9:00 am Chair’s Opening Remarks

How Can We Best Integrate Targets & Tools into Clinical Development Programs?

9:05 am Panel Discussion – Translation of Therapeutic Efficacy in Neuroinflammation: Importance of Identifying the Best Biomarkers & Relevant Models

Synopsis

• How should we develop an assay for each biomarker to better understand whether modulating our target impacts the activity of microglia?
• How do we leverage our translational tools to measure neuroinflammation and better understand the underlying activation pathways?
• How do we best understand the role of specific targets with regard to expression timeline at different stages of disease and activity level and in neuroinflammatory pathways?
• How can we create a physiologically relevant model that actually provides predictive results for clinical trials?
• What critical translational questions do we need to unravel to truly develop effective drugs targeting neuroinflammation?

9:40 am Implementing Immune Repertoire Sequencing to Monitor Immunotherapy in Neurdegenerative Disease

  • Ned Sherry MPH, Senior Manager, Research & Business Development, Adaptive Biotechnologies

Synopsis

• Learn about Adaptive Biotechnologies’ immunoSEQ® Technology, an end-to-end immunosequencing solution, and how it can propel your research from experimental design to publication-ready data

• Discuss studies and applications of large-scale immunosequencing in the field of neurobiology research

• How the immunoSEQ Assay can be leveraged to study drug candidate selection, optimize dosing, determine smart drug combinations, select biomarker endpoints, optimize patient selection, predict response to therapy and monitor for adverse events

*immunoSEQ is for Research Use Only. Not for use in diagnostic procedures.

10:05 am Networking Break

Targeting the Inflammasomes & Their Role in Innate Immune & Inflammatory Responses

10:40 am Targeting Inflammasomes for the Treatment of Inflammatory Diseases – Potential for CNS Disorders?

  • Rebecca Coll Principal Investigator, Lecturer in Immunobiology, Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, UK

Synopsis

• Overview of inflammasome signalling pathways.
• Overview of inflammasomes in relation to CNS disorders.
• Discussion of currently available inflammasome inhibitors and the development of these to target neurological diseases.
• Discussion of mechanisms of activation and potential targets in the inflammasome pathway in CNS disorders.
• Discussion of the therapeutic implications of targeting inflammasomes in CNS disorders.

11:05 am Exploring the NLRP3 Inflammasome in Neurodegenerative Diseases

Synopsis

• Dissecting neuroimmune connections in aging and neurodegenerative diseases
• Driving our understanding of molecular mechanisms of inflammatory regulation
• Identification of new therapeutic approaches for neurodegenerative disease

11:30 am GPCR19 Regulates P2X7R-mediated NLRP3 Inflammasomal Activation of Microglia by Amyloid β in Alzheimer’s Diseases

  • SY Seong Chief Executive Officer, Shaperon ; Professor, Department of Microbiology & Immunology, Seoul National University College of Medicine

Synopsis

• A GPCR19 agonist improved memory and cognition of 5xFAD mice
• Targeting GPCR19 and P2X7 ion channel therby regulate NLRP3 inflammasome activation
• Reducing neuroinflammation by decreasing Aβ plaques, number of activated microglia, ROS production and also by preventing neuronal apoptosiss in the brain of 5XFAD mice
• GPCR19 might provide clinical benefits by inhibiting redundant inflammasome pathways downstream of polymorphic P2X7

11:55 am Exploring Inflammasome Activation After Traumatic Brain Injury

Synopsis

• The inflammasome contributes to the innate immune response after traumatic brain injury.
• Traumatic brain injury induces a systemic inflammatory response that is in part mediated by the inflammasome.
• IC100 inhibits inflammasome activation after traumatic brain injury.
• Inflammasome proteins are reliable biomarkers of traumatic brain injury.

12:20 pm Live Speaker Q&A

  • Rebecca Coll Principal Investigator, Lecturer in Immunobiology, Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, UK
  • SY Seong Chief Executive Officer, Shaperon ; Professor, Department of Microbiology & Immunology, Seoul National University College of Medicine
  • Juan Pablo De Rivero Vaccari Research Assistant Professor , University of Miami Miller School of Medicine
  • Michael Heneka Professor, University of Bonn Medical Centre

12:50 pm Networking Lunch

1:30 pm Targeting the Peripheral Nervous System

Synopsis

• What is the role of peripheral immune cells in the brain and to what extent to we understand peripheral-central neuroimmune crosstalk?
• What are our advances in peripheral inflammatory markers and clinical correlations?
• Exploring our philosophy – It’s not a solo performance, it’s a symphony
• How best to modulate Tcell function for neuroprotection (e.g. mechanistic work to elucidate various pathway overlaps including antigens, 2nd messengers, STING and the inflammasome work in the peripheral system)?
• Approaches we use to stratifying patients quantitatively with different forms of disease based on immune function and cell phenotypes

1:55 pm Untapping Astrocytes as a Source of New Targets for Neurodegenerative Disorders

  • Shane Liddelow Assistant Professor, Neuroscience Institute , NYU Langone

Synopsis

  • Why are astrocytes such a hugely overlooked cell population?
  • Elucidating the role of astrocytes in influencing the inflammatory response
  • What have we uncovered about astrocytes biology and the cross talk between the different cell type?
  • What are we missing to push forward new discoveries in astrocyte biology – particularly in relation to neurodegenerative diseases?

2:20 pm Identifying the Right Biomarkers to Track Neuroinflammation

Synopsis

• Developing biomarkers to fast track drug development targeting neuroinflammation, exploring various biomarker strategies
• What are the key targets that can help monitor neuroinflammation in the cns?
• Shall we aim to define a specific signature of neuroinflammation that would help define the state of disease and understand treatment response?
• Exploring senescence-induced inflammation: Is this an important player in drug development? Discovering the interplay between immunosenescence and age-related diseases
• Can we utilize markers of senescence to monitor inflammation?

2:45 pm Live Speaker Q&A

3:10 pm Afternoon Break

3:40 pm Developing Remyelination Therapies for Neurodegenerative Diseases

Synopsis

• Myelin degeneration and/or dysregulation is a common characteristic of neurodegenerative and neuropsychiatric diseases
• Remyelination and neuroprotection therapies are the next frontier in drug development for neuroimmune and neurodegenerative pathologies
• How can we develop novel methodologies and medications to promote remyelination and repair of the affected nerve cells?
• How can we best translate this into clinical trials?
• Exploring our biomarker strategies for clinical development of remyelination therapies

4:05 pm Disease-associated Oligodendrocyte Responses in Neurodegenerative Diseases

  • Shristi Pandey Associate Scientist, Bioinformatics & Computational Biology , Genentech

Synopsis

• Oligodendrocyte dysfunction and myelin degeneration is a common feature in the pathogenesis and progression of neurodegenerative diseases

• However, the spectrum of possible activation states of oligodendrocytes in different neurodegenerative contexts is not well understood.

• Using an integrative analysis of single-cell RNAseq datasets collected across diverse models of Alzheimer’s Disease and Multiple Sclerosis, we derived a catalog of activation states of disease-associated oligodendrocytes and their respective molecular signatures.

• We also observed an elevated expression of these gene signatures in oligodendrocytes from MS patients.

• This catalog of disease-associated oligodendrocytes will inform our understanding of disease progression and help develop novel therapeutic interventions

4:30 pm Genetic Ablation of Mouse Gpnmb Does Not Alter SynucleinRelated Pathology

  • Brad Friedman Senior Scientist, Department of OMNI Bioinformatics, Genentech

Synopsis

• Gpnmb is a transmembrane secreted protein that is expressed by activated myeloid cells in mouse and human
• Human genetics suggests that Gpnmb inhibition might provide therapeutic benefit for Parkinson’s disease
• Therefore, we characterized Gpnmb-KO mice in three different models of neurological disease, including two alpha-synuclein-driven models.
• Although all three models exhibited robust behavioral, neurochemical, histological, cellular and gene expression phenotypes, none of these was altered in Gpnmb-KO animals
• Therefore, these models are not suitable for studying the role of Gpnmb in development or progression of Parkinson’s disease

4:55 pm Role of C9orf72 in Inflammation & Neurodegeneration

  • Robert Baloh VP, Global Head of Research in Neuroscience & Rare Diseases, pRED at Roche

Synopsis

• Repeat expansions in C9orf72 are the major genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia
• Loss of function of C9orf72 in dendritic cells drives an autoinflammatory state that includes STING activation of type I IFN signaling
• Microglia lacking C9orf72 have an altered response to aging and amyloid plaque accumulation
• Endolysosomal regulation by the C9orf72/SMCR8 complex in myeloid cells has potential relevance to neurodegeneration, inflammatory diseases and cancer

5:20 pm Live Speaker Q&A

  • Carlos Pedraza Director of CNS Biology , Alkermes
  • Brad Friedman Senior Scientist, Department of OMNI Bioinformatics, Genentech
  • Robert Baloh VP, Global Head of Research in Neuroscience & Rare Diseases, pRED at Roche
  • Shristi Pandey Associate Scientist, Bioinformatics & Computational Biology , Genentech

5:50 pm Chair’s Closing Remarks

End of Neuroimmunology Drug Development Summit