First-in-human intrapulmonary intratarget microdosing of a novel dual inflammasome inhibitor of NLRP 1/ NLRP 3 in ex vivo human lungs and patients with interstitial lung disease
medRxiv Preprint Server May 5, 2026 Tom Quinn, Feng Li, Becky Wheeler et al. preprint
A first-in-human Phase 0 intratarget microdosing study shows that delivering a tiny dose of a new inflammasome inhibitor directly into the lungs of patients with interstitial lung disease is feasible. A 100 microgram microdose of ADS032, a dual NLRP1/NLRP3 inhibitor, was administered to distal airways via bronchoscopy. The drug was detected in plasma, bronchoalveolar lavage fluid, distal airway micro-aspirates, and recovered cells without cross-contamination. Fluorescent labeling allowed direct visualization of alveolar drug uptake in ex vivo human lung tissue. This intrapulmonary microdosing approach offers a human-relevant platform for early pharmacological evaluation of lung therapeutics before Phase 1 trials.