WALTHAM, Mass. — September 14, 2026

Sionna Therapeutics, Inc. announced plans to advance its preferred proprietary dual combination of SION-451 + SION-2222 into the AscenSION CF Phase 2a proof-of-concept trial, following a comprehensive review of clinical, pharmacokinetic and nonclinical data from the PreciSION CF program. The decision follows post hoc analyses of SION-719, an NBD1 stabilizer that did not meet its key activity endpoint when added to Trikafta. In the analysis of 14 evaluable participants, placebo-adjusted sweat chloride changes were similar under the primary and prespecified secondary baseline methodologies. However, excluding three participants identified as PK outliers resulted in a mean placebo-adjusted sweat chloride reduction of up to -8.6 mmol/L, which Sionna said was consistent with biological activity of NBD1 stabilization. The company plans to initiate the AscenSION CF Phase 2a study in the first quarter of 2027.

Post Hoc Analysis Supports NBD1 Biological Activity

Sionna identified several factors that may have complicated interpretation of the PreciSION CF results, including inconsistent drug exposure and interactions between SION-719 and components of Trikafta. Three participants had drug exposures at key timepoints consistent with non-adherence, and excluding those participants produced the stronger sweat chloride signal. The company also observed that exposure to elexacaftor, tezacaftor and ivacaftor declined by approximately 25% to 30% on average during SION-719 treatment periods, while remaining relatively stable during placebo periods. In addition, post hoc preclinical CFHBE assay analysis suggested that combining an NBD1 stabilizer with ivacaftor may have limited the additional benefit of NBD1 stabilization, while this interaction was not observed with complementary correctors targeting TMD1 or ICL4. Sionna believes these findings suggest SION-719 was biologically active, although PK variability and the interaction with Trikafta may have blunted the treatment signal. The company is not advancing SION-719 as an add-on to standard of care.

AscenSION CF Will Evaluate Dual CFTR Modulation

The planned AscenSION CF Phase 2a trial will directly test SION-451 + SION-2222 in adults with CF who are homozygous for F508del. The open-label study will treat participants for 28 days after switching from Trikafta to the dual combination and will evaluate sweat chloride, safety and pharmacokinetics. The trial design incorporates lessons from PreciSION CF, particularly around treatment adherence and variability in sweat chloride measurements. The selected regimen consists of SION-451 twice daily and SION-2222 once daily, based on Phase 1 findings showing favorable tolerability and exposure coverage. In the healthy-volunteer Phase 1 study, SION-451-based dual combinations met safety, tolerability and PK objectives, with SION-451 + SION-2222 identified as the preferred combination. Sionna said exposure at the planned Phase 2a doses fell within the range associated with meaningful CFTR-function improvement in its preclinical CFHBE assay.

Advertisement

cGxPJobs Banner

Sionna Restructures to Extend Runway Through 2029

Sionna is simultaneously restructuring its operations to prioritize the dual-combination program and extend its financial runway. The company’s Board approved an approximately 46% workforce reduction, alongside other cost-saving measures and the discontinuation of investment in SION-719 as an add-on to standard of care. Sionna expects to retain core clinical, scientific, regulatory, technical and corporate capabilities needed to advance SION-451 + SION-2222 and estimates aggregate restructuring and related charges of approximately $6.4 million. The company ended the second quarter of 2026 with approximately $268.3 million in cash, cash equivalents and marketable securities and expects the cost reductions to extend its operating runway into the second half of 2029. With the Phase 2a program targeted for early 2027, Sionna is concentrating its resources on determining whether direct NBD1 stabilization combined with complementary CFTR modulation can deliver meaningful improvements in CFTR function for people with cystic fibrosis..

Source: Agomab Therapeutics press release