Ponatinib Hydrochloride

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) therapies1-3 Patients on Scemblix also had fewer dose reductions and half the rate of adverse reactions leading to treatment discontinuation1-3 Nearly 50% of CML patients do not meet efficacy milestones (MMR) with current SoC and almost 25% discontinue or switch therapies within one year of treatments4-5 Scemblix 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 481-2 Scemblix 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%)1-3 Patients 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 481-2 In 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

ROCKVILLE, Md. and SUZHOU, China, Aug. 22, 2024 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in discovering, developing and commercializing both first-in-class and best-in-class therapies for malignancies, today announced its 2024 interim results. During the reporting period, Ascentage Pharma continued to execute its global innovation strategy, having achieved breakthroughs across various aspects of its business including external collaborations, commercialization, and clinical development. In particular, the company has set a new record with its revenue for the first half of 2024 and reported profit for the first time. During the reporting period, Ascentage Pharma has set a new record for its revenue that grew by 477% from the same period last year to RMB824 million, with most of the revenue generated from sales of pharmaceutical products and license income. For the very first time in its history, Ascentage Pharma reached profitability, having reported a net profit of RMB163 million. Ascentage Pharma made rapid progress with the commercialization of its first approved product, olverembatinib (HQP1351). During the reporting period, olverembatinib generated a sales revenue of RMB113 million, which grew by 120% from the second half of 2023 and 5% year-over-year. Ascentage Pharma and Takeda, a multinational pharmaceutical company, have entered into an exclusive option agreement that granted Takeda an exclusive option to enter into an exclusive license agreement for olverembatinib. Once exercised, the Option would allow Takeda to license global rights to develop and commercialize olverembatinib in all territories outside of, among others, the mainland China, Hong Kong China, Macau China, and Taiwan China. Ascentage Pharma has received US$100 million in option payment and a US$75 million equity investment. The company's cash flows continued to improve. As of June 30, 2024, the company's cash balances were RMB1.1 billion and rose to RMB1.8 billion by early July, 2024. Entered into a landmark global collaboration that is the largest BD deal among small molecule oncology drugs in China Ascentage Pharma constantly seeks global partnerships. During the reporting period, the company and Takeda, a multinational pharmaceutical company, entered into an exclusive option agreement for olverembatinib. This collaboration, with a total value reaching US$1.3 billion, includes an option payment of US$100 million and an option exercise fee and potential milestone payments totaling US$1.2 billion. Additionally, Ascentage Pharma is eligible for tiered double-digit royalties on annual net sales. To date, this is the largest out-licensing deal for any small molecule oncology drug in China. Furthermore, Ascentage Pharma also received an equity investment from Takeda. This collaboration highlights the significant clinical and commercial potential of olverembatinib in the global market and laid a solid foundation for the future global commercialization of the drug. Ascentage Pharma has already received the US$100 million option payment and US$75 million equity investment from Takeda. Commercialization of olverembatinib accelerated and strengthened the company ' s revenue generating ability Following the inclusion of the first approved indication of Ascentage Pharma's novel drug candidate olverembatinib into the China National Reimbursement Drug List (NRDL) in January 2023 and the regulatory approval for its new indication in November 2023, olverembatinib continued to realize its growth potential while boosting company's ability to generate revenue through product sales. During the reporting period, the sales revenue of olverembatinib grew by 120% from the second half of 2023 and by 5% year-over-year, to RMB113 million. Ascentage Pharma is expeditiously expanding the commercialization of its approved product. As of June 30, 2024, olverembatinib has entered 670 hospitals and direct-to-patient (DTP) pharmacies nationwide and its number of listed hospitals has grown by 79% compared to the end of last year. Since the approval of its new indication in November 2023 till June 30, 2024, olverembatinib has been included into 114 supplemental insurance for major diseases and Huimin insurance plans of 20 provinces and 83 municipalities. Additionally, olverembatinib was included into the special drugs catalog of the Huimin insurance plan of 20 provinces and municipalities such as Hebei, Hainan, Inner Mongolia Autonomous Region, Wuxi, Huzhou, Shenzhen, and Yantai, which greatly improved the drug's accessibility and alleviated the burden on patients. As the first China-approved third-generation BCR-ABL inhibitor, olverembatinib's clinical value and therapeutic potential continued to received high profile recognition during the reporting period, both in China and globally. In January 2024, clinical trial results of olverembatinib were included into the US National Comprehensive Cancer Network® (NCCN) Guidelines for the Management of Chronic Myeloid Leukemia (CML). Moreover, olverembatinib has received upgraded recommendations from the 2024 Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Hematologic Malignancies in CML and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL), plus a number of additional Level I recommendations from the guideline. In July 2024, olverembatinib was approved in Macau China for the treatment of adult patients with tyrosine kinase inhibitor (TKI)-resistant chronic-phase CML (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation; and adult patients with CML-CP resistant to and/or intolerant of first- and second-generation TKIs, marking another major milestone for olverembatinib following initial approvals it received in the Chinese mainland. Global innovation strategy yielding more encouraging results with eight registrational studies being simultaneously advanced Guided by its global innovation strategy, Ascentage Pharma delivered multiple milestone achievements and swiftly advanced its global clinical development programs during the reporting period. To date, two of the company's key drug candidates, olverembatinib and lisaftoclax (APG-2575), have been cleared to enter 11 registrational studies, including 3 registrational studies that have been completed and 8 registrational studies currently ongoing. In February 2024, olverembatinib was cleared by the US Food and Drug Administration (FDA) to enter a global registrational Phase III study in previously treated adult patients with CML-CP. This is the first FDA-cleared registrational Phase III study of olverembatinib and it represents a big step forward for Ascentage Pharma's global clinical development in hematologic malignancies. Outside hematology, the Center for Drug Evaluation (CDE) of China's National Medical Product Administration (NMPA) cleared a global registrational Phase III study of olverembatinib in patients with succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) who had failed prior systemic treatment. This clearance represents a crucial step in Ascentage Pharma's clinical development in solid tumors. Meanwhile, Ascentage Pharma also made notable strides with the clinical development of lisaftoclax in hematologic malignancies. During the reporting period, the China CDE cleared a Phase III study of lisaftoclax in combination with azacitidine (AZA) for the first-line treatment of newly-diagnosed patients with higher-risk myelodysplastic syndrome (MDS). This is the fourth cleared registrational Phase III study of lisaftoclax. Winning recognition from around the world with robust clinical data spanning multiple indications As an innovative biopharmaceutical company focused on global innovation, Ascentage Pharma has built a high value pipeline composed of assets with first- and best-in-class potentials and conducted more than 40 clinical trials in China, the US, Australia, Europe, and Canada. In this process, Ascentage Pharma made steady progress exploring and validating a number of its drug candidates across multiple indications and presented updated results from its clinical programs at a number of international congresses, showcasing its prowess in R&D and clinical development. During the reporting period, results from four clinical studies of olverembatinib, lisaftoclax, and APG-2449, the company's three key drug candidates, were selected for presentations at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. This is the seventh consecutive year for Ascentage Pharma to present at the meeting. Among these results, the data of olverembatinib in patients with TKI-resistant SDH-deficient GIST were selected for an Oral Report. In the data, olverembatinib showed promising clinical benefit including a clinical benefit rate (CBR) of 92.3% and a median progression-free survival (PFS) of 25.7 months in patients with SDH-deficient GIST, an indication that currently lacks standard of care treatment. At the same meeting, Ascentage Pharma presented the latest data that further demonstrated the therapeutic potential of its FAK/ALK/ROS1 TKI APG-2449 for the treatment of non-small cell lung cancer (NSCLC). At the 2024 European Hematology Association Hybrid Congress (EHA 2024) which took place in June this year, Ascentage Pharma released update results from five studies of olverembatinib, lisaftoclax, and APG-5918, three of the company's key drug candidates. These data highlighted the company's competitiveness in the field of hematologic malignancies. The three studies of olverembatinib presented at EHA 2024 include one that reported the latest median 1-year follow-up data of olverembatinib in patients with CML and Ph+ ALL, updated from the data released at the 2023 American Society of Hematology (ASH) Annual Meeting. In the results, olverembatinib showed excellent durable clinical benefits and favorable long-term tolerability in patients who had been treated with multiple TKIs (including those who were resistant to ponatinib and/or asciminib), regardless of whether they harbored the T315I mutation. The latest data from multiple studies of lisaftoclax were also selected for presentations at the 2024 ASCO Annual Meeting and EHA 2024. These results highlighted lisaftoclax' therapeutic potential in a range of hematologic malignancies. Data released at this year's ASCO Annual Meeting include the latest promising results from a Phase Ib/II study of lisaftoclax in combination with AZA in patients with treatment-naïve (TN) or relapsed/refractory (R/R) acute myeloid leukemia (AML), and a global, multicenter Phase Ib/II study of lisaftoclax alone or in combinations for the treatment of patients with Waldenström macroglobulinemia (WM). At EHA 2024, the company presented encouraging updated data of lisaftoclax in patients with R/R multiple myeloma (MM) or immunoglobulin light-chain (AL) amyloidosis. Furthermore, results from three preclinical studies of olverembatinib, alrizomadlin (APG-115), APG-2449, and APG-5918 were announced at the 2024 American Association of Cancer Research Annual Meeting (AACR 2024), providing important scientific rationale for the future clinical development of these assets. Deepening global innovation while opening a whole new chapter on growth and development To support its long-term strategy and growth, during the reporting period, Ascentage Pharma has confidentially submitted a draft registration statement on Form F-1 to the US Securities and Exchange Commission (SEC) relating to the proposed initial public offering of American depositary shares (ADSs) representing its ordinary shares. Ascentage Pharma is steadfastly committed to its global innovation strategy and strengthening its intellectual property portfolio. As of June 30, 2024, Ascentage Pharma holds 520 issued patents globally, among of which 367 patents were issued outside of China. Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma, said, "In the first half of 2024, Ascentage Pharma has achieved multiple milestones in global business development, product commercialization, and global clinical development. These achievements highlight our global innovative capabilities and competitiveness in the field of hematologic malignancies. During the reporting period, we entered into a global collaboration valued at up to US$1.3 billion with Takeda, a multinational pharmaceutical company, for olverembatinib, in an agreement that also includes tiered double-digit royalties on annual net sales. This is the largest BD deal for any small molecule oncology drug in China. Moreover, we have already received US$75 million in equity investment from Takeda. This collaboration is another validation of our leadership in the industry and olverembatinib's value in the global market that will hopefully demonstrate clinical potential in more conditions that currently lack treatment options. In February 2024, the US FDA cleared a global registrational Phase III study of olverembatinib, marking yet another major milestone in the global clinical development of the drug. It is worth emphasizing that during the reporting period, Ascentage Pharma achieved profitability for the first time in its history. With olverembatinib included into the China NRDL and approved for a new indication in the country, we are empowered to further strengthen our commercialization capabilities. At the same time, we made broad progress with our global clinical development programs, expanded the potential indications of our key drug candidates, and reinforced our competitiveness in the field of hematologic malignancies. Pressing ahead with our patient-centric global innovation strategy, we will continue to build out our commercialization capabilities and accelerate the global clinical development of our investigational assets. To fulfill our mission of addressing unmet clinical needs in China and around the world, we aspire to bring our innovative drugs to the global market as soon as possible for the benefit of more patients around the world and create additional value for societies and our investors." About Ascentage Pharma Ascentage Pharma (6855.HK) is a global, integrated biopharmaceutical company engaged in discovering, developing and commercializing both first-in-class and best-in-class therapies to address global unmet medical needs primarily in malignancies. 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. The company has built a pipeline of 9 clinical-stage 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 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 has conducted more than 40 clinical trials in the US, Australia, Europe, and China, including 11 registrational studies (completed/ ongoing/planned). Olverembatinib, the company's first lead asset developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company's first approved product in China, 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 National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted Orphan Drug Designations (ODDs) 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 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 and other relationships with numerous leading biotechnology and pharmaceutical companies such as Takeda, AstraZeneca, Merck, Pfizer and Innovent; and research and development relationships with leading research institutions such as Dana-Farber Cancer Institute, Mayo Clinic, MD Anderson Cancer Center, National Cancer Institute and the University of Michigan. The company has built a talented team with a wealth of global experience in the discovery and development of innovative drugs and fully functional 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 and expectations or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions and expectations may alter in light of future development. SOURCE Ascentage Pharma