Sionna Therapeutics Initiates Phase 1 Trial for SION-451 in Dual Combinations for Cystic Fibrosis Treatment

Sionna Therapeutics has dosed the first subjects in a Phase 1 trial evaluating SION-451, a nucleotide binding domain 1 stabilizer, in proprietary dual combinations with SION-2222 and SION-109 for the treatment of cystic fibrosis. The trial aims to assess safety, tolerability, and pharmacokinetics of varying doses of dual combinations. Topline data are expected in mid-2026 and will inform selection of a dual combination for a planned Phase 2b trial in people living with CF.

Sionna Therapeutics, a clinical-stage biopharmaceutical company, has initiated dosing in a Phase 1 trial evaluating SION-451, a first-in-class nucleotide binding domain 1 (NBD1) stabilizer, in proprietary dual combinations with SION-2222 and SION-109 for the treatment of cystic fibrosis. The trial aims to assess safety, tolerability, and pharmacokinetics of varying doses of dual combinations. Topline data are expected in mid-2026 and will inform selection of a dual combination for a planned Phase 2b trial in people living with CF.

The trial, a randomized, double-blind, placebo-controlled study in healthy volunteers, will test the safety, tolerability, and pharmacokinetics of SION-451 combined with SION-2222 and SION-109. SION-2222 is a transmembrane domain 1 (TMD1)-directed CFTR corrector, while SION-109 is an intracellular loop 4 (ICL4)-directed CFTR corrector. This approach represents a novel therapeutic strategy targeting the root cause of CFTR misfolding, a critical mechanism in cystic fibrosis pathophysiology.

Previous Phase 1 trials showed that SION-451 was generally well-tolerated and achieved pharmacokinetic targets suggesting potential clinical benefits, including possible wild-type levels of CFTR function. The unmet need in cystic fibrosis treatment remains substantial, with two-thirds of patients still lacking normal CFTR function despite current standard therapies.

Sionna Therapeutics' Chief Medical Officer, Dr. Charlotte McKee, noted, "At Sionna, our research and understanding of the CFTR protein and the underlying causes of CF have led us to this exciting point, where we are taking the first ever NBD1-anchored dual combinations forward in clinical trials with the goal of revolutionizing the treatment paradigm for CF patients."

Cystic fibrosis is a progressive and life-threatening genetic disease affecting over 100,000 people globally. While advances in the discovery and development of modulators have significantly improved patient outcomes, the need for more effective and efficient treatments remains.

References:
[1] https://www.ainvest.com/news/sionna-therapeutics-disrupting-vertex-cf-empire-class-nbd1-targeting-2508/
[2] https://www.stocktitan.net/news/SION/sionna-therapeutics-announces-first-subjects-dosed-in-phase-1-trial-ghg0dsp3fe74.html