8:00 am Chair’s Opening Remarks

Preclinical Models: Recapitulating the Human Neuroimmune System

8:15 am Using iPS-Microglia & Chimeric Models to Examine the Neuroimmunology of Alzheimer’s Disease

  • Matt Blurton-Jones Associate Professor, Department of Neurobiology & Behavior, University of California, Irvine

Synopsis

• The development, validation, and use of human iPS-microglia to study
Neurodegenerative Diseases
• The generation and use of chimeric models to study human microglial function in vivo
• How in vitro and in vivo models of human microglia are being used to test new
therapeutic approaches

8:45 am Development of Targets Identified from Patients & Validated With Ex Vivo & In Vivo Models of Neuroinflammation

  • Sue Bruhn Chief Executive Officer & President, Tiaki Therapeutics

Synopsis

• How can we best validate neuroinflammatory targets identified in patients?
• What are the key requirements to re-create the complex cellular
microenvironment essential to study microglia function?
• What are the best translational tools for studying neuroinflammation?

9:15 am Audience Discussion: Working with the Right Cells In Vitro

Synopsis

Discuss the greatest challenges of working with preclinical models with your peers to
share, learn and debate to guide your future research.
• Moving away from human primary myeloid cells
• Discussing the limited availability of models and difficulty of manipulating cells in vitro
• What’s new with leveraging human models or human data?

9:45 am Morning Refreshments & Networking

Improving Biological Understanding of Innate Immunity in the CNS

10:45 am TREM2, from Basic Functions to a Therapeutic Target

  • Christian Haass Professor, Laboratory of Neurodegenerative Disease, University of Munich

Synopsis

• Disease associated TREM2 mutations cause a loss of function
• TREM2 KO locks microglia in a homeostatic state
• Soluble Biomarkers: sTREM2 as a CSF marker for TREM2 dependent functions
• Modulation of TREM2 function with a therapeutic antibody

11:15 am Mechanisms of Targeting TREM2 with a Dual Function Antibody

  • Kate Monroe Associate Director and Senior Scientist , Denali Therapeutics

Synopsis

• Microglia lipid accumulation is a hallmark of TREM2 lof in vivo upon chronic myelin challenge
• The R47H AD risk allele recapitulates lipid metabolism defects in human iPSCderived
microglia
• A TREM2 antibody reduces microglia lipid accumulation in vitro while reducing
Abeta plaque levels in an AD mouse model

11:45 am The Role of Innate Immune Dysfunction & Chronic Inflammatory Disease in Neurodegeneration

  • Malu Tansey Director, Center for Translational Research in Neurodegenerative Disease & the Parkinson’s Foundation Research Center, The University of Florida College of Medicine

Synopsis

• Exploring evidence of inflammation in neurodegeneration
• Age-related immune dysfunction arising from gene-environment interactions
triggers chronic peripheral inflammation
• Discussing the need to target innate immune dysfunction without
immunocompromising patients
• Targeting solTNF mitigates the harmful effects of diet-induced inflammation in
the periphery and the CNS

12:15 pm SAM Microglia, a Novel Storage-Body Accumulating Subset in Steady- State & Aging

  • Michael Mingueneau Associate Director, Multiple Sclerosis & NeuroInflammation Research, Biogen

Synopsis

• Two discrete and novel subsets of microglia can be identified solely by the
presence or absence of cellular autofluorescence (AF) in healthy brains of both
rodent and non-human primates
• Autophagosomal and lysosomal pathways are key mechanisms for the formation
of these microglia subsets whereas myelin, FcR-mediated and TREM2-mediated
phagocytosis have little contribution
• Aging and impaired lysosomal function have convergent effects on the AF+ subset
by linearly increasing storage body load solely within this subset and directly
contributing to aging-related microglia dysfunction and cell loss

12:45 pm Lunch & Networking

Encouraging Collaboration & Investment to Safeguard Neuroimmunological Research

1:45 pm Beyond the Usual Suspects: Promoting Novel Thinking

Synopsis

• Encouraging the pursuit of target diversity, including discussion of the Association’s
dedicated funding mechanisms
• Why biomarkers are essential and fundamental tools that are needed to improve
efficacy and efficiency of clinical trials
• Importance of the recruitment of diverse populations in clinical trials

2:15 pm The Michael J. Fox Foundation’s Efforts to Improve Understanding of Inflammation in Parkinson’s Disease

  • Nicole Polinski Senior Associate Director, Research Programs, The Michael J Fox Foundation

Synopsis

• Discussing MJFF’s investment in uncovering and improving inflammation-related
biomarkers for Parkinson’s disease
• Highlighting our inflammation-related strategy to date and the strategy we seek
to employ for the coming years
• Providing an overview of the MJFF funding programs and additional resources
MJFF provides to support Parkinson’s disease research

2:45 pm Panel Discussion: Investing in Neuroinflammatory Targets & Backing Smaller Companies Research

Synopsis

• What do investors look for?
• Improving the collaboration and funding efforts between pharma and biotech
• Discussing the importance of investing in neuroscience

Reviewing Clinical Data to Inform Future Drug Development

3:15 pm Recipe for Success: Design Neuro Trials to Look Like Oncology Trials!

  • RJ Tesi Chief Executive Officer & Chief Medical Officer, INmune Bio

Synopsis

• Proposing that clinical trial success in oncology drug development is due to smart trial design
• Highlighting the role of biomarkers in driving the success of oncology drug development
• Using INmune Bio’s biomarker direct Phase Ib study in AD patients with
neuroinflammation as a case study to highlight “real world” application of these
principles

3:45 pm Afternoon Networking & Refreshments

Reviewing Clinical Data to Inform Future Drug Development

4:15 pm Discovery to Clinical Evaluation of Neuroinflammation: The Microglial P2X7-NLRP3 Axis

Synopsis

• Neuroinflammation in CNS disorders: preclinical and clinical evidence
• Role of P2X7-NLRP3 axis in neuroinflammation
• Discovery and early development of a brain penetrant P2X7 antagonist

4:45 pm Reviewing Early Biomarker Read Outs to Improve Drug Development

Synopsis

• Biomarker for neuro-immunology targets
• Early dose finding using PD markers
• Leveraging biomarkers to establish proof of mechanism and concept

5:15 pm Panel Discussion: Optimizing Clinical Trial Study Design & Finding the Appropriate Controls for Patients

  • Robert Paul Chief Medical Officer, Alector
  • RJ Tesi Chief Executive Officer & Chief Medical Officer, INmune Bio

Synopsis

• Accounting for immune component variance in patients
• Avoiding overly sanitised cohorts for neuroimmunology research
• Incorporating multiple components into clinical studies such as gender
• Leveraging biomarkers for disease progression to reduce the length of clinical studies

5:45 pm Chair’s Closing Remarks