Vigil Neuroscience is advancing its innovative microglia-targeting therapeutic programs for both rare and common neurodegenerative diseases, with significant progress reported in its first quarter 2025 financial results and business updates.
The clinical-stage biotechnology company, focused on harnessing microglial function to treat neurodegenerative conditions, is progressing two key TREM2 (triggering receptor expressed on myeloid cells 2) agonist programs that show promise for addressing serious unmet medical needs.
Iluzanebart Program Approaches Critical Milestone
Vigil's lead candidate iluzanebart, a fully human monoclonal antibody TREM2 agonist, is nearing a significant development milestone. The company expects to report the final analysis from its IGNITE Phase 2 clinical trial in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) in the second quarter of 2025.
The final analysis will include data from all patients who received either 20 mg/kg or 40 mg/kg of iluzanebart over a 12-month treatment period. Notably, Vigil intends to pursue an accelerated approval pathway for iluzanebart in ALSP, a rare and fatal neurodegenerative disease with no approved treatments, and plans to provide regulatory strategy updates when the final analysis is reported.
VG-3927 Shows Promising Phase 1 Results for Alzheimer's Disease
The company's second TREM2 program, VG-3927, a novel small molecule TREM2 agonist targeting Alzheimer's disease (AD), demonstrated positive Phase 1 clinical trial results reported in January 2025.
The comprehensive Phase 1 single and multiple ascending dose (SAD/MAD) trial evaluated VG-3927 across 14 cohorts, including:
- 8 SAD cohorts of healthy volunteers up to a 140 mg dose
- 4 MAD cohorts of healthy volunteers up to a 50 mg dose
- A multiple dose elderly cohort
- A single dose cohort of AD patients, including some with TREM2 or other genetic risk factors
The trial enrolled 115 participants total, with 89 receiving VG-3927, including 34 participants aged 55 and older. Results demonstrated a favorable safety and tolerability profile across all cohorts. All treatment-related adverse events were mild or moderate in severity and self-resolving without requiring drug discontinuation. No serious adverse events were reported.
Pharmacokinetic data revealed that VG-3927 is highly CNS penetrant with favorable properties supporting once-daily dosing. Importantly, the drug achieved robust, dose-dependent reduction of soluble TREM2 (sTREM2) of up to approximately 50% in cerebrospinal fluid, demonstrating strong pharmacokinetic/pharmacodynamic relationship, sustained target engagement, and TREM2 agonist activity.
Based on these promising results, Vigil plans to advance a once-daily oral dose of 25 mg that fully engages the desired pharmacology and expects to initiate a Phase 2 trial in Alzheimer's disease in the third quarter of 2025.
Scientific Presentations Highlight Differentiated Mechanism
In April 2025, Vigil presented two oral presentations featuring VG-3927 at the AD/PD™ 2025 International Conference on Alzheimer's and Parkinson's Diseases. The preclinical presentation highlighted key pharmacological differentiations of VG-3927, demonstrating its unique synergistic activation of TREM2 with endogenous TREM2 ligands such as aggregated amyloid-beta (Aβ). This mechanism is expected to drive enhanced potency and specificity in regions of pathology.
"During the quarter, we continued to make meaningful progress across our two TREM2 programs, VG-3927 and iluzanebart," said Ivana Magovčević-Liebisch, Ph.D., J.D., President and Chief Executive Officer of Vigil. "For VG-3927, we reported positive Phase 1 data in January 2025 that support the planned initiation of a Phase 2 trial in Alzheimer's disease patients in Q3. We also presented these findings at the AD/PD™ scientific conference, further highlighting VG-3927's potential as a differentiated next-generation therapeutic candidate for the treatment of AD."
Financial Position Supports Continued Development
As of March 31, 2025, Vigil reported cash, cash equivalents, and marketable securities of $87.1 million, compared to $97.8 million as of December 31, 2024. The company expects its current financial resources will fund operational plans into 2026.
Research and development expenses for the first quarter of 2025 were $16.5 million, compared to $14.3 million for the same period in 2024. The increase was primarily driven by higher preclinical and manufacturing-related costs associated with the small molecule TREM2 agonist program and increased headcount to support pipeline advancement.
General and administrative expenses remained consistent at $7.0 million for the first quarter of 2025, compared to $7.1 million for the same period in 2024. The company reported a net loss of $22.4 million for the first quarter of 2025, compared to $19.9 million for the same period in 2024.
Microglia-Targeting Approach Shows Promise
Vigil's therapeutic approach focuses on restoring the vigilance of microglia, the sentinel immune cells of the brain, which play a critical role in maintaining brain health and responding to pathology. By targeting TREM2, a receptor expressed on microglia that regulates their function, Vigil aims to enhance the brain's natural defense mechanisms against neurodegenerative processes.
This strategy represents a novel approach to treating both rare diseases like ALSP and common conditions like Alzheimer's disease, potentially addressing fundamental disease mechanisms rather than just symptoms.
With continued momentum across both programs, Vigil is positioned to deliver on key clinical milestones in 2025 that could advance these potentially transformative therapies for patients with serious neurodegenerative conditions.
