CAMBRIDGE, Mass., Aug 01, 2022 (GLOBE NEWSWIRE) — Vigil Neuroscience, Inc. (Nasdaq: VIGL), a clinical-stage biotechnology 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 TREM2 agonism continue to support the therapeutic potential of our lead clinical product candidate, VGL101, for the treatment of ALSP, an underdiagnosed, rapidly progressive, lethal autosomal dominant neurodegenerative disease caused by CSF1R gene mutations that result in microglial dysfunction,” said Spyros Papapetropoulos, MD, Ph.D., Vigil’s Chief Medical Officer. “In addition, we continue to make progress in raising disease awareness by elucidating the disease progression of ALSP, including the onset and rapid progression of symptoms, family history and global presence of the disease, which support our ongoing clinical development efforts in this rare leukoencephalopathy. . Importantly, ALSP is often misdiagnosed as a neurodegenerative dementia and in the presence of family history and radiologic findings, physicians should consider genetic testing for ALSP.”
The first poster titled “VGL101 rescues CSF1R dysfunction in human microglia and macrophages: evaluation of In vitro TREM2 agonism in models of a CSF1R-dependent leukodystrophy” shows that TREM2 agonism by VGL101 was able to induce CSF1R dysfunction in in vitro ALSP models utilizing healthy human monocyte-derived macrophages (hMDM) and induced pluripotent stem cell-derived human microglia (iMGL), which provide a rational basis for the development of VGL101 as a potential therapeutic agent for ALSP.
The main highlights from the presentation are:
CSF1R inhibition by PLX5622 (known inhibitor of CSF1R) or withdrawal of CSF1R ligands resulted in decreased viability, increased caspase 3/7 activation and altered morphology.
Administration of VGL101 induced phosphorylation of SYK in both hMDM and iMGL models, demonstrating agonism of the TREM2 receptor.
VGL101 rescued CSF1R inhibition-induced morphology and cell death in both hMDM and iMGL.
Increases in soluble CSF1R and decreases in soluble TREM2 after VGL101 administration in iMGLs may provide information on target engagement studies.
In a separate poster titled “Phenotypic Features of Leukoencephalopathy in Adults with Axonal Spheroids and Pigmented Glia (ALSP): Presentation of Symptoms and Clinical Course,” Vigil conducted a systematic literature search of published case studies on the clinical and genetic features of ALSP to a better understanding of the phenotypic features of ALSP, with data extracted from a cohort of 292 patients, representing the largest set of cases to date of ALSP. The findings of this study supported and expanded the previous, smaller case reports on the phenotypic features of ALSP.
The main highlights from the presentation are:
Mean (SD) age of onset (years) of symptoms was 43.2 (11.6), survival time (years) was 6.1 (4.7), age at death (years) was 52.2 (11 ,1) and the number of deaths was 118.
Family history was significantly more common (58.9%) than absence of family history (26.4%), supporting that genetic testing for CSF1R mutations should be used as an important marker for early and accurate diagnosis of ALSP.
The most common initial symptoms were cognitive impairment (45.9%), behavioral and psychiatric disorders (26.4%), extrapyramidal and pyramidal motor abnormalities (15.4%, 11.6%, respectively) and speech difficulties (11.3 %).
The clinical signs associated with progression of ALSP were more frequent compared to the same initial symptoms and consisted of cognitive impairment (80.8%), behavioral and psychiatric dysfunction (72.9%), extrapyramidal and pyramidal motor abnormalities (65. 1%, 49.0%), speech difficulties (41.1%) and seizures (25.3%).
The posters can be found on the Publications page from the company’s website.
VGL101, Vigil’s lead product candidate, is a fully human monoclonal antibody agonist that targets the human triggering receptor expressed on myeloid cells 2 (TREM2), which is responsible for maintaining microglial cell function. TREM2 deficiency is believed to be the cause of certain neurodegenerative diseases. VGL101 is under development for the treatment of rare microgliopathies, such as adult leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), as well as other neurodegenerative diseases where TREM2 and/or microglia deficiency is believed to be a major cause of disease pathway .
About Vigil Neuroscience
Vigil Neuroscience is a microglia-focused therapeutic company focused on developing treatments for both rare and common neurodegenerative diseases by restoring the vigilance of microglia, the brain’s sentinel immune cells. We use 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.
This press release contains certain disclosures that contain “forward-looking statements” by Vigil Neuroscience’s (“Vigil” or the “Company”) made in accordance with the safe harbor provisions of the federal securities laws, including, but not limited to, express or implied statements about the progress and timing of the preclinical and clinical development of Vigil’s programs and expectations regarding the development of VGL101 in ALSP and other indications, beliefs about findings and analysis of data from preclinical studies, and support for the therapeutic potential of VGL101 for the treatment of ALSP and beliefs advancing in increasing disease awareness will inform 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 associated with uncertainties inherent in the identification and development of product candidates, including conducting research activities and initiating and completing preclinical studies and clinical trials; uncertainties regarding the availability and timing of results and data from preclinical and clinical studies; the timing of the Company’s ability to file and obtain regulatory approval for investigational applications for new drugs and to initiate additional clinical trials; whether the results of preclinical studies will be predictive of the results of subsequent preclinical studies and clinical studies; the Company’s ability to initiate and complete its current and projected clinical trials and its ability to work with the FDA to successfully lift the partial clinical block; whether Vigil’s cash resources will be sufficient to fund foreseeable and unforeseen operating and capital expenditures; uncertainties related to the impact of the COVID-19 pandemic on its operations and operations; as well as 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 make with the SEC, including its quarterly report on Form 10- Q for the three months ended March 31, 2022 and the 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 obligation to update such information, except as required by applicable law. Readers should not rely on the information on this page to be current or accurate after the date of publication.
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