Company: SION
Filing Date: 2025-02-07
Form Type: 424B4
Source: 0001193125-25-022709
Chunk: 170

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-07
Form: 424B4
Chunk 170
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 mg and 80 mg of SION-719 twice daily over 10 dosing days, and the next MAD cohort will evaluate 160 mg
twice daily over 10 dosing days. We plan to continue enrolling healthy subjects in the trial. All data remain blinded to individual subject treatment assignment, with the exception of selected individual subjects unblinded for administrative
and study planning purposes according to the clinical trial protocol.

SION-719 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. There were no serious adverse events (“SAEs”). Most treatment-emergent adverse events (“TEAEs”) were mild to moderate (Grade 1 or Grade 2). No TEAEs
led to the discontinuation of trial drug. The most common TEAEs, occurring in >1 subject, were headache, hypoglycemia and diarrhea. All TEAEs occurring in >1 subject were Grade 1 or Grade 2, except a single Grade 4 hypoglycemia TEAE in a
placebo subject in a SAD cohort. There were no TEAEs related to liver function tests. No dose-limiting TEAEs or safety trends of concern have been observed.

Increasing exposure was observed with increasing single and multiple doses. The concentration targets for
SION-719 as 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-719 is shown in Figures 14 and 15 below. The observed PK was consistent with
twice daily (“BID”) dosing.

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Figure 14. Preliminary Phase 1 PK Summary for SION-719in the SAD Portion of the Trial

(Each solid line shows mean concentration data from a dosing cohort. 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-719 is administered in a proprietary dual combination with either SION-2222 or SION-109, or as an add-on to SOC.)

Figure 15. Preliminary Phase 1 PK Summary for SION-719in 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