Company: SION
Filing Date: 2025-02-03
Form Type: S-1/A
Source: 0001193125-25-018825
Chunk: 155

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-03
Form: S-1/A
Chunk 155
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 1. CFTR Structure

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

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each product candidate in healthy subjects. These trials are randomized (3:1 active:placebo), doubled-blinded, placebo-controlled and are 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, and six SAD cohorts and three MAD cohorts of SION-451 have been completed, with over 70 subjects dosed. 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
additional MAD cohorts.

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 Global Enterprises Ltd. (“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.

Our vision is to build a CF franchise anchored by our NBD1 stabilizers to deliver clinically meaningful benefit to CF patients. We believe our robust
pipeline of NBD1 stabilizers and complementary modulators provide multiple potential pathways to achieving that vision, 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