Company: SION
Filing Date: 2025-02-03
Form Type: S-1/A
Source: 0001193125-25-018825
Chunk: 157

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-03
Form: S-1/A
Chunk 157
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ors, 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.                                                                                                                                                                                                                      |

| • |     | Galicaftor (SION-2222) and SION-2851 are TMD1-directed CFTR correctors. Galicaftor was generally well-tolerated in Phase 1                                                                                                                  
 and Phase 2 trials, and 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 clinical trial in healthy volunteers. SION-109 was generally well tolerated at all dose levels administered in all parts of this Phase 1 trial. The target exposure for SION-109 as part of a dual combination with SION-451 or 
 SION-719 was achieved with single and multiple doses.                                                                                                                                                                                             |

| • |     | Navocaftor (SION-3067), a potentiator, has been evaluated in Phase 2 trials, in which it demonstrated potential as a 
 combination therapy.                                                                                                 |

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Figure 3 below captures the targeted binding locations within the CFTR structure for our pipeline of
NBD1 stabilizers and complementary modulators.

Figure 3. Our Multi-Prong Approach to Potentially Improving CFTR Function

Our current portfolio of programs is summarized in Figure