Company: SION
Filing Date: 2025-02-07
Form Type: 424B4
Source: 0001193125-25-022709
Chunk: 153

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-07
Form: 424B4
Chunk 153
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 and other ions and regulate the flow of water. Within the NBD1
domain, F508del severely destabilizes CFTR, preventing normal folding and trafficking of CFTR to a cell’s surface and impairing chloride channel function. We have employed biophysical, cell-based and virtual screening campaigns and extensive
use of structural biology to guide the optimization of novel small molecule NBD1 stabilizers.

Figure 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