SEP-786

SEP-786 is a novel, potent, and selective oral small molecule agonist of the parathyroid hormone 1 receptor (PTH1R), developed by Septerna for the treatment of hypoparathyroidism. Hypoparathyroidism is a rare endocrine disorder characterized by insufficient production of parathyroid hormone (PTH), leading to low calcium levels and increased phosphorus in the blood. Current treatments primarily involve calcium and vitamin D supplementation or PTH peptide replacements that require daily injections. SEP-786 was designed to provide convenient, disease-modifying therapy with full-day calcium control through oral administration. Preclinical studies demonstrated its ability to normalize serum calcium levels and modulate bone biomarkers, with generally good tolerability in toxicology studies. However, development was discontinued during Phase 1 due to unanticipated severe elevations in unconjugated bilirubin observed in some participants[1][2][5][6][7].