Sheng medicine on November 10 (today) in its WeChat public announcement said (the original below), the company in research original new class 1 embryonic ectodermal development protein (EED) inhibitor APG-5918 obtained the national drug administration (NMPA) drug review center (CDE) clinical trial license, will carry out the treatment of advanced solid tumors or hematological malignancy phase I clinical trials.
Prior to this, the research variety has been approved in the United States to carry out clinical trials for advanced solid tumors or blood tumor indications, which is another major achievement of the company's "China-Us Double News" strategy, basically realizing the synchronous promotion of China and the United States. APG-5918 is the first original Chinese research EED inhibitor to enter the clinical stage.
This is a multicenter, open-label phase I dose-escalation and dose-expansion clinical trial designed to evaluate the safety, pharmacokinetics, and efficacy of oral APG-5918 in patients with advanced solid tumors or hematologic malignancies. Professor Xu Ruihua, president of the Chinese Society of Clinical Oncology and director of the Center for Cancer Prevention and Treatment of Sun Yat-sen University, will serve as the principal investigator (PI) of the clinical trial.
EZH2 is highly expressed in a variety of human cancers and promotes cancer development and malignant degeneration, and targeted inhibition of the methyltransferase activity of EZH2 has been shown to be a successful cancer treatment strategy. Nonetheless, secondary mutations in EZH2 can confer acquired drug resistance, and its homology, EZH1, also has methyltransferase activity, both causing restricted EZH2 inhibitor activity. It was found that the polyproteinogenicity of the PRC2 complex and the EZH2 activity are highly dependent on the scaffolding and regulatory effects of the EED. Compounds that inhibit the PRC2 subunit EED disrupt the protein – protein interaction (PPI) of EED-EZH2, subsequently impaired PRC2 function, resulting in loss of PRC2 activity stimulated by H3K27me3, and preventing trimethylated [1] of H3K27. Therefore, targeting EED proteins has gained great attention as an alternative inactivation strategy to inhibit PRC2.
APG-5918 is a new small molecule inhibitor of EED protein active and highly selective. It has high binding affinity. By regulating tumor tissue epigenetics and tumor microenvironment, it has broad clinical application prospects in blood tumor, solid tumor and non-tumor indications. APG-5918 can selectively bind to the H3K27me3 domain on the EED protein, resulting in a conformational change in the EED H3K27me3 binding pocket, preventing the interaction of EED with the histone methyltransferase EZH2. Preliminary data demonstrate the antitumour viability of APG-5918 in vitro antitumour cell proliferation viability in multiple tumor cell lines and in PDX / CDX models of EZH2-mutant B cell non-Hodgkin's lymphoma, INI1-negative malignant rhabdomyoma, BAP1-mutated mesothelioma, and prostate cancer.
Professor Xu Ruihua, director and dean of the Cancer Prevention and Control Center of Sun Yat-sen University, said:
Targeting PRC2 complex proteins, especially EED, may be effective in tumors with certain genetic features. The EED inhibitor APG-5918 showed clear target-binding effects and target-related antitumor activity in both in vitro and animal in vivo assays. Further clinical studies are worthwhile to explore its efficacy. Targeting PRC2 complex proteins, especially EED, may be effective in tumors with certain genetic features. The EED inhibitor APG-5918 showed clear target-binding effects and target-related antitumor activity in both in vitro and animal in vivo assays. Further clinical studies are worthwhile to explore its efficacy.
Dr. Zhai Yifan, chief medical officer of Yasheng Pharmaceutical, said:
This is another major progress after the approval of APG-5918 tumor indications in the United States, and is also a reflection of asasheng's adherence to the Sino-US strategy and global innovation strength. We look forward to working together with President Xu to actively promote the clinical development of APG-5918 and benefit more patients as soon as possible.
