Asthma is characterized by increased recruitment of inflammatory cells from the circulation into the airways. As selectins mediate tethering and rolling of leukocytes on the vascular endothelium, they constitute a promising target for the therapeutic modulation of inflammation. We evaluated the effect of inhaled bimosiamose (TBC1269), a synthetic pan-selectin antagonist, on allergen-induced late asthmatic reactions (LAR) in mild asthmatics.Twelve male subjects with mild allergic asthma (only beta-agonists prn) with demonstrable LAR (fall of FEV 1 3–8h after allergen inhalation >15% of baseline) at screening completed a randomized, double-blind, placebo-controlled clinical cross-over-trial. Subjects were treated with inhaled bimosiamose 70mg bid or matching placebo on days 1–3 and 70mg once on the morning of day 4. On day 4 following the last inhalation of study drug, an allergen challenge was performed. The primary endpoint was the maximum fall in FEV 1 between 3 and 8h after allergen inhalation on active treatment vs. placebo. Secondary endpoints included early asthmatic response, exhaled nitric oxide, and airway hyperresponsiveness to methacholine 24h post allergen.Bimosiamose significantly attenuated the maximum LAR compared to placebo by 50.2% (placebo mean±SEM fall −13.10±2.30%, bimosiamose −6.52±3.86%, treatment effect p=0.045; linear mixed-effects model). There was no effect of active treatment on early asthmatic response, post allergen airway hyperresponsiveness or exhaled nitric oxide, and peripheral blood cells.Administration of the pan-selectin antagonist bimosiamose is effective in a human allergen challenge model of asthma. The result of this proof-of-concept exploratory trial is the first study that demonstrates clinical efficacy of selectin-antagonists as novel therapeutic strategy in asthma.