Sionna Therapeutics Targets 10 mmol/L Sweat Chloride Reduction, Dual Combo Readouts Mid-2026
Sionna Therapeutics plans mid-2026 Phase 2a PreciSION-CF trial results for NBD1 stabilizer SION-719 added to TRIKAFTA, targeting at least 10 mmol/L sweat chloride reduction in F508del homozygous patients. It also expects mid-2026 healthy volunteer data on dual NBD1 stabilizer SION-451 plus two correctors to inform combination therapy selection.
1. PreciSION-CF Phase 2a Trial
Sionna will evaluate SION-719 added to TRIKAFTA in a randomized double-blind crossover study of F508del homozygous patients. Each patient will receive two 14-day dosing periods with SION-719 and placebo, separated by a 28-day washout, aiming for at least 10 mmol/L sweat chloride reduction above TRIKAFTA baseline.
2. Dual Combination Phase 1 Study
A healthy volunteer study will test dual NBD1 stabilization with SION-451 plus TMD1 corrector SION-2222 and ICL4 corrector SION-109. Readouts will assess pharmacokinetics, safety and tolerability to select the optimal combination for patient trials.
3. NBD1 Stabilization Rationale
The F508del mutation in the NBD1 region causes irreversible unfolding at body temperature, reducing CFTR half-life. Sionna’s first-in-class NBD1 stabilizers aim to restore wild-type CFTR stability, complementing existing correctors that do not directly target NBD1.