Ascentage Pharma Announces First Patient Dosed in the Phase Ib Study of MDM2-p53 Inhibitor APG-115 as Single Agent and in Combinations for the Treatment of Hematologic Malignancies in China

SUZHOU,China and ROCKVILLE,Md.,July 22,2020 -- 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 Phase Ib study of the company's novel MDM2-p53 inhibitor candidate APG-115 as a single agent or in combinations for the treatment of Chinese patients with relapsed/refractory acute myeloid leukemia (r/r AML),or relapsed/progressed high/very high risk myelodysplastic syndrome (MDS) has dosed its first patient in China. As the first MDM2-p53 inhibitor entering clinical studies for the treatment of solid tumors in China,this is the first study of APG-115 in patients with hematologic malignancies.

This multicenter Phase Ib clinical study in China is designed to evaluate the safety,pharmacokinetics,and pharmacodynamics of APG-115 as a single agent or in combination with azacitidine or cytarabine in patients with hematologic malignancies,including r/r AML and relapsed/progressed high/very high risk MDS.

AML is a clonal proliferative disease of the bone marrow,of which the incidence rate increases with age. AML is the most common type of leukemia in China,with an incidence rate of 1.62-2.32 cases per 100,000[1]. The standard induction therapy for AML comprises the "7+3" regimen (7 days of cytarabine plus 3 days of anthracycline drugs),but up to 40% of newly diagnosed AML patients do not achieve complete response (CR) during initial induction therapy,which is considered as refractory,or relapse within 6 months after achieving CR[2].

MDS is a heterogeneous hematopoietic disease caused by abnormal pluripotent stem cells,and the condition is characterized by poor hematopoietic function,bone marrow failure,reduction in peripheral blood cells,and reduced survival rates. The incidence rate of MDS in China is approximately 5 cases per 100,000. Although hypomethylating agents can produce a high response rate in patients with MDS,many patients eventually develop drug resistance to hypomethylating agents. Patients who have developed the acquired drug resistance commonly face a very poor prognosis. In patients with high-risk MDS,treatment failure with hypomethylating agents is associated with an average survival of less than 6 months[3]. As a result,both refractory/progressed AML and MDS represent an urgent medical need for more effective therapies.

APG-115 is an orally administered,selective,small-molecule inhibitor of the MDM2-p53 protein-protein interaction (PPI). APG-115 has strong binding affinity to MDM2 and is designed to activate tumor suppression activity of p53 by blocking the MDM2-p53 PPI. APG-115 is the first MDM2-p53 inhibitor entering clinical development in China,with multiple ongoing clinical studies in solid tumors in China and the US. At present,APG-115 is being investigated in a range of hematologic malignancies globally.

"Currently,there remains to be significant unmet medical needs in the treatment of hematologic malignancies,including AML and MDS," said Dr. Yifan Zhai,Chief Medical Officer of Ascentage Pharma. "We have also noticed that drug development targeting the MDM2-p53 pathway has received growing interest. As the first MDM2-p53 inhibitor entering clinical study in China,APG-115 has already demonstrated favorable safety profiles and preliminary efficacy in solid tumors. We will actively explore APG-115's therapeutic potential in hematologic malignancies,to hopefully provide more options of AML and MDS treatment to patients in China and around the world."

References:

1.Chang R,Wu S,Chen W,et al. Analysis on epidemiological characteristics of leukemia in Gansu Province from 2003 to 2012 [Article in Chinese]. Modern Preventive Med. 2014;41(21):3841-04.

2.Thol F,Schlenk RF,Heuser M,Ganser A. 2015. How I treat refractory and early relapsed acute myeloid leukemia. Blood 126: 319-27

3.Prebet T,Gore SD,Esterni B,Gardin C,Itzykson R,et al. 2011. Outcome of high-risk myelodysplastic syndrome after Azacitidine treatment failure. J Clin Oncol 29: 3322-7

About APG-115

APG-115 is an orally administered,small-molecule inhibitor of the MDM2-p53 PPI. APG-115 has strong binding affinity to MDM2 and is designed to activate p53 tumor suppression activity by blocking the MDM2-p53 PPI. Ascentage Pharma has previously commenced three clinical trials of APG-115 in the US,including a Phase I study as single agent,a Phase Ib/II study in combination with pembrolizumab for treatment of metastatic melanoma and other advanced solid tumors,and a Phase I/II study as a single agent or in combination with chemotherapy for treatment of salivary gland cancer. APG-115 is the first MDM2-p53 inhibitor to enter clinical studies in China. A Phase I study as a single agent,and a Phase Ib study as a single agent or in combination with chemotherapy for treatment of AML (acute myeloid leukemia) or MDS (myelodysplastic syndrome) are ongoing in China.

About Ascentage Pharma

Ascentage Pharma (6855.HK) is a globally,CHB,and senesce 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 30 Phase I/II clinical trials in the US,Australia,and China. The company's core drug candidate HQP1351 was recently granted orphan drug and fast-track designations by the US Food and Drug Administration (FDA),and a New Drug Application for HQP1351 has been submitted in China. APG-2575,another key drug candidate of the company,was recently granted orphan drug designation by the FDA.

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