1. Primary Human Cell Systems Analysis of Drug Mechanisms Ellen L. Berg, PhD BioSeek, Inc. SBS 15th Annual Conference Lille, France 28 April 2009 Bio Seek

4. BioMAP ® Technology Platform Complementary to biochemical target and phenotypic screening Assays Human primary cells Disease-like culture conditions LPS BF4T SM3C Profile Database Informatics Biological responses to drugs and stored in the database Specialized informatics tools are used to mine and analyze biological data

7. Assays are Robust and Highly Reproducible High Correlation of Experimental Replicates 5  M dose Pearson Correlation Coefficient Consistent data experiment-to-experiment Pearson correlation >0.8 (perfect match = 1)

8. Microtubule Stabilizers Mitochondrial ET chain Retinoids Hsp90 CDK NF  B MEK DNA synthesis JNK Protein synthesis Microtubule Destabilizers Estrogen R PI-3K Ca ++ Mobilization Classification of Drugs By Mechanism Pairwise Correlation of BioMAP Reveals Functional Similarities mTOR PKC Activation p38 MAPK HMG-CoA reductase Calcineurin Transcription

9. BioMAP Systems are Validated Corticosteroids (Prednisolone) Are Active in Inflammation Systems Profiles retain shape over multiple concentrations BioMAP Systems Readout Parameters (Biomarkers) Cytotoxicity Readouts Log expression ratio (Drug/DMSO control) Control (no drug) 99% significance envelope Dose Response

10. E-selectin TNF-  IL-8 BioMAP Systems are Validated Activities of Corticosteroids Match Clinical Effects PGE 2 IL-8 MCP-1 Readouts in BioMAP show the same pattern as has been reported for patients receiving steroid therapy Log expression ratio (Drug/DMSO control) MCP-1, IL-8, E-sel. decrease Leukocyte recruitment Many, e.g. Jilma et al., 2000 PGE 2 decrease Pain, swelling Sebaldt et al., 1990 Collagen I & III Collagen I, III decrease Skin atrophy Autio et al., 1994 MMP-1 PAI-1 SAA PAI-1, SAA increase CV complications Sartori et al., 1999 Fyfe et al., 1997 PAI-1

16. Rosiglitazone Upregulation of PGE2 is not a Class Effect Search of BioMAP Database for Compounds that Increase PGE2 Retinoids Microtubule Destabilizers TXA2 inhibitor PPAR  PPAR  RNA Synthesis Inhibitor mTOR Inhibitor AMPK activator JNK Inhibitor CYP450 Inhibitor Compound Specific Effect Mechanism Class Effect