Sionna Drops SION-719 Add-On After PreciSION Miss

The Tip Desk · November 12, 2026 · 3 min read

The company posted a $32.4 million third-quarter net loss and said cash of $249.8 million is expected to fund operations into the second half of 2029.

Sionna Therapeutics, Inc. (SION), a clinical-stage biopharmaceutical company developing medicines for cystic fibrosis, said the PreciSION CF Phase 2a trial of SION-719 added to Trikafta did not achieve its key activity endpoint and that it is not advancing SION-719 as an add-on to standard of care. The company instead plans to initiate the AscenSION CF Phase 2 proof-of-concept trial of the SION-451 + SION-2222 dual combination in the first quarter of 2027.

President and Chief Executive Officer Mike Cloonan said the company established a focused path centered on that proprietary, NBD1-anchored dual combination, citing PreciSION CF post hoc analyses and the dual combination’s Phase 1 results.

The open-label AscenSION CF study will evaluate participants with CF homozygous for F508del treated with SION-451 + SION-2222 for 28 days after switching from Trikafta. It will assess sweat chloride, safety, and pharmacokinetics, and its design will incorporate learnings from PreciSION CF related to dosing adherence and sweat chloride variability. SION-451 is an NBD1 stabilizer; SION-2222 (galicaftor) is a TMD1-directed CFTR corrector. The company said the dual combination was selected on the totality of clinical, PK, and nonclinical data, including achievement of safety, tolerability, and PK objectives in a Phase 1 healthy-volunteer trial.

Post hoc analyses of PreciSION CF excluding three participants with drug exposures consistent with dosing non-adherence showed a mean placebo-adjusted sweat chloride reduction of up to -8.6 mmol/L when SION-719 was added to Trikafta, which Sionna said is indicative of NBD1 biological activity. The company also said the analyses identified other potential confounding factors related to the interaction of SION-719 with Trikafta that may have blunted additional benefit from NBD1 stabilization. Those findings, together with Phase 1 dual-combination results, informed the decision to advance SION-451 + SION-2222 and the AscenSION CF design.

In October 2026, Sionna presented clinical and nonclinical data at the North American Cystic Fibrosis Conference in Atlanta. A poster evaluated SION-451 and SION-719 in combination with complementary CFTR modulators, including SION-2222 and SION-109, in primary CF human bronchial epithelial cells from donors with two copies of F508del or one copy of F508del and a null mutation. Across both donor groups, the company said the NBD1 stabilizer-based combinations demonstrated improved CFTR trafficking and function up to wild-type levels.

In September 2026, following a comprehensive review of operations, Sionna implemented a workforce reduction of approximately 46% and other cost-saving measures to focus resources on the dual combination and extend its operating runway.

Research and development expenses were $22.0 million for the third quarter of 2026, compared with $16.0 million a year earlier. The company said the increase was primarily driven by development expenses, personnel-related costs including stock-based compensation, and restructuring related to the workforce reduction. General and administrative expenses were $12.8 million, compared with $7.8 million a year earlier, primarily due to personnel-related costs including stock-based compensation and restructuring related to the workforce reduction.

Net loss was $32.4 million for the third quarter of 2026, compared with a net loss of $20.3 million a year earlier, or $0.72 a share versus $0.46 a share.

Cash, cash equivalents and marketable securities totaled $249.8 million as of September 30, 2026, down from $268.3 million as of June 30, 2026. Sionna said the cash position is expected to fund operations into the second half of 2029, later than the prior quarter’s “into 2028” runway.