Company: SION
Filing Date: 2025-02-03
Form Type: S-1/A
Source: 0001193125-25-018825
Chunk: 132

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-03
Form: S-1/A
Chunk 132
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 We believe stabilizing NBD1 is central to unlocking
dramatic improvements in clinical outcomes and quality of life for CF patients.

We are conducting ongoing Phase 1 trials of our two highly potent
NBD1 stabilizers—SION-719 and SION-451—evaluating the safety, tolerability and PK of single and multiple ascending doses of each product candidate in healthy subjects. These trials are randomized, doubled-blinded, placebo-controlled trials
being conducted in Australia. As of January 14, 2025, five SAD cohorts and three MAD cohorts of SION-719 have been completed, with over 60 healthy subjects dosed (randomized 3:1 active:placebo), and six SAD cohorts and three MAD cohorts of SION-451
have been completed, with over 70 healthy subjects dosed (randomized 3:1 active:placebo). Both SION-719 and SION-451 have been generally well tolerated based on interim Phase 1 clinical data as of the cutoff date of January 14, 2025. In these
trials, at both single and multiple doses, SION-719 and SION-451 exposures were achieved that have the potential, based on our preclinical CFHBE model, to provide clinically meaningful benefit if SION-719 or SION-451 were administered as part of a
dual combination or as an add-on to the standard of care (“SOC”). We plan to continue enrolling healthy subjects in the trial.

We are
also developing a portfolio of complementary CFTR modulators designed to work synergistically with our NBD1 stabilizers to improve CFTR function, as seen in preclinical models. In July 2024, we in-licensed
three clinical-stage compounds from AbbVie to expand our portfolio of combination product opportunities, including galicaftor (SION-2222), which targets CFTR’s transmembrane domain 1 (“TMD1”), and has completed Phase 2 clinical
trials. In addition, we have recently completed a Phase 1 clinical trial evaluating SION-109, which targets CFTR’s intracellular loop 4 (“ICL4”) region.

We believe our robust pipeline of NBD1 stabilizers and complementary modulators provide multiple potential pathways to achieving our goal, either in
combination with each other to produce a proprietary combination CF therapy, or in combination with the current standard of care. We plan to evaluate multiple NBD1 stabilizer candidates and complementary