Intravenously administered AL 002 was safe and generally well tolerated in cynomolgus monkey toxicology studies, up to 250 mg/kg weekly dose for 4 weeks. No adverse findings were observed. The no observed adverse effect level (NOAEL) was 250 mg/kg  .
In preclinical study, administration of AL 002 activated microglia and increased clustering of microglia around amyloid plaques in 5xFAD mice models. Also a reduced amyloid deposition and improved cognition was reported with AL 002 in mice model  .
After multiple weekly dosing in cynomolgus monkeys, systemic exposure of intravenously administered AL 002 increased slightly less than dose proportionally with increasing doses. Some accumulation of AL 002 was observed. The ratio of serum and CSF levels of AL 002 appeared consistent across the three doses tested. A dose dependent effect on pharmacodynamic biomarkers in both serum and CSF was observed  .
In preclinical study the peripheral injection of antibodies triggered TREM2 signaling microglial proliferation and activation in mouse brains. These data suggested that the antibodies efficiently cross the blood-brain barrier and that TREM2 signal induction was sufficient to shift the microglia phenotype. In 5xFAD mice, chronic treatment with a TREM2 agonist caused increased expression of synaptic and myelin genes  .