VRN19

VRN19 is an orally available small molecule inhibitor of Ubiquitin-specific protease 1 (USP1), developed by Voronoi Productions. It leverages the mechanism of synthetic lethality to selectively target cancers with BRCA1/2 mutations, including breast and gynecologic malignancies. By binding directly to USP1 and inhibiting the catalytic activity of the USP1-UAF1 complex, VRN19 disrupts DNA damage repair pathways, leading to selective cell death in repair-deficient tumors. Preclinical data indicates that VRN19 possesses high selectivity (over 500-fold) for BRCA-mutated cells over wild-type cells and demonstrates potent antitumor activity, including in models resistant to PARP inhibitors. It is currently being evaluated in Phase 1/2 clinical trials for the treatment of various solid tumors.