Reduction in sputum inflammatory cells after a single dose of cepeprubart in COPD patients

Neutrophils play a prominent role in the pathogenesis of chronic obstructive pulmonary disease (COPD) by secreting inflammatory mediators and proteases [1, 2]. A subset of COPD patients also has type 2 inflammation which can be identified by increased eosinophil counts in the blood or lung [3]. Neutrophils and eosinophils are recruited from the blood into the lungs through initial tethering and rolling of these cells on the endothelium, followed by firm adhesion and extravasation [4]. Initial tethering is mediated by p-selectin glycoprotein ligand-1 (PSGL-1; expressed by neutrophils and eosinophils) binding to p-selectin (upregulated by endothelial cells during inflammation) [5]. PSGL-1 expression is up-regulated on blood leukocytes from COPD patients [6]. Diapedesis of eosinophils into the lung is further enhanced by PSGL-1 dependent interaction with platelets leading to an increase in adhesion markers such as the α4ß1 integrin [7, 8]. Inhibition of the PSGL-1/selectin interactions is a potential anti-inflammatory strategy in COPD. Cepeprubart is a humanised monoclonal antibody that binds PSGL-1 with high affinity and specificity, and blocks PSGL-1 ligand interactions. We have conducted a phase 2a study to test the hypothesis that cepeprubart would inhibit the recruitment of neutrophils and eosinophils into the lungs of COPD patients.