Company: SION
Filing Date: 2025-02-03
Form Type: S-1/A
Source: 0001193125-25-018825
Chunk: 164

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-03
Form: S-1/A
Chunk 164
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 reported revenues in 2023 from global sales of its then-approved
CFTR modulators of approximately $9.9 billion, more than $8.9 billion of which the company attributed to Trikafta. Vertex’s approved CFTR modulators target approximately 92,000 CF patients in North America, Europe and Australia, and
more than 20% of eligible patients are currently not on CFTR modulators. CF screening of newborn infants has served to identify CF patients as early as possible in their lives. For example, newborn screening for CF has been required in the U.S.
since 2010, and in 2021, 64.4% of newly diagnosed people with CF in the U.S. were identified by newborn screening, based on CFF registry data. The availability of CFTR modulators has also increased the use of genetic testing to determine eligibility
for treatment.

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Current Standard of Care and its Limitations

The approved CFTR modulators are oral small molecule therapies that improve CFTR function either by potentiating channel gating or by improving cellular
processing and trafficking of the CFTR protein. The current standard of care for people with the F508del mutation is a triple combination product marketed by Vertex as Trikafta (elexacaftor, tezacaftor, ivacaftor and ivacaftor). In addition, in
December 2024, Vertex received approval from 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. The drugs and their approved indications in the U.S. are summarized in Figure 7.

Figure 7. FDA-ApprovedCFTR Modulators and Summary Indications

Despite the clinical benefits Trikafta provides CF patients, including improved lung function and quality of life, at
least two-thirds of people with CF being treated on Trikafta or another approved CFTR modulator do not have normal CFTR function. CF progression is most commonly assessed through a patient’s mean lung
function, as measured by FEV improvement. In addition, sweat chloride level, the clinical biomarker of CFTR function, has been used for
decades as a diagnostic test for CF and has served as a highly useful tool in the