Vigil Neuroscience presents preclinical data on VGL101 for adult leukoencephalopathy with axial spheroids and pigmented glia (ALSP) and the clinical phenotype of ALSP at the Alzheimer’s Society International Conference 2022

Vigil Neuroscience, Inc.

Vigil Neuroscience, Inc.

Cambridge, Massachusetts, August 1, 2022 (Globe Newswire) – Vigil Neuroscience, Inc. (Nasdaq: VIGL), a clinical-stage biotech company committed to harnessing the power of microglia to treat neurodegenerative diseases, today presented two posters at the Alzheimer’s Association International Conference (AAIC) in San Diego.

“Findings from our preclinical studies evaluating the TREM2 agonist continue to support the therapeutic potential of our flagship clinical product, VGL101 for the treatment of ALSP, a fatal, underdiagnosed and rapidly progressive neurodegenerative disease caused by CSF1R “Gene mutations that lead to dysfunction of microglia,” said Spyros Papapetropoulos, MD, PhD, chief medical officer of Vigil. “In addition, we continue to make progress in raising awareness of the disease by elucidating disease progression in ALSP, including symptom onset and rapid progression of symptoms, family history and global presence of the disease, which will guide our ongoing clinical development efforts in this rare form of leukoencephalopathy.” Importantly, ALSP is misdiagnosed as a neurodegenerative dementia and in the presence of a family history and radiological findings clinicians should consider genetic testing for ALSP.”

First poster “VGL101 Rescues CSF1R Dysfunction in Human Microglia and Macrophages: An Evaluation” in the laboratory TREM2 agonist in models of CSF1R-dependent leukodystrophy demonstrates that TREM2 agonist by VGL101 was able to compensate for CSF1R dysfunction in in the laboratory ALSP models use healthy human monocyte-derived (hMDM) and inducible human microglia (iMGL) stem cell-derived macrophages, providing a rationale for the development of VGL101 as a potential treatment for ALSP.

Highlights of the presentation include:

  • Inhibition of CSF1R by PLX5622 (a known inhibitor of CSF1R) or withdrawal of CSF1R ligands resulted in decreased viability, increased caspase 3/7 activation, and altered conformation.

  • VGL101 administration induced SYK phosphorylation in both hMDM and iMGL models, indicative of TREM2 receptor tone.

  • VGL101 rescued the morphology induced by CSF1R inhibition and cell death in both hMDM and iMGL.

  • Increases in soluble CSF1R and decreases in soluble TREM2 upon administration of VGL101 in iMGLs may lead to targeted engagement studies.

In a separate poster titled “Phenotropic features of adult leukoencephalopathy with axial spheroids and pigmented glia (ALSP): Presentation of symptoms and clinical course,” Vigil conducted a systematic literature review of published case studies on the clinical and genetic features of ALSP to better understand the phenotypic characteristics of ALSP, With data extracted from a cohort of 292 patients, it represents the largest case series to date for ALSP. The results of this study supported and extended previous smaller case reports on the phenotypic characteristics of ALSP.

Highlights of the presentation include:

  • The median age (SD) of symptom onset (years) was 43.2 (11.6), survival time (years) was 6.1 (4.7), age of death (years) was 52.2 (11.1) and the number of deaths was 118.

  • Family history was more frequent (58.9%) than absence of family history (26.4%), supporting that genetic testing for CSF1R mutations should be used as a key marker for early and accurate diagnosis of ALSP.

  • The most common initial symptoms were cognitive impairment (45.9%), behavioral and psychological dysfunction (26.4%), extrapyramidal and pyramidal motor abnormalities (15.4%, 11.6%, respectively) and speech difficulty (11.3%).

  • Clinical symptoms associated with the development of ALSP were more prevalent compared to the initial symptoms themselves and consisted of cognitive impairment (80.8%), behavioral and psychological dysfunction (72.9%), extrapyramidal and pyramidal motor abnormalities (65.1%, 49.0%, respectively), speech difficulty (41.1 %) and seizures (25.3%).

Stickers can be found at Publications page from the company’s website.

About VGL101
VGL101, a lead product candidate for Vigil, is a fully human monoclonal antibody agonist that targets the human myeloid stimulatory receptor 2 (TREM2), which is responsible for maintaining microglia function. TREM2 deficiency is thought to be a driver of some neurodegenerative diseases. VGL101 is in development for the treatment of rare microgliopathies, such as adult leukoencephalopathy with axonal spheroids and pigmented microglia (ALSP), as well as other neurodegenerative diseases in which TREM2 and/or microglia deficiency is thought to be a major driver of the disease pathway .

About Vigil Neuroscience
Vigil Neuroscience is a microglia-focused treatment company focused on developing treatments for both rare and common neurodegenerative diseases by restoring the awakening of microglia, the brain’s sentinel immune cells. We use the tools of modern neuroscience drug development across multiple therapeutic approaches in our efforts to develop precision-based therapies to improve the lives of patients and their families.

forward-looking statements
This press release includes certain disclosures that contain “forward-looking statements” from Vigil Neuroscience (“Vigil” or the “Company”) that are made in accordance with the safe harbor provisions of the federal securities laws, including, but not limited to, express or implied statements Concerning the progress and timing of preclinical clinical development of Vigil, expectations for VGL101 development in ALSP, other indications, beliefs about outcomes, data analyzes from preclinical studies, support for the therapeutic potential of VGL101 for the treatment of ALSP, and beliefs that advances in disease awareness will guide ongoing clinical development efforts. Forward-looking statements are based on Vigil’s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties related to the uncertainties inherent in the identification and development of candidate products, including the conduct of research activities and the initiation and completion of preclinical studies and clinical trials; Uncertainty about the availability and timeliness of results and data from preclinical and clinical studies; timing of the Company’s ability to submit and obtain regulatory approval for applications for experimental new drugs and to initiate additional clinical trials; whether the results of preclinical studies are predictive of the results of preclinical studies and subsequent clinical trials; The company’s ability to initiate and complete its current and projected clinical trials and ability to work with the Food and Drug Administration to successfully remove partial clinical suspension; whether Vigil’s cash resources will be sufficient to fund expected and unforeseen operating expenses and capital expenditure requirements; Uncertainties related to the impact of the COVID-19 pandemic on its business and operations; In addition to the risks and uncertainties identified in the company’s filings with the Securities and Exchange Commission (SEC), including Vigil’s IPO registration statement and in subsequent filings it may file with the Securities and Exchange Commission, including its quarterly report on Form 10-Q for the three months ended March 31, 2022 and its annual report on Form 10-K for the year ended December 31, 2021. Forward-looking statements in this announcement are made as of this date, and Vigil undertakes no duty to update such information except as required by applicable law. Readers should not rely on the information on this page as being current or accurate after the date of its publication.

CONTACT: Investor Contact Sarah Carmody Media Contact Megan McGrath MacDougall Advisors