Ascentage Pharma Received Clearance from U.S. FDA to Proceed with Global Registrational Phase III Clinical Trial for Lisaftoclax (APG-2575) in Previously Treated Patients with CLL/SLL

ROCKVILLE, Md. and SUZHOU, China, Aug. 7, 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 lisaftoclax (APG-2575), a novel Bcl-2 inhibitor and one of the company's core assets, has been cleared by the US Food and Drug Administration (FDA) to enter a global registrational Phase III study for treatment of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who were BTKi previously treated . This clearance marks a major step-forward in the global development of lisaftoclax and another important milestone following the approval by the Center for Drug Evaluation (CDE) in China for the registrational Phase II study of lisaftoclax (APG-2575) in patients with relapsed/refractory CLL/SLL (R/R CLL/SLL) in December 2021, as it could potentially pave the way for lisaftoclax to become the second Bcl-2 inhibitor approved anywhere globally.

This global, multi-center, randomized-controlled, registrational Phase III study (APG2575CG301) is designed to assess the efficacy and safety of lisaftoclax (APG-2575) plus a Bruton's tyrosine kinase inhibitor (BTKi) in patients with CLL/SLL who were BTKi previously treated. The study is set to commence in the second half of 2023.

CLL/SLL is the most common form of leukemia in adults, accounting for one-quarter of all leukemia cases in the Western World, with over 100,000 new diagnoses globally every year¹. Despite significant initial responses to current first-line treatments such as immunotherapies, chemotherapies, and BTKis, relapse and drug resistance remain a major clinical challenge. At present, patients with CLL/SLL still have a huge unmet medical need for new treatment options.

Lisaftoclax (APG-2575) is a novel, orally administered small-molecule Bcl-2 selective inhibitor developed by Ascentage Pharma to treat a range of malignancies by selectively blocking the antiapoptotic protein Bcl-2, thus restoring the normal apoptosis process in cancer cells. With strong global best-in-class potential, lisaftoclax (APG-2575) is the first Bcl-2 inhibitor in China and the second anywhere globally that has demonstrated compelling clinical activity and entered a pivotal study.

Currently, Ascentage Pharma initiated a total of 19 clinical studies of lisaftoclax (APG-2575) globally, having treated more than 600 patients with the drug thus far, including more than 300 patients with CLL/SLL. In prior studies, lisaftoclax, both as a monotherapy and in combinations, showed clear therapeutic potential as a safe, effective, and easy-to-use therapy for patients with CLL/SLL. According to the initial results from a global Phase II study, lisaftoclax (APG-2575) combined with the next-generation BTKi acalabrutinib achieved encouraging objective response rates (ORRs) in patients with CLL/SLL, including an ORR of 100% (16/16) in treatment-naïve patients and 98% (56/57) in relapsed/refractory patients. In terms of safety, combination regimens demonstrated a safety profile that was on par with lisaftoclax (APG-2575) monotherapy and an extremely low incidence of tumor lysis syndrome (TLS). Furthermore, the study of lisaftoclax (APG-2575) was initiated with a daily dose ramp-up schedule that was friendly to patients and allowed them to quickly reach target doses².

"With progress in the research and development of targeted therapies, we have seen considerable improvement to the survival of patients with CLL/SLL. However, there remain major clinical challenges and urgent unmet medical needs for novel therapies that are safe and effective," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma.  "Lisaftoclax, a key drug candidate of our apoptosis-targeted pipeline with global best-in-class potential, has shown promising efficacy and favorable safety in earlier studies. We are very encouraged by the FDA's clearance for the global registrational Phase III study as it marks a major milestone in the development of lisaftoclax. Fulfilling the mission of addressing unmet clinical needs in China and around the world, we will press ahead with the global registrational Phase III study of lisaftoclax(APG-2575) to allow patients around the world to benefit from this novel therapeutic as soon as possible."

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 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.

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