CAMBRIDGE, Mass., August 1, 2022 (GLOBE NEWSWIRE) — wakeful neuroscience, inc. (Nasdaq: VIGL), a clinical-stage biotechnology company committed to harnessing the power of microglia for the treatment of neurodegenerative diseases, today unveiled 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, a fatal, rapidly progressive, and underdiagnosed autosomal dominant neurodegenerative disease caused by CSF1R genetic mutations that result in microglial dysfunction,” said Spyros Papapetropoulos, MD, Ph.D., Vigil’s chief medical officer. “Furthermore, we continue to make progress in raising awareness of the disease by elucidating the disease progression of ALSP, including the onset and rapid progression of symptoms, family history, and the global presence of the disease, which our researchers will inform. 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 radiological findings, clinicians should consider genetic testing for ALSP.”
The first poster entitled “VGL101 rescues CSF1R dysfunction in human microglia and macrophages: evaluation of in vitro TREM2 agonism in CSF1R-dependent leukodystrophy models” demonstrates that TREM2 agonism by VGL101 was able to compensate for CSF1R dysfunction in in vitro ALSP models using healthy human monocyte-derived macrophages (hMDM) and induced pluripotent stem cell-derived human microglia (iMGL), providing a rational basis for developing VGL101 as a potential therapeutic for ALSP.
Highlights of the presentation include:
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Inhibition of CSF1R by PLX5622 (known CSF1R inhibitor) or removal of CSF1R ligands resulted in reduced viability, increased caspase 3/7 activation, and altered morphology.
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VGL101 administration induced SYK phosphorylation in hMDM and iMGL models, demonstrating TREM2 receptor agonism.
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VGL101 rescued CSF1R inhibition-induced morphology and cell death in both hMDM and iMGL.
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Increases in soluble CSF1R and decreases in soluble TREM2 following administration of VGL101 in iMGL can inform target engagement studies.
In a separate poster titled “Phenotypic Characteristics of Adult-Onset Leukoencephalopathy With Axonal Steroids and Pigmented Glia (ALSP): Symptom Presentation and Clinical Course,” Vigil conducted a systematic literature review of published case studies on the clinical features and genetics of ALSP to better understand the phenotypic characteristics of ALSP, with data drawn from a cohort of 292 patients, representing the largest case series of ALSP to date. The findings of this study supported and extended previous smaller case reports on the phenotypic features of ALSP.
Highlights of the presentation include:
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Mean (SD) age at 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.
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Family history was considerably more common (58.9%) than no family history (26.4%), supporting that genetic testing for CSF1R mutations should be used as a key marker for early and accurate diagnosis of CSF1R. ALSP.
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The most frequent initial symptoms were cognitive impairment (45.9%), behavioral and psychiatric dysfunction (26.4%), extrapyramidal and pyramidal motor abnormalities (15.4%, 11.6%, respectively), and speech difficulty (11 ,3%).
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Clinical symptoms associated with the progression of ALSP were more prevalent compared to the same initial symptoms and included cognitive impairment (80.8%), behavioral and psychiatric dysfunction (72.9%), extrapyramidal and pyramidal motor abnormalities (65 .1%, 49.0%, respectively), speech difficulty (41.1%) and seizures (25.3%).
Posters can be accessed at Posts Page from the Company’s website.
About VGL101
VGL101, Vigil’s lead product candidate, is a fully human monoclonal antibody agonist that targets the human activating receptor expressed on myeloid cells 2 (TREM2), which is responsible for maintaining microglial cell function. TREM2 deficiency is thought to be a driver of certain neurodegenerative diseases. VGL101 is in development for the treatment of rare microgliopathies, such as adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), as well as other neurodegenerative diseases for which TREM2 and/or microglia deficiency is thought to be a factor. disease key. route.
About Vigil Neuroscience
Vigil Neuroscience is a microglia-focused therapeutics company focused on developing treatments for rare and common neurodegenerative diseases by restoring vigilance to microglia, the brain’s sentinel immune cells. We are using 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.
Forward-looking statements
This news release includes certain disclosures containing “forward-looking statements” by Vigil Neuroscience (“Vigil” or the “Company”) that are made pursuant to the safe harbor provisions of the federal securities laws, including, without limitation, statements express or implied. statements regarding the progress and timing of preclinical and clinical development of the Vigil programs and expectations regarding the development of VGL101 in ALSP and other indications, beliefs about the findings and analysis of data from preclinical studies, and support for the therapeutic potential of VGL101 for the treatment of ALSP and beliefs that progress in increasing awareness of the disease 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 related to the uncertainties inherent in the identification and development of product candidates, including the conduct of research activities and the commencement and completion of preclinical studies and trials. clinical; uncertainties regarding the availability and timing of results and data from preclinical and clinical studies; the timing of the Company’s ability to submit and obtain regulatory authorization for investigational new drug applications and initiate additional clinical trials; whether the results of preclinical studies will be predictive of the results of subsequent preclinical studies and clinical trials; the Company’s ability to initiate and complete its current and expected clinical trials and its ability to work with the FDA to successfully remove the partial clinical hold; whether Vigil’s cash resources will be sufficient to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements; uncertainties associated with the impact of the COVID-19 pandemic on its business 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 in the 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. The forward-looking statements contained 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 as current or accurate after its publication date.
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