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
• Contribution of innate immune cells at the blood-brain barrier to neurodegenerative disease
• 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

• NULISA™ combines ultra-sensitive femtogram level detection with barcode-based high-plex biomarker analysis
• Broad matrix compatibility and highest sensitivity in plasma, serum, synovial fluid, nasal lining fluid, sputum, lysates and other matrices
• Single- to five-, and high-plex assays run fully automated on the ARGO HT System
• Custom assay development kits for end-users and CRO development services
• NULISAseq™ Inflammation Panel 250 provides comprehensive analysis of 250 cytokines, chemokines and other immune regulatory proteins from 25uL of biofluid
• NULISAseq Inflammation Panel AQ provides 156 absolute quantification measurements 
• NULISAseq Neuro220 Panel is unmatched for high-plex analysis of hundreds of neuroinflammation, vascular, and synaptic dysfunction, and proteinopathy biomarker
• NULISAseq Mouse Panel 120 for disease model analysis of immune, neuro and growth factors
• Unique capability to translate multiplexed discoveries to single and 5-plex biomarker assays with the same antibodies, antigen, and ARGO
• NULISA IVD and ARGO DX in development with funding from Gates Ventures and DxA.

• 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

• BrainXell is a leading provider of hiPSC-derived neurons and glia, working with over 75% of the world’s largest pharmaceutical companies
• Review our comprehensive off-the-shelf portfolio, highlighting microglia and region-specific cortical/spinal astrocytes, as well as disease models and isogenic controls
• Robust, scalable manufacturing processes generate billions of cells, and flexible custom workflows deliver the same high-quality cell types from any customer-supplied iPSC line
• Assay services integrate functional and molecular readouts to support target validation, drug screening, disease modeling and accelerated discovery through direct scientific collaboration

• How protective human genetic variants provide a blueprint for discovering genetically validated targets across ALS, FTD, PD, and Alzheimer’s disease
• Exploring the known and unknown roles of the innate immune system in the progression of age-related neurodegeneration
• Demonstrating therapeutic targeting of CD33 can be employed in several neurodegenerative diseases to reduce pathologic neuroinflammation
• The translational importance of genetically informed targets and biomarker-driven development for advancing next-generation therapies for neurodegeneration

• 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

• Neuroimmune drug development is advancing rapidly, but translating emerging biology into actionable clinical insights remains a major challenge.
• Neuroimmune drug development is focused on microglial biology, peripheral immune engagement, and novel innate immune targets.
• Despite progress, many programs face a critical bottleneck: a lack of sensitive, quantitative biomarkers capable of translating emerging biology into actionable clinical readouts.
• Ultra‑sensitive biomarker detection enables measurement of low‑abundance neuroimmune signals in blood and CSF.
• Use of established biomarkers such as NfL and GFAP, alongside emerging, novel markers of microglial activation and inflammatory signaling, support mechanistic insight, pharmacodynamic assessment, and patient stratification across the drug development pipeline.
• Integrating fluid‑based biomarkers with spatial biology approaches provides a more complete view of neuroimmune mechanisms.

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?

• FUJIFILM research services will be introduced, emphasizing its strength in human iPSC-derived neuron-astrocyte-microglia tri-cultures
• Compared with conventional monoculture systems, the tri-culture system enables more sensitive and quantitative evaluation of cytokine release in response to stimuli such as LPS and α-synuclein
• Visualization of NF-κB subcellular localization allows elucidation of the signaling cascade propagating from microglia to astrocytes
• Combining signal cascade visualization with the tri-culture system is useful for mechanism-of-action analysis of anti-inflammatory reagents and other drugs of interest

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.

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?

• Human and rodent data demonstrate cross-species alignment of peripheral and central biomarkers linking immune signalling to neuronal dysfunction
• The back-translational IFN-α rodent model of depression shows that peripheral immune activation drives central neuroinflammation, alters neuroplasticity and induces depressive-like phenotypes, recapitulating clinically relevant features
• Integrated biomarker readouts strengthen the translational value of preclinical platforms for CNS drug discovery and enable assessment of target engagement and disease progression

• 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.