Ascentage Pharma Announces New Drug Application for Its Novel Bcl-2 Inhibitor Lisaftoclax Received and Recommended for Critical Review Designated by China’s CDE NMPA

ROCKVILLE, Md. again SUZHOU, China, Nov. 17, 2024 /PRNewswire/ — Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in the discovery, development and commercialization of therapeutics to address unmet medical needs particularly in terminal diseases, today announced that its in-house New Drug Application (NDA) developed a novel investigational Bcl- 2 selective inhibitor, lisaftoclax (APG-2575), for the treatment of patients with relapsed or refractory (r/r) lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) was accepted and recommended for critical review designation by Center for Drug Evaluation (CDE) of China Nationally Medicine (TASE:) Product Management (NMPA). This NDA, is the first Bcl-2 inhibitor developed internally Chinamay lead lisaftoclax to become the second Bcl-2 inhibitor approved anywhere in the world.

This NDA is based on the results of a pivotal Phase II registration study China (APG2575CC201) evaluated the efficacy and safety of lisaftoclax in patients with r/r CLL/SLL. The primary endpoint of the study is overall response rate (ORR).

CLL/SLL is a hematologic malignancy caused by mature B-cell neoplasms. It mainly affects the elderly and is among the most common types of leukemia in The Western Worldwith more than 100,000 new diagnoses reported worldwide each year¹. In Chinawhile the prevalence of CLL/SLL is lower than in western countries, the disease occurs at a rate that increases rapidly, when a person begins to grow and is more aggressive.². SLL and CLL are two different manifestations of the same disease and about 20% of all cases of SLL will progress to CLL.³. Treatments such as immunotherapies and Bruton’s tyrosine kinase inhibitors (BTKis) have greatly improved patients’ response to initial treatment. However, due to the limitations of existing treatment options, the poor prognosis of patients, the negative impact on patients’ quality of life and the high complexity of the disease, patients with r/r CLL/SLL are in great need of new available treatment options. safe and effective.

The introduction of Bcl-2 inhibitors has revolutionized the treatment of CLL/SLL. Bcl-2 is an apoptosis suppressor factor that regulates cell survival by regulating mitochondrial membrane permeability. It suppresses apoptosis by preventing the release of cytochrome C from mitochondria or by binding to apoptotic activators to inhibit caspase activity. Overexpression of Bcl-2, found in a variety of hematological malignancies, especially CLL/SLL, is a key mechanism by which tumor cells avoid apoptosis.

However, the development of Bcl-2 as a therapeutic is particularly challenging because its mechanism of action is based on protein-protein interactions (PPI). The binding interface of Bcl-2 is relatively large, making it difficult for small molecules to exert inhibitory effects. Additionally, the Bcl-2 protein is located in the mitochondrial membrane, and mitochondria, with their double membrane structure, are among the most complex and challenging cellular components. Drugs must first penetrate the cell membrane before they can continue to act on the mitochondrial membrane. Almost 40 years since this target was discovered, only one Bcl-2 inhibitor has been approved worldwide, a fact that highlights the difficulties and major challenges in this field of research and development. In Western countries, the treatment of CLL/SLL has entered a new era of free and long-lasting drugs, while no Bcl-2 inhibitor has been approved China in this treatment area. Therefore, patients in China they have an urgent unmet need for new therapies that can provide both efficacy and safety.

Lisaftoclax is a novel, investigational orally administered Bcl-2 selective inhibitor developed by. Ascentage Pharma to treat toxic patients by selectively inhibiting the antiapoptotic protein Bcl-2 and thereby restoring the normal process of apoptosis in cancer cells. Lisaftoclax is the first Bcl-2 inhibitor China and the second time anywhere in the world that we have demonstrated a compelling clinical benefit and entered a pivotal registry study. Lisaftoclax has broad therapeutic potential in a variety of hematological malignancies and solid tumors, particularly as a single agent and in combinations in CLL/SLL. Lisaftoclax is a potential drug that could offer patients a safe, effective, and easy-to-use treatment.

Lisaftoclax is being evaluated in several Phase III registration studies, including a global Phase III registration study of lisaftoclax in combination with BTKi in previously treated patients with CLL/SLL (cleared US FDA); a global Phase III registration study of lisaftoclax in combination with acalabrutinib for first-line treatment of patients with CLL/SLL; a global Phase III registration study of lisaftoclax in combination with azacitidine (AZA) for the first-line treatment of elderly/unfit patients with acute myeloid leukemia (AML) who were refractory to standard induction chemotherapies; and a global Phase III registration study of lisaftoclax in combination with AZA for the first-line treatment of newly diagnosed patients with high-risk myelodysplastic syndrome (MDS).

“Ascentage Pharma’s The founding team has more than 20 years of deep experience in developing therapies targeting apoptosis and has made a significant step forward with the Bcl-2 vaccine,” said Dr. Dajun YangChairman and CEO of Ascentage Pharma. “Until now, only one Bcl-2 inhibitor has been approved worldwide, a fact that underlines the great difficulties and challenges in this field of research and development. This NDA submission for lisaftoclax may pave the way for lisaftoclax to become the first to be approved. China-developed a Bcl-2 inhibitor, thus marking another major milestone Ascentage Pharma’s deep dedication and persistent work over the past 15 years.”

Dr. Yang he continued, “Globally, ir/r CLL/SLL represents an area of ​​urgent unmet clinical need. For lisaftoclax to be successfully advanced so far, it is a testament to the fact Ascentage Pharma’s strong capabilities in global pharmaceutical innovation. Going forward, we will accelerate the global development of lisaftoclax in other indications to bring benefit to patients as quickly as possible. We remain firmly committed to our mission to address unmet clinical needs China and around the world, we will strive to develop new treatments for patients who need them.”

References:

1. Yao, Y., Lin, X., Li, F., et al. Global burden and risk factors of chronic lymphocytic leukemia in 204 countries and territories from 1990 to 2019: an analysis based on the global burden of disease survey 2019. Biomed Eng Online. 2022 Jan 11;21(1):4. DOI: 10.1186/s12938-021-00973-6

2. Liu Peng. Practice guidelines for the diagnosis and treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma Zhongshan Hospital, Fudan University (v1.2018). [J]. Chin J Clin Med, 2018, 25(1): 157-160. DOI 10.12015/j. etc. 1008-6358. 2018. 20180

3. Li Jianyong, Qiu Lugui. Hematology Committee of the Chinese Medical Association; Hematological Oncology Committee of China Anti-Cancer Association; Chinese Chronic Lymphocytic Leukemia Working Group. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma China (2022). Zhonghua Xue Ye Xue Za Zhi. 2022 May 14;43(5):353-358. DOI: 10.3760/cma.j.issn.0253-2727.2022.05.001

About Ascentage Pharma

Ascentage Pharma (6855.HK) is a global, integrated biopharmaceutical company engaged in the discovery, development and commercialization of therapeutics to address global unmet medical needs primarily in malignancies. Opened October 28, 2019, Ascentage Pharma was listed on the Board Hong Kong Limited share price with stock code 6855.HK.

The company has built a rich pipeline of innovative drugs including novel, highly potent Bcl-2 and dual Bcl-2/Bcl-xL inhibitors, as well as candidates targeting the IAP and MDM2-p53 pathways, as well as next-generation TKIs . Ascentage Pharma and is the only company in the world with active clinical programs targeting all three known classes of key regulators of apoptosis. The company has conducted more than 40 clinical trials in the US, Australia, In Europeagain Chinaincluding 13 enrollment courses (completed/ ongoing/ planned).

Olverembatinib, the company’s first product for the treatment of drug-resistant myeloid leukemia (CML) and the company’s first approved product Chinahas been awarded a Critical Review Designation and a Breakthrough Therapy Designation by Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). Until now, the drug was included in the China National Reimbursement Drug List (NRDL). In addition, olverembatinib has been granted Orphan Drug Designations (ODDs) and Fast Track Designation (FTD) by US FDAand Orphan Designation by the EU EMA.

Until now, Ascentage Pharma got a total of 16 ODDs from US FDA and 1 Orphan Designation from the EU EMA for the company’s 4 investigational drug designations. Using its strong R&D capabilities, Ascentage Pharma built a portfolio of global intellectual property rights and entered into global partnerships and other partnerships with many leading biotechnology and pharmaceutical companies such as Takeda, AstraZeneca (NASDAQ:), Merck (NS:), Pfizer (NYSE:) and Innovent; and research and development partnerships with leading research institutes such as Dana-Farber Cancer Institute, Mayo Clinic, MD Anderson Cancer Center, National Cancer Institute as well as University of Michigan.

The company has built a talented team with extensive global experience in discovery and development of innovative drugs and fully functional commercial manufacturing and Sales and Marketing teams. One important objective Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to achieve its goal of addressing unmet clinical needs. China and worldwide for the benefit of more patients.

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