Ride the Winds and Break the Waves -EZH2 inhibitor XNW5004 developed independently by Evopoint will be launched at the ASH meeting
XNW5004 is a specific substrate-competitive EZH2 inhibitor with independent intellectual property rights owned by Evopoint Biosesciences Co., Ltd. (hereinafter referred to as Evopoint). In Phase I clinical trial, XNW5004 showed good druggability and potential best-in-class efficacy and safety. Meanwhile, XNW5004 had good anti-tumor effect in all dose groups and different tumor types, especially in follicular lymphoma population, which was far superior to selective EZH2 inhibitors Tazemetostat and PF-06821497 of the same category. Simultaneously, XNW5004 also had good safety and tolerance that were also better than Tazemetostat and PF-06821497, without DLT event occurred in each dose group during dose-increase phase. Partial results of Phase I clinical trial have been successfully included in the 64th Annual Meeting of American Society of Hematology (hereinafter referred to as ASH Meeting). The detailed results will be announced at the ASH Meeting held in Louisiana, USA, on December 10-13, 2022. In addition, IND of XNW5004 for combined use with three drugs has been approved, and the proposed therapeutic regimens have been included in solid tumor R&D phase officially. Further study will be conducted in combination with PARPi, PD-1 inhibitor and ARi respectively based on multiple solid tumor indications.
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.
