Sionna to advance SION-451 plus SION-2222 into Phase 2a after PreciSION CF post hoc analysis

Sionna Therapeutics announced on September 14, 2026 that it plans to move its dual combination of SION-451 and SION-2222 into a Phase 2a proof-of-concept trial called AscenSION CF, following a review of clinical, pharmacokinetic, and nonclinical data from the PreciSION CF trial testing SION-719 along with results from a post hoc analysis of that Phase 2a study.¹

PreciSION CF (NCT07108153) was a randomized, double-blind, placebo-controlled, crossover trial that evaluated the safety and tolerability of SION-719 when added to Trikafta in 15 adult participants with CF homozygous for F508del.¹ The trial did not meet its key activity endpoint, and Sionna is discontinuing SION-719 as an add-on to standard of care.¹ Across 14 evaluable participants, the company reported placebo-adjusted sweat chloride changes of negative 1.0 mmol/L under the primary analysis method and negative 1.1 mmol/L under a secondary method.¹

In a subsequent post hoc analysis, the company identified confounding factors including drug exposure irregularities in some participants and lower Trikafta component exposure during SION-719 dosing periods. After excluding participants judged non-adherent, the company calculated a mean placebo-adjusted sweat chloride reduction of up to negative 8.6 mmol/L using the secondary analysis method.¹

The AscenSION CF trial will be open-label, enrolling adults with CF homozygous for F508del who switch from Trikafta to the SION-451 plus SION-2222 combination for 28 days, assessing sweat chloride, safety, and pharmacokinetics, and is expected to begin in the first quarter of 2027.¹

Separately, Sionna's board approved a restructuring plan on September 9, 2026 that includes a roughly 46% workforce reduction while retaining core clinical, regulatory, technical, and corporate capabilities.¹ The company estimates aggregate restructuring charges of approximately $6.4 million.¹ Sionna ended the second quarter of 2026 with about $268.3 million in cash and equivalents, and expects the cost cuts to extend its runway into the second half of 2029.¹