0001549595false00015495952024-06-162024-06-16

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): June 16, 2024
___________________________________________
NURIX THERAPEUTICS, INC.
(Exact Name of Registrant as Specified in its Charter)
___________________________________________
Delaware001-3939827-0838048
(State or Other Jurisdiction
of Incorporation or Organization)
(Commission
File Number)
(IRS Employer
Identification No.)
1700 Owens StreetSuite 205
San FranciscoCalifornia
94158
(Address of Principal Executive Offices)(Zip Code)
(415660-5320
(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:
oWritten communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
oSoliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
oPre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
oPre-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 classTrading symbol(s)Name of each exchange on which registered
Common Stock, $0.001 par value per shareNRIXNasdaq Global Market
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 June 16, 2024, Nurix Therapeutics, Inc. (the “Company”) issued a press release announcing the presentation at the European Hematology Association Congress (“EHA2024”) of updated clinical data from the Company’s Phase 1 clinical trial of NX-5948. As previously announced, the Company hosted a webcast on June 16, 2024, to discuss the data presented at EHA2024. Copies of the press release and the presentation materials for the webcast, which include the data presented at EHA2024, 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 June 16, 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 Phase 1a dose escalation study of NX-5948 regardless of diagnosis (n=79) and include efficacy findings for those patients with relapsed or refractory chronic lymphocytic leukemia (CLL) (n=31). Patients were treated with NX-5948 at doses ranging from 50 mg to 600 mg once daily by oral administration. NX-5948 was well tolerated across all doses evaluated with the most common treatment emergent adverse events of purpura/contusion, thrombocytopenia and neutropenia. Among the efficacy evaluable patients with CLL (n=26), NX-5948 treatment resulted in an objective response rate (ORR) of 69.2% across all doses tested with responses observed as early as the first scan (8 weeks) and with many patients experiencing deepening of their response with longer time on treatment. All responses remained ongoing as of the April 17, 2024 data cutoff. This cohort of CLL patients was a heavily pretreated population that had received a median of four prior lines of therapy (range = 2–14) including prior covalent BTK inhibitors (96.8%), prior BCL2 inhibitors (90.3%), and prior non-covalent BTK inhibitors (25.8%). At baseline, a large number of patients had mutations associated with BTK inhibitor resistance including mutations in BTK (43.3%) and PLC2G (20.0%). Poor prognostic features were common including TP53 mutations (46.7%), and two patients (6.5%) had central nervous system (CNS) involvement. Responses were observed across all populations regardless of prior treatment, baseline mutations, or CNS involvement.


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
104Cover Page Interactive Data File (embedded within the Inline XBRL document)



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: June 17, 2024
By:/s/ Christine Ring
Christine Ring, Ph.D., J.D.
Chief Legal Officer
3
Exhibit 99.1
[Nurix logo]
Nurix Therapeutics Presents Positive Results from Ongoing Clinical Trial of
NX-5948 in Patients with Relapsed Refractory Chronic Lymphocytic Leukemia (CLL) at the European Hematology Association Congress (EHA2024)

Objective response rate of 69.2% observed in heavily pretreated patient population including patients with BTK inhibitor resistance mutations
Clinical responses in CLL patients were rapid and deepening with longer time on treatment
Nurix intends to advance NX-5948 into pivotal trial(s) in 2025
Company will host a webcast conference today, June 16, 2024, at 9:00 a.m. ET (3:00 p.m. CEST)

SAN FRANCISCO, June 16, 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 announced the presentation of updated clinical data for NX-5948, an orally bioavailable degrader of Bruton’s tyrosine kinase (BTK), being evaluated in an ongoing Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies, including CLL and non-Hodgkin lymphoma (NHL). Dr. Kim Linton, M.B.Ch.B, MRCP, Ph.D., FRCP, senior lecturer at the University of Manchester, a consultant at The Christie NHS Foundation Trust and an investigator on the clinical trial, presented the data in an oral session at the European Hematology Association Congress, which is being held from June 13–16, 2024, in Madrid, Spain.
“The current results from this study of advanced patients are very impressive for this early stage of development and we are optimistic that NX-5948 has the potential to be an exciting breakthrough for patients with relapsed CLL, particularly in light of the emerging patterns of resistance to the currently available targeted therapies,” said Dr. Linton. “As a clinical investigator, it is highly gratifying to be able to offer patients who are refractory to other therapies a once daily, oral drug that can address a range of CLL disease states.”
The data presented at EHA include safety findings for all patients in the Phase 1a dose escalation study regardless of diagnosis (n=79) and include efficacy findings for those patients with relapsed or refractory CLL (n=31). Patients were treated with NX-5948 at doses ranging from 50 mg to 600 mg once daily by oral administration. NX-5948 was well tolerated across all doses evaluated with most common treatment emergent adverse events of purpura/contusion, thrombocytopenia and neutropenia. Among the efficacy evaluable patients with CLL (n=26), NX-5948 treatment resulted in a robust objective response rate (ORR) of 69.2% across all doses tested with responses observed as early as the first scan (8 weeks) and with many patients experiencing deepening of their response with longer time on treatment. All responses remained ongoing as of the April 17 data cutoff. This cohort of CLL patients was a heavily pretreated population that had received a median of four prior lines of therapy (range = 2–14) including prior covalent BTK inhibitors (96.8%), prior BCL2 inhibitors (90.3%), and prior non-



covalent BTK inhibitors (25.8%). At baseline, a large number of patients had mutations associated with BTK inhibitor resistance including mutations in BTK (43.3%) and PLC2G (20.0%). Poor prognostic features were common including TP53 mutations (46.7%), and two patients (6.5%) had central nervous system (CNS) involvement. Responses were observed across all populations regardless of prior treatment, baseline mutations, or CNS involvement.
Dr. Linton also presented an updated case report that detailed the response of one patient who entered the study with CLL with CNS involvement after having undergone three prior therapies, including treatment with a BTK inhibitor. After daily treatment with 100 mg, and later 300 mg, of NX-5948, the patient exhibited a deepening response approaching complete response criteria by 36 weeks, with elimination of malignant cells in the cerebrospinal fluid (CSF) by 24 weeks.
Another case report presented by the company involved a patient who had received eleven prior lines of therapy, including all available BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib, and pirtobrutinib). After daily treatment with 200 mg of NX-5948, the patient achieved a response by week 8 which deepened over time and was ongoing with over 6 months of follow up.
“The responses we are observing across the entire CLL cohort at all dose levels are extremely encouraging. As a next step, we will expand the Phase 1b portion of the trial across a range of CLL subpopulations to prepare for initiation of pivotal, registration-directed clinical evaluation in 2025.” said Paula G. O’Connor, M.D., chief medical officer of Nurix. “While we did not cover the clinical activity data from the NX-5948 study in the various subtypes of NHL in this presentation, we have observed responses across subtypes including complete responses in patients with advanced DLBCL, MCL, MZL, and PCNSL, as well as consistent responses in advanced WM. We look forward to presenting additional data from the study for both CLL and NHL as it matures and to providing further details around our plans for the next stage of development of NX-5948.”
“With a growing body of positive clinical data, demonstrated activity in the CNS and a favorable safety profile, NX-5948 is emerging as a best-in-class medicine that has the potential to provide an important treatment option for patients with CLL and NHL,” said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix “We intend to move rapidly forward with the goal of initiating pivotal trial(s) with NX-5948 in 2025.”
Conference Call Details
On June 16, 2024, at 9:00 a.m., ET (3:00 p.m., CEST), Nurix will host a conference call and webcast to discuss data from the NX-5948 clinical trial and plans for the program. The live webcast, with an accompanying presentation, will be accessible under the Events and Presentations page in the Investors section of the company’s website here. To participate in the live conference call please pre-register online here. A replay of the webcast and call will be archived on the Nurix website for approximately 30 days after the event.



About NX-5948
NX-5948 is an investigational, orally bioavailable, brain penetrant, small molecule degrader of BTK. NX-5948 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies including chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), primary central nervous system lymphoma (PCNSL) and Waldenström's macroglobulinemia (WM). Additional information on the ongoing clinical trial can be accessed at clinicaltrials.gov (NCT05131022).
About Nurix
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 cell and NK cells. Nurix is 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 and strategies with respect to NX-5948, including Nurix’s plans with respect to presenting additional data from the NX-5948 clinical trial, Nurix’s plans to expand the Phase 1b portion of the NX-5948 clinical trial across a range of CLL subpopulations, and Nurix’s intention to advance NX-5948 into pivotal trial(s) in 2025; and the potential advantages and therapeutic benefits of NX-5948, including its potential role in the treatment B-cell lymphomas and CLL involving the CNS. 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) whether Nurix will be able to fund its research and development activities and achieve its research and development goals; (iv) the impact of economic and market conditions and global and regional events on Nurix’s business, clinical trials, financial condition, liquidity and results of operations; (v) whether Nurix will be able to protect intellectual property and (vi) other risks and uncertainties described under the heading “Risk Factors” in Nurix’s Quarterly Report on Form 10-Q for the fiscal period ended February 29, 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
ir@nurixtx.com
Elizabeth Wolffe, Ph.D.
Wheelhouse Life Science Advisors
lwolffe@wheelhouselsa.com
Media
Aljanae Reynolds
Wheelhouse Life Science Advisors
areynolds@wheelhouselsa.com




Nurix Therapeutics NX-5948 Clinical Update European Hematology Association Congress EHA2024 June 16, 2024


 
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, business or development 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 updates and 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, increasing interest rates, 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 February 29, 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.


 
Agenda I. Introduction Arthur T. Sands, MD, PhD Chief Executive Officer, Nurix Therapeutics II. NX-5948 clinical presentation from EHA Kim Linton, MBChB, MRCP, PhD, FRCP University of Manchester and The Christie NHS Foundation Trust III. Patient journey and program next steps Paula G. O’Connor, MD Chief Medical Officer, Nurix Therapeutics IV. Concluding remarks & Q&A 3


 
MOA Oncology program Target Therapeutic area Discovery – Lead Op IND enabling Phase 1a Phase 1b TPD NX-5948 BTK B-cell malignancies NX-2127 BTK-IKZF B-cell malignancies TPE NX-1607 CBL-B Immuno-Oncology TPD Multiple Undisclosed Undisclosed Multiple Undisclosed Undisclosed Multiple Undisclosed Undisclosed DAC Multiple Undisclosed Oncology Nurix Is Advancing a Pipeline of Propriety and Partnered Programs in Oncology and Inflammation & Immunology 4 MOA I&I program Target Therapeutic area Discovery – Lead Op IND enabling Phase 1a Phase 1b TPD NX-5948 BTK Inflammation / autoimmune NX-0479 / GS-6791 IRAK4 Rheumatoid arthritis and other inflammatory diseases STAT6 degrader STAT6 Type 2 inflammatory diseases Undisclosed Undisclosed Inflammation / autoimmune TPD: Targeted Protein Degradation; TPE: Targeted Protein Elevation; DAC: Degrader Antibody Conjugate


 
• NX-5948 has demonstrated positive results from the ongoing Phase 1a clinical trial in patients with an objective response rate of 69.2% in heavily pretreated CLL patients including those with BTK inhibitor resistance mutations • Clinical responses in CLL patients were rapid and deepening with longer time on treatment and NX-5948 has been well tolerated with extended treatment durations in many patients • With an emerging best-in-class profile, Nurix is expanding to Phase 1b in CLL with plans to initiate pivotal development in 2025 5 Executive Summary NX-5948, an emerging best-in-class profile in CLL


 
Kim Linton, MBChB, MRCP, PhD, FRCP University of Manchester and The Christie NHS Foundation Trust 6


 
Latest Results from an Ongoing First-in-Human Phase 1a/b Study of NX-5948, a Selective Bruton’s Tyrosine Kinase (BTK) Degrader, in Patients with Relapsed/Refractory CLL and Other B-cell Malignancies Kim Linton, Graham P. Collins, Francesco Forconi, Nirav N. Shah, Karan Dixit, Talha Munir, Zulfa Omer, Dima El-Sharkawi, Jeanette Doorduijn, Alvaro Alencar, Pam McKay, John Riches, Mary Gleeson, David Lewis, Allison Winter, Sarah Injac, Ted Shih, Srinand Nandakumar, May Tan, Ganesh Cherala, Erin Meredith, Alexey Danilov EHA Hybrid Congress – June 16, 2024


 
• Targeted therapy focusing on two key pathways (BTK/BCL2) is standard of care in CLL and has changed the treatment landscape in front-line and relapsed/refractory settings • Emerging patterns of resistance limit the utility of currently available therapies: – BTK mutations confer resistance to both covalent and non-covalent BTK inhibitors (cBTKi and ncBTKi)1 – Some mutations lead to ‘kinase dead’ or ‘kinase overactive’ BTK mutants with intact B-cell receptor signaling through a scaffolding function of BTK2 8 Unmet Clinical Need: Relapsed/Refractory CLL Acquired resistance to BTK inhibitors presents a growing challenge in the treatment of CLL There is a need for a new treatment modality that can target both emerging resistant mutations and BTK scaffolding activity References 1. Noviski et al. XX Biennial International Workshop on CLL Meeting, Boston, MA. October 6-9, 2023 (Poster #2020) 2. Montoya et al. Science 2024;383


 
9 NX-5948 Mechanism of Action Utilize the ubiquitin-proteasome pathway to degrade BTK, a well-validated target in B-cell malignancies BTK degraders can overcome treatment-emergent resistance mutations BTK degraders have the potential to replace BTK inhibitors in the clinic BTK degraders show emerging activity in various B-cell malignancies BTK degraders address BTK scaffolding function


 
NX-5948-301: Trial Design Phase 1a/b trial in adults with relapsed/refractory B-cell malignancies Phase 1a dose escalation Potential 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 dose A Prior BTKi and BCL2i MCL Prior BTKi and anti-CD20 CIT WM Prior BTKi and ≥2 prior LoT PCNSL/SCNSL 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 dose B 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 10CLL, chronic lymphocytic leukemia; SLL, small lymphocytic lymphoma; NHL, non-Hodkgin’s lymphoma; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma; WM, Waldenstrom’s macroglobulinemia; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; PCNSL, primary CNS lymphoma; SCNSL, secondary CNS lymphoma; CIT, chemo-immunotherapy; LoT, lines of treatment; BCL2i, Bcl-2 inhibitor; ECOG PS, Eastern Cooperative Oncology Group (ECOG) performance status


 
Screened (N=121)a Screen failure (n=39) Patient Disposition Patients were dosed in CLL (n=31) and NHL/WM (n=48) dose-escalation cohorts aIncludes 3 patients at screening but not yet enrolled on study at time of data cutoff; bPercent of total patient population Data cutoff: 17 April 2024 Dosed (n=31) 50 mg: n=3 100 mg: n=5 200 mg: n=9 300 mg: n=8 450 mg: n=4 600 mg: n=2 CLL dose escalation (n=31) NHL/WM dose escalation (n=48) Discontinued treatment (n=4) Radiological progression: n=2 Clinical progression: n=1 Death: n=1 Assigned cohort (N=79) 11 Dosed (n=48) 50 mg: n=4 100 mg: n=3 200 mg: n=5 300 mg: n=9 450 mg: n=13 600 mg: n=14 Discontinued treatment (n=26) Radiological progression: n=16 Clinical disease progression: n=6 Adverse event: n=2 Physician decision: n=1 Withdrew consent: n=1 DLBCL: n=14 (17.7%)b MCL: n=12 (15.2%)b PCNSL: n=9 (11.4%)b MZL: n=6 (7.6%)b WM: n=4 (5.1%)b FL: n=3 (3.8%)b On treatment (n=27) On treatment (n=22)


 
Baseline Demographics/Disease Characteristics Elderly population with multiple prior lines of targeted therapies Characteristics Patients with CLL (n=31) Patients with NHL/WM (n=48) Overall population (N=79) Median age, years (range) 69.0 (35–88) 66.5 (42–87) 67.0 (35–88) Male, n (%) 19 (61.3) 33 (68.8) 52 (65.8) ECOG PS, n (%) 0 1 13 (41.9) 18 (58.1) 13 (27.1) 33 (68.8) 26 (32.9) 51 (64.6) CNS involvement, n (%) 2 (6.5) 10 (20.8) 12 (15.2) Median prior lines of therapy (range) 4.0 (2–14) 4.0 (2–13) 4.0 (2–14) Previous treatmentsa, n (%) BTKi ≥2 BTKi Pirtobrutinib BCL2i BTKi and BCL2i CAR-T therapy Bispecific antibody PI3Ki Chemo/chemo-immunotherapies 30 (96.8) 11 (35.5) 7 (22.6) 28 (90.3) 27 (87.1) 2 (6.5) 1 (3.2) 9 (29.0) 24 (77.4) 29 (60.4) NA 7 (14.6) 7 (14.6) 7 (14.6) 11 (22.9) 7 (14.6) 4 (8.3) 48 (100.0) 59 (74.7) NA 14 (17.7) 35 (44.3) 34 (43.0) 13 (16.5) 8 (10.1) 13 (16.5) 72 (91.1) Mutation status, n (%) TP53 BTK PLCG2 14/30 (46.7) 13/30 (43.3) 6/30 (20.0) 4/42 (9.5) 0/42 (0.0) 2/42 (4.8) 18/72 (25.0) 13/72 (18.1) 8/72 (11.1) aPatients could have received multiple prior treatments; NA, not applicable; PI3Ki, PI3 kinase inhibitor; CAR-T, chimeric antigen receptor T-cell. 12Data cutoff: 17 April 2024


 
NX-5948 Is Well Tolerated TEAEs in ≥10% of overall population or grade ≥3 TEAEs or SAEs in >1 patient Patients with CLL (n=31) Overall population (N=79) TEAEs, n (%) Any grade Grade ≥3 SAEs Any grade Grade ≥3 SAEs Purpura/contusiona 13 (41.9) – – 28 (35.4) – – Thrombocytopeniab 7 (22.6) 1 (3.2) – 21 (26.6) 7 (8.9) – Neutropeniac 7 (22.6) 6 (19.4) – 16 (20.3) 12 (15.2) – Fatigue 7 (22.6) – – 14 (17.7) 2 (2.5) – Anemia 6 (19.4) 1 (3.2) – 13 (16.5) 3 (3.8) – Petechiae 7 (22.6) – – 13 (16.5) – – Rashd 8 (25.8) – 1 (3.2) 13 (16.5) 1 (1.3) 1 (1.3) Headache 6 (19.4) – – 12 (15.2) – – Cough 4 (12.9) – – 11 (13.9) 1 (1.3) – Diarrhea 5 (16.1) 1 (3.2) – 9 (11.4) 1 (1.3) – COVID-19e 2 (6.5) – – 8 (10.1) 2 (2.5) 2 (2.5) Hypertension 1 (3.2) 1 (3.2) – 6 (7.6) 4 (5.1) – Pneumoniaf 2 (6.5) 1 (3.2) 1 (3.2) 5 (6.3) 4 (5.1) 4 (5.1) aPurpura/contusion includes episodes of contusion or purpura; bAggregate of ‘thrombocytopenia’ and ‘platelet count decreased’; cAggregate of 'neutrophil count decreased' or 'neutropenia’; dAggregate of ‘rash’ and ‘rash maculopapular’ and ‘rash pustular’; eAggregate of 'COVID-19' and 'COVID-19 pneumonia’; fAggregate of 'pneumonia’ and ‘pneumonia klebsiella' 13 • 1 DLT (non-protocol mandated drug hold; NHL) • 2 TEAEs resulting in drug discontinuation (both NHL) • 1 related SAE (TLS based on labs, no clinical sequelae) • Grade 5 AE (pulmonary embolism, not deemed NX-5948 related) • No additional safety signal with higher doses Data cutoff: 17 April 2024 AE, adverse event; TEAE, treatment emergent adverse event; DLT, dose-limiting toxicity; SAE, serious adverse event; TLS, tumor lysis syndrome.


 
NX-5948 Efficacy: Clinical Response Broad antitumor activity in CLL as demonstrated by significant lymph node reduction and ORR 14Data cutoff: 17 April 2024SPD, sum of products diameters; CR, complete response; CRi, complete response with incomplete marrow recovery; PR, partial response; nPR, nodular partial response; PR-L, partial response with rebound lymphocytosis; SD, stable disease; PD, progressive disease. * ## Ly m ph n od e si ze % c ha ng e fr om b as el in e in S PD o f t ar ge t l es io n CLL disease-evaluable patientsa n=26 Objective response rate (ORR)b, % (95% CI) 69.2 (48.2–85.7) Best response, n (%) CR 0 (0.0) PR / PR-L 18 (69.2) SD 6 (23.1) PD 2 (7.7) aPatients without identified target lesion(s) at baseline are evaluated as disease-evaluable per iwCLL, while they may not be represented in waterfall plot; bObjective response rate includes CR + CRi + nPR + PR-L + PR Patient with Richter’s Transformation (RT) to Hodgkin's on biopsy Patients with CNS involvement at baseline* #


 
15 NX-5948 Efficacy: Duration of Treatment Durable responses seen in heavily pretreated patients with CLL BCL2i cBTKi ncBTKi ≥2 prior BTKi Select prior therapies * *Patient with Richter’s transformation to Hodgkin's on biopsy Median duration of treatment, months (range) 2.8 (0.2–15.2) Patients dose escalated during treatment, n 9 Data cutoff: 17 April 2024 Yes


 
0 10 20 30 40 50 60 0 50 100 150 200 250 300 Ce ll Co un ts (K /µ L) Study day ALC 16 16 weeks: Partial Response LN: –64% (>50% PR) Spleen: –68% (>50% PR) Plts: >100 (CR) Hgb: >11 g/dL (CR) Malignant cells in CSF: Y Case Study: Patient with CLL and CNS Involvement Deepening response over time approaching complete response criteria Baseline LN SPD: 625 cm2 Spleen: 16.1 cm Plts: 93 x 109/L Hgb: 10.4 g/dL Malignant cells in CSF: Y 24 weeks: Partial Response LN: –65% (>50% PR) Spleen: –55% (>50% PR) Plts: >100 (CR) Hgb: >11 g/dL (CR) Malignant cells in CSF: N 36 weeks: Partial Response LN: all <1.5 cm (CR) Spleen: –87% (>50% PR)* Plts: >100 (CR) Hgb: >11 g/dL (CR) Malignant cells in CSF: N Data cutoff: 17 April 2024 References Hansen GM. Oral presentation at AACR Annual Meeting 2024, San Diego, CA. April 9, 2024 Prior treatments 1. Idelalisib: 2015 – 2018 2. Venetoclax-Rituximab: 2018 – 2022 3. Acalabrutinib: 2022 – June 2023 Molecular and cytogenetic features TP53, BCL2, SF3B1, Del (17p) *Normal spleen: 13 cm; 36 week: 13.4 cm The overall response assessments are from the investigators while the individual parameter response assessment criteria are calculated per iwCLL from the data entered LN, lymph nodes; Plts, platelets; Hgb, hemoglobin; CSF, cerebrospinal fluid 8 weeks: Stable Disease LN: –53% (>50% PR) Spleen: –13% (–49% to +49% SD) Plts: >100 (CR) Hgb: >11 g/dL (CR) Malignant cells in CSF: Y


 
Mutation Status and BTK Degradation NX-5948 induces rapid and robust degradation of wild-type and mutant BTK 17 Patients with CLL (n=30) Mutation status, n (%) BTKa 13 (43.3) C481S 7 (23.3) L528b 2 (6.7) T474c 3 (10.0) V416d 1 (3.3) G541V 1 (3.3) aPatients could have multiple BTK mutations; BTK mutations were tested at baseline by NGS centrally. ≥5% allelic frequency is reported. bL528W, L528S; cT474F,T474I; dV416L, V416M. Data cutoff: 17 April 2024MFI, mean fluorescence intensity 0 1000 2000 3000 4000 5000 BTK degradation in CLL with BTK mutations BT K M FI (b ac kg ro un d su bt ra ct ed ) M ea n ± SE M Day 2 Day 15 Day 22 Day 29Day 8 BTK T474F/I (n=3) BTK C481S (n=7) BTK L528W/S (n=2*) BTK V416L/M (n=1) *1 patient has both BTK L528S and G541S Wild type (n=15) *1 patient has both BTK L S and G541S B F/I (n=3) B 481S (n=7) B 528 / (n=2*) B L/ ild type (n=15)


 
18 Clinical Activity in Patients with Baseline Mutations Treatment resistance and poor-prognosis genetic mutations *Patient with Richter’s transformation to Hodgkin's on biopsy • Baseline treatment-resistance and poor prognosis mutations were common, indicating a genetically diverse and hard-to-treat CLL patient population • No genotypic profile was linked to intrinsic NX-5948 resistance Data cutoff: 17 April 2024 * * Treatment resistance mutations Poor- prognosis mutations BTK PLCG2 TP53 SF3B1 ATM NOTCH1


 
19 Clinical Activity in Patients with Baseline Mutations Treatment resistance and poor-prognosis genetic mutations • Baseline treatment-resistance and poor prognosis mutations were common, indicating a genetically diverse and hard-to-treat CLL patient population • No genotypic profile was linked to intrinsic NX-5948 resistance * Data cutoff: 17 April 2024 * BTK mutations (43% of patients) BTK T474F BTK V416M BTK T474I BTK V416L BTK C481S BTK L528S BTK G541V BTK L528W *Patient with Richter’s transformation to Hodgkin's on biopsy


 
• NX-5948 was well tolerated in patients with NHL and CLL, with no increased safety signal at higher doses • Deep and durable clinical responses were observed in a difficult-to-treat CLL patient population: – Heavily pretreated patient population with unfavorable genetic mutations associated with poor prognosis and BTK inhibitor resistance mutations – Robust clinical activity in patients with CLL with 69.2% ORR and all responses ongoing as of April 17, 2024: o Rapid responses - majority of responses (15/18) seen at the first scan (8 weeks) o Durable and deepening responses with longer time on treatment (27/31 patients still on study) o No patient profile associated with intrinsic resistance to NX-5948 • These data support the continued development of NX-5948 in the treatment of CLL where Phase 1b dose expansion is planned. Additional data in NHL/WM will be presented in 2H 2024 20 Conclusions: Positive results from the ongoing Phase 1 study of novel BTK degrader NX-5948


 
Paula G. O’Connor, MD Chief Medical Officer Nurix Therapeutics 21


 
Two additional case studies highlighting the activity of NX-5948 to address patients with high unmet medical needs NX-5948: The Patient Journey


 
Relevant Medical History • Atrial fibrillation: Dx Jul 2022 • Hypothyroidism: Dx May 2022 • Hypertension: Dx Jul 2022 • Fatigue: Dx Oct 2023 • Disease related cytopenias: Dx 2022-23 Molecular, Cytogenetics and other baseline features • Del(11q, 13q)*, IGHV unmutated* • BTK T474I mutation** • Bulky disease (5 of 6 target lymph nodes >5 cm in longest diameter) • Splenomegaly 23 Case Study 1: CLL Patient with Extensive Prior Treatment Site City of Hope Age, M/F 61, male Diagnosis CLL Initial diagnosis 2008 Prior progression 12 Sep 2023 Dose 200 mg daily IwCLL response PR Status On treatment Current cycle Cycle 8 Prior Systemic Therapies • FCR: 2009-2010 • Ibrutinib + rituximab: 2012 • Venetoclax: 2018 • Acalabrutinib: 2021 • Chlorambucil + obinutuzumab: 2021 • Zanubrutinib: 2022 • Lisocabtagene maraleucel: 2022 • Duvelisib: 2022-23 • Pirtobrutinib + obinutuzumab: 2023 • R-CHOP: 2023 • Pirtobrutinib + bendamustine + obinutuzumab: 2023 Reason for pirtobrutinib + bendamustine + obinutuzumab discontinuation: Progressive disease Data cutoff: 31 May 2024* From medical records; ** Central lab


 
0 5 10 15 20 25 0 20 40 60 80 100 120 140 160 180 200 Ce ll Co un t ( K/ uL ) Study Day ALC 24Data cutoff: 31 May 2024 Case Study 1: CLL Patient with Extensive Prior Treatment Rapid and sustained lymph node reduction with improving hematologic features Baseline LN SPD: 163.2 cm2 Spleen: 16.1 cm (abnl) Plts: 109 K/µl (normal per iwcLL) Hgb: 10.3 g/dL (low) Constitutional sx: fatigue 8 weeks: Partial Response LN: -64.5% ( > 50% PR) Spleen: -19.4% (SD) Plts: 156 K/µL (Normal per iwCLL) Hgb: 12 g/dL (CR) Constitutional sx: resolved 16 weeks: Partial Response LN: -71.2% ( > 50% PR) Spleen: +16.1 % (SD) Plts: 137 K/µL (Normal per iwCLL) Hgb: 12.2 g/dL (CR) Constitutional sx: resolved The overall response assessments are from the investigators, while the individual parameter response assessment criteria are calculated per iwCLL from the data entered.


 
25 Relevant Medical History • Supraventricular tachycardia: Jun 2018 - present • Peripheral neuropathy: Oct 2018 - present • Hearing loss: Apr 2008 - present • Tinnitus: Apr 2008 - present • Chronic kidney disease: Jul 2019 – present Prior Systemic Therapies • Campath + rituximab: Nov 2008 – Mar 2009 • Bendamustine + rituximab: Nov 2010 – Mar 2011 • Ibrutinib: Dec 2013- Aug 2018 • Acalabrutinib: Aug 2018 – Aug 2019 • Ublituximab+ umbralisib+ venetoclax: 13 Aug 2019 – 13 Jul 2020 Molecular/ Cytogenetics • IgHV unmutated*, Del 11q, Del13q* • TP53 mutated**, SF3B1 mutated**, NOTCH1 mutated** • PLCG2 mutated** Baseline clinical features • Bulky disease (1 target lymph node >5cm longest diameter, 6 total) • Splenomegaly Site Northwestern Age, M/F 66, M Diagnosis CLL Initial diagnosis 2008 Prior progression 2 Nov 2023 Dose 200 mg daily IwCLL response PR Status On treatment Current cycle Cycle 8 Case Study 2: CLL Patient with High-Risk Features Extensive prior treatment with CIT, nBTKi, BCL2i, and PI3K Data cutoff: 31 May 2024* From medical records; ** Central lab


 
0 20 40 60 80 100 120 140 160 180 0 20 40 60 80 100 120 140 160 180 200 Ce ll Co un t ( K/ ul ) Study Day ALC 26 8 weeks: Partial Response LN: -59% ( > 50% PR) Spleen: -68% (> 50% PR) Plts: 332 K/µl (Normal) Hgb: + 21% (SD) Initial lymphocytosis consistent with BTK targeted MOA.*Normal spleen= <13 cm 24 wk: 12.8 cm The overall response assessments are from the investigators, while the individual parameter response assessment criteria are calculated per iwCLL from the data entered. 16 weeks: Partial Response LN: -72% ( > 50% PR) Spleen: - 92% ( > 50% PR) Plts: 306 K/µl (Normal) Hgb: > 11 (CR) 24 weeks: Partial Response LN: -80% ( > 50% PR) Spleen*: <13 cm (CR) Plts: 299 K/µl (Normal) Hgb: > 11 (CR) Case Study 2: CLL Patient with High-Risk Features Early clinical activity deepening over time Baseline LN SPD: 85.22 cm2 Spleen*: 18.9 cm (abnl) ALC: 130 K/µl (high) Plts: 242 K/µl (normal) Hgb: 8 g/dL (low) Data cutoff: 31 May 2024


 
NX-5948: Next Steps in CLL


 
Next Steps: Expand Phase 1b in Select CLL Populations Enable Pivotal Trial Initiation in 2025 Phase 1b expansion in CLL Pivotal trials in 3L+ CLLCLL/SLL (n = 80-160) Two monotherapy dose levels to be selected from Phase 1a dose escalation Includes multiple cohorts in clinically meaningful populations e.g. prior BTKi and BCL-2i, BTKi resistance mutations, 2L with high- risk genetics (TP53 mut/del 17p) 3L+ monotherapy post-BTKi/post-BCL2i (Fast Track Designation) Single-arm and randomized controlled trial options 1L/2L monotherapy study Randomized controlled trial 1L/2L fixed duration combinations Randomized controlled trial 28 Combination basket study CLL/SLL (n = TBD) Potential combinations for CLL: • venetoclax • obinutuzumab • rituximab Pivotal trials in 1L/2L CLL


 
Conclusions: Nurix Plans To Accelerate Development of NX-5948 with First Pivotal Study To Be Initiated in 2025  CLL: Clear demonstration of clinical activity in difficult to treat populations • Advancing to an expanded Phase 1b across a wide range of CLL subpopulations • Preparing for initiation of pivotal trial(s) in 2025 in 3L+ CLL where we have Fast Track Designation with a ~70% ORR observed to date • Planning for a broad and parallel Phase 3 program across lines of therapy as monotherapy and in combination with other approved agents  NHL: Broad activity with deep responses seen across NHL subtypes • Preparing for Phase 1b expansion in selected NHL subtypes with initial focus on monotherapy in indolent indications • Additional data in NHL patients will be presented in 2H 2024 29


 
Arthur T. Sands, MD, PhD Chief Executive Officer Nurix Therapeutics 30


 
Nurix Therapeutics: Planning for Success  We believe NX-5948 is a potential best-in-class drug that can replace BTK inhibitors and offer patients important treatment options  We have a team that can successfully accelerate development to move to pivotal trial(s) in 2025  We have built a robust and growing pipeline of oncology and immunology drugs both wholly-owned and with industry leading partners and retained product rights  We are appreciative of support from our investors, our investigators, and most importantly from our patients 31


 
Questions & Answers 32


 
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