Company: SION
Filing Date: 2025-01-17
Form Type: S-1
Source: 0001193125-25-008474
Chunk: 172

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-01-17
Form: S-1
Chunk 172
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 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 SION-451 is shown in Figures 16 and 17 below. The observed PK was
consistent with BID dosing.

Figure 16. Preliminary Phase 1 PK Summary for SION-451in 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-451 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 17. Preliminary Phase 1 PK Summary for SION-451in 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.)

Phase 2 Clinical Development Plans

Based on our current clinical development strategy, we anticipate conducting a Phase 2a add-on to Trikafta proof-of-concept trial and a Phase 2 dual combination treatment trial after the completion of our ongoing Phase 1 trials of SION-719
and SION-451. Our current expectations for our clinical development strategy are depicted in Figure 18 below.

Figure 18. Our Strategic Development