Joseph T. Coyle
Director, Laboratory for Psychiatric and Molecular Neuroscience, McLean Hospital, Eben S. Draper Professor of Psychiatry Harvard Medical School
Seminars
Thursday 17th September 2026
Panel Discussion: Redefining Therapeutic Potential in Muscarinics: Interrogating the M1/M4 Debate to Advance Next Generation Neuropsychiatric Treatments
3:30 pm
- How the recent FDA approval of an M1/M4 targeting muscarinic agonist–antagonist therapy has opened the door for next generation mechanisms, prompting the field to explore which muscarinic pathways hold the greatest future therapeutic potential
- How M1 and M4 receptor modulation may diverge in future clinical applications, with emerging evidence suggesting distinct roles in cognitive processing, behavioural regulation, and symptom domains underserved by dopamine based treatments
- How advancing Phase 1 muscarinic programs is helping define optimal translational strategies for the future, including biomarker guided dosing, refined safety monitoring, and strategic choices around patient versus healthy volunteer enrolment
- How next generation M4 selective PAMs and other muscarinic focused innovations may expand the therapeutic footprint across neuropsychiatric and neurodegenerative indications, positioning muscarinic pathways as a long term pillar of future CNS drug development
- Will PAMs recapitulate efficacy of orthosteric agonists, as seen with Cobenfy?
Tuesday 15th September 2026
EEG & AI to Identify Glutamatergic Responders: A Path to Overcoming Schizophrenia’s Etiologic Heterogeneity
11:00 am
- Highlight the limitations of DSM 5 diagnostic categories in schizophrenia and illustrate how etiologic heterogeneity has contributed to repeated failures of mechanistically novel drug candidates
- Demonstrate how EEG derived cortical activity patterns, paired with AI driven analysis, can provide a mechanistic basis for prospectively identifying patients whose glutamatergic pathology aligns with specific therapeutic mechanisms
- Present evidence from pomaglumetad Phase 3 re analysis showing that baseline EEG markers can identify a ~20% subgroup with substantial cognitive and negative symptom improvement, revealing responders concealed within a non significant overall trial
- Outline how ongoing work in schizophrenia and autism aims to validate EEG based responder identification across disorders with shared cortical circuit disruption, supporting a broader precision therapy framework
