Company: SION
Filing Date: 2025-01-17
Form Type: S-1
Source: 0001193125-25-008474
Chunk: 176

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-01-17
Form: S-1
Chunk 176
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 the light gray bands. The results with SION-451

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presented in Figure 20 (bottom) are similar. The western blots below demonstrate the importance of NBD1 stabilization to the correction of F508del maturation. Figure 20. F508del-CFTR Maturation in CFSMEo- Cells Was Fully Restored with Our SION-719and SION-451Corrector Combinations SION-719and SION-451Normalized CFTR Function in CFHBE Model at E max In our CFHBE model, SION-719and SION-451as single agents at E maximproved F508del-CFTR activity to levels observed near those with triple combination ETI at E max. The results of the SION-719and SION-451 studies are shown in Figure 21. In Figure 21, CFTR activity is expressed as a ratio relative to ETI at E max. The vertical bars represent the mean CFTR channel activity (+/- standard error of eight replicates) from a representative study in homozygous F508del CFHBE cells in response to the treatments indicated. The dashed line represents the average response to ETI in each study. Figure 21. SION-719and SION-451 Were Highly Active in the CFHBE Model at E max

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In our CFHBE model, both SION-719 and SION-451, in dual combinations with galicaftor or SION-109, improved in vitroF508del-CFTR activity to wild-type levels, when administered at E max. 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 maxin the same experiment. As noted above, improvements in CFTR function we observed in our CFHBE model have been highly correlated with mean improvements in sweat chloride levels and mean improvements in lung function. Figure 22. SION-719 and SION-451 Combinations with Galicaftor or SION-109 Were Highly Active in the CFHBE Model at E max

Based on our findings in these preclinical studies and the strong correlation between chloride conductance and improved clinical activity, we believe that both SION-719and SION-451,in combination with a complementary CFTR modulator, have the potential to achieve significant improvement in CFTR function, as measured by sweat chloride levels and lung function, and thereby have the potential