Vigil Neuroscience (VIGL) Stifel 2024 Healthcare Conference summary

Program overviews and clinical progress

• Lead program is iluzanebart (IBART), a monoclonal antibody TREM2 agonist in phase II for ALSP, with a readout expected in the first half of 2025.

• Small molecule TREM2 agonist (VG-3927) showed supportive interim data; further data expected in Q1 2025.

• ALSP trial is the first interventional study in this disease, focusing on safety, tolerability, and biomarker endpoints.

• Natural history study (ILLUMINATE) informs trial design and serves as a synthetic control arm.

• Most patients in the current trial have progressive disease, with final data expected to reflect this population.

Regulatory strategy and FDA engagement

• Ongoing, productive discussions with the FDA, including a recent type C meeting, led to a decision to forego a second interim analysis.

• Endpoints and analysis plans are being pre-specified in collaboration with the FDA.

• Optimistic that current phase II data could support a filing, using MRI biomarkers (ventricular volume) and natural history as comparators.

• Next regulatory update expected with new data in the first half of 2025.

• Future phase III or confirmatory trial plans will be shaped by ongoing FDA dialogue.

Key data insights and biomarker strategy

• Statistically significant correlation found between cognitive scores (MoCA) and MRI changes at 12 months in natural history study.

• Biomarker and clinical endpoint correlations are central to regulatory discussions.

• Ventricular volume is considered a strong, measurable surrogate endpoint for accelerated approval.

• Soluble TREM2 (sTREM2) is used as a functional biomarker for target engagement in both antibody and small molecule programs.