Septerna, Inc. (SEPN) began dosing the first participants in its Phase 1 clinical trial of SEP‑479, an oral small‑molecule parathyroid hormone 1 receptor (PTH1R) agonist for hypoparathyroidism, on April 13, 2026.
The single‑ascending‑dose and multiple‑ascending‑dose study will enroll up to 150 healthy adult volunteers and will evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of SEP‑479. The company expects to report topline data in late 2026 or early 2027.
Hypoparathyroidism is caused by a deficiency of parathyroid hormone, leading to muscle cramps, fatigue and cognitive dysfunction. Current therapies rely on high doses of calcium and vitamin D supplements or daily injectable PTH, which impose a substantial burden on patients. In preclinical studies, SEP‑479 normalized serum calcium in a rat model and demonstrated activity comparable to PTH peptides, positioning it as a potential once‑daily oral alternative that could improve adherence and quality of life.
Septerna leverages its proprietary Native Complex Platform® to discover and develop oral small‑molecule GPCR therapies. The SEP‑479 program expands the company’s pipeline beyond dermatology into endocrinology, complementing other programs such as SEP‑631 for mast‑cell driven diseases. The company’s market capitalization is approximately $1.04 billion, and it reported Q4 2025 earnings of a $24.12 million revenue that beat expectations and an EPS of –$0.24 that missed estimates, while maintaining a cash balance of $548.7 million and an at‑the‑market equity program of $150 million.
CEO Jeffrey Finer said, “Hypoparathyroidism is a lifelong condition that patients must manage with either high doses of calcium supplements several times a day or daily parathyroid hormone (PTH) injections, both of which can place a substantial burden on patients over time. We are encouraged by the preclinical data for SEP‑479, which underscore its potential to be a disease‑modifying therapy for hypoparathyroidism by directly targeting the PTH receptor to provide patients full‑day calcium control and relief from their debilitating symptoms. Based on these findings, we believe SEP‑479 has the potential to be differentiated as a once‑daily oral therapy for patients, and we look forward to advancing our Phase 1 trial as rapidly as possible.” He added, “In the third quarter, we made meaningful progress across our portfolio, highlighted by the selection of SEP‑479 as our next‑generation PTH1R agonist development candidate for hypoparathyroidism and the initiation of our Phase 1 clinical trial for SEP‑631 which targets MRGPRX2 for mast‑cell‑driven diseases. Both programs exemplify the power of our Native Complex Platform™ to generate differentiated oral small‑molecule GPCR therapies with the potential to address serious diseases across a range of indications. With multiple milestones anticipated in the first half of 2026, we are executing with focus and momentum as we work to deliver meaningful therapies for patients.”
The announcement was met with a muted market response, with peers showing mixed performance.
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