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Vigil Neuroscience Presents Data on its Small Molecule TREM2 Agonist VG-3927 in Two Oral Presentations at AD/PD™ 2025 International Conference

Core Insights - Vigil Neuroscience presented topline clinical data from the Phase 1 SAD/MAD trial of VG-3927, a potential treatment for Alzheimer's disease, at the AD/PD™ 2025 International Conference [1][2] Group 1: VG-3927 Overview - VG-3927 is an orally bioavailable small molecule TREM2 agonist with high potency and CNS penetrance, designed to target multiple contributors to Alzheimer's disease progression [2][8] - The drug's unique mechanism as both an agonist and a positive allosteric modulator may enhance microglial responses to aggregated amyloid and tau without increasing inflammation [8] Group 2: Phase 1 Trial Results - The Phase 1 trial included 115 participants, demonstrating a favorable safety and tolerability profile with no serious adverse events reported [5][7] - VG-3927 showed a predictable and dose-dependent pharmacokinetic profile, supporting once-daily dosing with an estimated cerebral spinal fluid to unbound plasma ratio of 0.91 [5][11] Group 3: Mechanism of Action - VG-3927 activates TREM2, engaging the brain's immune system to counteract multiple pathologies associated with Alzheimer's disease [3][4] - The drug promotes microglial uptake of both Aβ and Tau, indicating broad efficacy potential beyond targeting a single driver of Alzheimer's pathology [4][6] Group 4: Future Development Plans - Vigil Neuroscience plans to advance VG-3927 into Phase 2 development in the third quarter of 2025, aiming to provide a differentiated therapeutic option for Alzheimer's disease [2][6]