Company: SION
Filing Date: 2025-02-03
Form Type: S-1/A
Source: 0001193125-25-018825
Chunk: 181

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-03
Form: S-1/A
Chunk 181
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 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 of navocaftor in combination with 
 placebo for galicaftor, and five treatment arms across a range                                                              |

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| of doses of galicaftor (doses 10 mg, 30 mg, 100 mg, 200 mg, 300 mg once daily (“QD”)) in combination with navocaftor 150 mg for 28 days. |