BCR

Ad hoc announcement pursuant to Art. 53 LR Scemblix, a new first-line option for adults with CML, is first to show superior efficacy and favorable safety and tolerability profile in a Phase III trial vs. all standard of care (SoC) therapies1-3Patients on Scemblix also had fewer dose reductions and half the rate of adverse reactions leading to treatment discontinuation1-3Nearly 50% of CML patients do not meet efficacy milestones (MMR) with current SoC and almost 25% discontinue or switch therapies within one year of treatments4-5Scemblix now approved for newly diagnosed and previously treated CML, allowing four times the patients access to potential new standard of care Basel, October 29, 2024 – Novartis announced today that Scemblix® (asciminib) was granted accelerated approval by the US Food and Drug Administration (FDA) for adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). The accelerated approval is based on major molecular response rate (MMR) at week 48 from the ASC4FIRST Phase III trial that compared once daily Scemblix to all other investigator-selected (IS) standard of care (SoC) tyrosine kinase inhibitors (TKIs) (imatinib, nilotinib, dasatinib, and bosutinib). In the study, Scemblix demonstrated superior MMR rates in both primary endpoints at week 48 vs. IS SoC TKIs and imatinib alone1-3. Continued approval for the newly diagnosed indication may be contingent upon verification and description of clinical benefit from confirmatory evidence. The expanded indication in Ph+ CML-CP increases the population eligible for Scemblix by approximately four times, including newly diagnosed and previously treated adults. Newly diagnosed patients will now have access to a treatment that has shown superior efficacy vs. all standard of care therapies and a favorable safety and tolerability profile. “Many patients who are newly diagnosed with CML struggle to navigate this chronic condition and may switch or even stop treatment because of side effects that interrupt their daily lives,” said Lee Greenberger, Ph.D., Chief Scientific Officer at The Leukemia & Lymphoma Society. “That’s why approvals of new first-line treatment options are so important. For patients, finding a medicine that’s right for them at the very beginning of treatment may lead to better long-term disease control with fewer side effects.” While TKIs have transformed CML into a chronic disease, efficacy and safety challenges continue to hinder long-term treatment success for many patients. Many newly diagnosed patients do not meet molecular response goals, and many discontinue or change treatment due to intolerance4-23. Nearly half of CML patients do not meet efficacy milestones (MMR) and almost one in four patients discontinue or switch treatment within one year4-5. “While there are a range of effective TKIs currently available for newly diagnosed patients, clinicians frequently have had to weigh sacrificing either efficacy or tolerability,” said Jorge Cortes, M.D., Director, Georgia Cancer Center. “In the first-of-its-kind ASC4FIRST trial, Scemblix achieved impressive results across all three parameters of efficacy, safety and tolerability versus all standard of care TKIs. This Scemblix data has the potential to be practice-changing.” The FDA approval of Scemblix is based on results from the Phase III ASC4FIRST trial in patients newly diagnosed with Ph+ CML-CP. Data showed: Nearly 20% more patients treated with Scemblix achieved MMR vs. IS SoC TKIs (imatinib, nilotinib, dasatinib and bosutinib) (68% vs. 49%, < 0.001) and nearly 30% more patients achieved MMR vs. imatinib alone (69% vs. 40%, < 0.001) at week 481-2Scemblix is the first CML treatment to show superior efficacy along with a favorable safety and tolerability profile vs. imatinib and second generation TKIs, with fewer treatment-related grade ≥3 ARs (25.5% vs. 33% and 42%), dose reductions (6% vs. 14% and 24%), and half the rate of ARs leading to treatment discontinuation (4.5% vs. 11% and 9.8%)1-3Patients treated with Scemblix also achieved deeper rates of molecular responses including MR4 compared with IS-TKIs and imatinib alone (41% vs. 22% and 16%) by week 481-2In newly diagnosed patients, the safety profile was consistent with previous registration studies with no new safety concerns observed. The most common ARs (≥ 20%) were musculoskeletal pain, rash, fatigue, upper respiratory tract infection, headache, abdominal pain and diarrhea1-3 The ASC4FIRST trial remains ongoing, with the next scheduled analysis at week 96 to evaluate the key secondary endpoint (MMR at week 96) and additional secondary endpoints. The approval was also supported by preliminary data from the Phase II ASC2ESCALATE study, which includes Ph+ CML-CP patients who have been previously treated with one prior TKI with discontinuation due to treatment failure, warning, or intolerance. Data will be shared at a future medical meeting. “We are proud to help redefine CML treatment once again with Scemblix, as we continue to deliver on our 20+ year commitment to innovation and support in CML,” said Victor Bulto, President US, Novartis. “Despite many advances in the field, patients still need treatment options that are highly effective with a favorable tolerability profile to help enable them to achieve meaningful outcomes as they manage chronic conditions. With this approval, we can offer newly diagnosed adult Ph+ CML-CP patients a new treatment option that combines both, with the potential to change the trajectory of many more people living with CML.” About ASC4FIRST Phase III Clinical TrialASC4FIRST (NCT04971226) is a Phase III, head-to-head, multi-center, open-label, randomized study of oral Scemblix® 80 mg QD vs. IS first- or second-generation TKIs (imatinib, nilotinib, dasatinib or bosutinib) in 405 adult patients with newly diagnosed Ph+ CML-CP1,24. The two primary endpoints of the study are to compare efficacy of asciminib vs. IS SoC TKIs and to compare efficacy vs. that of TKI within the stratum of participants with imatinib as pre-randomization selected TKI, based on proportion of patients that achieve MMR at week 481,24. The study remains ongoing with key secondary endpoints of proportion of patients that achieve MMR at week 96 and a safety endpoint of discontinuation of study treatment due to an AE (TTDAE) by week 961,24. The study also assesses additional secondary safety and efficacy endpoints, including MMR, MR4, MR4.5, complete hematological response (CHR) and BCR::ABL1 ≤1% at and by all scheduled data collection time points; duration of and time to first MMR, MR4 and MR4.5; time to treatment failure; event-free survival, failure-free survival, progression-free survival and overall survival1,24. About Scemblix® (asciminib)Scemblix® is the first CML treatment that works by Specifically Targeting the ABL Myristoyl Pocket (referred to as a STAMP inhibitor in scientific literature)25-27. The current approved CML treatments are TKIs that target the ATP-binding site (ATP-competitive) 27. Scemblix was granted accelerated approval in the US to treat newly diagnosed adults and is also approved for previously treated adult patients with Ph+ CML-CP. Scemblix received Breakthrough Therapy designation for the treatment of newly diagnosed adult patients and was reviewed under the FDA’s Real-Time Oncology Review (RTOR) program28-30. It is approved in more than 75 countries, including the EU, to treat those who have previously been treated with two or more TKIs with Ph+ CML-CP28,29,31. In some countries, including the US, Scemblix is also approved in patients with Ph+ CML-CP with the T315I mutation28-30. Scemblix is being studied across multiple treatment lines for Ph+ CML-CP, both as a monotherapy and in combination1,24-26,29,32-44. Patient Access and SupportNovartis, with its 20+ year history in CML, is committed to continuing to address areas of unmet patient need and reducing barriers to patient access and affordability that prevent patients from benefiting from innovation. Novartis Patient Support is available to help guide eligible patients through the various aspects of getting started on treatment including help understanding insurance coverage and identifying potential financial assistance options. Patients or providers can call 866-433-8000 or visit support.scemblix.com to learn more. About Novartis Commitment to CMLNovartis has a long-standing scientific commitment to patients living with CML. For more than two decades, our bold science has helped transform CML from a life-limiting condition for many patients. Despite these advancements, there’s still work to be done. We continue to research ways to target the disease more selectively and to address the challenges of not reaching treatment efficacy goals, experiencing treatment resistance and/or intolerance that many patients face. Our legacy inspires our future innovation – we continue to lead the way in developing novel medicines to address serious unmet needs in CML. Our commitment also goes beyond science. Our 20+ year collaboration with the Max Foundation has provided access to Gleevec (imatinib), Tasigna (nilotinib) and now Scemblix and is delivering tremendous patient impact in low- and middle-income countries, with over 100,000 patients supported to date. DisclaimerThis press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “may,” “committed,” “contingent,” “lead,” “continue,” “ongoing,” “to deliver,” “allowing,” “continuing,” “commitment,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for Scemblix, or regarding potential future revenues from Scemblix. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that Scemblix will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that Scemblix will be commercially successful in the future. In particular, our expectations regarding Scemblix could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. About Novartis Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide. Reimagine medicine with us: Visit us at https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram. References Scemblix (asciminib) Prescribing information. East Hanover, New Jersey, USA: Novartis Pharmaceuticals Corporation; October 2024.Hochhaus A, Wang J, Dong-Wook K, et al. Asciminib in Newly Diagnosed Chronic Myeloid Leukemia. N Engl J Med. 2024. doi:10.1056/NEJMoa2400858 CABL001J SCS/RMP. Novartis Pharmaceuticals Corp; 2024.Kota VK, Wei D, Yang D, et al. Treatment Patterns and Modifications of Tyrosine Kinase Inhibitors (TKI) Therapy in Early Lines in Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Real-World Analysis from a Large Commercial Claims Database in the United States (US). Blood. 2023;142:5190. Hochhaus, A., & Ernst, T. 2021. TKI discontinuation in CML: How do we make more patients eligible? How do we increase the chances of a successful treatment-free remission? Hematology Am Soc Hematol Educ Program, 2021(1), 106–112. Hochhaus A, Saglio G, Hughes TP, et al. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia. 2016;30(5):1044-1054. doi:10.1038/leu.2016.5 Brümmendorf TH, Cortes JE, de Souza CA, et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukaemia: results from the 24-month follow-up of the BELA trial. Br J Haematol. 2015;168(1):69-81. doi:10.1111/bjh.13108 Cortes JE, Gambacorti-Passerini C, Deininger MW, et al. Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial. J Clin Oncol. 2018;36(3):231-237. doi:10.1200/JCO.2017.74.7162 Hehlmann R, Cortes JE, Zyczynski T, et al. Tyrosine kinase inhibitor interruptions, discontinuations and switching in patients with chronic-phase chronic myeloid leukemia in routine clinical practice: SIMPLICITY. Am J Hematol. 2019;94(1):46-54. doi:10.1002/ajh.25306 Claudiani S, Chughtai F, Khan A. et al. Long-term outcomes after upfront second-generation tyrosine kinase inhibitors for chronic myeloid leukemia: managing intolerance and resistance. Leukemia. 2024;38:796 - 802. doi:10.1038/s41375-024-02187-w Kohlbrenner K, Galuschek N, Fabarius A, et al. Therapy in Patients with Chronic Myeloid Leukemia Outside of Clinical Trials: Results of the German CML-Registry (CML-VI). Blood. 2022;140(Supplement 1):947 - 949. doi:10.1182/blood-2022-159412 Cortes JE, Khoury HJ, Kantarjian HM, et al. Long-term bosutinib for chronic phase chronic myeloid leukemia after failure of imatinib plus dasatinib and/or nilotinib. Am J Hematol. 2016;91(12):1206-1214. doi:10.1002/ajh.24536 Garg RJ, Kantarjian H, O'Brien S, et al. The use of nilotinib or dasatinib after failure to 2 prior tyrosine kinase inhibitors: long-term follow-up. Blood. 2009;114(20):4361-4368. doi:10.1182/blood-2009-05-221531 Steegmann JL., Baccarani M, Breccia M, et al. European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia. Leukemia. 2016;30:1648-1671. doi:10.1038/leu.2016.104 Hochhaus A, Larson RA, Guilhot F, et al. Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia. N Engl J Med. 2017;376: 917 - 927. doi:10.1056/NEJMoa1609324 Cortes JE, Saglio G, Kantarjian HM, et al. Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial. J Clin Oncol. 2016;34:2333-2340. doi:10.1200/JCO.2015.64.8899 Akard LP, Albitar M, Hill CE, Pinilla-Ibarz, J. The “Hit Hard and Hit Early” Approach to the Treatment of Chronic Myeloid Leukemia: Implications of the Updated National Comprehensive Cancer Network Clinical Practice Guidelines for Routine Practice. Clin Adv Hematol Oncol. 2013;11(7):421-432. Cortes JE, Kim DW, Pinilla-Ibarz J, et al. Ponatinib efficacy and safety in Philadelphia chromosome–positive leukemia: final 5-year results of the phase 2 PACE trial. Blood. 2018;132(4):393-404. doi:10.1182/blood-2016-09-739086 Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34:966-984. doi:10.1038/s41375-020-0776-2 Flis S, Chojnacki T. Chronic myelogenous leukemia, a still unsolved problem: pitfalls and new therapeutic possibilities. Drug Des Devel Ther. 2019;13:825-843. doi:10.2147/DDDT.S191303 Cortes, J., Lang, F. Third-line therapy for chronic myeloid leukemia: current status and future directions. J Hematol Oncol. 2021;14:44. doi:10.1186/s13045-021-01055-9 Shyam Sunder S., Sharma UC, Pokharel S. Adverse effects of tyrosine kinase inhibitors in cancer therapy: pathophysiology, mechanisms and clinical management. Sig Transduct Target Ther. 2023;8:262. doi:10.1038/s41392-023-01469-6 Yoshifuji K, Sasaki K. Adverse events and dose modifications of tyrosine kinase inhibitors in chronic myelogenous leukemia. Front Oncol. 2022;12. doi:10.3389/fonc.2022.1021662 A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP (ASC4FIRST). ClinicalTrials.gov identifier: NCT04971226. Updated March 25, 2024. Accessed March 26, 2024. https://clinicaltrials.gov/study/NCT04971226 Rea D, Mauro MJ, Boquimpani C, et al. A Phase 3, Open-Label, Randomized Study of Asciminib, a STAMP Inhibitor, vs Bosutinib in CML After 2 or more prior TKIs. Blood. 2021;138(21):2031-2041. doi:10.1182/blood.2020009984 Cortes JE, Hughes TP, Mauro MJ, et al. Asciminib, a First-in-Class STAMP Inhibitor, Provides Durable Molecular Response in Patients (pts) with Chronic Myeloid Leukemia (CML) Harboring the T315I Mutation: Primary Efficacy and Safety Results from a Phase 1 Trial. Oral presentation at: ASH Annual Meeting; Dec. 7, 2020. Schoepfer J, Jahnke W, Berellini G, et al. Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1. J Med Chem. 2018;61(18):8120-8135. doi:10.1021/acs.jmedchem.8b01040 Scemblix. US FDA Prescribing Information. Novartis Pharmaceuticals; 2021. Novartis data on file. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Chronic Myeloid Leukemia Version 2.2024. December 5, 2023. Accessed April 3, 2024. https://www.nccn.org/professionals/physician_gls/pdf/cml.pdf Scemblix. EMA Summary of Product Characteristics. Novartis Europharm Limited; 2022. Wylie AA, Schoepfer J, Jahnke W, et al. The allosteric inhibitor ABL001 enables dual targeting of BCR–ABL1. Nature. 2017;543(7647):733-737. doi:10.1038/nature21702 Hughes TP, Mauro MJ, Cortes JE, et al. Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure. N Engl J Med. 2019; 381(24):2315-2326. doi:10.1056/NEJMoa1902328 Hughes TP, et al. Expanded Phase 1 Study of ABL001, a Potent, Allosteric Inhibitor of BCR-ABL, Reveals Significant and Durable Responses in Patients with CML-Chronic Phase with Failure of Prior TKI Therapy. Presented at: ASH Annual Meeting & Exposition; Dec. 5, 2016. Ottmann OG, Alimena G, DeAngelo DJ, et al. ABL001, a Potent, Allosteric Inhibitor of BCR-ABL, Exhibits Safety and Promising Single- Agent Activity in a Phase I Study of Patients with CML with Failure of Prior TKI Therapy. Blood. 2015;126(23):138. doi:10.1182/blood.V126.23.138.138 Mauro MJ, Kim DW, Cortes J, et al. Combination of Asciminib Plus Nilotinib (NIL) or Dasatinib (DAS) in Patients (PTS) with Chronic Myeloid Leukemia (CML): Results from a Phase 1 Study. Presented at: EHA Annual Meeting; June 15, 2019. Cortes JE, Lang F, Kim DW, et al. Combination Therapy Using Asciminib Plus Imatinib (IMA) in Patients (PTS) with Chronic Myeloid Leukemia (CML): Results from a Phase 1 Study. Presented at: EHA Annual Meeting; June 15, 2019. Manley PW, Barys L, Cowan-Jacob SW. The specificity of asciminib, a potential treatment for chronic myeloid leukemia, as a myristate-pocket binding ABL inhibitor and analysis of its interactions with mutant forms of BCR-ABL1 kinase. Leuk Res. 2020;98:106458. doi:10.1016/j.leukres.2020.106458 Study of Efficacy of CML-CP Patients Treated with ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs. ClinicalTrials.gov identifier: NCT03106779. Updated February 7, 2024. Accessed April 3, 2024. https://clinicaltrials.gov/ct2/show/NCT03106779 Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and WithoutT315I Mutation (AIM4CML). ClinicalTrials.gov identifier: NCT04666259. Updated September 7, 2023. Accessed April 3, 2024. https://clinicaltrials.gov/ct2/show/NCT04666259 Study of Efficacy And Safety Of Asciminib In Combination With Imatinib In Patients With Chronic Myeloid Leukemia In Chronic Phase (CML-CP). ClinicalTrials.gov identifier: NCT03578367. Updated March 22, 2024. Accessed April 3, 2024. https://clinicaltrials.gov/ct2/show/NCT03578367 Study of Efficacy and Safety of CML-CP Patients Treated With Asciminib Versus Best Available Therapy, Previously Treated With 2 or More Tyrosine Kinase Inhibitors. ClinicalTrials.gov identifier: NCT04795427. Updated October 19, 2023. Accessed April 3, 2024. https://clinicaltrials.gov/ct2/show/NCT04795427 A Phase I Study of Oral ABL001 in Patients With CML or Ph+ ALL. ClinicalTrials.gov identifier: NCT02081378. Updated March 18, 2024. Accessed April 3, 2024. https://clinicaltrials.gov/ct2/show/NCT02081378 Asciminib Treatment Optimization in ≥ 3rd Line CML-CP. ClinicalTrials.gov identifier: NCT04948333. Updated February 28, 2024. Accessed April 3, 2024. https://clinicaltrials.gov/ct2/show/NCT04948333 # # # Novartis Media RelationsE-mail: media.relations@novartis.com Central North America Anja von Treskow +41 79 392 9697 Michael Meo +1 862 274 5414 Anna Schäfers +41 79 801 7267 SwitzerlandSatoshi Sugimoto +41 79 619 2035 Novartis Investor RelationsCentral investor relations line: +41 61 324 7944E-mail: investor.relations@novartis.com Central North America Isabella Zinck +41 61 324 7188 Sloan Simpson +1 862 345 4440 Nicole Zinsli-Somm +41 61 324 3809 Jonathan Graham +1 201 602 9921 Imke Kappes +41 61 324 8269 Parag Mahanti +1 973 876 4912

Initiated Phase 1b dose expansion of NX-5948 in chronic lymphocytic leukemia patient population with Fast Track Designation from the FDA Initiated Phase 1b dose expansion of NX-5948 in Waldenstrom’s macroglobulinemia, follicular lymphoma and marginal zone lymphoma patients Reinitiated enrollment for NX-2127 in a Phase 1a/b trial in oncology Presented preclinical data on Degrader-Antibody Conjugates (DACs), a new class of therapeutics Well capitalized with cash and marketable securities of $ 457.5 million SAN FRANCISCO, Oct. 11, 2024 (GLOBE NEWSWIRE) -- 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 reported financial results for the third quarter ended August 31, 2024, and provided a corporate update. “We continue to make great progress and remain focused on execution as we advance our pipeline of wholly owned and partnered programs in oncology, inflammation and immunology,” said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. “As we approach the end of the year, we are well capitalized and look forward to building further momentum as we head into clinical data readouts in the fourth quarter of 2024 and the initiation of pivotal studies of NX-5948 in 2025.” Recent Business Highlights Expanded clinical development of NX-5948: In the third quarter of 2024, Nurix initiated the Phase 1b portion of its ongoing Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies. The Phase 1b expansion includes a randomization to a low dose (200mg QD) or a high dose (600mg QD) of NX-5948 in patients with chronic lymphocytic leukemia (CLL) who have been treated with at least two prior regimens including a Bruton’s tyrosine kinase (BTK) inhibitor and a BCL2 inhibitor. This is the patient population for which the FDA granted Nurix Fast Track designation in January 2024. Cohorts were also initiated to evaluate NX-5948 in patients with Waldenstrom’s macroglobulinemia (WM), marginal zone lymphoma and follicular lymphoma. Re-initiated enrollment in NX-2127 Phase 1a/b trial: Nurix recently reinitiated enrollment with its new chirally controlled drug product in a standard dose escalation study within the current Phase 1a/1b trial. As previously announced, in March 2024, the U.S. Food and Drug Administration (FDA) lifted a manufacturing-related, partial clinical hold on the NX-2127 clinical trial. Patients enrolled prior to the partial clinical hold who are deriving clinical benefit continue to receive uninterrupted treatment with the original drug product. Presented early preclinical data from ongoing collaboration with Pfizer to develop Degrader-Antibody Conjugates, a new class of therapeutics: On September 10, 2024, at the ADC & Radiopharmaceuticals Pharma & Biotech Partnering Summit, Nurix’s chief scientific officer, Gwenn M. Hansen, Ph.D., presented an outline of the advantages of DACs, Nurix’s matrixed approach to the generation and optimization of DACs using its DELigase platform, and early preclinical data demonstrating cell-type selective degradation of targeted proteins by DACs. Nurix believes that DACs may represent a next generation of antibody drug conjugate (ADC) technology that could broaden its use in oncology and potentially other indications. DACs combine the catalytic activity of a targeted protein degrader with the tissue specificity of an antibody which has the potential to provide improved therapeutic index and broader applicability than standard ADCs and which can potentially be applied to any protein target in any tissue. Upcoming Program Highlights* NX-5948: NX-5948 is an investigational, orally bioavailable degrader of BTK that is currently being evaluated in the Phase 1b portion of a Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies. By year-end 2024, Nurix plans to present additional clinical data from this study for patients with CLL. Later this month, at the 12th International Workshop on Waldenstrom’s Macroglobulinemia (IWWM 12), Nurix will present a clinical update from this study on patients with WM. Additional information on the Phase 1a/b clinical trial can be accessed at ( NCT05131022 ). Nurix is also conducting a Phase 1 healthy volunteer study to assess food effects and drug-drug interactions in anticipation of initiating pivotal development in 2025. Additional information on this Phase 1 clinical trial can be accessed at ( NCT06593457 ). Nurix continues to lay the groundwork for indication selection in autoimmune and inflammatory diseases and expects to complete ongoing preclinical studies in 2024 that can enable an investigational new drug (IND) application for NX-5948 in autoimmune indications. An abstract titled “NX-5948, a Clinical-Stage BTK Degrader, Achieves Deep Suppression of BCR, TLR, and FcR Signaling in Immune Cells and Demonstrates Efficacy in Preclinical Models of Arthritis and Other Inflammatory Diseases” was accepted for a poster presentation at the upcoming annual meeting of the American College of Rheumatology (ACR 2024), being held November 14–19, 2024, in Washington, D.C. NX-2127: NX-2127 is an orally bioavailable BTK degrader that also degrades cereblon neosubstrates IKZF1 (Ikaros) and IKZF3 (Aiolos) for the treatment of relapsed or refractory B‑cell malignancies. Nurix is conducting a Phase 1a/b clinical trial of NX-2127, which includes Phase 1b expansion cohorts focused on patients with diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). Nurix recently introduced a new chirally controlled drug product, which is being evaluated in a dose escalation within this Phase 1a/b trial. Future clinical updates are anticipated in 2025. Additional information on the clinical trial can be accessed at ( NCT04830137 ). NX-1607: NX-1607 is an orally bioavailable inhibitor of the E3 ligase Casitas B-lineage lymphoma proto-oncogene B (CBL-B) for immuno-oncology indications, including a range of solid tumor types and lymphoma. Nurix is evaluating NX-1607 in an ongoing Phase 1 trial in monotherapy and in a combination cohort utilizing paclitaxel in adults in a range of oncology indications. This study includes a thorough investigation of both dose and schedule in Phase 1a. Nurix anticipates providing a program update by year-end 2024. Additional information on the clinical trial can be accessed at ( NCT05107674 ). GS-6791 (previously NX-0479): GS-6791 is a potent, selective, oral IRAK4 degrader. Degradation of IRAK4 by GS-6791 has potential applications in the treatment of rheumatoid arthritis and other inflammatory diseases. Nurix’s partner, Gilead, is responsible for conducting IND-enabling studies and advancing this program to clinical development. An abstract titled “IRAK4 Degrader GS-6791 Inhibits TLR and IL-1R-Driven Inflammatory Signaling, and Ameliorates Disease in a Preclinical Arthritis Model” was accepted for a poster presentation at ACR 2024. STAT6 degrader: In April 2024, Nurix announced an extension of the ongoing research program with Sanofi for STAT6 (signal transducer and activator of transcription 6), a key drug target in type 2 inflammation, with the goal of nominating a development candidate in the first year of the extended term. Nurix remains on track for this goal. Continued pipeline advancement of strategic collaborations with Gilead, Sanofi and Pfizer: Nurix expects to continue to achieve substantial research collaboration milestones throughout the terms of its collaborations with Gilead, Sanofi and Pfizer. * Expected timing of events throughout this press release is based on calendar year quarters. Fiscal Third Quarter 2024 Financial Results Collaboration revenue for the three months ended August 31, 2024, was $12.6 million compared with $18.5 million for the three months ended August 31, 2023. Revenue from the collaboration with Gilead decreased as the initial research term for certain drug targets ended. The decrease was offset by an increase in revenue from the collaboration agreement with Pfizer that was entered into in the fourth quarter of fiscal year 2023. Research and development expenses for the three months ended August 31, 2024, were $55.5 million compared with $47.9 million for the three months ended August 31, 2023. The increase was primarily due to clinical and contract manufacturing costs as Nurix continued to accelerate the enrollment of NX-5948 and progress its other clinical trial programs for NX-2127 and NX-1607. General and administrative expenses for the three months ended August 31, 2024, were $11.7 million compared with $10.6 million for the three months ended August 31, 2023. The increase was primarily due to an increase in professional service and consulting costs. Net loss for the three months ended August 31, 2024, was $49.0 million, or ($0.67) per share, compared with $37.0 million, or ($0.68) per share, for the three months ended August 31, 2023. Cash, cash equivalents and marketable securities was $457.5 million as of August 31, 2024, compared to $452.5 million as of May 31, 2024. 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 cell and NK cells. Nurix is headquartered in San Francisco, California. For additional information visit . Forward-Looking Statements This press release contains statements that relate to future events and expectations and as such constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. When or if used in this press release, the words “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “may,” “outlook,” “plan,” “predict,” “should,” “will,” and similar expressions and their variants, as they relate to Nurix, may identify forward-looking statements. All statements that reflect Nurix’s expectations, assumptions or projections about the future, other than statements of historical fact, are forward-looking statements, including, without limitation, statements regarding: Nurix’s future financial or business performance; Nurix’s future plans, prospects and strategies; Nurix’s plans and expectations with respect to its current and prospective drug candidates; the tolerability, safety profile, therapeutic potential and other advantages of Nurix’s drug candidates; the planned timing and conduct of Nurix’s clinical trials; the planned timing for the provision of updates and findings from Nurix’s preclinical studies and clinical trials; the potential benefits of and Nurix’s expectations with respect to its strategic collaborations, including the achievement of research milestones; and the potential benefits and advantages of Nurix’s scientific approach, DELigase™ platform and Degrader-Antibody Conjugates. Forward-looking statements reflect Nurix’s current beliefs, expectations, and assumptions regarding the future of Nurix’s business, its future plans and strategies, its development plans, its preclinical and clinical results, future conditions and other factors Nurix believes are appropriate in the circumstances. 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) whether Nurix will be able to advance its drug candidates, obtain regulatory approval of and ultimately commercialize its drug candidates; (ii) uncertainties related to the timing and results of preclinical studies and clinical trials; (iii) whether Nurix will be able to fund development activities and achieve development goals; (iv) uncertainties related to the timing and receipt of payments from Nurix’s collaboration partners, including milestone payments and royalties on future product sales; (v) the impact of global business, political and macroeconomic conditions, cybersecurity events, instability in the banking system, and global events, including regional conflicts around the world, on Nurix’s business, clinical trials, financial condition, liquidity and results of operations; (vi) whether Nurix will be able 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 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. ir@nurixtx.com Elizabeth Wolffe, Ph.D. Wheelhouse Life Science Advisors lwolffe@wheelhouselsa.com Media Aljanae Reynolds Wheelhouse Life Science Advisors areynolds@wheelhouselsa.com - More - Nurix Therapeutics, Inc. Condensed Consolidated Statements of Operations (in thousands, except share and per share amounts) (unaudited) Three Months Ended Nine Months Ended August 31, August 31, 2024 2023 2024 2023 Revenue: Collaboration revenue $ 12,588 $ 18,467 $ 41,265 $ 41,828 License revenue — — — 20,000 Total revenue 12,588 18,467 41,265 61,828 Operating expenses: Research and development 55,481 47,856 154,408 139,435 General and administrative 11,718 10,623 35,227 32,122 Total operating expenses 67,199 58,479 189,635 171,557 Loss from operations (54,611 ) (40,012 ) (148,370 ) (109,729 ) Interest and other income, net 5,737 3,030 13,612 7,737 Loss before income taxes (48,874 ) (36,982 ) (134,758 ) (101,992 ) Provision for income taxes 82 — 262 — Net loss $ (48,956 ) $ (36,982 ) $ (135,020 ) $ (101,992 ) Net loss per share, basic and diluted $ (0.67 ) $ (0.68 ) $ (2.13 ) $ (1.88 ) Weighted-average number of shares outstanding, basic and diluted 72,779,381 54,390,859 63,384,174 54,227,491 Nurix Therapeutics, Inc. Condensed Consolidated Balance Sheets (in thousands) (unaudited) August 31, November 30, 2024 2023 Assets Current assets: Cash and cash equivalents $ 99,044 $ 54,627 Marketable securities, current 349,008 233,281 Prepaid expenses and other current assets 7,991 7,595 Total current assets 456,043 295,503 Marketable securities, non-current 9,472 7,421 Operating lease right-of-use assets 27,083 31,142 Property and equipment, net 17,069 16,808 Restricted cash 901 901 Other assets 3,032 3,823 Total assets $ 513,600 $ 355,598 Liabilities and stockholders’ equity Current liabilities: Accounts payable $ 3,918 $ 6,401 Accrued expenses and other current liabilities 27,828 24,970 Operating lease liabilities, current 6,553 7,489 Deferred revenue, current 47,997 48,098 Total current liabilities 86,296 86,958 Operating lease liabilities, net of current portion 20,590 23,125 Deferred revenue, net of current portion 29,858 45,022 Total liabilities 136,744 155,105 Stockholders’ equity: Common stock 67 49 Additional paid-in-capital 1,056,665 746,299 Accumulated other comprehensive loss 344 (655 ) Accumulated deficit (680,220 ) (545,200 ) Total stockholders’ equity 376,856 200,493 Total liabilities and stockholders’ equity $ 513,600 $ 355,598

SAN FRANCISCO, Oct. 09, 2024 (GLOBE NEWSWIRE) -- 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 that preclinical data will be presented from NX-5948, Nurix’s proprietary BTK degrader currently in Phase 1b development for B-cell malignancies and in IND enabling studies for autoimmune disease, and GS-6791/NX-0479, an IRAK4 degrader discovered in collaboration with Gilead Sciences and also in IND-enabling studies, in two posters at ACR Convergence 2024, the annual meeting of the American College of Rheumatology (ACR), being held November 14–19, 2024, in Washington, D.C. Poster Presentation Details: Title: NX-5948, a Clinical-Stage BTK Degrader, Achieves Deep Suppression of BCR, TLR, and FcR Signaling in Immune Cells and Demonstrates Efficacy in Preclinical Models of Arthritis and Other Inflammatory Diseases Presenting author: Mark Noviski, Ph.D. (Nurix Therapeutics, Inc.) Session: B Cell Biology & Targets in Autoimmune & Inflammatory Disease Session date and time: Saturday, November 16, 2024, 10:30 AM - 12:30 PM Abstract ID: 1857761 Title: IRAK4 Degrader GS-6791 Inhibits TLR and IL-1R-Driven Inflammatory Signaling, and Ameliorates Disease in a Preclinical Arthritis Model Presenting authors: Grace Teng, Ph.D. (Gilead Sciences, Inc.) Session: Innate Immunity Session date and time: Sunday, November 17, 2024, 10:30 AM - 12:30 PM Abstract ID: 1861825 Abstracts are available online at: acrabstracts.org 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 ( NCT05131022 ). About GS-6791 (previously NX-0479): GS-6791 is a potent, selective, oral IRAK4 degrader. Degradation of IRAK4 by GS-6791 has potential applications in the treatment of rheumatoid arthritis and other inflammatory diseases. Nurix’s collaborator, Gilead Sciences, is responsible for conducting IND-enabling studies and advancing this program to clinical development. 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 cell and NK cells. Nurix is headquartered in San Francisco, California. For additional information visit . Forward-Looking Statements This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 and other federal securities laws. Any statements contained herein that do not describe historical facts, including, but not limited to, statements regarding the planned timing for the provision of updates and findings from preclinical studies, including Nurix’s intention to present preclinical data from NX-5948 and GS-6791/NX-0479 at ACR Convergence 2024, are forward-looking statements that involve risks and uncertainties that could cause actual results to differ materially from those discussed in such forward-looking statements. Such risks and uncertainties include, among others, the risks described under the heading “Risk Factors” in Nurix’s Quarterly Report on Form 10-Q for the period ended May 31, 2024, and subsequent filings with the SEC. Any of these risks and uncertainties could materially and adversely affect Nurix’s business and results of operations, which could, in turn, have a significant and adverse impact on Nurix’s stock price. Nurix cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. Nurix undertakes no obligation to update publicly any forward-looking statements to reflect new information, events or circumstances after the date they were made or to reflect the occurrence of unanticipated events. Contacts: Investors Jason Kantor, Ph.D. Nurix Therapeutics, Inc. ir@nurixtx.com Elizabeth Wolffe, Ph.D. Wheelhouse Life Science Advisors lwolffe@wheelhouselsa.com Media Aljanae Reynolds Wheelhouse Life Science Advisors areynolds@wheelhouselsa.com