Fig. 1

Potency of iluzanebart across in vitro human model systems. Activation of TREM2 via protein phosphorylation was assessed using AlphaLISA assays. A HEK-hTREM2 Cells. In HEK293T cells expressing human TREM2 and DAP12, pDAP12 in response to iluzanebart for 45 min was analyzed, resulting in an EC50 potency of 1.09 nM (n = 2 independent experiments). Results are shown as normalized to IgG control, which did not stimulate SYK phosphorylation, and reported as % of maximal activation. B HEK-hTREM2 Cells. Similarly, in the same HEK293T cell line, iluzanebart had a potency of 0.19 nM (n = 3 independent experiments) when measuring phosphorylation of SYK. Results are shown as normalized to IgG control, which did not stimulate SYK phosphorylation, and reported as % of maximal activation. C Human Monocyte Derived Macrophages (hMDM). In human MDM cells, treatment with iluzanebart for 45 min stimulated phosphorylation of SYK with an average EC50 potency of 4.77 nM (n = 4 independent experiments). Results are shown as normalized to IgG control, which did not stimulate SYK phosphorylation, and reported as % of maximal activation. D iPSC Derived Human Microglia (iMGL). In human iPSC-derived microglia cells, iluzanebart treatment for 5 min stimulated phosphorylation of SYK with an average EC50 potency of 0.63 nM (n = 6 independent experiments), and is shown as normalized to IgG control, which did not stimulate SYK phosphorylation, and reported as % of maximal activation