Abstract Details

Title Interim Results on VGL101 from IGNITE: First Interventional Phase 2 Study in Patients with Adult-onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP)

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S28 - Vascular and Other Non-Alzheimer’s Dementias (1:48 PM-2:00 PM)

Poster/Presentation
Number 005

Background ALSP is a rare, fatal, inherited, autosomal-dominant, rapidly progressing neurodegenerative disorder caused by a loss-of-function mutation in the colony-stimulating factor-1 receptor gene (CSF1R), resulting in microglial dysfunction. ALSP is characterized by progressive cognitive, psychological, and motor dysfunction. Average survival is 6-8 years from diagnosis. VGL101 is a fully human IgG1 monoclonal antibody TREM2 receptor agonist. Preclinical evidence indicates VGL101-induced TREM2 activation enhances the neuroprotective function of microglia, supporting a disease-modifying therapeutic potential in ALSP. VGL101 was well tolerated and demonstrated durable target engagement and pharmacological activity following multiple dosing in a phase 1 healthy volunteer study at all administered doses.

Objective To report interim results of a TREM2 (triggering receptor expressed on myeloid cells 2) agonist from the first interventional study in ALSP.

Design/Methods IGNITE is a phase 2, proof-of-concept, multicenter, open-label study evaluating safety, tolerability, and clinical effects of VGL101 on MRI and disease progression biomarkers in ALSP (NCT05677659). Eligible patients are ≥18 years old with a documented CSF1R gene mutation and clinical and MRI findings consistent with ALSP. Intravenous VGL101 is administered every 28±7 days for a total of 13 doses. Primary endpoint is safety and tolerability assessed by adverse events. Week 24 change from baseline in MRI brain volume, MRI ALSP severity score, NfL (neurofilament light chain), and additional biomarkers are secondary endpoints. Exploratory clinical endpoints associated with ALSP are assessed. Enrollment is ongoing (target 15 patients).

Results Detailed study design plus safety, tolerability, longitudinal MRI findings, disease-related biomarkers, and/or clinical measures from the interim analysis of 6 patients after the 24-week treatment period from IGNITE will be presented.

Conclusions No therapies are currently approved for ALSP, and disease-modifying therapies are a critical unmet need. These are the first clinical trial results of a potential disease-modifying therapy for ALSP and of TREM2 agonism as a therapeutic approach in a neurodegenerative disorder.

Authors/Disclosures
Zbigniew K. Wszolek, MD, FAAN (Mayo Clinic- Jacksonville) PRESENTER	Dr. Wszolek has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Polish Neurological Society/Via Medica.
David S. Lynch, MBBS, PhD	Dr. Lynch has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vigil Neuroscience. Dr. Lynch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Lynch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vigil Neuroscience.
Jeffrey M. Gelfand, MD, MAS, FAAN (University of California, San Francisco)	Dr. Gelfand has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. Dr. Gelfand has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ventyx Bio. An immediate family member of Dr. Gelfand has received personal compensation in the range of $50,000-$99,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Headache: The Journal of Head and Face Pain. The institution of Dr. Gelfand has received research support from Genentech/Roche. The institution of Dr. Gelfand has received research support from Vigil Neurosciences. An immediate family member of Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant and Expert, Vaccine Injury Compensation Program with United States Health and Human Services and Department of Justice. Dr. Gelfand has a non-compensated relationship as a Trial Steering Committee Chairperson and member with Roche / Genentech that is relevant to AAN interests or activities.
Rajeev Kumar, MD, FRCPC (Rocky Mountain Movement Disorders Center)	The institution of Dr. Kumar has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Supernus. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. The institution of Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Teva Pharmaceuticals. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Annexon. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Acorda Therapeutics. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Cerevel Therapeutics. Dr. Kumar has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Impel Pharma. Dr. Kumar has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Supernus. The institution of Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for Teva. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acorda Therapeutics. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Kyowa Kirin. Dr. Kumar has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Research Catalyst, LLC. Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for CenExel RMCR. Dr. Kumar has stock in Research Catalyst, LLC. Dr. Kumar has stock in CenExel. The institution of Dr. Kumar has received research support from Supernus. The institution of Dr. Kumar has received research support from Sage Therapeutics. The institution of Dr. Kumar has received research support from Prilenia Therapeutics. The institution of Dr. Kumar has received research support from Roche. The institution of Dr. Kumar has received research support from Triplet Therapeutics. The institution of Dr. Kumar has received research support from CHDI Foundation. The institution of Dr. Kumar has received research support from Neurocrine Biosciences. The institution of Dr. Kumar has received research support from Biovie. The institution of Dr. Kumar has received research support from Neuroderm. The institution of Dr. Kumar has received research support from Sanofi. The institution of Dr. Kumar has received research support from Addex Pharma. The institution of Dr. Kumar has received research support from Integrative Research Laboratories. The institution of Dr. Kumar has received research support from Takeda Pharmaceuticals. The institution of Dr. Kumar has received research support from Neuraly. The institution of Dr. Kumar has received research support from Abbvie. The institution of Dr. Kumar has received research support from Cerevel Therapeutics. The institution of Dr. Kumar has received research support from Transposon Therapeutics. The institution of Dr. Kumar has received research support from Lundbeck. The institution of Dr. Kumar has received research support from Biohaven. The institution of Dr. Kumar has received research support from Revance Therapeutics. The institution of Dr. Kumar has received research support from Impax Laboratories. The institution of Dr. Kumar has received research support from Pharma Two B. The institution of Dr. Kumar has received research support from Enterin. The institution of Dr. Kumar has received research support from CND Life Sciences. The institution of Dr. Kumar has received research support from Neuron23. The institution of Dr. Kumar has received research support from Annexon Biosciences. The institution of Dr. Kumar has received research support from Annovis. The institution of Dr. Kumar has received research support from PTC Therapeutics. The institution of Dr. Kumar has received research support from Uniqure. The institution of Dr. Kumar has received research support from Alexza. The institution of Dr. Kumar has received research support from SparkNeuro. The institution of Dr. Kumar has received research support from Praxis. The institution of Dr. Kumar has received research support from Scion Neurostim. The institution of Dr. Kumar has received research support from Cognition Therapeutics. The institution of Dr. Kumar has received research support from Eli Lilly. Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving as a Medical Director with CenExel RMCR. Dr. Kumar has received personal compensation in the range of $1,000,000+ for serving as a Managing Member with Research Catalyst, LLC.
Donald McLaren	No disclosure on file
Andreas Meier, MD	Dr. Meier has received personal compensation for serving as an employee of Vigil Neuroscience. Dr. Meier has received personal compensation for serving as an employee of Voyager Therapeutics. Dr. Meier has stock in Vigil Neuroscience. Dr. Meier has stock in Voyager Therapeutics.
Rajasimhan Rajagovindan, PhD (Vigil)	Dr. Rajagovindan has received personal compensation for serving as an employee of Biogen. Dr. Rajagovindan has received personal compensation for serving as an employee of Vigil. Dr. Rajagovindan has stock in Biogen. Dr. Rajagovindan has stock in Vigil .