Ascentage Pharma and Merck Announce Global Clinical Collaboration to Evaluate MDM2-p53 Inhibitor APG-115 in Combination with KEYTRUDA® for Advanced Solid Tumors

SUZHOU, China and ROCKVILLE, Md., July 6, 2020 /PRNewswire/ -- Ascentage Pharma (6855.HK), a clinical-stage biopharmaceutical company dedicated to developing innovative drugs in the therapeutic areas of oncology, hepatitis B, and age-related diseases, today announced that the company has established a partnership with MSD (MSD is the trade name of Merck & Co., Inc., headquartered in Kenilworth, New Jersey, USA).GlobalClinical Research Partnership. The two parties will collaborate on Ascentage Pharma’s investigational original MDM2-p53 inhibitor APG-115 and Merck Sharp & Dohme’s PD-1 monoclonal antibody KEYTRUDA^®Clinical studies were conducted on the combination therapy with (pembrolizumab) to evaluate its clinical efficacy in patients with advanced solid tumors.

Under the terms of collaboration, Ascentage Pharma will support this multicenter, open-label Phase Ib/II clinical study aimed at evaluating APG-115 in combination with KEYTRUDA^®Safety and efficacy in treating various solid tumors, including non-small cell lung cancer, melanoma, urothelial carcinoma, liposarcoma, malignant peripheral nerve sheath tumors, and ATM-mutant/p53-wild-type tumors that are resistant to or have relapsed after PD-1/PD-L1 inhibitor therapy, as well as those untreated with PD-1/PD-L1 inhibitors. The Phase II clinical trial is now underway, with a planned enrollment of 80 patients across multiple sites in the United States. Ascentage Pharma and Merck Sharp & Dohme (MSD) will share relevant research information through a jointly established development committee.

Preclinical studies have shown that APG-115 can promote the production of pro-inflammatory cytokines by T cells and enhance CD4⁺ T-cell activation enhances PD-L1 expression in various tumor cells. The antitumor activity of APG-115 in combination with PD-1 inhibitors was significantly enhanced in multiple tumor models. The results of the Phase Ib clinical trial were presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrating that the combination of APG-115 and pembrolizumab was well tolerated and exhibited significant antitumor activity across multiple tumor types.

Dr. Yang Dajun, Chairman and CEO of Ascentage Pharma, stated, “We are pleased to enter into this clinical collaboration with Merck & Co., Inc., a global leader in the healthcare industry. APG-115 is a key investigational asset in Ascentage Pharma’s apoptosis product pipeline and holds significant potential for the treatment of advanced solid tumors. Based on the favorable data from the Phase Ib trial, we look forward to working closely with Merck to further explore the combination of APG-115 and KEYTRUDA”^®the synergistic effects of combination therapy, providing more effective treatment options for patients with advanced solid tumors.”

KEYTRUDA^® ® is a registered trademark owned by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, USA.

AboutAPG-115

APG-115 is an orally bioavailable, highly selective small-molecule MDM2 inhibitor independently developed by Ascentage Pharma. APG-115 exhibits high binding affinity for MDM2 and restores p53 tumor suppressor activity by blocking the MDM2-p53 interaction. Three clinical studies of APG-115 have been initiated in the United States: a Phase I monotherapy trial, a Phase Ib/II trial evaluating combination therapy with pembrolizumab for advanced solid tumors/metastatic melanoma, and a Phase I/II trial assessing monotherapy or combination with chemotherapy for salivary gland cancer. As the first MDM2-p53 inhibitor to enter clinical development in China, APG-115 has also received approval to conduct clinical trials in China, including a Phase I monotherapy study and a Phase Ib study evaluating monotherapy or combination with chemotherapy for acute myeloid leukemia (AML)/myelodysplastic syndromes (MDS).

About Ascentage Pharma

Ascentage Pharma is a China-based, globally oriented clinical-stage biopharmaceutical company dedicated to developing innovative drugs in therapeutic areas such as oncology, hepatitis B, and age-related diseases. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Hong Kong Stock Exchange, with stock code: 6855.HK.

Ascentage Pharma possesses a proprietary protein-protein interaction (PPI)-targeted drug design platform and stands at the global forefront of novel drug development in the apoptosis pathway. The company has established a pipeline of eight Class 1 small-molecule new drug candidates currently in clinical development, including inhibitors targeting key apoptotic proteins such as Bcl-2, IAPs, or the MDM2-p53 interaction, as well as next-generation inhibitors directed against kinase mutants emerging in cancer therapy. Ascentage Pharma is the only innovative company worldwide with clinical-stage candidates targeting all key proteins in the apoptosis pathway. Currently, the company is conducting more than 30 Phase I/II clinical trials in China, the United States, and Australia. Its core product, HQP1351, for the treatment of drug-resistant chronic myeloid leukemia (CML), has been granted Fast Track designation and Orphan Drug status by the U.S. FDA, and a New Drug Application (NDA) has been submitted in China.

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