The Market for Circulating Tumor Cells (CTCs) and Cancer Stem Cells (CSCs)

Table of Contents

ONE: EXECUTIVE SUMMARY

Circulating Tumor Cells in Cancer

Current and Potential Clinical Applications of CTCs

CTCs Detection, Isolation and Analysis Technologies

Industry and Market Structure

TWO: CANCER OVERVIEW

Disease Overview

Risk Factors

Prevalence and Incidence of Cancer

THREE: CIRCULATING TUMOR CELLS OVERVIEW

Overview

CTCs Applications

Characteristics of CTCs

CTCs Isolation and Characterization Challenges

Current Markers for CTCs Identification and Analysis

Epithelial Cell Adhesion Molecule (EpCAM)

Ephrin Receptor B4 (EpB4)

Epidermal Growth Factor Receptor (EGFR)

Human Epidermal Growth Factor (HER2)

Mucin-1 (MUC-1)

Carcinoembryonic Antigen (CEA)

Cytokeratins

Other CTCs Markers Investigated for Clinical Applications

Cyclophilins

Plastin3 (PLS3)

Vimentin

Conclusions

Current and Potential Clinical Applications of CTCs

Prognostic Tool for Survival

Non-Invasive Early Diagnosis of Cancer

Predictors of Disease Evolution and Metastatic Potential

Therapy Guidance and Monitoring/ Predictor of Response to Therapy

Patient Stratification in Clinical Trials

Surrogate Endpoint in Clinical Trials

Drug Development – Selection of Drug Targets

FOUR: CTCs ISOLATION AND DETECTION TECHNOLOGIES

Overview

Enrichment Methods Based on Physical Properties

Size-based Methods

Density-based Methods

Electrophysiological-based Methods

Immuno-Mediated Capture Methods

Magnetic Platforms

Microfluidic Platforms

Conclusion

Optical Identification and Enumeration

Bioview’s Duet Cell Imaging System (Israel)

CytoTrack’s Optical Scanning Technology (Denmark)

Epic Sciences (San Diego, California, USA)

Ikonisys (New Haven, CT, USA)

Nucleic Acid-based CTC Detection Methods

RNAscope (Advanced Cell Diagnostics, USA)

Cytometric Detection and Enumeration Methods

FASTcell Cytometer (SRI Biosciences, USA)

On-chip Sort Cell Sorter (On-chip Biotechnologies, Japan)

Other CTCs Isolation and Detection Approaches

Virus Vectors Fluorescence

Selectin-Mediated Capture

Cell Adhesion Matrix

Other Combination Negative Depletion/ Positive Selection Methods

Rheology-based Methods

In Vivo Detection Methods

FIVE: INDUSTRY AND MARKET LANDSCAPE

Industry Structure

Competitive Factors

Products Analysis

CellSearch

AdnaTests

Significant Market Trends

Increasing Incorporation of CTCs Technologies in Clinical Trials to Accelerate

Market Growth

The Quest for Personalized Medicine to Spur the Use of CTCs in Research &

Development

Increasing Development of CTC-based Diagnostics Tests to Augment Market

Revenues

Increasing Global Incidence of Cancer and Life Expectancy to Increase Testing

Volumes

The Impact of Clinical Utility on Adoption of CTCs Tests in Clinical Practice

The Impact of New Technologies Approved by Regulatory Agencies on Market

Growth

The Impact of Insurance Coverage on Utilization and Market Revenues

Notable Industry Events

CTCs Enumeration by CellSearch Demonstrated Potential as Efficacy-Response

Surrogate

The Menarini Group Acquired Silicon Biosystems

Cynvenio Biosystems Launched ClearID Breast Cancer Monitoring Test

Vitatex Licenses Cell Adhesion Matrix Technology to Noble Life Sciences

SWOG S0500 Clinical Trial Results Presented in December 2013

Parsorter PS1 Launched to Market in Europe

Clearbridge Biomedics Launched the ClearCell FX System for Capturing CTCs in

Whole Blood Samples

Fluxion Biosciences Launched Next Generation Sequencing Assay Kits for IsoFlux

System

Janssen Diagnostics and Asuragen Introduce NGS technology for CellSearch

Biocept Collaborates with Rosetta Genomics to Evaluate CTCs’ microRNA

Biocept Launches Lung Cancer CTC Tests

Parsortix Collaborates with EKF Diagnostics and Undisclosed Pharmaceutical

Company to Develop “Liquid Biopsy” Applications

ThermoFisher Scientific Enters into Distribution Agreement with Cynvenio

Biosystems for LiquidBiopsy Platform

QIAGEN Acquired AdnaGen’s CTC’s Technology

Total Market Revenues and Forecast

Market Snapshot

Total Market Forecast

SIX: COMPANY PROFILES

Janssen Diagnostics

AdnaGen AG (currently QIAGEN Hannover GmbH)

Acousys Biodevices, Inc.

Advanced Cell Diagnostics, Inc.

ApoCell, Inc.

BioCEP Ltd.

Biocept, Inc.

Biofluidica

BioView Ltd.

Clearbridge Biomedics Pte Ltd

Creatv MicroTech, Inc.

Cynvenio Biosystems

CytoTrack ApS

DeNovo Sciences Inc.

Epic Sciences

Fluidigm Corporation

Fluxion Biosciences

GILUPI GmbH

iCellate Medical AB

Ikonisys, Inc.

IVDiagnostics, LLC

Miltenyi Biotec GmbH

On-chip Biotechnologies

Oncolys Biopharma Inc.

Parsortix/ANGLE plc

QIAGEN N.V.

RareCells Diagnostics

RareCyte, Inc.

ScreenCell

Silicon Biosystems

SRI Biosciences

Vitatex Inc.

Vortex Biosciences

LIST OF EXHIBITS

TWO: CANCER OVERVIEW

Table 2-1: Top Ten Causes of Death in the World by Geographic Region, 2012

Table 2-2: Top Ten Causes of Death in the World, 2012

Table 2-3: Projected Top Ten Causes of Death in the World, 2015

Table 2-4: Projected Top Ten Causes of Death in the World in High Income Countries, 2015

Table 2-5: Projected Top Ten Causes of Death in the World in Upper Middle Income Countries, 2015

Table 2-6: Global Incidence of Cancer by Geographic Region, 2012

Table 2-7: Global Incidence of the Five Most Common Types of Cancer in Men,2012

Table 2-8: Global Incidence of the Five Most Common Types of Cancer in Women, 2012

Table 2-9: Global Incidence of Most Common Types of Cancer in Both Genders,2012

Table 2-10: Projected Growth in Global Incidence of Cancer by Geographic Region, 2012-2030

THREE: CIRCULATING TUMOR CELLS OVERVIEW

Table 3-1: Typical Human Blood Cellular Composition

Table 3-2: Challenges in the Detection and Isolation of CTCs, 2015

Table 3-3: Selected Markers for CTCs Identification and Analysis

Table 3-4: Selected EpCAM-based Methods

Table 3-5: Current and Potential Clinical Uses of CTCs, 2015

FOUR: CTCs ISOLATION AND DETECTION TECHNOLOGIES

Table 4-1: Selected Size-Based CTCs Enrichment Methods

Table 4-2: Selected Density-Based CTCs Enrichment Methods

Table 4-3: Selected CTCs Detection and Isolation Methods Based on

Electrophysiological Properties

Table 4-4: Selected CTCs Magnetic Platforms Based on Cell Surface Markers

Table 4-5: Selected CTCs Immunomagnetic Microfluidics Platforms

Table 4-6: Selected CTCs Optical Identification Methods

Table 4-7: Selected Nucleic Acid-based CTCs Detection Methods

Table 4-8: Comparison of Selected Cytometric CTCs Detection Methods

Table 4-9: Selected CTCs In Vivo Detection Platforms

FIVE: INDUSTRY AND MARKET LANDSCAPE

Table 5-1: Industry Structure – Selected Competitors and Marketed Products, 2014

Table 5-2: CellSearch System (IVD Use) Analysis, 2015

Table 5-3: AdnaTest (IVD Use) Analysis, 2015

Table 5-4: Significant Trends in the CTCs Market, 2015

Figure 5-1: Estimated Market Breakdown, 2014 (Research Segment, Diagnostics Segment)

Figure 5-2: Estimated Market Breakdown by Type of Cancer, 2014 (Breast,

Prostate, Colorectal, Lung, Others)

Figure 5-3: Estimated Market Breakdown by Geographic Region, 2014 (US, EU, ROW)

Table 5-5: Global Revenues and Forecast for the CTCs Market by Application, 2013-2015 and 2019 (Diagnostics Segment, Research Segment, Total Market)

Figure 5-4: Global Revenues and Forecast for the CTCs Market, 2013-2015 and 2019 (Diagnostics Segment, Research Segment, Total Market)

Table 5-6: Global Revenues for the CTCs Market by Geographic Region, 2013-2015 and 2019 (US Market, EU Market, ROW Market, Total Market)

Figure 5-5: Global Revenues for the CTCs Market by Geographic Region, 2013- 2015 and 2019 (US Market, EU Market, ROW Market, Total Market)