Ascentage Pharma Announces Updates on the Clinical Development of APG-2575, including an ORR of 70% in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia

SUZHOU,China and ROCKVILLE,MD,Dec. 10,2020 -- 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 updates on the clinical development of the company's novel Bcl-2 inhibitor APG-2575,further demonstrating the drug candidate's therapeutic potential.

APG-2575 is a novel,orally administered small-molecule Bcl-2‒selective inhibitor being developed by Ascentage Pharma. APG-2575 is designed to treat hematologic malignancies and solid tumors by selectively blocking antiapoptotic protein Bcl-2 to restore the normal apoptosis process in cancer cells. As a bona fide Bcl-2 inhibitor,APG-2575 demonstrated desired target engagement. APG-2575 selectively binds to Bcl-2,disrupts Bcl-2:BIM complexes,and releases the proapoptotic protein BIM. Freed BIM subsequently activates BAX/BAK for pore formation on the mitochondria membrane,leading to mitochondrial outer-membrane permeabilization (MOMP),cytochrome c release,caspase activation,and apoptosis of cancer cells. APG-2575 is the first China-developed Bcl-2 inhibitor having entered clinical development in China. As a single agent,APG-2575 has potent antitumor activity in Bcl-2-dependent tumor cells,and has shown a broad range of antitumor activities when combined with other oncologic drugs. Previously,APG-2575 had 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.

Highlights of the update

In total,9 clinical studies are ongoing globally,with over 100 patients who have been administered APG-2575 at doses ranging from 20 mg to 1200 mg for the treatment of chronic lymphocytic leukemia (CLL),follicular lymphoma (FL),mantle cell lymphoma (MCL),diffuse large B-cell lymphoma (DLBCL),multiple myeloma (MM),acute myeloid leukemia (AML),and high leukocyte acute leukemia (HCL),etc.

Studies of APG-2575 in the treatment of relapsed/refractory CLL (r/r CLL) have enrolled over 30 patients. Preliminary results show that an objective response rate (ORR) of 70% has been reached in evaluable patients.

On safety:

Maximum tolerated dose (MTD) has not been reached,and no dose-limiting toxicity (DLT) was observed.

No clinical or laboratory tumor lysis syndrome (TLS) was observed.

Most treatment-related adverse events (TRAEs) were of Grade 1 or 2.

Limited cases of neutropenia and thrombocytopenia.

APG-2575 has been granted three Orphan Drug Designations (ODDs) by the US FDA,for the treatment of CLL,MM,and Waldenström macroglobulinemia (WM).

"APG-2575 is a key drug candidate of Ascentage Pharma's apoptosis-targeted pipeline," said Dr. Yifan Zhai,Chief Medical Officer of Ascentage Pharma. "As the first China-developed Bcl-2 inhibitor having entered clinical development in China,APG-2575 as a single agent or in combinations has demonstrated great therapeutic potential and clinical advantages. We are accelerating the global clinical development of this drug candidate,which we hope will soon translate into a new therapeutic option for patients in China and around the world."

About Ascentage Pharma

Ascentage Pharma (6855.HK) is a globally focused,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 (TKIs). 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 (CML),has been granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA,and a New Drug Application (NDA) for the drug candidate has been submitted in China. To date,Ascentage Pharma has obtained a total of eight ODDs from the US FDA for four of the company's investigational drug candidates.

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