Company: SION
Filing Date: 2025-02-03
Form Type: S-1/A
Source: 0001193125-25-018825
Chunk: 165

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-03
Form: S-1/A
Chunk 165
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 development of approved CFTR modulators. A sweat chloride level greater than or equal to 60mmol/L indicates that CF is likely, while a sweat chloride level under
30 mmol/L is normal and indicates that CF is unlikely. Sweat chloride levels between 30 mmol/L and 59 mmol/L are considered abnormal, indicating partial CFTR dysfunction or “residual function” in diagnostic settings. An
observational study of 3,131 individuals with CF from the CFF Registry found that, while treatment with Trikafta resulted in improvements in sweat chloride level to below 60 mmol/L in most patients, two-thirds of patients still had sweat chloride
levels above normal levels (i.e., above 30 mmol/L) (Figure 8).

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Figure 8. Approximately Two-Thirds of Patients on Approved Therapies Do Not Have Normal CFTR Function as Measured by Sweat Chloride Levels

(Sweat chloride levels less than or equal to 29 mmol/L indicate that CF is unlikely; levels of 30 - 59 mmol/L indicate that CF is possible and additional testing is needed; and levels greater than or equal to 60 mmol/L indicate that CF is likely.)

Two-year interim data from a five-year post-marketing real-world observational trial of patients taking Trikafta showed that mean rates of pulmonary exacerbations and the presence of bacterial pathogens improved but
were not normalized after initiating treatment on Trikafta. The three-year interim data, presented at the European CF Society meeting in Glasgow in 2024, showed numerical increases in mean rates of pulmonary exacerbations and decreases in mean lung
function compared to the two-year interim data, supporting the opportunity for clinical improvements over the current standard of care. In addition to continued pulmonary complications, patients also
experienced negative mental health side effects, including numerical increases in rates of depression, anxiety disorder and hypertension after initiating treatment on Trikafta. Another side effect associated with ivacaftor is cataracts, which can
complicate use and requires monitoring, especially in children. In addition, in December 2024, the Trikafta label was updated to include a boxed warning for the risks of drug-induced liver injury and liver failure. The Alyftrek label includes the
same boxed warning.

Alyftrek demonstrated non-inferiority to Trikafta in the primary endpoint of two Phase
3 clinical trials, providing patients with similar FEV as Trikafta and