Company: SION
Filing Date: 2025-02-07
Form Type: 424B4
Source: 0001193125-25-022709
Chunk: 178

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-07
Form: 424B4
Chunk 178
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 our NBD1
stabilizers work synergistically with complementary modulators, and with the standard of care, to significantly improve CFTR function in preclinical models. Given the correlation seen in our preclinical studies between CFTR function and clinical
activity, we believe that achieving target exposure levels for our product candidates in our ongoing and future clinical trials has the potential to translate to significant improvements in sweat chloride and lung function, as measured by FEV, in CF patients.

Preclinical Safety/Pharmacology and Toxicology to Support Clinical Trials

For both SION-719 and SION-451, we conducted standard in vitro and
in vivo toxicology and safety pharmacology studies necessary to support first in human studies. The preclinical study results supported early clinical testing above exposure levels that we have predicted can be effective.

Additional NBD1 Stabilizer Candidates

Our portfolio
includes additional NBD1 stabilizer candidates with differentiated profiles from SION-719 and SION-451.

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We have nominated two additional NBD1 stabilizers as development candidates. Complementary Programs We have established a pipeline of proprietary complementary modulators, representing three different mechanisms of action, TMD1-directed correctors, an ICL4-directed corrector, and a potentiator, that can potentially be combined with our NBD1 stabilizers. Our two prioritized clinical-stage complementary modulators are galicaftor (SION-2222) and SION-109.Following completion of our NBD1 stabilizer Phase 1 clinical trials, we plan to evaluate galicaftor and/or SION-109in dual combination with our selected lead NBD1 stabilizer in Phase 1 MAD trials in healthy volunteers. Our portfolio includes additional complementary compounds that we may advance for future combination development with an NBD1 stabilizer, including navocaftor, which has been evaluated in Phase 1 and Phase 2 clinical trials, including in combination with galicaftor, provides our pipeline with a third mechanism of action complementary to NBD1 stabilizers and future opportunities to develop additional combination products to potentially expand our CF franchise. Clinical Data — Complementary Modulators TMD1 Programs—Galicaftor (SION-2222) and SION-2851 In a Phase 2 clinical trial conducted by AbbVie prior to our in-licensing transaction, galicaftor demonstrated clinical activity in improving sweat chloride and lung function as part of a combination trial with navocaftor. Galicaftor has