Day One

• Emerging evidence shows that TREM2 is only part of the story; microglial activation can occur independently, and in some cases, peripheral myeloid cells infiltrate the brain and contribute to inflammation
• Dysregulation of HDACs and other epigenetic regulators alters microglial and astrocyte function, suggesting novel therapeutic angles through age-related epigenomic reprogramming
• Disease-associated microglial phenotypes evolve, what is protective in early stages may be harmful later, complicating decisions about when and how to intervene
• Many interventions may also affect peripheral myeloid cells. Biomarker discovery remains critical to distinguish microglial subsets and measure target engagement non-invasively in clinical settings

• Complement activation is a key aspect of the neuroimmunological response to neurodegenerative disorders
• Glial cell reactivity is modulated by multiple complement system components that could be leveraged for therapeutic benefit
• Brain-penetrant complement therapeutics: efforts to develop a small molecule inhibitor of C3aR to overcome the limitations of antibody-based complement inhibitors
• Evaluating pharmacodynamic biomarkers of C3aR inhibition in preclinical models of neurodegeneration

A focused opportunity to connect face-to-face with leading experts in neuroimmunology drug development: engage in high-impact, peer-to-peer conversations on the latest scientific advances, preclinical strategies, & translational challenges.

• The discovery and characterization of the CNS-penetrant IRAK4 inhibitor BIO- 8169 previously positioned for neuroimmune and inflammatory models
• How TLR pathway modulation reveals the potential trade-offs in therapies targeting CNS-innate immunity, such as the balance between phagocytic function and cytokine production
• Insights from the BIO-8169 discovery program on how targets can be prioritized and evaluated against complex microglial phenotypes and disease-specific inflammatory signatures

• Vascular dysfunction leads to the toxic accumulation of fibrin deposits outside of blood vessels, sparking chronic innate immune cell activation; this emerging pathway represents a novel, highly specific target for neurodegenerative disease intervention
• Targeting this pathway with highly specific antibodies restores a beneficial microglial population and is protective in preclinical models of Alzheimer’s disease, multiple sclerosis, and retinal diseases
• THN391, a first-in-class high-affinity humanized monoclonal antibody targeting the fibrin inflammatory epitope, is in Phase 1b trials for early Alzheimer's disease and diabetic macular edema

• Unlock a previously underexploited microglial pathway to help restore homeostatic, disease-resolving activity without relying solely on TREM2-centric strategies
• Enables a more direct and tractable mechanism for restoring microglial phagocytosis and immune balance, supporting clearer translation from biology to therapeutic design
• Strengthen the foundation for precision microglial therapeutics by broadening the set of actionable immune checkpoints that shape microglial behaviour across disease stages

• How organoid models are used to simulate the BBB and enable small molecule screening for CNS drug candidates
• Addressing challenges in organoid maturity, reproducibility, and relevance to human disease biology
• The importance of incorporating multiple CNS cell types, including microglia and astrocytes, for inflammation studies
• Comparing organoid approaches with traditional animal and cell-based models in neuroinflammation research
• Emerging efforts to harmonize organoid protocols and enhance translatability to clinical settings

Despite decades of reliance on rodent models in neuroinflammation and neurodegeneration, there is growing consensus that animal systems often fail to capture key human disease mechanisms. This panel will debate whether we are entering a postanimal-model era or simply shifting expectations and redefining how in vivo studies are used.

• What have we truly learned from animal models and where have they fallen short in reflecting the complexity of human neuroimmune diseases?
• How do chimeric and humanized mouse models help bridge the translational gap, and what are their limitations?
• When is reliance on animal models necessary, and when can strong human genetic or phenotypic data support a “modellight” approach?
• How should we balance phenotypic versus target-driven strategies in preclinical testing, especially given the artificial nature of many models (e.g., amyloid beta overexpression)?
• Are current in vitro models a step backward or an important complement in understanding multifactorial diseases where secondary mechanisms matter?
• How do different companies weigh model necessity depending on target confidence and therapeutic strategy, and what does the future hold for smarter, more selective use of in vivo models?

Despite promising advances like GFAP and neurofilament light (NFL), fluid and blood biomarkers still face major hurdles before they can reliably predict neuroimmune disease progression or serve as clinical decision tools. This panel will explore the current state of biomarker science, including the challenges of patient heterogeneity, distinguishing brain-specific inflammation from systemic signals, and validating markers for clinical use.

• What is the current predictive value of fluid biomarkers in neuroimmune diseases, and how do they complement genetic or omics data?
• How does patient heterogeneity, such as in Parkinson’s disease subtypes, effect biomarker utility and trial design?
• What are the biggest challenges in distinguishing CNS-derived inflammatory markers from systemic inflammation, and how might technologies like extracellular vesicles or PET tracers help?
• How close are we to having reliable progression or efficacy biomarkers, and what gaps remain for clinical validation?

• Demonstrating how brain specific disease pathologies can potentially be detected in CSF and blood and how new imaging and molecular techniques could enhance this
• Developing specific tools to monitor neuroimmune markers and showing how they can be employed across neuroinflammatory and neurodegenerative conditions
• Highlighting the importance of early detection through sensitive diagnostic biomarkers, and the ways in which standardized collections and discovery biomarker studies are supporting this.

This session highlights cutting-edge research and innovative approaches in neuroimmunology drug development, featuring advances in biomarker identification, translational models, target validation, and early-phase clinical studies. Join us to explore the latest strategies driving therapeutic innovation for neuroinflammatory and neurodegenerative diseases.