Vigil Presents Key Findings from ILLUMINATE & IGNITE Studies in ALSP at the 2024 American Academy of Neurology Annual Meeting - Seite 2

Poster presented by David S. Lynch, M.D., Ph.D., National Hospital for Neurology & Neurosurgery; University College London Institute of Neurology: Findings from the ILLUMINATE Prospective Natural History Study (NHS) in Individuals with Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP)

“The findings from ILLUMINATE highlight sensitive markers of ALSP pathophysiology that have the potential to provide valuable insight into clinical endpoints and improve the overall understanding of ALSP disease progression to inform future study designs,” said David Lynch, Ph.D., Honorary Research Fellow, Department of Neuromuscular Diseases, University College London.

Data on clinical measures, biomarkers, and MRI from ILLUMINATE were presented at the conference. Key findings included:

• Baseline sCSF1R was substantially reduced in prodromal and symptomatic participants vs healthy volunteers, indicating reduced microglial activity
• At baseline, CSF and serum levels of neurofilament light chain (NfL), a marker of neuroaxonal injury, were elevated multifold in symptomatic participants vs prodromal and healthy volunteers
• Longitudinally, greater ventricle volume enlargement and gray matter volume reduction were observed in symptomatic vs prodromal participants
• Symptomatic participants demonstrated greater cognitive impairment at baseline and progression over time, as measured by the Montreal Cognitive Assessment scale (MoCA), vs prodromal participants
• Changes in ventricle volume over time demonstrated a statistically significant correlation with cognitive decline
  

Poster presented by Abbie Renoux, Ph.D., Vigil Neuroscience: VGL101: An Immunotherapy that Enhances Microglial Survival for Adult Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP)

The preclinical study demonstrated iluzanebart as a highly potent human TREM2 (hTREM2) agonist monoclonal antibody, and preclinically validated its pharmacological potential to therapeutically circumvent CSF1R dysfunction in human microglia, the pathophysiological process underlying ALSP. Key supportive findings highlighting the mechanism of action of iluzanebart included:

• Demonstration that iluzanebart promotes human microglia resilience across multiple CSF1R loss-of-function states, including rescue in an ALSP-associated human genetic model system
• Mechanistic evidence that iluzanebart potently engages its target TREM2 and thereby indirectly modulates CSF1R biology, including the disease-associated biomarker sCSF1R
• Unbiased in vivo validation that TREM2-dependent activation of microglia is well-aligned with iluzanebart drug levels in mouse brains supporting its ability to achieve pharmacologically active CNS concentrations