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TriMark Publications January 2016 Volume: TMRCDTWM16-0101 CANCER DIAGNOSTIC TESTING WORLD MARKETS (SAMPLE COPY, NOT FOR RESALE) Trends, Industry Participants, Product Overviews and Market Drivers

CANCER DIAGNOSTIC TESTING WORLD MARKETS Siemens Healthcare Diagnostics ADVIA Centaur CP Immunoassay System, the ADVIA Centaur XP ... Cancer Diagnostic Testing World Markets January

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Page 1: CANCER DIAGNOSTIC TESTING WORLD MARKETS Siemens Healthcare Diagnostics ADVIA Centaur CP Immunoassay System, the ADVIA Centaur XP ... Cancer Diagnostic Testing World Markets January

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January 2016

Volume: TMRCDTWM16-0101

CANCER DIAGNOSTIC TESTING WORLD MARKETS (SAMPLE COPY, NOT FOR RESALE)

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Page 2: CANCER DIAGNOSTIC TESTING WORLD MARKETS Siemens Healthcare Diagnostics ADVIA Centaur CP Immunoassay System, the ADVIA Centaur XP ... Cancer Diagnostic Testing World Markets January

Cancer Diagnostic Testing World Markets January 2016

© 2016 TriMark Publications, LLC. All rights reserved. 1 www.trimarkpublications.com

TABLE OF CONTENTS 1. Overview 7 1.1 Statement of Report 7 1.2 About This Report 7 1.3 Scope of the Report 9 1.4 Objectives 9 1.5 Methodology 9 1.6 Executive Summary 11 2. Introduction to Cancer Biology and the Diagnostic Industry 17 2.1 Cancer 17 2.1.1 The Disease 17 2.1.2 Metastasis 18 2.1.3 Demographics and Statistics of Cancer 18 2.2 The Drivers of the Biotech and Diagnostics Industry 23 2.2.1 Technological Innovation 25 2.2.2 Government Funding 25 2.3 Outlook for Tumor Markers 25 3. Tumor Markers Market Segment Analysis: Size, Growth and Share 28 3.1 Market Description 29 3.2 Clinical Diagnostic Serum-based Cancer Markers 36 3.3 PSA Testing Market Size 36 3.4 DNA Markers 38 3.5 Serum Proteins 38 3.6 Enzymes 39 3.7 Occult Blood 39 3.8 Histology and In Situ Hybridization (ISH) 39 3.9 Cervical Cytology 40 3.10 Immunohistochemistry (IHC) 42 3.11 In Vivo Detection Cancer Products 43 3.12 Radionuclides and X-Ray Detection Products 43 3.13 HPV Testing 43 3.14 Bladder Cancer Testing 46 3.15 Tumor Assays for Adjuvant Chemotherapy 49 4. Diagnostic Methods for Cancer Detection 60 4.1 Organ-Specific Tumor Markers 60 4.1.1 Colon Cancer 60 4.1.2 Prostate Cancer 70 4.1.3 Pancreatic Cancer 104 4.1.4 Breast Cancer 108 4.1.5 Ovarian Cancer 121 4.1.6 Cervical Cancer 127 4.1.7 Lung Cancer 132 4.1.8 Testicular Cancer 144 4.1.9 Bladder Cancer 145 4.1.10 Hepatic Cancer 153 4.1.11 Stomach Cancer 156 4.1.12 Malignant Melanoma 157 4.1.13 Acute Myeloid Leukemia (AML) and Acute Lymphoblastoid Leukemia (ALL) 158 4.1.14 Lymphoma 159 4.2 Clinical Laboratory Methods for Measuring Tumor Markers 159 4.2.1 Abbott Diagnostics 159

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Cancer Diagnostic Testing World Markets January 2016

© 2016 TriMark Publications, LLC. All rights reserved. 2 www.trimarkpublications.com

4.2.2 Roche Diagnostics Systems 160 4.2.3 Beckman Coulter Diagnostics Immunoassay Systems 160 4.2.4 Siemens Healthcare Diagnostics ADVIA Centaur CP Immunoassay System, the ADVIA Centaur XP Immunoassay System and ADVIA Centuar XPT Immunoassay System 161 4.2.5 Tosoh Bioscience AIA-2000 162 4.2.6 Thermo Fisher Scientific B.R.A.H.M.S. KRYPTOR 162 4.2.7 Ortho-Clinical Diagnostics Vitros ECiQ (Johnson and Johnson) 163 4.2.8 Fujirebio Diagnostics, Inc. 163 4.2.9 bioMérieux Vidas 164 4.3 New Technologies for Cancer Diagnostics 165 4.3.1 New and Improved Immunoassays 165 4.3.2 IHC Tests 166 4.3.3 Molecular (DNA and Genomic) Diagnostic Assays 167 4.3.4 Genomics and Genetic Markers 167 4.3.5 Proteomics and New Protein Markers 169 4.3.5.1 Inside the ProteinChip System 169 4.3.5.2 Rapid Biological Assays on a Chip 170 4.3.5.3 Proteome Pattern Recognition 170 4.3.6 New Platform Technologies Including Flow Cytometry 170 4.3.7 Stem Cell Markers 173 4.3.8 mAbs 174 4.3.9 Pharmacogenomics and Oncology Diagnostics 175 4.3.10 DNA Microarrays 177 4.3.11 In Vitro Diagnostic Multivariate Index Assays (IVDMIA) 180 4.3.12 Prostate-63 180 4.3.13 Future Directions 180 5. Companies Entering the Cancer Diagnostics Market with Novel Technology Platforms 181 5.1 Abbott Diagnostics 181 5.2 Agendia BV 184 5.3 bioMérieux 185 5.4 DRG International, Inc. 185 5.5 Eisai Co., Ltd. 186 5.6 Exact Sciences Corporation 187 5.7 Fujirebio Diagnostics, Inc. 187 5.8 Genomic Health, Inc. 188 5.9 Hologic, Inc. 189 5.10 LabCorp 192 5.11 Myriad Genetics, Inc. 193 5.12 Neogenomics 195 5.13 Roche 195 5.14 Siemens 197 5.15 Tosoh Corporation (Bioscience Division) 198 6. Business Trends in the Industry 199 6.1 Industry Consolidation 199 6.2 Breadth of Product Offering and Pricing 201 6.3 Government Regulation of Medical Devices 202 6.4 Commercial Opportunities in Cancer Markers 203 6.5 Moderators of Growth 204 6.6 Biotechnology Industry Trends 205 6.7 Pharmaceutical Industry Trends 206 6.8 Sales and Marketing Strategies for Tumor Marker Tests 208 6.8.1 North American Market 209 6.8.2 International Markets 210

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6.8.2.1 Europe 210 6.8.2.2 Central and South America 210 6.8.2.3 Asia-Pacific 211 6.9 Mergers and Acquisitions (M&As) of Diagnostic Companies 211 7. New Cancer Markers in Basic Research 214 7.1 Genetics of Cancer 214 7.1.1 Activator Genes (Oncogenes) 214 7.1.2 Inactivating Genes (Tumor Suppressor Genes) 217 7.2 DNA Mismatch Repair Genes (MMRs) 219 7.3 Telomeres 220 7.4 Diseases 223 7.4.1 t(15;17) in Acute Promyelocytic Leukemia (APL) 223 7.4.2 t(12;21) in Acute Lymphoblastic Leukemia (ALL) 223 7.4.3 Retinoblastoma and Constitutional 13q14 Deletion 224 7.4.4 Stomach Cancer 224 7.4.5 Head and Neck Cancer 225 7.4.6 Breast and Ovarian Cancers 226 7.4.7 Prostate Cancer 227 7.4.8 Cervical Cancer: NMPI79 229 7.4.9 Uterine and Kidney Cancer: Transmembrane Protein Carbonic Anhydrase IX (CA IX) 229 7.4.10 Colon Cancer: Serum Vascular Endothelial Growth factor (VEGF) 230 7.4.11 Lung Cancer: Ribonucleoprotein A2/B1 and microRNA Markers 230 7.5 Tumor Markers 231 7.5.1 Oncology Biomarker Qualification Initiative 231 7.5.2 CRC: Carcinoembryonic Antigen (CEA) Doubling Time 231 7.5.3 MUC1, 2, 3 and 4 232 7.5.4 Cytokeratins 233 7.5.5 RAK Antigens 233 7.5.6 Serum Amyloid A (SAA) 233 7.5.7 Survivin 234 7.5.8 Reg-4 Protein 234 7.5.9 NADPH Oxidases 1 and 2 (NOX1 and NOX2) 234 7.5.10 Prostate Secretory Protein 94- (PSP94)-Binding Protein 234 7.5.11 Shc Proteins 235 7.5.12 Anti-Glycan Antibodies 235 7.5.13 YKL-40 235 7.5.14 Alpha-Fetoprotein (AFP)-L3 236 7.5.15 Transthyretin and Apo Lipoprotein A1 (Apo A1) 236 7.5.16 A Disintegrin and Metalloproteinase (ADAM) 236 7.6 Technology 236 7.6.1 Chips 236 7.6.2 Ettan DIGE Technology 237 7.6.3 DNA Methylation Technology 237 7.7 Disease-Specific Technology 238 7.7.1 Ovarian Cancer: Bio-Rad’s SELDI-Based ProteinChip 238 7.7.2 Lung Cancer: Labeled Porphyrin Binding 238 7.7.3 Lung Cancer: Pro-Gastrin-Releasing Peptide (ProGRP) 238 7.7.4 Prostate Cancer: PCA3 238 7.7.5 Bladder Cancer: ImmunoCyt/uCyt+ 241 7.8 Ultrasensitive Cancer Tests 242 7.9 Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) 243 7.10 Genetic Tests of Hereditary Cancer Risk 243 7.11 Technical and Practical Issues for Potential New Markers 244 7.12 Genetic Profiling 245

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7.13 Ploidy 246 7.14 Worldwide Healthcare Spending 246 Appendix 1: Web Links 247 Appendix 2: Cancer Information Resources 250 Appendix 3: Colon Cancer Staging 251 Appendix 4: Reimbursement for Tumor Marker Testing 254 Appendix 5: The Pathology of Prostate Cancer 257 Appendix 6: Government Regulation of Tumor Marker Tests 259 Appendix 7: The Clinical Laboratory Improvement Act (CLIA) 262 Appendix 8: Marketers of Occult Blood Diagnostic Test Kits 265 INDEX OF FIGURES Figure 1.1: Medicines in Development in Cancer 13 Figure 4.1: Bowel Cancer including Anal Cancer: Estimates: World Age-Standardized Incidence Rates per 100,000 Population, World Regions 61 Figure 4.2: Percentage of Adults Aged 50-75 Years Who Reported Being Up-to-Date with Colorectal Test Screening, by State Behavioral Risk Factor Surveillance System in the U.S., 2010 64 Figure 4.3: Progression of CRC Development 65 Figure 4.4: Prostate Cancer (C61): Estimates: World Age-Standardized Incidence Rates per 100,000 Population, Males, World Regions 73 Figure 4.5: Prostate Cancer (C61): Estimated Incidence 74 Figure 4.6: Estimates for PCA3 Test Volume in U.S., 2005-2012 95 Figure 4.7: Pancreatic Cancer: Estimates: World Age-Standardized Incidence Rates per 100,000 Population, Male and Females, World Regions 105 Figure 4.8: Breast Cancer: Estimates: World Age-Standardized Incidence Rates per 100,000 Population, Females, World Regions 109 Figure 4.9: ASCO-CAP Guidelines for HER2 Testing in Breast Cancer, 2013 118 Figure 4.10: ASCO-CAP Guidelines for HER2 Testing in Breast Cancer, 2013 119 Figure 4.11: Ovarian Cancer: Estimates: European Age-Standardized Incidence Rates per 100,000 Population, Females, World Regions 122 Figure 4.12: Cervical Cancer: Estimates: World Age-Standardized Incidence Rates per 100,000 Population, Females, World Regions 127 Figure 4.13: Lung Cancer: Estimates: World Age-Standardized Incidence Rates per 100,000 Population, World Regions 133 Figure 4.14: The BTA stat Test vs. Cytology 151 INDEX OF TABLES Table 2.1: Organ-Specific Medicines in Development for Cancer 19 Table 2.2: Estimates for the Leading Sites of New Cancer Cases in the U.S. by Gender, 2015 20 Table 2.3: Estimates for the Leading Sites of Cancer Deaths in the U.S. by Gender, 2015 20 Table 2.4: Worldwide Number of New Cancer Cases and Deaths by Type of Cancer (Men) 20 Table 2.5: Worldwide Number of New Cancer Cases and Deaths by Type of Cancer (Women) 21 Table 2.6: Estimated Incidence, Mortality and Prevalence Worldwide in 2012 22 Table 2.7: Cancer-Associated Genes 22 Table 2.8: Carcinogens in the Workplace 23 Table 2.9: Private Funding Levels for the Biotechnology Segment, 1995-2014 24 Table 2.10: Herceptin Worldwide Sales, 2000-2017 26 Table 2.11: Classes of Drugs Used to Treat Breast Cancer 27 Table 3.1: Tumor Biomarkers Currently in Common Use 31 Table 3.2: Global IVD Cancer Tumor Marker Testing Market Segments Growth Rates, 2011-2021 33

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Table 3.3: Worldwide Market Size in Dollar Volume for Tumor Marker Assays Product Market, 2011-2021 33 Table 3.4: U.S. Market Size in Dollar Volume for Tumor Marker Assays Product Market, 2011-2021 33 Table 3.5: Worldwide In Vitro Cancer Tumor Marker Diagnostics Market Size, 2011-2021 34 Table 3.6: U.S. In Vitro Cancer Tumor Marker Diagnostics Market Size, 2011-2021 34 Table 3.7: Japanese In Vitro Cancer Tumor Marker Diagnostics Market Size, 2011-2021 35 Table 3.8: European In Vitro Cancer Tumor Marker Diagnostics Market Size, 2011-2021 35 Table 3.9: Market Share of Major Competitors in U.S. Cancer Tumor Marker Diagnostics Market 35 Table 3.10: Major Presence in Cancer Tumor Marker Diagnostics Market 36 Table 3.11: Worldwide PSA Sales, 2011-2021 37 Table 3.12: U.S. PSA Sales, 2011-2021 37 Table 3.13: Serum Markers Used Clinically 38 Table 3.14: Drivers of IHC Growth 43 Table 3.15: Bladder Cancer Testing Efforts in the U.S. and Germany 47 Table 3.16: Worldwide Bladder Cancer Marker Sales, 2011-2021 48 Table 3.17: U.S. Bladder Cancer Marker Sales, 2011-2021 48 Table 3.18: Worldwide NMP22 Sales, 2011-2021 49 Table 3.19: Breast Cancer Products and Product Opportunities 55 Table 3.20: Products in Various Stages of Development for Cancers Other than Breast Cancer 56 Table 4.1: CRC Stages 62 Table 4.2: Colon Cancer Facts 63 Table 4.3: Number of Procedures Based on Patients Aged e50 Years who Reported Receiving a Fecal Occult Blood Test within One Year or a Lower Endoscopy within Ten Years, by Age and Sex in the U.S. 64 Table 4.4: Worldwide CEA Sales, 2011-2021 65 Table 4.5: U.S. CEA Sales, 2011-2021 66 Table 4.6: Japan CEA Sales, 2011-2021 66 Table 4.7: Europe CEA Sales, 2011-2021 66 Table 4.8: Rest of the World CEA Sales, 2011-2021 67 Table 4.9: Worldwide PSA Sales, 2011-2021 71 Table 4.10: U.S. PSA Sales, 2011-2021 71 Table 4.11: Japan PSA Sales, 2011-2021 72 Table 4.12: Europe PSA Sales, 2011-2021 72 Table 4.13: Rest of the World PSA Sales, 2011-2021 73 Table 4.14: Population Statistics of Serum Levels of PSA in Men Over 50 Years of Age 80 Table 4.15: Cell Doubling Time and Time to Reach PSA Level of 1,000 ng/mL 81 Table 4.16: Human tissue Kallikreins as Cancer Markers 84 Table 4.17: New Diagnostic Tests for Prostate Cancer 90 Table 4.18: Gen-Probe Genetic Testing Product Line 96 Table 4.19: Prostate Cancer Molecular Diagnostic Testing Market: Market Drivers Ranked in Order of Impact 102 Table 4.20: Prostate Cancer Molecular Diagnostic Testing Market: Market Restraints Ranked in Order of Impact 102 Table 4.21: Summary of Strengths, Weaknesses, Opportunities and Threats of the Prostate Cancer Molecular Diagnostic Market 103 Table 4.22: Worldwide CA 19-9 Sales, 2011-2021 106 Table 4.23: U.S. CA 19-9 Sales, 2011-2021 106 Table 4.24: Japan CA 19-9 Sales, 2011-2021 106 Table 4.25: Europe CA 19-9 Sales, 2011-2021 107 Table 4.26: Rest of the World CA 19-9 Sales, 2011-2021 107 Table 4.27: CA 19-9 Levels in Management of Pancreatic Cancer 108 Table 4.28: Worldwide CA 15-3 Sales, 2011-2021 111 Table 4.29: U.S. CA 15-3 Sales, 2011-2021 111 Table 4.30: Japan CA 15-3 Sales, 2011-2021 111 Table 4.31: Europe CA 15-3 Sales, 2011-2021 112 Table 4.32: Rest of the World CA 15-3 Sales, 2011-2021 112

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Table 4.33: TPA Marker Sensitivity 115 Table 4.34: ASCO-CAP Guidelines for HER2 Testing in Breast Cancer: How to Interpret Test Results 117 Table 4.35: Worldwide CA-125 Sales, 2011-2021 123 Table 4.36: U.S. CA-125 Sales, 2011-2021 123 Table 4.37: Japan CA-125 Sales, 2011-2021 124 Table 4.38: Europe CA-125 Sales, 2011-2021 124 Table 4.39: Rest of the World CA-125 Sales, 2011-2021 124 Table 4.40: Worldwide HVP Sales, 2011-2021 128 Table 4.41: U.S. HPV Sales, 2011-2021 129 Table 4.42: Japan HVP Sales, 2011-2021 129 Table 4.43: Europe HVP Sales, 2011-2021 129 Table 4.44: Rest of the World HVP Sales, 2011-2021 130 Table 4.45: HCPCS Codes for Screening Pap Tests 131 Table 4.46: HCPCS Codes for Screening Pap Tests Rate 131 Table 4.47: Number of Pap Smears Performed by Country 132 Table 4.48: Lung Cancer Survival Rates 134 Table 4.49: American Cancer Society Lung Cancer Facts 135 Table 4.50: Predictive and Prognostic Rates 140 Table 4.51: Tests Identifying Molecular Markers in Urine 146 Table 4.52: Worldwide NMP22/BTA Sales, 2011-2021 147 Table 4.53: U.S. NMP22/BTA Sales, 2011-2021 147 Table 4.54: Japan NMP22/BTA Sales, 2011-2021 148 Table 4.55: Europe NMP22/BTA Sales, 2011-2021 148 Table 4.56: Rest of the World NMP22/BTA Sales, 2011-2021 148 Table 4.57: Patient Category Applications 149 Table 4.58: Worldwide Alpha-Fetal Protein (AFP) Sales, 2011-2021 154 Table 4.59: U.S. Alpha-Fetal Protein (AFP) Sales, 2011-2021 155 Table 4.60: Japan Alpha-Fetal Protein (AFP) Sales, 2011-2021 155 Table 4.61: Europe Alpha-Fetal Protein (AFP) Sales, 2011-2021 155 Table 4.62: Rest of the World Alpha-Fetal Protein (AFP) Sales, 2011-2021 156 Table 4.63: Key Oncology Diagnostic Tests, Roche, 2015 160 Table 4.64: Potential Uses of Molecular Diagnostics in Cancer Management 167 Table 4.65: Markers Frequently Used to Identify Adult Stem Cells in the Prostate, Breast and Intestine 173 Table 4.66: MammaPrint: Key Features 179 Table 5.1: Tumor Diagnosis Immunoassays 186 Table 5.2: Tumor Diagnosis Radioimmunoassays 186 Table 6.1: List and Discounted Prices for Abbott Tumor Marker Tests 202 Table 7.1: Categories of Oncogenes 215 Table 7.2: Familial Cancer Syndromes and Tumor Suppressor Genes 219 Table A7.1: Financial Comparison for Moderate and Waived CLIA Labs 262 Table A8.1: List of Marketers of Fecal Occult Blood Diagnostic Test Kits 265

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Cancer Diagnostic Testing World Markets January 2016

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1. Overview 1.1 Statement of Report Cancer is a generic term for a large group of diseases that can affect any part of the body, characterized by uncontrolled growth and spread (or metastasis) of abnormal cells. As such, there is an urgent need for diagnostic tests to detect cancer earlier, allowing physicians to make more informed therapeutic decisions. Recently, the growth in this field has been extremely rapid with a large number of tumor markers being identified. Tumor markers are a group of proteins, hormones, enzymes, receptors and other cellular products that are over-expressed (i.e., produced in higher than normal amounts) by malignant (cancerous) cells. Tumor markers are sometimes normal cellular constituents that are present at normal or very low levels in the blood of healthy individuals. The purpose of this report is to evaluate the technological developments that are occurring in the tumor marker testing segment of the cancer diagnostics market. This study reviews all of the generally-accepted clinical and research methods that are currently available for detection of cancer cells in patients. It examines the clinical measurement devices, including their reagents and supplies, utilized in hospitals, clinics, commercial laboratories and doctor’s offices to diagnose and monitor cancer. All cancers involve the malfunction of genes that control cell growth, division and death. As such, scientists are working hard to develop tests based on molecular and genetic RNA/DNA that can detect individuals at high risk for specific cancers. These include serological assays, cellular assays and molecular and genetic assays. Some of the most widely-tested and clinically-utilized diagnostic tumor markers include prostate-specific antigen (PSA) for prostate cancer, alpha-fetoprotein (AFP) for liver cancer, carcinoembryonic antigen (CEA) for colon cancer, carbohydrate antigen (CA)-125 for ovarian cancer, CA 19-9 for gastrointestinal cancer, the β sub-unit of human chorionic gonadotropin (β-hCG) in germ cell tumors, and CA 15-3 and CA 27.29 for breast cancer. With the rapid development of new systems and methodologies for diagnostic testing, early diagnosis and successful treatment of cancer is now a reality. 1.2 About This Report This examination describes the analysis related to the common chemical constituents of blood, plasma or serum that are connected to the growth and progress of cancer. Emphasis is on those companies that are actively developing and marketing clinical laboratory instrumentation, reagents, supplies and products for performing tumor marker tests. The main objectives of this report are:

• Identifying viable technology drivers through a comprehensive examination of platform technologies for cancer diagnostics, including probe-based nucleic acid assays, microarrays and sequencing.

• Obtaining a complete understanding of the chief cancer diagnostics tests—i.e., predictive, screening, prognostic, monitoring, pharmacogenomic and theranostic—from their basic principles to their applications.

• Discovering feasible market opportunities by identifying high-growth applications in different clinical diagnostic areas, focusing on the biggest and expanding markets in oncology.

• Focusing on global industry development through an in-depth analysis of the major world markets for cancer diagnostics, including growth forecasts.

By purchasing this analysis, the reader will have:

• An understanding of the most influential cancer marker market segments. • The latest information on leading products and research and development (R&D) initiatives. • Familiarity with recent developments and their effects on selected markets. • Knowledge of the cancer marker market as an area of growth, research and investment.

The report defines the dollar volume of sales of the tumor marker testing segment, both worldwide and in the U.S., and it analyzes the factors that influence the size and growth of the market segments. Key questions answered in this study are:

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Cancer Diagnostic Testing World Markets January 2016

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• How can cancer marker measuring tools and technologies facilitate improved patient care? • What are the main types of cancer marker technologies that are currently available? • Who are the current key players in this marketplace? • Which cancer marker market areas have the greatest potential for growth? • What is the current state of the cancer marker market? • Which biotechnology and diagnostic companies are investing in new cancer marker technology platform

solutions? • What are the main cancer marker business strategies adopted by leading companies? • What are the benefits of various cancer marker technology platforms?

This review contains:

• Detailed analysis of recent trends in the cancer marker marketplace. • In-depth profiles of the leading companies with cancer marker tools and technologies. • Opinions on the cancer marker industry from leading industry experts. • Analysis of potential new cancer marker applications in the clinical sector. • Market predictions and trends analysis concerning U.S. expenditures on cancer markers. • Projections of cancer marker market sizes for European and Asian markets. • Projections for future applications of non-invasive tests in cancer marker screening. • Analysis of commercial cancer marker business strategies, such as co-branding. • A comprehensive overview and insight into cancer marker business strategies for growth in foreign

markets. • An in-depth examination of the subsections of each cancer marker market segment. • An industry structure analysis including companies in the field and their focus.

Analysis includes charts and graphs measuring product growth and trends within the marketplace. Company-specific information, including sales figures, product pipeline status and R&D trends, is provided. Also, this report will:

• Assess cancer marker market drivers and bottlenecks from medical and scientific community perspectives. • Discuss the potential benefits of cancer markers for various sectors of the oncology community. • Establish the current total market size and future growth of the cancer marker market and analyze the

current size and growth of individual segments. • Provide current and forecasted market shares by company. • Discuss profit and business opportunities by oncology segment. • Provide strategic recommendations for near-term business opportunities.

The following questions will also be addressed in this study:

• What are the near-term business opportunities in the cancer marker market? • What are the current and forecasted cell therapy market sizes in the U.S., European Union (E.U.) and Asia? • What are the business models currently used by companies in the cancer marker market? • How will manufacturers, researchers, physicians and patients influence this market? • What are the drivers and bottlenecks influencing the cancer marker market? • What are the barriers to entry for the cancer marker market? • What are the key technologies used in cancer marker testing? • Who holds the proprietary rights to the cancer marker technology platforms? • How is this technology currently being applied and utilized? • How will new cancer marker technologies reduce healthcare expenditures? • How will new cell therapy technologies affect cancer therapy decisions?

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The analysis contains:

• A comprehensive overview of several categories of cancer marker technology platforms that are of use as diagnostic tests in hospitals and doctor’s offices.

• A chapter on each of the important cancer categories and applications of cancer marker tests to diagnosis and treatment.

• Full descriptions of the technologies involved and how these differ from existing and emerging technologies.

• Analysis of the technological approaches undertaken by various competitors, as well as industry, and end-user response to these products.

• Regulatory issues and legislation affecting use and marketing of cancer marker products. • Complete review of the clinical uses of cancer marker tests.

1.3 Scope of the Report This study emphasizes companies that are actively developing and marketing clinical laboratory instrumentation, reagents and supplies for performing cancer diagnostics tests. The reader should consult other TriMark Publications reports at http://www.trimarkpublications.com for detailed discussions of important individual market segments related to the cancer diagnostics market, such as Biomarker Technology Platforms for Cancer Diagnoses and Therapies, Cancer Cell Therapy Markets, Cancer Therapeutics Markets, Companion Diagnostics in Personalized Medicine and Cancer Therapy, Cytology and HPV Testing World Markets and Molecular Diagnostics in Cancer Testing. The U.S., Japan and Europe—the world’s three largest cancer diagnostics markets—are the focus of this report. Primary attention is paid to the hospital market segment, and separately, to the instruments, reagents and supplies marketed by major companies in this segment. Market size, growth rates and market components for instruments, reagents, controls and consumables used in this area are also analyzed. Specialty cancer diagnostics testing is examined, since it is often part of the overall analytical focus of companies that market general laboratory automation equipment. However, no effort is made to quantify this broader market. In addition, this report does not cover disposable plastic supplies for the clinical laboratory. These subjects are discussed in other TriMark Publications reports. 1.4 Objectives The goal of this survey is to review the market for tumor marker testing equipment and supplies using screening reagents and instruments for analysis of individual components in blood, serum or plasma. It defines the dollar volume of sales, both worldwide and in the U.S., and analyzes the factors that influence the size and growth of the market segments. Also examined are the subsections of each market segment, including the physician office labs, hospital labs and commercial laboratories. Additionally, the numbers of institutions using this type of testing and the factors that influence purchases are discussed. The study surveys almost all of the companies known to be marketing, manufacturing or developing instruments and reagents for the clinical oncology market in the U.S. Each company is discussed in depth with a section on its history, product line, business and marketing analysis, and a subjective commentary of the company’s market position. 1.5 Methodology The author of this report holds a Ph.D. in biochemistry from the University of Minnesota and has had post doctoral experience at the University of Connecticut School of Medicine. He has taught at Quinnipiac University and the Tufts School of Medicine, and has been a senior scientist at Pfizer Pharmaceutical Laboratories in drug development. He also has many decades of experience in science writing and as a medical industry analyst. He has over 30 years of experience in laboratory testing and instrument and reagent development technology as a licensed clinical laboratory director, as well as extensive experience in senior level management positions in biotech and medical service companies. He was the first director and a founder of Dianon Laboratories, now part of LabCorp, and was a pioneer in bringing cancer diagnostic tests, including an early PSA, to the clinic. The editor of this report

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Cancer Diagnostic Testing World Markets January 2016

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holds a Ph.D. in biochemistry from the University of Liverpool and has many decades of experience in science writing and as a medical industry analyst. Company-specific information is obtained mainly from industry trade publications, academic journals, news and research articles, press releases and corporate websites, as well as annual reports for publicly-held firms. Additionally, sources of information include the non-governmental organizations (NGOs) such as the World Health Organization (WHO) and the American Cancer Society (ACS), as well as governmental entities like the U.S. Department of Health and Human Services (HHS) and U.S. federal agencies such as the National Cancer Institute (NCI), the National Institutes of Health (NIH), the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC). Where possible and practicable, the most recent data available have been used. Some of the statistical information was taken from Biotechnology Associates’ databases and from TriMark’s private data stores. The information in this study was obtained from sources that we believe to be reliable, but we do not guarantee the accuracy, adequacy or completeness of any information or omission, or for the results obtained by the use of such information. Key information from the business literature was used as a basis to conduct dialogue with and obtain expert opinion from market professionals regarding commercial potential and market sizes. Senior managers from major company players were interviewed for part of the information in this report. Primary Sources TriMark collects information from hundreds of Database Tables and many comprehensive multi-client research projects, as well as Sector Snapshots that we publish annually. We extract relevant data and analytics from TriMark’s research as part of this data collection. Secondary Sources TriMark uses research publications, journals, magazines, newspapers, newsletters, industry reports, investment research reports, trade and industry association reports, government-affiliated trade releases, and other published information as part of its secondary research materials. The information is then analyzed and translated by the Industry Research Group into a TriMark study. The Editorial Group reviews the complete package with product and market forecasts, critical industry trends, threats and opportunities, competitive strategies and market share determinations. TriMark initially researches market share, market size and growth rate information from secondary sources. This gives a “feel” for the market. Analysts then contact individuals with the appropriate information (usually marketing product managers are the best source) from the leading suppliers and elicit information to either corroborate or reject data from the initial secondary searches. At the same time they will query them about the other aspects of the market, drivers, restraints, regulatory, etc. Secondary sources are many and varied and include websites of national governments, international organizations such as the World Trade Organization (WTO), trade and professional organizations e.g., The Pharmaceutical Research and Manufacturers of America (PhRMA), etc. A considerable amount of further information is obtained from numerous publications in the scientific and trade literature including information and data from Scrip, Clinica, etc. In addition, a significant amount of information has also been obtained from various national government sources who have kindly provided up-to-date information about the regulatory and legislative position on research funding in specific geographic regions. In addition to the use of corporate annual and quarterly reports, data was obtained from security offering prospectuses, Forms 10-K and 10-Q. This data was used along with other sources of data from investment analysts’ reports, Reuters, Dun & Bradstreet, IMS and the CorpTech Directory. Market Forecasts and Modeling The numerical data on market size, growth rates and sales forecasts are obtained from a well-examined model based upon quantitative market information obtained from the leading global companies in the sector, private seminar presentations by company experts and public SEC filings. Many industry experts are also consulted to confirm these

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Cancer Diagnostic Testing World Markets January 2016

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market estimates. The numbers used are washed of discounts and returns, and represent the final sale numbers. In addition, global numbers are assessed by region components as well, taking into account differences in market conditions between the U.S., Europe and Asian markets in particular. For projection for the future values and growth rates of specific markets, the analysts use a proprietary forecast spreadsheet, which takes into account a wide variety of market indices such as inflation rates, anticipated increases/decreases in funding of specific markets. Then other factors such as new market introductions, acquisitions, etc. are manually incorporated into the spreadsheet. TriMark Publications Report, Research and Data Acquisition Structure The general sequence of research and analysis activity prior to the publication of every report includes the following items:

• Formulating a study outline with the assigned writer, including important items, as follows:

• Market and product segment grouping and evaluating their relative significance. • Key competitors’ evaluations including their relative positions in the business and other relevant

facts to prioritize diligence levels and assist in designing a primary research strategy. • End-user research to evaluate analytical significance in market estimation. • Supply chain research and analysis to identify any factors affecting the market. • New technology platforms and cutting edge applications.

• Identifying the key technology and market trends that drive or affect these markets. Assessing the regional

significance for each product and market segment for proper emphasis of further regional/national primary and secondary research.

• Launching a combination of primary research activities, including two levels of questionnaires, executive-

direct focused, company-specific and region-specific communications to qualified and experienced senior executives worldwide.

• Completing a confirmatory primary research assessment of the report’s findings with the assistance of

expert panel partners from the industry.

• The final published report is reviewed by editors, fact checkers and proof readers, and then released by the Editor-in-Chief.

1.6 Executive Summary People suffering from some of the most common forms of cancer are twice as likely to survive for at least ten years, compared with patients diagnosed in the early 1970s. Breast, bowel and prostate cancer survival rates have shot up, as have those for non-Hodgkin’s lymphoma (NHL) and leukemia. On average, 45.2% of cancer patients are now expected to survive at least ten years, compared with 23.7% in the 1970s. Since peaking in the 1990s, cancer death rates have declined nearly 22%. Approximately 83% of survival gains in cancer are attributable to new treatments, including medicines. The improvement in survival reflects progress in diagnosing certain cancers at an earlier stage and improvements in treatment. Cancer testing is one of the most important growth opportunities in the diagnostics segment. The Agency for Healthcare research and Quality (AHRQ) estimates that the direct medical costs (total of all healthcare costs) for cancer in the U.S. in 2015 were $88.7 billion.

• 50% of this cost is for hospital outpatient or doctor office visits. • 35% of this cost is for inpatient hospital stays. • 11% of this cost is for prescription drugs.

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Cancer Diagnostic Testing World Markets January 2016

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Based on growth and aging of the U.S. population, medical expenditures for cancer in the year 2020 are projected to reach at least $158 billion, an increase of 27% over 2010, according to a National Institutes of Health analysis. If newly developed tools for cancer diagnosis, treatment, and follow-up continue to be more expensive, medical expenditures for cancer could reach as high as $207 billion, said the researchers from the National Cancer Institute (NCI), part of the NIH. The analysis appeared online, January 12, 2011, in the Journal of the National Cancer Institute. The Pharmaceutical Research and Manufacturers of America (PhRMA) have estimated that in 2015 a total of over 7,000 medicines and treatments are in development globally. Approximately 3,500 compounds are currently being studied in the U.S.—more than in any other region around the world. They estimate that in 2015, 1,813 new medicines are currently under development to help treat cancer. Furthermore, in a United Nations report it was published that cancer deaths will double by 2030. The director of the International Agency for Research on Cancer, Christopher Wild, said that by 2030, there will be 21.4 million cases of cancer diagnosed, the rate being highest in the developing countries, given the fact the rates of cancer would remain constant in next 20 years. The four leading causes of cancer death—lung, colorectal, breast and pancreas—are believed to have accounted for approximately 52% of all cancer deaths in the U.S. in 2013, or one in eight of every death. The American Cancer Society (ACS) estimates that:

• About 1,658,370 new cancer cases are expected to be diagnosed in 2015. • In 2015, about 589,430 Americans are expected to die of cancer, or about 1,620 people per day. • In 2015, almost 171,000 of the estimated 589,430 cancer deaths in the U.S. will be caused by tobacco

smoking. • Men and women who smoke are about 25 times more likely to develop lung cancer than non-smokers, • Cancer is the second most common cause of death in the U.S., exceeded only by heart disease, and

accounts for nearly one of every four deaths. • The Agency for Healthcare Research and Quality (AHRQ) estimates that the direct medical costs (total of

all healthcare expenditures) for cancer in the U.S. in 2011 were $88.7 billion. The World Cancer Research Fund estimates that about one-quarter to one-third of the new cancer cases expected to occur in the U.S. in 2015 will be related to overweight or obesity, physical inactivity, and poor nutrition, and thus could also be prevented. Certain cancers are related to infectious agents, such as human papillomavirus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and Helicobacter pylori; many of these cancers could be prevented through behavioral changes, vaccines, or antibiotics. Many of the more than two million skin cancers that are diagnosed annually could be prevented by protecting skin from excessive sun exposure and avoiding indoor tanning. The ACS estimated that approximately 1,660,290 new cancer cases were expected to be diagnosed in 2015. This estimate excluded basal cell and squamous cell skin cancers and in situ carcinomas except urinary bladder. The ACS have also predicted that about 580,350 Americans are expected to die of cancer, in 2015, almost 1,600 people per day. Cancer is the second most common cause of death in the U.S., exceeded only by heart disease. In the U.S., cancer accounts for nearly one in four deaths. New technology in the diagnosis and treatment of these diseases and conditions should lead to attractive commercial opportunities. For example, the worldwide cancer treatment market currently is $21.2 billion and growing at a rate of 8% annually. The size and growth of the diagnostic tumor marker markets are influenced by a number of factors, including:

• Financing for biotech companies. • Technological innovation in diagnostic practice. • Government funding (including supplemental stimulus financing) for basic and disease-related research

(for example, heart disease, AIDS and cancer). • R&D spending by biotechnology and pharmaceutical companies.

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The specific products in this segment include:

• Immunoassays for serum cancer markers, receptor assays and hormone assays. • Mammography equipment. • Clinical chemistry reagents (occult blood reagents, enzymes and serum proteins). • Deoxyribonucleic acid (DNA) reagents. • Cytological products. • Histological reagents. • Immunocytochemistry (ICC) products. • Immunohistochemistry (IHC) reagents.

Biotechnology Associates estimates that the global product market for in vitro cancer detection products—including clinical chemistry reagents (occult blood reagents, enzymes, serum proteins), DNA reagents, cytological products, histological reagents, ICC products and IHC reagents—grew to over $4,442 million in 2014. The U.S. market for all in vitro cancer detection products, including the tumor marker category, is estimated to be $2,031 million, or about 46% of the total worldwide market. The worldwide tumor marker product segment, comprising proteins detected with immunological technologies in serum or plasma, is expected to grow with a CAGR rate of 8.6% and is expected to be valued at $7,924 million by the end of the forecast period in the year 2021. This market sector is primarily driven by the increasing number of people in the population who fall within the higher risk demographics of cancer and the increased marketing of new tests to doctors. The tumor marker product segment in the U.S. is expected to grow with a CAGR rate of 8.8% and is expected to be valued at $3,663 million by the end of the forecast period in the year 2021. During the first quarter of 2010, however, the ACS has pulled back from previous PSA screening guidelines. The newer guidelines recommend that men whose PSA level is less than 2.5 ng/mL need only be screened every two years. The previous guidelines called for men with a PSA level of less than 4.0 ng/mL to be screened annually. In general, the tumor marker product segment in the U.S. will be primarily driven by the increasing number of people in the population who fall within the higher risk demographics of cancer. The U.S. market is still constrained by the cost pressures from third-party payers who are reluctant to reimburse for new procedures, and the conservative stance of the FDA, which is slow to approve new diagnostic tests for cancer. The Japanese cancer marker market is recognized as being the second largest single market and has been valued at $711.7 million in 2014, and is anticipated to continue to grow with a CAGR of 7.5% over the forecast period reaching a value of $1,183.4 million by 2021. It is estimated that the tumor marker products market in Europe has been valued at $1,225 million in 2014, and is anticipated to continue to grow with a CAGR of 8.3% over the forecast period reaching a value of $2,141 million by 2020. Continued growth for tumor marker products is also expected for Germany and France in the European market. In fact, the European market uses a wider variety of cancer tumor markers, although the dollar volume is still third to the U.S. and Japan. Primarily because of marketing forces, the tumor marker nuclear matrix protein 22 (NMP22) sells very well in Germany. It is estimated that the tumor marker products market in the Rest of the World has been valued at $2,146 million in 2014, and is anticipated to continue to grow with a CAGR of 8.8% over the forecast period reaching a value of $3,876 million by 2021. The existing FDA-approved assays which comprise the main tumor marker assay segment in the U.S. are:

• Diphtheria toxin A (DTA) and NMP22, which were approved for monitoring bladder cancer. • CEA, which is used primarily for monitoring colorectal and breast cancers. • PSA, which is used primarily for monitoring and screening prostate cancer. • Truquant BR radioimmunoassay (RIA), which is used for monitoring breast cancer.

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• hCG, for monitoring testicular cancers, trophoblastic tumors and choriocarcinoma. • CA-125, used for the diagnosis and monitoring of ovarian cancer.

Serum PSA testing has revolutionized the diagnosis and management of prostate cancer and several million tests are performed every year in the U.S. to screen for this malignancy. It is estimated that over $400 million is now spent on PSA testing. The market for cancer detection products generally encompasses diagnostic products companies like Johnson & Johnson, Abbott Diagnostics, Roche Diagnostics, Tosoh, bioMérieux and Diagnostic Automation/Cortez Diagnostics, Inc., which all market instruments and reagents for measuring serum protein tumor markers in vitro, i.e., in the clinical lab. Another subsection of the cancer detection market consists of companies like General Electric, Siemens, Philips, Toshiba and Hitachi that market in vivo detection products. In addition, there are radionuclides (DuPont, Covidien and Bristol-Myers Squibb), X-ray contrast media (Covidien and Bristol-Myers Squibb) and X-ray film (DuPont, Agfa, Eastman Kodak, Fuji and 3M). Tumor markers used and approved in the U.S. by the FDA include:

• PSA. • Prostatic acid phosphatase (PAP). • CA-125 for ovarian cancer (but only to follow the course of the disease). • CEA in colon cancer. • AFP in liver cancer and combined with β-hCG in germ cell tumors. • Terminal transferase used in T-cell leukemia, tissue estrogen and progesterone receptors in breast cancer. • CA 15-3 and CA 27.29 currently for breast cancer.

In other parts of the world, a wider variety of tumor biomarkers are used:

• CA 547, M26, M29, MCA for breast cancer. • CA 19-9, CA 195, TAG72, CA 245, M43 for gastrointestinal cancers. • Cytokeratin 19 fragment (CYFRA™) 21-1 in non-small cell lung cancer (NSCLC), neuron specific enolase

(NSE) and calcitonin in neuroendocrine tumors. • Squamous cell carcinoma antigen in squamous cell tumors of the cervix-uterus or head and neck. • Non-specific markers like TPS, LSA and sialic acid.

The clinical value of serum tumor markers CEA, CA-50 and CA 242 in the distinction between malignant versus benign diseases causing jaundice and cholestasis is also being examined.