Company: SION
Filing Date: 2025-02-03
Form Type: S-1/A
Source: 0001193125-25-018825
Chunk: 167

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-03
Form: S-1/A
Chunk 167
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Clinical evidence obtained by third parties has illustrated
that further reductions in sweat chloride, the clinical biomarker of CFTR function, towards wild-type levels, are associated with improved clinical outcomes, even for patients who have already experienced some benefits from an approved modulator
therapy. According to a trial published in the New England Journal of Medicine, when CF patients heterozygous for F508del and a “gating” mutation were switched from Kalydeco, which does not target F508del, to Trikafta, which targets
F508del, they experienced significant improvements in CFTR function, as measured by improvements in the mean sweat chloride levels, and in mean lung function, as measured by FEV. Patients with
a gating mutation represent approximately 6% of the CF patient population. Their mean sweat chloride level at baseline was 50.9 mmol/L. After eight weeks of treatment with Trikafta, the patients’ mean sweat chloride level was 32.7 mmol/L,
representing an improvement of approximately 20 mmol/L, and their mean lung function level, as measured by FEV, improved by 5.8 percentage points.

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Our Approach and Leveraging the CFHBE Model

Our programs leverage an industry standard, clinically predictive CFHBE model to measure CFTR protein function in vitro. Activity in this model
has been shown to be correlated to chloride transport activity, which in turn, has been shown to be correlated to improved lung function in clinical trials designed to evaluate product candidates in CF patients. We have used, and plan to continue to
use, insights from the CFHBE model to inform critical pipeline prioritization and development decisions. For example, we selected SION-719 and SION-451 to advance based
on their preclinical profiles, including potency in the CFHBE model. We assessed SION-719 and SION-451 in our CFHBE model in direct, head-to-head comparison to ETI, the components of Trikafta. When evaluated in our CFHBE model at E concentrations, both SION-719 and SION-451, in dual combination with one of our complementary modulators, improved in vitro CFTR protein activity to wild-type, or normal, levels. This was
a more than 1.5-fold improvement in CFTR protein activity compared to the improvement in such activity observed with ETI at E in the same experiment. We believe that we can leverage the
reproducible correlation