SION-451 + SION-109

**SION-451 + SION-109** is a proprietary combination of two investigational small molecule CFTR modulators being developed by Sionna Therapeutics for the treatment of cystic fibrosis. SION-451 is a nucleotide binding domain 1 (NBD1) stabilizer targeting the NBD1 region of the CFTR protein, while SION-109 is a corrector targeting the intracellular loop 4 (ICL4) region. Together, they aim to simultaneously stabilize distinct domains of the CFTR protein to enhance folding, stability, trafficking, and function of mutant CFTR (notably the F508del mutation) at the cell surface, potentially restoring near-normal chloride channel function. The combination is currently in Phase 1 clinical evaluation in healthy volunteers to assess safety, tolerability, and pharmacokinetics, with data expected mid-2026[1][4][6].