Vigil Neuroscience (VIGL) 2024 Cantor Fitzgerald Global Healthcare Conference summary

Company overview and strategy

• Focuses on microglia-targeted therapeutics for rare and common neurodegenerative diseases, founded in 2020 with assets from Amgen and a partnership with Atlas.

• Utilizes a precision-based approach, targeting diseases with strong genetic and mechanistic links to microglia dysfunction to reduce translational risk.

• Pipeline includes a fully human monoclonal antibody (iluzanebart) and a first-in-class small molecule TREM2 agonist.

• Secured a $40 million investment from Sanofi, extending financial runway into 2026 and granting Sanofi right of first negotiation on the small molecule program.

• Key milestones expected in 2025 include phase I data for the small molecule and final phase II data for ALSP.

ALSP program and clinical development

• ALSP is a fatal, rapidly progressing, monogenic neurodegenerative disease caused by CSF1R mutations affecting microglia.

• TREM2 agonism is pursued to compensate for CSF1R dysfunction, with preclinical and early clinical data supporting this approach.

• The ILLUMINATE natural history study mapped disease progression, validated MRI as a dynamic biomarker, and identified key biomarker changes (ventricular volume, NfL, soluble CSF1R).

• IGNITE phase II is an open-label study with 20 patients, assessing two doses over 12 months, showing early signs of slowed progression and biomarker improvement.

• MRI is prioritized as the primary biomarker for regulatory discussions, with NfL and soluble CSF1R as supportive endpoints.

Small molecule TREM2 agonist and Alzheimer's program

• TREM2 activation is supported by genetic and biomarker data linking increased TREM2 to neuroprotection in Alzheimer's.

• The small molecule is designed as a once-daily oral therapy with confirmed brain penetration and robust target engagement, as shown by reductions in soluble TREM2 in phase I.

• A partial clinical hold was lifted after alignment with the FDA on exposure, with no impact on development pace.

• Ongoing phase I includes a MAD portion and an AD cohort to assess biomarker shifts across TREM2 and APOE variants, informing phase II design.

• Plans for phase II in Alzheimer's are contingent on continued biomarker progress, with co-development partnerships sought for future advancement.