® TitleBioMAP goes EChere50 ELECT BridgingTagline goes the Gaphere from In Vitro to In Vivo

Picture goes here

Quantitate compound effects in any available BioMAP System EC50 Analysis of Prednisolone readout. Activity-based assays provide EC50 values, which are defined as a measure of a compound’s effectiveness 1.0 in modulating a specific phenotypic endpoint and the concentration of compound required to reduce (or increase) 0.9 the activity by 50%. EC50 values are determined from triplicate 7-point dose-response curves. Measurements are made under 0.8 optimized conditions that facilitate direct comparison of (Drug/Control) compounds. 0.7 Ratio of Biomarker Readout Levels BioMAP EC ELECT may be used as a follow-up study tool to 0 1 2 3 4 50 10 10 10 10 10 quantify activities identified in BioMAP profiling, to supplement Compound Concentration, nM existing data, or to support lead optimization and SAR.

EC50 curve for inhibition of the biomarker readout PGE2 by prednisolone, 2 measured in the BioMAP sLPS system. EC50 = 32 nM, R = 0.97. DRUG DISCOVERY APPLICATIONS

• Follow up studies from Diversity PLUS™ or Predictive Tox Panel

• Quantitative EC50 determination • Compound prioritization and lead optimization

EC50 ELECT ADVANTAGES

• Quantify compound potency in human primary cells

• Select from a menu of over 500 readouts in >40 systems

• Rapid turnaround time

BioMAP EC50 ELECT

Service EC50 determination on any individual BioMAP System readout 7 concentrations in triplicate

2 Deliverables Study Report: EC50 curve image for each BioMAP System readout, confidence interval, Hill slope, R

Data Report: EC50 and log ratio data tables with metrics (average and standard deviation)

www.biomapsystems.com www.discoverx.com ® TitleBioMAP of filyer EC50 secondELECT page

BioMAP Systems ELECT Systems Primary Human System Cell Types Disease /Tissue Relevance Readouts

Cardiovascular Disease, Chronic MCP-1, VCAM-1, TM, TF, ICAM-1, E-selectin, uPAR, IL-8, Venular endothelial cells Inflammation MIG, HLA-DR, Proliferation, SRB 3C

Venular endothelial cells Asthma, Allergy, Oncology MCP-1, Eotaxin-3, VCAM-1, P-selectin, uPAR, SRB, VEGFRII

4H

Peripheral blood mononuclear cells + Venular Cardiovascular Disease, Chronic MCP-1, VCAM-1, TM, TF, CD40, E-selectin, CD69, IL-8, IL- endothelial cells Inflammation 1α, M-CSF, sPGE2, SRB, sTNFα LPS

Peripheral blood mononuclear cells + Venular Autoimmune Disease, Chronic MCP-1, CD38, CD40, E-selectin, CD69, IL-8, MIG, PBMC endothelial cells Inflammation Cytotoxicity, Proliferation, SRB SAg

Asthma, Allergy, Oncology, B cell Proliferation, PBMC Cytotoxicity, Secreted IgG, sIL- B cells + Peripheral blood mononuclear cells Autoimmunity 17A, sIL-17F, sIL-2, sIL-6, sTNFα BT

ICAM-1, uPAR, IP-10, I-TAC, IL-8, MIG, EGFR, HLA-DR, IL- Bronchial epithelial cells COPD, Lung Inflammation 1α, Keratin 8/18, MMP-1, MMP-9, PAI-1, SRB, tPA, uPA BE3C

MCP-1, Eotaxin-3, VCAM-1, ICAM-1, CD90, IL-8, IL-1α, Bronchial epithelial cells + Dermal fibroblasts Asthma, Allergy, Fibrosis, Lung Keratin 8/18, MMP-1, MMP-3, MMP-9, PAI-1, SRB, tPA, uPA BF4T

MCP-1, VCAM-1, ICAM-1, Collagen I, Collagen III, IP- Dermal Fibroblasts Fibrosis, Chronic Inflammation 10, I-TAC, IL-8, MIG, EGFR, M-CSF, MMP-1, PAI-1, Proliferation_72hr, SRB, TIMP-1, TIMP-2 HDF3CGF

Keratinocytes + Psoriasis, Dermatitis, Skin MCP-1, ICAM-1, IP-10, IL-8, MIG, IL1α, MMP-9, PAI-1, SRB, Dermal fibroblasts Biology TIMP-2, uPA KF3CT

Cardiovascular Inflammation, MCP-1, VCAM-1, TM, TF, uPAR, IL-8, MIG, HLA-DR, IL-6, Coronary artery smooth muscle cells Restenosis LDLR, M-CSF, PAI-1, Proliferation, SAA, SRB CASM3C

Fibrosis, Chronic Inflammation, α-SM Actin, bFGF, VCAM-1, Collagen I, Collagen III, Collagen Lung fibroblasts Wound Healing, Matrix IV, IL-8, Decorin, MMP-1, PAI-1, SRB, TIMP-1 Remodeling MyoF

Cardiovascular Inflammation, MCP-1, MIP-1α, VCAM-1, CD40, E-selectin, CD69, IL-8, IL- Venular endothelial cells + macrophages Restenosis, Chronic 1α, M-CSF, sIL-10, SRB, SRB-Mphg Inflammation lMphg

Eotaxin-3, ICAM-1, uPAR, IP-10, I-TAC, IL-8, MIG, EGFR, Bronchial epithelial cells Epithelial, Lung Biology HLA-DR, IL1α, Keratin 8/18, MMP-1, MMP-9, PAI-1, SRB, uPA, tPA BENo

310 Utah Ave. Suite 100 South San Francisco, CA 94080 • tel | 1.510.979.1415 or +44.121.260.6142 • web | www.biomapsystems.com ® TitleBioMAP of filyer EC50 secondELECT page

BioMAP Systems ELECT Systems Primary Human System Cell Types Disease /Tissue Relevance Readouts

B cell Proliferation, PBMC Cytotoxicity, Secreted IgG, sIL- B cells + Peripheral blood mononuclear cells B and T Cell Biology 17A, sIL-17F, sIL-2, sIL-6, sTNFα

BTNo

MCP-1, ICAM-1, IP-10, IL-8, MIG, IL1α, MMP-9, PAI-1, SRB, Keratinocytes + Dermal Fibroblasts Skin Biology TIMP-2, uPA KFNo

MCP-1, ICAM-1, IP-10, IL-8, MIG, IL-1α, MMP-9, PAI-1, SRB, Keratinocytes Psoriasis, Dermatitis, Skin TIMP-2, uPA

K3CT

MCP-1, VCAM-1, ICAM-1, Collagen I, Collagen III, IP- Dermal Fibroblasts Fibrosis, Chronic Inflammation 10, I-TAC, IL-8, MIG, EGFR, M-CSF, MMP-1, PAI-1, Proliferation_72hr, SRB, TIMP-1, TIMP-2 HDF3C

MCP-1, VCAM-1, ICAM-1, Collagen 1, IP-10, IL-8, MIG, Dermal Fibroblasts Fibrosis, Chronic Inflammation M-CSF, MMP-1, PAI-1, SRB, TIMP-2

HDF3CT

MCP-1, VCAM-1, ICAM-1, Collagen I, Collagen III, IP- Dermal Fibroblasts Fibroblast Biology 10, I-TAC, IL-8, MIG, EGFR, M-CSF, MMP-1, PAI-1, Proliferation_72hr, SRB, TIMP-1, TIMP-2 HDFNo

Dermal Fibroblasts Fibrosis, Chronic Inflammation Collagen I, Collagen III, PAI-1, SRB, TIMP-1, TIMP-2

HDFT

Autoimmune Disease, Chronic MCP-1, VCAM-1, Collagen I, IP-10, MMP-1, sIL10, sIL17A, Dermal Fibroblasts + PBMC Inflammation, Infection sIL17F, sIL-2, sIL-6, SRB, sTGFb, sTNFa, sVEGF, IL-8, MIG, responses MCSF HDFLPS

Autoimmune Disease, Chronic MCP-1, VCAM-1, Collagen I, IP-10, MMP-1, sIL10, sIL17A, Dermal Fibroblasts + PBMC Inflammation, Rheumatoid sIL17F, sIL2, sIL-6, SRB, sTGFb, sTNFa, sVEGF, IL-8, MIG, Arthritis MCSF HDFSAg

α-SM Actin, bFGF, VCAM-1, Collagen I, ColIagen III, Lung fibroblasts Fibroblast Biology Collagen IV, IL-8, Decorin, MMP-1, PAI-1, SRB, TIMP-1

MyoFNo

Cardiovascular Disease, Chronic MCP-1, VCAM-1, TM, TF, ICAM-1, E-selectin, uPAR, IL-8, Coronary artery endothelial cells Inflammation MIG, HLA-DR, PAI-1, Proliferation, SRB CAEC3C

MCP-1, VCAM-1, Collagen I, IP-10, MMP-1, sIL10, sIL17A, Dermal Fibroblasts + PBMC Immune sIL17F, sIL-2, sIL-6, SRB, sTGFb, sTNFa, sVEGF, IL-8, MIG, MCSF HDFPNo

310 Utah Ave. Suite 100 South San Francisco, CA 94080 • tel | 1.510.979.1415 or +44.121.260.6142 • web | www.biomapsystems.com ® TitleBioMAP of filyer EC50 secondELECT page

BioMAP Systems ELECT Systems Primary Human System Cell Types Disease /Tissue Relevance Readouts

Cardiovascular Disease, Chronic MCP-1, VCAM-1, TM, TF, ICAM-1, E-selectin, uPAR, IL-8, Venular endothelial cells Inflammation MIG, HLA-DR, Proliferation, SRB

l3C

Venular endothelial cells Asthma, Allergy, Oncology MCP-1, Eotaxin-3, VCAM-1, P-selectin, uPAR, SRB, VEGFRII

l4H

MCP-1, VCAM-1, TM, TF, ICAM-1, E-selectin, uPAR, IL-8, Venular endothelial cells Vascular Biology MIG, HLA-DR, Proliferation, SRB

HNo

Peripheral blood mononuclear cells + Venular Vascular Biology, Immune MCP-1, VCAM-1, TM, TF, CD38, CD40, E-selectin, CD69, endothelial cells Biology IL-8, MIG, M-CSF, sPGE2, SRB, sTNFα HPNo

Peripheral blood mononuclear cells + Venular Vascular Biology, Immune MCP-1, VCAM-1, TM, TF, CD38, CD40, E-selectin, CD69, endothelial cells Biology IL-8, MIG, M-CSF, sPGE2, SRB, sTNFα

lHPNo

Peripheral blood mononuclear cells + Venular Cardiovascular Disease, Chronic MCP-1, VCAM-1, TM, TF, CD40, E-selectin, CD69, IL-8, endothelial cells Inflammation IL1α, M-CSF, sPGE2, SRB, sTNFα

lLPS

Peripheral blood mononuclear cells + Venular Autoimmune Disease, Chronic MCP-1, CD38, CD40, E-selectin, CD69, IL-8, MIG, PBMC endothelial cells Inflammation Cytotoxicity, Proliferation, SRB lSAg

MCP-1, Eotaxin-3, VCAM-1, CD38, CD40, E-selectin, Venular endothelial cells + TH2 blasts Asthma, Allergy, Oncology P-selectin, CD69, uPAR, Collagen IV, IL-8, MIG, PBMC Cytotoxicity, sIL-17A, sIL-17F, SRB lTH2

MCP-1, Eotaxin-3, VCAM-1, CD38, CD40, E-selectin, Vascular Biology, Immune Venular endothelial cells + TH2 blasts P-selectin, CD69, uPAR, Collagen IV, IL-8, MIG, PBMC Biology Cytotoxicity, sIL17A, sIL17F, SRB lTH2No

Vascular Biology, Immune MCP-1, MIP-1α, VCAM-1, CD40, E-selectin, CD69, IL-8, IL- Venular endothelial cells + M1 macrophages Biology 1α, M-CSF, SRB, SRB-Mphg lMphgNo

MCP-1, VCAM-1, TM, TF, uPAR, IL-8, MIG, HLA-DR, IL-6, Coronary artery smooth muscle cells Vascular Biology LDLR, M-CSF, PAI-1, Proliferation, SAA, SRB CASMNo

310 Utah Ave. Suite 100 South San Francisco, CA 94080 • tel | 1.510.979.1415 or +44.121.260.6142 • web | www.biomapsystems.com ® TitleBioMAP of filyer EC50 secondELECT page

BioMAP Systems ELECT Systems Primary Human System Cell Types Disease /Tissue Relevance Readouts

MCP-1, VCAM-1, TM, TF, uPAR, Collagen I, Collagen IV, Cardiovascular Inflammation, Vascular smooth muscle cells IL-8, MIG, HLA-DR, IL-6, LDLR, M-CSF, PAI-1, Proliferation, Restenosis SAA, SRB SM3C

Skeletal Muscle Cells Muscle Glycogen, SRB

SkMC

αSMA, MCP-1, VCAM, Collagen I, Collagen III, ITAC, EGFR, Renal Proximal Tubule Epithelial Cells + Renal Fibrosis Ker8/18, MMP-1, MMP-9, PAI-I, sIL-6, sIL-8, SRB, sVEGF, tPA, Lung Fibroblasts uPA, E-cadherin, N-cadherin REMyoF

VCAM-1, uPAR, Collagen I, Collagen III, IP-10, MMP-9, PAI-1, HT-29 colon Adenocarcinoma cell line + Oncology: Host Tumor-Stromal PBMC Cytotoxicity, sGranzyme B, sIFNγ, sIL10, sIL17A, sIL-2, Primary Human Fibroblasts + PBMC Microenvironment sIL-6, SRB, sTNFα, sVEGF, TIMP2, tPA, uPA, CEA, CK20 StroHT29

MCP-1, VCAM-1, CD40, CD69, uPAR, Collagen IV, IP-10, HT-29 colon Adenocarcinoma cell line + Oncology: Host Tumor-Vascular MIG, PBMC Cytotoxicity, sGranzyme B, sIFNγ, sIL10, sIL17A, Primary Human Endothelial cells + PBMC Microenvironment sIL-2, sIL-6, SRB, sTNFα, CEA, CK20 VascHT29

αSM-Actin, MCP-1, VCAM, Collagen I, Collagen III, ITAC, Renal proximal tubule epithelial cells + Lung Renal Epithelial Cell Biology EGFR, Ker8/18, MMP-1, MMP-9, PAI-I, sIL-6, sIL-8, SRB, fibroblasts sVEGF, tPA, uPA, E-cadherin, N-cadherin REMyoFNo

MCP-1, VCAM-1, TM, TF, CD40, ICAM-1, E-selectin, uPAR, Venular endothelial cells + Vascular smooth Cardiovascular Inflammation, Collagen I, Collagen IV, IL-8, MIG, Endothelin-1, HLA-DR, muscle cells Restenosis LDLR, M-CSF, PAI-1, SAA, SRB HSM3C

© 2013 DiscoveRx Corporation. All Rights Reserved. DiscoveRx logo, DiscoveRx, BioMAP and BioSeek are registered trademarks of DiscoveRx Corporation. 100913

310 Utah Ave. Suite 100 South San Francisco, CA 94080 • tel | 1.510.979.1415 or +44.121.260.6142 • web | www.biomapsystems.com