Company: SION
Filing Date: 2025-02-03
Form Type: S-1/A
Source: 0001193125-25-018825
Chunk: 179

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-03
Form: S-1/A
Chunk 179
---
 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 our NBD1
stabilizers work synergistically with complementary modulators, and with the standard of care, to significantly improve CFTR function in preclinical models. Given the correlation seen in our preclinical studies between CFTR function and clinical
activity, we believe that achieving target exposure levels for our product candidates in our ongoing and future clinical trials has the potential to translate to significant improvements in sweat