SEP-631 / Septerna - LARVOL DELTA

Phase 2 Development Strategy (GlobeNewswire) - "Septerna plans to initiate a Phase 2b clinical trial of SEP-631 in chronic spontaneous urticaria (CSU) in the second half of this year, following the completion of ongoing long-term toxicology studies. The planned Phase 2b study will be a randomized, double-blind, placebo-controlled, global trial evaluating once-daily oral SEP-631 in adult patients with moderate-to-severe CSU who remain symptomatic despite treatment with second-generation antihistamines. Following the CSU study initiation, the company also plans to pursue an open-label study in chronic inducible urticaria (CIndU), specifically in patients with symptomatic dermatographism."

New P2 trial • Chronic Spontaneous Urticaria • Immunology • Urticaria

First-In-Human, Proof-of-Mechanism Phase 1 Study of the Oral MRGPRX2 Antagonist SEP-631 Utilizing Short Wave Infrared Imaging to Assess Response to an Icatibant Skin Challenge (AAAAI 2026) - P1 | "SWIR assessment provided accurate and precise quantification of skin wheal responses, supporting its potential as a sensitive tool to assess dermal inflammatory responses. (NCT07069036)"

First-in-human • Late-breaking abstract • P1 data • Chronic Spontaneous Urticaria • Dermatology • Immunology • Inflammation • Urticaria

Septerna Announces Positive Phase 1 Data for SEP-631, an Oral MRGPRX2 NAM for the Treatment of Mast Cell-Driven Diseases… (GlobeNewswire) - "SEP-631 was well-tolerated across all doses studied: Adverse event profile comparable to placebo; No severe or serious adverse events; No clinically meaningful laboratory or ECG abnormalities; SEP-631 demonstrated a PK profile supportive of convenient once-daily oral dosing, including: Half-life of approximately 24 hours; No clinically meaningful effect of food on exposure, supporting dosing without food restrictions."

P1 data • Chronic Spontaneous Urticaria • Immunology

A Study to Evaluate Single and Multiple Doses of SEP-631 in Healthy Adult Volunteers (clinicaltrials.gov) - P1 | N=150 | Not yet recruiting | Sponsor: Septerna, Inc.

New P1 trial

SEP-631: A Novel Selective and Potent Oral MRGPRX2 Inhibitor for the Treatment of Chronic Spontaneous Urticaria (EAACI 2025) - "This targeted mechanism minimizes the risk of broad immunosuppression. Our results support further development of SEP-631 as a promising novel oral therapy for potential treatment of CSU and other mast cell-mediated diseases."

Immunology • Inflammation • CORT

Septerna Provides Corporate Overview and Reports Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "Septerna is advancing several lead compounds with distinct chemical structures unrelated to SEP-786 and favorable pharmacokinetics profiles. The Company plans to select a next-generation oral small molecule PTH1R agonist development candidate to accelerate toward clinical development by the end of 2025....Septerna continues to advance SEP-631, a selective oral small molecule MRGPRX2 negative allosteric modulator (NAM), for the treatment of mast cell diseases, including chronic spontaneous urticaria. The company anticipates initiating a Phase 1 clinical trial in 2025 to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of SEP-631 in healthy volunteers."

New P1 trial • Pipeline update • Chronic Spontaneous Urticaria • Hypoparathyroidism