Company: SION
Filing Date: 2025-02-03
Form Type: S-1/A
Source: 0001193125-25-018825
Chunk: 172

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-03
Form: S-1/A
Chunk 172
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 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 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.)

128

Interim Phase 1 Trial Data for SION-451

As of January 14, 2025, over