ROCKVILLE,Md. and SUZHOU,China,Nov. 22,2024 -- Ascentage Pharma (6855.HK),a global biopharmaceutical company engaged in discovering,developing and commercializing therapies to address global unmet medical needs primarily for malignancies,announced today that findings from a phase Ib multicenter clinical trial (NCT04260022) of its third-generation BCR-ABL1 tyrosine kinase inhibitor (TKI) have been published in the November 2024 issue of JAMA Oncology,marking a milestone in global awareness concerning the agent.

JAMA Oncologyis among the most influential and high-ranking oncology publications,with a 2023 impact factor of 28.4. It is read widely by the clinical-oncology community,with 6.4 million original downloads or views per annum. In 2023,the journal accepted only about 155 (7%) of 2,223 research-article submissions.

Olverembatinib may help to address critical unmet clinical needs related to TKI treatment resistance and intolerance,which can impose formidable humanistic and economic burdens especially in heavily pretreated patients with suboptimal outcomes. For instance,arterial occlusive events (AOEs) constitute one salient and potentially dose-limiting treatment challenge with certain second- and third-generation TKIs.

This study (NCT04260022) randomly allocated 80 patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph⁺ ALL) to receive oral olverembatinib 30,40,or 50 mg on alternate days. The study population was heavily pretreated: approximately 18% of patients had received two prior TKIs,28% three,and 54% at least four. Forty-six patients (57.5%) had received ponatinib; 25 (31.3%),asciminib; and 11 (13.8%),both medications.1

Among all evaluable patients with chronic-phase CML (CP-CML),the complete cytogenetic response (CCyR) rate was approximately 61% and the major molecular response (MMR) rate,approximately 42%. Cytogenetic and molecular responses were similar irrespective of the presence of the T315I mutation,which confers resistance against imatinib and all second-generation TKIs.1

Importantly,approximately 58% of patients with prior ponatinib treatment failure achieved CCyR and about 37%,MMR. Corresponding values in patients with asciminib treatment resistance were 50% and 33%.1

Olverembatinib was also well tolerated,with leading (typically mild or moderate) treatment-emergent adverse events including elevated blood creatine phosphokinase and thrombocytopenia. There were no fatal treatment-related adverse events. Treatment-related AOEs were infrequent (3%) and mild or moderate (grade 1 or 2); no such olverembatinib-related event was considered serious.

"I am delighted to showcase the strength and progress of the 'lead' asset of Ascentage Pharma,which exemplifies the richness and diversity of our product pipeline of innovative,patient-centric therapies for a range of hematologic malignancies," said Dr. Yifan Zhai,Chief Medical Officer of Ascentage Pharma. "In the future,we will continue to advance these development programs in efforts to bring more treatment options to patients with unmet clinical needs around the world."

"One potential explanation for the response of olverembatinib in patients with ponatinib and asciminib resistance is its broad (pan-BCR::ABL1-kinase domain) mutational coverage," said principal investigator Elias Jabbour,MD,Professor of Leukemia at The University of Texas MD Anderson Cancer Center. "In studies to date,olverembatinib has shown greater sensitivity and clinical benefit against compound mutations – two or more mutations within the same allele of BCR::ABL1 – compared with other approved TKIs and the STAMP inhibitor asciminib."

Findings from this trial have also been presented at leading hematologic-oncology congresses around the world,including the 29th European Hematology Association Congress,which convened June 13-16,2024,in Madrid; the 12th annual meeting of the Society of Hematologic Oncology,on September 4-7,in Houston,Texas; and the ESH-iCMLf 26th Annual John Goldman Conference on Chronic Myeloid Leukemia (Biology and Therapy),on September 27-29,in Prague. Updated results will be presented at the 66th American Society of Hematology Annual Meeting and Exposition,December 8,2024 (6:00-8:00 PM),in San Diego,CA (poster/publication #3151).

"Publication of our trial results in JAMA Oncology represents a major milestone for olverembatinib,and the study established the recommended dose for our ongoing phase III registrational trial: POLARIS-2 [NCT06423911]," said Dr. Dajun Yang,Chairman & CEOof Ascentage. "We look forward to that trial and,in the future through our option agreement with Takeda,to potentially bring this medication to underserved populations around the world,including patients with CML or Ph⁺ ALL that is resistant to or intolerant of other medications."

On June 14,Ascentage signed an exclusive option agreement to enter into an exclusive license agreement with Takeda (www.takeda.com) for olverembatinib. In the event that Takeda exercises the option,Takeda would license the global rights to develop and commercialize olverembatinib in all territories outside of,among others,mainland China,Hong Kong,Macau,and Taiwan,China.

Olverembatinib is currently approved in China for the treatment of adult patients with tyrosine kinase inhibitor (TKI)-resistant chronic phase CP-CML or accelerated-phase CML harboring the T315I mutation as confirmed by a validated diagnostic test. It is also approved for adult patients with CP-CML resistant to and/or intolerant of first- and second-generation TKIs. It remains investigational in other parts of the world.

Reference

1. Jabbour E,Oehler VG,Koller PB,et al. Olverembatinib after failure of tyrosine kinase inhibitors,including ponatinib or asciminib: a phase 1b randomized clinical trial. JAMA Oncol 2024. doi:10.1001/jamaoncol.2024.5157

About Ascentage Pharma

Ascentage Pharma (6855.HK) is a global,integrated biopharmaceutical company engaged in discovering,developing and commercializing 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 rich pipeline of innovative drug candidates that includes 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 13 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,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.

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