Ascentage Pharma and AstraZeneca launch clinical collaboration on registration phase III study of Bcl-2 inhibitor Lisaftoclax combined with BTK inhibitor Acalabrutinib in first-line CLL/SLL treatment-naïve patients

Suzhou, Chinaand Rockville, Maryland, October 15, 2023 /PRNewswire/ — Ascentage Pharma (6855.HK), a global biopharmaceutical company committed to the development of new treatments for cancer, chronic hepatitis B (CHB) and age-related diseases, today announced a clinical collaboration investment with AstraZeneca (China) Ltd. (or “AstraZeneca”). The companies will jointly conduct a registrational Phase III study of the Bcl-2 inhibitor APG-2575 (lisaftoclax) in combination with AstraZeneca’s Bruton’s tyrosine kinase (BTK) inhibitor CALQUENCE® (acalabrutinib) in treatment-naive patients. . Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

This global multicenter, randomized controlled, open-label, pivotal Phase III confirmatory trial is designed to evaluate the efficacy and safety of lisaftoclax in combination with acalabrutinib and immunochemotherapy in patients with previously untreated CLL/SLL.

This collaboration marks another step forward for Ascentage Pharma and AstraZeneca in the joint clinical development of lisaftoclax combined with acalabrutinib.exist June 2020, Ascentage Pharma and Acerta Pharma, the research and development center of Ascentage Pharma, have reached a clinical cooperation to jointly conduct a global phase II study to evaluate the safety, tolerability and effectiveness of Ascentage Pharma’s Bcl-2 selective inhibitor lisaftoclax. . inhibitor, in combination with Acerta Pharma’s BTK inhibitor acalabrutinib.In this study, lisaftoclax combined with acalabrutinib showed strong therapeutic potential, with an objective response rate (ORR) of 98% in patients with relapsed/refractory (R/R) CLL/SLL and 98% in patients with treatment-naïve CLL/SLL. ORR of 100% for CLL/SLL and excellent safety profile comparable to lisaftoclax monotherapy⁽¹⁾. These results were presented as an oral presentation at the 2022 American Society of Hematology (ASH) Annual Meeting.

CLL/SLL is a hematologic malignancy caused by mature B-cell tumors. CLL/SLL primarily affects the elderly and is one of the most common leukemia subtypes in adults, accounting for a quarter of all leukemia cases in the Western world, with more than 100,000 new diagnosed cases reported globally each year⁽²⁾.exist ChinaThe incidence of CLL/SLL is rising rapidly, with younger onset age and higher aggressiveness⁽³⁾, thereby posing a serious threat to public health in the country. Advances in basic research and targeted therapies have brought meaningful survival benefits to patients with CLL/SLL. However, CLL/SLL still faces significant clinical challenges, and new treatment options that offer efficacy and safety are urgently needed.

Lisaftoclax is a new oral small molecule Bcl-2 selective inhibitor developed by Ascentage Pharma. It treats malignant tumors by selectively blocking the anti-apoptotic protein Bcl-2, thereby restoring the normal apoptosis process of cancer cells. lisaftoclax has strong global best-in-class potential and is the world’s first Bcl-2 inhibitor China It is the second company in the world to demonstrate compelling clinical activity and enter a pivotal registration study. Currently, lisaftoclax is being evaluated in multiple clinical studies around the world, and more than 300 CLL/SLL patients have been treated with the drug. Interim results indicate that lisaftoclax, either as monotherapy or in combination, provides effective efficacy for patients with CLL/SLL and has the potential to become a safer, more effective and more patient-friendly treatment option.It is also worth noting that in August 2023Lisaftoclax has been approved by the U.S. Food and Drug Administration (FDA) to enter a global registrational Phase III study to evaluate the efficacy and safety of lisaftoclax in combination with a BTK inhibitor in patients with previously treated CLL/SLL.

Acalabrutinib is a new generation of highly selective BTK inhibitor that specifically inhibits the BTK pathway and is the standard of care for CLL patients adopted globally. In 2017, acalabrutinib was approved for the second-line treatment of patients with mantle cell lymphoma (MCL) through the priority review process of the U.S. Food and Drug Administration (FDA). Subsequently, in 2019, the drug was approved for patients with additional indications. Adult patients with CLL/SLL. At the same time, acalabrutinib has been approved in more than 50 countries/regions including the EU and EU. Japan so far.exist China This year, acalabrutinib was approved for two indications, including MCL patients who have received at least one prior therapy; and adult patients with CLL/SLL who have received at least one prior therapy.

PhD. Zhai YifanChief Medical Officer, Ascentage Pharma”, said, “Combining Bcl-2 inhibitors and BTK inhibitors as therapeutic approaches has long attracted interest from the research community and industry. The Bcl-2 inhibitor lisaftoclax is a key drug candidate in Ascentage Pharma’s apoptosis-targeted pipeline. . The global phase II study of lisaftoclax combined with acalabrutinib shows that the combination regimen is expected to be a patient-centered treatment strategy with huge therapeutic potential. The clinical management of overseas CLL/SLL has entered the chemotherapy-free era, and patients in China There is also an urgent need for a safer and more effective Bcl-2 inhibitor that can be used in combination with BTK inhibitors.Fulfilling our mission to address unmet clinical needs China Globally, we will work closely with AstraZeneca to actively promote the clinical development project of lisaftoclax and strive to bring the drug to the market as soon as possible to benefit more patients. “

Multiple sclerosis. Yang HaiyingVice President and Head of Medical Affairs, AstraZeneca Chinacommented: “Phase III results from the ASCENT, ELEVATE-TN and ELEVATE-RR trials solidify AstraZeneca’s position in hematology, while acalabrutinib-based combination regimens have been widely adopted as standard of care treatments. BTK inhibitors can deliver Survival Benefit However, significant clinical challenges remain in this therapeutic area, and patients are in urgent need of safe and effective new therapies, especially fixed-duration therapies. We believe acalabrutinib-based combinations can lead to more effective and efficient treatment regimens. Hematology Precision targeted therapy for patients with malignant tumors China As we take further steps to transform hematological malignancies into manageable chronic diseases. Through these innovative partnerships with local Chinese companies, we are eager to expand into more therapeutic areas and bring clinical benefits to a wider range of cancer patients. China“

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About Ascentage Pharma

Ascentage Pharma (6855.HK) is a globally focused biopharmaceutical company dedicated to developing new treatments for cancer, chronic hepatitis B and age-related diseases.exist October 28, 2019Ascentage Pharmaceuticals is listed on the main board of The Stock Exchange of Hong Kong Limited, 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 established a pipeline of nine clinical 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, as well as next-generation tyrosine Acid kinase inhibitors (TKIs). Ascentage Pharma is also the only company in the world with active clinical programs targeting all three classes of known key regulators of apoptosis. The company is conducting more than 40 clinical trials in the United States, Australia, Europeand China. Ascentage Pharma has been approved for a number of major national R&D projects, including 5 major new drug projects, 1 new drug incubator, 4 innovative drug projects, and 1 major infectious disease prevention and treatment project.

The company’s core drug candidate for the treatment of drug-resistant chronic myelogenous leukemia (CML) and the company’s first approved product, Olverembatinib, received priority review and breakthrough designation from the National Center for Drug Evaluation (CDE) Therapeutics Approved Medical Products Administration (NMPA). As of now, the drug has been included in the drug catalog. China 2022 National Reimbursement Drug List (NRDL). In addition, olverembatinib has received Orphan Drug Designation (ODD) and Fast Track Designation (FTD) from the US FDA, and Orphan Drug Designation from the EU EMA. As of now, Ascentage Pharma’s four drug candidates have received 16 ODD, 2 FTD, and 2 rare pediatric disease (RPD) designations from the U.S. FDA, as well as 1 orphan drug designation from the European Union EMA.

With strong R&D capabilities, Ascentage Pharma owns global intellectual property rights and has established global partnerships with many well-known biotechnology and pharmaceutical companies and research institutions such as UNITY Biotechnology, MD Anderson Cancer Center, Mayo Clinic, and Dana-Farber Cancer Institute. , MSD and AstraZeneca. The company has built a talented team with global experience in innovative drug discovery and development and is building world-class commercial manufacturing and sales and marketing teams. One of Ascentage Pharma’s core goals is to continuously enhance its research and development capabilities and accelerate clinical development plans to fulfill its mission of solving unmet clinical needs. China and around the world, benefiting more patients.

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Source: Ascentage Pharma