Lonodelestat (POL6014) is a potent, orally active, and selective peptide inhibitor of human neutrophil elastase (hNE).

Lonodelestat (POL6014), when intranasally administered to HNE-treated mice, significantly attenuated the inflammatory responses associated with Acute Lung Injury (ALI)[1]. Administered at varying doses (0.1, 0.5, 2, and 10 mg/kg), Lonodelestat demonstrated a dose-dependent decrease in inflammatory markers, prominently reducing the presence of macrophages, epithelial cells, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL). The optimal effect was observed at a dose of 2 mg/kg, achieving a significant reduction in neutrophils (65%, p<0.001), epithelial cells (68%, p<0.001), macrophages (33%, p<0.001), and lymphocytes (77%, p<0.001). The study utilized ten-week-old male C57BL/6j mice, with dosages ranging from 0.05 to 5 mg/kg. Administration took place intranasally 15 minutes prior to HNE exposure (30 UI), effectively mitigating ALI's inflammatory processes[1].