SEP-204

SEP-204 is an investigational, oral small-molecule negative allosteric modulator (NAM) of the thyroid-stimulating hormone receptor (TSHR). Developed by Septerna, Inc., SEP-204 is designed to block the overactivation of TSHR caused by disease-driving autoantibodies in thyroid cells and orbital fibroblasts. In preclinical models of Graves' disease and thyroid eye disease (TED), SEP-204 demonstrated potent and selective TSHR inhibition, restored normal thyroid hormone T4 levels, and reduced thyroid enlargement and orbital proptosis. The drug has shown a favorable pharmacokinetic profile supporting once-daily oral dosing and was well tolerated in 28-day GLP toxicology studies in rats and dogs. A Phase 1 clinical trial in healthy volunteers is planned to initiate in the first quarter of 2027.