Company: SION
Filing Date: 2025-02-07
Form Type: 424B4
Source: 0001193125-25-022709
Chunk: 8

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-07
Form: 424B4
Chunk 8
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 SION-109, or as an add-onto SOC.)

Interim Phase 1TrialData for SION-451

SION-451 was generally well tolerated at all dose levels administered based on interim Phase 1 clinical data as of the data cutoff date of January 14,
2025. SION-451 was generally well tolerated at all dose levels administered. 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. No dose limiting AEs or safety trends of
concern have been observed.

Increasing exposure was observed with increasing single and multiple doses. The concentration targets for SION-451 as
both an add-on to SOC and as part of a dual combination with SION-2222 or SION-109 were achieved with single and multiple doses. A PK summary of SION-451 in the MAD portion of the trial is shown in Figure 5 below. The observed PK was consistent with
BID dosing.

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Figure 5. Preliminary Phase 1 PK Summary for SION-451 in the MAD Portion of the Trial (Each solid line shows mean concentration data from a dosing cohort on Day 10. Dotted lines represent average PK concentration exposure targets that have the potential, based on our preclinical CFHBE model, to provide clinically meaningful benefit, if SION-451 is administered in a proprietary dual combination with either SION-2222 or SION-109, or as an add-on to SOC.) Next Steps Following completion of our ongoing Phase 1 clinical trials of SION-719 and SION-451, we plan to select a lead NBD1 stabilizer and conduct a drug-drug interaction trial before initiating a Phase 2a proof-of-concept trial in CF patients. We expect the Phase 2a trial to be a two-way crossover trial in which we enroll up to 20 trial subjects with CF who are stable on physician-prescribed Trikafta. We expect to select safety as the primary endpoint, and PK and improvements to sweat chloride levels as the secondary endpoints. We expect to initiate the Phase 2a clinical trial in the second half of 2025. Galicaftor and SION-109 Galicaftor has completed Phase 1 and Phase 2 trials in approximately 400 subjects and was well-tolerated in CF subjects and healthy volunteers, with improvements in sweat chloride levels observed as