Company: SION
Filing Date: 2025-02-07
Form Type: 424B4
Source: 0001193125-25-022709
Chunk: 179

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-07
Form: 424B4
Chunk 179
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 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 comparison between treatment groups by minimizing potential biases from imbalanced covariates. A confidence interval (“CI”) is a range of values, derived from the sample data, that is believed to contain the treatment effect with a specified level of confidence, usually 95%. In clinical trials, the p-value quantifies the probability of observing the trial results (or more extreme results) assuming there is no effect or no difference between treatment groups. A p-value of < 0.05 is generally considered statistically significant, meaning that the probability of the results occurring by chance alone is less than five percent.

| • |     | Trial M19-530 was a Phase 2 dose-ranging trial conducted by AbbVie in Europe and the U.S. to evaluate the safety,                                                                                                                                                                                                   
 tolerability and efficacy of navocaftor alone and in combination with galicaftor in 76 CF patients that were homozygous for F508del mutation. The primary efficacy endpoint of this trial was absolute change in lung function (ppFEV1) from baseline (day 1) through day 29. The trial was completed in June 2022. |

| • |     | This trial included eight total arms: a single placebo arm, two arms with different doses