UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
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FORM 8-K
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CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of Earliest Event Reported): January 13, 2025
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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) | (Commission File Number) | (IRS Employer Identification No.) | ||||||
| (Address of Principal Executive Offices) | (Zip Code) | |||||||
(415 ) 660-5320
(Registrant’s Telephone Number, Including Area Code)
N/A
(Former Name or Former Address, if Changed Since Last Report)
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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) | |||||
| Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) | |||||
| Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) | |||||
| Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) | |||||
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class | Trading symbol(s) | Name of each exchange on which registered | ||||||
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company o
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
Item 2.02 Results of Operations and Financial Condition.
On January 13, 2025, Nurix Therapeutics, Inc. (the “Company”) will present an investor presentation at the 43rd Annual J.P. Morgan Healthcare Conference (the “JPM Conference”), which reports the preliminary, unaudited amount of the Company’s cash, cash equivalents and marketable securities position as of November 30, 2024, as $609.6 million, and reports that, based on its current operating plan, the Company expects that it will be able to fund its operating activities into the first half of 2027. This estimated, unaudited cash, cash equivalents and marketable securities amount has been prepared by management and is based upon information available to management as of the date of this Current Report on Form 8-K. This amount is subject to the completion of financial closing procedures that could result in changes to the amount. Furthermore, this amount does not present all information necessary for a complete understanding of the Company’s financial condition as of or for the fiscal year ended November 30, 2024. The Company’s independent registered public accounting firm, PricewaterhouseCoopers LLP, has not audited, reviewed, compiled or performed any procedures with respect to this preliminary financial data and, accordingly, does not express an opinion or any other form of assurance with respect thereto. The Company’s audited results as of and for the year ended November 30, 2024, will be included in the Company’s Annual Report on Form 10-K for the year ended November 30, 2024.
The information furnished with this Item 2.02 shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, regardless of any general incorporation language in such filing.
Item 7.01 Regulation FD Disclosure.
In addition to the Company’s presentation at the JPM Conference, on January 13, 2025, the Company issued a press release regarding its performance in 2024 and its major goals for 2025. A copy of the Company’s press release and its presentation materials for the JPM Conference are attached hereto as Exhibit 99.1 and Exhibit 99.2, respectively, and are incorporated herein by reference.
In accordance with General Instruction B.2 of Form 8-K, the information in Item 7.01 of this Current Report on Form 8-K shall not be deemed to be “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liability of that section, and shall not be incorporated by reference into any registration statement or other document filed under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in such filing. In addition, the information set forth under this Item 7.01, including Exhibits 99.1 and 99.2, shall not be deemed an admission as to the materiality of any information in this Current Report on Form 8-K.
Item 9.01 Financial Statements and Exhibits.
(d)Exhibits
The following exhibits are filed herewith and this list is intended to constitute the exhibit index:
| Exhibit No. | Exhibit Title or Description | |||||||
| 99.1 | ||||||||
| 99.2 | ||||||||
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |||||||
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SIGNATURES
Pursuant to the requirements 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 hereunto duly authorized.
| NURIX THERAPEUTICS, INC. | ||||||||
| Date: January 13, 2025 | By: | /s/ Christine Ring | ||||||
| Christine Ring, Ph.D., J.D. | ||||||||
| Chief Legal Officer | ||||||||
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Exhibit 99.1
[Nurix Logo]
Nurix Therapeutics Outlines 2025 Goals and Objectives for Advancement of Its Robust Pipeline in Cancer and Autoimmune Diseases
Initiate a suite of clinical trials in 2025 intended to support global registration of NX-5948 for the treatment of chronic lymphocytic leukemia
Expand the development of NX-5948 in additional cancer indications and inflammatory diseases
Advance our portfolio of partnered programs in inflammation and immunology, including degraders of IRAK4 and STAT6
Invest in our highly productive DEL-AI discovery engine to create and advance novel degrader-based treatments in our wholly owned and partnered portfolios
Maintain a strong financial position, building on our estimated $609.6 million in cash and investments at fiscal 2024 year-end*
San Francisco, CA, January 13, 2025 — Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines, the next frontier in innovative drug design aimed at improving treatment options for patients with cancer and inflammatory diseases, today outlined key objectives and anticipated milestones for 2025, which will be the subject of Nurix’s corporate update at the 43rd Annual J.P. Morgan Healthcare Conference today at 3:00 p.m. PT, in San Francisco.
“Nurix had an exciting year of successful execution of our clinical trials and significant progress in several key business areas,” said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. “We recently presented impressive clinical responses from our NX-5948 Phase 1a/1b clinical trial both in patients with relapsed or refractory chronic lymphocytic leukemia and in patients with Waldenstrom’s macroglobulinemia. We received Fast Track Designation from the U.S. Food and Drug Administration for both of these indications as well as PRIME designation for CLL from the European Medicines Agency. Nurix is positioned to initiate a suite of late-stage clinical studies of NX-5948 in 2025, including pivotal studies in CLL. We also anticipate significant advances in our portfolio of wholly owned and partnered programs in the area of inflammation and immunology, including degraders of IRAK4 and STAT6.”
“2024 was a year of significant advancement in our research and discovery organization,” said Gwenn M. Hansen, Ph.D., chief scientific officer of Nurix. “We not only advanced several preclinical programs that are approaching key development milestones within our wholly owned and partnered portfolios, but we also expanded our discovery platform to include AI-powered drug discovery that leverages our early investments in E3 ligase research, DEL
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discovery, chemistry automation and machine learning. Nurix has developed a suite of AI tools applicable across the breadth of our technical workflows, but with a specific focus on prospective ligand discovery informed by our years of accumulated DEL know-how and screening data, which we are calling DEL-AI.”
2024 Accomplishments and Business Highlights
Clinical Development Pipeline
•Advanced NX-5948 and presented positive clinical data at oncology-focused medical meetings throughout 2024. New positive clinical data were presented at the 66th American Society of Hematology Annual Meeting (ASH2024) in December 2024 and at the 12th International Workshop on Waldenstrom’s Macroglobulinemia (IWWM-12) in October 2024, from patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (r/r CLL/SLL) and patients with Waldenstrom’s macroglobulinemia (WM) treated in the Phase 1a/1b clinical trial of NX-5948. NX-5948 is an orally bioavailable, brain penetrant degrader of Bruton’s tyrosine kinase (BTK). At ASH2024, Nurix reported a robust objective response rate (ORR) of 75.5% among the 49 efficacy-evaluable r/r CLL patients across all doses tested, with the majority of responses occurring at the first assessment (Week 8). With longer time on treatment, the ORR increased to 84.2% based on an exploratory efficacy analysis of patients who had at least two response assessments (Week 16). Responses and robust BTK degradation were observed across all populations regardless of prior treatment, baseline mutations including those with BTK mutations associated with treatment resistance to both covalent and non-covalent BTK inhibitors, high-risk molecular features, or central nervous system (CNS) involvement. NX-5948 was well-tolerated in all patient populations and across all doses tested from 50 to 600 mg daily. In the nine efficacy-evaluable WM patients treated with NX-5948 an ORR of 77.8% was observed with increasing depth of response over time, supporting continued development of NX-5948 for this indication. Additional information on the ongoing clinical trial can be accessed at www.clinicaltrials.gov (NCT05131022). A webcast of Nurix’s ASH2024 presentation and additional discussion on the company’s programs and plans is available in the Investors section of the Nurix website.
•Successfully executed on regulatory strategy for global development of NX-5948 with U.S. FDA Fast Track and European Medicines Agency PRIME designations: In 2024, NX-5948 received two separate Fast Track designations from the U.S. Food and Drug Administration (FDA): the first for the treatment of adult patients with r/r CLL/SLL after at least two lines of therapy, including a BTK inhibitor and a B-cell lymphoma 2 (BCL2) inhibitor, and the second for the treatment of adult patients with r/r WM after at least two lines of therapy, including a BTK inhibitor. In Europe, NX-5948 received PRIME designation for the treatment patients with r/r CLL/SLL after treatment with at least a BTK inhibitor and a BCL2 inhibitor. Regulatory clearance for clinical site initiations was
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received in several countries and clinical trial expansion is ongoing in France, Poland, Italy and Spain. Additional countries are anticipated to come online in 2025.
•Re-initiated enrollment in NX-2127 Phase 1a/b trial: Following a decision in March 2024 in which the FDA lifted a manufacturing-related, partial clinical hold on the NX-2127 clinical trial, Nurix reinitiated enrollment in a dose escalation study within the current Phase 1a/1b trial, using its new chirally controlled drug product of NX-2127, a novel orally bioavailable bifunctional molecule that degrades BTK and the cereblon neosubstrates Ikaros (IKZF1) and Aiolos (IKZF3). Nurix is focusing development on aggressive lymphomas where the combination of BTK degradation and IKZF1/3 degradation have the potential for synergy and significant therapeutic benefit. Additional information on the clinical trial can be accessed at www.clinicaltrials.gov (NCT04830137).
•Advanced Phase 1a dose escalation trial of NX-1607 in monotherapy and in a combination cohort with paclitaxel in adults in a range of oncology indications. Nurix’s lead drug candidate from its E3 ligase inhibitor portfolio, NX-1607, is an orally bioavailable inhibitor of Casitas B-lineage lymphoma proto-oncogene (CBL-B) for immuno-oncology indications, including a range of solid tumor types. The company has evaluated dosing and scheduling regimens to optimize tolerability and maximize pharmacodynamic effects. Additional information on the clinical trial can be accessed at www.clinicaltrials.gov (NCT05107674).
Research and Discovery
•Advanced a pipeline of wholly owned and partnered programs in inflammation and immunology: At ACR Convergence 2024, the annual meeting of the American College of Rheumatology, Nurix presented preclinical data, including mechanism of action and activity in relevant disease models of inflammation and autoimmune diseases, from NX-5948. Nurix announced plans to initiate clinical testing of NX-5948 in autoimmune cytopenias such as warm autoimmune hemolytic anemia (wAIHA) in 2025, initially as an addition to its ongoing Phase 1b trial in patients with B-cell malignancies. At ACR Convergence 2024, positive preclinical data were also presented from Nurix’s collaboration with Gilead to develop GS-6791/NX-0479, an IRAK4 degrader, that has potential applications in the treatment of rheumatoid arthritis and other inflammatory diseases. In addition, Nurix’s ongoing research program with Sanofi was extended for the development of a degrader of STAT6 (signal transducer and activator of transcription 6), a key drug target in type 2 inflammation, with the goal of nominating a development candidate in the first half of 2025.
•Expanded Nurix’s portfolio of brain penetrant degraders: At the annual meeting of the American Association for Cancer Research (AACR) in April 2024, Nurix presented the first clinical evidence of brain penetration and clinical activity in the CNS for its BTK degrader NX-5948. In addition, data from Nurix’s previously undisclosed program to develop an orally available, brain penetrant pan-mutant B-RAF degrader for the treatment of mutant B-RAF driven solid tumors were presented at the 7th Annual TPD & Induced Proximity
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Summit. These programs, along with other scientific presentations throughout 2024, clearly demonstrate Nurix’s ability to achieve brain penetrant and CNS active degraders.
•Published the first description of BTK’s clinically important scaffolding function: Nurix scientists and clinical collaborators published a manuscript in the journal Science titled “Kinase Impaired BTK Mutations Are Susceptible to Clinical Stage BTK and IKZF1/3 Degrader NX-2127” that elucidates a previously unappreciated oncogenic scaffold function of BTK responsible for clinical resistance to enzymatic inhibitors and shows that NX-2127, a potent targeted protein degrader with differentiated activity against BTK and IKZF1/3, can overcome this resistance across a broad range of acquired mutations. The elimination of BTK’s scaffolding function is a critical attribute of both NX-2127 and NX-5948, with potential clinical relevance in both B-cell malignancies and inflammation.
•Demonstrated cellular proof of concept for its degrader antibody conjugate (DAC) platform: Early preclinical data from Nurix’s ongoing collaboration with Pfizer to develop DACs were presented at the ADC & Radiopharmaceuticals Pharma & Biotech Partnering Summit. The data from two separate DACs demonstrated cell-type selective degradation of targeted proteins by DACs and highlighted the potential advantages of this new drug class and Nurix’s novel approach to DAC optimization.
•Achieved significant milestones in collaborations with Gilead, Sanofi and Pfizer: In April 2024, Nurix announced that Gilead elected to extend the research term of the companies’ ongoing collaboration, originally established in 2019, by an additional two years, which resulted in a payment of $15 million to Nurix. In April 2024, Nurix also announced the extension of its research term with Sanofi for its previously undisclosed STAT6 degrader program. In 2024, Nurix also achieved its first milestone in its ongoing Pfizer collaboration and received a $5 million payment. In total, in 2024, Nurix earned milestones and fees in these ongoing strategic collaborations totaling $22 million through the third fiscal quarter of 2024 (August 31, 2024).
Corporate and Leadership
•Strengthened leadership team with C-suite appointments and new Board of Directors member with drug commercialization expertise: In 2024, Nurix announced the promotions of Paula G. O'Connor, M.D., as chief medical officer and Pasit Phiasivongsa, Ph.D., as chief technical officer of Nurix. These appointments strengthen leadership in clinical operations and CMC ahead of planned pivotal studies for NX-5948 in 2025. In addition, Anil Kapur, a senior leader in commercial operations in hematology and oncology with over 25 years of executive experience in pharmaceutical and biotech companies across both U.S. and international markets joined the Nurix board of directors.
•Strengthened balance sheet to support development of pipeline: Nurix ended its fiscal year with an estimated, unaudited $609.6 million in cash and investments as of November 30, 2024.* Based on its operating plan, Nurix anticipates that the company will be able to fund its operating activities into the first half of 2027.
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2025 Goals and Catalysts
•NX-5948
oInitiate pivotal studies for NX-5948: Nurix is evaluating NX-5948 in an ongoing Phase 1b clinical trial in adults with relapsed or refractory B-cell malignancies and expects to initiate a suite of clinical trials in 2025 intended to support global registration of NX-5948 for the treatment of patients with CLL.
oExpand the development of NX-5948 in additional cancer indications and inflammatory diseases: Nurix expects to complete the ongoing Phase 1b clinical trial in patients with WM and determine Phase 2 dose(s) as well as to continue to explore regulatory paths for this indication. In inflammation and immunology (I&I), Nurix plans to implement a sequenced, multi-organ system approach to evaluating NX-5948 to generate the greatest opportunity for patients and value creation, seeking first proof of concept through the study of CLL patients with secondary autoimmune-mediated hemolytic anemia with plans to explore non-malignant cytopenias, such as warm autoimmune hemolytic anemia (wAIHA), before potentially moving to dermatologic indications, such as hidradenitis suppurativa (HS), and neurologic indications, such as multiple sclerosis (MS).
•NX-2127
oDrive NX-2127 to proof-of-concept data: Nurix is focusing development on aggressive lymphomas where the combination of BTK degradation and IKZF1/3 degradation have the potential for synergy and significant therapeutic benefit. The company plans to complete dose escalation with new chirally controlled drug product and select recommended Phase 1b dose for selected indications and expects to share additional clinical data after selection of a Phase 1b expansion dose(s) and indication(s).
•NX-1607:
oDrive NX-1607 to proof-of-concept data: Nurix is testing both once daily (QD) and twice daily (BID) dosing of NX-1607. With additional patients in the BID dosing arms, Nurix plans to establish a Phase 1b monotherapy dose and expects to share additional clinical data after selection of a Phase 1b expansion dose(s) and indication(s).
•Preclinical-development pipeline:
oAdvance IRAK4 degrader program into Phase 1: GS-6791 (previously NX-0479) is a potent, selective, oral IRAK4 degrader. Nurix’s partner Gilead exercised its option to exclusively license GS-6791 in March 2023 and is responsible for conducting IND-enabling studies and advancing this program to clinical development, which Nurix anticipates in 2025. Nurix retains its option to co-develop and co-promote in the United States, splitting U.S profits and losses evenly and receiving royalties on ex-U.S. sales.
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oNominate a STAT6 degrader development candidate: Nurix anticipates nominating a STAT6 degrader development candidate in the first half of 2025. Under its collaboration with Sanofi, delivery of a development candidate data package triggers a licensing option decision for Sanofi. If licensed by Sanofi, Nurix retains its option to co-develop and co-promote in the United States, splitting U.S profits and losses evenly and receiving royalties on ex-U.S. sales.
oNominate a development candidate within Nurix’s wholly owned degrader pipeline: Nurix is advancing several preclinical programs within its wholly owned pipeline. In 2025, Nurix anticipates nominating at least one development candidate to advance to IND-enabling studies.
About Nurix
Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines, the next frontier in innovative drug design aimed at improving treatment options for patients with cancer and inflammatory diseases. Powered by a fully AI-integrated discovery engine capable of tackling any protein class, and coupled with unparalleled ligase expertise, Nurix’s dedicated team has built a formidable advantage in translating the science of targeted protein degradation into clinical advancements. Nurix aims to establish degrader-based treatments at the forefront of patient care, writing medicine’s next chapter with a new script to outmatch disease. Nurix’s wholly owned, clinical stage pipeline includes 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. Nurix also is advancing multiple potentially first-in-class or best-in-class degraders and DACs in its preclinical pipeline. Nurix’s partnered drug discovery pipeline consists of preclinical stage degraders of IRAK4 and STAT6, as well as multiple additional programs under collaboration agreements with Gilead Sciences, Inc., Sanofi S.A. and Pfizer Inc., within which Nurix retains certain options for co-development, co-commercialization and profit sharing in the United States for multiple drug candidates. Nurix is headquartered in San Francisco, California. For additional information visit http://www.nurixtx.com.
* The estimated cash and investment amount included herein is a preliminary, unaudited estimate based upon information available to Nurix’s management as of the date of this press release and is subject to the completion of financial closing procedures. The amount does not present all information necessary for a complete understanding of Nurix’s financial condition as of or for the year ended November 30, 2024. Nurix’s audited results as of and for the year
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ended November 30, 2024, will be included in Nurix’s Annual Report on Form 10-K for the year ended November 30, 2024.
Forward Looking Statements
This press release contains statements that relate to future events and expectations and as such constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. When or if used in this press release, the words “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “may,” “outlook,” “plan,” “predict,” “should,” “will,” and similar expressions and their variants, as they relate to Nurix, may identify forward-looking statements. All statements that reflect Nurix’s expectations, assumptions or projections about the future, other than statements of historical fact, are forward-looking statements, including, without limitation, statements regarding: Nurix’s future plans, prospects and strategies, including its plans for the development of NX-5948, NX-2127 and NX-1607; Nurix’s plans and expectations for its collaborations and preclinical pipeline; the tolerability, safety profile, therapeutic potential and other advantages of Nurix’s drug candidates the planned timing and conduct of the clinical trials for Nurix’s drug candidates; the planned timing for the provision of updates and findings from Nurix’s preclinical and clinical studies; the tolerability, safety profile, therapeutic potential and other advantages of Nurix’s drug candidates; the therapeutic potential of DACs; the potential benefits of Nurix’s collaborations, including potential milestone and sales-related payments; the potential advantages of Nurix’s drug discovery platform; Nurix’s future financial or business performance; Nurix’s estimated, unaudited cash and investment position as of November 30, 2024; and Nurix’s ability to fund its operating activities into the first half of 2027. Forward-looking statements reflect Nurix’s current beliefs, expectations and assumptions. Although Nurix believes the expectations and assumptions reflected in such forward-looking statements are reasonable, Nurix can give no assurance that they will prove to be correct. Forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and changes in circumstances that are difficult to predict, which could cause Nurix’s actual activities and results to differ materially from those expressed in any forward-looking statement. Such risks and uncertainties include, but are not limited to: (i) risks and uncertainties related to Nurix’s ability to advance its drug candidates, obtain regulatory approval of and ultimately commercialize its drug candidates; (ii) risks and uncertainties related to the timing and results of preclinical studies and clinical trials; (iii) risks and uncertainties related to Nurix’s ability to fund development activities and achieve development goals; (iv) uncertainties related to the timing and receipt of payments from Nurix’s collaboration partners, including milestone payments and royalties on future potential product sales; (v) the impact of macroeconomic conditions and global or regional events on Nurix’s business, clinical trials, financial condition, liquidity and results of operations; (vi) risks and uncertainties related to Nurix’s ability to protect intellectual property and (vii) other risks and uncertainties described under the heading “Risk Factors” in Nurix’s Quarterly Report on Form 10-Q for the fiscal quarter ended August 31, 2024, and other SEC filings. Accordingly,
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readers are cautioned not to place undue reliance on these forward-looking statements. The statements in this press release speak only as of the date of this press release, even if subsequently made available by Nurix on its website or otherwise. Nurix disclaims any intention or obligation to update publicly any forward-looking statements, whether in response to new information, future events, or otherwise, except as required by applicable law.
Contacts:
Investors
Jason Kantor, Ph.D.
Nurix Therapeutics
ir@nurixtx.com
Elizabeth Wolffe, Ph.D.
Wheelhouse Life Science Advisors
lwolffe@wheelhouselsa.com
Media
Aljanae Reynolds
Wheelhouse Life Science Advisors
areynolds@wheelhouselsa.com
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Medicines to Outmatch Disease Investor Presentation January 13, 2025 Exhibit 99.2
Important Notice and Disclaimers This presentation contains statements that relate to future events and expectations and as such constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. When or if used in this presentation, the words “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “may,” “outlook,” “plan,” “predict,” “should,” “will,” and similar expressions and their variants, as they relate to Nurix Therapeutics, Inc. (“Nurix”, the “Company,” “we,” “us” or “our”), may identify forward-looking statements. All statements that reflect Nurix’s expectations, assumptions or projections about the future, other than statements of historical fact, are forward-looking statements, including, without limitation, statements regarding our future financial or business plans; our future performance, prospects and strategies; future conditions, trends, and other financial and business matters; our current and prospective drug candidates; the planned timing and conduct of the clinical trial programs for our drug candidates; the planned timing for the provision of clinical updates and initial findings from our clinical studies; the potential benefits of our collaborations, including potential milestone and sales-related payments; the potential advantages of DEL-AI and our drug candidates; the extent to which our scientific approach, our drug discovery engine, targeted protein degradation, and Degrader Antibody Conjugates may potentially address a broad range of diseases; the extent animal model data predicts human efficacy; the timing and success of the development and commercialization of our current and anticipated drug candidates; our estimated, unaudited cash and investment position; and our ability to fund our operations into the first half of 2027. Forward-looking statements reflect Nurix’s current beliefs, expectations, and assumptions. Although Nurix believes the expectations and assumptions reflected in such forward-looking statements are reasonable, Nurix can give no assurance that they will prove to be correct. Forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and changes in circumstances that are difficult to predict, which could cause Nurix’s actual activities and results to differ materially from those expressed in any forward-looking statement. Such risks and uncertainties include, but are not limited to: (i) risks and uncertainties related to Nurix’s ability to advance its drug candidates, obtain regulatory approval of and ultimately commercialize its drug candidates; (ii) the timing and results of clinical trials; (iii) Nurix’s ability to fund development activities and achieve development goals; (iv) risks and uncertainties relating to the timing and receipt of payments from Nurix's collaboration partners, including milestone payments and royalties on future potential product sales; (v) the impact of macroeconomic events and conditions, including increasing financial market volatility and uncertainty, inflation, interest rate fluctuations, instability in the global banking system, uncertainty with respect to the federal budget and debt ceiling, the impact of war, military or regional conflicts, and global health pandemics, on Nurix’s clinical trials and operations; (vi) Nurix’s ability to protect intellectual property and (vii) other risks and uncertainties described under the heading “Risk Factors” in Nurix’s Quarterly Report on Form 10-Q for the fiscal quarter ended August 31, 2024, and other SEC filings. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. The statements in this presentation speak only as of the date of this presentation, even if subsequently made available by Nurix on its website or otherwise. Nurix disclaims any intention or obligation to update publicly any forward-looking statements, whether in response to new information, future events, or otherwise, except as required by applicable law. Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the Company’s own internal estimates and research. While the Company believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Furthermore, while we believe our own internal estimates and research are reliable, such estimates and research have not been verified by any independent source. The estimated cash and investments amount included in this presentation is a preliminary, unaudited estimate based upon information available to Nurix's management as of the date of this presentation. It is subject to the completion of financial closing procedures, including the completion of audit procedures by Nurix's independent public accounting firm, and therefore is subject to adjustment. The amount does not present all information necessary for a complete understanding of Nurix’s financial condition as of or for the year ended November 30, 2024. Nurix’s audited results as of and for the year ended November 30, 2024, will be included in Nurix’s Annual Report on Form 10-K for the year ended November 30, 2024. 2
Key accomplishments in 2024 Another Great Year at Nurix 3 Demonstrated clear clinical proof of concept for BTK degradation with NX-5948 • Completed Phase 1a dose escalation • Demonstrated robust efficacy in CLL and WM with favorable safety profile • Oral presentations at ASH and EHA Established unmet medical need with key regulatory agencies • Fast Track Designation for CLL and WM from the U.S. Food and Drug Administration (FDA) • PRIME designation from the European Medicines Agency (EMA) Advanced two other wholly owned assets in the clinic • NX-2127, a dual degrader of BTK and IKZF1/3 • NX-1607, an inhibitor of CBL-B Progressed three major partnerships with Sanofi, Gilead, and Pfizer • Extension of the STAT6 degrader program with Sanofi • Presented first preclinical data for IRAK4 degrader clinical candidate and advanced toward IND submission • Achieved potent cell-based activity of degrader antibody conjugates Ended fiscal year in a strong cash position with $609.6M* NX-5948 BTK Degrader Pipeline BTK, Bruton’s tyrosine kinase; CLL chronic lymphocytic leukemia, CBL-B, casitas B lymphoma-b; WM, Waldenstrom’s macroglobulinemia * This estimated cash and investment amount is a preliminary, unaudited estimate based upon information available to Nurix's management as of the date of this presentation. The amount is subject to the completion of financial closing procedures, including the completion of audit procedures by Nurix’s independent registered public accounting firm, and therefore is subject to adjustment.
Meeting the needs of patients with breakthrough therapies Drug Discovery Pipeline Strategy 4 Clinically validated targets where inhibitors fail to address resistance and scaffolding Unmet medical need where inhibitors are not sufficient to drive efficacy "Undruggable" targets Kinase targets in cancer BTK – B-cell malignancies and I&I Signaling proteins with scaffolding function IRAK4 – rheumatoid arthritis STAT6 – T2 inflammatory diseases Transcriptions factors; fusion proteins; E3 ligases BTK, Bruton’s tyrosine kinase; I&I, inflammation and immunology; IRAK4, interleukin-1 receptor-associated kinase 4; STAT6, signal transducer and activator of transcription 6
Establish Degrader-Based Medicines at the Forefront of Patient Care • Degraders act as molecular matchmakers, bringing together two key players: • An E3 ligase (a key part of a cell’s protein degradation machinery) • A disease-causing target protein • This process, called induced proximity, enables the E3 ligase to tag the target protein with ubiquitin to mark it for disposal by the proteasome – the cell’s protein recycling center • Given their ability to eliminate target proteins, degraders can achieve effects similar to genetic therapies that silence disease-causing genes 5
Industry Leading DEL-AI Discovery Engine for TPD and DAC Drug Discovery Our DEL-AI discovery engine leverages the combined power of our data-rich DEL capabilities, automated chemistry, and advanced machine learning to accelerate drug discovery 6 TPD, targeted protein degradation; DAC, degrader antibody conjugate; DEL, DNA encoded library
Nurix Is Advancing a Pipeline of Proprietary and Partnered Programs in Oncology and Inflammation & Immunology 7 Program Target Modality Therapeutic area Discovery IND-Enabling Phase 1A Phase 1B/2 NX-5948 BTK Degrader B-cell malignancies NX-2127 BTK-IKZF Degrader B-cell malignancies NX-1607 CBL-B Inhibitor of degradation Immuno-oncology BRAF degrader Pan-mutant BRAF Degrader Solid tumors Multiple Undisclosed Degrader Undisclosed Multiple Undisclosed Degrader Undisclosed Undisclosed Undisclosed Degrader Undisclosed Multiple Undisclosed DAC Undisclosed Program Target Modality Therapeutic area Discovery IND-Enabling Phase 1A Phase 1B/2 NX-5948 BTK Degrader Autoimmune cytopenia NX-0479 / GS-6791 IRAK4 Degrader Rheumatoid arthritis and other inflammatory diseases STAT6 degrader STAT6 Degrader Type 2 inflammatory diseases Undisclosed Undisclosed Degrader Inflammation / autoimmune Multiple Undisclosed DAC Inflammation / autoimmune O nc ol og y In fla m m at io n & Im m un ol og y
• Next generation BTK inhibitors are currently taking market share from Imbruvica • All BTK inhibitors share resistance mutation vulnerabilities Current market for BTK inhibitors annualizing at over $10 billion BTK Targeted Agents Are a Major Value Driver Across Biotech and Pharma 8 0 1000 2000 3000 4000 5000 6000 7000 8000 9000 2016 2017 2018 2019 2020 2021 2022 2023 SA LE S ($ M IL LI O N S) Dynamic Blockbuster Market Opportunity Ibrutinib Acalabrutinib Zanubrutinib Pirtobrutinib Nurix’s Strategy • Displace inhibitors in key oncology markets • Expand market for degraders into I&I Note: $10 billion annualized estimate based on reported Q3 2024 sales Source: Earnings reports from Johnson & Johnson, Abbvie, AstraZeneca, Beigene, and Eli Lilly
Why Do We Need BTK Degraders? 9 • BTK degraders address BTK scaffolding function • BTK degraders have demonstrated clinical activity in difficult to treat B-cell malignancies • BTK degraders have the potential to address significant unmet needs in autoimmune and inflammatory disorders • BTK degraders can overcome treatment-emergent resistance mutations
NX-5948-301 Trial Design Phase 1a/b Trial in Adults with Relapsed/Refractory B-cell Malignancies CLL, chronic lymphocytic leukemia; SLL, small lymphocytic lymphoma; NHL, non-Hodgkin’s lymphoma; WM, Waldenström macroglobulinemia; BTKi, BTK inhibitor; BCL2i, Bcl-2 inhibitor; QD, once daily Phase 1a dose escalation (fully enrolled) Ongoing CLL Phase 1b expansion cohorts 50 mg QD 100 mg QD 200 mg QD 300 mg QD 450 mg QD 600 mg QDNHL/WM CLL/SLL 50 mg QD 100 mg QD 200 mg QD 300 mg QD 450 mg QD 600 mg QD CLL/SLL (200 mg) Prior BTKi and BCL2i CLL/SLL (600 mg) Prior BTKi and BCL2i Randomized Fast Track Designation WM Waldenstrom’s macroglobulinemia MZL Marginal zone lymphoma FL Follicular lymphoma Ongoing NHL/WM Phase 1b expansion cohorts 10
Baseline disease characteristics Heavily Pre-Treated Patients With a High Prevalence of Baseline Mutations aBaseline disease characteristics in CLL cohort were comparable to those in the overall population; bPatients could have received multiple prior treatments; cAll patients who received ncBTKi have also previously received cBTKi; dMutations presented here were centrally sequenced. BCL2, B-cell lymphoma 2; BCL2i, BCL2 inhibitor; BTK, Bruton’s tyrosine kinase; BTKi, BTK inhibitor; cBTKi, covalent BTKi; CAR-T, chimeric antigen receptor T-cell; CLL, chronic lymphocytic leukemia; CNS, central nervous system; ECOG PS, Eastern Cooperative Oncology Group (ECOG) performance status; ncBTKi, non-covalent BTKi; PI3Ki, phosphoinositide 3-kinase inhibitor; PLCG2, phospholipase C gamma 2; SLL, small lymphocytic lymphoma Characteristics Patients with CLL/SLLa (n=60) ECOG PS, n (%) 0 1 24 (40.0) 36 (60.0) CNS involvement, n (%) 5 (8.3) Median prior lines of therapy (range) 4.0 (1–12) Previous treatmentsb, n (%) BTKi cBTKi ncBTKic BCL2i BTKi and BCL2i CAR-T therapy Bispecific antibody PI3Ki Chemo/chemo-immunotherapies (CIT) 59 (98.3) 59 (98.3) 17 (28.3) 50 (83.3) 49 (81.7) 3 (5.0) 4 (6.7) 18 (30.0) 43 (71.7) Mutation statusd (n=57), n (%) TP53 BTK PLCG2 BCL2 23 (40.4) 22 (38.6) 7 (12.3) 6 (10.5) Data cutoff: 10 Oct 2024 11
NX-5948 degrades gatekeeper, kinase-proficient and kinase-dead BTK mutations NX-5948 Degrades Wild-Type and Mutated BTK Reference 1. Montoya et al. Science 2024;383 Patients with CLL/SLL (n=57)c Baseline mutation status, n (%) BTK mutations1,a,b 22 (38.6) C481S 12 (21.1) C481R 2 (3.5) L528W 4 (7.0) L528S 1 (1.8) T474I 5 (8.8) T474F 1 (1.8) V416M 1 (1.8) V416L 1 (1.8) G541V 1 (1.8) aPatients could have multiple prior treatments and BTK mutations; BTK mutations were tested at baseline by next-generation sequencing centrally; ≥5% allelic frequency is reported bPatients can have more than one resistance mutation cPatients with available mutation status Note: Some patients have multiple BTK mutations BTK degradation BTK, Bruton’s tyrosine kinase; CLL, chronic lymphocytic leukemia; MFI, mean fluorescence intensity; SLL, small lymphocytic lymphoma Data cutoff: 10 Oct 2024 12
NX-5948 overall response assessment Response Rate Deepens with Longer Time on Treatment CLL, chronic lymphocytic leukemia; CR, complete response; iwCLL, International Workshop on CLL; ORR, objective response rate; PD, progressive disease; PR, partial response; PR-L, partial response with rebound lymphocytosis; SD, stable disease CLL response-evaluable patients Primary ORR analysisb ≥1 response assessment(s) at 8 weeks Exploratory ORR analysisb ≥2 response assessments at 16 weeks n=49c n=38c Objective response rate (ORR),a % (95% CI) 75.5 (61.1–86.7) 84.2 (68.7–94.0) Best response, n (%) CR 0 (0.0) 0 (0.0) PR 36 (73.5) 32 (84.2) PR-L 1 (2.0) 0 (0.0) SD 10 (20.4) 4 (10.5) PD 2 (4.1) 2 (5.3) aObjective response rate includes CR + PR + PR-L bPatients who progressed prior to their first response assessment and patients who discontinued for any reason after their first response assessment are included in the denominators cPatients without identified target lesion(s) at baseline are evaluated as disease-evaluable per iwCLL criteria, while they may not be represented in waterfall plot Data cutoff: 10 Oct 2024 13
Clinical Activity in CLL Patients Including Those with Baseline Mutations and CNS Involvement ATM, Ataxia-telangiectasia mutated; BTK, Bruton’s tyrosine kinase; BTKi, BTK inhibitor; CLL, chronic lymphocytic leukemia; CNS, central nervous system; iwCLL, International Workshop on CLL; NOTCH1, neurologic locus notch homolog protein 1; PLCG2, phospholipase C gamma 2; SPD, sum of products diameters *Patient with Richter’s transformation to Hodgkin's on biopsy Note: patients without identified target lesion(s) at baseline are evaluated as disease-evaluable per iwCLL criteria, while they may not be represented in waterfall plot Patients with CNS involvement at baseline BTK PLCG2 TP53 SF3B1 ATM NOTCH1 BTKi resistance mutations Poor- prognosis mutations BT PLCG TP5 SF3B AT NOTCH * Data not available Multiple Single Wild-type C ha ng e in ly m ph n od e si ze % c ha ng e fro m b as el in e in SP D o f t ar ge t l es io n( s) Patients with CNS involvement at baseline Dashed line indicates iwCLL response criteria threshold (50%) Data cutoff: 10 Oct 2024 14
TEAEs in ≥10% of overall population or Grade ≥3 TEAEs or SAEs in >1 patient NX-5948 Safety Profile aPurpura/contusion includes episodes of contusion or purpura; bFatigue was transient; cAggregate of ‘thrombocytopenia’ and ‘platelet count decreased’; dAggregate of ‘rash’ and ‘rash maculopapular’ and ‘rash pustular’; eAggregate of 'neutrophil count decreased' or 'neutropenia’; fAggregate of 'COVID-19' and 'COVID-19 pneumonia’; gAggregate of 'pneumonia’ and ‘pneumonia klebsiella’ AE, adverse event; AFib, atrial fibrillation; CLL, chronic lymphocytic leukemia; NHL, non-Hodgkin’s lymphoma; SAE, serious adverse event; SLL, small lymphocytic lymphoma; TEAE, treatment emergent AE TEAEs, n (%) Patients with CLL/SLL (n=60) Overall population (N=125) Any grade Grade ≥3 SAEs Any grade Grade ≥3 SAEs Purpura/contusiona 22 (36.7) – – 42 (33.6) – – Fatigueb 16 (26.7) – – 29 (23.2) 2 (1.6) – Petechiae 16 (26.7) – – 28 (22.4) – – Thrombocytopeniac 10 (16.7) 1 (1.7) – 26 (20.8) 7 (5.6) – Rashd 14 (23.3) 1 (1.7) 1 (1.7) 24 (19.2) 2 (1.6) 1 (0.8) Neutropeniae 14 (23.3) 11 (18.3) – 23 (18.4) 18 (14.4) – Anemia 11 (18.3) 4 (6.7) – 21 (16.8) 10 (8.0) – Headache 10 (16.7) – – 21 (16.8) 1 (0.8) 1 (0.8) COVID-19f 10 (16.7) – – 19 (15.2) 2 (1.6) 2 (1.6) Diarrhea 12 (20.0) 1 (1.7) – 18 (14.4) 1 (0.8) – Cough 9 (15.0) – – 16 (12.8) 1 (0.8) – Pneumoniag 4 (6.7) 2 (3.3) 2 (3.3) 10 (8.0) 6 (4.8) 6 (4.8) Lower respiratory tract infection 3 (5.0) 1 (1.7) 1 (1.7) 9 (7.2) 3 (2.4) 2 (1.6) Fall 1 (1.7) 1 (1.7) 1 (1.7) 8 (6.4) 2 (1.6) 2 (1.6) Hypertension 2 (3.3) 1 (1.7) – 7 (5.6) 5 (4.0) – Hyponatremia – – – 3 (2.4) 2 (1.6) – Pulmonary embolism 1 (1.7) 1 (1.7) 1 (1.7) 2 (1.6) 2 (1.6) 2 (1.6) Subdural hematoma 1 (1.7) – 1 (1.7) 2 (1.6) 1 (0.8) 2 (1.6) • Tolerable safety profile consistent with prior disclosures • 1 case of Grade 1 AFib in a CLL patient with pre-existing AFib • 6 TEAEs resulted in drug discontinuation (1 CLL; 5 NHL) • 2 Grade 5 AEs (1 pulmonary embolism; 1 case pending) deemed not related to NX-5948 Data cutoff: 10 Oct 2024 15
Preliminary efficacy presented at the International Workshop on Waldenström Macroglobulinemia NX-5948 High Preliminary Overall Response in Patients with Waldenström Macroglobulinemia CR, complete response; MR minor response; ORR, objective response rate; PD, progressive disease; PR, partial response; PR-L, partial response with rebound lymphocytosis; SD, stable disease; WM, Waldenström macroglobulinemia aObjective response rate includes CR + PR + MR bPatients who progressed prior to their first response assessment and patients who discontinued for any reason after their first response assessment are included in the denominators Data cutoff: 10 Oct 2024 16 WM response-evaluable patients Primary ORR analysisb ≥1 response assessment(s) at 8 weeks n=9 Objective response rate (ORR),a % 77.8 Best response, n (%) CR 0 (0.0) PR / MR 7 (77.8) SD 2 (22.2) PD 0 (0.0)
Rapid and Durable Responses to NX-5948 in Patients with Waldenström Macroglobulinemia Data cutoff: 10 Oct 2024 Select prior therapies Select mutations BTKi BCL2i Pirto CXCR4 MYD88 *Ineligible, identified post 1st dose #Transformed to DLBCL * # WM disease-evaluable patients n=9 ORR, % 77.8 Best response, n (%) CR 0 (0.0) PR / MR 7 (77.8) SD 2 (22.2) PD 0 (0.0) 17 BCL2i, B-cell leukemia/lymphoma 2 inhibitor; BTKi, Bruton’s tyrosine kinase inhibitor; CR, complete response; DLBCL, diffuse large B-cell lymphoma; MR, minor response; PD, progressive disease; Pirto, pirtobrutinib; PR, partial response; SD, stable disease
NX-5948 Regulatory Milestones 18 CLL WM Advancing NX-5948 program globally in CLL and WM • U.S. Fast Track Designation from the FDA in January 2024 • Type B End of Phase 1 meeting held with the FDA, key takeaways: • Reviewed dose levels of 200 mg QD and 600 mg QD in the context of Project Optimus • Feedback on principles of pivotal trial designs including Fast Track population and considerations for randomized controlled trials • Nurix plans future interactions in 2025 as sufficient data is accumulated • EU expansion of enrollment into France, Poland, Italy and Spain approved in Q3 2024 • EU PRIME designation from EMA in November 2024 • U.S. Fast Track Designation from the FDA in December 2024 CLL, chronic lymphocytic leukemia; WM, Waldenström macroglobulinemia
Nurix Is Accelerating Development of NX-5948 in CLL with First Pivotal Study To Be Initiated in 2025 • Clear demonstration of clinical activity in difficult to treat CLL population • Phase 1b cohorts enrolling rapidly with post-BTKi/post-BCL2i CLL patients randomized between 200mg QD and 600mg QD • Planning for a broad Phase 3 program across lines of therapy as monotherapy and in combination with other approved agents Current status in CLL Outline of potential pivotal plans in CLL* 19 Potential path for accelerated approval 1. Single-arm monotherapy trial in post-BTKi/post- BCL2i patients (Fast Track population) Confirmatory study in 2L+ 2. Randomized head-to-head trial vs. comparator(s)* in the post-BTKi, 2L+ population Expansion to 1L+ 3. Monotherapy head-to-head vs. investigator choice BTKi* including BTKi treatment naïve patients 4. NX-5948 in combination with BCL2i head-to-head vs. standard of care* *All plans subject to change based on regulatory feedback including definition of control arms of all studies BTKi, Bruton’s tyrosine kinase inhibitor; BCL2i, B-cell leukemia/lymphoma 2 inhibitor; CLL, chronic lymphocytic leukemia; QD, once daily
Inflammation & Immunology 20 Leveraging our expertise in B- and T-cell biology, Nurix is building a pipeline of innovative degrader drugs to address the unmet medical need for patients living with inflammation and autoimmune disorders
Advancing NX-5948 in Immunology and Inflammation The genetics of BTK are compelling: highly specific with potent biology • Human and mouse knockouts are associated with reduced immune function yet have otherwise normal physiology Positive clinical experience • BTK inhibitors have shown positive clinical results across a wide range of I&I diseases in hematology, dermatology, and neurology Inhibitors leave room for improvement • The same scaffolding functions that limit efficacy of inhibitors in oncology may also be limiting their efficacy in autoimmune disease settings Key observations underpinning Nurix’s NX-5948 I&I strategy 21 BTK, Bruton’s tyrosine kinase; I&I, inflammation and immunology; LPS, lipopolysaccharide; TLR, toll-like receptor; BCR, B cell receptor; ssRNA/DNA, single-stranded RNA/DNA
Potent Suppression of Myeloid Cell Stimulation NX-5948 More Potently Suppresses Activation of Stimulated B Cells and Myeloid Cells Compared to a Range of BTK Inhibitors 22 Potent Suppression of B Cell Stimulation 0.001 0.01 0.1 1 10 100 1000 -75 -50 -25 0 25 50 75 100 125 Compound (nM) N or m al iz ed C D 69 NX-5948 Rilzabrutinib Remibrutinib Acalabrutinib Fenebrutinib Bead-bound anti-IgM stimulation 0.001 0.01 0.1 1 10 100 1000 0.00 0.25 0.50 0.75 1.00 1.25 Compound (nM) IL -8 F ol d C ha ng e NX-5948 Rilzabrutinib Remibrutinib Acalabrutinib Fenebrutinib Plate-bound IgG2 stimulation Source: Noviski et al., ACR 2024, November 2024
Wide dose range produces robust BTK degradation NX-5948 Has the Right Clinical Profile To Address Unmet Clinical Needs in Both Oncology and I&I 23 Elimination of BTK’s scaffolding function Demonstrated ability to cross the blood-brain barrier Favorable safety profile in oncology clinical trials 0 2000 4000 6000 8000 10000 BTK degradation in all patients receiving NX-5948 BT K Pr ot ei n Le ve l (M FI , M ea n +/ - S EM ) Day 2 Day 15 Day 22 Day 29Day 8 50 mg 100 mg 200 mg 300 mg 450 mg 600 mg DEGRADED BTK SCAFFOLD DISRUPTION
Nurix’s Systematic Approach To Expand Development of NX-5948 Across Multiple I&I Indications Next Steps: 1. Plan to open a new Phase 1b cohort for patients with CLL and associated autoimmune hemolytic anemia in H1 2025 2. Plan non-malignant hematology IND in 2025 for autoimmune cytopenias (e.g., wAIHA) 3. Conduct a healthy volunteer study of a new formulation to address potential need for broader range of doses and dose regimens for I&I indications (study underway) 4. Explore potential for additional indications in other organ systems based on evolving data (e.g., dermatology and neurology) 24
IRAK4 Degrader NX-0479/GS-6791 for the Potential Treatment of Rheumatoid Arthritis and Other Inflammatory Diseases Source: Teng et al., ACR 2024, November 2024 .25 IND anticipated in 2025; Nurix has a co-development and 50/50 profit share option in the United States • IRAK4 is a master regulator of the Toll-like Receptor (TLR) and Interleukin-1 Receptor (IL-1R) signaling pathways • Inappropriate activation of these receptors promotes inflammation and autoimmunity through the release of inflammatory cytokines and chemokines • IRAK4 exhibits both kinase and scaffolding functions • Degradation of IRAK4 achieves more complete blockade of the TLR/IL-14 signaling pathways and yields broader anti-inflammatory effects than inhibition alone PBMC, peripheral blood mononuclear cell; TNF, tumor necrosis factor
STAT6 Degrader for the Potential Treatment of Th2-Mediated Inflammatory Disorders Such as Allergies, Asthma, and Eczema JAK, Janus kinase; pSTAT, phosphorylated Janus kinase26 • Signal Transducer and Activator of Transcription 6 (STAT6) is a key transcription factor in the JAK/STAT signaling pathway • STAT6 acts downstream of the inflammatory cytokines IL-4 and IL-13, driving Th2-mediated inflammatory disorders such as allergies, asthma, and eczema • STAT6 is considered undruggable by standard inhibitors • Degradation of STAT6 offers a compelling new modality to target this clinically validated pathway Development candidate nomination anticipated in H1 2025 Nurix has a co-development and 50/50 profit share option in the United States
27 DACs represent the next evolution in targeted protein degradation, combining the highly potent and catalytic activity of degraders with the cell and tissue specificity of antibodies Degrader Antibody Conjugates (DACs)
Advancing a New Therapeutic Class • DACs combine the catalytic activity of a degrader with the specificity of an antibody • DACs represent the next generation of antibody drug conjugates (ADCs) Degrader Antibody Conjugates (DACs) 28 Seagen* Deal Terms • $60 million upfront cash payment • $3.4 billion in potential research, development, regulatory and commercial milestone payments • Mid-single to low double-digit percentage tiered royalties on future product sales • Option for U.S. profit sharing and co-promotion on up to two products arising from the collaboration DEGRADER DAC * Seagen is now part of Pfizer
DACs Provide Exquisite Selectivity 29 ADCs DegradersDACs Antigen provides cell and tissue selectivity Degrader target and ligase expression provide cell and tissue selectivity DAC provides multi-layer selectivity DACs Degrade Target Protein Only in Cells Expressing a Select Antigen 0.001 0.01 0.1 1 10 100 0 20 40 60 80 100 120 Concentration (nM) % B TK R em ai ni ng Anti-HER2/BTK DAC Unconjugated Degrader Anti-CD19/BTK DAC BTK Degradation in CD19+ B Cells
Estimated $609.6 million in cash and investments at fiscal year-end 2024, November 30, 2024* Well Funded to Execute on Our Strategy Key initiatives for 2025 • Initiate a suite of clinical trials in 2025 intended to support global registration of NX-5948 for the treatment of patients with chronic lymphocytic leukemia • Expand the development of NX-5948 in additional cancer indications and inflammatory diseases • Advance our portfolio of partnered programs in inflammation and immunology, including degraders of IRAK4 and STAT6 • Advance Nurix’s two other wholly owned clinical-stage assets, NX-2127 and NX-1607 • Invest in our highly productive DEL-AI discovery engine to create and advance novel degrader-based treatments in our wholly owned and partnered portfolios • Maintain a strong cash position with the ability to fund and control our most valuable programs and co-development options 30 Cash runway to fund operations into H1 2027** * The estimated cash and investment amount is a preliminary, unaudited estimate based upon information available to Nurix's management as of the date of this presentation. The amount is subject to the completion of financial closing procedures, including the completion of audit procedures by Nurix’s independent registered public accounting firm, and therefore is subject to adjustment. ** Cash runway guidance is based on Nurix’s current operating plan
