Company: SION
Filing Date: 2025-02-07
Form Type: 424B4
Source: 0001193125-25-022709
Chunk: 183

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-07
Form: 424B4
Chunk 183
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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.

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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 in combination with galicaftor.

In Phase 1 trials evaluating safety and tolerability in healthy subjects, navocaftor was generally well-tolerated in combination with galicaftor, in
each case at doses up to 500 mg twice daily for 14 days. These trials were conducted in Europe and the U.S. In addition, navocaftor has been generally well-tolerated in both CF subjects and healthy volunteers. When navocaftor was given as a
monotherapy or in combination with galicaftor, all AEs were mild to moderate