Company: SION
Filing Date: 2025-01-17
Form Type: S-1
Source: 0001193125-25-008474
Chunk: 177

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-01-17
Form: S-1
Chunk 177
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 to lead to clinically meaningful benefit for CF patients. However, the results observed from our preclinical studies may not necessarily be predictive of clinical outcomes, and actual outcomes may differ. We will need to complete additional clinical studies to determine the safety and efficacy of SION-719 and SION-451. Setting Initial Clinical Exposure Targets Based on CFHBE Model To set exposure targets in our Phase 1 clinical trials with SION-719and SION-451in healthy volunteers, we conducted multiple dose response studies of both compounds in our CFHBE model that assessed F508del-CFTR activity as a function of each compound’s predicted total plasma concentration at a given dose. We selected a target exposure and dosing for our Phase 1 trials based on an average of these preclinical dose response studies along with studies to define an adequate safety margin. Figure 23 below presents illustrative dose responses of SION-719,as a single agent and in combination with ETI, SION-109or 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 dotted horizontal line indicates ETI’s maximum improvement in F508del-CFTR activity, and the X-axisshows increasing drug concentrations on a logarithmic scale. A roughly two-foldincrease over ETI, as seen with SION-719 treatment at its E maxin each of the three combinations, is in the range of wild-type channel activity. 133

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