SION-451 + SION-109

August 10, 2026: Sionna Therapeutics (NASDAQ: SION) reported topline cystic fibrosis data from two programs. In the Phase 2a PreciSION CF proof-of-concept trial (NCT07108153), SION-719 added to Trikafta in 15 adults with CF homozygous for F508del failed the key activity endpoint: mean placebo-adjusted sweat chloride change was -1.0 mmol/L (p=0.7). The company cited potential confounders, including higher-than-expected sweat chloride variability and differences in Trikafta exposure between SION-719 and placebo periods. SION-719 was generally well tolerated over 14 days, with mostly mild to moderate TEAEs, no serious adverse events, and no meaningful liver test signal, but Sionna said it will not advance SION-719 as an add-on to standard of care.

In the Phase 1 healthy volunteer dual-combination trial (NCT07035990), SION-451 combined with either SION-2222 or SION-109 met safety, tolerability, and pharmacokinetic objectives, including target exposures set before the Phase 2a results. SION-451 + SION-2222 was selected as the preferred dual combination. Across cohorts, regimens were generally well tolerated; one discontinuation occurred due to rash, and in twice-daily SION-451 + twice-daily SION-2222 cohorts, two participants discontinued due to elevated liver function tests and flu-like symptoms. Sionna is evaluating next steps for SION-451 and ended Q2 with about $268.3 million in cash while planning capital-preservation actions.