This presentation describes a BioMAP® system in detail. BioMAP® systems are primary human cell-based disease models. The BioMAP® systems platform is a drug discovery technology from BioSeek, LLC

1. Detail of a BioMAP® System
Bridging the Gap From In Vitro to In Vivo
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2. 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 Platform
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3. 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 SM3C
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4. BioMAP® 3C System
System Cell Type Tissue Setting Biomarkers
MCP-1, VCAM, CD141,
Chronic Th1 Inflammation
Endothelial Cells CD142, ICAM, E-selectin,
IL-1b + TNFa + IFNg
uPAR, IL-8, MIG, HLA-DR
3C

5. Chronic Inflammation Model
System Cell Type Tissue Setting Biomarkers
MCP-1, VCAM, CD141,
Chronic Th1 Inflammation
Endothelial Cells CD142, ICAM, E-selectin,
IL-1b + TNFa + IFNg
uPAR, IL-8, MIG, HLA-DR
3C
Multiple
Stroke Sclerosis
Cardiovascular
Disease Arthritis
Autoimmune
Disease
Respiratory
Disease
Heart
Disease COPD

6. Biomarker Readouts Are Disease Relevant
System Cell Type Tissue Setting Biomarkers
MCP-1, VCAM, CD141,
Chronic Th1 Inflammation
Endothelial Cells CD142, ICAM, E-selectin,
IL-1b + TNFa + IFNg
uPAR, IL-8, MIG, HLA-DR
3C
Multiple
Stroke Sclerosis
Cardiovascular
Disease Arthritis
Autoimmune
Disease
Respiratory
Disease
Heart
Disease COPD

7. Biomarkers Cover Diverse Biological Processes
System Cell Type Tissue Setting Biomarkers
MCP-1, VCAM, CD141,
Chronic Th1 Inflammation
Endothelial Cells CD142, ICAM, E-selectin,
IL-1b + TNFa + IFNg
uPAR, IL-8, MIG, HLA-DR
3C
Biomarker Biological Process
MCP-1 Vascular inflammation, monocyte, T cell recruitment
VCAM Chronic inflammation, redox stress; monocyte, T cell recruitment
CD141/Thrombomodulin Fibrinolysis, thrombosis (-)
CD142/Tissue Factor Angiogenesis, coagulation, thrombosis
ICAM Acute and chronic inflammation; leukocyte adhesion and recruitment
E-Selectin Leukocyte adhesion, neutrophil recruitment, skin T cell recruitment
CD87/uPAR Cell migration, proliferation, angiogenesis
IL-8 Acute inflammation, neutrophil recruitment, angiogenesis
MIG Chronic inflammation, T cell recruitment, angiogenesis (-)
HLA-DR Th1 immune responses, infection, antigen presentation

8. Biomarkers Cover Diverse Clinical Indications
System Cell Type Tissue Setting Biomarkers
MCP-1, VCAM, CD141,
Chronic Th1 Inflammation
Endothelial Cells CD142, ICAM, E-selectin,
IL-1b + TNFa + IFNg
uPAR, IL-8, MIG, HLA-DR
3C
Biomarker Clinical Indications (Biomarker or Risk Factor)
MCP-1 Acute coronary syndrome, Atherosclerosis, Diabetes, Heart disease
VCAM Atherosclerosis, Multiple sclerosis, Rheumatoid arthritis, Diabetes
CD141/Thrombomodulin Coronary artery disease, Lupus, Stroke, Vasculitis
CD142/Tissue Factor Coronary Artery Disease, Stroke, Myocardial Infarction
ICAM Infection, Acute inflammation, Multiple sclerosis
E-Selectin Psoriasis, Diabetes, Cancer
CD87/uPAR Atherosclerosis, Cancer, COPD, Restenosis
IL-8 COPD, Lung cancer (NSCLC), Rheumatoid arthritis, Ulcerative colitis
MIG Transplant rejection, Pulmonary sarcoidosis
HLA-DR Rheumatoid arthritis, Lupus, Multiple sclerosis, Transplant rejection

9. Biomarker Levels are Modulated by Drugs
System Cell Type Tissue Setting Biomarkers
MCP-1, VCAM, CD141,
Chronic Th1 Inflammation
Endothelial Cells CD142, ICAM, E-selectin,
IL-1b + TNFa + IFNg
uPAR, IL-8, MIG, HLA-DR
3C
MCP-1
VCAM
Thrombomodulin
Tissue Factor
ICAM
E-selectin Drug
uPAR Control
IL-8
Mig
HLA-DR
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6
Relative Level of Protein Expression

10. Pattern of Biomarker Level Changes -> Profile
Example: p38 MAPK inhibitor
BioMAP System Significant Increase
3C in Biomarker Level
(Drug/DMSO control)
Log expression ratio 99% Significance Envelope
Significant
Decrease in
Biomarker Level
Control
(no drug)
Drug
Control
Biomarkers (Readout
Parameters)
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11. Pattern of Biomarker Level Changes -> Profile
Example: p38 MAPK inhibitor
BioMAP System Significant Increase
3C in Biomarker Level
(Drug/DMSO control)
Log expression ratio 99% Significance Envelope
Significant
Decrease in
Biomarker Level
Control
(no drug)
Drug
Control
Biomarkers (Readout
Parameters)
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12. BioMAP® Profile of a p38 MAP Kinase Inhibitor
BioMAP System
3C
(Drug/DMSO control)
Log expression ratio 99% Significance Envelope
Dose
Control
Response
(no drug)
Drug
Biomarkers (Readout
Parameters)
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13. Biomarkers Provide Insight on Biological Processes
3C Monocyte recruitment into
MCP-1
inflammatory tissues
(Drug/DMSO control)
Log expression ratio
Tissue Platelet activation and
Factor thrombosis
Antigen presentation and T cell
HLA-DR
activation
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14. Biomarkers Provide Insight on Disease Indications
Acute coronary
3C
MCP-1 syndrome, Atherosclerosis, Dia
(Drug/DMSO control)
Log expression ratio
betes, Heart Disease
Coronary artery
Tissue
disease, Myocardial
Factor
infarction, Stroke
Rheumatoid
HLA-DR arthritis, Lupus, Multiple
Sclerosis, Transplant rejection
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15. In Vivo Confirmation of BioMAP® Biomarkers
Example: p38 MAPK Inhibitor
Sheryanna A, et al. Inhibition of p38 mitogen-
activated protein kinase is effective in the
3C treatment of experimental crescentic
MCP-1 glomerulonephritis and suppresses monocyte
(Drug/DMSO control)
Log expression ratio
chemoattractant protein-1 but not IL-1beta or IL-6.
J Am Soc Nephrol. 2007, 18:1167-79.
Sakurai K, et al. Role of p38 mitogen-activated
Tissue protein kinase in thrombus formation. J Recept
Factor Signal Transduct Res. 2004, 24:283-96.
Wada T, et al. Reduction in chronic allograft
HLA-DR nephropathy by inhibition of p38 mitogen-activated
protein kinase. Am J Nephrol. 2006, 26:319-25.
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16. Contacts
Ellen L. Berg, PhD
General Manager, BioSeek LLC
650-416-7621
eberg@bioseekinc.com
www.bioseekinc.com
Bridging the Gap From In Vitro to In Vivo
BioSeek, LLC
310 Utah, #100
South San Francisco, CA 94080