NeuroMab™ Anti-CD182 BBB Shuttle Antibody(NRZP-1022-ZP3794)

Figure 1A illustrates the measurement in a Tango™ cell-based assay by selecting the anti-CXCR2 antibody BKO-4A8 and optimizing the antibodies BKO-4A8-101c, BKO-4A8-103c, BKO-4A8-104c, and BKO-4A8-105c.

Figure 1B illustrates the measurement in a Tango™ cell-based assay by selecting the anti-CXCR2 antibody BKO-4A8 and optimizing the antibodies BKO-4A8-101c, BKO-4A8-103c, BKO-4A8-104c, and BKO-4A8-105c.

Figure 2 illustrates the results of a dose response inhibition study of the published anti-CXCR2 antibody BKO-4A8-101c on ELR+CXC chemokine-mediated CXCR2 activation measured in a Tango™ cell-based assay.

Figure 3 illustrates the results of a dose response inhibition study of CXCL1-, CXCL5- and CXCL8-mediated CXCR2 activation by the published anti-CXCR2 antibody BKO-4A8-101c measured in a calcium flux assay.

Figure 4 illustrates the human CXCR2 binding activity of the disclosed anti-CXCR2 antibody BKO-4A8 formatted on different human IgG constant regions as determined by flow cytometry analysis.

Figure 5 illustrates the results of a dose response inhibition study of CXCL8-mediated activation of the published anti-CXCR2 antibody BKO-4A8 formatted on different human IgG constant regions as measured in a Tango™ cell-based assay.

Figure 6 illustrates the results of a binding study of anti-CXCR2 antibody BKO-4A8-101c to various human CXCR family members. The results showed that BKO-4A8-101c binds only to CXCR2, a member of the human CXCR family.

Figure 7 illustrates exemplary binding profiles of BKO-4A8-101c (shaded histogram) to phenotype-defined human peripheral blood hematopoietic cells assessed by flow cytometry (N=8), combined with an isotype control ( Human-IgG unshaded histogram). Neutrophils express high levels, while monocytes express intermediate levels of CXCR2.

Figure 8A illustrates the results of anti-CXCR2 activity of antibody BKO-4A8-101c in a model of acute lung inflammation in cynomolgus monkeys.

Lipopolysaccharide (LPS) aerosol inhalation (day 0) successfully induced acute neutrophil inflammation in the lungs of cynomolgus monkeys. Treatment with the anti-CXCR2 antibody BKO-4A8-101c (1 mg/kg) 1 hour before challenge with LPS on day 0 resulted in a significant reduction in neutrophil counts in bronchoalveolar lavage 24 hours after LPS challenge. Three repeated administrations of BKO-4A8-101c at twice-weekly intervals on days 0, 14, and 28 did not affect peripheral blood neutrophil counts.

Figure 8B illustrates the results of anti-CXCR2 activity of antibody BKO-4A8-101c in a model of acute lung inflammation in cynomolgus monkeys.

Lipopolysaccharide (LPS) aerosol inhalation (day 0) successfully induced acute neutrophil inflammation in the lungs of cynomolgus monkeys. Treatment with the anti-CXCR2 antibody BKO-4A8-101c (1 mg/kg) 1 hour before challenge with LPS on day 0 resulted in a significant reduction in neutrophil counts in bronchoalveolar lavage 24 hours after LPS challenge. Group medians and ranges are shown, N=4.