U.S. Profit-Share Opt-In Veto. Notwithstanding the foregoing in this Article 11 (U.S. Profit-Share Option), Seagen will have the right to veto Nurix’s exercise of a Profit-Share Option for a maximum of [*] Licensed Products by providing written notice to Nurix of Seagen’s veto within [*] Business Days after Seagen’s receipt of the applicable Profit-Share Option Exercise Notice; provided, that Seagen may [*]. If Seagen exercises a veto right, Nurix will be deemed not to have exercised the applicable Profit-Share Option.
11.4Nurix Opt-Out.
11.4.1Opt-Out Notice. Subject to the terms and conditions of this Agreement (including this Section 11.4 (Nurix Opt-Out)), on a Profit-Share Product-by-Profit-Share Product basis, Nurix shall have the right, exercisable in its sole discretion, to elect to opt-out of: (a) all of the Nurix Opt-In Agreements then in effect with respect to such Profit-Share Product and instead receive the royalty payments described in Section 13.10 (Royalties); or (b) if a Profit-Share Product Agreement has been executed and remains in effect, only the Co-Promotion Agreement with respect to such Profit-Share Product, in which case the terms and conditions of the Profit-Share Product Agreement and of this Agreement with respect to Profit-Share Products shall continue to apply, subject to any applicable terms of the relevant Nurix Opt-In Agreements. Nurix may exercise its right to opt-out under this Section 11.4.1 (Opt-Out Notice) by delivery to Seagen of written notice indicating such exercise and whether such exercise is under clause (a) or (b) of this Section 11.4.1 (Opt-Out Notice) (each such notice, a “Nurix Opt-Out Notice”); provided, however, that Nurix may not, without the prior written consent of Seagen, deliver a Nurix Opt-Out Notice under clause (a) or (b) prior to [*] anniversary of Nurix’s exercise of its Profit-Share Option. For clarity, following the Nurix Opt-Out Date with respect to all Nurix Opt-In Agreements for a Profit-Share Product, subject to this Section 11.4 (Nurix Opt-Out) and Section 13.7.2(b), each Licensed Product that prior to such Nurix Opt-Out Date was a Profit-Share Product will remain a Licensed Product and thereafter be eligible to receive the Milestone Payments achieved by such Licensed Product as further described in Section 11.4.2 (Opt-Out Date and Wind-Down), including the Sales Milestone Payments, and royalty payments for Net Sales of such Licensed Product for the remainder of the applicable Royalty Term as further described in Article 13 (Financial Terms).
11.4.2Opt-Out Date and Wind-Down. Subject to the terms of a relevant Nurix Opt-In Agreement, if applicable, any Nurix opt-out described in Section 11.4.1 (Opt-Out Notice) shall be effective upon the expiration of the first Calendar Quarter the last day of which is at least [*] after delivery of the relevant Nurix Opt-Out Notice (such date with respect to the applicable Nurix Opt-In Agreement(s), the “Nurix Opt-Out Date”). During the period between receipt by Seagen of a Nurix Opt-Out Notice and the relevant Nurix Opt-Out Date (such period the “Opt-Out Wind-Down Period”), the Parties shall cooperate to wind-down Nurix’s operational activities (if any) with respect to the applicable Profit-Share Product, as specified in further detail in the applicable Nurix Opt-In Agreement(s). Solely to the extent Nurix elected to opt-out of all
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of the Nurix Opt-In Agreements with respect to a Profit-Share Product, upon the relevant Nurix Opt-Out Date (a) the terms of the applicable Nurix Opt-In Agreements (including the Profit-Share Product Agreement) shall cease to apply to such Profit-Share Product, and (b) the applicable Profit-Share Product shall no longer be a Profit-Share Product hereunder, but, subject to Section 13.7.2(b), shall remain a Licensed Product, including for the purposes of Article 13 (Financial Terms) such as for any Development and Regulatory Milestone Event that occurs following the Nurix Opt-Out Date with respect to all applicable Nurix Opt-In Agreements; provided, that no Milestone Event shall be deemed to have been achieved pursuant to Section 13.7.2(e), and no Milestone Payment shall be payable in respect of any Milestone Event so deemed to have been achieved, as a result of the achievement of any Milestone Event by a former Profit-Share Product that occurs following the Opt-Out Wind-Down Period with respect to all applicable Nurix Opt-In Agreements for such Profit-Share Product. For clarity, (x) no Milestone Payment in respect of a Foregone Milestone shall be owed with respect to any Milestone Event that occurs following the applicable Profit-Share Option Exercise Notice and prior to the expiration of the relevant Opt-Out Wind-Down Period for all Nurix Opt-In Agreements with respect to the applicable Profit-Share Product, irrespective of whether the applicable Milestone Events are actually achieved or are deemed to be achieved, and (y) the achievement of a Milestone Event after the end of the relevant Opt-Out Wind-Down Period by any former Profit-Share Product shall be payable in accordance with Section 13.7 (Development and Regulatory Milestones).
11.4.3No Opt-Back-In. After the Nurix Opt-Out Date with respect to all applicable Nurix Opt-In Agreements, Seagen shall be responsible for all applicable costs and expenses associated with the Development and Commercialization of the Licensed Product and Nurix shall not have any option to buy back into any profit-share or any other rights.
ARTICLE 12
ASSISTANCE; TRANSITION; UPSTREAM LICENSE AGREEMENTS
12.1Assistance. Subject to the costs provisions of Section 12.2 (Know-How Transfer), Nurix will, and will cause its Affiliates to, cooperate with Seagen and its designees and provide assistance to Seagen and its designees with respect to Seagen’s and its designees’ Research, Development, Manufacture and Commercialization of each applicable Licensed Product after the occurrence of a Degrader License Effective Date for a Collaboration Degrader Target Set, as and to the extent reasonably requested in writing by Seagen, including by: (a) providing Seagen and its designees assistance with respect to Research, Development, regulatory and Manufacturing transition matters related to such Licensed Products; and (b) providing Seagen and its designees with reasonable access by teleconference or in-person (as requested by Seagen) to Nurix personnel (and personnel of its Affiliates and Third Party contractors) involved in Research, Development, regulatory or Manufacturing matters related to such Licensed Products to assist with the transition and answer questions related to such Licensed Products.
12.2Know-How Transfer. Without limiting the provisions of Section 12.1 (Assistance), as soon as reasonably practicable following the occurrence of the applicable Degrader License Effective Date, and thereafter during the Term as may be reasonably requested in writing by Seagen from time to time, Nurix will disclose to Seagen and its designees in English, including by providing hard and electronic copies thereof: all data, information, regulatory filings, assets, DNA, protein sequences, constructs, synthesis routes and cell lines, and materials included therein and any other physical embodiments thereof, in each case, relating to such Licensed Products or the Research Program, as applicable. Nurix will bear all costs of the first [*] of such assistance per Collaboration Degrader Target Set under this Agreement (including under Section 12.1 (Assistance)); thereafter, Seagen will reimburse Nurix for all reasonable costs actually incurred in connection with its assistance at the rate of [*]. At Seagen’s reasonable request (which shall be no more frequently than once per Calendar Quarter), Nurix shall provide Seagen an
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estimated budget for such assistance so requested by Seagen. Such assistance shall be tracked by Nurix using its standard practice and methodologies and upon reasonable written request from Seagen, Nurix shall provide Seagen with a written summary sufficient for Seagen to verify the hours of assistance or costs incurred, as applicable.
12.3Upstream License Agreements. Other than with respect to Change of Control transactions (as further described in Section 20.4 (Assignment, Change of Control)), in the event that Nurix enters into a contract or agreement with a Third Party pursuant to which Nurix in-licenses or otherwise acquires any Patents, Know-How or other intellectual property rights that, but for this Section 12.3 (Upstream License Agreements), would be Controlled by Nurix and constitute Nurix IP for purposes of this Agreement (each an “Upstream License Agreement”), then Nurix will promptly provide Seagen with written notice and a copy of the applicable Upstream License Agreement. To the extent that such Upstream License Agreement provides an in-license of or rights to Patents, Know-How or other intellectual property that are necessary or reasonably useful to practice Nurix Background IP (“Nurix Background In-Licensed IP”), such Nurix Background In-Licensed IP shall automatically, upon Nurix’s execution of such Upstream License Agreement, constitute Nurix IP (sub)licensed to Seagen under and in accordance with the terms of this Agreement. If such Upstream License Agreement provides an in-license of or rights to any Patents, Know-How or other intellectual property that are necessary or reasonably useful to practice Nurix Foreground IP but are not included in the Nurix Background In-Licensed IP (“Nurix Foreground In-Licensed IP”), then within thirty (30) days following receipt of such notice, Seagen will decide, in its sole discretion, whether or not to accept such Nurix Foreground In-Licensed IP as Nurix IP (sub)licensed to Seagen under this Agreement and provide Nurix written notice of such decision. In the event of acceptance by Seagen in accordance with the foregoing, such Nurix Foreground In-Licensed IP will constitute Nurix IP (sub)licensed to Seagen under and in accordance with the terms of this Agreement so long as Seagen complies with the terms of this Section 12.3 (Upstream License Agreements). Seagen shall pay Nurix for any payments arising in connection with any Nurix Foreground In-Licensed IP so accepted by Seagen that occur solely as a result of the activities of Seagen, its Affiliates or Sublicensees under this Agreement, such payment to be made by Seagen within [*] days following Seagen’s receipt of an invoice therefor. For the avoidance of doubt, the foregoing payment obligation shall only apply to use by Seagen, its Affiliates or Sublicensees of Nurix Foreground In-Licensed IP (to the extent applicable) and Seagen shall have no payment obligations with respect to any Nurix Background In-Licensed IP (which are and shall remain the sole responsibility of Nurix). In the event that Seagen does not so accept a (sub)license under Nurix Foreground In-Licensed IP with respect to an Upstream License Agreement (including by failing to respond within the applicable thirty (30) day period), then Seagen and its Affiliates and Sublicensees will have no payment obligations with respect to such Upstream License Agreement, and such Nurix Foreground In-Licensed IP licensed to Nurix under such Upstream License Agreement shall not be Controlled by Nurix, shall not be Nurix Foreground IP, and shall not be (sub)licensed to Seagen under this Agreement. For the avoidance of doubt, this Section 12.3 (Upstream License Agreements) shall not require Nurix to enter into any Upstream License Agreement.
ARTICLE 13
FINANCIAL TERMS
13.1Upfront Consideration. No later than [*] after the Effective Date, Seagen shall pay to Nurix a one (1) time payment of sixty million dollars ($60,000,000) in immediately available funds by wire transfer, in accordance with the Wire Instructions.
13.2Joint Research Term Extension Fee. Subject to the terms and conditions herein, on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, if Seagen wishes to extend the applicable Joint Research Term pursuant to Section 4.3 (Joint Research Term Extension), Seagen shall make a one (1) time payment to Nurix of [*] in
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immediately available funds by wire transfer, in accordance with the Wire Instructions, for each Joint Research Term Extension pursuant to Section 4.3 (Joint Research Term Extension) (the “Joint Research Term Extension Fee”).
13.3Degrader Target Set [*] Reservation Fee. For each Reservation Period with respect to a given Reserved Degrader Target Set, Seagen shall pay Nurix [*]. Such payment shall be made (a) for the initial designation of the Reserved Degrader Target Set, within [*] Business Days after the designation of such Reserved Degrader Target Set, or (b) for an extension of a Reservation Period, [*] Business Days prior to the expiration of the Reservation Period for the applicable Reserved Degrader Target Set (each such payment a “Degrader Target Set [*] Reservation Fee”); provided, that with respect to any Reserved Degrader Target Set, if the applicable Proposed Degrader Target Set Notice or Degrader Target Set Reservation Extension Notice is delivered [*], the Degrader Target Set [*] Reservation Fee payable by Seagen shall be a prorated amount equal to [*].
13.4Research Milestones. Subject to the terms and conditions herein (including this Section 13.4 (Research Milestones) and Section 13.11 (Additional Payment Terms)), and on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, Seagen shall pay the applicable amount set forth in the table below in this Section 13.4 (Research Milestones) (each a “Research Milestone Payment”) associated with the corresponding milestone event (“Research Milestone Event”) set forth opposite such Research Milestone Payment in the table below, in each case, once upon first achievement of the applicable Research Milestone Event with respect to a Collaboration Degrader Target Set:
| Research Milestone Event | Research Milestone Payment | ||||
(1) [*] | [*] | ||||
(2) [*] | [*] | ||||
(3) [*] | [*] | ||||
(4) [*] | [*] | ||||
Notwithstanding anything to the contrary contained in this Agreement, [*].
13.5Degrader License Option Period Extension Fee. Subject to the terms and conditions herein and on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, if Seagen wishes to extend the Degrader License Option Period for such Collaboration Degrader Target Set pursuant to Section 5.3 (Degrader License Option Period Extension), Seagen shall make a one (1) time payment to Nurix of [*] in immediately available funds by wire transfer, in accordance with the Wire Instructions, for each Degrader License Option Period Extension exercised by Seagen pursuant to Section 5.3 (Degrader License Option Period Extension) (each, a “Degrader License Option Period Extension Fee”), such payment to be made no later than [*] following delivery of the written notice described in Section 5.3 (Degrader License Option Period Extension).
13.6Degrader License Fee. Subject to the terms and conditions herein and on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, in the event that Seagen exercises a Degrader License Option with respect to such Collaboration Degrader Target Set as further described in Section 5.2 (Degrader License Option Exercise), Seagen shall pay to Nurix a one (1) time payment of [*] in immediately available funds by wire transfer, in accordance with the Wire Instructions, no later than [*] following the applicable Degrader License Effective Date (each, a “Degrader License Fee”). Notwithstanding the foregoing, (a) if Seagen has
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exercised the Degrader License Option for a Collaboration Degrader Target Set in accordance with Section 5.2 (Degrader License Option Exercise) prior to the achievement of [*] for such Collaboration Degrader Target, then [*] payment shall not be payable with respect to such Collaboration Degrader Target Set, and (b) if Seagen has paid the [*] for a Collaboration Degrader Target Set prior to the exercise of the Degrader License Option for such Collaboration Degrader Target Set, then the applicable Degrader License Fee for such Collaboration Degrader Target Set will be deemed to have been paid with respect to such Collaboration Degrader Target Set.
13.7Development and Regulatory Milestones. Subject to the terms and conditions herein (including this Section 13.7 (Development and Regulatory Milestones), Section 13.11 (Additional Payment Terms) and, in the event Nurix exercises a Profit-Share Option, Section 11.2.3 (Profit-Share Products) and Section 11.2.4 (Milestone Payments Related to the Profit-Share Triggering Events), as applicable), and on a Licensed Product-by-Licensed Product basis, Seagen shall pay the applicable amount set forth in the table below in this Section 13.7 (Development and Regulatory Milestones) associated with the corresponding milestone event set forth opposite such payment in the table below, in each case, once upon first achievement (including by any Affiliate of Seagen or any Sublicensee) of the applicable Development and Regulatory Milestone Event with respect to a Licensed Product (each event described in #1-#10 in the table below, a “Development and Regulatory Milestone Event,” and each respective payment, a “Development and Regulatory Milestone Payment”) under this Agreement for a Licensed Product:
| Development and Regulatory Milestone Event | Development and Regulatory Milestone Payment due upon first achievement of the milestone by a Licensed Product containing the applicable Licensed Degrader | ||||
(1) [*] | [*] | ||||
(2) [*] | [*] | ||||
(3) [*] | [*] | ||||
(4) [*] | [*] | ||||
(5) [*] | [*] | ||||
(6) [*] | [*] | ||||
(7) [*] | [*] | ||||
(8) [*] | [*] | ||||
(9) [*] | [*] | ||||
(10) [*] | [*] | ||||
13.7.1[*].
13.7.2Each Development and Regulatory Milestone Payment is payable up to a maximum of one (1) time per Licensed Product as set forth in the table above, upon first achievement of the applicable Development and Regulatory Milestone Event for such Licensed Product, regardless of the number of times the applicable Development and Regulatory Milestone Event is achieved with respect to such Licensed Product; provided, that:
(a)the maximum aggregate amount payable by Seagen to Nurix with respect to all Development and Regulatory Milestone Events shall be [*];
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(b)if, after a Development and Regulatory Milestone Event is achieved by a Licensed Product (including a Licensed Degrader-Antibody Conjugate) that contains one (1) or more specific Licensed Degrader(s), such Development and Regulatory Milestone Event is subsequently achieved by another distinct Licensed Product (as determined in accordance with Section 13.11.1 (Determining Same vs Distinct Licensed Products or Licensed Degraders for Milestones, Royalties, and Option-Triggering Events)) that contains the same Licensed Degrader(s) (as determined in accordance with Section 13.11.1 (Determining Same vs Distinct Licensed Products or Licensed Degraders for Milestones, Royalties, and Option-Triggering Events)), then the corresponding Development and Regulatory Milestone Payment shall be payable at an amount that is [*] of the amount listed above for such Development and Regulatory Milestone Payment. By way of example and not limitation, if a Licensed Product (“First Licensed Product”) contains the same Licensed Degrader that is contained in another Licensed Product (“Second Licensed Product”), and the Second Licensed Product achieves a Development and Regulatory Milestone Event that had previously been achieved by such First Licensed Product, then the applicable Development and Regulatory Milestone Payment for such achievement by the Second Licensed Product shall be [*] described in this Section 13.7.2(b). For clarity, (x) [*] shall apply to any Second Licensed Product that (i) was a Profit-Share Product prior to the Nurix Opt-Out Date for such Second Licensed Product, and (ii) achieves a Development and Regulatory Milestone Event after the applicable Nurix Opt-Out Date, regardless of when the First Licensed Product achieved the relevant Development and Regulatory Milestone Event (including if such achievement occurred while the Second Licensed Product was a Profit-Share Product), and (y) any Development and Regulatory Milestone Event achieved by a Profit-Share Product prior to the Nurix Opt-Out Date for such Profit-Share Product shall [*] for purposes of this Section 13.7.2(b) (i.e., if a Second Licensed Product achieves a Development and Regulatory Milestone Event after the achievement of such Development and Regulatory Milestone Event by a First Licensed Product that is a Profit-Share Product at the time of such achievement, the Milestone Payment for the achievement of such Development and Regulatory Milestone Event by the Second Licensed Product shall [*]);
(c)if, after a Development and Regulatory Milestone Event is achieved by a Licensed Product that contains one (1) or more specific Licensed Degrader(s), such Development and Regulatory Milestone Event is subsequently achieved by another distinct Licensed Product that contains any distinct Licensed Degrader(s), then the corresponding Development and Regulatory Milestone Payment shall be payable at [*] of the amount listed above for such Development and Regulatory Milestone Payment;
(d)with respect to Development and Regulatory Milestone Events [*], the achievement of [*] shall be deemed to include [*]; and
(e)(i) upon achievement of any of Development and Regulatory Milestone Events [*] above with respect to a Licensed Product, if the first achievement of any of Development and Regulatory Milestone Events [*] with respect to such Licensed Product has not occurred, such unachieved milestone shall simultaneously be deemed achieved and payable, and (ii) upon achievement of any of Development and Regulatory Milestone Events [*] above with respect to a Licensed Product, if the first achievement of Development and Regulatory Milestone Event [*] with respect to such Licensed Product has not occurred, such unachieved milestone shall simultaneously be deemed achieved and payable.
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13.7.3Notwithstanding the foregoing, no Development and Regulatory Milestone Payments shall be due with respect to any Unprotected Licensed Product, and [*].
13.8Sales-Based Milestones. Subject to the terms and conditions herein (including this Section 13.8 (Sales-Based Milestones), Section 13.11 (Additional Payment Terms) and Section 13.11.7 (Records; Audit Rights)), on a Licensed Product-by-Licensed Product basis, Seagen will notify Nurix in writing within [*] days after the end of the Calendar Quarter during which a given milestone event described below in this Section 13.8 (Sales-Based Milestones) (each, a “Sales Milestone Event”) was first achieved by Seagen under this Agreement, and Seagen will thereafter pay the applicable [*] amount set forth opposite such Sales Milestone Event in the table below for such Licensed Product in accordance with Section 13.9.2 (Sales-Based Milestones) (each, a “Sales Milestone Payment”):
Sales Milestone Event (for Licensed Products other than Profit-Share Products) | Sales Milestone Payment (for Licensed Products other than Profit-Share Products) | ||||
| [*] | [*] | ||||
| [*] | [*] | ||||
| [*] | [*] | ||||
Sales Milestone Event (for Profit-Share Products) | Sales Milestone Payment (for Profit-Share Products) | ||||
| [*] | [*] | ||||
| [*] | [*] | ||||
| [*] | [*] | ||||
Each Sales Milestone Payment is payable up to a maximum of one (1) time per Licensed Product (including any Profit-Share Product, as applicable) as set forth in the table above, upon first achievement of the applicable Sales Milestone Event for such Licensed Product, regardless of the number of times the applicable Sales Milestone Event is achieved with respect to such Licensed Product. The maximum aggregate amount payable by Seagen to Nurix with respect to all Sales Milestone Events shall be [*].
Notwithstanding the foregoing, no Sales Milestone Payments shall be due with respect to any Unprotected Licensed Product.
13.9Invoice and Payment of Milestone Payments.
13.9.1Research, Development, and Regulatory Milestones.
(a)In the event that Seagen, its Affiliates or its Sublicensees under this Agreement achieves a Research Milestone Event or Development and Regulatory Milestone Event, Seagen shall notify Nurix thereof [*] after such achievement and request an invoice from Nurix for the applicable Milestone Payment, and Seagen, subject to any good faith Dispute regarding the applicable Milestone Event or Milestone Payment, shall pay such Milestone Payment [*] after receipt of such invoice.
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(b)In the event that Nurix or its Affiliates achieves a Research Milestone Event, Nurix shall notify Seagen thereof in writing within [*] after such achievement and invoice Seagen for the applicable Milestone Payment, and Seagen, subject to any good faith Dispute regarding the applicable Milestone Event or Milestone Payment (including, if applicable, as to whether such Research Milestone Event has been achieved), shall pay such Milestone Payment within [*] after receipt of such invoice.
13.9.2Sales-Based Milestones. Seagen shall notify Nurix in writing if the aggregate Annual Global Net Sales or Annual Ex-U.S. Net Sales, as applicable, of any applicable Licensed Product first achieved a Sales Milestone Event during a Calendar Quarter in the royalty report for such Calendar Quarter (or the royalty report for the first Calendar Quarter in which Seagen determines the achievement of such Sales Milestone Event, if later) as described in Section 13.10.3 (Royalty Payments and Reporting) and request an invoice from Nurix for any such Sales Milestone Payment, and Seagen shall pay to Nurix such Sales Milestone Payment within [*] after the receipt of the corresponding invoice from Nurix.
13.10Royalties.
13.10.1Royalty Rates. Seagen shall pay, on a Licensed Product-by-Licensed Product basis and for all Licensed Products other than any Unprotected Licensed Product, a royalty equal to a tiered percentage of Annual Global Net Sales of the applicable Licensed Product (or, with respect to any Profit-Share Product, of the Annual Ex-U.S. Net Sales of such Profit-Share Product) as set forth in the table below and during the Royalty Term for such Licensed Product:
| Tier | Royalty rate | ||||
| (1) [*] | [*] | ||||
| (2) [*] | [*] | ||||
| (3) [*] | [*] | ||||
13.10.2Royalty Reductions.
(a)During the Royalty Term and on a Licensed Product-by-Licensed Product and country-by-country basis, if such Licensed Product is not Covered by a Valid Claim of a Royalty Patent in such country, then the royalties payable with respect to such Licensed Product pursuant to Section 13.10.1 (Royalty Rates) in such country will be reduced by [*].
(b)On a Licensed Product-by-Licensed Product and country-by-country basis, if Seagen or any of its Affiliates obtains a license under any Patent, Know-How or other intellectual property right of a Third Party after the Effective Date that are necessary or reasonably useful for Seagen to make, have made, sell, or offer for sale any Licensed Product in such country that results in any payment(s) to such Third Party as a result of such license by Seagen or its Affiliates, then Seagen may deduct from any [*] payments under this Agreement that would otherwise have been due to Nurix in a particular Calendar Quarter an amount equal to [*] of the amount of any such payments (including payments for obtaining such right or license, royalties, milestones, amounts paid in settlement and any other amounts) paid by Seagen or any of its Affiliates at arm’s length to such Third Party for such license or the exercise thereof during such Calendar Quarter; provided, however, that, in no event shall the royalty amount due to Nurix in any Calendar Year be reduced by more than [*] of the amount that would have otherwise been due.
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(c)On a Licensed Product-by-Licensed Product and country-by-country basis, if in a Calendar Quarter, any Generic/Biosimilar Product(s) of such Licensed Product is sold in such country, then the royalties payable with respect to such Licensed Product pursuant to Section 13.10.1 (Royalty Rates) in such country will be reduced by [*].
(d)Notwithstanding anything in this Section 13.10.2 (Royalty Reductions) to the contrary, in no event will royalties payable to Nurix by Seagen under this Agreement be reduced to less than [*] of the amount that would otherwise be payable to Nurix under Section 13.10 (Royalties) (the “Floor”); provided, that in the event there are royalty reduction amounts described in Section 13.10.2(b) that Seagen is unable to apply to royalty payments due to the Floor, then Seagen shall have the right to carry over such amounts and credit them in future Calendar Quarters subject to such Floor [*].
13.10.3Royalty Payments and Reporting. Seagen will calculate all amounts payable to Nurix pursuant to Section 13.10 (Royalties) at the end of each Calendar Quarter. Within [*] days after the end of each Calendar Quarter, commencing with the Calendar Quarter during which the First Commercial Sale of a Licensed Product is made anywhere in the Territory, Seagen will provide to Nurix a report stating the amount of gross sales and Net Sales of each Licensed Product in each country of the Territory during the applicable Calendar Quarter, a summary of the type and amount of permitted deductions from gross sales to determine Net Sales as set forth in the definition of Net Sales, and a reasonably detailed calculation of the amount of royalty payments due on such Net Sales for such Calendar Quarter, in each case, reasonably sufficient to allow Nurix to assess Seagen’s compliance with its royalty payment obligations hereunder. Concurrent with the provision of each such royalty report, Seagen will request an invoice from Nurix for the royalty payment shown in the royalty report, and shall, within [*] after the receipt of the corresponding invoice, pay to Nurix the royalty amounts due, less any applicable withholding tax that is required by Applicable Law in accordance with Section 13.11.6 (Taxes; Withholding), with respect to the applicable Calendar Quarter.
13.11Additional Payment Terms.
13.11.1Determining Same vs Distinct Licensed Products or Licensed Degraders for Milestones, Royalties, and Option-Triggering Events. Two (2) Licensed Products shall be deemed to be the same Licensed Product for purposes of Milestone Payments, royalties, and Profit-Share Options if both such Licensed Products may be, or would reasonably be expected to be, marketed in the United States under the same MAA (for clarity, as such MAA may be amended or supplemented from time to time). For purposes of determining whether two (2) Licensed Degraders are the same for purposes of Sections 13.7.2(b) and 13.7.2(c), two (2) Licensed Degraders shall be deemed to be the same Licensed Degrader if both such Licensed Degraders may be, or would reasonably be expected to be, marketed in the United States under the same MAA (for clarity, as such MAA may be amended or supplemented from time to time), if such Licensed Degraders were marketed as Licensed Products that did not contain a Licensed Degrader-Antibody Conjugate. For the avoidance of doubt, the same Licensed Degrader may be contained in two (2) or more different Licensed Products.
13.11.2Currency. All payments hereunder will be made in United States dollars by wire transfer to a bank account designated in writing by Nurix in the Wire Instructions. Conversion of sales recorded in local currencies to United States dollars will be performed in a manner consistent with the Accounting Standard and Seagen’s normal practices used to prepare its audited financial statements.
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13.11.3Invoices and Payments. Notwithstanding anything to the contrary contained in this Agreement or any Ancillary Agreement, each Party shall deliver an invoice, together with reasonable supporting documentation in the case of any reimbursement of costs, to the other Party’s Alliance Manager and such other recipient(s) as such Party may reasonably request for all payments owed to the invoicing Party under this Agreement or any Ancillary Agreement. Except where a different timeframe is expressly provided in another Section of this Agreement or in any Ancillary Agreement, the owing Party will make all undisputed payments owed to the invoicing Party within [*] after the date on which the owing Party receives an undisputed invoice for such owed amount, and shall pay any disputed amounts owed to the invoicing Party within [*] of final resolution of the applicable Dispute.
13.11.4Late Payments; Dispute Payments. If Nurix does not receive payment of any sum due to it under this Agreement on or before the due date therefor, simple interest shall thereafter accrue on the sum due to Nurix from the due date until the date of payment at a per-annum rate of [*] above the prime rate as reported in The Wall Street Journal, Eastern Edition (or any other qualified source reasonably acceptable to both Parties) or the maximum rate allowable by Applicable Law, whichever is less. In the event of a good faith Dispute regarding any payments owing under this Agreement, all undisputed amounts will be paid promptly when due and the balance, if any, promptly after resolution of the Dispute in accordance with Section 13.11.3 (Invoices and Payments), and the interest contemplated by this Section 13.11.4 (Late Payments; Dispute Payments) shall not be payable on any disputed amount.
13.11.5General Right to Reconcile Payments. Each Party will have the right to offset any amount owed by the other Party under or in connection with this Agreement or any Ancillary Agreement which obligation is not being contested by the other Party in good faith, against any payments owed to the other Party under this Agreement or any Ancillary Agreement. Such offsets will be in addition to any other rights or remedies available under this Agreement, any Ancillary Agreement, or Applicable Law.
13.11.6Taxes; Withholding.
(a)Generally. Each Party will be liable for all taxes legally assessable against it arising from any payment received under this Agreement, including income, applicable sales or use, goods and services, value added and consumption or other similar fees or taxes (“Taxes”).
(b)Tax Withholding. If Applicable Law requires the withholding of Taxes, Seagen will subtract the amount thereof from the Agreement Payments and remit such withheld amount to the relevant Governmental Authority in a timely manner. For the avoidance of doubt, Seagen’s remittance of such withheld Taxes, together with payment to Nurix of the remaining Agreement Payments, will constitute Seagen’s full satisfaction of Agreement Payments under this Agreement. Seagen will promptly (as available) submit to Nurix appropriate proof of payment of the withheld Taxes as well as the official receipts within a reasonable period of time. The Parties agree to cooperate with one another and use reasonable efforts to reduce or eliminate such withholding of Taxes under Applicable Law, including under the benefit of any present or future treaty against double taxation. Upon request from Seagen, Nurix shall furnish to Seagen appropriate IRS W-8 or W-9 series forms (collectively, “U.S. Tax Forms”). Seagen reserves the right to withhold payments due under this Agreement until the valid U.S. Tax Forms have been provided.
(c)Tax Treatment in Profit-Share Product Agreements. The Parties anticipate that any Profit-Share Product Agreement shall include appropriate and
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customary provisions regarding tax treatment applicable to such Profit-Share Product Agreement.
13.11.7Records; Audit Rights.
(a)Records. Each Party (as applicable to such Party) will keep, and will cause their Affiliates and, as applicable, Sublicensees, to keep, complete, true, and accurate books and records, to the extent applicable to their respective activities under this Agreement, and, in the case of Seagen, in relation to Net Sales, royalties, Milestone Payments and any other payments required hereunder, as applicable and in accordance with its Accounting Standard. Each Party will keep such books and records for at least [*] following the Calendar Year to which they pertain or for such longer period of time as required under any Applicable Law.
(b)Audit Rights. Subject to the other terms of this Section 13.11.7(b) (Audit Rights), during the Term, at the request of Nurix, which will not be made more frequently than [*], upon at least [*] prior written notice from Nurix, and at the expense of Nurix, Seagen will permit an independent, nationally-recognized certified public accountant selected by Nurix and reasonably acceptable to Seagen (the “Auditor”) to inspect, during regular business hours, the relevant records required to be maintained by Seagen under Section 13.11.7(a) (Records); provided, that such audit right will not apply to records beyond [*] years from the end of the Calendar Year to which they pertain and that records for a particular period may only be audited once. Prior to its inspection, the Auditor will enter into a confidentiality agreement with both Parties having obligations of confidentiality and non-use no less restrictive than those set forth in Article 16 (Confidentiality) and limiting the disclosure and use of such information by such accountant to authorized representatives of the Parties and the purposes germane to Section 13.11.7(a) (Records). The Auditor will report to Nurix only whether the particular amount being audited was accurate and, if not, the amount of any discrepancy and a reasonable summary of the reason for such discrepancy, and the Auditor will not report any other information to Nurix. Nurix will treat the results of the Auditor’s review of Seagen’s records as Confidential Information of Seagen subject to the terms of Article 16 (Confidentiality). In the event such audit leads to the discovery of an underpayment by Seagen, Seagen will, within [*] after receipt of such report from the Auditor, pay Nurix the amount of such underpayment. Nurix shall pay the full cost of the audit unless the underpayment of amounts due to Nurix is either (i) greater than [*] of the amount due for the entire period being examined, or (ii) such underpayment exceeds [*], in either case (i) or (ii) Seagen shall pay the reasonable cost charged to Nurix by the Auditor for the performance of such review. Any undisputed overpayments by Seagen revealed by such an examination will be creditable by Seagen against future payments owed by Seagen to Nurix under this Agreement. Seagen will include substantially similar rights as set forth in this Section 13.11.7(b) (Audit Rights) in any sublicense agreement with its Sublicensee; provided, however, that such sublicense agreement may provide that such audit be conducted by Seagen, its Affiliate or an independent auditor designated by Seagen instead of by an independent auditor designated by Nurix.
ARTICLE 14
LICENSE GRANT; EXCLUSIVITY
14.1Research Licenses.
14.1.1Subject to the terms and conditions of this Agreement, and on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, Seagen hereby grants to Nurix a non-exclusive, worldwide, non-transferrable (except pursuant to Section 20.4
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(Assignment; Change of Control)) and sublicensable (solely to Nurix’s subcontractors in accordance with Section 14.4 (Subcontracting) and Section 14.5 (Sublicensing)) license, under Seagen IP, solely to the extent necessary for Nurix to perform the Research activities assigned to Nurix under the applicable Joint Research Plan during the applicable Joint Research Term and in accordance with such Joint Research Plan.
14.1.2Subject to the terms and conditions of this Agreement, and on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, Nurix hereby grants to Seagen a co-exclusive, worldwide, non-transferrable (except pursuant to Section 20.4 (Assignment; Change of Control)) and sublicensable (solely to Seagen’s subcontractors in accordance with Section 14.4 (Subcontracting) and Section 14.5 (Sublicensing)) license, under Nurix IP and Nurix’s interest in the Joint Foreground IP, solely (a) to the extent necessary for Seagen to perform the Seagen Research activities assigned to Seagen under the applicable Joint Research Plan during the applicable Joint Research Term and in accordance with such Joint Research Plan, and (b) to otherwise perform internal research on Collaboration Degrader-Antibody Conjugates and Collaboration Degraders that are Directed To the applicable Collaboration Degrader Target Set, during the applicable Joint Research Term and Degrader License Option Period, and subject to Section 14.7 (Negative Covenant).
14.2Licensed Degrader License. Subject to the terms and conditions of this Agreement (including Article 5 (Degrader License Option)), on a Licensed Degrader Target Set-by-Licensed Degrader Target Set basis, Nurix hereby grants to Seagen an exclusive (even as to Nurix, except if and to the extent expressly provided in an applicable Nurix Opt-In Agreement (if executed)), non-transferrable (except pursuant to Section 20.4 (Assignment; Change of Control)) and sublicensable (through multiple tiers in accordance with Section 14.5 (Sublicensing)) license under the Nurix IP and Nurix’s interest in the Joint Foreground IP, to research, Develop, Manufacture, Commercialize and otherwise Exploit Licensed Products that contain Licensed Degraders that are Directed To such Licensed Degrader Target Set (for clarity, or a Subset thereof) (including as part of any Licensed Degrader-Antibody Conjugates) in the Field in the Territory (such license, the “Degrader License”); provided, that Seagen will not exercise its rights under the foregoing Degrader License with respect to any Licensed Degrader Target Set until the Degrader License Effective Date for the applicable Collaboration Degrader Target Set.
14.3Reversion Licenses.
14.3.1Reversion Product License Agreement. After a Licensed Degrader Target Set becomes a Former Licensed Degrader Target Set, upon Nurix’s written request to Seagen (which request shall be delivered to Seagen within [*] of such Licensed Degrader Target Set becoming a Former Licensed Degrader Target Set), Seagen shall grant to Nurix an exclusive license to Develop, Manufacture and Commercialize any applicable Reversion Product as it exists at the time the relevant Licensed Degrader Target Set becomes a Former Licensed Degrader Target Set, under the Seagen IP and Seagen’s interest in Joint Foreground IP, in each case, that is necessary or reasonably useful for such Development, Manufacture and Commercialization, in the Field worldwide, pursuant to a license and transition agreement with respect to the Reversion Product in form and substance to be negotiated in good faith and mutually agreed by the Parties as promptly as practicable following the date of Nurix’s request (such agreement, a “Reversion Product License Agreement”); provided, that a Reversion Product License Agreement shall not be inconsistent with the terms or conditions of, or require Seagen or its Affiliates to breach or terminate, any agreement between Seagen or its Affiliate and a Third Party related to any Seagen IP; provided, further, that in the event of any such inconsistency, Seagen shall use Commercially Reasonable Efforts for a reasonable period of time (not to exceed [*] unless otherwise mutually agreed in writing by the Parties) to remove any such inconsistency so that Seagen can grant to Nurix the rights and licenses contemplated by this Section 14.3.1 (Reversion Product License Agreement). In the event the Parties cannot mutually
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agree on the form and substance of a Reversion Product License Agreement within [*] following Nurix’s request, either Party may refer the matter to resolution pursuant to Section 20.6 (Choice of Law; Dispute Resolution; Jurisdiction), and the matter shall not be deemed to be fully and finally resolved until the Parties enter into a Reversion Product License Agreement consistent with the terms of this Section 14.3.1 (Reversion Product License Agreement). Each Reversion Product License Agreement shall provide for the continuing Exploitation by Nurix of the Reversion Product worldwide following the effective date of termination on a commercially reasonable basis consistent with this Section 14.3.1 (Reversion Product License Agreement), including with respect to the wind-down or transition of any ongoing Development, Manufacturing and Commercialization activities with respect to the Reversion Product in accordance with a mutually agreed transition plan attached to the Reversion Product License Agreement. Nurix shall pay to Seagen royalties on [*] (as such term is applied mutatis mutandis to Nurix and its Affiliates and sublicensees) of such Reversion Product to the extent Covered by any Patent included in the Seagen IP or Joint Foreground IP, at rates to be mutually agreed and set forth in the Reversion Product License Agreement.
14.3.2Potential Reversion Products. After a Licensed Degrader Target Set becomes a Former Licensed Degrader Target Set, upon Nurix’s written request with respect to any Licensed Product other than a Reversion Product (a “Potential Reversion Product”) (which request shall be delivered to Seagen within [*] of such Licensed Degrader Target Set becoming a Former Licensed Degrader Target Set), Seagen agrees to discuss in good faith for a period of not less than [*] the terms and conditions of an agreement (an “Other Reversion License Agreement”) pursuant to which Seagen would grant to Nurix such rights and licenses (including under the Seagen IP, if applicable) as are necessary for Nurix to continue Exploiting the Potential Reversion Product as it exists at the time the relevant Licensed Degrader Target Set becomes a Former Licensed Degrader Target Set worldwide on a commercially reasonable basis consistent with this Section 14.3.2 (Potential Reversion Products). The terms and conditions of any such agreement must be mutually agreed in writing by the Parties, and a failure to so agree shall not be subject to binding arbitration pursuant to Section 20.6.3 (Arbitration). Neither Party shall have any obligation to enter into an Other Reversion License Agreement.
14.4Subcontracting. During the Joint Research Term, each Party may subcontract the performance of tasks and other obligations hereunder to its Affiliates or Third Parties, which subcontract(s) may include a sublicense of rights necessary for the performance of the subcontract as reasonably required; provided, that any such Third Party will not be deemed to be a Sublicensee as a result of such sublicense and such subcontracting Party will continue to be liable for full performance of its obligations under this Agreement and will be liable for all actions of such Third Party subcontractor or Affiliate (including any Permitted Subcontractors). Notwithstanding the foregoing, Nurix may not subcontract the performance of any of its activities under a Joint Research Plan to any Third Party without Seagen’s prior written consent; provided, that such prior written consent shall not be required for (a) a subcontract between Nurix and a Third Party service provider (such service providers, “Permitted Subcontractors”) performing obligations of Nurix under a Joint Research Plan on a fee-for-service basis (provided, that each Joint Research Plan will include a list of Permitted Subcontractors, as applicable, and describe in reasonable detail the activities so subcontracted to each such Permitted Subcontractor (if any)), or (b) a subcontract between Nurix and a Third Party vendor providing Nurix with materials or supplies that enable Nurix to perform its obligations under a Joint Research Plan. Each contract between a Party or its Affiliate and a Third Party entered into pursuant to this Section 14.4 (Subcontracting) shall be in writing and consistent with the provisions of this Agreement, and include confidentiality and intellectual property provisions that allow the relevant Party to comply with its obligations hereunder as if such Party were directly performing the relevant activity under the Joint Research Plan.
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14.5Sublicensing. If a Party is permitted to grant a sublicense under the rights licensed to such Party under Section 14.1 (Research Licenses) or Section 14.2 (Licensed Degrader License), then such Party may grant such sublicense to Third Parties and Affiliates; provided, that such Party complies with the following terms for each such sublicense: (a) any such permitted sublicense shall be consistent with and subject to the terms and conditions of this Agreement; and (b) such Party will provide the other Party with written notice of such sublicense as well as a copy of such sublicense (where financial terms and other provisions that do not affect the rights and obligations of the Parties under this Agreement may be redacted) within thirty (30) days of the sublicense becoming effective; and (c) such Party will continue to be liable for full performance of its obligations under this Agreement and will be liable for all actions of such sublicensed Affiliate or Third Party, as applicable, as if such Affiliate or Third Party, as applicable, were such Party hereunder.
14.6Retained Rights. Each Party retains all rights under Patents, Know-How or other intellectual property rights Controlled by such Party which are not expressly granted to the other Party pursuant to this Agreement. Except as otherwise expressly provided in this Agreement, under no circumstances will a Party or any of its Affiliates, as a result of this Agreement, obtain any ownership interest, license or other right in or to any Patents, Know-How or other intellectual property rights of the other Party, including tangible or intangible items owned, controlled or developed by the other Party, or provided by the other Party to the receiving Party at any time, in each case, pursuant to this Agreement.
14.7Negative Covenant. Notwithstanding anything to the contrary in this Agreement, Seagen shall not modify, and shall not permit any Affiliate or Sublicensee to modify, any Collaboration Degrader or Licensed Degrader other than (a) to conjugate such Collaboration Degrader or Licensed Degrader to an Antibody to make or optimize a Collaboration Degrader-Antibody Conjugate or Licensed Degrader-Antibody Conjugate or (b) as permitted under Section 4.5 (Additional Conjugation Candidates). Without limiting the foregoing sentence, Seagen shall not modify, and shall not permit any Affiliate or Sublicensee to modify, any Collaboration Degrader or Licensed Degrader to be Directed To any Degrader Target(s) other than those within the applicable Collaboration Degrader Target Set or Licensed Degrader Target Set, and shall not Research, Develop or Commercialize, or permit any Affiliate or Sublicensee to Research, Develop or Commercialize, any Licensed Degrader or Licensed Degrader-Antibody Conjugate that is Directed To any Degrader Target(s) other than those within the applicable Licensed Degrader Target Set. Without the express prior written consent of Nurix, in its sole discretion, Seagen shall not make or create, nor permit any Affiliate or Sublicensee to make or create, any Degrader-Antibody Conjugate that contains both (x) a Collaboration Degrader or a Licensed Degrader, and (y) any Degrader that is not a Collaboration Degrader or a Licensed Degrader.
14.8Certain Uses of Foreground IP.
14.8.1No Restriction on Former Degrader Targets. Notwithstanding anything to the contrary in this Agreement, nothing in this Agreement shall be construed to prevent or limit Nurix or its Affiliates in exercising any rights under any Nurix IP or Nurix’s interest in Joint Foreground IP to research, Develop, Manufacture, Commercialize or otherwise Exploit any Degrader that is Directed To (a) any Former Collaboration Degrader Target or (b) Former Licensed Degrader Target and, in each case ((a) and (b)), not Directed To any Collaboration Degrader Target, any Licensed Degrader Target, or any Degrader Target in a Reserved Degrader Target Set.
14.8.2Restriction on Collaboration Degrader Targets. Without limiting Section 14.9.1 (Collaboration Degrader Target Set Exclusivity), except as expressly permitted under a Reversion Product License Agreement or Other Reversion License Agreement or as required to perform Nurix’s obligations under this Agreement or an Ancillary Agreement, neither
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Nurix nor its Affiliates shall, whether alone, with or through a Third Party, (a) use any Foreground IP (for clarity, including any Joint Foreground IP and any Nurix IP that is Foreground IP) to research, Develop, Manufacture, Commercialize or otherwise Exploit anywhere in the Territory any Degrader (or any product containing any such Degrader) that is Directed To any Collaboration Degrader Target (or any Degrader Target Set that includes any Collaboration Degrader Target), or (b) research, Develop, Manufacture, Commercialize or otherwise Exploit anywhere in the Territory any Degrader (or any product containing any such Degrader) that is (i) Directed To any Collaboration Degrader Target (or any Degrader Target Set that includes any Collaboration Degrader Target) and (ii) Covered by any Foreground IP (for clarity, including any Joint Foreground IP and any Nurix IP that is Foreground IP).
14.8.3Restriction on Licensed Degrader Targets. Without limiting Section 14.9.3 (Licensed Degrader Target Set Exclusivity) or Section 14.9.4 ([*] Licensed Degrader Target Set Exclusivity), except as expressly permitted under a Reversion Product License Agreement or Other Reversion License Agreement or as required to perform Nurix’s obligations under this Agreement or an Ancillary Agreement, neither Nurix nor its Affiliates shall, whether alone, with or through a Third Party, (a) use any Foreground IP (for clarity, including any Joint Foreground IP and any Nurix IP that is Foreground IP) to research, Develop, Manufacture, Commercialize or otherwise Exploit anywhere in the Territory any Degrader (or any product containing any such Degrader) that is Directed To any Licensed Degrader Target (or any Degrader Target Set that includes any Licensed Degrader Target), or (b) research, Develop, Manufacture, Commercialize or otherwise Exploit anywhere in the Territory any Degrader (or any product containing any such Degrader) that is (i) Directed To any Licensed Degrader Target (or any Degrader Target Set that includes any Licensed Degrader Target) and (ii) Covered by any Foreground IP (for clarity, including any Joint Foreground IP and any Nurix IP that is Foreground IP).
14.9Exclusivity.
14.9.1Collaboration Degrader Target Set Exclusivity. Subject to Section 14.9.5 (Exceptions to Exclusivity), on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis during the applicable Exclusivity Period described in Section 1.92(a), neither Nurix nor its Affiliates will, whether alone, with or through a Third Party, research, Develop, Manufacture, Commercialize, or otherwise Exploit anywhere in the Territory any Degrader that is Directed To (a) such Collaboration Degrader Target Set or any Subset thereof, or (b) any Degrader Target Set for which a Degrader Target Set described in clause (a) is a Subset.
14.9.2Reserved Degrader Target Set Exclusivity. Subject to Section 14.9.5 (Exceptions to Exclusivity), on a Reserved Degrader Target Set-by-Reserved Degrader Target Set basis during the applicable Exclusivity Period described in Section 1.92(d), neither Nurix nor its Affiliates will, whether alone, with or through a Third Party, research, Develop, Manufacture, Commercialize, or otherwise Exploit anywhere in the Territory any Degrader that is Directed To (a) any Reserved Degrader Target Set or any Subset thereof or (b) any Degrader Target Set for which a Degrader Target Set described in clause (a) is a Subset.
14.9.3Licensed Degrader Target Set Exclusivity. Subject to Section 14.9.5 (Exceptions to Exclusivity), on a Licensed Degrader Target Set-by-Licensed Degrader Target Set basis during the applicable Exclusivity Period described in Section 1.92(b), neither Nurix nor its Affiliates will, whether alone, with or through a Third Party, research, Develop, Manufacture, Commercialize, or otherwise Exploit anywhere in the Territory any Degrader that is Directed To (a) such Licensed Degrader Target Set or any Subset thereof or (b) any Degrader Target Set for which a Degrader Target Set described in clause (a) is a Subset.
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14.9.4[*] Licensed Degrader Target Set Exclusivity. Subject to Section 14.9.5 (Exceptions to Exclusivity), on an [*] Licensed Degrader Target Set-by-[*] Licensed Degrader Target Set basis during the applicable Exclusivity Period described in Section 1.92(c), neither Nurix nor its Affiliates will, whether alone, with or through a Third Party, research, Develop, Manufacture, Commercialize or otherwise Exploit anywhere in the Territory any Degrader that is (a) Pan-Directed To the [*] Licensed Degrader Target Set or (b) Pan-Directed To any Degrader Target Set for which such [*] Licensed Degrader Target Set is a Subset. For clarity, this Section 14.9.4 ([*] Licensed Degrader Target Set Exclusivity) will not prevent Nurix or its Affiliates, whether alone, with or through a Third Party, from researching, Developing, Manufacturing, Commercializing or otherwise Exploiting Degraders that are not (i) Pan-Directed To the applicable [*] Licensed Degrader Target Set or (ii) Pan-Directed To a Degrader Target Set for which such [*] Licensed Degrader Target Set is a Subset.
14.9.5Exceptions to Exclusivity.
(a)Notwithstanding anything in this Agreement to the contrary, Nurix’s performance of an assay or test for a Degrader Target Set for the purposes of screening or determining a Degrader’s off-target activity shall not be considered performing Research on any Degrader that is Directed To such Degrader Target Set and shall not be a breach of Section 14.9 (Exclusivity).
(b)At any time during the Term of this Agreement, if Seagen or its Affiliate(s) (excluding any Affiliates in any Acquiring Entity Family) obtains ownership of, or an exclusive license to Commercialize, any product containing or comprising a Degrader (other than a Licensed Degrader) that is Directed To any Licensed Degrader Target Set or any Subset of such Licensed Degrader Target Set and such product is then currently the subject of an active internal research or development program by Seagen or such Affiliates, then Seagen shall notify Nurix within [*] days after obtaining such ownership or license or initiating such research or development program (to the extent such ownership, license or research or development program results in such Degrader being subject to this clause (b)), which notice shall indicate the applicable date such Degrader became subject to this clause (b), and after the [*] day following Seagen obtaining such ownership or license, or initiating such research or development program, as applicable (and subject to the remainder of this Section 14.9.5(b)), Nurix shall no longer be subject to any exclusivity obligations with respect to such Licensed Degrader Target Set under Section 14.9.3 (Licensed Degrader Target Set Exclusivity) or Section 14.9.4 ([*] Licensed Degrader Target Set Exclusivity); provided, that if Nurix reasonably determines that it is no longer subject to such exclusivity obligations with respect to a Licensed Degrader Target Set pursuant to this clause (b) and Nurix has not received a written notice to that effect from Seagen hereunder, Nurix shall notify Seagen in writing of its determination; provided, further, that if Seagen disputes whether Nurix is subject to such exclusivity obligations pursuant to this clause (b) or the material facts set forth in Nurix’s notice, and so notifies Nurix within [*] Business Days following delivery to Seagen of Nurix’s written notice, Nurix shall remain subject to the applicable exclusivity obligations unless and until (i) the Parties mutually agree in writing that this clause (b) applies and Nurix is no longer subject to such exclusivity obligations under the relevant circumstances, or (ii) the conclusion of a dispute resolution process under Section 20.6 (Choice of Law; Dispute Resolution; Jurisdiction) resulting in a final determination that this clause (b) applies and Nurix is no longer subject to such exclusivity obligations under the relevant circumstances.
(c)Notwithstanding anything in Section 14.9 (Exclusivity) to the contrary, if Nurix undergoes a Change of Control, and on the date of the closing of such Change of Control, the Acquiring Entities are researching, Developing, Manufacturing or
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Commercializing a product that is subject to Section 14.9.1 (Collaboration Degrader Target Set Exclusivity), Section 14.9.2 (Reserved Degrader Target Set Exclusivity), Section 14.9.3 (Licensed Degrader Target Set Exclusivity) or Section 14.9.4 ([*] Licensed Degrader Target Set Exclusivity) at such time for use in the Field (such product a “Competing Product”), then Nurix will not be in breach of Section 14.9 (Exclusivity) as a result of such Change of Control or the continuation of such activities by such Acquiring Entities thereafter; provided, that Nurix, its Affiliates and such Acquiring Entities Segregate such Competing Product.
ARTICLE 15
INTELLECTUAL PROPERTY MATTERS
15.1Ownership.
15.1.1Background IP. As between the Parties, each Party will retain ownership (including all prosecution, maintenance, defense and enforcement rights) of all Patents, Know-How and other intellectual property rights that are existing and owned or Controlled by such Party prior to the Effective Date or are otherwise developed or obtained independently by such Party and outside the scope of conducting the Joint Research Plans or the Research, Development, Manufacture, or Commercialization of Collaboration Degraders, Collaboration Degrader-Antibody Conjugates, or Licensed Products contemplated by this Agreement (with respect to such Party, its “Background IP”). For clarity, Background IP that is solely owned or Controlled by Seagen will be “Seagen Background IP.” Background IP that is solely owned or Controlled by Nurix will be “Nurix Background IP.”
15.1.2Foreground IP. As between the Parties, with respect to any and all data, results, discoveries, improvements, or Inventions (whether or not patentable) conceived, made, created, or reduced to practice solely by or on behalf of either Party or jointly by the Parties during the Term of this Agreement and in the course of conducting the Joint Research Plans or the Research, Development, Manufacturing, or Commercialization of Collaboration Degraders, Collaboration Degrader-Antibody Conjugates, or Licensed Products contemplated by this Agreement (together with all intellectual property rights therein, including all Patents related thereto, the “Foreground IP”), any Foreground IP made, created conceived of or reduced to practice (a) solely by a Party’s or any of its Affiliates’ employees, independent contractors or consultants will be owned by such Party, or (b) jointly by each Party’s (or any of its Affiliates’) employees, independent contractors or consultants will be jointly owned by the Parties; provided, that notwithstanding anything to the contrary in clauses (a) or (b) above and irrespective of inventorship: (x) Seagen will solely own any and all Foreground Antibody/Conjugation IP; and (y) Nurix will solely own any and all Foreground DEL IP and Foreground Degrader IP. Subject to the terms and conditions of this Agreement, including those in Article 14 (License Grant; Exclusivity), either Party will be able to freely Exploit the Joint Foreground IP without accounting to the other Party. Foreground IP that is solely owned by Seagen under this Section 15.1.2 (Foreground IP) will be “Seagen Foreground IP,” and Patents included in the Seagen Foreground IP will be “Seagen Foreground Patents.” Foreground IP that is solely owned by Nurix under this Section 15.1.2 (Foreground IP) will be “Nurix Foreground IP,” and Patents included in the Nurix Foreground IP shall be “Nurix Foreground Patents.” Foreground IP that is jointly owned by the Parties under this Section 15.1.2 (Foreground IP) will be “Joint Foreground IP,” and Patents included in the Joint Foreground IP will be “Joint Foreground Patents.” All determinations of inventorship under this Agreement will be made in accordance with U.S. patent law. For clarity, ownership of Foreground IP that primarily relates to (i) attachment moieties, generally, or (ii) without limiting the definition of “Foreground DEL IP” hereunder, any process or method of attaching attachment moieties to chemical entities, generally, shall follow inventorship, as determined in accordance with this Section 15.1.2 (Foreground IP), and such Foreground IP shall not be considered Foreground DEL IP,
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Foreground Degrader IP or Foreground Antibody/Conjugation IP hereunder. Notwithstanding any of the rights allocated in this Section 15.1.2 (Foreground IP), Seagen Foreground IP and Joint Foreground IP will be subject to the Nurix rights and other terms and conditions set forth in Section 14.3 (Reversion Licenses).
15.1.3Invention Assignments. Each Party shall cause all employees and contractors who perform activities for such Party or its Affiliate under this Agreement to be under an obligation to assign their rights in any Inventions, Know-How and works of authorship resulting therefrom to such Party or its Affiliate. At the written request of the Party controlling the relevant Prosecution and Maintenance, enforcement or defense activities with respect to a Patent under this Agreement in accordance with this Article 15 (Intellectual Property Matters), the other Party shall cause its employees and contractors who are inventors on any such Patent to cooperate and provide assistance to its employer or its Affiliate in relevant intellectual property-related matters, including by executing all appropriate documents, cooperating in discovery and, if legally required to continue any such enforcement activities, joining as a party to any Action or providing a power of attorney solely for such purpose.
15.2Prosecution and Maintenance of Foreground IP.
15.2.1Before Exercise of Degrader License Option.
(a)On a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, during the applicable Degrader License Option Period: (i) the Parties shall, through the JPC, share jointly responsibility and the cost and expense for the Prosecution and Maintenance of any and all Joint Foreground Patents; (ii) Seagen shall control the Prosecution and Maintenance of any and all Seagen Foreground Patents at Seagen’s sole cost and expense; and (iii) Nurix shall control the Prosecution and Maintenance of any and all Nurix Foreground Patents at Nurix’s sole cost and expense.
(b)Notwithstanding anything to the contrary contained in Section 15.2.1(a), prior to an applicable Degrader License Effective Date the Parties shall discuss and coordinate in good faith via the JPC regarding the filing of and filing strategies for all Foreground Patents that [*]. In the event that the Parties are unable to agree on any such filing through the JPC, such matter shall be referred to the JSC for resolution pursuant to Section 10.6.2 (JSC Decisions); provided, that if the JSC cannot reach consensus on any such matter, the matter shall be referred to the Executive Officers for resolution in accordance with Section 10.6.2 (JSC Decisions), and if the Executive Officers do not reach agreement on such matter within thirty (30) days after such matter is first referred to the Executive Officers, neither Party may file any such Patent or Patent application prior to the applicable Degrader License Effective Date without the mutual written agreement of both Parties, and such matter shall not be subject to resolution pursuant to Sections 20.6.2 (Dispute Escalation) or 20.6.3 (Arbitration).
15.2.2After Exercise of Degrader License Option. On a Licensed Degrader Target Set-by-Licensed Degrader Target Set basis, after the Degrader License Effective Date with respect to Seagen’s exercise (if any) of the applicable Degrader License Option:
(a)Seagen shall have the sole right, at its sole cost and expense, to Prosecute and Maintain any and all Product Patents;
(b)Subject to Section 15.2.2(a), Seagen shall have the first right, at its sole cost and expense, to Prosecute and Maintain any and all Joint Foreground Patents;
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(c)Subject to Section 15.2.2(a), each Party shall have the sole right, at its sole cost and expense, to Prosecute and Maintain any and all Foreground Patents that are solely owned by such Party in accordance with Section 15.1.2 (Foreground IP); provided, that Seagen shall have the first right (subject to the remainder of this Section 15.2.2), at its sole cost and expense, to Prosecute and Maintain any and all (i) Degrader Target Binder Patents and (ii) Nurix Foreground Patents that Cover a Licensed Degrader or a Licensed Degrader-Antibody Conjugate and that are not (A) Product Patents, or (B) Patents included in the Foreground Antibody/Conjugation IP (each Patent described in clauses (i) and (ii) of this subsection (c), a “Seagen Prosecution Step-In Patent”); and
provided, further, that, in each case of subsections (b) and (c) above, the non-prosecuting Party shall have the right, through the JPC, to review and comment on the Prosecution and Maintenance by the prosecuting Party of such Joint Foreground Patents or Seagen Prosecution Step-In Patents, as the case may be, and the prosecuting Party shall, and shall direct its patent counsel to, provide the non-prosecuting Party, through the JPC, with copies of all substantive filings and responses reasonably promptly upon filing with or receipt from the applicable patent office, as applicable, and in reasonably sufficient time for the non-prosecuting Party to exercise such review and comment right, and shall consider in good faith the reasonable comments and requests of the non-prosecuting Party; provided, that the prosecuting Party will have no obligation to consider any comments provided by the non-prosecuting Party if the time required for consideration of such comments would result in (A) not meeting a deadline imposed by the applicable patent office or paying any extension fee(s) to extend such deadline, or (B) a loss of rights with respect to the applicable Patents; and in the event the prosecuting Party decides to abandon a Joint Foreground Patent or Seagen Prosecution Step-In Patent, as the case may be, the prosecuting Party shall notify the non-prosecuting Party, through the JPC, of any such decision, which notice shall be provided a reasonable amount of time prior to any filing or payment due date, or any other due date that requires action, in connection with such Patent to enable the non-prosecuting Party, at its sole discretion and expense, to file or to continue Prosecution and Maintenance of such Patent. In the event the non-prosecuting Party decides to file or to continue the Prosecution and Maintenance of such Patent, the initially prosecuting Party shall have no further right to Prosecute and Maintain such Patent, or to review and comment with respect thereto.
15.2.3Cooperation Regarding Certain Prosecution and Maintenance. As between the Parties, in the event that each Party owns or Controls an invention or intellectual property rights (other than Joint Foreground IP) primarily relating to a specific attachment moiety, and the relevant Nurix invention or intellectual property rights primarily relate to such attachment moiety as attached to a Proteasome Protein Binder or Degrader Spacer, the Parties will reasonably cooperate on a case-by-case basis, through the JPC, to enable one another to Prosecute and Maintain separate Patent filings with respect to such inventions or intellectual property rights while minimizing any loss of rights to either Party (e.g., coordinating the timing of filing for such filings such that neither Party’s filing is prior art to the other Party’s filings).
15.3Enforcement or Defense.
15.3.1Notification. Each Party will promptly notify the other Party of any infringement, misappropriation or other violation by a Third Party of any Nurix Patent, Seagen Foreground Patent, Product Patent, or Joint Foreground Patent, in the Territory of which it becomes aware, including any declaratory judgment or similar Action alleging invalidity, unenforceability or non-infringement with respect to any such Patent (collectively, “Infringement”).
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15.3.2Right to Enforce or Defend Before Exercise of Degrader License Option. On a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, during the applicable Degrader License Option Period, the Parties shall, through the JPC, jointly control and bring, and shall share equally the costs and expenses related to, any enforcement or defense Action (and settlements thereof) as the JPC deems appropriate in connection with any Infringement of any Patent included in the Joint Foreground IP at a cost and expense to be equally shared between the Parties. Seagen shall control any enforcement or defense Action in connection with any Infringement of any Seagen Foreground Patent at Seagen’s sole cost and expense. Nurix shall control any enforcement or defense Action in connection with any Infringement of any Nurix Foreground Patent at Nurix’s sole cost and expense.
15.3.3Right to Enforce or Defend After Exercise of Degrader License Option. On a Licensed Degrader Target Set-by-Licensed Degrader Target Set basis, after the Degrader License Effective Date with respect to Seagen’s exercise (if any) of the applicable Degrader License Option:
(a)Seagen shall have the sole right, at its sole cost and expense, but not the obligation, to bring and control any enforcement or defense Action (and settlements thereof) as it deems appropriate, including in connection with any Infringement, with respect to any and all Product Patents. Nurix will have the right to be represented in any such enforcement Action by counsel of its own choice at Nurix’s sole cost and expense;
(b)Subject to Section 15.3.3(a), Seagen shall have the first right, at its sole cost and expense, to bring and control any enforcement or defense Action (and settlements thereof) as it deems appropriate, including in connection with any Infringement, with respect to any and all Patents included in the Joint Foreground IP;
(c)Subject to Section 15.3.3(a), each Party shall have the sole right, at its sole cost and expense, but not the obligation, to bring and control any enforcement or defense Action as it deems appropriate, including in connection with any Infringement, with respect to any and all Foreground Patents that are solely owned by such Party in accordance with Section 15.1.2 (Foreground IP); provided, that Seagen shall have the sole right, at its sole cost and expense, but not the obligation, to bring and control any enforcement or defense Action as it deems appropriate, including in connection with any Infringement, with respect to any and all Seagen Prosecution Step-In Patents; provided, further, that Nurix shall have the right to review and comment on the enforcement and defense Actions by Seagen of such Seagen Prosecution Step-In Patents, and Seagen shall, and shall direct its counsel to, provide Nurix, through the JPC, with copies of all filings and responses reasonably promptly upon filing or receipt as applicable, and in sufficient time for Nurix to exercise such review and comment right, and shall consider in good faith the reasonable comments and requests of Nurix which are timely received by Seagen; and
(d)At the request and expense of the Party that controls any Action under this Section 15.3.3 (Right to Enforce or Defend After Exercise of Degrader License Option) (the “Enforcing Party”) the other Party (the “Non-Enforcing Party”) will join as a party to the Action if required and provide reasonable assistance in connection with such Action, including by executing reasonably appropriate documents and cooperating in discovery. The Enforcing Party will in no event settle or otherwise compromise any legal Action by admitting that any Product Patent is invalid or unenforceable, in each case without first obtaining the prior written consent of the Non-Enforcing Party, which consent will not be unreasonably withheld, conditioned, or delayed.
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15.4Defense of Third Party Infringement Claims.
15.4.1Notification. Each Party will promptly notify the other Party of any claim alleging that the Research, Development, Manufacture or Commercialization of any Collaboration Degrader, Collaboration Degrader-Antibody Conjugate, Licensed Degrader, Licensed Degrader-Antibody Conjugate, or Licensed Products in the Territory infringes, misappropriates or otherwise violates any Patents, Know-How or other intellectual property rights of any Third Party (“Third Party Infringement Claim”).
15.4.2Right to Defend Before Exercise of Degrader License Option. On a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, during the applicable Degrader License Option Period, the Parties shall, through the JPC, share jointly responsibility and the costs and expenses to defend, or take other Actions (including to settle), with respect to any Third Party Infringement Claim relating to any Collaboration Degrader or Collaboration Degrader-Antibody Conjugate Directed To the applicable Collaboration Degrader Target Set.
15.4.3Right to Defend After Exercise of Degrader License Option. On a Licensed Degrader Target Set-by-Licensed Degrader Target Set basis, after the Degrader License Effective Date with respect to Seagen’s exercise (if any) of the applicable Degrader License Option, Seagen will have the sole right, at its sole cost and expense, but not the obligation, to defend, and take other Actions (including settle) with respect to any Third Party Infringement Claim relating to any Licensed Product at its sole discretion, cost and expense, and Nurix will have the right to be represented in any such Action by counsel of its own choice at Nurix’s sole cost and expense provided that in no event will Seagen settle or otherwise compromise any such Third Party Infringement Claim by admitting that any Product Patent, Seagen Prosecution Step-In Patent, or Joint Foreground Patent is invalid or unenforceable, in each case, without first obtaining the prior written consent of Nurix, which consent will not be unreasonably withheld, conditioned, or delayed.
15.5Recovery. Subject to the terms and conditions of an applicable Profit-Share Product Agreement (if executed):
15.5.1Enforcement Actions. Any recovery (including any settlement) received as a result of any Action under Section 15.3 (Enforcement or Defense) will be allocated in the following order: (a) to reimburse the Enforcing Party (if the enforcement was not done jointly) for the costs and expenses (including attorneys’ and professional fees) that the Enforcing Party incurred in connection with such Action, to the extent not previously reimbursed; (b) to reimburse the Non-Enforcing Party to the extent not already reimbursed, where it joins an Action as provided under Section 15.3.3(d), for the costs and expenses (including attorneys’ and professional fees) that such Party incurred in connection with such Action, to the extent not previously reimbursed; and (c) any recoveries in excess of such costs and expenses shall be [*].
15.5.2Defense Actions. Any recovery (including any settlement) received as a result of any Action under Section 15.4 (Defense of Third Party Infringement Claims) will be allocated in the following order: (a) to reimburse the defending Party (if the defense was not done jointly) for the costs and expenses (including attorneys’ and professional fees) that the defending Party incurred in connection with such Action, to the extent not previously reimbursed; (b) to reimburse the non-defending Party to the extent not already reimbursed, where it joins such defense as provided under Section 15.3.3(d); and (c) any recoveries in excess of such costs and expenses shall be [*].
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ARTICLE 16
CONFIDENTIALITY
16.1Nondisclosure and Non-Use. Each Party agrees that a Party (the “Receiving Party”) which receives the Confidential Information of the other Party (the “Disclosing Party”) pursuant to this Agreement or any Ancillary Agreement shall: (a) maintain in confidence such Confidential Information using not less than the efforts that such Receiving Party uses to maintain in confidence its own proprietary information of similar kind and value, but in no event less than a reasonable degree of efforts; (b) not disclose such Confidential Information to any Third Party without first obtaining the prior written consent of the Disclosing Party, except for disclosures expressly permitted pursuant to this Article 16 (Confidentiality); and (c) not use such Confidential Information for any purpose except those expressly permitted under this Agreement or any Ancillary Agreement. The obligations of confidentiality, non-disclosure and non-use under this Section 16.1 (Nondisclosure and Non-Use) will be in full force and effect from the Effective Date until [*] years following the Term for any Confidential Information that is not identified by either Party as a trade secret, and for all such Confidential Information that is identified by either Party as a trade secret, in perpetuity. Upon the expiration or termination of this Agreement and at the request of the Disclosing Party, the Receiving Party will return or destroy the Confidential Information of the Disclosing Party, promptly (but in any case within [*] after the Disclosing Party’s request); provided, however, that a Party may retain: (i) Confidential Information of the Disclosing Party as necessary to exercise rights and licenses which expressly survive such termination or expiration pursuant to this Agreement; (ii) access to all other Confidential Information in archives solely for the purpose of establishing the contents thereof or in accordance with Applicable Law; and (iii) Confidential Information contained in any electronically stored backup files or other media created by or on behalf of such Party in accordance with its standard policies in the ordinary course of business.
16.2Exceptions. Section 16.1 (Nondisclosure and Non-Use) will not apply with respect to the following information of the Disclosing Party:
(a)information that was known to the Receiving Party or any of its Affiliates, as evidenced by written records, without any obligation to the Disclosing Party to keep it confidential or restrict its use, prior to disclosure by the Disclosing Party;
(b)information that is subsequently disclosed to the Receiving Party or any of its Affiliates by a Third Party lawfully in possession thereof and without any obligation to the Disclosing Party to keep it confidential or restrict its use;
(c)information that is published by a Third Party or otherwise becomes publicly available or enters the public domain, either before or after it is disclosed to the Receiving Party, without any breach by the Receiving Party of its obligations hereunder; or
(d)information that is independently developed by or for the Receiving Party or any of its Affiliates, as evidenced by written records, without reference to or reliance upon the Disclosing Party’s Confidential Information.
Any combination of features or disclosures will not be deemed to fall within the foregoing exclusions merely because individual features or disclosures are published or available to the general public or in the rightful possession of the Receiving Party unless the combination itself and principle of operation are published or available to the general public or in the rightful possession of the Receiving Party.
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16.3Authorized Disclosure.
16.3.1Disclosure. Notwithstanding Section 16.1 (Nondisclosure and Non-Use), the Receiving Party may disclose Confidential Information belonging to the Disclosing Party in the following instances:
(a)as required by and in accordance with Section 16.6 (Securities Filings; Disclosure under Applicable Law), to the U.S. Securities and Exchange Commission or any national securities exchange in any jurisdiction in the Territory (each, a “Securities Regulator”);
(b)in response to a valid order of a court of competent jurisdiction or other Governmental Authority or Regulatory Authority or, if in the reasonable opinion of the Receiving Party’s legal counsel, such disclosure is otherwise required by Applicable Law (other than to a Securities Regulator); provided, however, that to the extent legally permissible the Receiving Party will first give written notice to the Disclosing Party and give the Disclosing Party a reasonable opportunity to quash such order or to obtain a protective order or confidential treatment requiring that the Confidential Information and documents that are the subject of such order or requirement be held in confidence by such court or agency or, if disclosed, be used only for the purposes for which the order was issued and redacted in accordance with the Disclosing Party’s instruction; provided, further, that the Confidential Information disclosed in response to such court or governmental order or Applicable Law will be limited to that information which is legally required to be disclosed in response to such court or governmental order or Applicable Law;
(c)by either Party, to the extent necessary or reasonably useful to exercise its rights to Prosecute and Maintain, enforce and defend any and all Patents for which it has such right under Article 15 (Intellectual Property Matters); provided, however, that, to the extent practicable, such Party will provide the other Party with at least [*] prior written notice of any such disclosure and take reasonable and lawful actions to avoid or minimize the degree of disclosure;
(d)by either Party, to a Regulatory Authority, as necessary or reasonably useful in connection with any filing, submission or communication with respect to any Licensed Product (or any Licensed Degrader or Licensed Degrader-Antibody Conjugate contained therein) Collaboration Degrader, Collaboration Degrader-Antibody Conjugate, or, following the execution and delivery by each Party of a Reversion Product License Agreement, Reversion Product; provided, however, that reasonable measures will be taken by such Party to obtain confidential treatment of such information, to the extent such protection is available;
(e)by Seagen, to the extent necessary or reasonably useful to research, Develop, Manufacture, Commercialize or otherwise Exploit Licensed Products (or any Licensed Degrader or Licensed Degrader-Antibody Conjugate contained therein), Collaboration Degraders, or Collaboration Degrader-Antibody Conjugates, or to otherwise exercise the rights and licenses granted to it under this Agreement, including under Article 14 (License Grant; Exclusivity);
(f)disclosure (i) to any of its officers, employees, consultants, agents or Affiliates who need to know such Confidential Information to perform on behalf of such Party under this Agreement, (ii) in the case of Seagen, to any actual or potential collaborators, partners, licensees, Sublicensees, contractors, subcontractors, agents and representatives in connection with the Research, Development, Manufacture,
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Commercialization or other Exploitation of Licensed Products or otherwise to the extent necessary or reasonably useful for Seagen, its Affiliates or Sublicensees to exercise its or their rights or to perform its or their obligations hereunder, (iii) in the case of either Party, to such Party’s actual or bona fide potential acquirers, investors, or lenders on a strictly need to know basis for the sole purpose of evaluating or carrying out a bona fide investment in or acquisition of such Party or its Affiliate; and (iv) in the case of Nurix, [*]; provided, further, that each such recipient (under clauses (i)-(iv)) is bound by obligations of confidentiality, non-disclosure and non-use substantially equivalent to the obligations set forth in this Article 16 (Confidentiality), except for a shorter duration, if customary, to maintain the confidentiality thereof and not to use such Confidential Information except as expressly permitted by customary terms thereunder; and
(g)disclosure to its advisors (including attorneys, financial advisors and accountants); provided, however, that each such recipient is bound by obligations of confidentiality, non-disclosure and non-use substantially equivalent to the obligations set forth in this Article 16 (Confidentiality) except for a shorter duration, if customary (provided, however, that in the case of advisors bound by professional obligations of confidentiality and non-use, no agreement will be required), to maintain the confidentiality thereof and not to use such Confidential Information except as expressly permitted;
provided, however, that, in each of the above situations in this Section 16.3.1 (Disclosure), the Receiving Party will remain responsible for any failure by any Person who receives Confidential Information from such Receiving Party pursuant to this Section 16.3.1 (Disclosure) to treat such Confidential Information as required under this Article 16 (Confidentiality).
16.3.2Terms of Disclosure. If and whenever any Confidential Information is disclosed in accordance with this Section 16.3 (Authorized Disclosure), such disclosure will not cause any such information to cease to be Confidential Information, except to the extent that such disclosure results in a public disclosure of such information other than by breach of this Agreement or any Ancillary Agreement.
16.4Residual Knowledge. Notwithstanding anything to the contrary contained in this Agreement or any Ancillary Agreement and subject to Section 14.9 (Exclusivity), nothing shall restrict any Party from using Residual Knowledge for any purpose; provided, that neither Party will specifically disclose any Residual Knowledge to any Third Party.
16.5Terms of this Agreement. The Parties agree that this Agreement and the Ancillary Agreements and the terms hereof will be deemed to be Confidential Information of both Nurix and Seagen, and each Party agrees not to disclose this Agreement or any Ancillary Agreement or any terms hereof or thereof without obtaining the prior written consent of the other Party; provided, that each Party may disclose this Agreement or any terms hereof in accordance with the provisions of Section 16.3 (Authorized Disclosure), or Section 16.6 (Securities Filings; Disclosure under Applicable Law), as applicable.
16.6Securities Filings; Disclosure under Applicable Law. Each Party acknowledges and agrees that the other Party may submit this Agreement to, or file this Agreement with, the Securities Regulators or to other Persons as may be required by Applicable Law, and if a Party submits this Agreement to, or files this Agreement with, any Securities Regulator or other Person as may be required by Applicable Law, such Party agrees to consult with the other Party with respect to the preparation and submission of a confidential treatment request for this Agreement and shall incorporate reasonable comments from the other Party to the extent legally permissible. Notwithstanding the foregoing, if a Party is required by any Securities Regulator or
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other Person as may be required by Applicable Law to make a disclosure of the terms of this Agreement in a filing or other submission as required by such Securities Regulator or such other Person, and such Party has: (a) provided copies of the disclosure to the other Party reasonably in advance under the circumstances of such filing or other disclosure; (b) promptly notified the other Party in writing of such requirement and any respective timing constraints; and (c) given the other Party reasonable time under the circumstances from the date of provision of copies of such disclosure to comment upon and request confidential treatment for such disclosure, then such Party will have the right to make such disclosure at the time and in the manner reasonably determined by its counsel to be required by the Securities Regulator or the other Person. Notwithstanding the foregoing, if a Party seeks to make a disclosure as required by a Securities Regulator or other Person as may be required by Applicable Law as set forth in this Section 16.6 (Securities Filings; Disclosure under Applicable Law) and the other Party provides comments in accordance with this Section 16.6 (Securities Filings; Disclosure under Applicable Law), the Party seeking to make such disclosure or its counsel, as the case may be, will use good faith efforts to incorporate such comments.
16.7Publicity.
16.7.1Press Release. Nurix will have the right to issue a press release in the form set forth in Schedule 16.7.1, which Nurix shall issue within five (5) Business Days after the Effective Date.
16.7.2Nurix Rights. Nurix will have the right to issue any press release or other public statement disclosing each exercise of a Degrader License Option and the payment of each Milestone Payment or Sales Milestone Payment; provided, that Nurix must first obtain the prior written consent of Seagen (which shall not be unreasonably withheld, conditioned or delayed); provided, however, that any such press release or other public statement does not include the Confidential Information of Seagen. Except as permitted under this Section 16.7 (Publicity) or Article 16 (Confidentiality), Nurix will not make any other press release or other public statement disclosing this Agreement or the activities hereunder without Seagen’s prior written consent. The contents of any press release or other public statement that has been reviewed and approved by Seagen may be re-released by Nurix in exactly the same language as previously approved by Seagen without first obtaining Seagen’s prior written consent in accordance with this Section 16.7 (Publicity).
16.8Publications. Before the Degrader License Effective Date for any Collaboration Degrader Target Set, neither Party will publish, publicly present or otherwise publicly disclose any paper, publication, oral presentation, abstract, poster, manuscript or other presentation relating to any activity or other matter under this Agreement (each, a “Publication”) relating to the applicable Collaboration Degrader Target Set, without the other Party’s prior written consent. Following the applicable Degrader License Effective Date, Seagen shall be responsible for and control all Publications relating to the applicable Licensed Degrader Target Set and solely to the extent permitted by the prior written consent of Seagen, Nurix shall have the right to make and disclose any such permitted Publications. To the extent a Party has a right pursuant to this Section 16.8 (Publications) to make a Publication, then the publishing Party (the “Publishing Party”) shall provide the other Party (a “Reviewing Party”) an opportunity to review such Publication to determine whether such Publication contains the Confidential Information of the Reviewing Party. The Publishing Party will deliver to the Reviewing Party a copy of any such proposed Publication or an outline of the proposed oral disclosure, together with any slides or other materials to be provided in connection with such oral disclosure (if any), at least [*] days prior to submission for publication or presentation for review by the Reviewing Party. The Reviewing Party will have the right, in its sole discretion, to: (a) require the removal of its Confidential Information from any such Publication by the Publishing Party or (b) request a reasonable delay in publication or presentation in order to protect patentable information. If the Reviewing Party requests such a
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delay, the Publishing Party will delay submission or presentation for a period of [*] days after its provision of the copy of the proposed Publication to enable patent applications protecting the Reviewing Party’s rights in such information.
16.9Use of Names. Except as otherwise expressly set forth herein, neither Party (or any of its respective Affiliates) will use any corporate name, trademark, trade name or logo of the other Party or any of its Affiliates, or its or their respective employees, in any publicity, promotion, news release or other public disclosure relating to this Agreement or its subject matter, without first obtaining the prior written consent of the other Party; provided, however, that such consent will not be required (a) to the extent use thereof may be required by Applicable Law, including the rules of any securities exchange or market on which a Party’s or its Affiliate’s securities are listed or traded, and (b) for use of the other Party’s name and company logo, in accordance with written specifications and standards to be provided by the other Party, solely to identify the other Party as a collaborator on such Party’s website and in public presentations. If Seagen at any time determines that the use of Seagen’s name and company logo for such purpose does not comply with such specifications and standards provided by Seagen and so notifies Nurix, then Nurix shall cease using Seagen’s name and company logo in such unapproved manner as soon as reasonably possible. Each Party shall retain all rights, title and interests in and to all such corporate names, trademarks, trade names and logos of such Party and its Affiliates.
16.10Clinical Trials Registry. For clarity, Seagen, its Affiliates and its designees will have the right to publish registry information and summaries of data and results from any Clinical Trials conducted in connection with Licensed Products, on its Clinical Trials registry or on a government-sponsored database, such as www.clinicaltrials.gov, without first obtaining the prior consent of Nurix. The Parties will reasonably cooperate if required or reasonably requested in writing by Seagen in order to facilitate any such publication by Seagen, any of its Affiliates or any of its designees.
ARTICLE 17
REPRESENTATIONS AND WARRANTIES; CLOSING CONDITIONS; COVENANTS
17.1Representations and Warranties of Each Party. Each Party hereby represents and warrants to the other Party, as of Effective Date, that:
(a)such Party is duly organized, validly existing and in good standing under the Applicable Law of the jurisdiction of its formation and has full corporate power and authority and the legal right to own and operate its property and assets and to carry on its business as it is now being conducted and as contemplated in this Agreement, including the full right to grant the licenses and sublicenses granted by it hereunder;
(b)such Party has the corporate power and authority and the legal right to enter into this Agreement and perform its obligations hereunder, and has taken all necessary corporate action on its part to authorize the execution and delivery of this Agreement and the performance of its obligations hereunder;
(c)this Agreement has been duly executed and delivered on behalf of such Party and constitutes a legal, valid and binding obligation, enforceable against it in accordance with its terms, except to the extent that enforcement of the rights and remedies created hereby is subject to: (a) bankruptcy, insolvency, reorganization, moratorium and other similar laws of general application affecting the rights and remedies of creditors; or (b) laws governing specific performance, injunctive relief and other equitable remedies;
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(d)the execution, delivery and performance of this Agreement by such Party does not breach, violate, or conflict with any agreement or any provision thereof (including any confidentiality or non-competition obligation, any exclusivity obligation, or any provisions with respect to the ownership, prosecution and enforcement of intellectual property rights), or any instrument or understanding, oral or written, to which such Party (or any of its Affiliates) is a party or by which such Party (or any of its Affiliates) is bound, nor violate any Applicable Law of any Governmental Authority having jurisdiction over such Party (or any of its Affiliates);
(e)no government authorization, consent, approval, license, exemption of or filing or registration with any court or governmental department, commission, board, bureau, agency or instrumentality, domestic or foreign, under any Applicable Law currently in effect, is or will be necessary for, or in connection with, any of the transactions contemplated by this Agreement, or for the performance by it of its obligations under this Agreement, except as may be required to conduct Clinical Trials or to seek or obtain Regulatory Approvals or applicable Regulatory Materials, or to Manufacture or Commercialize any Licensed Product(s);
(f)it has obtained all necessary authorizations, consents and approvals of any Third Party that is required to be obtained by it for, or in connection with, any of the transactions contemplated by this Agreement, or for the performance by it of its obligations under this Agreement, except as may be required to conduct Clinical Trials or to seek or obtain Regulatory Approvals or applicable Regulatory Materials, or to Manufacture or Commercialize any Licensed Product(s); and
(g)Neither it nor any of its Affiliates (i) has been debarred or is subject to debarment pursuant to Section 306 of the FFDCA or analogous provisions of Applicable Law outside the United States or listed on any excluded list; (ii) has used in any capacity, in connection with the activities to be performed under this Agreement, any individual or entity that has been debarred pursuant to Section 306 of the FFDCA or analogous provisions of Applicable Law outside the United States, or that is the subject of a conviction described in such Section or analogous provisions of Applicable Law outside the United States; (iii) has been listed by any Governmental Authority as ineligible to participate in any government healthcare program or government procurement or non-procurement program, or is excluded, debarred, or suspended from participating in any such program; or (iv) has been convicted of a criminal offense related to the provision of healthcare items or services. Each Party agrees to inform the other Party in writing promptly if such Party or any individual or entity performing activities under this Agreement on behalf of such Party becomes subject to any of the foregoing.
17.2Representations and Warranties of Nurix. Nurix hereby represents and warrants to Seagen as of the Effective Date that:
(a)Schedule 17.2(a) sets forth a complete and accurate list of all the Nurix Patents existing as of the Effective Date that are (i) necessary or reasonably useful for the Joint Research Plans for the Initial Degrader Target Sets or (ii) necessary or reasonably useful to Research, Develop, Manufacture, Commercialize or otherwise Exploit Licensed Products that contain any Collaboration Degrader Directed To the Initial Degrader Target Sets (including as part of any Licensed Degrader-Antibody Conjugates) in the Field in the Territory.
(b)Nurix is the sole and exclusive owner of the Nurix IP free and clear of all liens and encumbrances that would adversely affect the rights to Seagen hereunder in any material respect. Nurix has the full right and authority to grant all of the
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rights and licenses granted to Seagen hereunder, and neither Nurix nor its Affiliates have granted any right or license, or committed to grant any right or license, to any Third Party relating to any of the Nurix IP in a manner that would conflict with or limit the scope of any of the options, rights or licenses granted to Seagen hereunder.
(c)Nurix has complied in all respects with all Applicable Law with respect to the Prosecution and Maintenance of the Nurix Patents. No dispute regarding inventorship or ownership has been alleged or threatened with respect to any Nurix Patents. There is no pending or threatened adverse Action (including any interference, inter partes review, post-grant review, re-examination, opposition, or inventorship or ownership challenge, in each case, in or before any patent office or other Governmental Authority) against Nurix in relation to any Nurix Patents. All Nurix Patents are: (i) subsisting and, to Nurix’s knowledge, not invalid or unenforceable, in whole or in part, (ii) in the case of pending applications, being diligently prosecuted in the respective patent offices in accordance with Applicable Law and Nurix has presented all relevant references, documents and information of which it and the inventors are aware to the relevant patent examiner at the relevant patent office and (iii) Prosecuted and Maintained properly and correctly (including by identifying every inventor of the claims thereof as determined in accordance with the laws of the jurisdiction in which such Patent is issued or pending) and all applicable fees have been paid by the due date for payment.
(d)Nurix has not misappropriated any Know-How of a Third Party or, to Nurix’s knowledge, infringed any Patents of a Third Party in connection with developing the Nurix IP. Neither Nurix nor its Affiliates have received any written notice or to Nurix’s knowledge, any threat of any claim or litigation that any Patent or Know-How (including any trade secret right) Controlled by a Third Party would be infringed, misappropriated or otherwise violated by the performance of the activities hereunder or by the Development, Manufacture, Commercialization or Exploitation of the Licensed Products in accordance with this Agreement. Neither (i) the Nurix Materials supplied by Nurix to Seagen hereunder, nor (ii) the use and practice of the Nurix IP as contemplated hereunder would misappropriate or, to Nurix’s knowledge, infringe any intellectual property rights of any Third Party. To Nurix’s knowledge, there are no activities by Third Parties within the Territory that would constitute misappropriation of Nurix Know-How or infringement of Nurix Patents. Neither Nurix nor its Affiliates have received any written notice or to Nurix’s knowledge, any threat, of a claim or litigation made by any Person against Nurix or its Affiliates that alleges that any Nurix Patent is invalid or unenforceable.
(e)Nurix and its Affiliates have obtained from all individuals who participated in any respect in the invention or authorship of any Nurix IP effective written assignments of all ownership rights of such individuals in such Nurix IP, as applicable. To Nurix’s knowledge, no Person who claims to be an inventor of an invention claimed in a Nurix Patent is not identified as an inventor of such invention in the filed patent documents for such Nurix Patent.
(f)The inventions claimed or covered by the Nurix Patents (i) were not conceived, discovered, developed or otherwise made in connection with any research activities funded, in whole or in part, by the federal government of the United States (or any agency thereof) or the government of any other country; (ii) are not a “subject invention” as that term is described in 35 U.S.C. §201(e); (iii) are not otherwise subject to the provisions of the Patent and Trademark Law Amendments Act of 1980, as amended, codified at 35 U.S.C. §§200-212, as amended, or any regulations promulgated pursuant thereto, including in 37 C.F.R. Part 401; and (iv) are not the subject of any licenses, options or other rights of any Governmental Authority, within or outside the United
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States; in the case of clauses (ii) or (iii), or similar obligations or restrictions under the Applicable Law of any other country.
(g)There are no exclusivity provisions or any other restrictions in any agreement between Nurix or its Affiliates, on the one hand, and any Third Party, on the other hand, that would limit (i) Nurix’s ability to (A) perform its obligations under this Agreement, or (B) grant such rights and licenses as granted under this Agreement to Seagen, or (ii) to Nurix’s knowledge, Seagen’s ability to Research, Develop, Manufacture, Commercialize or otherwise Exploit the Licensed Products as contemplated by this Agreement. Neither Nurix nor any of its Affiliates are delinquent in any payment obligations to any Third Party, or engaged in any dispute with any Third Party, that would limit (x) Nurix’s ability to (A) perform its obligations under this Agreement, or (B) grant such rights and licenses as granted under this Agreement to Seagen or (y) to Nurix’s knowledge, Seagen’s ability to Research, Develop, Manufacture, Commercialize or otherwise Exploit the Licensed Products as contemplated by this Agreement.
(h)There are no claims, judgments, settlements, litigations, suits, actions, disputes, arbitration, judicial, or legal, administrative or other proceedings, or governmental investigations pending or, to the knowledge of Nurix, threatened against Nurix or its Affiliates which could reasonably be expected to adversely affect or restrict the ability of Nurix to consummate or perform the transactions contemplated under this Agreement.
17.3Representations and Warranties of Seagen. Seagen hereby represents and warrants to Nurix, as of the Effective Date, that:
(a)Neither (i) the Seagen Materials supplied by Seagen to Nurix hereunder, nor (ii) the use and practice of the Seagen IP as contemplated hereunder would, to Seagen’s knowledge, misappropriate or infringe any intellectual property rights of any Third Party.
(b) There are no claims, judgments, settlements, litigations, suits, actions, disputes, arbitration, judicial, or legal, administrative, or other proceedings or governmental investigations pending or, to the actual knowledge of Seagen, threatened against Seagen which would reasonably be expected to adversely affect or restrict the ability of Seagen to consummate or perform the transaction contemplated under this Agreement.
17.4Covenants. Each Party hereby covenants to the other Party that during the Term: (a) such Party and its Affiliates will perform its activities pursuant to this Agreement in compliance (and will ensure compliance by any of its subcontractors) with all Applicable Law, including, to the extent applicable, FCPA, GCP, GLP and GMP and in accordance with good scientific, clinical and manufacturing practices and applicable industry ethical codes; (b) will not employ, or otherwise use in any capacity, the services of any Person suspended, proposed for debarment or debarred under United States law, including under 21 U.S.C. § 335a, or any foreign equivalent thereof, with respect to the performance of activities hereunder; (c) such Party will not enter into any agreement, contract, commitment or other arrangement that could reasonably be expected to conflict with the rights granted to the other Party hereunder or otherwise prevent the other Party from exercising the rights granted to it hereunder; (d) such Party will not misappropriate any trade secret of a Third Party in connection with the performance of its activities hereunder; and (e) such Party will maintain all permits, licenses, registrations and other forms of authorizations and approvals from any Governmental Authority, necessary or required to be obtained or maintained by such Party in order for such Party to execute and deliver this Agreement
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and to perform its obligations hereunder and thereunder in a manner which complies with all Applicable Law.
17.5Disclaimer. EXCEPT AS OTHERWISE EXPRESSLY PROVIDED IN THIS AGREEMENT, NEITHER PARTY MAKES ANY REPRESENTATIONS OR EXTENDS ANY WARRANTY OF ANY KIND, EITHER EXPRESS OR IMPLIED (AND EACH PARTY HEREBY EXPRESSLY DISCLAIMS ANY AND ALL REPRESENTATIONS AND WARRANTIES NOT EXPRESSLY PROVIDED IN THIS AGREEMENT), INCLUDING WITH RESPECT TO ANY PATENTS OR KNOW-HOW, INCLUDING WARRANTIES OF VALIDITY OR ENFORCEABILITY, MERCHANTABILITY, FITNESS FOR A PARTICULAR USE OR PURPOSE, PERFORMANCE AND NON-INFRINGEMENT OF ANY THIRD PARTY PATENT OR OTHER INTELLECTUAL PROPERTY RIGHT. WITHOUT LIMITING THE FOREGOING, THE PARTIES AGREE THAT THE MILESTONE EVENTS AND NET SALES LEVELS SET FORTH IN THIS AGREEMENT OR THAT HAVE OTHERWISE BEEN DISCUSSED BY THE PARTIES ARE MERELY INTENDED TO DEFINE THE MILESTONE PAYMENTS AND ROYALTY OBLIGATIONS IF SUCH MILESTONE EVENTS OR NET SALES LEVELS ARE ACHIEVED. NEITHER PARTY MAKES ANY REPRESENTATION OR WARRANTY, EITHER EXPRESS OR IMPLIED, THAT IT WILL BE ABLE TO SUCCESSFULLY ADVANCE ANY DEGRADER PRODUCT OR DEVELOP, ACHIEVE REGULATORY APPROVAL FOR, MANUFACTURE OR COMMERCIALIZE ANY LICENSED PRODUCT OR, IF COMMERCIALIZED, THAT ANY PARTICULAR SALES LEVEL OR PROFIT OF SUCH LICENSED PRODUCT WILL BE ACHIEVED.
ARTICLE 18
INDEMNIFICATION; INSURANCE
18.1Indemnification.
18.1.1Indemnification by Seagen. Seagen will indemnify, defend and hold harmless Nurix, its Affiliates and its and their respective directors, officers, employees, agents, successors and assigns (each, a “Nurix Indemnitee”) from and against any and all Damages to the extent arising out of or relating to, directly or indirectly, any Third Party Claim based upon:
(a)any Research activities conducted by Seagen or its Affiliates or contractors under this Agreement;
(b)the Development, Manufacture or Commercialization of Licensed Products in the Field in the Territory by Seagen, its Affiliates or its Sublicensees (provided, that in the event Nurix exercises its Profit-Share Option and the Parties enter into a Profit-Share Product Agreement with respect to a Profit-Share Product, the relevant Profit-Share Product Agreement will control with respect to any Third Party Claim based on the Development, Manufacture or Commercialization of Profit-Share Products);
(c)the gross negligence or willful misconduct of Seagen or its Affiliates or its or their respective directors, officers, employees or agents, in connection with Seagen’s performance of its obligations under this Agreement or any Ancillary Agreement; or
(d)any breach by Seagen of any of its representations, warranties, covenants, agreements or obligations under this Agreement or any Ancillary Agreement;
provided, however, that in each case ((a)-(d)), such indemnity will not apply to the extent Nurix has an indemnification obligation pursuant to Section 18.1.2 (Indemnification by Nurix) for such Damages.
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18.1.2Indemnification by Nurix. Nurix will indemnify, defend and hold harmless Seagen, its Affiliates and its and their respective directors, officers, employees, agents, successors, assigns and Sublicensees (each, a “Seagen Indemnitee”), from and against any and all Damages to the extent arising out of or relating to, directly or indirectly, any Third Party Claim based upon:
(a)any Research activities conducted by Nurix or its Affiliates or contractors under this Agreement;
(b)the gross negligence or willful misconduct of Nurix or its Affiliates or its or their respective directors, officers, employees or agents, in connection with Nurix’s performance of its obligations under this Agreement or any Ancillary Agreement; or
(c)any breach by Nurix of any of its representations, warranties, covenants, agreements or obligations under this Agreement or any Ancillary Agreement;
provided, however, that in each case ((a)-(c)), such indemnity will not apply to the extent Seagen has an indemnification obligation pursuant to Section 18.1.1 (Indemnification by Seagen) for such Damages.
18.2Indemnification Procedure.
18.2.1Indemnification Notice. If a Nurix Indemnitee or Seagen Indemnitee is seeking indemnification under Section 18.1.1 (Indemnification by Seagen) or Section 18.1.2 (Indemnification by Nurix), as applicable (the “Indemnitee”), Nurix or Seagen, as applicable, will inform the other Party (the “Indemnitor”) of the claim giving rise to the obligation to indemnify pursuant to Section 18.1.1 (Indemnification by Seagen) or Section 18.1.2 (Indemnification by Nurix), as applicable, as soon as reasonably practicable after receiving notice of the claim (an “Indemnification Claim Notice”); provided, however, that any delay or failure to provide such notice will not constitute a waiver or release of, or otherwise limit, the Indemnitor’s obligation to indemnify under Section 18.1.1 (Indemnification by Seagen) or Section 18.1.2 (Indemnification by Nurix), as applicable, except to the extent that such delay or failure materially prejudices the Indemnitor’s ability to defend against the relevant claims.
18.2.2Control of Defense. The Indemnitor will have the right, upon written notice given to the Indemnitee and the non-indemnifying Party within [*] days after receipt of the Indemnification Claim Notice, to assume the defense of any such claim for which the Indemnitee is seeking indemnification pursuant to Section 18.1.1 (Indemnification by Seagen) or Section 18.1.2 (Indemnification by Nurix), as applicable. The non-indemnifying Party will cause the Indemnitee to cooperate with the Indemnitor and the Indemnitor’s insurer as the Indemnitor may reasonably request, and at the Indemnitor’s cost and expense. The Indemnitee will have the right to participate, at its own expense and with counsel of its choice, in the defense of any claim or suit that has been assumed by the Indemnitor.
18.2.3Settlements; No Presumption of Liability. The Indemnitor will not settle any claim without first obtaining the prior written consent of the non-indemnifying Party, not to be unreasonably withheld, conditioned or delayed; provided, that the Indemnitor shall have the right to settle claims that are exclusively for money damages without such prior written consent so long as the settlement does not impose any liability or admit any fault on behalf of the Indemnitee. The assumption of the defense of a claim by the Indemnitor will not be construed as an acknowledgment that the Indemnitor is liable to indemnify the Indemnitee in respect of the claim, nor will it constitute a waiver by the Indemnitor of any defenses it may assert against the Indemnitee’s claim for indemnification. In the event that it is ultimately determined that the
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Indemnitor is not obligated to indemnify, defend or hold harmless the Indemnitee from and against the claim, the non-indemnifying Party will reimburse the Indemnitor for any and all costs and expenses (including attorneys’ fees and costs of suit) and any Damages incurred by the Indemnitor in its defense of the claim.
18.2.4Separate Defenses; Cooperation. If the Parties cannot agree as to the application of Section 18.1.1 (Indemnification by Seagen) or Section 18.1.2 (Indemnification by Nurix), as applicable, to any claim, pending the resolution of the Dispute pursuant to Section 20.6 (Choice of Law; Dispute Resolution; Jurisdiction), the Parties may conduct separate defenses of such claims, with each Party retaining the right to claim indemnification from the other Party in accordance with Section 18.1.1 (Indemnification by Seagen) or Section 18.1.2 (Indemnification by Nurix), as applicable, upon resolution of the underlying claim. In each case, the non-indemnifying Party will cause each applicable Indemnitee to reasonably cooperate with the Indemnitor and make available to the Indemnitor all pertinent information under the control of the Indemnitee, which information will be subject to Article 16 (Confidentiality).
18.3Insurance. During the Term and for a period of [*] years thereafter, each Party will have and maintain in full force and effect, at its own expense, insurance coverage (with a Third Party insurance company with a current AM Best rating of A- or equivalent or higher, or through a commercially reasonable program of self-insurance) to include:
(a)Commercial general liability insurance (including product liability coverage and completed operations liability coverage and covering bodily injury and property damage) with limits of liability not less than [*] per occurrence and [*] in the aggregate;
(b)Statutory workers’ compensation insurance in compliance with Applicable Law (including the local law requirements of the state or jurisdiction in which the work is to be performed);
(c)Employer’s liability insurance with limits of liability not less than [*] per occurrence and [*] in the aggregate; and
(d)Umbrella/excess liability insurance providing additional limits above the commercial general liability insurance policy with limits of liability not less than [*] per occurrence and [*] in the aggregate.
For the avoidance of doubt, none of the coverage under this section shall serve to limit or expand the Parties’ indemnification obligations or other liability under this Agreement. As reasonably requested by the other Party (such request not more than once per Calendar Year), and to the extent applicable, a Party shall furnish one (1) or more certificates of insurance evidencing that the coverage required by this Section 18.3 (Insurance) is in full force and effect in compliance with the provisions of this Section 18.3 (Insurance). Each such certificate shall state the relevant policy number(s), date(s) of expiration and required limits of coverage.
18.4Limitation of Liability. NEITHER NURIX NOR SEAGEN, NOR ANY OF THEIR RESPECTIVE AFFILIATES, WILL BE LIABLE TO THE OTHER PARTY OR ITS AFFILIATES UNDER OR IN CONNECTION WITH THIS AGREEMENT OR ANY ANCILLARY AGREEMENT FOR ANY INDIRECT, INCIDENTAL, CONSEQUENTIAL, SPECIAL, PUNITIVE OR EXEMPLARY DAMAGES (INCLUDING LOST PROFITS OR LOST REVENUES), WHETHER LIABILITY IS ASSERTED IN CONTRACT, TORT (INCLUDING NEGLIGENCE AND STRICT PRODUCT LIABILITY), INDEMNITY, CONTRIBUTION OR OTHERWISE, AND IRRESPECTIVE OF WHETHER THAT PARTY OR ANY REPRESENTATIVE OF THAT PARTY HAS BEEN ADVISED OF, OR
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OTHERWISE MIGHT HAVE ANTICIPATED THE POSSIBILITY OF, ANY SUCH LOSS OR DAMAGE. NOTWITHSTANDING THE FOREGOING, NOTHING IN THIS SECTION 18.4 (LIMITATION OF LIABILITY) IS INTENDED TO OR WILL LIMIT OR RESTRICT: (A) THE INDEMNIFICATION RIGHTS OR OBLIGATIONS OF ANY PARTY UNDER SECTION 18.1.1 (INDEMNIFICATION BY SEAGEN) OR SECTION 18.1.2 (INDEMNIFICATION BY NURIX), AS APPLICABLE, IN CONNECTION WITH A CLAIM FOR SUCH LOSSES OR DAMAGES BY A THIRD PARTY; (B) THE LIABILITY OF A PARTY FOR BREACH OF ITS EXCLUSIVITY OBLIGATIONS UNDER SECTION 14.9 (EXCLUSIVITY); (C) DAMAGES AVAILABLE FOR A PARTY’S GROSS NEGLIGENCE, INTENTIONAL MISCONDUCT OR FRAUD; OR (D) LIABILITY OF EITHER PARTY FOR BREACH OF ARTICLE 16 (CONFIDENTIALITY).
ARTICLE 19
TERM AND TERMINATION
19.1Term; Expiration. The term of this Agreement (the “Term”) will begin on the Effective Date and expire upon the first to occur of (a) the expiration of the last-to-expire Degrader License Option Period under this Agreement if no Degrader License Option has been exercised prior to such expiration, or (b) the expiration of the last-to-expire Royalty Term under this Agreement (or as otherwise provided in a relevant Nurix Opt-In Agreement, if applicable), in each case, unless earlier terminated in accordance with this Article 19 (Term and Termination). For clarity, if a Degrader License Option is exercised in accordance with this Agreement, the Term shall continue following such exercise until the commencement and expiration of all applicable Royalty Terms, subject to the foregoing clause (b), regardless of whether any Royalty Term has commenced or is ongoing as of the date of such exercise or any determination of the Term hereunder.
19.2Termination.
19.2.1Termination for Material Breach.
(a)Material Breach. This Agreement may be terminated (i) in its entirety for a material breach by the other Party that (A) fundamentally frustrates the value and essential purpose of the transactions contemplated by this Agreement and (B) affects this Agreement in its entirety, or (ii) in part, on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis or a Licensed Degrader Target Set-by-Licensed Degrader Target Set basis, as applicable, for a material breach by the other Party with respect to and affecting such Collaboration Degrader Target Set or Licensed Degrader Target Set, as applicable, in each case ((i) and (ii)), upon written notice to the breaching Party if the breaching Party has not cured such material breach within [*] if for breach of a payment obligation under this Agreement or [*] for all other breaches, in each case, after the date of written notice to the breaching Party of such breach (which notice will describe such material breach in reasonable detail and will state the non-breaching Party’s intention to terminate this Agreement, in its entirety or in part) (such [*] or [*] period, as applicable, the “Cure Period”).
(b)Disagreement as to Material Breach. Notwithstanding Section 19.2.1(a) (Material Breach), if the Parties in good faith disagree as to whether there has been a material breach of this Agreement or a cure of any such breach, then: (i) the Party that disputes whether there has been a material breach or cure may contest the allegation by referring such matter, within the applicable Cure Period in the event of a Dispute regarding whether there has been a material breach or within [*] following the expiration of the appliable Cure Period in the event of a Dispute regarding whether there has been a cure of any such breach, for resolution in accordance with Section 20.6
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(Choice of Law; Dispute Resolution; Jurisdiction); (ii) if a Party disputes such material breach or cure as described in clause (i) above, then the relevant Cure Period and the Parties’ rights to terminate this Agreement will be tolled from the date on which the Party that disputes the existence of such material breach or cure notifies the other Party of such Dispute through final resolution of such Dispute in accordance with Section 20.6 (Choice of Law; Dispute Resolution; Jurisdiction) (or, if earlier, until abandonment of the Dispute by the disputing Party); and (iii) subject to the foregoing (including tolling of the Parties’ rights to terminate this Agreement) and Section 19.4 (Surviving Provisions), during the pendency of such Dispute, all other terms and conditions of this Agreement and the Ancillary Agreements will remain in effect and the Parties will continue to perform all of their respective obligations hereunder and thereunder.
19.2.2Termination at Will. Seagen may terminate this Agreement at will, in Seagen’s sole discretion (a) on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis prior to the Degrader License Effective Date for a Collaboration Degrader Target Set, upon delivery of [*] written notice to Nurix; and (b) on a Licensed Degrader Target Set-by-Licensed Degrader Target Set basis after the Degrader License Effective Date for a Licensed Degrader Target Set, upon delivery of [*] written notice to Nurix. Without limiting the foregoing, Seagen may terminate this Agreement at will, in Seagen’s sole discretion, in this Agreement’s entirety: (i) prior to the Degrader License Effective Date for any Collaboration Degrader Target Set, upon delivery of [*] prior written notice to Nurix; and (ii) after the Degrader License Effective Date for any Licensed Degrader Target Set, upon delivery of [*] prior written notice to Nurix.
19.2.3Termination for Outside Date. Either Party may terminate this Agreement, on a Collaboration Degrader Target Set-by-Collaboration Degrader Target Set basis, if and to the extent permitted in accordance with Section 5.4.3 (Outside Date).
19.2.4Termination for Bankruptcy.
(a)Termination Right. In the event that either Party (i) commences a voluntary case under the Bankruptcy Code or any similar bankruptcy or insolvency law foreign or domestic, (ii) makes an assignment for the benefit of, or an arrangement or composition generally with, its creditors, (iii) appoints an examiner or of a receiver or trustee over all or substantially all of its property or suffers the appointment of such party that is not discharged within [*] after such filing or appointment, (iv) proposes or is a party to any dissolution, liquidation or winding up of such Party, (v) has an involuntary petition filed against it under the Bankruptcy Code or any similar bankruptcy or insolvency law that is not discharged or dismissed within [*] of the filing thereof, or (vi) admits in writing its inability generally to meet its obligations as they fall due in the ordinary course, then the other Party may terminate this Agreement in its entirety effective immediately upon written notice to such Party.
(b)Section 365(n) Rights. For purposes of Section 365(n) of the Bankruptcy Code and any similar law, foreign or domestic, all rights and licenses granted under or pursuant to any Section of this Agreement are rights to “intellectual property” (as defined in Section 101(35A) of the Bankruptcy Code). The Parties agree that the licensee of such rights under this Agreement will retain and may fully exercise all of its protections, rights and elections under the Bankruptcy Code and any similar laws in any other country. Each Party hereby acknowledges that copies of research data, laboratory samples, product samples and inventory, formulas, laboratory notes and notebooks, pre-clinical research data and results, tangible Know-How and rights of reference, in each case, that relate to such intellectual property, constitute “embodiments” of such intellectual property pursuant to Section 365(n) of the Bankruptcy Code. The
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Parties agree that in the event of the commencement of a case by or against a Party under the Bankruptcy Code, then the other Party will be entitled to a complete duplicate of (or complete access to, as appropriate) any intellectual property licensed to such other Party and all embodiments of such intellectual property, and the same, if not already in the other Party’s possession, will be (i) promptly delivered to the other Party, unless and until this Agreement or any license of rights to intellectual property hereunder is rejected, and (ii) if not delivered under clause (i), upon the other Party’s written request therefor, following (A) the rejection of this Agreement or any license of rights to intellectual property hereunder, and (B) such other Party’s election to retain its rights under Section 365(n)(1)(B) of the Bankruptcy Code. The provisions of this Section 19.2.4(b) (Section 365(n) Rights) are without prejudice to any rights the non-bankrupt Party may have arising under the Bankruptcy Code, laws of other jurisdictions governing insolvency and bankruptcy or other Applicable Law. The Parties agree that they intend the following rights to extend to the maximum extent permitted by law, including for purposes of the Bankruptcy Code and any similar laws in any other country: (x) the right of access of the licensee to any intellectual property (including all embodiments thereof) of (i) the licensor, or (ii) any Third Party with whom the licensor contracts to perform an obligation of such licensor under this Agreement which is necessary for the Development, Manufacture or Commercialization of a Licensed Product; (y) the right of licensee to contract directly with any Third Party described in (x)(ii) to complete the contracted work and (z) the right of licensee to cure any breach of or default under any such agreement with a Third Party and set off the costs thereof against amounts payable to such licensor under this Agreement.
19.2.5Termination for Material Safety Matters. Seagen will have the right to terminate this Agreement (and all Ancillary Agreements) in its entirety or in part on a Licensed Degrader Target Set-by-Licensed Degrader Target Set basis upon [*] prior written notice to Nurix, if the Seagen Safety Review Committee has recommended, in accordance with Seagen’s internal operating procedures consistently applied across its own pharmaceutical products, cessation of Development or Commercialization of [*]. Seagen shall include in its notice of termination a summary of the Seagen Safety Review Committee’s concerns.
19.3Effects of Expiration and Termination.
19.3.1Termination with respect to Collaboration Degrader Target Sets. Upon termination of this Agreement with respect to a Collaboration Degrader Target Set (including as a result of termination of this Agreement in its entirety): (i) by Seagen, in accordance with Section 19.2.2 (Termination at Will); or (ii) by Nurix, in accordance with Section 19.2.1 (Termination for Material Breach) or Section 19.2.4 (Termination for Bankruptcy); or (iii) by either Party, in accordance with Section 19.2.3 (Termination for Outside Date), such Collaboration Degrader Target Set and all of its Subsets shall become Former Collaboration Degrader Target Sets, and:
(a)the license grant by Nurix to Seagen as further described in Section 14.1 (Research Licenses) with respect to such Former Collaboration Degrader Target Sets shall immediately terminate and Seagen will not have any rights to use or exercise any rights under the Nurix IP with respect to any Collaboration Degraders or Collaboration Degrader-Antibody Conjugates Directed To such Former Collaboration Degrader Target Sets;
(b)Nurix’s exclusivity obligations described in Section 14.9.1 (Collaboration Degrader Target Set Exclusivity) shall no longer apply to such Former Collaboration Degrader Target Sets;
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(c)the license grant by Seagen to Nurix as further described in Section 14.1 (Research Licenses) with respect to such Former Collaboration Degrader Target Sets shall immediately terminate and Nurix will not have any rights to use or exercise any rights under the Seagen IP with respect to any Collaboration Degraders or Collaboration Degrader-Antibody Conjugates Directed To such Former Collaboration Degrader Target Sets;
(d)Nurix and its Affiliates may research, Develop, Manufacture, Commercialize, or otherwise Exploit Degraders that are Directed To such Former Collaboration Degrader Target Sets including as set forth in Section 14.8.1 (No Restriction on Former Degrader Targets);
(e)Seagen will have no further obligations under this Agreement with respect to Researching, Developing, Manufacturing or Commercializing any Collaboration Degraders or Collaboration Degrader-Antibody Conjugates that are Directed To such Former Collaboration Degrader Target Sets; and
(f)Nurix will have no further obligations under this Agreement with respect to performing the Joint Research Plan or Research activities for such Former Collaboration Degrader Target Sets.
19.3.2Termination with respect to Licensed Degrader Target Sets. Upon termination of this Agreement with respect to a Licensed Degrader Target Set that is not a Collaboration Degrader Target Set (including as a result of termination of this Agreement in its entirety): (i) by Seagen, in accordance with Section 19.2.2 (Termination at Will); or (ii) by Nurix, in accordance with Section 19.2.1 (Termination for Material Breach), or Section 19.2.4 (Termination for Bankruptcy), such Licensed Degrader Target Set and all of its Subsets (including any [*] Licensed Degrader Target Set that is a Subset thereof) shall become Former Licensed Degrader Target Sets, and:
(a)the license grant by Nurix to Seagen as further described in Section 14.2 (Licensed Degrader License) with respect to such Former Licensed Degrader Target Sets shall immediately terminate and Seagen will not have any rights to use or exercise any rights under the Nurix IP with respect to any Licensed Degraders or Licensed Degrader-Antibody Conjugates Directed To such Former Licensed Degrader Target Sets;
(b)Nurix’s exclusivity obligations described in Section 14.9.3 (Licensed Degrader Target Set Exclusivity) and Section 14.9.4 ([*] Licensed Degrader Target Set Exclusivity) shall no longer apply to such Former Licensed Degrader Target Sets;
(c)Nurix and its Affiliates may research, Develop, Manufacture, Commercialize, or otherwise Exploit Degraders that are Directed To such Former Licensed Degrader Target Sets including as set forth in Section 14.8.1 (No Restriction on Former Degrader Targets);
(d)if and to the extent applicable, the terms and conditions of Section 14.3 (Reversion Licenses) shall apply;
(e)Seagen will have no further obligations under this Agreement with respect to Researching, Developing, Manufacturing or Commercializing any Licensed Degraders or Licensed Degrader-Antibody Conjugates Directed To such Former Licensed Degrader Target Sets; and
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(f)Nurix will have no further obligations under this Agreement with respect to performing the Joint Research Plan or Research activities for such Former Licensed Degrader Target Sets.
19.3.3Termination with Respect to Profit-Share Products. Without limiting Section 19.3.2 (Termination with respect to Licensed Degrader Target Sets), upon termination of this Agreement with respect to a Licensed Degrader Target Set (including as a result of termination of this Agreement in its entirety): (i) by Seagen, in accordance with Section 19.2.2 (Termination at Will); or (ii) by Nurix, in accordance with Section 19.2.1 (Termination for Material Breach), or Section 19.2.4 (Termination for Bankruptcy), then:
(a)Upon Nurix’s written request delivered to Seagen pursuant to Section 14.3.1 (Reversion Product License Agreement), the Parties shall enter into a Reversion Product License Agreement in accordance with Section 14.3.1 (Reversion Product License Agreement); and
(b)the Parties shall work together in good faith, as soon as reasonably practicable following the effective date of termination, to plan and implement an orderly wind-down or transition of all ongoing Research, Development, Manufacturing and Commercialization activities by or on behalf of the Parties with respect to any Profit-Share Product Directed To such Licensed Degrader Target Set, including the wind-down or transition of any ongoing Clinical Trials with respect to such Profit-Share Product, taking into account the protection of patient health and safety, and in accordance with any requirements under Applicable Law or from applicable Regulatory Authorities and applicable ethical standards.
19.3.4Termination with Respect to Potential Reversion Products. Without limiting Section 19.3.2 (Termination with respect to Licensed Degrader Target Sets), upon termination of this Agreement with respect to a Licensed Degrader Target Set (including as a result of termination of this Agreement in its entirety): (i) by Seagen, in accordance with Section 19.2.2 (Termination at Will); or (ii) by Nurix, in accordance with Section 19.2.1 (Termination for Material Breach), or Section 19.2.4 (Termination for Bankruptcy), the following shall apply with respect to any Licensed Product that is a Potential Reversion Product Directed To such Licensed Degrader Target Set as of the effective date of termination:
(a)Upon Nurix’s written request delivered to Seagen pursuant to Section 14.3.2 (Potential Reversion Products), the Parties shall discuss in good faith the potential terms and conditions of an Other Reversion License Agreement with respect to the applicable Potential Reversion Product pursuant to Section 14.3.2 (Potential Reversion Products); and
(b)if the Parties enter into an Other Reversion License Agreement with respect to the Potential Reversion Product, the Parties shall work together in good faith, as soon as reasonably practicable following the effective date of termination, to plan and implement an orderly wind-down or transition of all ongoing Research, Development, Manufacturing and Commercialization activities by or on behalf of the Parties with respect to the Potential Reversion Product, including the wind-down or transition of any ongoing Clinical Trials with respect to such Potential Reversion Product, taking into account the protection of patient health and safety, and in accordance with any requirements under Applicable Law or from applicable Regulatory Authorities and applicable ethical standards.
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19.3.5Termination for Material Safety Matters. Upon termination of this Agreement pursuant to Section 19.2.5 (Termination for Material Safety Matters), the following provisions shall apply with respect to the terminated Degrader Target Set(s):
(a)the Parties shall work together in good faith, as soon as reasonably practicable following the effective date of termination, to plan and implement an orderly wind-down of all ongoing Research, Development, Manufacturing and Commercialization activities by or on behalf of the Parties with respect to the terminated Degrader Target Set(s) and Licensed Products Directed To such terminated Degrader Target Set(s), including the wind-down of any ongoing Clinical Trials with respect to such Licensed Product(s), taking into account the protection of patient health and safety, and in accordance with any requirements under Applicable Law or from applicable Regulatory Authorities and applicable ethical standards;
(b)notwithstanding anything contained herein to the contrary, except for the activities contemplated by clause (a), following the effective date of termination (i) the licenses granted by each Party to the other Party with respect to the terminated Degrader Target Set(s) and Licensed Products Directed To such Degrader Target Set(s) shall terminate, and (ii) neither Party shall have the right to continue to conduct any research, Development, Manufacturing or Commercialization activities with respect to any Licensed Product(s) that are subject to such termination without the prior written consent of the other Party;
(c)Seagen will have no further obligations under this Agreement with respect to researching, Developing, Manufacturing or Commercializing any Licensed Degraders or Licensed Degrader-Antibody Conjugates Directed To the terminated Degrader Target Set(s) except as set forth in this Section 19.3.5 (Termination for Material Safety Matters); and
(d)each Party shall be responsible for its own costs incurred in the performance of wind-down activities contemplated by this Section 19.3.5 (Termination for Material Safety Matters).
19.3.6Certain Termination by Seagen. Upon termination of this Agreement with respect to a Collaboration Degrader Target Set or a Licensed Degrader Target Set (including as a result of termination of this Agreement in its entirety) by Seagen in accordance with Section 19.2.1 (Termination for Material Breach) or Section 19.2.4 (Termination for Bankruptcy):
(a)any such Collaboration Degrader Target Set and all of its Subsets shall become Former Collaboration Degrader Target Sets and any such Licensed Degrader Target Set and all of its Subsets shall become Former Licensed Degrader Target Sets; and
(b)the effects of termination set forth in Section 19.3.1 (Termination with respect to Collaboration Degrader Target Sets) and Section 19.3.2 (Termination with respect to Licensed Degrader Target Sets) shall apply, as applicable.
19.3.7Right to Maintain License. Notwithstanding anything to the contrary contained in this Agreement, if Seagen would have the right to terminate this Agreement in its entirety pursuant to Section 19.2.1(a)(i) with respect to a material breach by Nurix that is not cured during the applicable Cure Period, in lieu of such termination Seagen may elect to continue this Agreement in full force and effect, except that any amounts that become due to Nurix under this Agreement after the date of Seagen’s right to terminate shall be [*]. Seagen’s election of the remedy set forth in this Section 19.3.7 (Right to Maintain License) shall be without prejudice to
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any other remedies that Seagen may have under this Agreement or otherwise under Applicable Law; provided, that if Seagen also pursues a claim for Damages arising from the applicable breach, then any resulting Damages award shall be reduced by the value of the remedies provided under this Section 19.3.7 (Right to Maintain License).
19.4Surviving Provisions.
19.4.1Accrued Rights; Remedies. The expiration or termination of this Agreement for any reason will be without prejudice to any rights that will have accrued to the benefit of any Party prior to such expiration or termination, and any and all Damages or remedies (whether at law or in equity) arising from any breach hereunder, each of which will survive expiration or termination of this Agreement. Such expiration or termination will not relieve any Party from obligations which are expressly indicated to survive expiration or termination of this Agreement. Except as otherwise expressly set forth in this Agreement, the termination provisions of this Article 19 (Term and Termination) are in addition to any other relief and remedies available to either Party under this Agreement, at law or in equity. Except as expressly stated herein with respect to the applicable Collaboration Degrader Target Set or Licensed Degrader Target Set, termination of this Agreement, in part, with respect to a Collaboration Degrader Target Set or a Licensed Degrader Target Set will have no effect on the terms and conditions of this Agreement or the rights and obligations of the Parties with respect to any other matter or Degrader Target Set.
19.4.2Survival. Without limiting the provisions of Section 19.4.1 (Accrued Rights; Remedies), the rights and obligations of the Parties set forth in the following Sections and Articles of this Agreement will survive (for the time periods set forth therein, as applicable) the expiration or termination of this Agreement in its entirety, in addition to those other terms and conditions that are expressly stated to survive termination or expiration of this Agreement: Article 1 (to the extent terms defined therein are used in or necessary to interpret other surviving provisions), Section 2.8 (Former Collaboration Degrader Target Sets), Section 2.9 (Former Licensed Degrader Target Sets), Section 4.6 (Seagen-Provided Property), Section 4.7 (Nurix-Provided Property), Section 4.9 (Records Retention), Section 4.10 (Research Costs) (first sentence only), Article 13 (Financial Terms) (solely with respect to any payment or obligation accrued prior to expiration or termination of this Agreement), Section 14.3 (Reversion Licenses), Section 14.6 (Retained Rights), Section 15.1 (Ownership), Section 15.5 (Recovery) (with respect to any Action initiated prior to expiration or termination of this Agreement), Article 16 (Confidentiality), Section 17.5 (Disclaimer), Article 18 (Indemnification; Insurance), Section 19.2.4(b) (Section 365(n) Rights), Section 19.3 (Effects of Expiration and Termination), Section 19.4 (Surviving Provisions) and Article 20 (Miscellaneous).
ARTICLE 20
MISCELLANEOUS
20.1Severability. If one (1) or more of the terms or provisions of this Agreement is held by a court of competent jurisdiction to be void, invalid or unenforceable in any situation in any jurisdiction, such holding will not affect the validity or enforceability of the remaining terms and provisions hereof or the validity or enforceability of the void, invalid or unenforceable term(s) or provision(s) in any other situation or in any other jurisdiction, and the relevant term(s) or provision(s) will be considered severed from this Agreement solely for such situation and solely in such jurisdiction, unless the void, invalid or unenforceable term(s) or provision(s) are of such essential importance to this Agreement that it is to be reasonably assumed that the Parties would not have entered into this Agreement without the void, invalid or unenforceable term(s) or provision(s) being valid and enforceable in such situation and in such jurisdiction. If the final judgment of such court declares that any term or provision hereof is void, invalid or unenforceable, the Parties shall endeavor in good faith to: (a) reduce the scope, duration, area or applicability of
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the term or provision or to delete specific words or phrases to the minimum extent necessary to cause such term or provision as so reduced or amended to be valid and enforceable; and (b) replace any void, invalid or unenforceable term or provision with a valid and enforceable term or provision such that the objectives contemplated by the Parties when entering this Agreement may be realized to the extent practicable, in each case ((a) and (b)), pursuant to an amendment to this Agreement to be negotiated in good faith and mutually agreed in writing by the Parties.
20.2Notices. Any notice required or permitted to be given by this Agreement will be in writing and in English and will be deemed to have been duly given when (a) scanned and converted into a portable document format file (i.e., pdf file) and sent as an attachment to an e-mail message, where, when such message is received, a read receipt e-mail is received by the sender, or (b) the earlier of when received by the addressee or five (5) days after the date it was sent, if sent by registered or certified mail or by an internationally recognized overnight courier with tracking capabilities (in each case, prepaid and receipt requested), to the appropriate addresses or e-mail addresses set forth below (or to such other addresses if changed by notice so given):
If to Seagen:
Seagen Inc.
21823 30th Drive SE
Seagen Inc.
21823 30th Drive SE
Bothell, WA 98021
[*]
With copies (which shall not constitute notice) to:
Goodwin Procter LLP
1900 N Street, NW
Washington, DC 20036
[*]
If to Nurix:
Nurix Therapeutics, Inc.
1700 Owens Street
Suite 205
San Francisco, CA 94158
[*]
Nurix Therapeutics, Inc.
1700 Owens Street
Suite 205
San Francisco, CA 94158
[*]
With copies (which shall not constitute notice) to:
Sidley Austin LLP
555 California Street, Suite 2000
San Francisco, CA 94104
[*]
[*]
provided, that any notice so received after 5:30 p.m. (in the time zone of the receiving Party) on a Business Day or so received on a non-Business Day, in each case, will be deemed to have been received on the next Business Day. A Party may add, delete or change the person or address to which notices should be sent at any time upon written notice delivered to the other Party in accordance with this Section 20.2 (Notices). Notwithstanding anything to the contrary contained in this Agreement, this Section 20.2 (Notices) is not intended to govern day-to-day business
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communications between the Parties in exercising their rights or performing their obligations under the terms of this Agreement.
20.3Force Majeure. A Party will not be liable for delay or failure in the performance of any of its obligations hereunder or under any Ancillary Agreement to the extent such delay or failure is due to a cause beyond the reasonable control of such Party, including (in each case, to the extent beyond the non-performing Party’s reasonable control) acts of God, fires, earthquakes, acts of war, terrorism, civil unrest, hurricane or other natural disaster, embargoes, shortages, epidemics, quarantines, strikes, lockouts or other labor disturbances (whether involving the workforce of the non-performing Party or of any other Person), or acts, omissions or delays in acting by any Governmental Authority (except to the extent such omission or delay results from the breach by the non-performing Party of obligations under this Agreement or any Ancillary Agreement); provided, that: (a) the affected Party promptly notifies the other Party in writing (but no later than thirty (30) days after such occurrence and stating the nature of the event, its anticipated duration and any action being taken to avoid or minimize the effect); (b) the affected Party uses its Commercially Reasonable Efforts to avoid or remove such causes of non-performance and to mitigate the effect of such occurrence, and otherwise continues performance of this Agreement and any Ancillary Agreements in accordance with the terms hereof and thereof; and (c) the suspension of performance by the affected Party will be of no greater scope and no longer duration than is necessary under the circumstances. When such circumstances arise, the Parties will negotiate in good faith any modifications of the terms of this Agreement or any Ancillary Agreement that may be necessary or appropriate in order to arrive at an equitable solution; provided, however, that in the event that the force majeure continues for more than ninety (90) days, the Party not affected by such force majeure will have the right, at its sole election and expense, and upon at least thirty (30) days’ prior written notice to the non-performing Party, and without limitation to any other right or remedy available to either Party, to assume and complete some or all of the activities that the non-performing Party is not performing as a result of such force majeure.
20.4Assignment; Change of Control. Except as provided in this Section 20.4 (Assignment; Change of Control), this Agreement may not be assigned or transferred, whether by operation of law or otherwise, nor may any right or obligation hereunder be assigned or transferred, by either Party without the prior written consent of the other Party; provided, however, that (and notwithstanding anything in this Agreement to the contrary) either Party may, without such consent, assign or transfer this Agreement and its rights and obligations hereunder in whole or in part: (a) to its successor in interest in the transfer or sale of (i) all or substantially all of its assets or business or (ii) all or substantially all of its assets or business related to the subject matter of this Agreement; or (b) to its successor in interest in a merger or consolidation (or similar transaction) of the assigning or transferring Party, including any Change of Control transaction; provided, that in each case, such Party will provide written notice to the other Party within thirty (30) days after the closing of any such transaction(s). Any (A) successor of either Party or (B) assignee of all of either Party’s rights under this Agreement that has also assumed all of such Party’s obligations hereunder in writing and notified the other Party of such assumption will, in each case (A) and (B), upon any such succession or assignment and assumption, as applicable, be deemed to be a “Party” to this Agreement as though named herein in substitution for such Party, whereupon such Party will cease to be a “Party” to this Agreement and will cease to have any rights or obligations hereunder. In addition, each Party will have the right, without the consent of the other Party, to assign any or all of its rights and delegate any or all of its obligations hereunder to any of its Affiliates; provided, that notwithstanding anything herein to the contrary, such Party will be jointly and severally liable with any such Affiliate assignee under this Agreement. Any attempted assignment not in accordance with this Section 20.4 (Assignment; Change of Control) will be void.
20.5Waivers, Amendments and Modifications. The failure of any Party to insist on the performance of any obligation hereunder will not be deemed to be a waiver of such obligation. Waiver of any breach of any provision hereof will not be deemed to be a waiver of any other
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breach of such provision or any other provision on such occasion or any succeeding occasion. No waiver of any obligation under or provision of this Agreement will be effective unless it has been given in writing and signed by the Party giving such waiver, and no provision of this Agreement may be amended or modified other than by a written document signed by authorized representatives of each Party.
20.6Choice of Law; Dispute Resolution; Jurisdiction.
20.6.1Choice of Law. This Agreement or any Ancillary Agreement and any Dispute arising from the performance or breach hereof or thereof will be governed by and interpreted in accordance with the laws of the State of New York, without giving effect to any choice of law rules that would result in the application of the laws of any other jurisdiction; provided, that any Dispute (a) concerning the inventorship of Patents shall be determined in accordance with Section 15.1 (Ownership), and (b) concerning the scope, validity, enforceability, or infringement of a Patent shall be determined in accordance with the laws of the country or other jurisdiction in which the particular Patent has been filed or granted, as the case may be (Disputes described in clause (a) and (b), collectively, “Patent Disputes”). The provisions of the United Nations Convention on Contracts for the International Sale of Goods will not apply to this Agreement or any subject matter hereof.
20.6.2Dispute Escalation.
(a)Other than a disagreement (including any failure to agree) with respect to any matter that is subject to the decision-making authority of the JSC, JRC, or JPC or to a Party’s final decision-making authority, in each case, as described in Section 10.6 (Committee Decisions) and subject to Section 10.7 (Scope of Committee Authority), in the event of any other unresolved matter, dispute or issue relating to this Agreement (“Dispute”), the Party claiming that such Dispute exists will give notice in writing (a “Notice of Dispute”) to the other Party regarding the nature of the Dispute. Within [*] Business Days following receipt of a Notice of Dispute, the Executive Officers will meet (which may be via teleconference) at a mutually agreed upon time and location for discussion and resolution. Except in the case of Patent Disputes and matters expressly requiring the mutual agreement of the Parties, and without limiting clause (i) of Section 20.6.3 (Arbitration) or Section 20.12 (Equitable Relief; Cumulative Remedies), if the Executive Officers are unable to resolve such Dispute within [*] Business Days following such meeting, either Party may, by written notice to the other Party (an “Arbitration Notice”), refer the applicable Dispute for resolution by confidential binding arbitration, under the procedures set forth in Section 20.6.3 (Arbitration), as the Parties’ sole and exclusive mechanism for the resolution of such Disputes.
(b)For clarity, (i) matters that are subject to the decision-making authority of the JSC, JRC, or JPC or to a Party’s final decision-making authority, in each case, as described in Section 10.6 (Committee Decisions) and subject to Section 10.7 (Scope of Committee Authority), (ii) matters that expressly require the mutual agreement of the Parties, (iii) matters that expressly require the consent, approval or agreement of one or both Parties, or that are subject to a Party’s sole discretion hereunder, (iv) Patent Disputes, and (v) any other matter expressly excluded from the resolution procedures contemplated by this Section 20.6.2 (Dispute Escalation) or 20.6.3 (Arbitration), in each case ((i)-(v)), shall not be subject to binding arbitration and the dispute resolution procedures set forth in Section 20.6.3 (Arbitration).
20.6.3Arbitration. Any Dispute referred for resolution under this Section 20.6.3 (Arbitration) in accordance with Section 20.6.2 (Dispute Escalation) will be resolved exclusively
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by binding arbitration administered by [*] in accordance with the [*] then in effect (the “Rules”), subject to this Section 20.6.3 (Arbitration). Pursuant to this Section 20.6.3 (Arbitration):
(a)Upon receipt of an Arbitration Notice by a Party, the applicable Dispute will be resolved by final and binding arbitration before three (3) neutral arbitrators mutually agreed by the Parties; provided, however, that if the Parties cannot agree on such arbitrators within [*] days of the commencement of the arbitration (i.e., when [*] issues a Commencement Letter), then each Party shall select one (1) arbitrator satisfying the conditions of this clause and the two (2) arbitrators so selected by the Parties shall select the third (3rd) arbitrator (the “Arbitrators”). The Arbitrators will not be current or former employees, agents, consultants or representatives of either Party or its Affiliates. The Arbitrators shall not be from academia, and the Arbitrators shall be qualified attorneys in private practice or retired judges with experience in complex commercial disputes, and professionally fluent in English. Each Arbitrator shall have not less than [*] of experience in the biotechnology or pharmaceutical industry and subject matter expertise with respect to the matter subject to arbitration.
(b)The arbitration will be conducted pursuant to the [*], or the equivalent successor rules in effect at the time such Dispute arises; provided, that in all respects, the Parties will use good faith efforts to agree on shorter periods for discovery cut-offs and the commencement of the hearing, and to expedite a ruling on the Dispute as quickly as practicable.
(c)The Arbitrators will, within [*] days after the closing of the hearing (in accordance with Rule 22(h)), issue a written award and statement of decision describing the material facts and the grounds for the conclusions on which the award is based, including the calculation of any Damages awarded. The Arbitrators will be authorized to award compensatory damages, but will not be authorized to reform, modify or change this Agreement. The proceedings and decisions of the Arbitrators will be confidential, final and binding on the Parties (subject to clause (j) below), and judgment upon the award of the Arbitrators may be entered in any court having jurisdiction thereof.
(d)Each Party will bear its own costs and expenses (including legal fees and expenses) relating to the arbitration proceeding, except that the fees of the Arbitrators and other related costs of the arbitration will be shared equally by the Parties, unless the Arbitrators determine that a Party has incurred unreasonable expenses due to vexatious or bad faith positions taken by the other Party, in which event the Arbitrators may make an award of all or any portion of such expenses (including legal fees and expenses) so incurred.
(e)The Arbitrators shall comply with, and the award will be limited by, any express provisions of this Agreement relating to Damages or the limitation thereof. The Arbitrators will not have the power to award punitive damages regardless of whether any such damages are contained in a proposal, and such award is expressly prohibited.
(f)All arbitration proceedings and decisions of the Arbitrators under this Section 20.6.3 (Arbitration) will be deemed Confidential Information of both Parties under Article 16 (Confidentiality).
(g)Unless otherwise mutually agreed by the Parties in writing, the arbitration proceedings will take place in New York, New York.
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(h)The arbitration will be conducted in the English language and there will be a stenographic record of the proceedings.
(i)Neither Party will have the right independently to seek recourse from a court of law or other authorities in lieu of arbitration, but, without limiting the rights set forth in Section 20.12 (Equitable Relief; Cumulative Remedies), each Party has the right before or during the arbitration to seek and (if granted) obtain from a court of competent jurisdiction appropriate provisional remedies to avoid irreparable harm, maintain the status quo or preserve the subject matter of the arbitration. Subject to Applicable Law (including 9 U.S.C. § 10), the decision of the Arbitrators will be final and binding and not subject to appeal of any kind, except in the case of fraud, willful misconduct, or manifest error.
20.6.4Interim Plans. To the extent necessary to continue to maintain the status quo, during the pendency of any Dispute, the Parties shall continue to perform their obligations and exercise their rights hereunder in a manner that maintains such status quo.
20.6.5Exclusive Jurisdiction; Venue. Except for Patent Disputes and as otherwise provided in Section 20.6.3 (Arbitration) or Section 20.12 (Equitable Relief; Cumulative Remedies), (a) each Party irrevocably submits to the exclusive jurisdiction of (i) the courts of the State of New York located in New York, NY, or (ii) the United States District Court for the Southern District of New York, for the purposes of any Dispute unresolved under Section 20.6.2 (Dispute Escalation) and arising out of or relating to this Agreement or any Ancillary Agreement, (b) each Party agrees to commence any such Action either in the United States District Court for the Southern District of New York or if such Action may not be brought in such court for jurisdictional reasons, in the courts of the State of New York located in New York, New York, and (c) each Party irrevocably and unconditionally waives any objection to the laying of venue of any such Action in (i) the courts of the State of New York located in New York, New York, or (ii) the United States District Court for the Southern District of New York, and hereby and thereby further irrevocably and unconditionally waives and agrees not to plead or claim before any Governmental Authority that any such Action brought in any such court has been brought in an inconvenient forum. Notwithstanding the foregoing, the Parties agree that any Patent Dispute shall be submitted to a court of competent jurisdiction or applicable Governmental Authority (including applicable intellectual property office) with sufficient authority to resolve such Patent Dispute. Each Party agrees that process may be served upon it in the manner specified in Section 20.2 (Notices) and irrevocably waives and covenants not to assert or plead any objection which it might otherwise have to such jurisdiction, or to such manner of service of process.
20.7Relationship of the Parties. Nurix and Seagen are independent contractors under this Agreement. Nothing contained herein is intended or is to be construed so as to constitute either Party as a partner, agent or joint venturer of the other Party, including for Tax purposes. In any communications (including in oral, written, visual, graphic or electronic form) with any Third Party (including any Governmental Authority), (a) Nurix shall not refer to Seagen as a partner, agent or joint venturer of Nurix and (b) Seagen shall not refer to Nurix as a partner, agent or joint venturer of Seagen. The Parties shall file all Tax returns and take all Tax positions in a manner consistent with this Section 20.7 (Relationship of the Parties), unless otherwise required pursuant to a final determination by a Governmental Authority. Neither Nurix nor Seagen, respectively, will have any express or implied right or authority to assume or create any obligations on behalf of or in the name of Nurix and Seagen, respectively, or to bind Nurix and Seagen, respectively, to any contract, agreement or undertaking with any Third Party.
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20.8Fees and Expenses. Except as otherwise specified in this Agreement, each Party will bear its own costs and expenses incurred in connection with this Agreement and the transactions contemplated hereby.
20.9Third Party Beneficiaries. There are no express or implied Third Party beneficiaries hereunder. The provisions of this Agreement are for the exclusive benefit of the Parties, and no other Person will have any right or claim against any Party by reason of these provisions or be entitled to enforce any of these provisions against any Party, except for the rights of the Nurix Indemnitees pursuant to Section 18.1.1 (Indemnification by Seagen) and Section 18.2 (Indemnification Procedure) and the Seagen Indemnitees pursuant to Section 18.1.2 (Indemnification by Nurix) and Section 18.2 (Indemnification Procedure).
20.10Entire Agreement. This Agreement, together with any Schedules or Exhibits hereto and the Ancillary Agreements, contains the entire agreement by the Parties with respect to the subject matter hereof and supersedes any prior express or implied agreements, understandings and representations, either oral or written, which may have related to the subject matter hereof in any way, including any and all term sheets or similar documents relating to the transactions contemplated by this Agreement and exchanged between the Parties prior to the Effective Date; provided, that this Agreement will not supersede the terms and provisions of the Mutual Confidential Disclosure Agreement executed by the Parties as of April 21, 2022 (“Prior CDA”), as applicable to any period prior to the Effective Date, and nothing in this Section 20.10 (Entire Agreement) shall prejudice any rights or obligations of the Parties accrued under the Prior CDA as of the Effective Date.
20.11Counterparts. This Agreement may be executed in counterparts with the same effect as if both Parties had signed the same document. All such counterparts will be deemed an original="https://cdn.kscope.io/77acf104da600259a62082d91e4ae15b-, will be construed together and will constitute one and the same instrument. Any such counterpart, to the extent delivered by means of facsimile by .pdf, .tif, .gif", .jpeg or similar attachment to electronic mail or through the use of a nationally recognized “eSignature” platform such as DocuSign® (any such delivery, an “Electronic Delivery”) will be treated in all manners and respects as an original executed counterpart and will be considered to have the same binding legal effect as if it were the original signed version thereof delivered in person. No Party will raise the use of Electronic Delivery to deliver a signature or the fact that any signature or agreement or instrument was transmitted or communicated through the use of Electronic Delivery as a defense to the formation of a contract, and each Party forever waives any such defense, except to the extent that such defense relates to lack of authenticity.
20.12Equitable Relief; Cumulative Remedies. Notwithstanding anything to the contrary contained in this Agreement or any Ancillary Agreement, the Parties will be entitled to seek from any court of competent jurisdiction equitable relief, whether preliminary or permanent, including an injunction or specific performance, as a remedy for any breach of this Agreement or any Ancillary Agreement. Such remedies will not be deemed to be the exclusive remedies for a breach of this Agreement or any Ancillary Agreement but will be in addition to all other remedies available at law or in equity. No remedy referred to in this Agreement or any Ancillary Agreement is intended to be exclusive, but each will be cumulative and in addition to any other remedy referred to in this Agreement or any Ancillary Agreement or otherwise available under Applicable Law.
20.13Interpretation.
20.13.1Generally. This Agreement has been diligently reviewed by and negotiated by and between the Parties, and in such negotiations each of the Parties has been represented by competent (in-house or external) counsel, and the final agreement contained herein, including the language whereby it has been expressed, represents the joint efforts of the
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Parties and their counsel. Accordingly, in interpreting this Agreement or any provision hereof, no presumption will apply against any Party as being responsible for the wording or drafting of this Agreement or any such provision, and ambiguities, if any, in this Agreement will not be construed against any Party, irrespective of which Party may be deemed to have authored the ambiguous provision. In the event of any conflict between the terms and conditions set forth in the body of the Agreement, on the one hand, and any Schedule or Exhibit on the other hand, the terms in the body of the Agreement will govern.
20.13.2Definitions; Interpretation. As used herein:
(a)The definitions of the terms herein will apply equally to the singular and plural forms of the terms defined and, where a word or phrase is defined herein, each of its other grammatical forms will have a corresponding meaning.
(b)Whenever the context may require, any pronoun will include the corresponding masculine, feminine and neuter forms.
(c)The word “will” will be construed to have the same meaning and effect as the word “shall.”
(d)References to a Party “and its Affiliates” or to a Party and “and any of its Affiliates,” and like phrases, will be construed to have the same meaning and effect, and refer to the Party and/or any one (1) or more of its Affiliates.
(e)The “U.S.” and “United States” will be construed to have the same meaning and mean the United States of America and its territories and possessions.
(f)The words “including,” “includes,” “include,” “for example,” “such as” and “e.g.,” and words of similar import, will be deemed to be followed by the words “without limitation.”
(g)The word “or” will be interpreted to mean “and/or,” unless the context requires otherwise.
(h)References to this Agreement and the words “hereof,” “herein” and “hereunder,” and words of similar import, will, unless otherwise stated, be construed to refer to this Agreement as a whole (including any Schedules or Exhibits hereto) and not to any particular provision of this Agreement.
(i)Unless the context requires otherwise or otherwise specifically provided, references to drugs or pharmaceutical products or therapies include biological products or therapies, and no distinction is intended between pharmaceutical or biological products or therapies.
(j)Unless the context requires otherwise or otherwise specifically provided: (i) all references herein to Articles, Sections, Schedules or Exhibits will be construed to refer to Articles, Sections, Schedules or Exhibits of this Agreement; and (ii) reference in any Section to any clauses are references to such clauses of such Section.
(k)Whenever this Agreement refers to a number of days, unless otherwise specified (including references to Business Days), such number refers to calendar days.
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(l)Unless otherwise specified, deadlines within which any payment is to be made or act is to be done within or following a specified time period after a date will be calculated by excluding the day, Business Day, month or year of such date, as applicable, and including the day, Business Day, month or year of the date on which the period ends.
(m)Whenever any payment is to be made or action to be taken under this Agreement is required to be made or taken on a day other than a Business Day, such payment will be made or action taken on the next Business Day following such day to make such payment or do such act.
(n)The word “optimized” means to make effective or functional for a given purpose, and shall not mean making as perfect, as effective, or as functional as possible (for example, the word “optimized” with respect to a Degrader will not be construed to require that the Degrader in question be optimal at degrading the applicable Degrader Target(s) or at causing pharmacologically relevant activity as a result of such degradation).
20.13.3Subsequent Events. Unless the context requires otherwise: (a) any definition of or reference to any agreement, instrument or other document herein will be construed as referring to such agreement, instrument or other document as from time to time amended, supplemented or otherwise modified (subject to any restrictions on such amendments, supplements or modifications set forth herein); (b) any reference to any Applicable Law herein will be construed as referring to such Applicable Law as from time to time enacted, repealed or amended; and (c) subject to Section 20.4 (Assignment; Change of Control), any reference herein to any Person will be construed to include the Person’s successors and permitted assigns.
20.13.4Headings. Headings, captions and the table of contents are for convenience only and will not be used in the interpretation or construction of this Agreement.
20.14Further Assurances. Each Party will execute, acknowledge and deliver such further instruments, and do all such other ministerial, administrative or similar acts, as may be reasonably necessary or appropriate in order to carry out the expressly stated purposes and the clear intent of this Agreement.
(Remainder of Page Intentionally Left Blank; Signature Page Follows)
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IN WITNESS WHEREOF, and intending to be legally bound hereby, the Parties have caused this Collaboration and License Agreement to be executed by their respective duly authorized officers as of the Effective Date.
| NURIX THERAPEUTICS, INC. | SEAGEN INC. | ||||
By: /s/ Arthur T. Sands | By: /s/ David R. Epstein | ||||
Name: Arthur T. Sands | Name: David R. Epstein | ||||
Title: President and CEO | Title: Chief Executive Officer | ||||
Exhibit 23.1
CONSENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM
We hereby consent to the incorporation by reference in the Registration Statements on Form S-3 (No. 333-258448) and Form S-8 (Nos. 333-240065, 333-253159, 333-262406 and 333-269671) of Nurix Therapeutics, Inc. of our report dated February 15, 2024 relating to the financial statements, which appears in this Form 10-K.
/s/ PricewaterhouseCoopers LLP
San Jose, California
February 15, 2024
Exhibit 31.1
CERTIFICATION OF PRINCIPAL EXECUTIVE OFFICER PURSUANT TO
SECTION 302 OF THE SARBANES-OXLEY ACT OF 2002
I, Arthur T. Sands, certify that:
1.I have reviewed this Annual Report on Form 10-K of Nurix Therapeutics, Inc.;
2.Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;
3.Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;
4.The registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:
a.Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared;
b.Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles;
c.Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and
d.Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant’s internal control over financial reporting; and
5.The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent functions):
a.All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial information; and
b.Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal control over financial reporting.
| By: | /s/ ARTHUR T. SANDS | |||||||
| Arthur T. Sands, M.D., Ph.D. | ||||||||
| President, Chief Executive Officer and Director | ||||||||
| (Principal Executive Officer) | ||||||||
| Date: February 15, 2024 | ||||||||
Exhibit 31.2
CERTIFICATION OF PRINCIPAL FINANCIAL AND ACCOUNTING OFFICER PURSUANT TO
SECTION 302 OF THE SARBANES-OXLEY ACT OF 2002
I, Hans van Houte, certify that:
1.I have reviewed this Annual Report on Form 10-K of Nurix Therapeutics, Inc.;
2.Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;
3.Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;
4.The registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:
a.Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared;
b.Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles;
c.Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and
d.Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant’s internal control over financial reporting; and
5.The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent functions):
a.All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial information; and
b.Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal control over financial reporting.
| By: | /s/ HANS VAN HOUTE | |||||||
| Hans van Houte | ||||||||
| Chief Financial Officer | ||||||||
| (Principal Financial and Accounting Officer) | ||||||||
| Date: February 15, 2024 | ||||||||
Exhibit 32.1
CERTIFICATIONS PURSUANT TO
SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002
(18 U.S.C. SECTION 1350)
Each of the undersigned officers of Nurix Therapeutics, Inc. (the Company) certifies, pursuant to 18 U.S.C. § 1350, as adopted pursuant to § 906 of the Sarbanes-Oxley Act of 2002, that:
1.The Annual Report on Form 10-K of the Company for the period ended November 30, 2023 (the Annual Report), as filed with the Securities and Exchange Commission, fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934, and
2.The information contained in the Annual Report fairly presents, in all material respects, the financial condition and results of operations of the Company.
| By: | /s/ ARTHUR T. SANDS | |||||||
| Arthur T. Sands, M.D., Ph.D. | ||||||||
| President, Chief Executive Officer and Director | ||||||||
| (Principal Executive Officer) | ||||||||
| By: | /s/ HANS VAN HOUTE | |||||||
| Hans van Houte | ||||||||
| Chief Financial Officer | ||||||||
| (Principal Financial and Accounting Officer) | ||||||||
| Date: February 15, 2024 | ||||||||
A signed original of this written statement required by Section 906, or other document authenticating, acknowledging, or otherwise adopting the signature that appears in typed form within the electronic version of this written statement required by Section 906, has been provided to the Company and will be retained by the Company and furnished to the Securities and Exchange Commission or its staff upon request.
The foregoing certification is being furnished to the Securities and Exchange Commission as an exhibit to the Form 10-K and shall not be considered filed as part of the Form 10-K.
Exhibit 97.1
COMPENSATION RECOVERY POLICY
THIS POLICY WAS ADOPTED BY THE BOARD AND IS EFFECTIVE AS OF JULY 25, 2023.
PURPOSE
The Board of Directors (the “Board”) of Nurix Therapeutics, Inc. (the “Company”) has determined that it is in the best interests of the Company and its stockholders to adopt this Compensation Recovery Policy (this “Policy”) to enable the Company to recover from specified current and former Company executives certain incentive-based compensation in the event of an accounting restatement resulting from material noncompliance with any financial reporting requirements under the federal securities laws. Capitalized terms are defined below.
This Policy is designed to comply with Rule 10D-1 of the Exchange Act and shall apply to Incentive-Based Compensation Received by Covered Persons on or after the Listing Rule Effective Date.
ADMINISTRATION OF THIS POLICY
This Policy shall be administered by the Compensation Committee of the Board, or in the absence of a committee of independent directors responsible for executive compensation decisions, a majority of the independent directors serving on the Board (the “Administrator”). The Administrator is authorized to interpret and construe this Policy and to make all determinations necessary, appropriate, or advisable for the administration of this Policy. The Administrator may retain, at the Company’s expense, outside legal counsel and such compensation, tax or other consultants as it may determine are advisable for purposes of administering this Policy.
PERSONS COVERED BY THIS POLICY AND APPLICABLE COMPENSATION
This Policy applies to any Incentive-Based Compensation Received by a person (a) after beginning service as a Covered Person; (b) who served as a Covered Person at any time during the performance period for that Incentive-Based Compensation; and (c) was a Covered Person during the Clawback Period.
However, recovery is not required with respect to:
i.Incentive-Based Compensation Received prior to an individual becoming a Covered Person, even if
the individual served as a Covered Person during the Clawback Period.
ii.Incentive-Based Compensation Received prior to the Listing Rule Effective Date.
iii.Incentive-Based Compensation Received prior to the Clawback Period.
iv.Incentive-Based Compensation Received while the Company did not have a class of listed securities on a national securities exchange or a national securities association, including the Exchange.
The Administrator will not consider the Covered Person’s responsibility or fault or lack thereof in enforcing this Policy with respect to recoupment under the Final Rules.
TRIGGERING EVENT
Subject to and in accordance with the provisions of this Policy, if there is a Triggering Event, the Administrator shall require a Covered Person to reimburse or forfeit to the Company the Recoupment Amount applicable to such Covered Person. A Company’s obligation to recover the Recoupment Amount is not dependent on if or when the restated financial statements are filed.
CALCULATION OF RECOUPMENT AMOUNT
The Recoupment Amount will be calculated in accordance with the Final Rules, as provided in the Calculation Guidelines attached hereto as Exhibit B.
METHOD OF RECOUPMENT
Subject to compliance with the Final Rules and applicable law, the Administrator will determine, in its sole discretion, the method for recouping the Recoupment Amount hereunder which may include, without limitation:
i.Requiring reimbursement or forfeiture of the pre-tax amount of cash
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Incentive-Based Compensation previously paid;
ii.Offsetting the Recoupment Amount from any compensation otherwise owed by the Company to the Covered Person, including without limitation, any prior cash incentive payments, executive retirement benefits, wages, equity grants or other amounts payable by the Company to the Covered Person in the future;
iii.Seeking recovery of any gain realized on the vesting, exercise, settlement, cash sale, transfer, or other disposition of any equity-based awards; and/or
iv.Taking any other remedial and recovery action permitted by law, as determined by the Administrator.
ARBITRATION
To the fullest extent permitted by law, any disputes under this Policy shall be submitted to mandatory binding arbitration (the “Arbitrable Claims”), governed by the Federal Arbitration Act (the “FAA”). Further, to the fullest extent permitted by law, no class or collective actions can be asserted in arbitration or otherwise. All claims, whether in arbitration or otherwise, must be brought solely in the Covered Person’s individual capacity, and not as a plaintiff or class member in any purported class or collective proceeding.
SUBJECT TO THE ABOVE PROVISO, ANY RIGHTS THAT A COVERED PERSON MAY HAVE TO TRIAL BY JURY IN REGARD TO ARBITRABLE CLAIMS ARE WAIVED. ANY RIGHTS THAT A COVERED PERSON MAY HAVE TO PURSUE OR PARTICIPATE IN A CLASS OR COLLECTIVE ACTION PERTAINING TO ANY CLAIMS BETWEEN A COVERED PERSON AND THE COMPANY ARE WAIVED.
The Covered Person is not restricted from filing administrative claims that may be brought before any government agency where, as a matter of law, the Covered Person’s ability to file such claims may not be restricted. However, to the fullest extent permitted by law, arbitration shall be the exclusive remedy for the subject matter of such administrative claims. The arbitration shall be conducted in the City and County of San Francisco, California, through JAMS before a
single neutral arbitrator, in accordance with the JAMS Comprehensive Arbitration Rules and Procedures then in effect, provided however, that the FAA, including its procedural provisions for compelling arbitration, shall govern and apply to this Arbitration provision. The arbitrator shall issue a written decision that contains the essential findings and conclusions on which the decision is based. If, for any reason, any term of this Arbitration provision is held to be invalid or unenforceable, all other valid terms and conditions herein shall be severable in nature and remain fully enforceable.
RECOVERY PROCESS; IMPRACTICABILITY
Actions by the Administrator to recover the Recoupment Amount will be reasonably prompt.
The Administrator must cause the Company to recover the Recoupment Amount unless the Administrator shall have previously determined that recovery is impracticable and one of the following conditions is met:
i.The direct expense paid to a third party to assist in enforcing this Policy would exceed the amount to be recovered; before concluding that it would be impracticable to recover any amount of erroneously awarded Incentive-Based Compensation based on expense of enforcement, the Company must make a reasonable attempt to recover such erroneously awarded Incentive-Based Compensation, document such reasonable attempt(s) to recover, and provide that documentation to the Exchange;
ii.Recovery would violate home country law where that law was adopted prior to November 28, 2022; before concluding that it would be impracticable to recover any amount of erroneously awarded Incentive-Based Compensation based on violation of home country law, the Company must obtain an opinion of home country counsel, acceptable to the Exchange, that recovery would result in such a violation, and must provide such opinion to the Exchange; or
iii.Recovery would likely cause an otherwise tax-qualified retirement
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plan, under which benefits are broadly available to employees of the Company, to fail to meet the requirements of 26 U.S.C. 401(a)(13) or 26 U.S.C. 411(a) and regulations thereunder.
NON-EXCLUSIVITY
The Administrator intends that this Policy will be applied to the fullest extent of the law. Without limitation to any broader or alternate clawback authorized in any written document with a Covered Person, (i) the Administrator may require that any employment agreement, equity award agreement, or similar agreement entered into on or after the effective date of this Policy shall, as a condition to the grant of any benefit thereunder, require a Covered Person to agree to abide by the terms of this Policy, and (ii) this Policy will nonetheless apply to Incentive-Based Compensation as required by the Final Rules, whether or not specifically referenced in those arrangements. Any right of recoupment under this Policy is in addition to, and not in lieu of, any other remedies or rights of recoupment that may be available to the Company pursuant to the terms of any similar policy in any employment agreement, equity award agreement, or similar agreement and any other legal remedies or regulations available or applicable to the Company (including SOX 304). If recovery is required under both SOX 304 and this Policy, any amounts recovered pursuant to SOX 304 may, in the Administrator’s discretion, be credited toward the amount recovered under this Policy, or vice versa.
NO INDEMNIFICATION
The Company shall not indemnify any Covered Persons against (i) the loss of erroneously awarded Incentive-Based Compensation or any adverse tax consequences associated with any incorrectly awarded Incentive-Based Compensation or any recoupment hereunder, or (ii) any claims relating to the Company enforcement of its rights under this Policy. For the avoidance of doubt, this prohibition on indemnification will also prohibit the Company from reimbursing or paying any premium or payment of any third-party insurance policy to fund potential recovery obligations obtained by the Covered Person directly. No Covered Person will seek or retain any such prohibited indemnification or reimbursement.
Further, the Company shall not enter into any agreement that exempts any Incentive-Based Compensation from the application of this Policy or that waives the Company’s right to recovery of any erroneously awarded Incentive-Based Compensation and this Policy shall supersede any such agreement (whether entered into before, on or after the effective date of this Policy).
COVERED PERSON ACKNOWLEDGMENT AND AGREEMENT
All Covered Persons subject to this Policy must acknowledge their understanding of, and agreement to comply with, the Policy by executing the certification attached hereto as Exhibit A. Notwithstanding the foregoing, this Policy will apply to Covered Persons whether or not they execute such certification.
SUCCESSORS
This Policy shall be binding and enforceable against all Covered Persons and their beneficiaries, heirs, executors, administrators or other legal representatives and shall inure to the benefit of any successor to the Company.
INTERPRETATION OF POLICY
To the extent there is any ambiguity between this Policy and the Final Rules, this Policy shall be interpreted so that it complies with the Final Rules. If any provision of this Policy, or the application of such provision to any Covered Person or circumstance, shall be held invalid, the remainder of this Policy, or the application of such provision to Covered Persons or circumstances other than those as to which it is held invalid, shall not be affected thereby.
In the event any provision of this Policy is inconsistent with any requirement of any Final Rules, the Administrator, in its sole discretion, shall amend and administer this Policy and bring it into compliance with such rules.
Any determination under this Policy by the Administrator shall be conclusive and binding on the applicable Covered Person. Determinations of the Administrator need not be uniform with respect to Covered Persons or from one payment or grant to another.
AMENDMENTS; TERMINATION
The Administrator may make any amendments to this Policy as required under applicable law,
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rules and regulations, or as otherwise determined by the Administrator in its sole discretion.
The Administrator may terminate this Policy at any time.
DEFINITIONS
“Clawback Measurement Date” is the earlier to occur of:
i.The date the Board, a committee of the Board, or the officer or officers of the Company authorized to take such action if Board action is not required, concludes, or reasonably should have concluded, that the Company is required to prepare an accounting restatement as described in this Policy; or
ii.The date a court, regulator, or other legally authorized body directs the Company to prepare an accounting restatement as described in this Policy.
“Clawback Period” means the three (3) completed fiscal years immediately prior to the Clawback Measurement Date and any transition period between the last day of the Company’s previous fiscal year end and the first day of its new fiscal year (that results from a change in the Company’s fiscal year) within or immediately following such three (3)-year period; provided that any transition period between the last day of the Company’s previous fiscal year end and the first day of its new fiscal year that comprises a period of 9 to 12 months will be deemed a completed fiscal year.
“Covered Person” means any Executive Officer (as defined in the Final Rules), including, but not limited to, those persons who are or have been determined to be “officers” of the Company within the meaning of Section 16 of Rule 16a-1(f) of the rules promulgated under the Exchange Act, and “executive officers” of the Company within the meaning of Item 401(b) of Regulation S-K, Rule 3b-7 promulgated under the Exchange Act, and Rule 405 promulgated under the Securities Act of 1933, as amended; provided that the Administrator may identify additional employees who shall be treated as Covered Persons for the purposes of this Policy with prospective effect, in accordance with the Final Rules.
“Exchange” means the Nasdaq Global Market or any other national securities exchange or
national securities association in the United States on which the Company has listed its securities for trading.
“Exchange Act” means the Securities Exchange Act of 1934, as amended.
“Final Rules” means the final rules promulgated by the SEC under Section 954 of the Dodd-Frank Act, Rule 10D-1 and Exchange listing standards, as may be amended from time to time.
“Financial Reporting Measure” are measures that are determined and presented in accordance with the accounting principles used in preparing the Company’s financial statements, and any measures that are derived wholly or in part from such measures. Stock price and TSR are also financial reporting measures. A financial reporting measure need not be presented within the financial statements or included in a filing with the SEC.
“Incentive-Based Compensation” means compensation that is granted, earned or vested based wholly or in part on the attainment of any Financial Reporting Measure. Examples of “Incentive-Based Compensation” include, but are not limited to: non-equity incentive plan awards that are earned based wholly or in part on satisfying a Financial Reporting Measure performance goal; bonuses paid from a “bonus pool,” the size of which is determined based wholly or in part on satisfying a Financial Reporting Measure performance goal; other cash awards based on satisfaction of a Financial Reporting Measure performance goal; restricted stock, restricted stock units, performance share units, stock options, and SARs that are granted or become vested based wholly or in part on satisfying a Financial Reporting Measure goal; and proceeds received upon the sale of shares acquired through an incentive plan that were granted or vested based wholly or in part on satisfying a Financial Reporting Measure goal. “Incentive-Based Compensation” excludes, for example, time-based awards such as stock options or restricted stock units that are granted or vest solely upon completion of a service period; awards based on non-financial strategic or operating metrics such as the consummation of a merger or achievement of non-financial business goals; service-based retention bonuses; discretionary compensation; and salary.
“Listing Rule Effective Date” means the effective date of the listing standards of the
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Exchange on which the Company’s securities are listed.
“Policy” means this Compensation Recovery Policy.
Incentive-Based Compensation is deemed “Received” in the Company’s fiscal period during which the relevant Financial Reporting Measure specified in the Incentive-Based Compensation award is attained, irrespective of whether the payment or grant occurs on a later date or if there are additional vesting or payment requirements, such as time-based vesting or certification or approval by the Compensation Committee or Board, that have not yet been satisfied.
“Recoupment Amount” means the amount of Incentive-Based Compensation Received by the Covered Person based on the financial statements prior to the restatement that exceeds the amount such Covered Person would have received had the Incentive-Based Compensation been determined based on the financial restatement, computed without regard to any taxes paid (i.e., gross of taxes withheld).
“SARs” means stock appreciation rights.
“SEC” means the U.S. Securities and Exchange Commission.
“SOX 304” means Section 304 of the Sarbanes-Oxley Act of 2002.
“Triggering Event” means any event in which the Company is required to prepare an accounting restatement due to the material noncompliance of the Company with any financial reporting requirement under the securities laws, including any required accounting restatement to correct an error in previously issued financial statements that is material to the previously issued financial statements, or that would result in a material misstatement if the error were corrected in the current period or left uncorrected in the current period.
“TSR” means total stockholder return.
* * *
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EXHIBIT A
Certification
I certify that:
1.I have read and understand the Company’s Compensation Recovery Policy (the “Policy”). I understand that the Company’s General Counsel is available to answer any questions I have regarding the Policy.
2.I understand that the Policy applies to all of my existing and future compensation-related agreements with the Company, whether or not explicitly stated therein.
3.I agree that notwithstanding the Company’s certificate of incorporation, bylaws, and any agreement I have with the Company, including any indemnity agreement I have with the Company, I will not be entitled to, and will not seek indemnification from the Company for, any amounts recovered or recoverable by the Company in accordance with the Policy.
4.I understand and agree that in the event of a conflict between the Policy and the foregoing agreements and understandings on the one hand, and any prior, existing or future agreement, arrangement or understanding, whether oral or written, with respect to the subject matter of the Policy and this Certification, on the other hand, the terms of the Policy and this Certification shall control, and the terms of this Certification shall supersede any provision of such an agreement, arrangement or understanding to the extent of such conflict with respect to the subject matter of the Policy and this Certification; provided that, in accordance with Section 8 of this Policy, nothing herein limits any other remedies or rights of recoupment that may be available to the Company.
5.I agree to abide by the terms of the Policy, including, without limitation, by returning any erroneously awarded Incentive-Based Compensation to the Company to the extent required by, and in a manner permitted by, the Policy.
Signature:
Name:
Title:
Date:
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EXHIBIT B
Calculation Guidelines
For purposes of calculating the Recoupment Amount:
i.For cash awards not paid from bonus pools, the erroneously awarded compensation is the difference between the amount of the cash award (whether payable as a lump sum or over time) that was received and the amount that should have been received applying the restated Financial Reporting Measure.
ii.For cash awards paid from bonus pools, the erroneously awarded compensation is the pro rata portion of any deficiency that results from the aggregate bonus pool that is reduced based on applying the restated Financial Reporting Measure.
iii.For equity awards, if the shares, options, restricted stock units, or SARs are still held at the time of recovery, the erroneously awarded compensation is the number of such securities received in excess of the number that should have been received applying the restated Financial Reporting Measure (or the value of that excess number). If the options or SARs have been exercised, but the underlying shares have not been sold, the erroneously awarded compensation is the number of shares underlying the excess options or SARs (or the value thereof). If the underlying shares have been sold, the Company may recoup proceeds received from the sale of shares.
iv.For Incentive-Based Compensation based on stock price or TSR, where the amount of erroneously awarded compensation is not subject to mathematical recalculation directly from the information in an accounting restatement:
a.The amount must be based on a reasonable estimate of the effect of the accounting restatement on the stock price or TSR upon which the Incentive-Based Compensation was Received; and
b.The Company must maintain documentation of the determination of that reasonable estimate and the Company must provide such documentation to the Exchange in all cases.
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