ROCKVILLE, Md. and SUZHOU, China, — December 19, 2018 — Ascentage Pharma, a global clinical-stage biopharmaceutical company dedicated to developing apoptosis-targeted therapies for cancers and other diseases, today announced that it has entered into a strategic collaboration with Genor Biopharma Co. Ltd. (“Genor”). As part of the agreement, the companies will explore the synergies of Ascentage’s MDM2-p53 inhibitor, APG-115, and Genor’s anti-PD-1 monoclonal antibody, genolimzumab (GB226), in preclinical and clinical studies in both solid tumors and hematologic malignancies.
MDM2 inhibits the function of p53 through direct protein-protein interaction (PPI) by binding to p53’s N-terminus, preventing p53 from binding to DNA and promoting the degradation of p53. Mutations that result in gene amplification or overexpression of MDM2 can inhibit the normal functioning of p53, leading to tumor development and poor response to current cancer therapies. Recent studies show that MDM2 amplifications have been implicated in hyper-progression in patients receiving PD-1/PD-L1 blockade immuno-oncology therapy, supporting the rationale of MDM2-p53 as an attractive pathway in immune modulation and a potential combination treatment with immuno-oncology therapeutics.
“We are looking forward to working closely with Genor’s clinical team to evaluate the potential benefits of combining APG-115, our novel MDM2-p53 specific inhibitor, with the anti-PD-1 mAb, genolimzumab, which has demonstrated promising anti-cancer results in preclinical studies,” said Dajun Yang M.D., Ph.D., Chairman and CEO of Ascentage. “We are encouraged by the potential synergistic effects of APG-115 and PD-1 inhibition for treating a wide range of cancers.”
Commented Dr. Joe Zhou, CEO of Genor: “Combination strategies of anti-tumor agents with immune checkpoint blockade are leading the trend of cancer therapy. We are actively pursuing the clinical innovation of genolimzumab and we expect that the innovative combination of genolizumab and APG-115, could represent an ideal clinical strategy in the treatment of various malignancies.”
APG-115 is a novel, orally bioavailable, highly selective small molecule MDM2 antagonist currently being investigated in Phase 1 clinical trials in China and the United States in patients with advanced solid tumors or lymphoma.
Genolimzumab (GB226) is an investigational, humanized mAb targeting PD-1 on immune cells and is currently in Phase 2 clinical trials for multiple tumor indications in China.
In Ascentage’s preclinical studies, the synergistic activity of APG-115 in combination with an anti-PD-1 mAb was observed in tumor models. The mechanisms underlying the synergy include an increase in T cell activation and cytokine release by T cells in response to APG-115 treatment, a substantial increase in tumor infiltrating cytotoxic CD8+ T cells and an increase in tumor infiltrating NK cells and M1 macrophages and a decrease in M2 macrophages.
APG-115 is an orally administered, selective, small molecule inhibitor of the MDM2-p53 Protein-Protein Interaction (PPI). The p53 protein plays an important role in preventing the formation and progression of cancer, and dysfunction of p53 can lead to various cancers. APG-115 was designed to activate p53 tumor suppression activity by blocking the MDM2-p53 PPI. Preclinical studies have shown that APG-115 has high binding affinity to MDM2 and an ability to activate p53. APG-115 could be used as a single agent for adenoid cystic carcinoma, or ACC, and sarcomas and in combination with IO therapies for solid tumors. The IND application for APG-115 went into effect with the FDA in June 2016. APG-115 is currently in Phase I clinical trials in China and the United States in patients with ACC and other sarcomas.
About Ascentage Pharma
Ascentage Pharma is a globally-focused, clinical-stage biopharmaceutical company developing novel small molecule therapies for cancers, hepatitis B and age-related diseases. Based on breakthrough technology from the University of Michigan, the Company’s expertise is in designing therapeutics that inhibit protein-protein interactions to restore apoptosis, or programmed cell death, in cancers. Ascentage has built a rich pipeline of seven clinical candidates, including a novel, highly potent Bcl-2/Bcl-xL inhibitor, APG-1252, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation tyrosine kinase inhibitors.
Genolimzumab (GB226) is an investigational, humanized, IgG4 monoclonal antibody targeting the programmed cell death-1 receptor (“PD-1”) on immune cells designed to restore the natural ability of the immune system to recognize and kill cancer cells by selectively blocking the dual ligand (PD-L1 and PD-L2) binding to the PD-1 protein. It is currently in Phase 2 clinical trials for multiple tumor indications in China. Outside China, genolimzumab is being developed by CBT Pharmaceuticals, Inc. as CBT-501.
About Genor Biopharma Co. Ltd.
Genor Biopharma is a leading biopharmaceutical company in China, developing and commercializing innovative therapeutic antibodies and recombinant fusion proteins. With ten products in different clinical stages, Genor has a strong pipeline in oncology and other major diseases, and has built a fully-integrated and well-proven technology platform in antibody drug research, development and manufacturing to serve China and international patients.
Genor is majority owned by HH CT Holdings Limited (affiliated funds to HillHouse Capital), and its other important shareholders include Zhejiang Conba Pharmaceutical Co., Ltd (Shanghai Stock Exchange: 600572), Walvax Biotechnology Co., Ltd. (Shenzhen Stock Exchange: 300142) and Jiaxing Guanyouxingwo Equity Investment Limited Partner. For additional information, please visit www.genorbio.com.