Vigil Neuroscience (VIGL) Jefferies London Healthcare Conference 2024 summary

Company overview and differentiation

• Focuses on microglia-targeted therapies for neurodegenerative diseases, using a precision-based approach to reduce translational risk.

• Only company with both a fully human monoclonal antibody and a first-in-class small molecule TREM2 agonist.

• Antibody is in phase II for ALSP, a rare microgliopathy; small molecule is in phase I, targeting Alzheimer's disease.

• Secured a $40 million strategic investment from Sanofi for rights of first negotiation on the small molecule program.

ALSP program and clinical progress

• ALSP prevalence estimated at 19,000 in the U.S. and 29,000 in Europe/UK, with significant underdiagnosis and misdiagnosis.

• Disease is fast progressing, with loss of ambulation in 2–3 years and death in 6–8 years post-symptom onset.

• Natural history study (ILLUMINATE) with over 50 patients informs biomarker selection and supports regulatory strategy.

• Phase II open-label study enrolled 20 patients; primary endpoint is safety, with focus on MRI and clinical biomarkers.

• FDA discussions ongoing regarding accelerated approval and use of MRI as a surrogate endpoint; final phase II data expected H1 next year.

Key clinical data and regulatory strategy

• Early phase II data (n=6) showed slowing of disease progression in MRI and biomarkers, using natural history as a control.

• Most patients in the study are mild to moderately affected, with elevated NfL and cognitive impairment.

• Positive phase II outcome would be continued slowing of progression in MRI and biomarkers at 12 months.

• Drug has shown strong safety profile with no serious adverse events or discontinuations.

• Ongoing dialogue with FDA; best case is sufficiency of current study for accelerated approval, otherwise a confirmatory or phase III study may be needed.