Septerna, a clinical-stage biotechnology company, has announced the initiation of a Phase 1 clinical trial for SEP-786, a novel oral small molecule parathyroid hormone 1 receptor (PTH1R) agonist, for the treatment of hypoparathyroidism. The trial is designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of SEP-786 in healthy adult volunteers.
Targeting Hypoparathyroidism with SEP-786
Hypoparathyroidism is a rare endocrine disorder characterized by insufficient production of parathyroid hormone (PTH), leading to decreased calcium levels and increased phosphorus levels in the blood. This deficiency can result in a range of debilitating symptoms, including muscle cramps, fatigue, cognitive dysfunction, and life-threatening complications such as cardiac arrhythmias, seizures, and renal failure. Current treatments primarily involve high doses of calcium and Vitamin D supplements or daily injections of PTH replacement therapy, which only partially address the underlying PTH deficiency.
SEP-786, a potent and selective oral small molecule PTH1R agonist, represents a potential advancement in the treatment of hypoparathyroidism. By directly targeting the PTH1R, SEP-786 aims to normalize serum calcium levels and alleviate the symptoms associated with PTH deficiency. Preclinical studies have demonstrated the ability of SEP-786 to normalize serum calcium levels and were generally well-tolerated in 28-day Good Laboratory Practice toxicology studies.
Phase 1 Trial Design
The Phase 1 clinical trial is a randomized, placebo-controlled study that includes single-ascending dose (SAD) and multiple-ascending dose (MAD) segments. It is expected to enroll up to 180 healthy adult participants. The SAD portion of the trial will evaluate the safety and tolerability of SEP-786 at escalating oral doses. The MAD portion is designed to assess the safety and tolerability of once-daily and twice-daily oral dosing of SEP-786 over multiple days of treatment. Secondary endpoints include PK, changes in serum calcium and urinary calcium, and other biomarkers.
Septerna's Native Complex Platform
Jeffrey Finer, M.D., Ph.D., Chief Executive Officer and Co-founder of Septerna, stated, "An oral small molecule PTH1R agonist has transformative potential as a convenient, disease-modifying treatment option that could provide patients with full-day calcium control, while resolving the serious effects of low blood calcium levels due to PTH deficiency." He also highlighted the role of Septerna's Native Complex Platform™ in discovering oral small molecule compounds for GPCRs, which have historically been challenging targets for small molecule drug discovery.
Potential Impact on Hypoparathyroidism Treatment
If successful, SEP-786 could offer a more convenient and effective treatment option for patients with hypoparathyroidism, potentially improving their quality of life and reducing the burden of current treatment regimens.
