Vigil Presents Data on its Small Molecule TREM2 Agonist Program at 2024 Alzheimer's Association International Conference (AAIC)  

Rhea-AI Summary

Vigil Neuroscience (NASDAQ: VIGL) presented data on its small molecule TREM2 agonist program at the 2024 Alzheimer's Association International Conference. The company shared clinical data from single ascending dose (SAD) cohorts in its ongoing Phase 1 trial of VG-3927, demonstrating proof-of-pharmacology with a robust decrease of sTREM2 in the CSF.

Key highlights include:

• In vivo data showing selective activation of downstream function leading to microglial amyloid-beta phagocytosis
• Acute modulation of AD pathophysiology comparable to an approved therapeutic
• In vitro data demonstrating preferential activity on cellular TREM2
• Phase 1 trial design details for VG-3927 in healthy volunteers
• Pharmacological and functional characterization of VG-3927 as a TREM2-specific, highly potent molecule

Vigil believes VG-3927 has the potential to offer a differentiated approach to treating Alzheimer's disease.

Positive

• First presentation of clinical data on sTREM2 from SAD cohorts in Phase 1 trial of VG-3927 demonstrates proof-of-pharmacology
• In vivo data shows selective activation of microglial amyloid-beta phagocytosis
• VG-3927 demonstrates acute modulation of AD pathophysiology comparable to an approved therapeutic
• Phase 1 trial design includes both single and multiple ascending dose cohorts
• VG-3927 characterized as a TREM2-specific, highly potent molecule with potential for treating Alzheimer's disease

Negative

• None.

Medical Research Analyst

As a Medical Research Analyst specializing in neurodegenerative diseases, I find Vigil Neuroscience's presentation of data on their TREM2 agonist program at AAIC 2024 to be highly significant. The company's small molecule TREM2 agonist, VG-3927, shows promising results in both preclinical and early clinical studies for Alzheimer's disease (AD) treatment.

Key points to consider:

• The proof-of-pharmacology demonstrated in the Phase 1 clinical trial is a important milestone. The robust decrease of sTREM2 in the CSF indicates that VG-3927 is effectively engaging its target in the brain.
• Preclinical data showing selective activation of microglial Aβ phagocytosis is particularly intriguing, as it suggests a potential mechanism for clearing amyloid plaques, a hallmark of AD pathology.
• The comparison to an approved therapeutic in modulating AD pathophysiology, without effector function liability, hints at a potentially improved safety profile.
• The activation of protective gene signatures and suppression of pro-inflammatory cytokines in various models further support the therapeutic potential of VG-3927.

While these results are encouraging, it's important to note that this is still early-stage research. The transition from Phase 1 to later-stage trials will be critical in determining the true efficacy and safety of VG-3927 in AD patients. Investors should closely monitor the progress of the ongoing Phase 1 trial and any announcements regarding plans for Phase 2 studies.

Biotechnology Industry Analyst

From a biotechnology industry perspective, Vigil Neuroscience's progress with VG-3927 is noteworthy for several reasons:

• First-mover advantage: As the first company to advance a small molecule TREM2 agonist into clinical development, Vigil has positioned itself at the forefront of this novel approach to AD treatment.
• Target validation: TREM2's strong causal link to AD risk provides a solid scientific rationale for this approach, potentially increasing the likelihood of success compared to less well-validated targets.
• Differentiated mechanism: The focus on modulating microglial function through TREM2 agonism offers a unique approach in the AD space, which has been dominated by amyloid-targeting therapies.
• Oral administration: The oral route of administration for VG-3927 could provide a significant advantage over injectable AD treatments in terms of patient convenience and compliance.

However, investors should be aware of the highly competitive and challenging nature of AD drug development. Many promising candidates have failed in late-stage trials and the bar for regulatory approval and market success is high. Vigil's ability to rapidly progress through clinical development and differentiate VG-3927 from other emerging AD therapies will be important for its long-term success.

The company's focus on biomarkers and mechanistic studies in early development is a positive sign, potentially allowing for better patient selection and increased chances of success in later-stage trials. As the program advances, key metrics to watch will include the durability of TREM2 engagement, cognitive and functional outcomes in AD patients and safety profiles in longer-term studies.

- First presentation of clinical data on sTREM2 from SAD cohorts in ongoing Phase 1 clinical trial of VG-3927 in healthy volunteers demonstrate proof-of-pharmacology -

- New in vitro and in vivo data demonstrate the Company’s small molecule TREM2 agonists modulate AD pathophysiology -

WATERTOWN, Mass., July 30, 2024 (GLOBE NEWSWIRE) -- Vigil Neuroscience, Inc. (Nasdaq: VIGL), a clinical-stage biotechnology company committed to harnessing the power of microglia for the treatment of neurodegenerative diseases, today presented one oral and two poster presentations at the 2024 Alzheimer's Association International Conference (AAIC) being held July 28 - August 1, 2024 in Philadelphia, Pennsylvania and virtually.

“As the first company to advance a small molecule TREM2 agonist into clinical development, we are excited to present data from this important program at AAIC,” said David Gray, Ph.D., Chief Science Officer at Vigil. “TREM2 has a strong causal link to Alzheimer’s disease risk and the data shared today further support our growing body of both preclinical and clinical findings that VG-3927 is a potent molecule that functionally engages TREM2 receptors in the brain. According to the World Health Organization, AD is the most common type of dementia, and we believe VG-3927 has the potential to offer a differentiated approach to treating this devastating disease.”

Oral presentation by Christian Mirescu, Ph.D., Vigil Neuroscience: Orally Administered Small Molecule TREM2 Agonists for Modulating AD Pathophysiology

The oral presentation highlighted new data from the Company’s small molecule Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Agonist program, including:

• In vivo data showing that Vigil’s small molecule TREM2 agonist selectively activates downstream function leading to microglial amyloid-beta (Aβ) phagocytosis.
• In vivo data from Vigil’s small molecule TREM2 agonist program demonstrating acute modulation of AD pathophysiology, comparable to an approved therapeutic, without effector function liability.
• In vitro data from VG-3927 demonstrating preferential activity on cellular TREM2 establishing sTREM2 as a target engagement biomarker linked to TREM2 signaling.
• Clinical data from single ascending dose (SAD) cohorts in the ongoing Phase 1 trial evaluating VG-3927 showing a robust decrease of sTREM2 in the CSF demonstrating proof-of-pharmacology.

Poster presentation by Raj Rajagovindan, Ph.D., Vigil Neuroscience: Design of a Phase 1, First-in-human, Randomized, Double-blind, Placebo-controlled, Single- and Multiple-Ascending Dose Study of a Novel Orally Administered TREM2 Agonist (VG-3927) in Healthy Volunteers

Poster details include:

• The Phase 1 clinical trial is a randomized, double-blind, placebo-controlled, SAD/MAD study evaluating the safety, tolerability, PK, and PD following oral administration of VG-3927 in healthy volunteers.
• Cohorts are conducted sequentially in a dose-escalating manner, and dosing may be adjusted based on safety and tolerability assessments and emerging PK data.
  • For each cohort, 8 participants are randomized in a 6:2 allocation ratio to VG-3927 or placebo.
  • Blood samples are collected in all cohorts to characterize PK of VG-3927.
  • Cerebrospinal fluid samples are collected in select cohorts to investigate biomarkers of target engagement.
    

Poster presentation by Borislav Dejanovic, Ph.D., Vigil Neuroscience: Pharmacological and Functional Characterization of the First Small Molecule TREM2 Agonist, VG-3927, for the Treatment of Alzheimer’s Disease

Poster details show that VG-3927:

• Is a TREM2 specific, highly potent molecule that potentiates signaling from lipid ligands.
• Induces functional agonism via unique clustering of TREM2 complexes in microglia.
• Activates protective gene signatures in mouse model of amyloidosis.
• Suppresses pro-inflammatory cytokines and protects against neurodegeneration in human CNS triculture model.

The presentation and posters are available on the Publications page of the Company’s website.

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. Vigil is utilizing the tools of modern neuroscience drug development across multiple therapeutic modalities in its efforts to develop precision-based therapies to improve the lives of patients and their families. Iluzanebart, Vigil’s lead clinical candidate, is a fully human monoclonal antibody agonist targeting human triggering receptor expressed on myeloid cells 2 (TREM2) in people with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a rare and fatal neurodegenerative disease. Vigil is also developing VG-3927, a novel small molecule TREM2 agonist, to treat common neurodegenerative diseases associated with microglial dysfunction, with an initial focus on Alzheimer’s disease (AD) patients, including some who carry TREM2 and other disease-associated variants.

Forward-Looking Statements 
This press release includes certain disclosures that contain “forward-looking statements” of Vigil Neuroscience (“Vigil” or the “Company”) that are made pursuant to the safe harbor provisions of the federal securities laws, including, without limitation, express or implied statements regarding: Vigil’s strategy, business plans and focus; the potential therapeutic benefit of our product candidates, including VG-3927, and the expected therapeutic benefits of such programs; VG-3927’s potential as a TREM2 agonist and its ability to convert microglia into a neuroprotective state. 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 uncertainties inherent in the development of product candidates, including the conduct of research activities and the conduct of clinical trials; whether results from preclinical studies and clinical trials will be predictive of the results of later preclinical studies and clinical trials; the timing and content of additional regulatory interactions with the FDA – including the Company’s discussions regarding the partial clinical hold on VG-3927; as well as the risks and uncertainties identified in the Company’s filings with the Securities and Exchange Commission (SEC), including Vigil’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2024 and in any subsequent filings Vigil makes with the SEC. Forward-looking statements contained in this announcement are made as of this date, and Vigil undertakes no duty to update such information except as required under applicable law. Readers should not rely upon the information on this page as current or accurate after its publication date.

Internet Posting of Information 
Vigil Neuroscience routinely posts information that may be important to investors in the 'Investors' section of its website at https://www.vigilneuro.com. The company encourages investors and potential investors to consult our website regularly for important information about Vigil Neuroscience. 

Investor Contact:  
Leah Gibson   
Vice President, Investor Relations & Corporate Communications   
Vigil Neuroscience, Inc.  
lgibson@vigilneuro.com  
  
Media Contact:  
Megan McGrath
CTD Comms, LLC
megan@ctdcomms.com

FAQ

What is the significance of Vigil's TREM2 agonist program for Alzheimer's disease treatment?

Vigil's TREM2 agonist program, particularly VG-3927, shows potential as a differentiated approach to treating Alzheimer's disease. TREM2 has a strong causal link to AD risk, and the data presented demonstrates that VG-3927 can functionally engage TREM2 receptors in the brain, potentially modulating AD pathophysiology.

What key data did Vigil Neuroscience (VIGL) present at the 2024 AAIC conference?

Vigil presented clinical data from single ascending dose (SAD) cohorts in its Phase 1 trial of VG-3927, showing a robust decrease of sTREM2 in the CSF. They also shared in vivo data demonstrating selective activation of microglial amyloid-beta phagocytosis and acute modulation of AD pathophysiology, as well as in vitro data showing VG-3927's preferential activity on cellular TREM2.

How is Vigil Neuroscience (VIGL) conducting its Phase 1 trial for VG-3927?

The Phase 1 trial is a randomized, double-blind, placebo-controlled, single and multiple ascending dose study in healthy volunteers. It evaluates the safety, tolerability, pharmacokinetics, and pharmacodynamics of oral VG-3927. Cohorts are conducted sequentially in a dose-escalating manner, with 8 participants per cohort randomized in a 6:2 ratio to VG-3927 or placebo.

What are the key characteristics of VG-3927 presented by Vigil Neuroscience (VIGL) at AAIC 2024?

VG-3927 was characterized as a TREM2-specific, highly potent molecule that potentiates signaling from lipid ligands. It induces functional agonism via unique clustering of TREM2 complexes in microglia, activates protective gene signatures in mouse models of amyloidosis, and suppresses pro-inflammatory cytokines while protecting against neurodegeneration in human CNS triculture models.