Company: SION
Filing Date: 2025-02-03
Form Type: S-1/A
Source: 0001193125-25-018825
Chunk: 185

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-03
Form: S-1/A
Chunk 185
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 U.S. and was designed to evaluate the safety, tolerability and PK profile of single and multiple ascending doses of SION-109,administered as an oral suspension. In a Part C of the Phase 1 trial, we also evaluated the effect of food on PK and the bioequivalence of a tablet formation compared to the oral suspension used in the Phase 1 SAD and MAD trials. 138

102 healthy adult subjects were dosed in this Phase 1 trial. The trial was designed to enroll 8
subjects, randomized 3:1 active:placebo, to each dosing cohort. Six SAD cohorts evaluated single doses from 50 mg to 400 mg. Five MAD cohorts evaluated from 50 mg to 150 mg twice daily over 10 dosing days. 15 subjects enrolled in the open-label food
effect and tablet bioequivalence part evaluating 100 mg single doses each of suspension fasted, tablet fasted, and tablet fed.

SION-109 was
generally well tolerated at all dose levels administered in all parts of this Phase 1 trial. A summary table of reported TEAEs is shown in Figure 26 below. There were no SAEs, and most TEAEs were mild to moderate (Grade 1 or Grade 2). No TEAEs led
to the discontinuation of trial drug, and no dose-limiting TEAEs were observed. Sporadic increases in potassium were observed that were determined to be related to sample collection and/or processing. A 150 mg MAD cohort was repeated with revised
sampling guidance, and no increased potassium values were observed. Isolated and transient increases in transaminases were observed associated with four AEs in three subjects in the MAD and Part C (one Grade 1 AE, two Grade 2 AEs and one Grade 3 AE)
whose values returned to the normal range in follow-up. Other liver function tests, including bilirubin, were unremarkable. There were no clinically meaningful, treatment-emergent trends in other safety
parameters, vital signs or electrocardiograms.

Figure 26. Phase 1 TEAEs for SION-109in the MAD Portion of the Trial

(Safety observations in the SAD and Part C portions of the trial were generally consistent with the MAD findings shown.)

Increasing exposure was observed with increasing single and multiple doses. The target exposure for SION-109 as part of a dual combination with SION-451 or SION-719