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This is an introduction to the BioMAP® Systems technology platform from BioSeek, LLC
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Bridging the Gap From In Vitro to In Vivo
Introduction to BioMAP® Systems
BioMAP® Systems Model Complex Biology
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BioMAP® Technology Platform
BioMAPAssay Systems
ReferenceProfile Database
Predictive Informatics Tools
Human primary cells Disease-models
30+ systems
Biomarker responses to drugs are stored in the
database
Specialized informatics tools are used to predict
clinical outcomes
Human Biology Integrated into a Robust, Scalable Platform
Human primary cell-based assays Engineered to model complex human disease biology
BioMAP® Systems
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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 drugs
LPS SAg HPNo
3C 4H
Mphg BT
HTh2HSM3C
HDF3CGFHDF3C HDFNo
HDF3CTHDFT
BF4T SM3C
BE3C BE4T
K3CT MyoF
KFNoKF3CT
Primary Human Cell Types Disease Relevance BioMAP*
Endothelial cells (EC)Th1 and Th2 inflammation, allergy, asthma, dermatitis, angiogenesis, wound healing, restenosis, atherosclerosis
EC+lymphocyte+monocytesTh1 inflammation, psoriasis, COPD fibrosis, monocyte and T cell responses
EC+Macrophages Macrophage responses, arthritis, COPD, fibrosis
B cells + T cells Immune responses
EC+Smooth Muscle Cells Vascular inflammation, restenosis, atherosclerosis
EC+Th2 blasts Allergy, asthma
FibroblastsArthritis, asthma, dermatitis, fibrosis, psoriasis, wound healing
Myofibroblasts Fibrosis, COPD, wound healing
Keratinocytes Psoriasis, dermatitis, wound healing
Keratinocytes+Fibroblasts Psoriasis, dermatitis, wound healing
Bronchial Epithelial CellsTh1 and Th2 inflammation Allergy, asthma, fibrosis, COPD
Bronchial Epithelial Cells +Fibroblasts Asthma, allergy, fibrosis, COPD
Smooth Muscle Cells Vascular inflammation, asthma, COPD, fibrosis
Current Validated BioMAP® Systems
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BioMAP® Assay Development Pipeline
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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 myofibroblasts
Informatics and Data Analysis
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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 curves
BioMAP® Analysis of Prednisolone
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BioMAP Systems
Readout Parameters (Biomarkers)
Cytotoxicity Readouts
Log
expr
essi
on ra
tio (D
rug/
DM
SO c
ontr
ol)
Control (no drug)
99% significance envelope
DoseResponse
Each Drug Induces a Signature ProfileProfiles retain shape over multiple concentrations
BioMAP® Analysis of Prednisolone - Clinical Validation
E-selectin
TNF-
IL-8
PGE2
IL-8MCP-1
MCP-1, IL-8, E-sel. decreaseLeukocyte recruitment
Many, e.g. Jilma et al., 2000
PGE2 decreasePain, swelling
Sebaldt et al., 1990
Collagen I & III
Collagen I, III decreaseSkin atrophy
Autio et al., 1994
MMP-1
PAI-1
SAA
PAI-1, SAA increaseCV complications
Sartori et al., 1999Fyfe et al., 1997
PAI-1
BioMAP® Profiling Can Bridge the Gap from In Vitro to In Vivo
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MicrotubuleStabilizers
Mitochondrial ET chain
Retinoids
Hsp90
CDK
NFkB
MEK
DNAsynthesis
JNK
Proteinsynthesis
MicrotubuleDestabilizers
Estrogen R
PI-3K
Ca++
Mobilization
BioMAP® Analysis Reveals Mechanism of ActionPairwise Correlation of BioMAP Reveals Functional Similarities
mTOR
PKC Activation
p38 MAPK
HMG-CoAreductase
Calcineurin
Transcription
Mechanism of Action(On-Target)
PathwayRelationships
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BioMAP® Reference Database
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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 receptors
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 markers 1212
Bridging the Gap From In Vitro to In Vivo
Contacts
Ellen Berg, PhD
General Manager
BioSeek, LLC
650-416-7621
BioSeek, LLC310 Utah, #100South San Francisco, CA 94080
