Sionna Therapeutics, Inc.

Sionna Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing new medicines for cystic fibrosis (CF). The company aims to normalize the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein to provide significant clinical benefits to individuals with CF. CF is a genetic disease caused by inherited mutations in the CFTR gene, resulting in insufficient CFTR function. While existing CFTR modulators have improved patient lives, at least two-thirds of patients on current standard care do not achieve normal CFTR function, defined as sweat chloride levels below 30 mmol/L. Sionna Therapeutics, Inc. seeks to restore CFTR function as close to normal as possible by directly stabilizing CFTR's nucleotide binding domain 1 (NBD1). NBD1 is a critical component for proper CFTR function, but no currently approved CF therapies directly stabilize it. The company is developing a pipeline of small molecules designed to correct defects caused by the F508del genetic mutation, the most common CFTR mutation, which occurs in the NBD1 domain. Approximately 90% of people with CF carry at least one copy of the F508del genetic mutation. The NBD1 domain is crucial for the folding, assembly, stability, and trafficking of CFTR to the cell surface, where it functions as an ion channel regulating chloride and water transport. The F508del mutation within NBD1 severely destabilizes CFTR, disrupting its assembly, impairing its half-life, and decreasing chloride channel function.