Vigil Neuroscience's Alzheimer's Candidate Shows Promising Safety Profile, Set for Mid-Stage Study in Q3

Vigil Neuroscience, Inc. (Nasdaq: VIGL), a clinical-stage biotechnology company, has announced encouraging results from its Phase 1 clinical trial evaluating VG-3927, a potential once-daily oral therapy for Alzheimer's disease (AD). The positive data supports the advancement of VG-3927 into a Phase 2 trial, with plans to initiate the mid-stage study in the third quarter of 2025.

The Phase 1 single and multiple ascending dose (SAD/MAD) trial assessed the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profile of VG-3927 across 14 cohorts. Key takeaways from the trial include:

1. Favorable safety and tolerability profile: VG-3927 demonstrated a positive safety and tolerability profile across all cohorts, including the elderly cohort. All related adverse events were mild or moderate in severity and self-resolving without drug discontinuations. No serious adverse events were reported.
2. High brain penetrance and predictable PK profile: The drug showed high brain penetrance and a favorable and predictable PK profile that supports once-daily dosing.
3. Robust and dose-dependent reduction of sTREM2: VG-3927 achieved robust and dose-dependent reductions 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.
4. Consistent results across cohorts: The PK and sTREM2 reduction observed in the AD cohort was consistent with healthy volunteers and similar across evaluated TREM2 and ApoE genetic variants, supporting development in AD across genotypes. The elderly cohort also showed consistent results with healthy volunteers.



Vigil Neuroscience 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. The company's Chief Medical Officer, Petra Kaufmann, M.D., F.A.A.N., expressed confidence in the well-characterized molecule's potential to harness the neuroprotective potential of microglia and provide a new and differentiated therapy for those impacted by AD.

VG-3927 is a potent orally bioavailable small molecule TREM2 agonist designed to enhance protective microglial responses to aggregated amyloid and tau without increasing inflammation. 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.

In conclusion, Vigil Neuroscience's Alzheimer's candidate, VG-3927, has shown encouraging safety and efficacy data in its Phase 1 trial, positioning it for a mid-stage study in the third quarter of 2025. The drug's favorable safety profile, high brain penetrance, and robust reduction of sTREM2 suggest that it has the potential to be a differentiated therapy for AD. As the company advances VG-3927 into the next phase of clinical development, investors will be watching closely to see if the drug can maintain its promising profile and demonstrate long-term efficacy and safety.