Ascentage Pharma and AstraZeneca's Hematology R&D Center Acerta Pharma Enter Clinical Collaboration to Evaluate Combination of Bcl-2 Inhibitor APG-2575 and BTK Inhibitor Calquence® in Relapsed/Refractory CLL/SLL

Suzhou, China and Rockville, Maryland, USA, June 22, 2020 /PRNewswire/ -- Ascentage Pharma (6855.HK), a clinical-stage biopharmaceutical company dedicated to developing innovative drugs in the therapeutic areas of oncology, hepatitis B, and age-related diseases, announced today that it has established a clinical research partnership with Acerta Pharma, the hematology R&D center of excellence of AstraZeneca (LSE/STO/NYSE: AZN). The two parties will collaborate on APG-2575, Ascentage Pharma’s investigational first-in-class selective Bcl-2 inhibitor, and Acerta’s BTK (Bruton’s tyrosine kinase) inhibitor CALQUENCE^®Clinical studies were conducted on the combination therapy with (acalabrutinib) to evaluate its clinical efficacy in patients with relapsed or refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL).

This study is a global, multicenter, open-label Phase Ib/II dose and efficacy exploration study, aiming to evaluate APG-2575 as monotherapy or in combination with CALQUENCE.^®To evaluate the safety and tolerability in patients with relapsed or refractory CLL/SLL, and to preliminarily assess efficacy. The trial is planned to be conducted across multiple sites in the United States, Europe, and Australia, with the first patient dosed in the United States.

CLL/SLL is a clonal proliferative tumor of mature B lymphocytes. It is the most prevalent adult leukemia in developed countries in Europe and America, accounting for approximately 30% of all leukemia cases. The annual incidence rate is 2–6 per 100,000 people, rising to as high as 12.8 per 100,000 among individuals aged 65 and older. Although first-line regimens have significantly improved initial remission rates in treatment-naïve CLL/SLL patients, long-term medication is required to control the disease, and prognosis is generally poor upon relapse. Recent studies have shown that combining BTK inhibitors with Bcl-2 inhibitors for the treatment of CLL/SLL offers the advantage of high deep response rates, potentially shifting from long-term therapy to fixed-duration treatment, thereby providing the possibility of clinical cure and treatment discontinuation for CLL/SLL patients.^[1,2] . This undoubtedly also provides a foundation for exploring the combination of APG-2575 with BTK inhibitors.

Dr. Yang Dajun, Chairman and CEO of Ascentage Pharma, stated, “We are pleased to enter into this clinical collaboration with Acerta, an AstraZeneca company. APG-2575 is a key investigational asset in Ascentage Pharma’s apoptosis product pipeline and has demonstrated significant potential in the treatment of hematologic malignancies. This collaboration will accelerate the global clinical development of APG-2575. Safe and effective combination therapies represent an important trend in oncology treatment, and the potential of combining Bcl-2 inhibitors with BTK inhibitors should not be overlooked. We look forward to the combination of APG-2575 and CALQUENCE^®The potential synergistic effects of combination therapy offer more treatment options for CLL/SLL patients worldwide.”

References

[1] Jain N, Keating M, Thompson P, et al. Ibrutinib and venetoclax for first-line treatment of CLL. N Engl J Med 2019;380:2095-2103.

[2] Wiestner A. Ibrutinib and venetoclax — doubling down on CLL. N Engl J Med 2019;380:2169-2171.

AboutAPG-2575

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. It is intended for the treatment of various hematologic malignancies. Previously, the company initiated Phase I monotherapy clinical trials of this drug in the United States, Australia, and China. Since March this year, APG-2575 has successively received approvals for multiple Phase Ib/II clinical trials in the United States and China, and clinical development for multiple hematologic oncology indications is being advanced concurrently.

About Ascentage Pharma

Ascentage Pharma is a China-based, globally oriented clinical-stage biopharmaceutical company dedicated to developing innovative drugs in therapeutic areas such as oncology, 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 has independently developed a protein-protein interaction (PPI)-targeted drug design platform and is at the global forefront of novel drug development in the apoptosis pathway. The company has established a pipeline of eight Class 1 small-molecule new drug candidates currently in clinical development, including inhibitors targeting key proteins in the apoptosis pathway such as Bcl-2, IAP, or MDM2-p53; next-generation inhibitors targeting kinase mutants emerging in cancer treatment; and other innovative therapies. Ascentage Pharma is the only innovative company worldwide with clinical-stage candidates targeting all key proteins in the apoptosis pathway. Currently, the company is conducting more than 30 Phase I/II clinical trials in China, the United States, and Australia. Its core product, HQP1351, for the treatment of resistant chronic myeloid leukemia (CML), has been granted Fast Track designation and Orphan Drug status by the U.S. FDA, and a New Drug Application (NDA) has been submitted in China.

Forward-Looking Statements

The forward-looking statements made in this document relate only to events or information as of the date on which such statements are made. Except as required by law, we undertake no obligation to update or publicly revise any forward-looking statements or unexpected events after the date on which they are made, whether as a result of new information, future events, or otherwise. Please read this document carefully and understand that our actual future results or performance may differ materially from expectations. All statements herein are made as of the publication date of this document and are subject to change due to future developments.