Figure 5.

BIIB091 potently inhibits myeloid cell effector functions with IC₅₀s in the same range as in B cells. (a, b) Histogram overlays showing levels of reactive oxygen species (ROS) indicator dihydrorhodamine 123 in purified human neutrophils stimulated with immune complexes (IC) (anti‐ribonucleoprotein (RNP) antibodies complexed with purified RNP) and treated with DMSO or titrating concentrations of BIIB091 (a). IC₅₀ values for four healthy donors (individual data points) are shown along with mean and SD (4.5 ± 4.9 nm) (b). (c, d) Histogram overlays showing CD63 expression levels as a measure of degranulation in CD123⁺ HLA‐DR⁻ basophils from human whole blood treated with DMSO or titrating concentrations of BIIB091 and stimulated with recombinant human IL‐3 and anti‐human IgE antibodies (c). IC₅₀ values for four healthy donors (individual data points) are shown along with mean and SD (106 ± 62 nm). (e, f) TNFα protein levels measured in supernatant from human primary monocyte cultures treated with DMSO or titrating concentrations of BIIB091 and stimulated with plate‐bound human IgG (circle), anti‐human CD16 (square) or anti‐human CD64 (inverted triangle) antibodies (e). For each stimulating agent, IC₅₀ values for three healthy donors are shown along with mean and SD (5.6 ± 1.5 nm, 8.0 ± 9.0 nm and 3.1 ± 1.4 nm, respectively) (f). (g) Dot plot showing IC₅₀ values (mean and SD) for CD69 expression in anti‐IgD‐stimulated B cells (CD69, x‐axis) and basophil degranulation (CD63, y‐axis) in whole blood assays. Data from n = 11 BTK inhibitors including Biogen BIIB091 and BIIB068 (early generation BTK inhibitor ¹¹ ), 2 reversible competitor inhibitors (R) and 7 covalent competitor inhibitors (C). The dashed line indicates the equipotency line.