Fig. 3

Pharmacodynamic effects of repeat-dose AL002 in cynomolgus monkeys. (A) CSF sTREM2 from the non-GLP DRF study (n = 4 per dose group). From the 4-week GLP study (n = 6 per dose group), (B) total TREM2 levels in the frontal cortex and (C) hippocampus. (D) Volcano plot of SomaScan data for CSF protein for 250 mg/kg group vs. vehicle 48 h after the Day 1 dose. (E) SPP1 mRNA expression in frontal cortex, normalized to control values, from the 4-week GLP study. (F) CSF SPP1 protein levels at predose baseline and Day 1 (i.e., 48 h after dose). (G) Longitudinal CSF SPP1 protein levels from the non-GLP interval study (n = 5 for the vehicle and 250 mg/kg dose group; n = 4–5 for the 80 mg/kg dose group). From the 4-week GLP study, (H) CSF1R mRNA expression in frontal cortex, normalized to control values, (I) CSF1R protein levels in frontal cortex, and (J) IL1RN protein levels in CSF at predose baseline, 48 h after Day 1 dose, and 48 h after Day 29 dose. Black arrows indicate time of dosing. Data are means ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. a.u., arbitrary units; CSF, cerebrospinal fluid; CSF1R, soluble colony-stimulating factor 1 receptor; DRF, dose range finding; GLP, good laboratory practices; h, hours; LLOQ, lower limit of quantification; sCSF1R, soluble CSF1R; SEM, standard error of the mean; sTREM2, soluble TREM2; TREM2, triggering receptor expressed on myeloid cells-2