ORV-499

ORV-499 (formerly OST-499 or ORB-499) is an orally active, non-steroidal small molecule antagonist of the progesterone receptor (PR) and glucocorticoid receptor (GR). Originally developed by Oncostellae and subsequently outlicensed to Oriva Therapeutics, the compound is being developed as a selective progesterone receptor modulator (SPRM) for the treatment of uterine fibroids. Unlike traditional steroidal SPRMs, ORV-499's non-steroidal dihydropyridine scaffold is designed to avoid chemical liabilities associated with hepatotoxicity, potentially eliminating the need for liver function monitoring. Additionally, it avoids the hypoestrogenic side effects (such as hot flashes and bone mineral density loss) associated with GnRH modulators. ORV-499 is expected to enter Phase I clinical trials for uterine fibroids in the first quarter of 2027. It has also been investigated in Phase I trials for advanced solid tumors, including colorectal cancer, due to its glucocorticoid receptor antagonist activity.