Vigil Neuroscience Reports Positive Data from its Phase 1 Clinical Trial Evaluating VG-3927 for the Potential Treatment of Alzheimer’s Disease
Vigil Neuroscience (VIGL) announced positive data from its completed Phase 1 clinical trial of VG-3927, an oral treatment for Alzheimer's disease (AD). The trial, involving 115 participants across 14 cohorts, demonstrated favorable safety and tolerability profiles with no serious adverse events.
Key findings include: highly brain penetrant properties, dose-dependent reduction of sTREM2 up to 50% in cerebral spinal fluid, and consistent pharmacokinetics across different genetic variants. The company selected a 25mg once-daily oral dose for its planned Phase 2 trial, scheduled to begin in Q3 2025.
VG-3927, as the first Phase 2-ready oral TREM2 agonist, functions as both an agonist and positive allosteric modulator. The drug is designed to enhance protective microglial responses to aggregated amyloid and tau without increasing inflammation, potentially offering advantages over antibody-based treatments by avoiding ARIA risks.
Vigil Neuroscience (VIGL) ha annunciato dati positivi dal suo completato trial clinico di Fase 1 per VG-3927, un trattamento orale per la malattia di Alzheimer (AD). Lo studio, che ha coinvolto 115 partecipanti suddivisi in 14 coorti, ha dimostrato profili di sicurezza e tollerabilità favorevoli, senza eventi avversi gravi.
Le principali scoperte includono: proprietà altamente penetranti nel cervello, riduzione dose-dipendente di sTREM2 fino al 50% nel liquido cerebrospinale, e farmacocinetica coerente attraverso diverse varianti genetiche. L'azienda ha selezionato una dose orale di 25mg da assumere una volta al giorno per il suo previsto trial di Fase 2, che dovrebbe iniziare nel terzo trimestre del 2025.
VG-3927, come primo agonista orale di TREM2 pronto per la Fase 2, funziona sia da agonista che da modulatore allosterico positivo. Il farmaco è progettato per potenziare le risposte microgliali protettive all'aggregazione di amiloide e tau senza aumentare l'infiammazione, offrendo potenzialmente vantaggi rispetto ai trattamenti basati su anticorpi evitando i rischi associati ad ARIA.
Vigil Neuroscience (VIGL) anunció datos positivos de su ensayo clínico de Fase 1 completado de VG-3927, un tratamiento oral para la enfermedad de Alzheimer (AD). El ensayo, que involucró a 115 participantes en 14 cohortes, demostró perfiles de seguridad y tolerabilidad favorables sin eventos adversos graves.
Los hallazgos clave incluyen: propiedades altamente penetrantes en el cerebro, reducción dependiente de la dosis de sTREM2 de hasta el 50% en el líquido cerebroespinal, y farmacocinética consistente a través de diferentes variantes genéticas. La compañía seleccionó una dosis oral de 25 mg una vez al día para su previsto ensayo de Fase 2, programado para comenzar en el tercer trimestre de 2025.
VG-3927, como el primer agonista oral de TREM2 listo para la Fase 2, actúa tanto como agonista como modulador alostérico positivo. El fármaco está diseñado para mejorar las respuestas microgliales protectoras a la agregación de amiloide y tau sin aumentar la inflamación, ofreciendo potencialmente ventajas sobre los tratamientos basados en anticuerpos al evitar riesgos de ARIA.
Vigil Neuroscience (VIGL)는 VG-3927의 1상 임상 시험에서 긍정적인 데이터를 발표했습니다. VG-3927은 알츠하이머병(AD)을 위한 경구 치료제입니다. 이 시험은 14개의 코호트에서 115명의 참가자가 참여했으며, 심각한 부작용 없는 안전성과 내약성을 보여주었습니다.
주요 발견사항으로는: 높은 뇌 침투력, 뇌척수액에서의 sTREM2의 용량 의존적 감소(최대 50%), 다양한 유전적 변형에 따라 일관된 약리학적 동태가 포함됩니다. 이 회사는 2025년 3분기에 시작될 예정인 2상 임상시험을 위해 하루 25mg의 경구 용량을 선택했습니다.
VG-3927은 Fase 2 진입이 준비된 최초의 경구 TREM2 작용제로, 작용제로서 긍정적인 알로스테릭 조절제의 역할도 수행합니다. 이 약물은 아밀로이드와 타우 응집체에 대한 미세교세포의 보호 반응을 증가시키도록 설계되었으며, 염증을 증가시키지 않으면서 항체 기반 치료의 ARIA 위험을 피함으로써 잠재적인 이점을 제공할 수 있습니다.
Vigil Neuroscience (VIGL) a annoncé des données positives issues de son essai clinique de Phase 1 terminé sur VG-3927, un traitement oral pour la maladie d'Alzheimer (AD). L'essai, impliquant 115 participants répartis en 14 cohortes, a démontré des profils de sécurité et de tolérance favorables sans événements indésirables graves.
Les résultats clés incluent : des propriétés hautement pénétrantes dans le cerveau, une réduction dépendante de la dose de sTREM2 allant jusqu'à 50% dans le liquide céphalorachidien, et une pharmacocinétique cohérente à travers différentes variantes génétiques. La société a choisi une dose orale de 25 mg à prendre une fois par jour pour son essai de phase 2 prévu, qui devrait commencer au T3 2025.
VG-3927, en tant que premier agoniste oral de TREM2 prêt pour la Phase 2, agit à la fois comme agoniste et comme modulateur allostérique positif. Le médicament est conçu pour améliorer les réponses microgliales protectrices face à l'agrégation de l'amyloïde et de la tau sans augmenter l'inflammation, offrant potentiellement des avantages par rapport aux traitements basés sur des anticorps en évitant les risques d'ARIA.
Vigil Neuroscience (VIGL) hat positive Daten aus seiner abgeschlossenen Phase-1-Studie zu VG-3927, einer oralen Behandlung für Alzheimer (AD), bekannt gegeben. Die Studie, in die 115 Teilnehmer in 14 Kohorten einbezogen wurden, zeigte günstige Sicherheits- und Verträglichkeitsprofile ohne schwerwiegende Nebenwirkungen.
Zu den wichtigen Ergebnissen gehören: hochgradig durchdringende Eigenschaften im Gehirn, dosisabhängige Reduktion von sTREM2 um bis zu 50 % in der cerebrospinalen Flüssigkeit und konsistente Pharmakokinetik bei verschiedenen genetischen Varianten. Das Unternehmen wählte eine Tagesdosis von 25 mg für die geplante Phase-2-Studie, die im dritten Quartal 2025 beginnen soll.
VG-3927, als erster oral TREM2-Agonist in der Phase 2, fungiert sowohl als Agonist als auch als positiver allosterischer Modulator. Das Medikament wurde entwickelt, um die schützenden Reaktionen der Mikroglia auf aggregierte Amyloid- und Tau-Proteine zu verstärken, ohne die Entzündung zu erhöhen, was potenziell Vorteile gegenüber auf Antikörpern basierenden Behandlungen bietet, indem es die Risiken einer ARIA vermeidet.
- Successful completion of Phase 1 trial with favorable safety profile
- Demonstrated up to 50% reduction in sTREM2 levels
- Consistent efficacy across different genetic variants
- First Phase 2-ready oral, once-daily TREM2 agonist
- No serious adverse events reported
- Advancing to Phase 2 trial in Q3 2025
- None.
Insights
The Phase 1 results for VG-3927 represent a significant milestone in Alzheimer's disease treatment development, particularly in the emerging field of microglial-targeted therapeutics. The data revealed several important advantages:
Key Clinical Achievements:
- Demonstrated robust target engagement with up to
50% reduction in sTREM2 levels in CSF - Favorable safety profile with no serious adverse events
- Consistent pharmacokinetics across different genetic variants (TREM2 and ApoE)
- Brain penetration supporting once-daily oral dosing
The therapeutic profile of VG-3927 addresses several critical limitations of current AD treatments. As an oral small molecule, it offers significant advantages over injectable antibody-based therapies like lecanemab and donanemab, potentially improving patient compliance and reducing healthcare system burden. The absence of an Fc domain particularly differentiates it from antibody approaches, potentially reducing ARIA risk - a significant safety concern with current amyloid-targeting therapies.
The drug's dual mechanism as both a TREM2 agonist and PAM is particularly noteworthy. This approach could provide more precise control over microglial activation, potentially offering better efficacy while maintaining a favorable safety profile. The 25mg daily dose selection suggests optimal pharmacological engagement while maintaining a practical dosing regimen.
From a market perspective, VG-3927's development represents a potential paradigm shift in AD treatment. The combination of oral administration, favorable safety profile and novel mechanism targeting microglial function positions it uniquely in the competitive landscape. While still early-stage, these results support advancement to Phase 2, with potential market implications for both patients and healthcare providers.
- Safety, tolerability, pharmacokinetic, and pharmacodynamic profile supports continued development of VG-3927 as potential once-daily oral therapy for Alzheimer’s disease (AD) -
- Robust and dose-dependent reductions of sTREM2 were achieved demonstrating sustained functional target engagement –
- Company plans to advance VG-3927 into a Phase 2 trial in the third quarter of 2025; Selects 25mg QD oral as a dose that fully engages desired pharmacology -
WATERTOWN, Mass., Jan. 23, 2025 (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 announced positive data from its completed Phase 1 clinical trial evaluating VG-3927 for the potential treatment of AD. Collectively, the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profile supports the advancement of VG-3927 into a Phase 2 clinical trial as a potential once-daily oral therapy for AD.
“We are very excited by these positive Phase 1 data, which further support continued development of VG-3927 as a potential next-generation therapy for AD,” said Ivana Magovčević-Liebisch, Ph.D., J.D., President and Chief Executive Officer of Vigil. “As the first and only Phase 2-ready oral, once-daily small molecule TREM2 agonist, VG-3927 is designed to provide a differentiated profile that can go beyond targeting amyloid plaques to address additional contributors of disease progression and has the potential to offer a more convenient treatment regimen for those struggling with the immense burden of this disease. We are delighted to have reached this key clinical milestone enabling VG-3927 to advance into a Phase 2 trial.”
The Phase 1 single and multiple ascending dose (SAD/MAD) trial assessed the safety, tolerability, PK, and PD of VG-3927 across 14 cohorts. As part of this trial, the Company evaluated 8 SAD cohorts of healthy volunteers up to a 140mg/kg dose and 4 MAD cohorts of healthy volunteers up to a 50mg/kg dose. The trial also included an elderly cohort and a single dose cohort of 11 AD patients, including some participants who carry TREM2 or other genetic risk factors for AD. The trial enrolled a total of 115 participants. Eighty-nine (89) participants received VG-3927, including 34 who were 55 years of age and older.
Key takeaways from the Phase 1 clinical trial of VG-3927 include the following:
- Demonstrated a favorable safety and tolerability profile across all cohorts, including the elderly cohort.
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- All related adverse events were mild or moderate in severity and self-resolving without drug discontinuations. No serious AEs were reported.
- Highly brain penetrant with a favorable and predictable PK profile that supports once-daily dosing.
- Achieved robust and dose-dependent reduction of sTREM2 of up to approximately
50% in the cerebral spinal fluid (CSF) demonstrating a strong PK/PD relationship, sustained target engagement and TREM2 agonist activity. - PK and sTREM2 reduction observed in the AD cohort was consistent with healthy volunteers and was similar across evaluated TREM2 and ApoE genetic variants supporting development in AD across genotypes.
- PK and sTREM2 reduction observed in the elderly cohort was consistent with healthy volunteers.
- Combined clinical and in vivo preclinical data confirm VG-3927 elicits neuroprotective activation of microglia downstream of TREM2 signaling.
- Vigil expects to provide additional data in an oral presentation at the AD/PD™ 2025 International Conference on Alzheimer’s and Parkinson’s Disease taking place April 1-5, 2025, in Vienna, Austria and online.
Based on the Phase 1 results and preclinical profile of VG-3927, the Company plans to advance a once-daily oral dose of 25mg that fully engages the desired pharmacology and expects to initiate the Phase 2 trial in the third quarter of 2025.
“We are happy to report that following our strong Phase 1 results, VG-3927 is a Phase 2-ready candidate that has demonstrated a favorable safety and tolerability profile,” said Petra Kaufmann, M.D., F.A.A.N., Chief Medical Officer of Vigil. “Based on our comprehensive dataset, we are confident that VG-3927 is a well-characterized molecule that is highly brain penetrant and engages TREM2 to harness the neuroprotective potential of microglia. We continue to work toward the goal of providing a potential new and differentiated therapy to those impacted by AD, a disease with significant unmet need.”
VG-3927 is a potent orally bioavailable small molecule TREM2 agonist. Its novel mode of action as both an agonist and a positive allosteric modulator (PAM) may amplify functional responses around sites of pathology leading to strong modulation of microglia and potentially greater neuroprotection. VG-3927 is designed to enhance protective microglial responses to aggregated amyloid and tau without increasing inflammation. In contrast to antibody TREM2 agonists, VG-3927 maximizes receptor activation and microglial function because it does not bind to sTREM2, which may increase its access to the site of therapeutic action in AD. Additionally, VG-3927 does not have an Fc (fragmented crystallizable region) domain, which engages elements of the immune system that have been associated with increased risk of amyloid-related imaging abnormalities (ARIA). Collectively across preclinical and clinical data, these key differentiators create a compelling profile for VG-3927 as an investigational next-generation therapy for the treatment of AD.
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).
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: the Company’s strategy, business plans and focus; the potential therapeutic benefit of the Company’s product candidates; the progress and timing of the clinical development of Vigil’s programs, including the expected progress and timing to advance VG-3927 into a Phase 2 clinical trial in the third quarter of 2025; and beliefs about observations made analyzing preclinical study and clinical trial data to date, including with respect to VG-3927. 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 inherent in the development of product candidates, including the conduct of research activities and clinical trials; whether results from prior preclinical studies and clinical trials will be predictive of the results of subsequent preclinical studies and clinical trials; whether Vigil’s cash resources will be sufficient to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements; and the timing and content of additional regulatory information from the FDA; 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 September 30, 2024 and 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
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FAQ
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