Company: SION
Filing Date: 2025-01-17
Form Type: S-1
Source: 0001193125-25-008474
Chunk: 173

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-01-17
Form: S-1
Chunk 173
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 Plan to Advance Our Pipeline of NBD1 Stabilizers and Complementary Modulators

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

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. All trial subjects would be randomly allocated to one of two trial arms and continue taking Trikafta throughout the trial. Trial subjects in “Arm A” would first
receive Trikafta in combination with our lead NBD1 stabilizer for 14 days, and, after a 28-day washout period, would then receive Trikafta in combination with placebo for 14 days. Trial subjects in “Arm
B” would receive the same treatments in reverse order. All subjects would 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. We expect to initiate the Phase 2a clinical trial in the second half of 2025.

Combination MAD Clinical Trials—NBD1 stabilizer + galicaftor or SION-109

Following completion of our ongoing Phase 1 clinical trials of SION-719 and
SION-451 and completion of combination toxicology studies, and our selection of a lead NBD1 stabilizer, we intend to begin one or two separate MAD trials of dual combinations, assessing the safety,
tolerability and PK of our lead NBD1 stabilizer in dual combination with galicaftor and/or SION-109 in healthy volunteers. We anticipate initiating these combination MAD trials in the second half of 2025.
Following the completion of such trials, we intend to select one dual combination to advance into Phase 2b dose-ranging trials in CF patients.

Preclinical Studies

We have used
numerous complementary methods to validate and characterize the activity of our compounds. In addition to the CFHBE model, we have utilized differential static light scattering (“DSLS”) experiments to measure the thermal stability of the
NBD1 protein, surface plasmon resonance (“SPR