Septerna Starts Phase 1 Trial of SEP-786 for Hypoparathyroidism Treatment

Septerna has begun administering its novel drug SEP-786 to participants in a Phase 1 clinical trial, marking a significant milestone for the company as it transitions to a clinical-stage enterprise. SEP-786 is an innovative, selective oral small molecule that targets the parathyroid hormone 1 receptor (PTH1R) and is being developed to treat hypoparathyroidism. This initial Phase 1 trial aims to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of SEP-786 in healthy adult volunteers.

Hypoparathyroidism is a serious endocrine disorder characterized by insufficient production of the parathyroid hormone (PTH), leading to a variety of symptoms such as muscle cramps, fatigue, cognitive issues, and severe complications including cardiac arrhythmias, seizures, and renal failure. Current treatment options involve high doses of calcium and Vitamin D supplements multiple times a day or daily injections of PTH replacement therapy.

“G protein-coupled receptor (GPCR)-targeted drugs have been among the most successful in drug discovery, accounting for about a third of all FDA-approved drugs,” stated Jeffrey Finer, M.D., Ph.D., Chief Executive Officer and Co-founder of Septerna. He further emphasized that the company’s Native Complex Platform™ is instrumental in discovering oral small molecule compounds for a range of GPCRs, including PTH1R, a validated target for hypoparathyroidism. According to Finer, an oral small molecule PTH1R agonist could revolutionize treatment by offering a convenient, disease-modifying option that provides full-day calcium control and mitigates the severe effects of PTH deficiency. The company looks forward to evaluating SEP-786's safety and its ability to normalize serum calcium levels during this Phase 1 trial, as observed in preclinical models.

The trial is structured as a randomized, placebo-controlled study involving up to 180 healthy adult participants. The single-ascending dose (SAD) component of the trial will assess the safety and tolerability of SEP-786 at increasing oral doses. Meanwhile, the multiple-ascending dose (MAD) segment will explore the safety and tolerability of once-daily and twice-daily oral dosing over several days, with secondary endpoints including pharmacokinetics, changes in serum calcium, urinary calcium, and other biomarkers.

SEP-786 is being developed as a potent, selective oral small molecule PTH1R agonist specifically for hypoparathyroidism—a rare endocrine disorder resulting from a deficiency of the parathyroid hormone. This deficiency leads to severe symptoms and life-threatening complications. Existing treatments only partially address PTH deficiency or require daily peptide injections. Preclinical studies have shown that SEP-786 can normalize serum calcium levels and was generally well-tolerated in 28-day Good Laboratory Practice toxicology studies, indicating its potential as a differentiated treatment option for hypoparathyroidism.

Septerna, established in 2022, is a clinical-stage biotechnology company focusing on the discovery and development of GPCR-targeted oral small molecule drugs. Utilizing its proprietary Native Complex Platform™, the company aims to unlock the potential of GPCR therapies. This platform has facilitated the development of a robust pipeline of product candidates aimed at treating conditions in endocrinology, immunology, inflammation, and metabolic diseases.