Nintedanib is a small molecule inhibitor of multiple tyrosine kinases, interrupting the cellular processes that lead to lung fibrosis, thus slowing the progression of pulmonary fibrosis. Unfortunately, oral nintedanib treatment is associated with adverse events attributable to its systemic delivery. These include diarrhea, hyperbilirubinemia (increased serum bilirubin, which can lead to jaundice), and drug-induced liver injury.
Avalyn has reformulated nintedanib for inhaled aerosol lung delivery. In animal models, an oral-superior, dose-dependent reduction in fibrosis was accomplished using a high dose equivalent to ~1/75th the human oral dose.
Phase 1a study dosing complete (N=38): 38 healthy volunteers and participants with IPF and PPF were administered a single dose of at either 0.5 mg, 1 mg or 2 mg AP02 or placebo and monitored for safety, tolerability and pharmacokinetics. Final results pending.