SNV5686 / Synnovation Therap - LARVOL DELTA

SNV5686 a differentiated inhibitor of Werner helicase with potent activity against both WT WRN and WRN-C727S mutant proteins for treatment of MSI-H tumors (AACR 2025) - "In vivo, oral administration of low daily doses of SNV5686 potently depletes WRN and induces p21 in tumors and leads to deep tumor regression in an MSI-H colorectal xenograft model.Irreversible WRN inhibitors and the non-covalent inhibitor HRO761 leverage binding to CYS727 in the active site to attain potency and selectivity, and published data show that mutation of CYS727 severely abrogates their activity. Furthermore, toxicology studies with SNV5686 have not revealed adverse findings in hematology or clinical chemistry supporting the potential to combine with standard of care agents including chemotherapy. These data support the clinical investigation of SNV5686 for tumors characterized by MSI-H."

MSI-H • Microsatellite Instability • Oncology • CDKN1A • EGFR • MSI • WRN