Company: SION
Filing Date: 2025-02-03
Form Type: S-1/A
Source: 0001193125-25-018825
Chunk: 5

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-03
Form: S-1/A
Chunk 5
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January 14, 2025. We have established target exposure levels for SION-719 and SION-451 to potentially provide clinically meaningful benefit, if administered as part of a dual combination or as an add-on
to the current standard of care (“SOC”), based on our preclinical cystic fibrosis human bronchial epithelial (“CFHBE”) model. In these trials, we have achieved the target concentrations for SION-719 and SION-451 with single and
multiple doses. 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

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trials. In addition, we recently completed a Phase 1 clinical trial evaluating SION-109, which targets CFTR’s intracellular loop 4 (“ICL4”)
region. We plan to evaluate multiple NBD1 stabilizer candidates and complementary modulator candidates and select the most promising candidates to advance into later-stage development. Initially, we intend to evaluate the lead NBD1 stabilizer
candidate in combination with the current standard of care, Trikafta, in a proof-of-concept trial. In parallel, we will determine the proprietary dual combination that
we believe is optimal to advance into a later-stage clinical trial in CF patients, as illustrated in Figure 1.

Figure 1. Our NBD1 Stabilizers Have Multiple Potential Pathways to Deliver Clinically Meaningful Benefit to CF Patients

CF Background and Unmet Need

An estimated 106,000 people have been diagnosed with CF across 94 countries, including approximately 33,000 adults and children living with CF in the
U.S., according to the Cystic Fibrosis Foundation (“CFF”). CF is caused by mutations to the CFTR gene that result in reduced or no function of the CFTR protein. Approximately 90% of people with CF carry at least one copy of the F508del
mutation. The F508del mutation (a deletion of the amino acid phenylalan