Thursday, February 27, 2025
7:30 am CHECK-IN & COFFEE
7:55 am Chair’s Opening Remarks
INVESTIGATING PRECLINICAL MODEL DEVELOPMENT TO DRIVE NEUROIMMUNOLOGY TRANSLATION INTO THE CLINIC
8:00 am Elucidating the Potential of Bruton’s Tyrosine Kinase Inhibitors to Modulate Microglial Inflammation using Advanced 2D/3D Human Brain Cell Systems
Synopsis
- Evaluating the functional and pharmacological properties of Fenebrutinib in blocking BTK-mediated disease-associated activation in human microglia and complex brain cell systems
- Fenebrutinib treatment attenuated pathogenic neuroinflammation associated with FcyR activation while preserving homeostatic innate immune cell functions
- This study increases understanding of potential BTK functions in human microglial signalling and neuroinflammation relevant to MS pathogenesis
8:30 am Reviewing Utility of Current Neuroinflammatory Models: Reviewing Stimuli, Transcriptomics, Comparative In Vitro & In Vivo Model Translatability
Synopsis
- Understanding if we have the right transcriptomic profile of microglia to reflect the human condition
- Evaluating relevance of various stimuli: are iPSCs and LPS still relevant for microglia?
- Exploring whether wild type microglia better at representing the clinical state (20yr aged microglia), or if APOE4 microglia are more relevant
- Navigating when to use TREM2 mutant in vivo model vs disease specific models for neuroinflammatory pathology
9:00 am Session Reserved for BrainXell
9:10 am Improving In Vitro Models to Better Recapitulate Human Biology of Neurodegeneration
Synopsis
- Covering limitations, pros and cons, of in vivo and in vitro models for drug discovery in neurodegeneration
- Development of in vitro iPSC models for AD drug discovery. Evaluation of donor differences by RNA-seq.
- Roadmap to scaling up production of iPSC-microglia and neurons using automation
9:40 am Sharing Insights on an Open-Access Living Inventory of Neuroinflammatory Preclinical Model & Target Data to Determine Rigor to Encourage Pre-Competitive Collaboration
Synopsis
- Overviewing the categorization of data and preclinical models of neuroinflammation in Alzheimer’s Disease to encourage pre-competitive collaboration
- Sharing perspectives on additional evidence generation required in day-to-day, aiming to increase model rigor, transparency and translatability in Alzheimer’s research
- Incentivizing stakeholders developing tools to share information to help others make informed decisions, towards pre-competitive collaboration
10:10 am MORNING BREAK & NETWORKING
NOVEL TECHNOLOGY & MODALITIES FOR IMPROVED TARGETING OF NEUROINFLAMMATION
10:40 am Integrating Blood-Brain Barrier Technology for Enhanced Delivery of Therapeutic Agents to the CNS
Synopsis
- Explaining the difference between transferrin receptor and CD98, and why they are good BBB targets
- Exploring transferrin CD98 and fine-tuning moiety and carrier protein for delivery of different cargos to the brain
- Unpacking use cases: enzyme replacement with GCASE
11:10 am T Cell Therapies Related to Neuroimmunological Indications & Mechanisms Are Entering Early Clinical Development & May Transform The Therapeutic Landscape
Synopsis
- CAR-T for neuroimmune indications
- Tregs for neuroimmune and neuroinflammatory indications
- CAR-T for brain tumor
- Other selected therapeutic initiatives
11:40 am Roundtable Discussion: To What Degree is Neuroinflammation the Cause of Disease vs Just Increases Susceptibility to CNS Diseases?
Synopsis
- Evaluate to what extent does disease cause neuroinflammation vs neuroinflammation causes disease?
- Reviewing the cause of early inflammatory response prior to disease onset and appearance of cognitive changes, as well as prevalence of neuroinflammation both before and after disease onset
- Navigating how the cause vs susceptibility ‘weighting’ changes across Alzheimer’s, Parkinson’s, FTS, Multiple Sclerosis, etc..
- Exploring relevance to treatment regime: should neuroinflammation-targeted therapeutics be considered as more of adjunct treatment in copathology? How does this vary between CNS diseases?
- What are the steps to further define this cause/susceptibility relationship in clinical development?
12:10 pm LUNCH & NETWORKING
INNOVATIVE TARGETS & MECHANISMS IN NEUROIMMUNOLOGY TO TARGET THE BREADTH OF NEUROINFLAMMATORY PATHOLOGY
1:00 pm Exploring In Vitro & In Vivo Tools to Model Inflammasome Activation in the Context of Neurodegeneration: Highlighting the NORP3 Inflammasome Program
Synopsis
- Addressing the limitations of demyelination models in immunodeficient mice and optimizing the use of chimeric microglial mice to better replicate human immune responses
- Investigating alternative immunodeficient mouse strains to enhance the demonstration of demyelination in preclinical studies, with a focus on improving translational relevance to human MS
- Developing and refining rodent models that more accurately mimic the progressive stages of MS, ensuring closer alignment with human disease pathology and progression for more effective therapeutic evaluation
1:30 pm Modulating Aberrant Activation of the cGAS Pathway to Treat Neurodegeneration in the Clinic
2:00 pm Non-selective Inhibition of Inflammasomes: Preclinical Data & Clinical Observations
Synopsis
- In vivo inhibition of inflammasomes in macular degeneration
- Preliminary clinical data
- In vitro and in vivo inhibition of inflammasomes in ALS, MS and AD models
2:30 pm Harnessing Inflammasome Activation to Decrease Activity in Neurodegeneration
Synopsis
- Uncovering the challenges in utilizing cytokines as surrogate markers for inflammasome activity at the individual level
- Explore cutting-edge technologies and methodologies for studying the molecular intricacies of inflammasome activation pathways for detection at the individual level
- Discuss the potential of these technologies to provide deeper insights into the molecular details of individual inflammasomes and their activation patterns
3:00 pm AFTERNOON BREAK & NETWORKING
3:30 pm Investigating Aβ Immunotherapy-Induced Vascular Inflammation & Cerebrovascular Damage
Synopsis
- Examining the connections between vascular integrity, blood-brain barrier permeability, and smooth muscle health in neurodegenerative disease
- Leveraging spatial omics to investigate cellular and molecular changes around specific vascular sites associated with disease progression
- Highlighting the involvement of immune cells, particularly a subset of macrophages, in maintaining vascular health and their relevance to disease-related changes
4:00 pm Vidofludimus Calcium (IMU-838) Combines the Best of Two Worlds: Neuroprotection & Relapse Prevention in Multiple Sclerosis
Synopsis
- Positive phase 2 data in relapsing-remitting multiple sclerosis (EMPHASIS)
- Hints to slowing down disability worsening
- Positive biomarker data from phase 2 trial in progressive multiple sclerosis (CALLIPER)
- Unique dual mode of action addressing relapsing and progressive disease by targeting Nurr1 and DHODH
- First-in-class Nurr1 activation going beyond inflammation
4:30 pm Panel Discussion: Bridging the Divide: Navigating Mechanistic Interplay Between the CNS & PNS for Target Discovery in Neuroimmunology
Synopsis
- Reviewing how immune signalling pathways in the PNS influence CNS inflammation and degeneration, and how this crosstalk can inform the identification of novel therapeutic targets
- Debate the utility of existing models that integrate both CNS and PNS components and evaluate their potential for accelerating target discovery
- Discuss the shared immune mechanisms underlying neuroinflammatory pathology in both the CNS and PNS, such as microglial activation and T cell infiltration and the unique features of each system