PVTX-321

PVTX-321 is an orally bioavailable, small molecule proteolysis-targeting chimera (PROTAC) designed to target and degrade the estrogen receptor alpha (ERα) protein. Developed by Proteovant Therapeutics (a Roivant Sciences company) in collaboration with SK Life Science Laboratories, it is primarily being investigated for the treatment of ER+/HER2- breast cancer. The molecule consists of a novel spirocyclic cereblon (CRBN) ligand linked to an ERα binder, enabling it to function as both a potent degrader and a full antagonist of the receptor. Preclinical studies have demonstrated its efficacy against wild-type ERα and clinically relevant ESR1 mutations (such as Y537S, D538G, and E380Q) that typically confer resistance to standard endocrine therapies. PVTX-321 was nominated as a development candidate in 2023 following successful preclinical safety and efficacy profiles, including tumor regression in xenograft models.