Company: SION
Filing Date: 2025-01-17
Form Type: S-1
Source: 0001193125-25-008474
Chunk: 9

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-01-17
Form: S-1
Chunk 9
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 drug. No dose limiting AEs 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 in the MAD portion of the trial is shown in Figure 5 below. The observed PK was consistent with
BID dosing.

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Figure 5. Preliminary Phase 1 PK Summary for SION-451 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-451 is administered in a proprietary dual combination with either SION-2222 or SION-109, or as an add-on to SOC.) Next Steps Following completion of our ongoing Phase 1 clinical trials of SION-719 and SION-451, we plan to select a lead NBD1 stabilizer and conduct a drug-drug interaction trial before initiating a Phase 2a proof-of-concept trial in CF patients. We expect the Phase 2a trial to be a two-way crossover trial in which we enroll up to 20 trial subjects with CF who are stable on physician-prescribed Trikafta. We expect to select safety as the primary endpoint, and PK and improvements to sweat chloride levels as the secondary endpoints. We expect to initiate the Phase 2a clinical trial in the second half of 2025. Galicaftor and SION-109 Galicaftor has completed Phase 1 and Phase 2 trials in approximately 400 subjects and was well-tolerated in CF subjects and healthy volunteers, with improvements in sweat chloride levels observed as a single agent and improvements in sweat chloride and lung function in combination with navocaftor (SION-3067), a clinical-stage potentiator of CFTR gating activity that we have licensed from AbbVie. We have also recently completed a Phase 1 clinical trial evaluating SION-109 to assess the safety, tolerability and PK of single and multiple ascending doses in healthy volunteers. Our Strategy Our mission is to revolutionize the current treatment paradigm for CF patients by developing novel medicines that normalize the function of the CFTR protein to deliver clinically