Ascentage Pharma Announces Approval for the Phase Ib/II Clinical Trial of APG-1387 in Combination with Chemotherapy for the Treatment of Advanced Pancreatic Cancer in China

SUZHOU,China and ROCKVILLE,MD.,Feb. 24,2020 -- 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 company has received approval from Center of Drug Evaluation (CDE),China NMPA,for the Phase Ib/II clinical trial of APG-1387,Ascentage Pharma's novel inhibitorof apoptosis proteins(IAP) inhibitor,in combination with chemotherapy (nab-paclitaxel plus gemcitabine) for the treatment of advanced pancreatic cancer.

This multi-center,open-label clinical trial is comprised of a Phase Ib dose-escalation study and a Phase II efficacy study,and it is designed to evaluate the safety,pharmacokinetics (PK),and preliminary efficacy of APG-1387 in combination with the nab-paclitaxel plus gemcitabine doublet chemotherapy in advanced pancreatic cancer.

APG-1387 is a novel,small molecule IAP inhibitor that induces apoptosis by mimicking the dimeric form of the SMAC protein. In a range of in vivo and in vitro studies in multiple xenograft tumor models,APG-1387,either as a monotherapy or in combination with targeted agents or chemotherapies,demonstrated its ability to effectively inhibit the growth of tumor cells,which provided supporting evidence to the further clinical investigation of APG-1387. APG-1387 is the first IAP inhibitor to enter clinical trials in China.

APG-1387 has completed Phase I clinical trials in advanced solid tumors in China and Australia,and it was shown to be well-tolerated. The preliminary result from the ongoing Phase I trial of APG-1387 in the U.S. was presented at the 2019 Annual Meeting of American Society of Oncology (ASCO). The data demonstrated APG-1387's promising anti-tumor activity in advanced pancreatic cancer patients who had failed multiple prior lines of treatments. Among 10 advanced pancreatic cancer patients treated with APG-1387 monotherapy,4 patients achieved SD (stable disease),including one patient at 45 mg who has been treated for over 9 cycles with confirmed SD. Overall,APG-1387 was well-tolerated with manageable adverse events.

Pancreatic canceris a highly aggressive form of gastrointestinal cancer. With a poor prognosis and an incidence rate at par with its mortality rate[1],pancreatic cancer has overtaken liver cancer as the deadliest type of all malignancies. Pancreatic cancer is ranked the ninth largest cancer type in China,with a rising incidence rate year after year. Due to the unique anatomical characteristics of the pancreas,the symptoms of early-stage pancreatic cancer are relatively silent. As a result,pancreatic cancer patients are commonly diagnosed at advanced stages or when they have developed metastasis,disqualifying them for surgery. The current median survival of patients with mPC (metastatic pancreatic cancer) is four to six months,and the 2015 statistics shows a five-year survival rate of just 7.2%,making pancreatic cancer the malignancy with the lowest survival rate in China[2].

In recent years,the rapid advancement in cancer therapies,particularly the introduction of targeted therapies and immunotherapies,has significantly improved the survival of many malignancies,including lung cancer,breast cancer,and liver cancer. However,the treatment standard for pancreatic cancer remains unchanged with very limited options. For patients with unresectable locally advanced or remotely metastasized pancreatic cancer,chemotherapy is still the primary treatment,although it only delivers a median post-treatment survival for shorter than one year. That being the case,there is urgent need to improve the clinical outcomes of pancreatic cancer treatment.

"For pancreatic cancer,in particular those cases that have progressed to advanced stage,there remains an urgent clinical need for more effective treatment options globally. As the first IAP inhibitor to enter clinical trials in China,early clinical data of APG-1387 has demonstrated its great potential for the treatment of advanced pancreatic cancer," said Dr. Yifan Zhai,Chief Medical Officer of Ascentage Pharma. "We will start this Phase Ib/II trial of APG-1387 in China as early as possible,with the hope to bring new treatment options to pancreatic cancer patients."

About APG-1387

APG-1387 is a novel small molecule IAP inhibitor (Inhibitor of Apoptosis Protein),which was discovered and is being developed by Ascentage Pharma. Ascentage is developing APG-1387 globally,and has completed dose escalation Phase I trials in solid tumors in China and Australia,and a Phase Ib/II clinical trial of APG-1387 and pembrolizumab combination is currently ongoing in the U.S. In addition,APG-1387 is also being investigated in a Phase Ib trial for the treatment of patients with Chronic Hepatitis B in China.

About Ascentage Pharma

Ascentage Pharma (6855.HK) is a globally-focused,and age-related diseases. The company focuses on developing therapeutics that inhibit protein-protein interactions to restore apoptosis,or programmed cell death. On October 28,2019,Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited.

Ascentage Pharma has built a pipeline of eight clinical drug candidates,

including a novel,highly potent Bcl-2/Bcl-xL inhibitor,as well as candidates aimed at IAP and MDM2-p53 pathways,and next-generation tyrosine kinase inhibitors. The company has been conducting 28 Phase I/II clinical trials to evaluate the eight drug candidates in the United States,Australia,and China,developing the potential therapies as a single agent or in combination.

References:

1.Prabhu Bray F,Ferlay J,Soerjomataram I,et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin; 68(6):394-424

2.Hongmei Zeng,Wanqing Chen,Rongshou Zheng,et al (2018) Changing cancer survival in China during 2003–15: a pooled analysis of 17 population-based cancer registries. Lancet Glob Health; 6: e555–67

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