UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
___________________________________________
FORM 8-K
___________________________________________
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of Earliest Event Reported): December 9, 2024
___________________________________________
(Exact Name of Registrant as Specified in its Charter)
___________________________________________
(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)
___________________________________________
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 7.01 Regulation FD Disclosure.
On December 9, 2024, Nurix Therapeutics, Inc. (the “Company”) issued a press release announcing the presentation at the 66th American Society of Hematology Annual Meeting and Exposition (the “ASH Annual Meeting”) of new clinical data from the Company’s novel Bruton's tyrosine kinase (BTK) degrader program NX-5948 and new preclinical data for NX-5948 and the Company's BTK and IKZF1/3 degrader NX-2127. As previously announced, the Company will host a webcast at 8:15 p.m. Pacific Time (11:15 p.m. Eastern Time) on December 9, 2024, to review the data presented at the ASH Annual Meeting and provide a corporate update. A copy of the press release and the presentation materials for the webcast, which includes the data presented at the ASH Annual Meeting, 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 Securities Exchange Act of 1934, as amended (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 8.01 Other Events.
On December 9, 2024, the Company announced updated clinical data from the Phase 1 clinical trial of NX-5948.
The updated data include safety findings for all patients in the NX-5948 Phase 1a/1b dose escalation and expansion cohorts (n=125), including those with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) and those with non-Hodgin’s lymphoma. Patients were treated with NX-5948 at starting doses ranging from 50 mg to 600 mg once daily by oral administration, and intra-patient dose escalation was permitted per the clinical trial protocol. NX-5948 was well tolerated across all doses evaluated, and safety findings in the CLL/SLL cohort were consistent with the overall population as well as previous safety analyses. Among the CLL/SLL patients, the most common treatment emergent adverse events were purpura/contusion (36.7%, all grade 1 or 2), fatigue (26.7%, all grade 1 or 2), petechiae (26.7%, all grade 1 or 2), neutropenia (23.3%, 18.3% grade 3 or higher), and rash (23.3%, 1.7% grade 3 or higher). Importantly, across the entire population, there was only one case of grade 1 atrial fibrillation in a patient with pre-existing atrial fibrillation.
As of the October 10, 2024 data cut, sixty (60) patients with relapsed or refractory CLL/SLL were enrolled in the NX-5948 Phase 1a/1b clinical trial. This cohort of CLL/SLL patients was a heavily pretreated population that had received a median of four prior lines of therapy (range = 1-12) including prior covalent BTK inhibitors (98.3%), prior BCL2 inhibitors (83.3%), and prior non-covalent BTK inhibitors (28.3%). At baseline, a large number of patients had mutations associated with BTK inhibitor resistance, including mutations in BTK (38.6%) and PLC2G (12.3%). Poor prognostic features were common, including TP53 mutations (40.4%), and five patients (8.3%) had central nervous system (CNS) involvement.
Among the efficacy evaluable patients with CLL/SLL (n=49), NX-5948 treatment resulted in a robust objective response rate (ORR) of 75.5% 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 were observed across all populations regardless of prior treatment, baseline mutations, high-risk molecular features, or CNS involvement. This includes patients with baseline BTK mutations associated with treatment resistance to both covalent and non-covalent BTK inhibitors. Robust BTK degradation was observed in all patients, including those with baseline BTK mutations.
Responses were durable with the median duration of response not reached. Thirteen patients had duration of response greater than six months, and five patients remain on treatment and in response beyond one year of treatment.
2
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) | |||||||
3
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: December 10, 2024 | By: | /s/ Christine Ring | ||||||
| Christine Ring, Ph.D., J.D. | ||||||||
| Chief Legal Officer | ||||||||
4
Exhibit 99.1
[Nurix logo]
Nurix Therapeutics Presents New Positive Data from Phase 1a/1b Clinical Trial of NX-5948 in Chronic Lymphocytic Leukemia at the 66th American Society of Hematology Annual Meeting
Durable responses are rapid and deepen on treatment as demonstrated by an initial 75.5% Objective Response Rate which increased to 84.2% in patients with at least two disease assessments
Treatment responses observed in heavily pre-treated population with mutations associated with poor prognosis and/or resistance to BTK inhibitors, including patients with CNS involvement
Favorable safety profile across all doses tested
Nurix will host a webcast to discuss the data presented at the ASH Annual Meeting and provide a corporate update today at 8:15 p.m. PT (11:15 p.m. ET)
SAN FRANCISCO, December 9, 2024 – Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with cancer and inflammatory diseases, today presented new positive clinical data from patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) treated in the Phase 1a/1b clinical trial of its Bruton’s tyrosine kinase (BTK) degrader NX-5948. These data were presented by Nirav N. Shah, M.D., M.S.H.P., Associate Professor of Medicine, Division of Hematology and Oncology, at the Medical College of Wisconsin, and a clinical investigator on the trial, in an oral session at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition being held December 7-10, 2024, in San Diego, CA. In addition, Nurix and its collaborators presented new preclinical data for NX-5948 and its BTK and IKZF1/3 degrader NX-2127 in separate poster and oral presentations at the ASH Annual Meeting.
“We are excited to report our latest results based on enrollment of sixty relapsed/refractory CLL/SLL patients, almost double the number of patients in our previous mid-year 2024 update. With a greater number of patients and longer duration of treatment, we are highly encouraged to see a deepening of therapeutic responses over time while maintaining a favorable safety profile,” said Paula G. O’Connor, M.D., chief medical officer of Nurix. “These positive results are particularly impressive given the inclusion of patients with a high incidence of baseline genetic mutations in BTK, PLCG2, and TP53, and challenging clinical factors, such as central nervous system involvement, which are associated with poor prognosis. We continue to enroll patients in the United States, the United Kingdom, and Europe in the Phase 1b portion of the trial and are on track to initiate pivotal trials of NX-5948 in 2025.”
NX-5948 Phase 1a/1b clinical update
As of the October 10, 2024 data cut, sixty (60) patients with relapsed or refractory CLL/SLL were enrolled. This cohort of CLL/SLL patients was a heavily pretreated population that had received a median of four prior lines of therapy (range = 1-12) including prior covalent BTK inhibitors (98.3%), prior BCL2 inhibitors (83.3%), and prior non-covalent BTK inhibitors (28.3%). At
As of the October 10, 2024 data cut, sixty (60) patients with relapsed or refractory CLL/SLL were enrolled. This cohort of CLL/SLL patients was a heavily pretreated population that had received a median of four prior lines of therapy (range = 1-12) including prior covalent BTK inhibitors (98.3%), prior BCL2 inhibitors (83.3%), and prior non-covalent BTK inhibitors (28.3%). At
baseline, a large number of patients had mutations associated with BTK inhibitor resistance, including mutations in BTK (38.6%) and PLC2G (12.3%). Poor prognostic features were common, including TP53 mutations (40.4%), and five patients (8.3%) had central nervous system (CNS) involvement.
The data presented at the ASH Annual Meeting include safety findings for all patients in the NX-5948 Phase 1a/1b dose escalation and expansion cohorts (n=125), including those with CLL/SLL and those with non-Hodgin’s lymphoma (NHL). Patients were treated with NX-5948 at starting doses ranging from 50 mg to 600 mg once daily by oral administration, and intra-patient dose escalation was permitted per protocol. NX-5948 was well tolerated across all doses evaluated, and safety findings in the CLL/SLL cohort were consistent with the overall population as well as previous safety analyses. Among the CLL/SLL patients, the most common treatment emergent adverse events were purpura/contusion (36.7%, all grade 1 or 2), fatigue (26.7%, all grade 1 or 2), petechiae (26.7%, all grade 1 or 2), neutropenia (23.3%, 18.3% grade 3 or higher), and rash (23.3%, 1.7% grade 3 or higher). Importantly, across the entire population, there was only one case of grade 1 atrial fibrillation in a patient with pre-existing atrial fibrillation.
Among the efficacy evaluable patients with CLL/SLL (n=49), NX-5948 treatment resulted in a robust objective response rate (ORR) of 75.5% 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 were observed across all populations regardless of prior treatment, baseline mutations, high-risk molecular features, or CNS involvement. This includes patients with baseline BTK mutations associated with treatment resistance to both covalent and non-covalent BTK inhibitors. Robust BTK degradation was observed in all patients, including those with baseline BTK mutations.
Responses were durable with the median duration of response not reached. Thirteen patients had duration of response greater than six months, and five patients remain on treatment and in response beyond one year of treatment.
Additional preclinical data presentations
Nurix and its collaborators presented new preclinical data for NX-5948 in an animal model of primary CNS lymphoma (PCNSL) and assessed the impact of NX-2127 on T cell function.
Nurix and its collaborators presented new preclinical data for NX-5948 in an animal model of primary CNS lymphoma (PCNSL) and assessed the impact of NX-2127 on T cell function.
Preclinical data were presented demonstrating the positive effects of brain-penetrant NX-5948 treatment on survival in a patient-derived xenograft model of primary central nervous system lymphoma (PCNSL) in a poster titled: BTK Degradation As a Novel Therapeutic Strategy in Relapsed CNS Lymphoma: Proof of Concept Studies in Intracranial Patient-Derived, Rodent Models. The data demonstrate that daily oral administration of NX-5948 drives potent degradation of BTK, inhibition of extracellular signal-regulated kinase (ERK) and prolonged survival in the setting of CNS lymphoma. In addition, transcriptional changes associated with enhanced tumor antigen presentation and reduced tumor progression were observed in NX-5948 treated animals. Notably, oral administration of ibrutinib resulted in similar level of ERK inhibition but did not lead to prolonged survival or the same pattern of transcriptional changes in the model, suggesting that BTK degradation by NX-5948 exhibits differential biology
2
relative to BTK inhibition by ibrutinib, a result that may be associated with the elimination of BTK’s scaffolding function by NX-5948.
In addition, preclinical results were presented demonstrating that although both NX-2127 and NX-5948 effectively degrade BTK in primary CLL cells while preserving T-cell activation and survival in vitro, NX-2127 demonstrates unique immunomodulatory activity. These data were the subject of an oral presentation titled: NX-2127 and NX-5948, Two Clinical Stage Cereblon-Recruiting BTK Degraders, Facilitate T Cell Functionality in Chronic Lymphocytic Leukemia. Specifically, the data demonstrate distinct immunomodulatory effects in NX-2127 treated CLL cells, including upregulation of CD38, an interferon (IFN)-response gene, bolstering the immune response, promotion of T cell differentiation towards a TH1 phenotype, enhancing anti-tumor immunity, reduction in Treg differentiation, which supports a shift toward a less immunosuppressive microenvironment and enhancement of immunological synapse formation, and T cell-mediated cytotoxicity. In addition, RNA sequencing revealed unique patterns of gene expression in NX-2127-treated CLL cells, distinguishing responders from non-responders and further demonstrating its distinctive T cell modulatory effects.
About NX-5948: NX-5948 is an investigational, orally bioavailable degrader of BTK that is currently being evaluated in a Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies. Additional information on the Phase 1a/b clinical trial can be accessed at www.clinicaltrials.gov (NCT05131022).
About NX-2127: NX-2127 is an investigational, orally bioavailable degrader of BTK and cereblon neosubstrates Ikaros (IKZF1) and Aiolos (IKZF3). NX-2127 is currently being evaluated in a Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies. Additional information on the ongoing clinical trial can be accessed at www.clinicaltrials.gov (NCT04830137).
About Nurix Therapeutics, Inc.
Nurix Therapeutics 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 extensive expertise in E3 ligases together with proprietary DNA-encoded libraries, Nurix 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. Nurix’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. Nurix’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. Nurix is
Nurix Therapeutics 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 extensive expertise in E3 ligases together with proprietary DNA-encoded libraries, Nurix 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. Nurix’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. Nurix’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. Nurix is
3
headquartered in San Francisco, California. For additional information visit http://www.nurixtx.com.
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 plans to initiate pivotal trials of NX-5948 in 2025 and statements regarding the tolerability, safety profile, therapeutic potential and other advantages of NX-5948 and NX-2127. 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) the risks inherent in the drug development process, including the unexpected emergence of adverse events or other undesirable side effects during clinical development; (ii) uncertainties related to the timing and results of clinical trials; (iii) the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; (iv) whether Nurix will be able to successfully complete clinical development for, obtain regulatory approval of, and ultimately commercialize NX-5948 and NX-2127; (v) whether Nurix will be able to fund its research and development activities and achieve its research and development goals; (vi) the impact of economic and market conditions and global and regional events on Nurix’s business and clinical trials; (vii) whether Nurix will be able to protect intellectual property and (viii) other risks and uncertainties described under the heading “Risk Factors” in Nurix’s Quarterly Report on Form 10-Q for the fiscal period 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 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.
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 plans to initiate pivotal trials of NX-5948 in 2025 and statements regarding the tolerability, safety profile, therapeutic potential and other advantages of NX-5948 and NX-2127. 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) the risks inherent in the drug development process, including the unexpected emergence of adverse events or other undesirable side effects during clinical development; (ii) uncertainties related to the timing and results of clinical trials; (iii) the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; (iv) whether Nurix will be able to successfully complete clinical development for, obtain regulatory approval of, and ultimately commercialize NX-5948 and NX-2127; (v) whether Nurix will be able to fund its research and development activities and achieve its research and development goals; (vi) the impact of economic and market conditions and global and regional events on Nurix’s business and clinical trials; (vii) whether Nurix will be able to protect intellectual property and (viii) other risks and uncertainties described under the heading “Risk Factors” in Nurix’s Quarterly Report on Form 10-Q for the fiscal period 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 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, Inc.
4
ir@nurixtx.com
Elizabeth Wolffe, Ph.D.
Wheelhouse Life Science Advisors
lwolffe@wheelhouselsa.com
Media
Aljanae Reynolds
Wheelhouse Life Science Advisors
areynolds@wheelhouselsa.com
5
Nurix Therapeutics Blazing a New Path in Medicine American Society of Hematology Investor Event December 9, 2024 Exhibit 99.2
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 our DELigase platform and drug candidates; the extent to which our scientific approach, our DELigase platform, targeted protein modulation, and Degrader- Antibody Conjugates may potentially address a broad range of diseases; the extent animal model data predicts human efficacy; and the timing and success of the development and commercialization of our current and anticipated drug candidates. 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. Finally, while we believe our own internal estimates and research are reliable, such estimates and research have not been verified by any independent source.
3 ASH 2024 Three abstracts on Nurix BTK degraders, including two oral presentations Program Title Authors Abst # Presentation NX-5948 Efficacy and Safety of the Bruton’s Tyrosine Kinase (BTK) Degrader NX-5948 in Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL): Updated Results from an Ongoing Phase 1a/b Study Nirav Shah et al. 884 ORAL Session Name: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Treating Refractory Disease-Novel Agents and Quality-of- Life Session Date: Monday, December 9, 2024 NX-5948 BTK Degradation As a Novel Therapeutic Strategy in Relapsed CNS Lymphoma: Proof of Concept Studies in Intracranial Patient-Derived, Rodent Models Jun Ma et al. 2988 POSTER Session Name: 622. Lymphomas: Translational – Non-Genetic: Poster II Date: Sunday, December 8, 2024 NX-5948 & NX-2127 NX-2127 and NX-5948, Two Clinical Stage Cereblon-Recruiting BTK Degraders, Facilitate T Cell Functionality in Chronic Lymphocytic Leukemia Tiana Huynh et al. 77 ORAL Session Name: 641. Chronic Lymphocytic Leukemia: Basic and Translational: Therapeutic Vulnerabilities, Signaling, and Microenvironment Date: Saturday, December 7, 2024
NX-5948: Efficacy and safety of NX-5948 in patients with relapsed/refractory chronic lymphocytic leukemia NX-5948: Preliminary findings in patients with Waldenstrom’s Macroglobulinemia Nirav N. Shah, M.D., MSHP Associate Professor of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin NX-5948: Advancing into pivotal development in 2025 Paula G. O’Connor, M.D. Chief Medical Officer, Nurix Therapeutics Section I: Q&A NX-2127 and NX-1607: Clinical updates and next steps Paula G. O’Connor, M.D. Chief Medical Officer, Nurix Therapeutics Rationale for assessing NX-5948 in inflammation and immunology (I&I) Gwenn M. Hansen, Ph.D. Chief Scientific Officer, Nurix Therapeutics Nurix’s I&I strategy Arthur T. Sands, M.D., Ph.D. Chief Executive Officer, Nurix Therapeutics Section II: Q&A Agenda 4
Efficacy and safety of the Bruton’s tyrosine kinase (BTK) degrader NX-5948 in patients with relapsed/refractory chronic lymphocytic leukemia: updated results from an ongoing Phase 1a/b study Nirav N. Shah, Zulfa Omer, Graham Collins, Francesco Forconi, Alexey Danilov, John C. Byrd, Dima El Sharkawi, Emma Searle, Alvaro Alencar, Shuo Ma, Sarah Injac, Talha Munir ASH 2024 Annual Meeting, San Diego CA – December 9, 2024
• The current standard of care in CLL focuses on utilizing the inhibitors of two key signaling pathways – BTK and BCL2 • Unmet need still exists in the CLL treatment landscape: – Covalent and non-covalent BTKi resistance mutations1 are found in more than half of patients who progress on BTKi therapies2 – Some mutations in BTK can maintain intact B-cell receptor signaling through a scaffolding function of BTK3 – The number of BCL2i refractory and double (BTKi/BCL2i) refractory patients is growing4 • Novel BTK degrader NX-5948 offers an additional treatment modality: – Can overcome treatment-emergent BTKi resistance mutations5 and disrupt BTK scaffolding3,5 6 Background Novel BTK degrader NX-5948 addresses current unmet need in CLL treatment References 1. Noviski et al. 20th Biennial International Workshop on CLL Meeting, Boston, MA. October 6–9, 2023 2. Molica et al. 66th ASH Annual Meeting, December 7–10, 2024 3. Montoya et al. Science 2024;383 4. Hayama and Riches. Onco Targets 2024;17 5. Linton K, et al. Oral presentation at European Hematology Association Hybrid Congress; 16 June 2024 NX-5948 BCL2, B-cell lymphoma 2; BCL2i, BCL2 inhibitor; BTK, Bruton’s tyrosine kinase; BTKi, BTK inhibitor; CLL, chronic lymphocytic leukemia
Phase 1a dose escalation (completed enrollment) Phase 1b dose expansion (N = up to 160 patients) Key eligibility criteria • Age ≥18 years • Relapsed/refractory disease • ≥2 prior lines of therapy (≥1 for PCNSL) • ECOG PS 0–1 (ECOG PS 0–2 for PCNSL) 50 mg QD 100 mg QD 200 mg QD 300 mg QD 450 mg QD 600 mg QDNHL/WM (up to 66 patients) CLL/SLL 200 mg QD Prior BTKi and BCL2i MCL Prior BTKi and anti-CD20 CIT PCNSL/SCNSL Patients who have progressed or had no response to ≥1 prior LoT DLBCL Prior anthracycline, anti-CD20 CIT + 1 LoT MZL Prior anti-CD20 CIT and ≥2 prior LoT FL Prior anti-CD20 CIT + 1 LoT CLL/SLL 600 mg QD Prior BTKi and BCL2iCLL/SLL (up to 66 patients) 50 mg QD 100 mg QD 200 mg QD 300 mg QD 450 mg QD 600 mg QD 7 NX-5948-301: Trial Design Phase 1a/b trial in adults with relapsed/refractory B-cell malignancies BCL2i, BCL2 inhibitor; BTKi, BTK inhibitor; CIT, chemo-immunotherapy; CLL, chronic lymphocytic leukemia; DLBCL, diffuse large B-cell lymphoma; ECOG PS, Eastern Cooperative Oncology Group performance status; FL, follicular lymphoma; LoT, lines of treatment; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma; NHL, non-Hodgkin’s lymphoma; PCNSL, primary CNS lymphoma; QD, once daily; SCNSL, secondary CNS lymphoma; SLL, small lymphocytic lymphoma; WM, Waldenstrom’s macroglobulinemia WM 3L+ post-BTKi WM 2L post-BTKi
8 CLL Patient Disposition and Demographics Phase 1a and 1b CLL, chronic lymphocytic leukemia; SLL, small lymphocytic lymphoma Dosed (n=60) 50 mg: n=3 100 mg: n=5 200 mg: n=14 300 mg: n=8 450 mg: n=7 600 mg: n=23 CLL/SLL (n=60) Discontinued treatment (n=14) Radiological progression: n=5 Clinical progression: n=4 Death: n=2 Physician decision: n=2 Adverse event: n=1 On treatment (n=46) Patient disposition Characteristics Patientsa (n=60) Median age, years (range) 67.0 (35–88) Sex, n (%) Male 38 (63.3) Ethnicity, n (%) Hispanic or Latino 4 (6.7) Race, n (%) Black or African American White Other 5 (8.3) 51 (85.0) 4 (6.7) Patient demographics aPopulation demographics in CLL cohort were comparable to those in the overall population Data cutoff: 10 Oct 2024
9 Baseline Disease Characteristics Multiple prior lines of therapy and high prevalence of baseline mutations 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) 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 Data cutoff: 10 Oct 2024
10 NX-5948 Safety Profile TEAEs in ≥10% of overall population or Grade ≥3 TEAEs or SAEs in >1 patient 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
11 NX-5948 Degrades Wild-Type and Mutated BTK NX-5948 degrades gatekeeper, kinase-proficient and kinase-dead BTK mutations 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 BTK, Bruton’s tyrosine kinase; CLL, chronic lymphocytic leukemia; MFI, mean fluorescence intensity; SLL, small lymphocytic lymphoma Note: Some patients have multiple BTK mutations Reference 1. Montoya et al. Science 2024;383 Data cutoff: 10 Oct 2024 BTK degradation
NX-5948 Overall Response Assessment Response rate deepens with longer time on treatment CLL response-evaluable patients Primary ORR analysisb ≥1 response assessment(s) at 8 weeks (n=49)c Exploratory ORR analysisb ≥2 response assessments at 16 weeks (n=38)c 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 12Data cutoff: 10 Oct 2024 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
*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 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 Lymph Node Assessment and High-Risk Molecular Features Clinical activity in patients with CLL including those with baseline mutations and CNS involvement 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%) 13Data cutoff: 10 Oct 2024
14 NX-5948 Duration of Treatment Durable responses regardless of prior therapy BCL2i, BCL2 inhibitor; BTKi, BTK inhibitor; cBTKi, covalent BTKi; CIT, chemo/chemo-immunotherapies; ncBTKi, non-covalent BTKi; PD, progressive disease; PR, partial response; PR-L, PR with rebound lymphocytosis; SD, stable disease; CI, confidence interval *Patient with Richter’s transformation to Hodgkin's on biopsy Median duration of treatment, months (range) 3.9 (0.1–21.0) Patients dose escalated during treatment, n 19 Median duration of response, months (95% CI) Not reached (6.9 – not reached) Patients with duration of response >6 months 13 (26.5%) Data cutoff: 10 Oct 2024
• In this ongoing Phase 1 study, the BTK degrader NX-5948 demonstrated an encouraging clinical profile in a heavily pre-treated population of patients with CLL • NX-5948 was well tolerated across B-cell malignancies, with no additional safety signals observed with longer duration on study or increased dose • Robust and deepening clinical responses were observed in a heavily pretreated CLL patient population including patients with baseline BTK and PLCG2 mutations, high risk molecular features and CNS involvement – 75.5% ORR deepening to 84.2% ORR in patients with longer follow-up • Durable responses achieved in patients with high unmet clinical need, post-BTKi, BCL2i – 13 patients with duration of response 6+ months and 5 patients remaining on treatment beyond 1 year Phase 1b dose expansion is underway and pivotal trial(s) initiation is planned in 2025 Conclusions 15
NX-5948: Preliminary findings in patients with Waldenstrom’s macroglobulinemia 16 Highlights from the International Workshop on Waldenstrom's Macroglobulinemia (IWWM) in October 2024
Phase 1a dose escalation (completed enrollment) Phase 1b dose expansion (N = up to 160 patients) Key eligibility criteria • Age ≥18 years • Relapsed/refractory disease • ≥2 prior lines of therapy (≥1 for PCNSL) • ECOG PS 0–1 (ECOG PS 0–2 for PCNSL) 50 mg QD 100 mg QD 200 mg QD 300 mg QD 450 mg QD 600 mg QDNHL/WM (up to 66 patients) CLL/SLL 200 mg QD Prior BTKi and BCL2i MCL Prior BTKi and anti-CD20 CIT PCNSL/SCNSL Patients who have progressed or had no response to ≥1 prior LoT DLBCL Prior anthracycline, anti-CD20 CIT + 1 LoT MZL Prior anti-CD20 CIT and ≥2 prior LoT FL Prior anti-CD20 CIT + 1 LoT CLL/SLL 600 mg QD Prior BTKi and BCL2iCLL/SLL (up to 66 patients) 50 mg QD 100 mg QD 200 mg QD 300 mg QD 450 mg QD 600 mg QD 17 NX-5948-301: Trial Design Phase 1a/b trial in adults with relapsed/refractory B-cell malignancies BCL2i, BCL2 inhibitor; BTKi, BTK inhibitor; CIT, chemo-immunotherapy; CLL, chronic lymphocytic leukemia; DLBCL, diffuse large B-cell lymphoma; ECOG PS, Eastern Cooperative Oncology Group performance status; FL, follicular lymphoma; LoT, lines of treatment; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma; NHL, non-Hodgkin’s lymphoma; PCNSL, primary CNS lymphoma; QD, once daily; SCNSL, secondary CNS lymphoma; SLL, small lymphocytic lymphoma; WM, Waldenstrom’s macroglobulinemia WM 3L+ post-BTKi WM 2L post-BTKi
Baseline Demographics/Disease Characteristics Elderly population with multiple prior lines of targeted therapies Characteristics Patients with WM (n=13) Median age, years (range) 74.0 (64–82) Male, n (%) 11 (84.6) ECOG PS, n (%) 0 1 3 (23.1) 10 (76.9) CNS involvement, n (%) 0 Median prior lines of therapy (range) 3.0 (2–5) Previous treatmentsa, n (%) BTKi Pirtobrutinib BCL2i BTKi and BCL2i CAR-T therapy Bispecific antibody PI3Ki Chemo/chemo-immunotherapies 13 (100.0) 3 (23.1) 1 (7.7) 1 (7.7) 0 (0.0) 0 (0.0) 0 (0.0) 13 (100.0) Mutation status*, n (%) MYD88 CXCR4 (n=13) 8 (61.5) 2 (15.4) aPatients could have received multiple prior treatments *Mutation status was gathered from historic patient records Data cutoff: 10 Oct 2024BTKi, Bruton’s tyrosine kinase inhibitor; BCL2i, B-cell lymphoma 2 inhibitor; CAR-T, chimeric antigen receptor T-cell; CNS, central nervous system; ECOG PS, Eastern Cooperative Oncology Group (ECOG) performance status; PI3Ki, PI3 kinase inhibitor; WM, Waldenstrom’s macroglobulinemia 18
NX-5948 Efficacy and Duration of Treatment in Patients with WM Data cutoff: 10 Oct 2024 Select prior therapies Select mutations BTKi BCL2i Pirto CXCR4 MYD88 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) *Ineligible, identified post 1st dose #Transformed to DLBCL * # 19
Steady Decrease in IgM Levels in Patients Treated with NX-5948 Percent change in IgM levels from baseline in patients with WM1 Data cutoff: 10 Oct 2024 #Transformed to DLBCL 1Response criteria used: Owen RG, Kyle RA, Stone MJ, et al. VIth International Workshop on Waldenström macroglobulinaemia. Response assessment in Waldenström macroglobulinaemia: update from the VIth International Workshop. Br J Haematol 2013;160:171–6 # % c ha ng e fro m b as el in e in Ig M le ve l 20
• NX-5948 was administered to 13 WM patients with a median of 3 prior lines of therapy, all of whom had been treated previously with both chemotherapy and BTK inhibitors • NX-5948 is well tolerated in WM patients, consistent with the overall NHL and CLL populations • Highly encouraging overall response rate of 77.8%, with increasing depth of response over time • These data support continued development of NX-5948 for WM; Phase 1b dose expansion is underway Conclusions – Waldenstrom’s Macroglobulinemia 21
NX-5948: Advancing into pivotal development in 2025 22 Regulatory update and development plans in CLL
• U.S. Fast Track Designation from the FDA in January 2024 • CLL 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 • Helpful 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 from 200 mg and 600 mg QD cohorts • EU expansion of enrollment into France, Poland, Italy and Spain approved in Q3 2024, site activation underway • EU PRIME designation from EMA in November 2024 NX-5948 Regulatory Milestones Advancing NX-5948 program globally toward pivotal trials in CLL 23
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 24 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* Current status in CLL Outline of potential pivotal plans in CLL* *All plans subject to change based on regulatory feedback including definition of control arms of all studies
Section I: Q&A 25
NX-1607 and NX-2127 26 Clinical updates and next steps
NX-1607: Phase 1a/b Trial in Patient with Advanced Solid Tumors Extensive exploration of dose and schedule to optimize tolerability and PD effects Phase 1a Monotherapy Dose Escalation Potential Phase 1b Monotherapy Dose Expansion Cohorts Key eligibility criteria • Age ≥18 years • Metastatic/unresect- able disease and exhausted available therapies • Measurable disease according to applicable response criteria • ECOG PS 0–1 15 mg BID 20 mg BID 30 mg BID BID Dosing Indication 1 dose A Indication 2 dose A Indication 2 Dose B Indication 1 dose B QD Dosing 5 mg QD 15 mg QD 20 mg QD 25 mg QD ECOG PS, Eastern Cooperative Oncology Group (ECOG) performance status Phase 1a Combination Dose Escalation Paclitaxel Pembrolizumab (potential) 50 mg QD 27
Dose Dependent Increase in Proprietary Proximal Biomarker Supports Benefit of Twice Daily Dosing Data cutoff: 22 November 2024 • Inhibition of CBL-B by NX-1607 blocks degradation of substrate proteins and enhances signaling through the T cell receptor • Elevation of phosphorylated HS1 (pHS1) serves as proximal biomarker of enhanced T cell signaling • Increased pHS1 is associated with efficacy in animal tumor models • Addition of twice daily (BID) dosing has allowed us to achieve desired levels of pHS1 with improved GI tolerability QD dosing BID dosing Overall # of pts enrolled 43 23 66 Dose-Dependent Increase in Proximal Biomarker Levels Following CBL-B Inhibition 28 HS1, Hematopoietic lineage cell-specific protein 1; pHS1, Phosphorylated HS1
29 NX-1607 Status and Next Steps Status • Phase 1a has enrolled 66 heavily pretreated patients across 11 different solid tumor indications • Oral dosing of NX-1607 has been associated with gastrointestinal tolerability issues that have been mitigated through exploration of ramp-up dosing, BID regimens, and anti-emetic prophylaxis • Drug exposures and proximal biomarker levels at the higher dose ranges are consistent with levels associated with anti-tumor activity in nonclinical models • Preliminary evidence of stable disease, tumor shrinkage, and biomarker and clinical responses have been observed Next Steps • Additional patients in the BID dosing arms are required to establish Phase 1b monotherapy dose • Additional clinical data will be shared after selection of a Phase 1b expansion dose(s) and indication(s)
30 NX-2127: Phase 1a/b Trial in Relapsed/Refractory B-cell Malignancies Enrollment ongoing in dose escalation with new drug product Phase 1a Dose Escalation Phase 1b Monotherapy Expansion Cohorts (no longer enrolling new patients) Key eligibility criteria • Age ≥18 years • Relapsed/Refractory disease • Ph1a: ≥2 prior lines of therapy (≥1 for WM or PCNSL) • Ph1b: Prior BTKi for CLL/SLL, MCL, WM New drug product CLL/SLL (100 mg) DLBCL, WM (300 mg) MCL (300 mg) Original drug product 50 mg QD 100 mg QD 150 mg QD 200 mg QD ECOG PS, Eastern Cooperative Oncology Group (ECOG) performance status Potential Phase 1b Monotherapy Expansion Cohorts (new drug product) 300 mg QD 100 mg QD 150 mg QD 225 mg QD 325 mg QD 450 mg QD MCL FL/MZL/WM MCL DLBCL
Updated Clinical Case Study 1 Rapid and sustained complete response in WM transformed to DLBCL with NX-2127 Confirmatory Week 16 scan Deauville score: 2 Baseline FDG-PET CT Scan Disease Assessment Deauville score: 5 Bladder Bladder • 84-year-old female with WM diagnosed in 2003 with DLBCL (ABC subtype) transformation in 2015 – MYD88 and CXCR4 mutation • 4 prior lines of aggressive therapy – R-CHOP (CR) – R-ICE (PR) – Rituximab, mogamulizumab (anti-CCR4), magrolimab (anti-CD47) – Rituximab, ibrutinib, and lenalidomide • Complete response on first assessment at week 8, confirmed at week 16 • As of November 18, 2024, this patient remains in complete response and on treatment with 33 months of follow up (2.75 years) Case history 31Status update as of November 18, 2024
Updated Clinical Case Study 2: Rapid and sustained complete response in relapsed/refractory MCL with NX-2127 32 Week 8 Scan Deauville score: 2 Baseline FDG-PET CT Scan Disease Assessment Deauville score: 5 Bladder Bladder • 64-year-old woman with multiply relapsed MCL, following: • 2016: Rituximab + CHOP; R-hyper-CVAD; cytarabine • 2017: Hematopoietic stem cell transplantation (HSCT) • 2016-2019: Rituximab, ibrutinib, cytarabine • Complete response on first assessment at week 8, confirmed at week 16 • She came off therapy on August 28, 2023, after 17 cycles of therapy • Approximately 1 year later, as of July 18, 2024, she had no evidence of disease by PET CT and was not on any active treatment for MCL. Her next PET CT is scheduled for January 2025. Status update as of November 25, 2024
33 NX-2127 Status and Next Steps Status • We have re-initiated enrollment with the new, chirally controlled drug product • We are focused on the aggressive lymphomas for development of NX-2127 where the combination of BTK degradation and IKZF1/3 degradation have the potential for synergy and significant therapeutic benefit Next Steps • Complete dose escalation with new drug product and select recommended Phase 1b dose for selected indications • Additional clinical data will be shared after selection of a Phase 1b expansion dose(s) and indication(s)
NX-5948 in inflammation and immunology (I&I) 34 Rationale & strategy
Key Observations Underpinning Nurix’s NX-5948 Immunology and Inflammation Strategy The genetics of BTK are compelling: highly specific with potent biology • Human knockouts, originally described by Dr. Bruton in 1952, show agammaglobulinemia (no antibody production) and associated reduced immune function yet have otherwise normal physiology • Mouse xid mutants show a similar phenotype as the humans and solidly confirm the biology of BTK as a powerful B-cell drug target 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 in oncology may also be limiting efficacy in autoimmune disease settings • Liver safety signals from BTK inhibitors may limit broad use 35 Multi-modal impact on inflammation
36 NX-5948 Is 10x to 100x More Potent in Blocking B Cell Activation than BTK Inhibitors Tested in I&I 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 B Ce ll Ac tiv at io n Source: Noviski et al., ACR 2024, November 2024
• IL-8 is a chemokine that recruits neutrophils into inflamed tissues 37 NX-5948 Potently Suppresses Activation of Myeloid Cells Stimulated Through Key Inflammatory Receptors 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 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 IL-1β Stimulation Fc Receptor Pathway Inflammatory Signaling Pathway M on oc yt e Ac tiv at io n M on oc yt e Ac tiv at io n
NX-5948 Is Active Across a Range of Autoimmune and Inflammation Models 38 Systemic Lupus Erythematosus (MRL/Ipr Model) Lupus Nephritis (AIG Model) Multiple Sclerosis (EAE Model) Rheumatoid Arthritis (Established CIA Model) 10 12 14 16 18 20 0 1 2 3 Animal Age (Weeks) U rin e Pr ot ei n Sc or e M ea n ± SE M (0 -5 S co re ) Vehicle NX-5948, 30 mg/kg Ibrutinib, 30 mg/kg Dexamethasone, 2 mg/kg* * ** 10 15 20 0 1 2 3 Days After Immunization M ea n C lin ic al E AE Sc or e (0 to 5 ) ± S EM **** Vehicle NX-5948, 30 mg/kg Ibrutinib, 30 mg/kg FTY720, 3 mg/kg 0 2 4 6 8 10 M ea n ± SE M S um m ed S co re (M ax 2 5) -0% -100% -90% -92% -91% -81% Vehicle NX-5948 (30 mg/kg) Ibrutinib (30 mg/kg) Rilzabrutinib (30 mg/kg) Dexamethasone (2 mg/kg) Naive +Autoantibodies 0 5 10 15 0 1 2 3 4 Days M ea n Pa w S co re * *** **** NX-5948, 30 mg/kg Vehicle Rilzabrutinib, 30 mg/kg Enbrel, 10 mg/kg Tofacitinib, 30 mg/kg, BID Ibrutinib, 30 mg/kg **** Source: Noviski et al., ACR 2024, November 2024
NX-5948 Has The Right Clinical Profile To Address Unmet Clinical Needs in Both Oncology and I&I 39 Wide dose range produces robust BTK degradation 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
NX-5948 I&I Vision: Introduce the First BTK Degrader with Practice Changing Potential Strategic considerations for introducing NX-5948 into immunology and inflammation: 1. Novel mechanism of action: First BTK degrader in I&I should be focused on areas where BTK has strong biologic rationale and an appropriate risk/benefit profile 2. Speed to proof of concept: Preference should be given to indications with potential for rapid proof of concept that could support additional indications requiring longer duration of therapy 3. Dosing and formulation: Expansion opportunities in I&I indications are significant and may require different dosages and/or formulation based on desired drug product profile and exposure 4. Medical marketplace: An oral BTK degrader could address multiple very large markets that should mesh with oncology pricing and reimbursement considerations 40 All of the above informed Nurix’s plan to introduce NX-5948 into I&I
Goal: Implement a sequenced, multi-organ system approach to generate the greatest opportunity for patients and value creation 1. Hematology: Leverage Nurix’s existing hematology expertise, seeking first proof of concept through study of CLL patients with secondary autoimmune-mediated hemolytic anemia with plans to explore non-malignant warm autoimmune hemolytic anemia (wAIHA) 2. Dermatology: Evaluate potential IND in hidradenitis suppurativa (HS); potential expansion in chronic spontaneous urticaria (CSU) 3. Neurology: Explore potential opportunity in multiple sclerosis (MS), given NX-5948’s CNS activity 41 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) 5. Provide additional information in 2025 on our broader I&I pipeline including the STAT6 (Nurix/Sanofi) and IRAK4 (Nurix/Gilead) programs 42 Implementing Nurix’s Systematic Approach to I&I
43 Nurix: Building Blocks of Success and Value Creation Drive NX-1607 and NX-2127 to proof-of-concept data Successfully execute NX-5948 development in CLL A core opportunity with Fast Track and Prime Designation, we are moving rapidly to pivotal trials in 2025 Advance our innovative degrader pipeline Developing a pipeline of novel oral degraders Pioneering the next gen technology of degrader antibody conjugates (DACs) Expanding our state-of-the-art platform to accelerated ligand and drug discovery Extend I&I opportunity with collaborators IRAK4 and STAT6 opt-in rights Expand NX-5948 as a pipeline in a product WM, NHL and I&I
Section II: Q&A 44