iluzanebart (VGL-101) / Vigil Neuro - LARVOL DELTA

Ignite: A Study of VGL101 in Patients With Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia (clinicaltrials.gov) - P2 | N=20 | Terminated | Sponsor: Vigil Neuroscience, Inc. | Trial completion date: Jan 2027 ➔ Jun 2025 | Active, not recruiting ➔ Terminated; No beneficial effects on biomarker or clinical efficacy endpoints

Trial completion date • Trial termination • CNS Disorders • CSF1R

Unraveling the Immune Puzzle: Role of Immunomodulation in Alzheimer's Disease. (PubMed, J Neuroimmune Pharmacol) - "Preclinical studies of immunomodulatory agents, including salidroside, festidinol, astragalin, sulforaphane, BM-MSC, simvastatin, Ab-T1, hTREM2, and XENP345, demonstrate promising effects. Additionally, clinical investigations of drugs such as simufilam, AL002, TB006, VGL101, DNL919, XPro1595, astragalus, and IBC-Ab002 underscore the therapeutic potential of targeting immune pathways in AD. This review emphasizes how neuroinflammation, microglial activation, and peripheral immune responses contribute to disease progression. By exploring immunomodulatory mechanisms, the article sheds light on potential therapeutic targets that could help mitigate AD pathology which may pave the way for novel interventions preventing neurodegeneration in AD."

Journal • Review • Alzheimer's Disease • CNS Disorders • Immunology • Oncology • CTNNB1 • TNFA

Ignite: A Study of VGL101 in Patients with Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (clinicaltrials.gov) - P2 | N=20 | Active, not recruiting | Sponsor: Vigil Neuroscience, Inc. | Trial primary completion date: Jul 2024 ➔ Mar 2025

Trial primary completion date • CNS Disorders • CSF1R

Trem2 agonism enhances microglial survival in models of csf1r-dependent adult-onset leukoencephalopathy (Neuroscience 2024) - "To explore the therapeutic hypothesis that loss of CSF1R signaling and related microglial hypofunction can be circumvented via activation of TREM2, we evaluated the potential that VGL101 (Iluzanebart), a human monoclonal TREM2 agonist antibody under development for treatment of ALSP, can compensate for CSF1R loss-of-function...Changes in protein levels of specific chemokines identified by gene expression analysis were also confirmed in vivo. These findings demonstrate Iluzanebart is a potent and selective TREM2 agonistic antibody, align with the hypothesis that TREM2 activation can compensate for CSF1R dysfunction, and support continued clinical development of Iluzanebart in individuals with ALSP."

Clinical • Alzheimer's Disease • CNS Disorders • Dementia • CSF1R • PI3K • SYK

Interim Results for Iluzanebart (VGL101) From IGNITE, the First Interventional Phase 2 Study in Patients With ALSP (EAN 2024) - P2 | "These interim clinical trial results of iluzanebart support its continued development as a potential disease- modifying therapy for ALSP and TREM2 agonism as a potential therapeutic approach for this neurodegenerative disorder."

Clinical • P2 data • CNS Disorders • Psychiatry • CSF1R

Ignite: A Study of VGL101 in Patients With Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia (clinicaltrials.gov) - P2 | N=20 | Active, not recruiting | Sponsor: Vigil Neuroscience, Inc. | Recruiting ➔ Active, not recruiting | N=15 ➔ 20 | Trial completion date: Jun 2024 ➔ Mar 2027 | Trial primary completion date: Dec 2023 ➔ Jul 2024

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • CSF1R

Interim Results on VGL101 from IGNITE: First Interventional Phase 2 Study in Patients with Adult-onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) (AAN 2024) - P2 | "No therapies are currently approved for ALSP, and disease-modifying therapies are a critical unmet need. These are the first clinical trial results of a potential disease-modifying therapy for ALSP and of TREM2 agonism as a therapeutic approach in a neurodegenerative disorder."

Clinical • P2 data • CNS Disorders • CSF1R • NEFL

VGL101: An Immunotherapy that Enhances Microglial Survival for Adult-onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) (AAN 2024) - "These findings demonstrate VGL101 is a potent and selective TREM2 agonistic antibody, align with the hypothesis that TREM2 activation can compensate for CSF1R dysfunction, and support continued clinical development of VGL101 for the treatment of patients with ALSP."

Clinical • IO biomarker • CNS Disorders • CSF1R

A Phase 1, First-in-human, Randomized, Double-blind, Placebo-controlled,nSingle and Multiple Ascending Intravenous Dose Study tonAssess the Safety, Tolerability, Pharmacokinetics of VGL101 in HealthynAdults (ANZCTR) - P1 | N=30 | Completed | Sponsor: Vigil Neuroscience, Inc | Not yet recruiting ➔ Completed

Trial completion • CNS Disorders

Ignite, a phase 2 proof-of-concept study of VGL101 in patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ECNP 2023) - P2 | "Conclusion : Individuals with ALSP experience rapid disease progression with significant morbidity and mortality due to lack of treatment options. The Phase 2 Ignite study aims to provide insights into safety, tolerability, and proof-of-concept of VGL101 for the treatment of patients with ALSP; enrollment continues."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy • Psychiatry • CSF1R • NEFL

A Phase 1, First-in-human, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Intravenous Dose Study of a novel TREM2 agonist (VGL101) in Healthy Volunteers (HVs) (AAN 2023) - "Conclusions VGL101 demonstrated a favorable safety, PK profile and confirmation of CNS target engagement in healthy volunteers. The Phase 1 data supports further clinical development of VGL101 in ALSP."

Clinical • P1 data • CNS Disorders • TREM2

A Study of VGL101 in Patients With Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia (clinicaltrials.gov) - P2 | N=15 | Recruiting | Sponsor: Vigil Neuroscience, Inc.

New P2 trial • CNS Disorders • CSF1R • NEFL

VGL101 Rescues CSF1R Dysfunction in Human Microglia And Macrophages: Evaluation of In Vitro Trem2 Agonism in Models Of A CSF1R-Dependent Leukodystrophy (AAIC 2022) - No abstract available

Preclinical • CSF1R