Ascentage Pharma and Genor Biopharma Announce Strategic Collaboration to Evaluate Combination of MDM2-p53 Inhibitor APG-115 and PD-1 Inhibitor Geptanolimab in Solid Tumors and Hematologic Malignancies
On December 19, 2018, Ascentage Pharma, a clinical-stage biopharmaceutical company dedicated to the development of first-in-class novel drugs for the treatment of cancer, hepatitis B, and age-related diseases, announced that it had entered into a strategic collaboration agreement with Genor Biopharma Co., Ltd. (“Genor Biopharma”). The two companies will jointly explore the combination therapy of APG-115, an MDM2-p53 inhibitor developed by Ascentage Pharma, and genolimzumab (GB226), a PD-1 inhibitor developed by Genor Biopharma, in the treatment of solid tumors and malignant hematologic cancers, and actively promote collaborative research in preclinical and clinical trials.
MDM2 directly inhibits p53 function through protein–protein interactions. MDM2 binds to the N-terminus of p53, preventing p53 from binding to DNA and promoting its degradation. Mutations that lead to MDM2 gene amplification or overexpression can suppress the normal function of p53, thereby contributing to tumor development and poor response to current cancer therapies.
Recent studies have shown that MDM2 amplification is associated with hyperprogressive disease in patients receiving PD-1/PD-L1 blockade immunotherapy. The role of the MDM2-p53 pathway in immune regulation, as well as its potential synergy with immunotherapy, has drawn the attention of developers of MDM2 inhibitors.
Dr. Yang Dajun, Chairman of Ascentage Pharma
It is understood that APG-115, an investigational oral bioavailable and highly selective small-molecule MDM2-p53 inhibitor developed by Ascentage Pharma, is currently undergoing Phase I clinical trials in China and the United States. Genor Biopharma’s investigational drug, genolimzumab (GB226), a humanized monoclonal antibody targeting PD-1 on immune cells, is currently conducting Phase II clinical trials for multiple tumor types in China.
In Ascentage Pharma’s preclinical studies, synergistic effects of APG-115 in combination with anti-PD-1 monoclonal antibodies have been observed in syngeneic tumor models. The mechanisms underlying this synergy include: increased T-cell activation and enhanced cytokine release from T cells following APG-115 treatment; a significant increase in cytotoxic CD8+ T cells within tumor infiltrates; an increase in tumor-infiltrating natural killer (NK) cells and M1 macrophages, along with a reduction in M2 macrophages.
Dr. Yang Dajun, Chairman of Ascentage Pharma, stated, “We look forward to close collaboration with the clinical team at Genor Biopharma to explore the potential efficacy of combining the innovative MDM2-p53 inhibitor APG-115 with genolimzumab.”
The therapeutic efficacy of the combination of these two drugs has achieved a breakthrough in the preclinical stage, and they are highly optimistic about the potential synergistic effects of APG-115 and PD-1 monoclonal antibody inhibitors in the treatment of various cancers.
Dr. Zhou Xinhua, CEO of Genor Biopharma, stated, “Combination therapy involving immune checkpoint inhibitors and anti-tumor agents represents a key trend in oncology treatment. Genor Biopharma has been actively exploring innovative clinical development strategies for genolimzumab. We look forward to collaborating with Ascentage Pharma to investigate the unique potential of the novel combination of genolimzumab and APG-115 in the treatment of malignant tumors.”