Septerna Initiates Phase 1 Trial for SEP-631 in Mast Cell-Driven Diseases

SOUTH SAN FRANCISCO, Calif. — August 21, 2025 — Leads & Copy — Septerna, Inc. (Nasdaq: SEPN) has dosed the first participants in its Phase 1 clinical trial of SEP-631, an oral small molecule Mas-related G protein-coupled receptor X2 (MRGPRX2) negative allosteric modulator (NAM) for chronic spontaneous urticaria (CSU) and other mast cell-driven diseases.

The Phase 1 trial will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of SEP-631 in healthy adult volunteers.

CSU, a systemic inflammatory skin disease, affects millions who often struggle with symptom relief. SEP-631 aims to inhibit mast cell activation by selectively blocking MRGPRX2.

The randomized, placebo-controlled Phase 1 trial is expected to enroll up to approximately 150 healthy adult volunteers.

SEP-631 has demonstrated potent and long-lasting inhibition of MRGPRX2 in preclinical studies.

Renee Leck, THRUST, renee@thrustsc.com

Carly Scaduto, carly@carlyscadutoconsulting.com

Source: Septerna, Inc.

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