Undisclosed P53 Y220C reactivator / Onco3R Therapeutics - LARVOL DELTA

Discovery of a Best-in-Class small molecule p53 Y220C reactivator: Breaking through the potency ceiling (AACR 2026) - "The first-generation small molecule reactivator (PC14586, Rezatapopt), designed to bind to this pocket, to refold p53 and to restore its tumor-suppressive functions, has shown clinical efficacy in patients harboring the Y220C mutations.However, this first-generation compound is limited by modest potency, necessitating high dosing in patients. In line with their superior cellular activity and in combination with optimized key ADME, safety parameters, and favorable in vivo PK profiles across species, our leads reach similar efficacy in vivo as PC145586 at much lower exposure.In conclusion, we have identified unique p53 Y220C small molecule reactivators with clear best-in-class cellular potency and favorable drug-like properties. We are currently further profiling these leads as potential drug candidates to achieve superior efficacy at substantially lower doses, maximizing the safety window to ultimately deliver better outcomes to cancer patients with p53 Y220C mutations."

Oncology • Solid Tumor • CDKN1A