Company: SION
Filing Date: 2025-02-07
Form Type: 424B4
Source: 0001193125-25-022709
Chunk: 177

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-07
Form: 424B4
Chunk 177
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 responses of SION-719, as a single agent and in combination with ETI, SION-109 or galicaftor (SION-2222), as a function of the fold efficacy (CFTR activity) of ETI at increasing dose concentrations, in CFHBE cells from single donors. The black dotted horizontal line indicates ETI’s improvement in F508del-CFTR activity at E max, the teal horizontal line indicates our minimum target for clinically meaningful improvement in F508del-CFTR activity based on our CFHBE assay, and the green horizontal line represents the lower bound of the CFTR activity range observed across a panel of eight CFTR wild-type CFHBE donors. The X-axis shows increasing drug concentrations on a logarithmic scale. A roughly two-fold increase over ETI, as seen with SION-719 treatment at its E maxin each of the three combinations, is in the range of wild-typechannel activity. 134

Figure 23. RepresentativeΔF508/ΔF508 CFHBE Dose-Response of SION-719as Single Agent and in Combination with ETI, SION-109or SION-2222

(ETI = 3 µM Elexacaftor + 45 µM Tezacaftor + 0.3 µM Ivacaftor. SION-109and SION-2222 were used at 3 µM.)

Figure 24 below presents illustrative dose responses
of SION-451, as a single agent and in combination with ETI, SION-109 or galicaftor (SION-2222), as a function of the fold efficacy (CFTR activity) of ETI at increasing
dose concentrations, in CFHBE cells from single donors. A roughly two-fold increase over ETI, as seen with SION-451 treatment at its E in each of the three combinations, is in the range of wild-type channel activity.

Figure 24. RepresentativeΔF508/ΔF508 CFHBE Dose-Response of SION-451as Single Agent and in Combination with ETI, SION-109or SION-2222

(ETI = 3 µM Elexacaftor + 45 µM Tezacaftor + 0.3 µM Ivacaftor. SION-109and SION-2222 were used at 3 µM.)

These dose response curves illustrate that