Ascentage Pharma has announced a New Drug Application for its novel Bcl-2 Inhibitor Lisaftoclax that has been accepted and recommended by the China NMPA of CDE for Priority Review Designation.

ROCKVILLE, Md. And Suzhou, China, November 17, 2024 /PRNewswire/ — Essentage Pharma (6855.HK), a global biopharmaceutical company primarily engaged in the discovery, development and commercialization of therapeutics to address global unmet medical needs for chronic diseases, today announced that a new drug application cation (NDA) has developed an investigational novel Bcl-2 selective inhibitor for its in-house lisaftoclax (APG-2575) for the treatment of patients with relapsed or refractory (r/r) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has received priority review designation. is recommended. China Center for Drug Evaluation (CDE) National Medical (TASE:) Product Administration (NMPA). This NDA, the first for a locally developed Bcl-2 inhibitor Chinapotentially making lisaftoclax the second Bcl-2 inhibitor approved anywhere in the world.

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

CLL/SLL is a hematologic malignancy caused by mature B-cell neoplasms. It mainly affects the older population and is one of the most common subtypes of leukemia. Western worldWith over 100,000 new diagnoses reported globally each year¹. i ChinaWhile the incidence rate of CLL/SLL is lower than in Western countries, the disease is occurring at a rapidly increasing rate, with a younger age of onset and greater aggressiveness.². SLL and CLL are two different manifestations of the same disease, and about 20 percent of all SLL cases will progress to CLL.³. Treatments such as immunotherapies and Burton’s tyrosine kinase inhibitors (BTKis) have significantly improved patient response to initial treatment. However, due to limitations of current treatment options, poor patient prognosis, severe impact on patients’ quality of life and high disease complexity, patients with r/r CLL/SLL are in dire need of new treatment options. Safe and effective.

The introduction of Bcl-2 inhibitors has further revolutionized the treatment of CLL/SLL. Bcl-2 is an apoptosis suppressor factor that regulates cell survival by controlling mitochondrial membrane permeability. It suppresses apoptosis by inhibiting 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 hematologic malignancies, particularly CLL/SLL, is a key mechanism by which tumor cells escape apoptosis.

However, the development of Bcl-2 as a therapeutic target is difficult because its mechanism of action is based on protein-protein interaction (PPI). The binding interface of Bcl-2 is relatively large, making it difficult for small molecule inhibitors to exert blocking effects. Furthermore, Bcl-2 protein is located on 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 further act on the mitochondrial membrane. In the nearly 40 years since the discovery of this target, only one Bcl-2 inhibitor has been approved globally, a fact that highlights the enormous difficulties and challenges in this area of ​​research and development. In Western countries, the treatment of CLL/SLL has entered a new era of chemotherapy-free and fixed-duration regimens, while Bcl-2 inhibitors have not been approved. China in this treatment area. Therefore, in patients China New treatments that offer both efficacy and safety are urgently needed.

Lisaftoclax is a novel, investigational orally administered small molecule Bcl-2 selective inhibitor in development. Essentage Pharma Treating malignancy patients by selectively blocking the antiapoptotic protein Bcl-2 and thereby restoring the normal apoptosis process in cancer cells. Lisaftoclax is the first Bcl-2 inhibitor in it. China and another globally that has demonstrated strong clinical benefit and entered a pivotal registration study. Lisaftoclax has broad therapeutic potential for a variety of hematologic malignancies and solid tumors, particularly as a single agent and in combination in CLL/SLL. Lisaftoclax is a potential drug that may offer patients a safe, effective, and easy-to-use treatment option.

Lisaftoclax is being evaluated in several registrational phase III studies, including a global registrational phase III study of lisaftoclax in combination with BTKi in patients with CLL/SLL. US FDA); A global registration phase III study of lisaftoclax in combination with acalabrutinib for the treatment of blinded patients with CLL/SLL; A global registration phase III study of lisaftoclax in combination with azacitidine (AZA) for the first-line treatment of elderly/refractory patients with acute myeloid leukemia (AML) and the first in newly diagnosed patients with high-risk myelodysplastic syndrome (MDS). A global registration phase III study of lisaftoclax in combination with AZA for line therapy.

“Ascentage Pharma’s The founding team has over 20 years of deep experience in developing apoptosis-targeted therapies and has made significant progress with the Bcl-2 target,” said Dr. Dajin YangChairman and CEO of Essentage Pharma. “To date, only one Bcl-2 inhibitor has been approved globally, a fact that highlights the enormous difficulties and challenges in this area of ​​research and development. This NDA submission for lisaftoclax is likely to But it could pave the way for lisaftoclax to become the first approved. Chinadeveloped a Bcl-2 inhibitor, thus marking another important milestone which Ascentage Pharma’s Deep commitment and continuous work over the last 15 years.”

Dr. Joe continued, “Globally, r/r CLL/SLL represents an urgent unmet medical need. To successfully advance lisaftoclax to this point, is a true testament.” Ascentage Pharma’s Strong capabilities in global pharmaceutical innovation. Going forward, we will accelerate the global development of lisaftoclax in other indications to benefit patients as soon as possible. I remain steadfast in our mission to address unmet medical needs China And around the world, we will strive to develop more innovative treatments for patients in need.”

References:

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

2. Liu Peng. Follow the guidelines for diagnosis and treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma. Zhongshan Hospital, Fudan University (v1.2018). [J]. Chen J Clin Med, 2018, 25(1): 157-160. DOI 10.12015/d issn 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 Working Group on Chronic Lymphocytic Leukemia. Guidelines for the Diagnosis and Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma China (2022 Zhonghua Xue Ye Xue Za Zhi) May 14; 43(5): 10.3760/cma.j.issn.0253-2722.05.001

about Essentage Pharma

Essentage Pharma (6855.HK) is a global, integrated biopharmaceutical company primarily engaged in discovering, developing and commercializing therapies to address global unmet medical needs in malignant diseases. But 28 October 2019, Essentage Pharma K was listed in the main board. The Stock Exchange of Hong Kong Limited With stock code 6855.HK.

The company has built a rich pipeline of advanced drug candidates including novel, highly potent Bcl-2 and dual Bcl-2/Bcl-xL inhibitors, as well as candidates targeting the IAP and MDM2-p53 pathways, and next-generation TKIs. are included. Essentage Pharma It is 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, Europeand Chinaincluding 13 registrational studies (completed/ongoing/planned).

Olverembatinib is the Company’s first lead asset developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the Company’s first approved product. Chinahas been given priority review designation and breakthrough therapy designation by Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, this drug has been included in the China National Reimbursement Drug List (NRDL). Additionally, olverembatinib has been granted Orphan Drug Designation (ODDs) and Fast Track Designation (FTD). US FDAand an orphan designation by the EU’s EMA.

to date, Essentage Pharma A total of 16 ODDs have been obtained from US FDA and 1 orphan designation from the EU’s EMA for 4 of the company’s investigational drug candidates. Leveraging its strong R&D capabilities, Essentage Pharma has built a portfolio of global intellectual property rights and established global partnerships and other relationships with several leading biotechnology and pharmaceutical companies such as Takeda, AstraZeneca (NASDAQ: Merck (NS:) Pfizer (NYSE: ) and Innovent; and research and development tie-ups with leading research institutes viz Dana Farber Cancer Institute, Mayo Clinic, MD Anderson Cancer Center, National Cancer Institute And University of Michigan.

The company has built a talented team with global experience in innovative drug discovery and development and fully functional commercial manufacturing and sales and marketing teams. An important purpose of Essentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfill its mission of addressing unmet medical needs. China And for the benefit of more and more patients around the world.

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