Sionna Therapeutics Announces First Subjects Dosed in Phase 1 Trial Evaluating NBD1 Stabilizer, SION-451, in Proprietary Dual Combinations in Development for the Treatment of Cystic Fibrosis

Core Viewpoint - Sionna Therapeutics has initiated dosing for SION-451 in combination with SION-2222 and SION-109 in a Phase 1 trial, aiming to transform cystic fibrosis treatment with novel CFTR modulators, with topline data expected in mid-2026 [1][2][3] Company Overview - Sionna Therapeutics is a clinical-stage biopharmaceutical company focused on developing medicines that normalize CFTR protein function, specifically targeting the NBD1 domain to improve clinical outcomes for cystic fibrosis patients [5] - The company aims to deliver differentiated therapies that restore CFTR function to near-normal levels, leveraging over a decade of research on NBD1 and developing small molecules to correct defects caused by the F508del mutation [5] Clinical Trial Details - The Phase 1 trial is randomized, double-blind, and placebo-controlled, assessing the safety, tolerability, and pharmacokinetics of SION-451 in dual combinations with SION-2222 and SION-109 [2] - Topline data from this trial is anticipated in mid-2026, which will guide the selection of a dual combination for a planned Phase 2b trial in cystic fibrosis patients [2] Scientific Rationale - Positive data from previous Phase 1 trials and preclinical studies support the advancement of the dual combination trial, with SION-451 showing good tolerability and exceeding pharmacokinetic concentration targets [4] - The NBD1 domain is critical for CFTR protein stability and function, and no approved therapies currently stabilize this domain directly, highlighting the innovative approach of Sionna's research [3][4]