First Dataset of Olverembatinib as Second-Line Therapy in Patients with Non-T315I-Mutant CP-CML Presented in Oral Report

Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in discovering, developing, and commercializing therapies to address global unmet medical needs primarily for malignancies, today announced that Prof. Weiming Li, of Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, has presented the latest clinical data of its novel drug candidate, olverembatinib (HQP1351), as a second-line therapy in patients with chronic-phase chronic myeloid leukemia (CP-CML), in an Oral Report at the 66th 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 represent leading scientific and clinical advances in the global hematology field. Garnering growing interest from the global research community, results from multiple clinical and preclinical studies on four of Ascentage Pharma's drug candidates (olverembatinib, lisaftoclax, APG-2449, and APG-5918) have been selected for presentations, including two Oral Reports, at this year's ASH Annual Meeting. Furthermore, this is the seventh consecutive year for studies of olverembatinib to be selected for Oral Reports at the meeting.

Results released through the Oral Report are the first batch of data of olverembatinib as a second-line therapy in patients with non-T315I-mutant CP-CML, which indicated that the drug may offer a safe and effective second-line therapy to patients with CP-CML, especially those who had failed on second-generation TKIs in the first-line setting. These data showed that, in patients with CP-CML who were resistant/intolerant to one prior line of TKIs, olverembatinib demonstrated a complete cytogenetic response (CCyR) rate of 74.1%, a major molecular response (MMR) rate of 40.6%; and in patients who had been treated with second-generation TKIs in the first-line setting, olverembatinib demonstrated a CCyR rate of 78.9% and an MMR rate of 43.5%, with efficacy improved over time. In terms of safety, olverembatinib showed a profile similar to that was previously reported. The study did not observe any new safety signals or report any arterial occlusive events (AOEs) or venous thromboembolisms (VTEs).

As the first approved third-generation BCR-ABL inhibitor in China, olverembatinib has already been approved for the treatment of adult patients with tyrosine kinase inhibitor (TKI)-resistant CP-CML or accelerated-phase (AP-) CML harboring the T315I mutation; and adult patients with CP-CML resistant to and/or intolerant of first- and second-generation TKIs. Olverembatinib is being jointly commercialized in China by Ascentage Pharma and Innovent Biologics.

Prof. Weiming Li, the principal investigator of the study, commented, "Among patients with CP-CML, it is a common situation in which patients need to switch to another therapy after failing the first-line treatment with TKIs, and the efficacy of first- and second-generation TKIs often falls short of the desired outcome. Therefore, patients have the desperate need for more second-line therapies that can offer higher efficacy. This is what propelled us to design such a study to evaluate the efficacy and safety of olverembatinib as a second-line therapy in patients with non-T315I-mutant CP-CML.

At the meeting, we released the first dataset of olverembatinib as a second-line therapy for patients with non-T315I-mutant CP-CML. These data showed that, olverembatinib as a second-line treatment offers promising responses and potential clinical benefits, as well as favorable safety and tolerability, especially in patients who had received second-generation TKIs in the first-line setting, thus suggesting that olverembatinib can potentially provide a new strategy for the second-line treatment of patients with CML.

In the future, we hope to release more clinical data that can support the adoption of olverembatinib for the second-line treatment and guideline inclusions. We will strive to bring a better new treatment option to patients and their physicians."

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, "When the very first batch of clinical data of olverembatinib came out in 2018, it was selected for Oral Report at the ASH Annual Meeting. Since then, clinical studies of the drug have been featured in Oral Reports at the meeting for seven consecutive years. For studies of a particular drug (olverembatinib) in a certain indication (CML) to be selected for Oral Reports for seven years in a row, it reflects the strong interest from the international hematology community. The data reported through the Oral Report this year reaffirmed the strong potential of olverembatinib in CML. Fulfilling our mission of addressing unmet clinical needs in China and around the world, we will expedite the global clinical development of our key drug candidates such as olverembatinib to bring more safe and effective therapies to patients as soon as possible."

Highlights of the data this study reported at ASH 2024 are as below:

Olverembatinib as Second-Line (2L) Therapy in Patients (pts) with Chronic Phase-Chronic Myeloid Leukemia (CP-CML)
Format: Oral Presentation
Abstract#: 480
Session: 632. Chronic Myeloid Leukemia: Novel Molecules in Clinical Practice

Highlights:

Background: Olverembatinib, a third-generation tyrosine kinase inhibitor (TKI), has demonstrated remarkable efficacy and a favorable safety profile in patients with CML resistant and/or intolerant to at least 2 TKIs or with the T315I mutation. The aim of this study was to assess the efficacy and safety of olverembatinib as a second-line treatment for patients with CP-CML without the T315I mutation.

Introduction: This is a single-arm, multicenter, open-label study designed to evaluate the efficacy, safety, and patients' quality of life of orally administered olverembatinib (40 mg QOD) in patients with CP-CML who were resistant/intolerant to one prior line of TKIs (including imatinib, flumatinib, nilotinib, and dasatinib) without the T315I mutation.

Enrolled Patients and Study Methods: As of November 15, 2024, the study enrolled a total of 43 patients with non–T315I-mutant CML-CP. These patients received orally administered olverembatinib 40 mg every other day (QOD) in 28-day cycles.

Efficacy Results:

• As of November 15, 2024, 33 (78.6%) patients had at least one efficacy assessment, 28 (66.7%) had at least two, 23 (54.8%) had at least three. Three patients had not yet undergone their first efficacy assessment.

• At data cutoff, 74.1% (20/27) of patients achieved a complete cytogenetic response (CCyR) and 40.6% (13/32) achieved a major molecular response (MMR). The CCyR and MMR rates evaluated at the end of Cycles 6, 9, 12, and 18 were 45.5% and 28.7%, 57.2% and 32.0%, 61.1% and 32.0%, and 68.9% and 40.7%, respectively, suggesting that efficacy improved over time.

• In 33 efficacy-evaluable patients, 24 were pretreated with second-generation TKIs as first-line treatment, of whom 78.9% (15/19) achieved CCyR, and 43.5% (10/23) achieved MMR. In 9 patients who were pretreated with imatinib, 50.0% achieved CCyR (4/8) and 33.3% achieved MMR (3/9).

Safety Results: The median (range) treatment duration was 16.0 (2-18) months. A total of 41 (95.3%) patients experienced any-grade treatment-related adverse events (TRAEs), of whom 21 (48.8%) had grade ≥ 3 treatment-related adverse events (TRAEs) and 6 (14.0%) had olverembatinib-related serious AEs (SAEs). Nonhematologic TRAEs included skin hyperpigmentation (51.2%), hyperuricemia (30.2%), and creatine phosphokinase increased (25.6%). Most of these TRAEs were grade 1 or 2. Grade ≥ 3 hematologic toxicities included platelet count decreased (46.5%), neutropenia (25.6%), and anemia (9.3%). Only one patient experience grade 1 hypertension that was possibly olverembatinib-related, and no AOEs or VTEs were reported during the study. Olverembatinib-related SAEs included platelet count decreased (7.0%), anemia and elevated ALT (2.3% each). No deaths were reported.

Conclusions: Olverembatinib may provide an effective and safe second-line treatment option for patients with CP-CML, especially those who have failed on second-generation TKIs in the first-line setting.

* Olverembatinib is an investigational drug that has not been approved for any indication outside China.

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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