SION-719 + Trikafta

SION-719 + Trikafta is an investigational combination regimen consisting of Sionna Therapeutics' SION-719, a first-in-class oral small molecule nucleotide-binding domain 1 (NBD1) stabilizer, and Vertex Pharmaceuticals' approved triple-combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator Trikafta (elexacaftor/tezacaftor/ivacaftor). SION-719 specifically targets the NBD1 region of the CFTR protein to address the conformational instability caused by the F508del mutation, a mechanism distinct from and complementary to the components of Trikafta. The combination was evaluated in the Phase 2a PreciSION CF trial (NCT07108153) in adults with cystic fibrosis homozygous for the F508del mutation. In August 2026, Sionna announced that the trial missed its key sweat chloride endpoint, and the company decided not to advance SION-719 as an add-on to standard of care.