Vigil Neuroscience (VIGL) Stifel 2025 Virtual CNS Forum summary

Company overview and strategic focus

• Focused on neurodegeneration by harnessing the brain's immune system, particularly microglia, to develop new treatment options.

• Lead programs target TREM2, a key microglial receptor, with both antibody and small molecule approaches.

• Achieved significant progress in four years as a public company, with multiple clinical programs advancing.

TREM2 program updates and differentiation

• Lead asset iluzanebart (TREM2 antibody) is in Phase II for ALSP, with a readout expected in Q2.

• Small molecule TREM2 agonist for Alzheimer's completed robust Phase I and will enter Phase II in Q3.

• Small molecule offers advantages over antibodies: better brain penetration, avoids Fc-mediated ARIA risk, and direct membrane-bound TREM2 engagement.

• Small molecule shows positive allosteric modulation with natural TREM2 ligands, enhancing efficacy.

Industry context and learnings from competitor trials

• Recent failure of a competitor's TREM2 antibody in Alzheimer's attributed to insufficient target engagement and lack of amyloid clearance.

• ARIA safety signals can occur without plaque clearance, suggesting antibody concentration and Fc engagement as key factors.

• Small molecule approach may clear plaques without ARIA, offering a safety advantage.