Vigil Neuroscience Announces FDA Has Lifted the Partial Clinical Hold on VGL101

Watertown, Mass. — Vigil Neuroscience, Inc. (Nasdaq: VIGL), a clinical-stage biotechnology company committed to harnessing the power of microglia for the treatment of neurodegenerative diseases, announced that the U.S. Food and Drug Administration (FDA) has lifted its partial clinical hold on doses greater than 20 mg/kg for VGL101 in its ongoing and future clinical trials in patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). VGL101, Vigil’s lead product candidate, is currently being studied in IGNITE, a Phase 2 proof-of-concept trial in patients with ALSP as well as in an ongoing Phase 1 single and multiple ascending dose (SAD and MAD) healthy volunteer trial.

“We are happy to share that the FDA has lifted the partial clinical hold on VGL101 based on supporting clinical data from our ongoing Phase 1 trial,” said Ivana Magovčević-Liebisch, Ph.D., J.D., President and Chief Executive Officer of Vigil. “Although we believe that 20 mg/kg is a clinically relevant dose in ALSP, we are very pleased that the hold has been lifted as we believe it’s important to maintain optionality to develop treatments that support patients suffering from both rare and common neurodegenerative indications.”

In November 2022, Vigil reported interim top-line data from the Phase 1 trial in healthy volunteers in the United States and Australia. Based on these data, VGL101 demonstrated favorable safety and tolerability profiles at doses up to 40 mg/kg SAD and 20 mg/kg MAD. The Company expects to report the full data analysis up to 60 mg/kg from the Phase 1 trial in the second half of 2023.

In December 2022, Vigil initiated a Phase 2 proof-of-concept clinical trial evaluating VGL101 in patients with ALSP. IGNITE, the first interventional trial in ALSP, is a global Phase 2, open-label trial designed to evaluate the safety and tolerability of VGL101 in up to 15 patients with symptomatic ALSP who have a CSF1R gene mutation. Patients enrolled in the trial will receive an intravenous (IV) infusion of 20 mg/kg of VGL101 approximately every 4 weeks for a treatment duration of one year. The Company expects to report six-month interim data from the first six patients in this trial in the second half of 2023.

The FDA previously granted Fast Track designation and Orphan Drug designation to VGL101 for the treatment of ALSP.

About VGL101
VGL101, Vigil’s lead product candidate, is a fully human monoclonal antibody targeting human triggering receptor expressed on myeloid cells 2 (TREM2), which is responsible for maintaining microglial cell function. TREM2 deficiency is believed to be a driver of certain neurodegenerative diseases. VGL101 is in development for rare microgliopathies, such as ALSP, as well as other neurodegenerative diseases for which TREM2 and/or microglia deficiency is believed to be a key driver of disease pathway.

About ALSP
ALSP is a rare, inherited, autosomal dominant neurological disease with high penetrance. It is caused by a mutation to the CSF1R gene and affects an estimated 10,000 people in the US, with similar prevalence in Europe and Japan. The disease generally presents itself in adults in their forties, is diagnosed through genetic testing and established clinical/radiologic criteria and is characterized by cognitive dysfunction, neuropsychiatric symptoms, and motor impairment. These symptoms typically exhibit rapid progression with a life expectancy of approximately six to seven years on average after diagnosis, causing significant patient and caregiver burden. There are currently no approved therapies for the treatment of ALSP, underlining the high unmet need in this rare indication.

About Vigil Neuroscience
Vigil Neuroscience is a clinical-stage biotechnology company focused on developing treatments for both rare and common neurodegenerative diseases by restoring the vigilance of microglia, the sentinel immune cells of the brain. We are utilizing the tools of modern neuroscience drug development across multiple therapeutic modalities in our efforts to develop precision-based therapies to improve the lives of patients and their families. VGL101, our lead candidate, is a fully human monoclonal antibody agonist targeting human triggering receptor expressed on myeloid 2 (TREM2) and is in a Phase 2 proof-of-concept trial in patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a rare and fatal neurodegenerative disease. We are also conducting IND-enabling studies with a novel small molecule TREM2 agonist program to treat common neurodegenerative diseases associated with microglial dysfunction, with an initial focus on Alzheimer’s disease (AD) in genetically defined subpopulations.