Vigil Neuroscience (VIGL) H.C. Wainwright 26th Annual Global Investment Conference 2024 summary

Company vision and strategy

• Focuses on developing microglia-targeted therapeutics for rare and common neurodegenerative diseases, emphasizing a precision-based approach to neuroinflammation.

• Differentiates itself with two TREM2 modalities: a monoclonal antibody in Phase II for ALSP and a first-in-class small molecule TREM2 agonist in Phase I.

• Strategic partnership with Sanofi includes a $40 million investment and right of first negotiation on the small molecule program, extending financial runway into 2026.

• Building a microglia platform to interrogate new targets and indications, aiming to become experts in microglia biology.

• Upcoming milestones include full Phase I data for the small molecule and final Phase II data for ALSP in the first half of next year.

ALSP program insights

• ALSP is a rare, inherited neurodegenerative disease caused by CSF1R mutations, leading to microglia dysfunction.

• TREM2 agonism is hypothesized to compensate for CSF1R deficiency, supported by in vitro and genetic evidence.

• Recent data suggest ALSP prevalence is higher than previously thought, with estimates of 19,000 in the U.S. and 29,000 in Europe/UK.

• The ILLUMINATE natural history study identified MRI as the most sensitive and dynamic biomarker, correlating with cognitive decline.

• Natural history data and early Phase II results enabled productive FDA discussions, with MRI considered as a surrogate endpoint for accelerated approval.

Clinical development and biomarker strategy

• IGNITE Phase II interim data showed excellent safety, tolerability, and PK, with increased antibody penetration in active disease areas.

• Early results indicate slowing of disease progression and increased soluble CSF1R in progressive patients.

• MRI is prioritized as the primary surrogate endpoint for regulatory discussions, with additional focus on CSF1R and NfL biomarkers.