Septerna Announces Positive Phase 1 Data for SEP-631, an Oral MRGPRX2 NAM

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Septerna, Inc. announced positive results from its Phase 1 clinical trial evaluating SEP-631, a potent and selective oral negative allosteric modulator (NAM) of Mas-related G protein-coupled receptor X2 (MRGPRX2). SEP-631 demonstrated robust, dose-dependent inhibition of icatibant-induced skin wheal formation, with complete inhibition observed at doses as low as 10 mg once-daily. The company plans to advance SEP-631 into Phase 2 development for chronic spontaneous urticaria (CSU) in the second half of 2026.

Why it matters

MRGPRX2 is known to play an important role in mast cell activation and degranulation, which can lead to debilitating symptoms for patients with mast cell-driven diseases. The positive Phase 1 results for SEP-631 suggest it could provide a differentiated oral treatment option for patients with CSU and other mast cell-driven conditions.

The details

In the Phase 1 trial, SEP-631 was well-tolerated across all doses studied, with an adverse event profile comparable to placebo. The pharmacokinetic profile supported once-daily oral dosing, with a half-life of approximately 24 hours and no clinically meaningful effect of food on exposure. The pharmacodynamic activity assessment using icatibant-induced skin wheal formation demonstrated robust, dose-dependent inhibition, with complete inhibition observed at doses as low as 10 mg once daily.

• The Phase 2b study in CSU is planned to begin in the second half of 2026, following the completion of ongoing long-term toxicology studies.

What they’re saying

What’s next

Septerna plans to initiate a Phase 2b clinical trial of SEP-631 in chronic spontaneous urticaria (CSU) in the second half of 2026, following the completion of ongoing long-term toxicology studies.