Company: SION
Filing Date: 2025-01-17
Form Type: S-1
Source: 0001193125-25-008474
Chunk: 184

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-01-17
Form: S-1
Chunk 184
---
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 was achieved with multiple doses of 75 mg BID and higher doses.

A PK summary of SION-109 is shown in Figure 27 below. The PK observed was consistent with BID dosing.

138

Figure 27. Phase 1 PK Summary for SION-109in the MAD Portion of the Trial

(Each solid line shows mean concentration data for a dosing cohort over 10 days of dosing. Data points for Day 2 through Day 9 are trough (pre-dose)concentrations. The dotted line represents the C minimum(trough) PK exposure target for SION-109,with the aim to achieve targeted exposure to deliver clinically meaningful benefit when administered in a proprietary dual combination with SION-451or SION-719,based on CFHBE assay data.

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

Potentiator Program—Navocaftor (SION-3067)

Navocaftor is a clinical-stage potentiator of CFTR gating activity that we have licensed from AbbVie. Navocaftor 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. Navocaftor has completed Phase 1, Phase 1b and Phase 2 trials in over 300 subjects and
was generally well-tolerated in CF subjects and healthy volunteers, with improvements observed in sweat chloride levels