Company: SION
Filing Date: 2025-02-07
Form Type: 424B4
Source: 0001193125-25-022709
Chunk: 3

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-07
Form: 424B4
Chunk 3
---
”) 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 healthy subjects dosed. Both SION-719 and SION-451 have been generally well tolerated based on interim Phase 1 clinical data as of the data cutoff date of
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

1

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