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

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-03-20
Form: 10-K
Item: Item 1
Chunk 25
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 Elexacaftor + 45 μM Tezacaftor + 0.3 μM Ivacaftor. SION-109 and 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 Emax in each of the three combinations, is in the range of wild-type channel activity.

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

(ETI = 3 μM Elexacaftor + 45 μM Tezacaftor + 0.3 μM Ivacaftor. SION-109 and 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 chloride and lung function, as measured by FEV1, in CF patients.

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Preclinical Safety/Pharmacology and Toxicology to Support Clinical Trials

For both SION-719 and SION-451, we conducted standard in vitro and in vivo toxicology and safety pharmacology studies necessary to support first in human studies. The preclinical study results supported early clinical testing above exposure levels that we have predicted can be effective.

Additional NBD1 Stabilizer Candidates

Our portfolio includes additional NBD1 stabilizer candidates with differentiated profiles from SION-719 and SION-451.

We have nominated two additional NBD1 stabilizers as development candidates.

Complementary Programs

We have established a pipeline of proprietary complementary modulators, representing three different mechanisms of action, TMD1-directed correctors, an ICL4-directed corrector, and a potentiator