Ascentage Pharma Receives Approvals for Two Phase Ib/II Clinical Studies of the Bcl-2 Inhibitor APG-2575 for the Treatment of Waldenström Macroglobulinemia and Multiple Myeloma in China

SUZHOU,China and ROCKVILLE,Md.,Nov.23,2020 -- Ascentage Pharma (6855.HK),a globally focused,clinical-stage biotechnology company engaged in developing novel therapies for cancers,chronic hepatitis B (CHB),and age-related diseases,today announced that the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) has approved two Phase Ib/II clinical studies of its novel Bcl-2 inhibitor APG-2575; one for APG-2575 as a single agent or in combination with ibrutinib/rituximab for the treatment of patients with Waldenström macroglobulinemia (WM),and the other one for APG-2575 as a single agent or in combination with lenalidomide/dexamethasone for the treatment of patients with multiple myeloma (MM).

APG-2575 is a novel,orally administered Bcl-2‒selective inhibitor being developed by Ascentage Pharma. APG-2575 is designed to treat several hematologic malignancies by selectively blocking Bcl-2 to restore the normal apoptosis process in cancer cells. APG-2575 is the first China-developed Bcl-2 inhibitor having entered clinical development in China. APG-2575 has received clearances and approvals for multiple Phase Ib/II clinical studies in China,Australia,and the US,and is currently being developed in a range of hematologic malignancies globally. Of those studies,the Phase Ib/II study of APG-2575 as a single agent or in combination with ibrutinib/rituximab for the treatment of WM is a global multicenter trial with centers in Australia,China,and the US.

The Phase Ib/II study of APG-2575 as a single agent or in combination with ibrutinib/rituximab for the treatment of patients with WM

This global multicenter,open-label Phase Ib/II dose-expansion study is designed to evaluate the safety,tolerability,pharmacokinetics,and preliminary efficacy of APG-2575 as a single agent or in combination with ibrutinib/rituximab for the treatment of patients with WM.

WM is a rare indolent B-cell lymphoma,accounting for <2% of all non-Hodgkin's lymphoma (NHL) cases. Treatment recommendations for WM from current guidelines suggest an objective response rate (ORR) of about 80% with contemporary therapies,but they deliver a very low rate of very good partial response (VGPR) or deeper responses (20% or lower),with most patients eventually relapsing or experiencing further disease progression. Furthermore,patients are diagnosed with WM at a median age of 70,when many individuals are intolerant of aggressive therapies because of poor health conditions,hence presenting an urgent clinical need for more effective therapies[1].

Preclinical study data of APG-2575 have shown responses generated in WM models resistant or insensitive to ibrutinib,as well as the synergistic effect with ibrutinib in various models of NHL,including follicular lymphoma,diffuse large B-cell lymphoma,and WM.

The Phase Ib/II study of APG-2575 as a single agent or in combination with lenalidomide/dexamethasone for the treatment of patients with MM

This multicenter,open-label Phase Ib/II dose-escalation study to be carried out in China is designed to evaluate the safety,pharmacodynamics,and preliminary efficacy of APG-2575 as a single agent or in combination with lenalidomide/dexamethasone in patients with relapsed/refractory MM.

MM is a plasma cell proliferative disorder with manifestations like hypercalcemia,anemia,renal failure,and bone disease. MM remains incurable. As reported,MM accounts for about 1.8% of all malignant tumors and 18.2% of all hematopoietic neoplasms. MM is the second most common hematological malignancy[2]. The age-standardized incidence rate of MM in the US is approximately 6.9 per 100,000[3]. The incidence rate of MM in China has increased significantly in recent years,and the mortality rate increased with age,especially for patients over 60 years. The median age at diagnosis in China is 59 years,much younger than US (~69 years). The incidence also increases with age. With an aging population and advanced diagnostic capabilities,the prevalence of MM is anticipated to keep growing in China[4].

In the preclinical studies of Ascentage Pharma,APG-2575 demonstrated potent antiproliferative activity in MM cell lines bearing the chromosomal t (11;14). I And in MM cell lines without t (11;14),the combinations with lenalidomide or pomalidomide and dexamethasone greatly enhanced APG-2575 cell sensitivity and triggered more potent cell death.

"APG-2575 is a key drug candidate in our apoptosis-targeted pipeline,and the first China-developed selective Bcl-2 small-molecule inhibitor,with great therapeutic potential as a single agent or in combinations in a range of hematologic malignancies including WM and MM," said Dr. Yifan Zhai,Chief Medical Officer of Ascentage Pharma. "There is a growing emphasis on combination therapy in cancer treatments. We will accelerate these studies of APG-2575 and strive to develop a new treatment option for patients in need."

References:

[1] NCCN Clinical Practice Guidelines in Oncology for Waldenström Macroglobulinemia,Version 1.2020-December 6,2019

[2] Siegel,R. L.,Miller,K. D.,& Jemal,A. (2019). Cancer statistics,2019. CA: a cancer journal for clinicians,69(1),7-34.

[3] Cancer Stat Facts: Myeloma; Surveillance,Epidemiology,and End Results Program,US National Cancer Institute. https://seer.cancer.gov/statfacts/html/mulmy.html Accessed on 2020.3.18

[4] Liu,J.,Liu,W.,Zeng,X.,Ma,et al. Incidence and Mortality of Multiple Myeloma in China,2006-2016: An Analysis of the Global Burden of Disease Study 2016. J Hematol Oncol. 2019; 12: 136.

About APG-2575

APG-2575 is a novel,orally administered Bcl-2‒selective inhibitor being developed by Ascentage Pharma. APG-2575 is designed to treat a variety of hematologic malignancies by selectively blocking Bcl-2 to restore the normal apoptosis process in cancer cells. Ascentage Pharma has previously commenced Phase I studies of APG-2575 single agent in China,and the United States. Since March 2020,the company has received approvals and clearances for several Phase Ib/II studies of APG-2575 in China,and is advancing clinical development of APG-2575 for a variety of hematologic malignancy indications,including relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma,Waldenström macroglobulinemia,relapsed/refractory multiple myeloma,and relapsed/refractory acute myeloid leukemia. APG-2575 was recently granted two orphan drug designations by the US Food and Drug Administration in the treatment of Waldenström Macroglobulinemia and Chronic Lymphocytic Leukemia.

About Ascentage Pharma

Ascentage Pharma (6855.HK) is a globally,CHB,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 eight 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. 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,and China. HQP1351,the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia has been granted an Orphan Drug Designation (ODD) and a Fast Track designation by the US Food and Drug Administration (FDA),and a New Drug Application for the drug candidate has been submitted in China. To date,Ascentage Pharma has obtained a total of six ODDs from the FDA for four of the company's investigational drug candidates.

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