Ascentage Pharma Announces First Patient Dosed in China Phase I Trial of APG-2575, the First Domestically Developed Bcl-2 Selective Inhibitor to Enter Clinical Development

On July 15, 2019, Ascentage Pharma, a clinical-stage biopharmaceutical company dedicated to developing innovative drugs in the fields of oncology, hepatitis B, and age-related diseases, announced that it had initiated a Phase I clinical trial in China for its novel, first-in-class Bcl-2 selective inhibitor, APG-2575, for the treatment of hematologic malignancies, and had completed dosing of the first patient. Previously, the company had launched a multicenter, dose-escalation, monotherapy Phase I clinical trial for this drug in the United States and Australia. APG-2575 is the first domestically developed Bcl-2 selective small-molecule inhibitor to enter clinical trials.

APG-2575 is a novel oral Bcl-2 selective inhibitor under development by Ascentage Pharma. It restores the programmed cell death mechanism (apoptosis) in tumor cells by selectively inhibiting Bcl-2, a member of the Bcl-2 protein family, thereby killing tumors. It is intended for the treatment of various hematologic malignancies.

Bcl-2 is a member of the Bcl-2 family, the earliest discovered group of anti-apoptotic proteins. Proteins in the Bcl-2 family play a crucial role in regulating apoptosis by forming heterodimers with pro-apoptotic proteins such as BIM and BAD, as well as through homodimerization. It has been nearly 30 years since the role of Bcl-2 family proteins in apoptosis and cancer therapy was first identified. Drug development targeting Bcl-2 family proteins has proven extremely challenging; however, the successful market launch of Venclexta (ABT-199), a selective Bcl-2 inhibitor, in April 2016 provided strong clinical validation for this therapeutic target. Ascentage Pharma’s APG-2575 is one of the few selective Bcl-2 inhibitors globally that remains active in clinical development following Venclexta.

This Phase I clinical study in China aims to evaluate the safety and tolerability of APG-2575 in patients with hematologic malignancies, and to determine the maximum tolerated dose (MTD) or the recommended Phase 2 dose (RP2D) of APG-2575. The target patient population for this clinical study includes individuals with chronic lymphocytic leukemia and non-Hodgkin lymphoma. The first subject has been dosed at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, and the first dose escalation cohort is currently underway.

Prior to this, APG-2575 had initiated Phase I clinical trials in the United States and Australia, with participating centers including MD Anderson Cancer Center and Mayo Clinic, among others. The indicated patient population covers various major hematologic malignancies, including chronic lymphocytic leukemia, non-Hodgkin lymphoma, myeloma, and acute myeloid leukemia. Currently, dose escalation across four cohorts has been completed in the United States and Australia. To date, APG-2575 has demonstrated a favorable safety profile and shown preliminary efficacy in patients with relapsed/refractory chronic lymphocytic leukemia.

Notably, multiple preclinical studies on APG-2575 were presented at this year’s American Association for Cancer Research (AACR) Annual Meeting, highlighting its potential in combination therapy.

Dr. Yang Dajun, Chairman of Ascentage Pharma, stated: “APG-2575 is a key asset in the Company’s apoptosis product pipeline. The administration of the first dose to a patient in the Phase I clinical trial in China marks the entry of APG-2575 into clinical development in China, the United States, and Australia, representing another milestone in the global clinical development of our apoptosis product pipeline. We aim to advance subsequent clinical studies smoothly and provide new treatment options for more patients with hematologic malignancies as soon as possible.”

APG-2575 is a novel oral Bcl-2 selective inhibitor under development by Ascentage Pharma. It restores the programmed cell death mechanism (apoptosis) in tumor cells by selectively inhibiting Bcl-2, a member of the Bcl-2 protein family, thereby killing tumor cells and is intended for the treatment of various hematologic malignancies. The Phase I clinical trial has been launched in China, with the first subject dosed and the initial dose escalation ongoing. Prior to this, APG-2575 had already initiated Phase I clinical studies in the United States and Australia.

Ascentage Pharma is a China-based, globally oriented clinical-stage biopharmaceutical company dedicated to developing innovative drugs in the therapeutic areas of oncology, hepatitis B, and age-related diseases. The company possesses an independently developed protein-protein interaction (PPI) targeted drug design platform. Ascentage Pharma’s R&D pipeline primarily focuses on inhibitors of key proteins in the apoptosis pathway, such as BCL-2, IAP, or MDM2-p53, to reactivate apoptotic programs in tumor cells; it also includes second- and third-generation inhibitors targeting kinase mutations that emerge during cancer treatment. Currently, eight Class 1 new drugs from the company have entered Phase I/II clinical development in China, the United States, and Australia.