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Introduction to BioMAP<sup>®</sup> Systems
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Introduction to BioMAP<sup>®</sup> Systems


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This is an introduction to the BioMAP® Systems technology platform from BioSeek, LLC

This is an introduction to the BioMAP® Systems technology platform from BioSeek, LLC

Published in: Technology, Health & Medicine

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  • 1. Introduction to BioMAP® Systems Bridging the Gap From In Vitro to In Vivo1
  • 2. BioMAP® Systems Model Complex Biology2
  • 3. BioMAP® Technology Platform BioMAP Reference Predictive Assay Systems Profile Database Informatics Tools Human primary cells Biomarker responses to drugs Specialized informatics tools are Disease-models are stored in the database used to predict clinical outcomes 30+ systems Human Biology Integrated into a Robust, Scalable Platform3
  • 4. BioMAP® Systems Human primary cell-based assays Engineered to model complex human disease biology  Physiologically relevant assay conditions  Mixtures of stimulation factors, co-cultures of cells  Complex culture conditions selected to achieve stable signaling networks that reflect in vivo tissue states  Clinically validated disease biomarkers  Quantitative and reproducible  Robust readouts (proteins, mediators); standardized assays, QMP, SOPs  Assay formats manage disease variations among donors  Validated with known drugs4
  • 5. Current Validated BioMAP® Systems Primary Human Cell Types Disease Relevance BioMAP* Th1 and Th2 inflammation, allergy, Endothelial cells (EC) asthma, dermatitis, angiogenesis, wound healing, 3C 4H restenosis, atherosclerosis Th1 inflammation, psoriasis, COPD EC+lymphocyte+monocytes LPS SAg HPNo fibrosis, monocyte and T cell responses EC+Macrophages Macrophage responses, arthritis, COPD, fibrosis Mphg BT B cells + T cells Immune responses HSM3C HTh2 EC+Smooth Muscle Cells Vascular inflammation, restenosis, atherosclerosis EC+Th2 blasts Allergy, asthma HDF3CT HDFT Arthritis, asthma, dermatitis, fibrosis, psoriasis, Fibroblasts wound healing HDF3C HDFNo HDF3CGF Myofibroblasts Fibrosis, COPD, wound healing K3CT MyoF Keratinocytes Psoriasis, dermatitis, wound healing Keratinocytes+Fibroblasts Psoriasis, dermatitis, wound healing KF3CT KFNo Th1 and Th2 inflammation Bronchial Epithelial Cells Allergy, asthma, fibrosis, COPD BE3C BE4T Bronchial Epithelial Cells +Fibroblasts Asthma, allergy, fibrosis, COPD Smooth Muscle Cells Vascular inflammation, asthma, COPD, fibrosis BF4T SM3C5
  • 6. BioMAP® Assay Development Pipeline  Innate immunity cells  Neutrophils, M1 and M2 macrophages  Renal epithelial cells  Astrocytes  Hepatic cells  Hepatocytes, sinusoidal endothelial cells (LSEC), stellate cells (HSC), liver fibroblasts  Skeletal muscle cells, adipocytes, foam cells  Skeletal myoblasts and myotubes  Adipocytes derived from adipose tissue derived mesenchymal stem cells (ADMSC), mesenchymal stem cells (MSC), and preadipocytes  Foam cells derived from monocytes  Bone / joint cell types  MSC and ADMSC-derived chondrocytes and osteoblasts, monocyte- derived osteoclasts  Intestinal cells  Intestinal epithelial cells and intestinal myofibroblasts6
  • 7. Informatics and Data Analysis  Optimized algorithms for profile matching and function similarity clustering (network pharmacology, systems biology)  Quantitative analysis for screening and lead optimization  Potency and efficacy ranking, EC50 curves7
  • 8. BioMAP® Analysis of Prednisolone BioMAP Systems Log expression ratio (Drug/DMSO control) 99% significance envelope Control (no drug) Dose Response Cytotoxicity Readouts Readout Parameters (Biomarkers) Each Drug Induces a Signature Profile Profiles retain shape over multiple concentrations8
  • 9. BioMAP® Analysis of Prednisolone - Clinical Validation SAA PAI-1 PAI-1 MMP-1 IL-8 MCP-1 IL-8 PGE2 E-selectin Collagen I & III TNF- MCP-1, IL-8, E-sel. decrease PGE2 decrease Collagen I, III decrease PAI-1, SAA increase Leukocyte recruitment Pain, swelling Skin atrophy CV complications Sartori et al., 1999 Many, e.g. Jilma et al., 2000 Sebaldt et al., 1990 Autio et al., 1994 Fyfe et al., 1997 BioMAP® Profiling Can Bridge the Gap from In Vitro to In Vivo9
  • 10. BioMAP® Analysis Reveals Mechanism of ActionPairwise Correlation of BioMAP Reveals Functional Similarities Protein Estrogen R synthesis Microtubule PKC Activation Destabilizers Transcription PI-3K JNK NFkB Pathway mTOR Relationships Hsp90 DNA Calcineurin synthesis Retinoids CDK HMG-CoA reductase Ca++ Mitochondrial Mobilization ET chain p38 MAPK Microtubule Stabilizers Mechanism of Action MEK10 (On-Target)
  • 11. BioMAP® Reference Database BioMAP database contains profiles of >2700 agents • Drugs – Clinical stage, approved, and failed • Experimental Chemicals - Research tool compounds, environmental chemicals • Biologics - Cytokines, factors, peptides, antibodies, soluble receptors11
  • 12. BioMAP® Applications  Screening and lead optimization using primary cells  Phenotypic screening and Indication Discovery  Screening for second-generation drugs  Biological annotation of compounds  Target and compound validation in human cells  Benchmarking to standard of care  Safety assessment  Translational biology  Specialized assays, also with patient cells, patient classification  Testing drug combinations  Annotation for pharmacodynamic markers12 12
  • 13. Contacts Ellen Berg, PhD General Manager BioSeek, LLC 650-416-7621 Bridging the Gap From In Vitro to In VivoBioSeek, LLC310 Utah, #100South San Francisco, CA 94080