Company: SION
Filing Date: 2025-03-20
Form Type: 10-K
Source: 0002036042-25-000005
Chunk: 23

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-03-20
Form: 10-K
Item: Item 1
Chunk 23
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. Treatment with SION-719 as a single agent demonstrated a greater effect on F508del maturation than ETI at 

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Emax. 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 Emax concentrations, as indicated by the light gray bands. The results with SION-451 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-719 and SION-451 Corrector Combinations

SION-719 and SION-451 Normalized CFTR Function in CFHBE Model at Emax

In our CFHBE model, SION-719 and SION-451 as single agents at Emax improved F508del-CFTR activity to levels observed near those with triple combination ETI at Emax. The results of the SION-719 and SION-451 studies are shown in Figure 21. In Figure 21, CFTR activity is expressed as a ratio relative to ETI at Emax. 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.

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Figure 21. SION-719 and SION-451 Were Highly Active in the CFHBE Model at Emax

In our CFHBE model, both SION-719 and SION-451, in dual combinations with galicaftor or SION-109, improved in vitro F508del-CFTR activity to wild-type levels, when administered at Emax. This was a more than 1.5-fold improvement in CFTR protein activity compared to the improvement in such activity observed with ETI at Emax in 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