Vigil presents data on oral small molecule program including VG-3927

Vigil Neuroscience (VIGL) presented data highlighting its oral small molecule program, including its lead clinical candidate VG-3927, in two oral presentations at the AD/PD 2025 International Conference on Alzheimer’s and Parkinson’s Diseases being held April 1 – April 5 in Vienna, Austria. Oral presentation by Christian Mirescu, Ph.D., Senior Vice President, Neuroimmunology: Small Molecule TREM2 Agonists as Next-Generation Therapeutics for Alzheimer’s Disease / Key highlights from this presentation demonstrated: VG-3927 is an orally bioavailable small molecule TREM2 agonist that has high specificity for membrane-bound TREM2 versus soluble TREM2, which leads to increased access to the therapeutic site of action. VG-3927 shows a unique, synergistic activation of TREM2 with endogenous TREM2 ligands such as aggregated amyloid-beta (Abeta) that is expected to drive enhanced potency and specificity in regions of pathology. New data in 5xFAD plaque-burdened mice illustrate that small molecule TREM2 agonism enhances microglial uptake of both Abeta and Tau supporting the broad efficacy potential of the TREM2 agonist approach to go beyond targeting a single driver of AD pathology. Oral presentation by Petra Kaufmann, M.D., F.A.A.N., Chief Medical Officer: Phase 1 Study of VG-3927, A Novel Oral TREM2 Agonist. Key highlights from the presentation: The Phase 1 trial of 115 participants provided a comprehensive and robust dataset evaluating healthy volunteers, elderly participants and a cohort of AD patients. VG-3927 demonstrated a favorable safety and tolerability profile across all cohorts with no serious adverse events. All treatment-related adverse events were mild or moderate and self-resolving. VG-3927 showed a predictable and dose-dependent pharmacokinetic profile that supports once-daily dosing. These data demonstrated that VG-3927 has high CNS penetrance with an estimated cerebral spinal fluid to unbound plasma ratio of 0.91. PK and sTREM2 reduction observed in the single dose AD cohort was consistent with healthy volunteers and the reduction in sTREM2 was similar across evaluated TREM2 and ApoE genetic variants supporting development in AD across genotypes. PK and sTREM2 reduction observed in the multiple ascending dose elderly cohort was consistent with healthy volunteers. At the 25 mg dose, VG-3927 achieved the maximum sTREM2 reduction in the CSF of approximately 50%. PK/PD data support the selection of a 25 mg once-daily oral dose for the Phase 2 trial in AD patients.