Company: SION
Filing Date: 2025-02-07
Form Type: 424B4
Source: 0001193125-25-022709
Chunk: 159

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-07
Form: 424B4
Chunk 159
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. Prospective investors should not rely on the past investment decisions of our investors, as our investors may have different risk tolerances and have received their shares in prior offerings at prices lower than the price offered to the public in this offering. Please see the section titled “ Certain Relationships and Related Person Transactions” included elsewhere in this prospectus for a description of the financings we have conducted to date. Overview of Cystic Fibrosis, CFTR Function and the F508del Mutation An estimated 106,000 people have been diagnosed with CF across 94 countries, including approximately 33,000 adults and children living with CF in the U.S., according to the CFF. While life expectancy for CF patients has improved significantly over the years since the first CFTR modulator was approved, the median predicted survival age for individuals with CF born in the U.S. between 2019 and 2023 is still just 61 years, according to the 2023 CFF patient registry. The majority of people who have been diagnosed with CF live in the U.S., the United Kingdom and Europe. CF is the most common fatal inherited disease in the U.S., and it can affect people of every racial and ethnic group. CF is caused by mutations to the CFTR gene that result in reduced or no function of the CFTR protein. The disease is autosomal recessive, meaning that two copies of a CFTR mutation are required to cause the disease, either two copies of the same mutation (“homozygous”) or two different mutations (“heterozygous”). Approximately 90% of people with CF carry at least one copy of the F508del mutation, and approximately 44% of people with CF are homozygous for F508del. The F508del mutation (a deletion of the amino acid phenylalanine at position 508, in NBD1) is considered a severe CF mutation, and individuals with this mutation tend to fall at the worst end of the CF severity spectrum because they have little or no CFTR function in epithelial cells. 117

In people with CF, mutations in the CFTR gene cause the CFTR protein to become dysfunctional. The CFTR
protein is found on the apical membrane, or surface, of epithelial cells throughout the body, including in the lungs, pancreas, sweat glands, biliary tract and intestines. The CFTR protein is critical for proper salt and water balance in the cell,
which drives production of freely flowing mucus for tissue