Company: SION
Filing Date: 2025-02-03
Form Type: S-1/A
Source: 0001193125-25-018825
Chunk: 177

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-03
Form: S-1/A
Chunk 177
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 of CFTR modulators. The high molecular weight bands, labeled
C-band, indicate the presence of the active, mature apical glycoform of CFTR (dark bands), which is responsible for CFTR channel function. The compounds were evaluated at their E.

In Figure 20, the far-left column in the C-band is F508del in dimethylsulfoxide (“DMSO”) alone, showing no mature protein, and the far-right column is wild-type CFTR in DMSO with a dark bank
indicating the presence of mature CFTR protein. As seen in Figure 20 (top), dual combinations of SION-719 with galicaftor or SION-109, or the addition of SION-719 to ETI, resulted in wild-type levels of corrected F508del-CFTR protein. Treatment with SION-719 as a single agent demonstrated a greater effect on F508del maturation
than ETI at E. On the other hand, there was little improvement in the maturation of F508del-CFTR protein with galicaftor alone, SION-109 alone or ETI
at their respective E concentrations, as indicated by 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