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

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-03-20
Form: 10-K
Item: Item 1
Chunk 20
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 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.)

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Phase 2 Clinical Development Plans

Our current expectations for our clinical development strategy are depicted in Figure 18 below.

Figure 18. Our Strategic Development Plan to Advance Our Pipeline of NBD1 Stabilizers and Complementary Modulators

Phase 2a Proof-of-Concept Clinical Trial—NBD1 stabilizer + Trikafta

We plan to initiate a Phase 2a proof-of-concept trial in CF patients in the second half of 2025, following completion of our Phase 1 clinical trials of SION-719 and SION-451 and a drug-drug interaction trial. 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. All trial subjects will be randomly allocated to one of two trial arms and continue taking Trikafta throughout the trial. Trial subjects in “Arm A” will first receive Trikafta in combination with an NBD1 stabilizer for 14 days, and, after a 28-day washout period, will receive Trikafta in combination with placebo for 14 days. Trial subjects in “Arm B” will receive the same treatments in reverse order. All subjects will have a 28-day safety follow-up period. We expect to select safety as the primary endpoint, and PK and improvements to sweat chloride levels as the secondary endpoints. 

Combination MAD Clinical Trial(s)—NBD1 stabilizer + galicaftor and/or SION-109

We intend to initiate combination MAD trial(s) in the second half of 2025, assessing the safety, tolerability and PK of dual combination(s) of an NBD1 stabilizer with galicaftor and/or SION-109 in healthy volunteers, following completion of combination toxicology studies. Following the completion of such trial(s), we intend to select a dual combination to advance into a Phase 2b dose-ranging trial in CF patients.

Preclinical Studies