Company: SION
Filing Date: 2025-02-07
Form Type: 424B4
Source: 0001193125-25-022709
Chunk: 168

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-07
Form: 424B4
Chunk 168
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 as seen in Figure 11 above, which in turn has been shown to correlate to improved lung function in clinical trials, as shown in Figure 12 above. We have observed this correlation with our CFHBE data and clinical lung
function data for approved and investigational CFTR modulators that demonstrated activity in clinical trials, including galicaftor and navocaftor, as shown in Figure 13 below.

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Figure 13. CFHBE Model Correlates to Improved Lung Function

We believe our CFHBE model allows us to predict the target exposure needed for our product candidates to achieve a
desired level of clinical activity, such as the level of improvement in patients’ lung function, as measured by FEV improvement, and sweat chloride levels. We have tested our product
candidates in the CFHBE model at E and generated a prediction of sweat chloride and FEV changes, based on the documented correlation,
observed in clinical trials of approved and investigational modulators, between improvements in sweat chloride levels and improvements in lung function. We believe that the CFTR function improvement observed in our CFHBE model of our product
candidates has the potential to translate clinically to deliver clinically meaningful benefit to CF patients.

Our CF Programs

We have a portfolio of NBD1 stabilizers and complementary modulators that target other regions of the CFTR protein, with the goal of advancing a
combination therapy that has the potential to deliver clinically meaningful benefit to CF patients. We are pursuing an approach to select the most promising NBD1 stabilizer candidate and NBD1 dual combination to advance into Phase 2 clinical trials
in CF patients based on initial human data on safety, tolerability and PK in healthy volunteers.

NBD1 Stabilizer Program

NBD1 is recognized as a key target in treating CF patients with the F508del mutation, as the mutation drives NBD1 instability and defects in its
interface assembly. However, NBD1 has presented significant challenges as a drug target due to the attributes of the region’s binding sites. Our NBD1 program builds on more than a decade of our cofounders’ research, which has combined
biophysical, cell-based and virtual screening campaigns, along with extensive use of structural biology. We believe the technical challenge associated with NBD1-targeted drug discovery, along with our intellectual property rights, represent a
substantial competitive barrier.

We selected SION-719 and SION-451
for clinical evaluation based on their potency, PK profiles and safety as