Three Trials on Evopoint’s EZH2 Inhibitor in Treating Solid Tumors Approved for the Phase II Clinical Trial
Three clinical trials on Evopoint’s EZH2 inhibitor XNW5004 combined with PARPi, ARi and PD-1 inhibitors respectively in treating several solid tumor indications were approved by the NMPA on October 26, 2022, and the Phase-Ib/II clinical trial will be carried out soon. The clinical trial of XNW5004 combined with PARPi will be led by Cancer Hospital Chinese Academy of Medical Sciences, the clinical trial of XNW5004 combined with ARi will be led by Fudan University Shanghai Cancer Center, and the clinical trial of XNW5004 combined with PD-1 inhibitor will be led by Sun Yat-Sen University Cancer Center. Evopoint will fully promote the clinical trials of the tri-combination therapy of XNW5004 for solid tumors, and strive for an early marketing for the benefit of the majority of patients.
XNW5004 is a specific substrate-competitive, selective and small-molecule EZH2 inhibitor with independent intellectual property rights owned by Evopoint. In Phase I clinical trial, XNW5004 showed good druggability and potential best-in-class efficacy and safety. XNW5004 had good anti-tumor effect especially in follicular lymphoma population, which was far superior to selective EZH2 inhibitors of the same category. Partial results of Phase I clinical trial will be announced at the ASH Meeting held in Louisiana, USA, on December 10-13, 2022.
About XNW5004
XNW5004 is a substrate-competitive specific small-molecule inhibitor of EZH2 with independent intellectual property rights owned by Evopoint. Existing clinical trials have confirmed that this type of drugs has good anti-tumor effect in lymphoma, which can be considered to be a novel therapeutic option for lymphoma patients. Meanwhile, in several preclinical in vitro and in vivo models on efficacy, XNW5004 was used jointly with multiple drugs for multiple solid tumor indications, with good anti-tumor activities and safety.
About EZH2
EZH2 is a catalytic subunit of the polycomb repressive complex 2 (PRC2). It can inhibit the transcription of target genes through tri-methylation of histone H3 lysine 27 (H3K27me3) and participate in the regulation of cell cycle, cell aging, cell differentiation, tumorigenesis and other pathophysiological processes. In B-cell lymphoma, EZH2 mutations were detected in 7-12% of follicular lymphoma (FL) and 22% of diffuse large B-cell lymphoma (DLBCL), which could induce continuous activation of EZH2. As supported by multiple translational medicine research, dual targeting of EZH2 and AR have strong synergistic effect and enhanced anti-tumor activities, which is expected to prolong the survival time and improve the survival rate of patients, with controllable safety. This combined therapy may break through the acquired drug resistance and poor durability of AR inhibitors. Furthermore, the interaction between EZH2 and PARP1 functions significantly in DNA repair. Simultaneous inhibition of EZH2 and PARP can significantly inhibit the proliferation of tumor cells, which may be effective to overcome drug resistance of PARP inhibitors. Besides, EZH2 inhibitors can regulate the immune microenvironment and may reverse drug resistance of PD-1. Therefore, it is speculated that EZH2 inhibitors combined with PD-1 may prolong the treatment duration of PD-1 and enhance the survival benefit of patients.
