Septerna names SEP-204 development candidate for Graves' disease and TED

Septerna, Inc. announced on November 4, 2026 that it had selected SEP-204 as its potential first-in-class development candidate for the treatment of Graves' disease and thyroid eye disease (TED), reporting initial preclinical data ahead of a poster presentation at the 2026 American Thyroid Association Annual Meeting on November 5.¹

The compound is described as a potent and selective oral small molecule thyroid-stimulating hormone receptor (TSHR) negative allosteric modulator (NAM)¹. In preclinical work, SEP-204 inhibited TSHR activation in Graves' disease animal models and has pharmacokinetic properties to support once daily dosing¹.

Among the preclinical findings, the company reported potent TSHR inhibition with desirable drug-like properties and a high level of selectivity over the closely related follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR)¹, as well as inhibition of thyroid-stimulating antibody (TSAb) activation of TSHR in human thyrocyte cell assays¹. In animal models of Graves' disease, findings included restoration of normal thyroid hormone T4 levels and reductions in thyroid enlargement and orbital proptosis¹. The drug was generally well tolerated in 28-day GLP toxicology studies in rats and dogs¹, and showed high oral bioavailability and low clearance across preclinical species, with a projected human half-life of approximately 20-40 hours, which is anticipated to support once-daily oral dosing in humans¹.

Septerna said a Phase 1 trial in healthy volunteers is anticipated to initiate in the first quarter of 2027¹. The company noted that current standard-of-care treatments do not address the shared underlying cause of both Graves' disease and TED¹. Septerna also filed an updated corporate presentation alongside the release, per the accompanying Form 8-K.