Abstract Details

VGL101 is a fully human monoclonal antibody targeting TREM2, in development for the treatment of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a rare, progressive, debilitating neurodegenerative disorder. TREM2, a receptor expressed on microglia in the brain is critical to microglial function in health and in disease. The activation of TREM2 by VGL101 is expected to enhance microglia function and neural tissue repair mechanisms regulated by microglia thereby slowing disease progression in ALSP.

To evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of VGL101 in healthy adult participants after both single- (SAD) and multiple-ascending dose (MAD) administration.

The Phase 1 study has enrolled 74 HVs in several cohorts at doses up to 40mg/kg SAD and 20mg/kg MAD or placebo. Safety was assessed by the incidence of adverse events (AEs), changes in vital signs, laboratory tests, ECGs, and clinical evaluations. VGL101 serum and CSF PK and the PD of CSF soluble TREM2 (a marker of microglia target engagement) were characterized across single and multiple doses.

VGL101 demonstrated a favorable safety and tolerability profile at studied doses. Adverse events were mild, did not require intervention and resolved spontaneously. To date, there are no reports of SAEs or clinically meaningful abnormalities in vital signs, laboratory parameters or ECGs. VGL101 demonstrated approximately dose proportional peripheral pharmacokinetics with half-life supporting monthly dosing and brain penetration typical of IgG1 monoclonal antibodies.  Dose and time dependent reduction in sTREM2 levels in the CSF was observed demonstrating CNS target engagement for VGL101.

VGL101 demonstrated a favorable safety, PK profile and confirmation of CNS target engagement in healthy volunteers. The Phase 1 data supports further clinical development of VGL101 in ALSP.