Company: SION
Filing Date: 2025-01-17
Form Type: S-1
Source: 0001193125-25-008474
Chunk: 155

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-01-17
Form: S-1
Chunk 155
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 increased chloride transport in the CFHBE model is strongly correlated with improved CFTR function in CF patients. In head-to-head preclinical studies
using the CFHBE model, we evaluated several of our proprietary dual combinations (combining each of SION-719 and SION-451 with each of SION-2222 and SION-109) in direct comparison to elexacaftor/tezacaftor/ivacaftor (“ETI”) (which we
synthesized using methods described in publicly available sources), with all compounds at their respective highest effective dose (“E”). In other head-to-head preclinical studies
using the CFHBE model, we evaluated “add-on” combinations (SION-719 and ETI, and 451 and ETI), in direct comparison to ETI alone, with all compounds at E. In all of these studies,
whether evaluating a proprietary dual combination or an “add-on” combination of an

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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. 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 healthy volunteer trials in Australia to evaluate their pharmacokinetic (“PK”) profile, safety and tolerability. We have completed SAD dosing and 3 MAD cohorts in each trial. 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.                                                                                                                                                                                                                      |