First peer-reviewed clinical data for San Diego-based Vividion Therapeutics, Inc.'s WRN inhibitor VVD-214 showed antitumor activity and prolonged disease control in heavily pretreated MSI-high/dMMR solid tumors, providing early clinical support for WRN inhibition as a synthetic-lethal strategy, according to a Nature Medicine publication. Vividion is a wholly owned subsidiary of Bayer AG.
VVD-214 (RO7589831) is an investigational oral selective covalent WRN helicase inhibitor designed to cause DNA damage accumulation and synthetic lethality in MSI-high/dMMR cancers. The molecule originated from a 2020 Vividion-Roche collaboration, while Vividion and Bayer secured exclusive worldwide rights in June 2025.
The single-arm Phase I trial enrolled 88 previously treated patients with advanced MSI-high and/or dMMR solid tumors. Among 66 efficacy-evaluable patients with MSI-high tumors, who had received a median of three prior lines of therapy and included 95.5% previously treated with immune checkpoint inhibitors, VVD-214 produced a disease control rate (DCR) of 74.2%, including seven confirmed partial responses (10.6%). Median progression-free survival was 6.7 months and median overall survival was 17.6 months.
In the colorectal cancer subset, DCR was 80.5%, including three confirmed partial responses (7.3%). Median progression-free survival was 7.3 months, estimated 12-month overall survival was 78.3%, and median overall survival was not yet estimable. All three CRC responders remained in response at data cutoff.