STAMP

Phase III ASC4FIRST trial met both primary endpoints with clinically meaningful and statistically significant results; Scemblix® (asciminib) demonstrated superior MMR rates at week 48 vs. investigator-selected SoC TKIs (imatinib, nilotinib, dasatinib and bosutinib) (67.7% vs. 49.0%) and imatinib alone (69.3% vs. 40.2%)1 Scemblix also demonstrated a favorable safety and tolerability profile vs. imatinib and 2G TKIs, with fewer grade ≥3 AEs, dose adjustments, and half the rate of AEs leading to treatment discontinuation1 TKIs have transformed CML treatment, but unmet need remains; many newly diagnosed patients do not meet molecular response goals, and many discontinue or change treatment due to intolerance2-17Scemblix was granted US FDA Breakthrough Therapy Designation, submission is now in review under the agency’s Oncology Center of Excellence RTOR program; data will be presented as a plenary at EHA and today as a late-breaking abstract at ASCO Basel, May 31, 2024 – Novartis today presents positive results from the pivotal Phase III ASC4FIRST trial as a late-breaking abstract at the 2024 American Society of Clinical Oncology (ASCO) meeting. Scemblix® (asciminib) demonstrated superior major molecular response (MMR) rates at week 48 compared to investigator-selected standard-of-care (SoC) tyrosine kinase inhibitors (TKIs) imatinib, nilotinib, dasatinib and bosutinib, and compared to imatinib alone in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP)1. Scemblix also showed a numerical improvement in MMR at week 48 vs. second generation (2G) TKIs (nilotinib, dasatinib and bosutinib)1. Additionally, Scemblix demonstrated a favorable safety and tolerability profile, with fewer adverse events (AEs) and treatment discontinuations vs. both imatinib and 2G TKIs1. “Scemblix is the first CML treatment to show significantly better efficacy compared to investigator-selected standard-of-care TKIs,” said Prof. Tim Hughes, MD, South Australian Health & Medical Research Institute (SAHMRI). “When you combine superior response with the excellent safety and tolerability profile of Scemblix, we have a very promising potential frontline option for newly diagnosed patients to support them in achieving their treatment goals.” The median follow-up was 16.3 and 15.7 months for Scemblix and investigator-selected SoC TKIs, respectively1. Nearly 20% more patients treated with Scemblix achieved MMR at week 48 vs. investigator-selected SoC TKIs and nearly 30% more patients achieved MMR at week 48 vs. imatinib alone1. Patients treated with Scemblix also achieved deeper rates of molecular responses (MR4 and MR4.5) compared with investigator-selected SoC TKIs and imatinib alone1. Overalla Scemblix (n=201)vs. investigator-selected SoC TKIs (n=204) Imatinib stratumb Scemblix (n=101)vs. imatinib (n=102) 2G TKI stratumcScemblix (n=100) vs. 2G TKIs (n=102) Primary endpoints Week 48 MMR rates 67.7% vs. 49.0% 69.3% vs. 40.2% – Week 48 MMR Treatment difference (95% CI) 18.9% (9.6%–28.2%) 29.6% (16.9%–42.2%) – Adjusted 1-sided p-value <.001 <.001 – Secondary endpointsd Week 48 MMR rates – – 66.0% vs. 57.8% Week 48 MR4 39% vs. 21% 43% vs. 15% 35% vs. 26% Week 48 MR4.5 17% vs. 9% 18% vs. 5% 16% vs. 13% a All patients receiving Scemblix (n=201) or investigator-selected SoC TKIs (n=204). Treatment difference after adjusting for pre-randomization selected TKI and EUTOS long-term survival (ELTS) risk groups at baseline.b The 203 patients within the pre-randomization-selected imatinib stratum were randomized to receive either Scemblix (n=101) or imatinib (n=102). Treatment difference after adjusting for ELTS risk groups at baseline.c The 202 patients within the pre-randomization selected 2G TKIs stratum were randomized to receive either Scemblix (n=100) or 2G TKIs (n=102: nilotinib, 48%; dasatinib, 41%; bosutinib, 11%).d Secondary endpoints were not powered for statistical significance. In newly diagnosed patients, the safety profile was consistent with previous registration studies with no new safety concerns observed1. Fewer grade ≥3 AEs, dose adjustments to manage AEs, and half the rate of AEs leading to treatment discontinuation were reported for Scemblix vs. both imatinib and 2G TKIs1. Scemblix Imatinib 2G TKIs Grade ≥3 AEsa 38% 44% 55% AEs leading to treatment discontinuationa 5% 11% 10% AEs leading to dose adjustments/ interruptionsa 30% 39% 53% a In patients who experienced ≥1 adverse event. “Patients living with CML need efficacious and well-tolerated treatment options that help them achieve meaningful outcomes as they manage their chronic condition,” said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis. “The compelling ASC4FIRST data highlight the potential of Scemblix to achieve better results than standard-of-care in newly diagnosed adults, while maintaining a favorable safety and tolerability profile. These results reinforce Scemblix as a proven treatment in Ph+CML-CP, as we continue to build on our 20-year legacy in CML innovation.” “CML is a chronic condition and the side effects of standard-of-care can be challenging for patients. They often affect their daily life and can lead to high rates of treatment switching,” said Gerald Clements, CML caregiver, patient advocate and Steering Committee Treasurer at CML Advocates Network. “Effective care that can be tolerated long-term is a key unmet need. By potentially bringing Scemblix to patients when they are first diagnosed, they may have an opportunity to be on a highly effective treatment while also maintaining their day-to-day from the start.” The trial remains ongoing, with the next scheduled analysis at week 96 to evaluate the key secondary endpoint (MMR at week 96) and additional secondary endpoints18. These results have been submitted to the US Food and Drug Administration (FDA) via the Oncology Center of Excellence Real-Time Oncology Review (RTOR) program and Scemblix has been granted Breakthrough Therapy Designation. They will also be presented as a plenary at the European Hematology Association (EHA) 2024 Congress in June. 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. investigator-selected first- or second-generation TKIs (imatinib, nilotinib, dasatinib or bosutinib) in 405 adult patients with newly diagnosed Ph+ CML-CP18. The two primary endpoints of the study are to compare efficacy of asciminib vs. investigator-selected 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 4818. 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 9618. 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 survival18. 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)19-21. The current approved CML treatments are TKIs that target the ATP-binding site (ATP-competitive) 21. Scemblix is approved in more than 70 countries, including the US and the EU, to treat adults with Ph+ CML-CP who have previously been treated with two or more TKIs22-24. In some countries, including the US, Scemblix is also approved in patients with Ph+ CML-CP with the T315I mutation23-25.Scemblix is an important treatment option for patients who experience resistance and/or intolerance after two prior TKI therapies2-17, and it is being studied across multiple treatment lines for Ph+ CML-CP, both as a monotherapy and in combination18-20,24,26-38. 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 into a chronic, vs. 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 collaboration with the Max Foundation has provided access to Glivec, Tasigna and now Scemblix, starting over 20 years ago, and 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,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. 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 the investigational or approved products described in this press release 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 such products will be commercially successful in the future. In particular, our expectations regarding such products 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 Hughes TP, Hochhaus A, Takahashi N, et al. ASC4FIRST, a pivotal ph 3 study of asciminib (ASC) vs investigator-selected tyrosine kinase inhibitors (IS TKIs) in newly diagnosed patients (pts) with chronic myeloid leukemia (CML): primary results [abstract]. Presented at: American Society for Clinical Oncology (ASCO) 2024 Annual Meeting; May 31 – June 4, 2024; Chicago, IL. 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.2016.5Brümmendorf 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.13108Cortes 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.2017.74.7162Kota 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.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.25306Claudiani 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-wKohlbrenner 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-2022-159412Cortes 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.24536Garg 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. Leuk. 2016;30:1648-1671. doi:10.1038/leu.2016.104Hochhaus 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/NEJMoa1609324Cortes 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-2016-09-739086Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leuk. 2020;34:966-984. doi:10.1038/s41375-020-0776-2Flis 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.S191303A 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.8b01040Scemblix. EMA Summary of Product Characteristics. Novartis Europharm Limited; 2022.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 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/nature21702Hughes 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.V126.23.138.138Mauro 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.2020.106458Study 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/NCT04666259Study 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/NCT03578367Study 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/NCT04795427A 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/NCT02081378Asciminib 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 Marlena Abdinoor +1 617 335 9525 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

MEDIA & INVESTOR RELEASE Novartis Scemblix® shows superior major molecular response (MMR) rates vs. standard-of-care TKIs in Phase III trial for newly diagnosed patients with chronic myeloid leukemia Ad hoc announcement pursuant to Art. 53 ASC4FIRST trial met both primary endpoints with clinically meaningful and statistically significant results; Scemblix® (asciminib) shows superior MMR rates at week 48 vs. standard-of-care TKIs (imatinib, nilotinib, dasatinib, and bosutinib) in newly diagnosed Ph+CML-CP patients1Scemblix demonstrated a favorable safety and tolerability profile with fewer adverse events (AEs) and treatment discontinuations vs. standard-of-care TKIs; no new safety signals were observed1With current standard-of-care TKIs, more than 60% of newly diagnosed patients with CML fail to meet molecular response goals at one year; intolerance and AEs remain a primary reason for discontinuing TKI therapy, with discontinuation rates due to AEs of up to 25% by five years2-13Data will be presented at an upcoming medical conference and submitted to regulatory authorities in 2024 Basel, January 08, 2024 — Novartis today announced positive results from the primary analysis of ASC4FIRST, a pivotal Phase III trial comparing Scemblix® (asciminib) with investigators’ choice of tyrosine kinase inhibitor (TKI) treatment in newly diagnosed patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP)1. ASC4FIRST is the first and only randomized head-to-head Phase III trial comparing a CML treatment vs. approved standard-of-care first- and second-generation TKIs1. The trial met both primary endpoints of major molecular response (MMR) rate for Scemblix compared to investigator-selected TKIs (imatinib, nilotinib, dasatinib, and bosutinib) and compared to imatinib, demonstrating clinically meaningful and statistically significant results for both endpoints1. Scemblix showed a favorable safety and tolerability profile with fewer adverse events (AEs) and treatment discontinuations vs. investigator selected standard-of-care TKIs1. The ASC4FIRST data showed no new safety signals compared to the established safety profile of Scemblix1,14. “We are very encouraged by these results given that a significant proportion of patients with newly diagnosed chronic myeloid leukemia, or CML, do not achieve their treatment goals,” said Prof. Tim Hughes, MD, South Australian Health & Medical Research Institute (SAHMRI). “There remains a significant need in first-line therapy of CML for tolerable treatment options, allowing people with CML to balance their treatment alongside their quality of life.” Improvements in treatment have transformed CML into a chronic disease, with a life expectancy similar to that of the general population, making tolerability an important treatment goal9. While many patients with CML may benefit from available TKI therapy, intolerance and AEs remain a primary reason for TKI therapy discontinuation, with discontinuation rates due to AEs of up to 25% by five years2-6. Additionally, over 60% of newly diagnosed CML patients fail to meet 12-month molecular response goals 5-13. “We are excited that Scemblix may help people newly diagnosed with CML achieve their treatment goals while continuing to live their lives,” said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis. “Given the chronic nature of their condition, patients often need to be on TKI therapy for many years, so treatment options that are well tolerated and highly efficacious are crucial to support adherence. This study outcome builds on our 20-year legacy in CML innovation as we strive to continue to address the remaining unmet needs for people living with this blood cancer.” The trial remains ongoing, with the next scheduled data readout planned for week 96, which will evaluate the key secondary endpoint (MMR at week 96) as well as additional secondary endpoints. Details will be presented at an upcoming medical conference and included as part of regulatory submissions in 2024. 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 versus investigator-selected first- or second-generation TKI (imatinib, nilotinib, dasatinib, or bosutinib) in 405 adult patients with newly diagnosed Ph+ CML-CP1. The two primary endpoints of the study are to compare efficacy of asciminib vs. investigator-selected TKI 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. The study remains ongoing with a key secondary endpoint 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 96. 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. About Scemblix® (asciminib)Scemblix® is the first CML treatment that works by specifically targeting the ABL myristoyl pocket15,16 and was intentionally designed to be highly specific and minimize off-target kinase mediated effects, which translates into an improved safety and tolerability profile compared to current standard of care. Scemblix is approved in more than 60 countries, including the US and the EU, to treat adults with Ph+ CML-CP who have previously been treated with two or more TKIs14,19. In some countries including the US, Scemblix is also approved in patients with Ph+ CML-CP with the T315I mutation2-14,18,19. Scemblix represents an important potential treatment option for patients who experience resistance and/or intolerance to currently available TKI therapies, and it is being studied across multiple treatment lines for Ph+ CML-CP, both as monotherapy and in combination15-18,20-33. 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 into a chronic, versus 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 collaboration with the Max Foundation has provided access to Glivec, Tasigna and now Scemblix, starting over 20 years ago, and delivering tremendous patient impact in low and middle income countries, with 90,000 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,” “planned,” “may,” “commitment,” “remain,” “goals,” “upcoming,” “excited,” “potentially,” “continuing,” “continue,” “strive,” “ongoing,” “to address,” 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 Novartis Data on File, 2024. Cortes JE, 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. Garg RJ, et al. 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SUZHOU, China, and ROCKVILLE, Md., Dec. 10, 2023 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, announced today that it has released updated data from a US study of the company's novel drug candidate, olverembatinib (R&D code: HQP1351), in patients with refractory chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), in a Poster Presentation at the 65th American Society of Hematology (ASH) Annual Meeting, taking place in San Diego, CA, the United States. The ASH Annual Meeting is one of the largest gatherings of the international hematology community, bringing together the most cutting-edge scientific research and latest data of investigational therapies that representleading scientific and clinical advances in the global hematology field. Garnering growing interest from the global research community, multiple studies of Ascentage Pharma's key drug candidates (olverembatinib and lisaftoclax) have been selected for presentations at this year's ASH Annual Meeting, including two Oral Presentations on olverembatinib. This is the sixth consecutive year in which clinical results on olverembatinib have been selected for Oral Presentations at the ASH Annual Meeting. After releasing preliminary results of the US study in an Oral Report at last year's ASH Annual Meeting, this year Ascentage Pharma presented updated data from a larger patient sample that reaffirmed the favorable clinical benefit and tolerability of olverembatinib, as a monotherapy and in combinations, in heavily pretreated patients with CML and Ph+ ALL, particularly those who have failed prior treatment with the third-generation TKI ponatinib or the allosteric STAMP inhibitor asciminib. Prof. Elias Jabbour, MD, Department of Leukemia, The University of Texas MD Anderson Cancer Center, and the Principal Investigator of the study, commented, "Once again, the follow-up data of study HQP1351CU101 showed olverembatinib' s excellent treatment response, especially in patients who were resistant to ponatinib or asciminib. Olverembatinib will provide an effective new treatment option for CML and Ph+ ALL patients." "Building on the encouraging results presented at last year's ASH Annual Meeting, the data released this year validated olverembatinib's promising therapeutic potential in patients resistant to ponatinib or asciminib. These encouraging results once again underscored the potential of this China-developed global best-in-class drug in addressing the unmet needs of patients with CML and Ph+ ALL worldwide," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "Remaining committed to the mission of the addressing unmet clinical needs in China and around the world, we will expedite our clinical development programs to bring more safe and effective therapies to patients in need." Highlights of the study presented at ASH 2023: Update of Olverembatinib (HQP1351) Overcoming Ponatinib and/or Asciminib Resistance in Patients (Pts) with Heavily Pretreated/Refractory Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) Format: Poster Presentation Abstract: #1798 Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster I Time: December 9, 2023, Saturday, 5:30 PM – 7:30 PM (Pacific Time) / December 10, 2023, Sunday, 9:30 AM – 11:30 AM (Beijing Time) Highlights: Background: Patients with CML who failed on first- and second-generation tyrosine kinase inhibitors (TKIs) have a poor prognosis. Olverembatinib, a novel third-generation TKI, has shown strong antitumor activity in patients with CML and Ph+ ALL. This presentation reports on the safety, efficacy, and pharmacokinetics (PK) of olverembatinib in patients with CML and Ph+ ALL outside of China, particularly in patients previously treated with third-generation TKI ponatinib and/or allosteric STAMP inhibitor asciminib. Methods: Olverembatinib was administered orally once every other day (QOD). In the monotherapy cohort, patients were enrolled after treatment failures on at least 2 prior TKIs (no limit on the number of prior TKIs for patients harboring the T315I mutation) and randomized to receive olverembatinib QOD at 30, 40, or 50 mg, in 28-day cycles. In the combination cohort, patients with Ph+ B-cell precursor ALL (BCP ALL) or lymphoid CML-BP (CML-LBP) resistant to at least 1 second-generation TKI were enrolled and administered olverembatinib (30 or 40 mg) QOD in combination with CD19/CD3 bispecific antibody (bispecific T-cell engager) blinatumomab. Patients: As of June 30, 2023, 76 patients were enrolled, including 57 with CML in chronic phase (CML-CP) and 19 with advanced Ph+ leukemia (CML-AP, CML-LBP, Ph+ ALL). The median (range) age was 54.5 (21-80) years, and 56.6% of patients were male. 11 (14.5%), 23 (30.3%), and 39 (51.3%) patients had received 2, 3, and ≥4 TKIs, respectively. A total of 40 (52.6%) patients were previously treated with ponatinib, of whom 67.5% were resistant, 25.0% were intolerant to the drug, and 7.5% of patients failed for other reasons. A total of 21 (27.6%) patients were previously treated with asciminib, of whom 71.4% were resistant and 19.1% were intolerant to the agent, and 9.5% failed for other reasons. At baseline, 31.6% of patients had T315I mutations, and 38.2% had hypertension. The median (range) duration of treatment was 24.1 (0-134) weeks. PK analysis showed that patients worldwide had a PK profile similar to historical data on Chinese patients. Efficacy results: Among 50 efficacy-evaluable patients with CML-CP, 56.8% (25/44) achieved a complete cytogenetic response (CCyR), and 42.9% (21/49) achieved a major molecular response (MMR). In patients with CML-CP harboring the T315I mutation, CCyR and MMR rates were 60.0% (9/15) and 43.8% (7/16), respectively; In patients without the T315I mutation, CCyR and MMR rates were 55.2% (16/29) and 42.4% (14/33), respectively; In patients who were ponatinib-resistant, CCyR and MMR rates were 53.3% (8/15) and 37.5% (6/16), respectively; In patients who were asciminib-resistant, CCyR and MMR rates were 42.9% (3/7) and 37.5% (3/8), respectively. Among the 13 efficacy-evaluable patients with advanced Ph+ leukemia, 23.1% (3/13) achieved MMR, of whom 1 patient harbored the T315I mutation and 2 were T315I mutation negative and resistant to ponatinib. In the combination cohort, 2 patients with Ph+ BCP ALL received olverembatinib 30 mg QOD in combination with blinatumomab. Both patients achieved CCyR and 1 achieved negative minimal residual disease (MRD) status after 1 treatment cycle. Safety results: A total of 12 patients with CML-CP and 7 with advanced Ph+ leukemia discontinued treatment for reasons including adverse events (AEs n=4), disease progression (n=7), and other reasons (n=8). A total of 54 (83.1%) patients experienced treatment-related AEs (TRAEs) of any grade after receiving olverembatinib. Grade ≥3 TRAEs occurring in ≥3 patients included thrombocytopenia (17.0%), neutropenia (13.8%), elevated blood creatine phosphokinase (13.8%), leukopenia (7.7%), anemia (4.6%), and elevated lipase (4.6%). 10 (15.4%) patients experienced treatment-related serious AEs (SAEs). Conclusions: Olverembatinib monotherapy or combined with blinatumomab was efficacious and well tolerated in heavily pretreated patients with CML or Ph+ ALL and was potent in patients who were resistant or intolerant to ponatinib and/or asciminib, regardless of the T315I mutation status. Olverembatinib may provide an effective treatment option for patients with CML or Ph+ ALL who have failed on two or more TKIs. * Olverembatinib is an investigational drug that has not been approved for any indication outside the Chinese mainland About Ascentage Pharma Ascentage Pharma (6855.HK) is a globally focused biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B, and age-related diseases. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK. Ascentage Pharma focuses on developing therapeutics that inhibit protein-protein interactions to restore apoptosis, or programmed cell death. The company has built a pipeline of 9 clinical drug candidates, including novel, highly potent Bcl-2, and dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation tyrosine kinase inhibitors (TKIs). Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company is conducting more than 40 Phase I/II clinical trials in the US, Australia, Europe, and China. Ascentage Pharma has been designated for multiple Major National R&D Projects, including five Major New Drug Projects, one New Drug Incubator status, four Innovative Drug Programs, and one Major Project for the Prevention and Treatment of Infectious Diseases. Olverembatinib, the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company's first approved product, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China 2022 National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU. To date, Ascentage Pharma has obtained a total of 16 ODDs, 2 FTDs, and 2 Rare Pediatric Disease (RPD) Designations from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company's investigational drug candidates. Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships with numerous renowned biotechnology and pharmaceutical companies and research institutes such as UNITY Biotechnology, MD Anderson Cancer Center, Mayo Clinic, Dana-Farber Cancer Institute, MSD, and AstraZeneca. The company has built a talented team with global experience in the discovery and development of innovative drugs and is setting up its world-class commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients. Forward-Looking Statements The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, Ascentage Pharma undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development. SOURCE Ascentage Pharma