Company: SION
Filing Date: 2025-01-17
Form Type: S-1
Source: 0001193125-25-008474
Chunk: 164

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-01-17
Form: S-1
Chunk 164
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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 sweat chloride level improvements of 3 to 8 mmol/L. Approximately 69% of Alyftrek patients in two Phase 3 clinical
trials did not achieve normal CFTR function. These results support our beliefs that NBD1 stabilization is required to meaningfully improve upon the current standard of care and that a high unmet need remains for an alternative therapy that can
provide clinically meaningful benefit to CF patients.

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Research Findings Support NBD1 as a Key Target for Stabilizing F508del-CFTR

Multiple studies by third parties have concluded that NBD1 is a key drug target for correcting the F508del mutation, including in vitro studies
that introduced mutations at other sites on NBD1 that suppressed the effect of the F508del mutation. For example, researchers at Utrecht University and University of Texas Southwestern Medical Center identified a second site NBD1 mutation
(“I539T”) that rescued the misfolding and instability of F508del