Company: SION
Filing Date: 2025-02-07
Form Type: 424B4
Source: 0001193125-25-022709
Chunk: 161

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-07
Form: 424B4
Chunk 161
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 have fallen short, leading to the view that NBD1 is “undruggable.” The current standard of care, Trikafta, as well as the
recently approved Alyftrek, are made up of three components that target certain domains of CFTR, but not NBD1. At least two-thirds of patients on Trikafta do not have normal CFTR function, defined as sweat
chloride levels below 30 mmol/L. Even treated CF patients can continue to experience the ongoing effects of reduced CFTR function over time, including respiratory infections, pulmonary exacerbations, or “lung attacks,” and continued lung
function decline. More than 6,000 patients have discontinued use of approved CFTR modulators, none of which target NBD1. Additionally, some patients on Trikafta reduce dosages due to tolerability issues, including elevated liver function tests and
mental health effects such as mood disturbances, depression, and mental fogginess. In December 2024, the Trikafta label was updated to include a boxed warning for the risks of drug-induced liver injury and liver failure, and the Alyftrek label
includes the same boxed warning. Seven to eight percent 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 FEV 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