Company: SION
Filing Date: 2025-02-07
Form Type: 424B4
Source: 0001193125-25-022709
Chunk: 171

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-07
Form: 424B4
Chunk 171
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 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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Interim Phase 1 Trial Data for SION-451

As of January 14, 2025, over 70 healthy subjects have 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. Four SAD cohorts have been completed, evaluating single doses of 75 mg, 150 mg, 300 mg and 450 mg. Two additional SAD cohorts have completed
dosing with 75 mg or 25 mg with food to provide a preliminary assessment of the effect of food on PK. Three MAD cohorts have been completed, evaluating 75 mg, 150 mg and 300 mg of SION-451 twice daily over 10
dosing days, and the next MAD cohort will evaluate 225 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.

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. 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. The most common TEAEs, occurring in more than one subject, were headache, abdominal pain, contact dermatitis,
influenza, presyncope, fatigue and upper respiratory tract infection. All TEAEs occurring in >1 subject were Grade 1 or Grade 2, and many were in an isolated dose cohort that was impacted by an outbreak of respiratory infection in the Phase
1 unit. One Grade 1 TEAE of increased transaminases has been observed, in a subject with influenza A infection. 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-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