Company: SION
Filing Date: 2025-03-20
Form Type: 10-K
Source: 0002036042-25-000005
Chunk: 9

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-03-20
Form: 10-K
Item: Item 1
Chunk 9
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 of patients on Trikafta have experienced significant mental health effects, and depression, including suicidal ideation and attempt, is listed in the warnings and precautions section of the summary of product characteristics for Kaftrio, the brand name for Trikafta in Europe. Patients who discontinue use of Trikafta or experience tolerability challenges have limited or no alternative treatments available to improve their clinical outcomes or quality of life. Currently, the alternatives for these patients are limited to less efficacious combination products that include one or more components of Trikafta, or Alyftrek, which demonstrated non-inferiority to Trikafta in the primary endpoint of two Phase 3 clinical trials, providing patients with similar FEV1 as Trikafta and sweat chloride level improvements of 3 to 8 mmol/L. Approximately 69% of Alyftrek patients in two Phase 3 clinical trials did not achieve normal CFTR function, defined as sweat chloride levels below 30 mmol/L. Our research with key opinion leaders has indicated the desire for more treatment options for CF patients, support for a new mechanism of action that could provide clinically meaningful benefit for people living with CF, and need for an alternative for those patients who experience tolerability issues on Trikafta. We aim to expand the current treatment paradigm through a proprietary dual combination or as an add-on to the standard of care.

Worldwide revenue for approved CFTR modulators was approximately $11 billion in 2024, and it is expected to grow to $15 billion by 2029. Vertex, which markets all five of the currently approved CFTR modulators, reported revenues in 2024 from global sales of its then-approved CFTR modulators of approximately $11.0 billion, more than $10.2 billion of which the company attributed to Trikafta. Vertex's approved CFTR modulators target approximately 92,000 CF patients in North America, Europe and Australia, and more than 20% of eligible patients are currently not on CFTR modulators. CF screening of newborn infants has served to identify CF patients as early as possible in their lives. For example, newborn screening for CF has been required in the U.S. since 2010, and in 2021, 64.4% of newly diagnosed people with CF in the U.S. were identified by newborn screening, based on CFF registry data. The availability of CFTR modulators has also increased the use of genetic testing to determine eligibility for