Sionna narrows focus to dual CFTR combination, plans Phase 2 trial for early 2027

Sionna Therapeutics reported third quarter 2026 results on November 10, 2026, and said it plans to initiate the AscenSION CF Phase 2 proof-of-concept trial in the first quarter of 2027.¹ The combination pairs SION-451, an NBD1 stabilizer, with SION-2222 (galicaftor), a transmembrane domain 1 (TMD1)-directed CFTR corrector.¹

The trial design calls for an open-label study of participants with CF homozygous for F508del treated with SION-451 plus SION-2222 for 28 days after switching from Trikafta, assessing sweat chloride, safety, and pharmacokinetics, with design features drawn from lessons on dosing adherence and sweat chloride variability learned in the PreciSION CF program.¹ Sionna said the combination was chosen based on the totality of clinical, pharmacokinetic, and nonclinical data, including meeting safety, tolerability, and PK objectives in the Phase 1 healthy volunteer trial.¹

On the prior program, the company confirmed that its PreciSION CF Phase 2a study testing SION-719 as an add-on to Trikafta "did not achieve its key activity endpoint," and Sionna said it will not pursue SION-719 further as an add-on to standard of care. A post hoc analysis that excluded three participants believed to have been non-adherent to dosing found a mean placebo-adjusted sweat chloride reduction of up to -8.6 mmol/L for SION-719 added to Trikafta, which the company said points to NBD1 biological activity.¹

In September 2026, Sionna cut its workforce by about 46% and took other cost-saving steps aimed at concentrating resources on the SION-451 plus SION-2222 program and extending its cash runway.¹ As of September 30, 2026, the company held $249.8 million in cash, cash equivalents and marketable securities, which it said should fund operations into the second half of 2029.¹