Company: SION
Filing Date: 2025-03-20
Form Type: 10-K
Source: 0002036042-25-000005
Chunk: 26

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-03-20
Form: 10-K
Item: Item 1
Chunk 26
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, that can potentially be combined with our NBD1 stabilizers. Our two prioritized clinical-stage complementary modulators are galicaftor (SION-2222) and SION-109. Following completion of our NBD1 stabilizer Phase 1 clinical trials, we plan to evaluate galicaftor and/or SION-109 in dual combination with an NBD1 stabilizer in Phase 1 MAD trials in healthy volunteers.

Our portfolio includes additional complementary compounds that we may advance for future combination development with an NBD1 stabilizer, including navocaftor, which has been evaluated in Phase 1 and Phase 2 clinical trials, including in combination with galicaftor, provides our pipeline with a third mechanism of action complementary to NBD1 stabilizers and future opportunities to develop additional combination products to potentially expand our CF franchise.

Clinical Data — Complementary Modulators

TMD1 Programs—Galicaftor (SION-2222) and SION-2851

In a Phase 2 clinical trial conducted by AbbVie prior to our in-licensing transaction, galicaftor demonstrated clinical activity in improving sweat chloride and lung function as part of a combination trial with navocaftor. Galicaftor has been evaluated in Phase 1, Phase 1b and Phase 2 clinical trials involving healthy subjects and CF patients. Galicaftor was generally well-tolerated at all doses administered. The majority of adverse events were mild to moderate in severity. No serious adverse events were reported in healthy volunteers, and among CF patients, serious adverse events were reported infrequently and consisted of common manifestations of the underlying CF disease. Based on galicaftor’s preclinical profile, we do not expect significant PK or drug/drug interactions with our NBD1 stabilizers or other complementary modulators. The PK profile of galicaftor in CF patients was similar to that observed in healthy volunteers. The activity of galicaftor in patients with CF has been evaluated in three randomized, double-blind, placebo-controlled Phase 2 trials, as summarized below.

Trials GLPG-2222-CL-201 and GLPG-2222-CL-202 had at least 80% power to detect selected changes in sweat chloride. In clinical trials, least squares means, or “LS means,” represent the average predicted values of the outcome variable in a statistical model and estimate the effect of a treatment while controlling for other covariates that may influence the outcome. These means provide a clearer