Company: SION
Filing Date: 2025-03-20
Form Type: 10-K
Source: 0002036042-25-000005
Chunk: 2

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-03-20
Form: 10-K
Item: Item 1
Chunk 2
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”) 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 December 2024, we 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 candidates and complementary modulator candidates and select the most promising candidates to advance into later-stage development. Initially, we intend to evaluate an NBD1 stabilizer candidate in combination with the current standard of care in a Phase 2a proof-of-concept trial, expected to begin in the second half of 2025. 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 2.

Figure 2. Our NBD1 Stabilizers Have Multiple Potential Pathways to Deliver Clinically Meaningful Benefit to CF Patients

Central to our development strategy is our use of the industry standard, clinically predictive preclinical cystic fibrosis human bronchial epithelial (“CFHBE”) model to measure CFTR function. The CFHBE model uses lung cells from CF patients and has been highly predictive of clinical outcomes for approved CFTR modulators. Vertex Pharmaceuticals, Inc. (“Vertex”), the manufacturer of the five approved CFTR modulators, has demonstrated that increased chloride transport in the CFHBE model is strongly correlated with improved CFTR function in CF patients. In head-to-head preclinical studies using the CFHBE model, we evaluated several of our proprietary dual combinations (combining each of SION-719 and SION-451 with each of SION-2222 and SION-109) in direct comparison to elexacaftor/tezacaftor/ivacaftor (“ETI”) (which we synthesized using methods described in publicly available sources), with all compounds at their respective highest effective dose (“Emax”). In other head-to-head preclinical studies using the CFHBE model