Company: SION
Filing Date: 2025-02-03
Form Type: S-1/A
Source: 0001193125-25-018825
Chunk: 6

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-03
Form: S-1/A
Chunk 6
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ine at position 508 in NBD1) is considered a severe CF mutation, and individuals with this mutation tend to fall at the worst end of the CF severity spectrum because they have
little or no CFTR function in epithelial cells.

The current standard of care for people with the F508del mutation is a triple combination product
marketed by Vertex Pharmaceuticals, Inc. (“Vertex”) as Trikafta (elexacaftor, tezacaftor, ivacaftor and ivacaftor). In addition, in December 2024, Vertex received approval from the U.S Food and Drug Administration (the “FDA”) for
a second-generation, triple modulator combination, Alyftrek, for the treatment of CF in patients aged six years and older who have at least one F508del mutation or another responsive mutation in the CFTR gene. Vertex also markets three other
approved CFTR modulators. None of the approved modulators directly stabilize NBD1.

While advances in the treatment of patients with CF have
improved the lives of patients, the median predicted survival age for individuals with CF born in the U.S. between 2019 and 2023 is still just 61 years, according to the 2023 CFF patient registry. We believe significant opportunity remains to
provide clinically meaningful benefit to CF patients through the development of NBD1-anchored treatments. NBD1 has long been considered an important target to normalize CFTR function because it is the site where the F508del mutation—the most
common mutation that causes CF—resides. At least two-thirds of patients on Trikafta do not have normal CFTR function, as measured by sweat chloride levels below 30 mmol/L. Even treated CF patients can continue to experience the ongoing effects
of reduced CFTR function over time, including respiratory infections, pulmonary exacerbations, or “lung attacks,” and continued lung function decline. More than 6,000 patients have discontinued use of approved CFTR modulators, none of
which target NBD1. Such patients have limited or no alternative treatments available to improve their clinical outcomes or quality of life. Additionally, some patients on Trikafta reduce dosages due to tolerability issues. Our research with key
opinion leaders has indicated the desire for more treatment options for CF patients, support for a new mechanism of

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action that could provide clinically meaningful benefit for people living with CF, and need for an alternative for those patients who experience toler