Company: SION
Filing Date: 2025-02-03
Form Type: S-1/A
Source: 0001193125-25-018825
Chunk: 169

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-03
Form: S-1/A
Chunk 169
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 and without 20% human serum—and benchmarked these against
published Phase 2 clinical results regarding sweat chloride levels for lumacaftor. Figure 10 shows that the predicted lumacaftor dose response, as depicted by the red line, closely matched lumacaftor’s clinical dose response, as depicted by the
black line. The CFHBE model without 20% human serum, depicted by the blue line, failed to accurately predict the clinical exposure of lumacaftor required for efficacy, even if adjusted for lumacaftor’s measured free fraction in human plasma,
depicted by the dotted green line.

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Figure 10. Our CFHBE Model is Designed to More Accurately Predict the Required Clinical Exposure than Standard CFHBE Model

Using published data from the clinical trials of Vertex’s approved CFTR modulators, we have validated internally
our CFHBE model by assessing the relationship between in vitro CFTR protein function, as measured by chloride transport in our CFHBE model, and the mean sweat chloride levels seen in Vertex’s clinical trials of these approved modulators.

As shown in Figure 11 below, improvements in CFTR function we observed in our CFHBE model for approved and investigational CFTR modulators have
been highly correlated with improvements in sweat chloride measurements from clinical trials for these therapies. Notably, we have used the CFHBE model to predict negative clinical trial outcomes, too. For example, we modeled other third-party
modulators previously in development and independently determined that these compounds had insufficient activity to demonstrate target clinical efficacy, which was supported by published clinical trial data.

Figure 11. CFHBE Model Has Been Predictive of Sweat Chloride Improvement

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Mean improvements in sweat chloride levels in clinical trials have been shown to be correlated with
mean improvements in lung function as measured by FEV, as shown in Figure 12 below.

Figure 12. Sweat Chloride Has Been Correlated With Lung Function Benefit

We consider our CFHBE model a translational roadmap because of its ability to correlate with sweat chloride
improvement in clinical trials, as seen in Figure 11 above, which in turn has been shown to correlate to improved lung function in clinical trials, as shown in Figure 12 above. We have observed this correlation with our CFHBE data and clinical lung
function data for approved and investigational CFTR modulators that demonstrated activity in clinical trials, including galicaftor and navocaftor, as shown in Figure