Ascentage Pharma Announces First Patient Dosed in the Phase II Clinical Study of IAP Antagonist APG-1387 in Combination with Entecavir for the Treatment of Patients with Chronic Hepatitis B

SUZHOU, China, and ROCKVILLE, Md., June 17, 2020 /PRNewswire/ -- 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 II clinical study of the company's novel inhibitor of apoptosis proteins (IAP) antagonist APG-1387 in combination with entecavir for the treatment of patients with CHB has dosed its first patient in China.

This global multi-center, open-label Phase II study is designed to evaluate the safety and efficacy of APG-1387 in combination with entecavir in patients with CHB who are treatment-naive or -experienced. The study is designed to enroll 104 patients with CHB globally.

According to the 2017 Global Hepatitis Report by the World Health Organization([1]), there were around 257 million patients with HBV (hepatitis B virus) infections globally, with approximately 650,000 deaths annually from HBV infection-induced hepatic failure, cirrhosis, and hepatocellular carcinoma. Standard of care treatments for HBV infection recommended by major international guidelines include entecavir, tenofovir disoproxil fumarate, tenofovir alafenamide, and long-acting interferon. However, the current available drugs can achieve clearance of hepatitis B surface antigen (HBsAg) and sustained post-treatment immune response only in a small proportion of patients, while most patients require long-term or even life-long treatments. As a result, there remains a significant unmet medical need for therapies that can effectively treat CHB and minimize the risk of disease progression within a limited duration of treatment.

APG-1387 is a novel and highly specific IAP antagonist being developed by Ascentage Pharma. APG-1387 degrades IAPs by mimicking the endogenous second mitochondria-derived activator of caspases (SMAC) molecule to induce programmed cell death or apoptosis. In the course of HBV infection, the virus and inflammatory factors can facilitate molecular expression of cellular inhibitor of apoptosis proteins (cIAPs) in hepatocytes, inhibit cellular immune-mediated apoptosis, and promote the survival of infected hepatocytes, leading to persistent infections([2]). In addition, APG-1387 has demonstrated its ability to suppress and clear HBV infections in various in vivo and in vitro models. APG-1387 is the first IAP antagonist entering clinical stage in China.

"Current treatment options for HBV infection are effective in suppressing viral replication, but much less effective in achieving clinical cure (clearance of HBsAg), necessitating long-term, and possibly life-time use of antiviral therapies," said Jinlin Hou, M.D., former President of the Society of Infectious Diseases of Chinese Medical Association (CMA), Director of Nanfang Hospital Liver Cancer of Southern Medical University (Guangzhou, China). "APG-1387 has the potential of clearing HBV infection in patients, and its unique mechanism has suggested a promising new approach to the treatment of CHB. Based on the favorable activity and safety observed in an earlier clinical study of single-agent APG-1387, we are initiating this global Phase II study of APG-1387 in combination with entecavir to further evaluate the therapeutic potential of this combination therapy."

"At present, CHB still presents considerable unmet medical needs. As the first IAP antagonist entering clinical stage in China, APG-1387's unique mechanisms in inducing apoptosis and host immune modulations has the potential in delivering a cure to patients with HBV infections," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "We hope our investigation of this combinational therapy will bring new approach to patients with CHB worldwide who are in urgent need for more effective therapies."


                        [1] WHO, Global Hepatitis
                         Report 2017.

                        [2] Ebert G., et al., Cellular
                         inhibitor of apoptosis
                         proteins prevent clearance of
                         hepatitis B virus. Proc Natl
                         Acad Sci, 2015.112(18): p.

About APG-1387

APG-1387 is a novel small molecule IAP (Inhibitor of Apoptosis Protein) antagonist, that was discovered and is being developed by Ascentage Pharma. APG-1387 degrades IAPs by mimicking endogenous SMAC molecule to induce programmed cell death or apoptosis. Ascentage Pharma is developing APG-1387 globally, and has completed Phase I dose-escalation trials in patients with solid tumors in China and Australia, and a Phase Ib/II clinical trial of APG-1387 and pembrolizumab combination is currently ongoing in the US. In addition, APG-1387 is also being investigated in a Phase Ib trial for the treatment of patients with Chronic Hepatitis B (CHB) in China. In February 2020, Ascentage Pharma was cleared to initiate a Phase Ib/II study of APG-1387 in combination with nab-paclitaxel plus gemcitabine for the treatment of advanced pancreatic cancer. In April 2020, the company received clearance for a Phase II study of APG-1387 in combination with entecavir for the treatment of CHB.

About Ascentage Pharma

Ascentage Pharma (6855.HK) is a globally, clinical-stage biotechnology company engaged in developing novel therapies for cancers, 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 30 Phase I/II clinical trials in the US, Australia, and China. The company's core drug candidate HQP1351 is in pivotal Phase II studies in China for the treatment of drug-resistant chronic myeloid leukemia, and recently granted orphan drug and fast-track designations by the US Food and Drug Administration (FDA).

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