Company: SION
Filing Date: 2025-03-20
Form Type: 10-K
Source: 0002036042-25-000005
Chunk: 18

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-03-20
Form: 10-K
Item: Item 1
Chunk 18
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AEs, 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, including in the additional MAD cohort completed after the interim data cutoff date. 

Increasing exposure was observed with increasing single and multiple doses as of the interim data cutoff date. 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 data as of the cutoff date of January 14, 2025 is shown in Figures 14 and 15 below. The observed PK was consistent with BID dosing.

Figure 14. Preliminary Phase 1 PK Summary for SION-719 in 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.) 

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Figure 15. Preliminary Phase 1 PK Summary for SION-719 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-719 is administered in a proprietary dual combination with either SION-2222 or SION-109, or as an add-on to SOC.) 

Interim Phase 1 Trial Data for SION-451 

As of January 14, 2025, over 70 healthy subjects had been dosed in the Phase 1 clinical trial of SION-451. The trial was designed to enroll eight subjects, randomized 3:1 active:placebo, in each dosing cohort. Six SAD cohorts had been completed, evaluating single doses of 75 mg, 150 mg, 300 mg