Vigil Neuroscience, Inc. announced the complete data analysis from its VGL101 Phase 1 single and multiple ascending dose (SAD and MAD) healthy volunteer trial in a poster presentation at the 2023 American Neurological Association (ANA) Annual Meeting. In addition, the Company presented a poster highlighting the study design for its ongoing IGNITE Phase 2 clinical trial. The Phase 1 SAD and MAD trial was designed to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of VGL101 in healthy volunteers.

The trial enrolled 136 healthy volunteers who received either VGL101 (n=113) at fixed single doses ranging from 1 to 60 mg/kg or three ascending doses ranging from 20 to 60 mg/kg, or placebo (n=23). An interim safety analysis of VGL101 for the 1 mg/kg to 40 mg/kg SAD cohorts and data for the 20 mg/kg MAD cohort were previously disclosed in November 2022. Highlights from the VGL101 Phase 1 healthy volunteer trial presented at the ANA Annual Meeting include: VGL101 demonstrated a favorable safety and tolerability profile in SAD and MAD cohorts at doses up to 60 mg/kg.

VGL101 showed linear and predictable pharmacokinetic characteristics and an observed half-life that supports monthly dosing. The Phase 1 cerebrospinal fluid (CSF) biomarker data demonstrated pharmacologic activity across multiple measures: Demonstrated proof-of-target engagement based on dose-dependent, robust and durable reductions in soluble TREM2 (sTREM2) following repeat dosing. Increased soluble CSF1R (sCSF1R) and osteopontin levels were durable following repeat dosing indicating that VGL101 impacted microglial activity downstream of TREM2 target engagement.

Target engagement and downstream pharmacodynamic responses of VGL101 at 20 mg/kg and 40 mg/kg support evaluating these doses in the ongoing IGNITE Phase 2 trial in ALSP patients. In a separate poster at the ANA Annual Meeting, the Company presented the trial design for its ongoing Phase 2 IGNITE trial. IGNITE is a global, open-label clinical trial evaluating VGL101 in approximately 15 patients with symptomatic ALSP who have a confirmed CSF1R gene mutation.

As part of the protocol, patients will receive an intravenous (IV) infusion of VGL101 at 20 mg/kg or 40 mg/kg approximately every four weeks, for a treatment duration of one year. The primary objective of the IGNITE trial is to evaluate the safety and tolerability of VGL101. Secondary objectives include evaluating the impact of VGL101 on magnetic resonance imaging (MRI) and its pharmacodynamic effect on fluid biomarkers in patients with symptomatic ALSP.

Clinical efficacy outcome measures are also being collected as exploratory endpoints. In the fourth quarter of 2023, the Company expects to report interim 6-month data from the IGNITE trial in the first 6 patients who have received 20 mg/kg of VGL101. VGL101, Vigil?s lead product candidate, is a fully human monoclonal antibody targeting human triggering receptor expressed on myeloid cells 2 (TREM2), which is responsible for maintaining microglial cell function.

TREM2 deficiency is believed to be a driver of certain neurodegenerative diseases. VGL101 is in development for rare microgliopathies, such as ALSP, as well as other neurodegenerative diseases for which TREM2 and/or microglia deficiency is believed to be a key driver of disease pathway.