Company: SION
Filing Date: 2025-03-20
Form Type: 10-K
Source: 0002036042-25-000005
Chunk: 3

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-03-20
Form: 10-K
Item: Item 1
Chunk 3
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, we evaluated “add-on” combinations (SION-719 and ETI, and 451 and ETI), in direct comparison to ETI alone, with all compounds at Emax. In all of these studies, whether evaluating a proprietary dual combination or an “add-on” combination of an NBD1 stabilizer and ETI, we observed a marked improvement in CFTR protein activity of more than 1.5-fold relative to ETI alone. The CFHBE model has helped us identify active compounds and predict the potential clinical exposures needed to achieve a target level of clinical activity in humans. We intend to continue to leverage insights from the CFHBE model as we make critical pipeline prioritization and development decisions.

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Table of Contents

Our Pipeline

Our proprietary portfolio includes NBD1 stabilizers and complementary modulators. There are two types of complementary modulators: correctors, which partially improve CFTR protein folding to aid its trafficking to the cell surface, and potentiators, which increase CFTR channel function by enabling chloride flow through the cell membrane. We believe the synergistic approach of combining NBD1 stabilizers with complementary modulators provides the highest probability of normalizing CFTR function for CF patients. Our portfolio includes:

•SION-719 and SION-451, our highly potent NBD1 stabilizers, are both in Phase 1 trials in Australia to evaluate their pharmacokinetic (“PK”) profile, safety and tolerability in healthy subjects. We have completed dosing in the SAD parts of both trials and the MAD part of the SION-451 trial; the final MAD cohort of the SION-719 trial is planned. Both NBD1 stabilizers have been generally well tolerated in these ongoing trials based on interim data to date. Topline results from our SION-719 and SION-451 Phase 1 clinical trials are expected in the first half of 2025.

•Galicaftor (SION-2222) and SION-2851 are TMD1-directed CFTR correctors. Galicaftor was generally well-tolerated in Phase 1 and Phase 2 trials. Improvement in sweat chloride as a monotherapy and improvements in sweat chloride and lung function as a combination therapy with navocaftor were observed. SION-2851 has completed a Phase 1 single ascending dose (“SAD”) trial in healthy volunteers.

•SION-109, an ICL4-directed CFTR corrector, has been evaluated in a recently completed Phase 1