Table of Content

i. Liquid Biopsy Market - Strategic Situation Analysis & Impact of COVID-19....................20 ii. Guide for Executives, Marketing, Sales and Business Development Staff .....................23 iii. Guide for Management Consultants and Investment Advisors ....................................25 1. Introduction and Market Definition ...................................................................................26
1.1 What is Liquid Biopsy? ............................................................................................................ 27 1.2 The Sequencing Revolution ................................................................................................... 28 1.3 Market Definition .................................................................................................................... 30
1.3.1 Revenue Market Size........................................................................................................ 30 1.4 Methodology .......................................................................................................................... 31 1.4.1 Authors .............................................................................................................................. 31 1.4.2 Sources.............................................................................................................................. 32 1.5 A Spending Perspective on Liquid Biopsy ............................................................................ 33 1.5.1 An Historical Look at Clinical Testing............................................................................... 34
2. Market Overview ................................................................................................................36
2.1 Players in a Dynamic Market ................................................................................................. 37 2.1.1 Academic Research Lab ................................................................................................ 38 2.1.2 Diagnostic Test Developer............................................................................................... 38 2.1.3 Genomic Instrumentation Supplier ................................................................................. 38 2.1.3.1 Cell Separation and Viewing Instrumentation Supplier ........................................ 39
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2.1.4 Pharmaceutical/Reagent Supplier ................................................................................. 39 2.1.5 Independent Testing Lab................................................................................................. 39 2.1.6 Public National/regional lab ........................................................................................... 40 2.1.7 Hospital lab ....................................................................................................................... 40 2.1.8 Physician Lab .................................................................................................................... 40 2.1.9 Audit Body ........................................................................................................................ 41 2.1.10 Certification Body.......................................................................................................... 41
2.2 Using Biopsies .......................................................................................................................... 43 2.2.1 Cancer .............................................................................................................................. 43 2.2.2 Precancerous conditions ................................................................................................. 44 2.2.3 Inflammatory conditions .................................................................................................. 44
2.3 Biopsy Sites .............................................................................................................................. 45 2.4 The Situation Today – Biopsy Analysis.................................................................................... 47 2.5 Evidence of Cancer - Liquid Biopsy Technology ................................................................. 48
2.5.1 The Big Picture on Liquid Biopsy Technology ................................................................. 48 2.5.2 The Role of CTCs............................................................................................................... 50 2.5.2.1 Types of CTCs............................................................................................................ 51 2.5.2.2 CellSearch Detection- Ultimate Sensitivity ............................................................. 52 2.5.2.3 Epic Sciences Detection- Imaging Takes the Lead............................................... 53 2.5.2.4 Maintrac Detection – The Microscope................................................................... 53 2.5.2.5 Other Methods ......................................................................................................... 55 2.5.3 ctDNA – Going Mainstream? .......................................................................................... 56 2.5.4 Exosomes and Micro Vesicles – New Kid on the Block.................................................. 57 2.5.5 The Multiple Play............................................................................................................... 60

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2.6 Cancer Treatment Protocol Under Siege ............................................................................. 62 2.6.1 Issues to Liquid Biopsy Adoption – Double Diagnostics................................................. 62 2.6.2 The Cancer Screening Market Opportunity................................................................... 63
2.6.2.1 GRAIL – What Is It?.................................................................................................... 64 2.6.3 Cancer Management vs. Diagnosis ............................................................................... 65 2.6.3.1 The Role of Risk Assessment ..................................................................................... 65 2.6.3.2 Managing Therapy................................................................................................... 66 2.6.3.3 Monitoring Disease – What Is It?.............................................................................. 66 2.6.4 Phases of Adoption – Looking into The Future ............................................................... 67 2.6.5 The Promise of Liquid Biopsy ............................................................................................ 68 2.7 Structure of Industry Plays a Part ........................................................................................... 70 2.7.1 Hospital Testing Share ...................................................................................................... 70 2.7.2 Economies of Scale.......................................................................................................... 70 2.7.2.1 Hospital vs. Central Lab ........................................................................................... 71 2.7.3 Physician Office Lab’s...................................................................................................... 72 2.7.4 Physician’s and POCT ...................................................................................................... 72
3. Market Trends......................................................................................................................74
3.1 Factors Driving Growth........................................................................................................... 75 3.1.1 Non Invasive Game Changer ......................................................................................... 75 3.1.2 Lower Cost ........................................................................................................................ 76 3.1.3 Greater Accuracy............................................................................................................ 76 3.1.4 Wide Range of Potential Uses ......................................................................................... 76 3.1.5 Aging Population.............................................................................................................. 76 3.2 Factors Limiting Growth.......................................................................................................... 78

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3.2.1 Lower prices...................................................................................................................... 78 3.2.2 Lack of Standards............................................................................................................. 79 3.2.3 Protocol Resistance.......................................................................................................... 79 3.2.4 Initial Adoption Cost......................................................................................................... 79 3.2.5 COVID-19 .......................................................................................................................... 79
3.3 Instrumentation and Automation.......................................................................................... 81 3.3.1 Instruments Key to Market Share..................................................................................... 81 3.3.2 Bioinformatics Plays a Role .............................................................................................. 81
3.4 Diagnostic Technology Development.................................................................................. 82 3.4.1 Next Generation Sequencing Fuels a Revolution.......................................................... 83 3.4.2 Impact of NGS on pricing................................................................................................ 84 3.4.3 Pharmacogenomics Blurs Diagnosis and Treatment..................................................... 84 3.4.4 CGES Testing, A Brave New World .................................................................................. 85 3.4.5 Biochips/Giant magneto resistance based assay......................................................... 86
4. Liquid Biopsy Recent Developments.................................................................................87
4.1 Recent Developments – Importance and How to Use This Section................................... 88 4.1.1 Importance of These Developments .............................................................................. 88 4.1.2 How to Use This Section.................................................................................................... 88 Liquid Biopsy NGS Panels - Diverse Test Claims .......................................................................... 88 CMS Colon Cancer Screening Memo Bodes Well for Assays ................................................... 94 Natera Liquid Biopsy Test Coverage to Expand ........................................................................ 96 Freenome Closes Financing to Support Early Cancer Detection Trial ..................................... 97 C$2.6M Liquid Biopsy Initiative .................................................................................................... 98 NeoGenomics, Inivata Partner for Lung Cancer Liquid Biopsy .............................................. 100

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Liquid Biopsy Shows Promise as Screen for Cancers ............................................................... 100 Inivata launches RaDaRTM for the detection of residual disease and recurrence ............... 101 Liquid Biopsy Assay Detects 50+ Types of Cancer ................................................................... 102 Liquid Biopsy Study Confirms Concordance with Tissue Biopsy.............................................. 104 Guardant Health Liquid Biopsy Expands Medicare Coverage .............................................. 106 Aethlon Medical Lands Grant for Exosome Isolation Device ................................................. 108 Biolidics to Develop Liquid Biopsy Breast Cancer Test............................................................. 108 Liquid Biopsy Equal to Tissue to Indicate Immunotherapy Response..................................... 109 Exact Sciences buys Genomic Health...................................................................................... 111 Multi-Gene Liquid Biopsy Breast Cancer Panel........................................................................ 113 Bio-Techne receives FDA breakthrough device for prostate cancer liquid biopsy.............. 113 Thrive to Develop Earlier Detection of Multiple Cancer Types ............................................... 115 Guardant Health Liquid Biopsy Test to be Covered by EviCore............................................. 117 Liquid biopsy combines Illumina’s ‘ultradeep’ sequencing with Grail’s machine learning. 118 Biocept Partnership Offering for Liquid Biopsy Adds Several Key Services ............................ 120 Natera Commercializes Tumor Whole Exome Sequencing from Plasma .............................. 120 Sienna Buys Liquid Biopsy & Exosome Isolation Technology ................................................... 122 Inivata Completes £39.8M Series B Funding Round................................................................. 123 Bio-Rad Clinical ddPCR Test, Diagnostic System Get FDA Clearance................................... 124 CellMax, Medigen Biotech Partner in Colorectal Cancer Clinical Trials ............................... 125 Biodesix Acquires Integrated Diagnostics ................................................................................ 126 Predicine, Kintor Pharmaceuticals Partner on Clinical Trials, CDx .......................................... 127 Bio-Techne to Acquire Exosome Dx for Up to $575M .............................................................. 127 GRAIL Announces Data on Detection of Early-Stage Lung Cancers .................................... 129

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Precision for Medicine Acquires ApoCell ................................................................................. 131 NeoGenomics to Acquire Genoptix for Cash, Stocks............................................................. 131 PGDx Liquid Biopsy Assay to be Used in Cancer Drug Study ................................................. 133 Liquid Biopsy IDs More NSCLC Mutations in Study of Guardant Test...................................... 134 Inivata Gets Draft Medicare Coverage Determination for Lung Cancer Test...................... 136
5. Profiles of Key Players .......................................................................................................138 Abbott Diagnostics..................................................................................................................... 139 AccuraGen Inc........................................................................................................................... 141 Acuamark Diagnostics............................................................................................................... 142 Admera Health, LLC................................................................................................................... 143 Agena Bioscience, Inc............................................................................................................... 145 Agilent ......................................................................................................................................... 147 Amoy Diagnostics Co., Ltd. ....................................................................................................... 149 Anchor Dx ................................................................................................................................... 150 ANGLE plc ................................................................................................................................... 151 ApoCell, Inc. ............................................................................................................................... 153 ArcherDx, Inc. ............................................................................................................................. 154 Asuragen..................................................................................................................................... 155 AVIVA Biosciences ..................................................................................................................... 157 Baylor Miraca Genetics Laboratories ....................................................................................... 158 Beckman Coulter, Inc. ............................................................................................................... 159 Becton, Dickinson and Company............................................................................................. 161 BGI Genomics Co. Ltd ............................................................................................................... 163 Bioarray Genetics ....................................................................................................................... 165

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Biocartis ....................................................................................................................................... 166 Biocept, Inc................................................................................................................................. 167 Biodesix Inc. ................................................................................................................................ 168 BioFluidica ................................................................................................................................... 169 bioMérieux Diagnostics.............................................................................................................. 170 Bioneer Corporation................................................................................................................... 172 Bio-Rad Laboratories, Inc........................................................................................................... 174 Bio-Techne .................................................................................................................................. 176 Bioview ........................................................................................................................................ 178 Bolidics......................................................................................................................................... 180 Boreal Genomics........................................................................................................................ 181 Caris Molecular Diagnostics ...................................................................................................... 182 CellMax Life................................................................................................................................. 183 Cepheid (now Danaher) ........................................................................................................... 184 Chronix Biomedical .................................................................................................................... 186 Circulogene................................................................................................................................ 187 Clinical Genomics ...................................................................................................................... 188 Cynvenio..................................................................................................................................... 189 Cytolumina Technologies Corp. ............................................................................................... 190 CytoTrack.................................................................................................................................... 191 Datar Cancer Genetics Limited................................................................................................ 192 Diagenode Diagnostics ............................................................................................................. 193 Diagnologix LLC.......................................................................................................................... 194 Enzo Life Sciences, Inc. .............................................................................................................. 195

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Epic Sciences.............................................................................................................................. 197 Epigenomics AG......................................................................................................................... 198 Eurofins Scientific ........................................................................................................................ 199 Exosome Diagnostics.................................................................................................................. 202 Exosome Sciences...................................................................................................................... 204 Fluidigm Corp ............................................................................................................................. 205 Fluxion Biosciences ..................................................................................................................... 207 Foundation Medicine................................................................................................................. 208 Freenome.................................................................................................................................... 209 GeneFirst Ltd. .............................................................................................................................. 210 Genetron Health (Beijing) Co., Ltd............................................................................................ 211 Genomic Health......................................................................................................................... 212 GILUPI Nanomedizin ................................................................................................................... 214 Grail, Inc. ..................................................................................................................................... 215 Guardant Health ........................................................................................................................ 217 HansaBiomed ............................................................................................................................. 218 HeiScreen.................................................................................................................................... 219 Helomics...................................................................................................................................... 221 Horizon Discovery ....................................................................................................................... 223 iCellate ........................................................................................................................................ 225 Illumina ........................................................................................................................................ 226 Incell Dx....................................................................................................................................... 228 Inivata.......................................................................................................................................... 229 Integrated Diagnostics............................................................................................................... 230

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Janssen Diagnostics ................................................................................................................... 231 MDNA Life SCIENCES, Inc........................................................................................................... 232 MDx Health ................................................................................................................................. 233 Menarini Silicon Biosystems ........................................................................................................ 235 Millipore Sigma............................................................................................................................ 236 Miltenyi Biotec............................................................................................................................. 237 miR Scientific............................................................................................................................... 238 Molecular MD ............................................................................................................................. 239 Myriad Genetics/Myriad RBM ................................................................................................... 240 NantHealth, Inc. ......................................................................................................................... 242 Natera ......................................................................................................................................... 244 NeoGenomics ............................................................................................................................ 246 New Oncology ........................................................................................................................... 248 Novogene Bioinformatics Technology Co., Ltd. ...................................................................... 249 Oncocyte.................................................................................................................................... 251 OncoDNA.................................................................................................................................... 252 Oxford Nanopore Technologies................................................................................................ 253 Perkin Elmer ................................................................................................................................. 255 Personal Genome Diagnostics.................................................................................................. 257 PrecisionMed .............................................................................................................................. 258 Promega ..................................................................................................................................... 259 Qiagen Gmbh ............................................................................................................................ 261 Quidel.......................................................................................................................................... 263 Rarecells SAS............................................................................................................................... 265

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RareCyte ..................................................................................................................................... 267 Resolution Biosciences, Inc ........................................................................................................ 268 Roche Molecular Diagnostics ................................................................................................... 269 Screencell ................................................................................................................................... 271 Siemens Healthineers ................................................................................................................. 272 simfo GmbH ................................................................................................................................ 274 Singlera Genomics Inc. .............................................................................................................. 275 SRI International .......................................................................................................................... 276 Sysmex Inostics............................................................................................................................ 278 Tempus Labs, Inc. ....................................................................................................................... 279 Thermo Fisher Scientific Inc. ....................................................................................................... 280 Thrive Earlier Detection .............................................................................................................. 282 Trovagene................................................................................................................................... 283 Volition......................................................................................................................................... 284
6. The Global Market for Liquid Biopsy Diagnostics ..........................................................285
6.1 Global Market Overview by Country.................................................................................. 286 6.1.1 Table – Global Market by Country................................................................................ 286 6.1.2 Chart - Global Market by Country................................................................................ 287 6.2 Global Market by Cancer - Overview ................................................................................ 288 6.2.1 Table – Global Market by Cancer ................................................................................ 288 6.2.2 Chart – Global Market by Cancer – Base/Final Year Comparison ............................ 289 6.2.3 Chart – Global Market by Cancer – Base Year ........................................................... 290 6.2.4 Chart – Global Market by Cancer – End Year ............................................................. 291 6.2.5 Chart – Global Market by Cancer – Share by Year .................................................... 292

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6.2.6 Chart – Global Market by Cancer – Segments Growth.............................................. 293 6.3 Global Market by Usage - Overview .................................................................................. 294 6.3.1 Table – Global Market by Usage................................................................................... 294 6.3.2 Chart – Global Market by Usage – Base/Final Year Comparison .............................. 295 6.3.3 Chart – Global Market by Usage – Base Year.............................................................. 296 6.3.4 Chart – Global Market by Usage – End Year ............................................................... 297 6.3.5 Chart – Global Market by Usage – Share by Year....................................................... 298 6.3.6 Chart – Global Market by Usage – Segments Growth ................................................ 299
7. Global Liquid Biopsy Diagnostic Markets – By Cancer ..................................................300
7.1 Breast ..................................................................................................................................... 301 7.1.1 Table Breast – by Country.............................................................................................. 301 7.1.2 Chart - Breast Growth .................................................................................................... 302 7.2 Colorectal ............................................................................................................................. 303 7.2.1 Table Colorectal – by Country ...................................................................................... 303 7.2.2 Chart - Colorectal Growth............................................................................................. 304 7.3 Cervical ................................................................................................................................. 305 7.3.1 Table Cervical – by Country.......................................................................................... 305 7.3.2 Chart - Cervical Growth ................................................................................................ 306 7.4 Lung ....................................................................................................................................... 307 7.4.1 Table Lung – by Country................................................................................................ 307 7.4.2 Chart - Lung Growth ...................................................................................................... 308 7.5 Prostate ................................................................................................................................. 309 7.5.1 Table Prostate – by Country .......................................................................................... 309 7.5.2 Chart – Prostate Growth ................................................................................................ 310

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7.6 Other...................................................................................................................................... 311 7.6.1 Table Other – by Country .............................................................................................. 311 7.6.2 Chart - Other Growth..................................................................................................... 312
8. Global Liquid Biopsy Diagnostic Markets – by Usage....................................................313
8.1 Screening .............................................................................................................................. 314 8.1.1 Table Screening – by Country ....................................................................................... 314 8.1.2 Chart - Screening Growth.............................................................................................. 315 8.2 Diagnostic ............................................................................................................................. 316 8.2.1 Table Diagnostic – by Country ...................................................................................... 316 8.2.2 Chart - Diagnostic Growth............................................................................................. 317 8.3 Therapy.................................................................................................................................. 318 8.3.1 Table Therapy – by Country........................................................................................... 318 8.3.2 Chart - Therapy Growth................................................................................................. 319 8.4 Monitor .................................................................................................................................. 320 8.4.1 Table Monitor – by Country ........................................................................................... 320 8.4.2 Chart - Monitor Growth.................................................................................................. 321
Appendices ..........................................................................................................................322
I. United States Medicare System: 2020 Clinical Laboratory Fees Schedule ......................... 322 II. COVID-19 Approved Assays .................................................................................................. 370

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Table of Tables
Table 1 Medicare Clinical Lab Expenditures Actual & Forecast 2014 to 2024 ($Billion) ............ 35 Table 2 Market Players by Type ..................................................................................................... 37 Table 3 Biopsy Sites .......................................................................................................................... 45 Table 4 Advantages of Liquid Biopsy in Screening Market .......................................................... 64 Table 5 Outlook - Phases of Liquid Biopsy Adoption by Year....................................................... 67 Table 6 Five Factors Driving Growth............................................................................................... 75 Table 7 Factors Limiting Growth ..................................................................................................... 78 Table 8 Key Diagnostic Laboratory Technology Trends ............................................................... 82 Table 9 Next Generation Sequencing Technologies – Speed and Cost .................................... 83 Table 10 - Global Market by Region ............................................................................................ 286 Table 11 Global Market by Cancer ............................................................................................. 288 Table 12 Global Market by Usage................................................................................................ 294 Table 13 Breast by Country ........................................................................................................... 301 Table 14 Colorectal by Country .................................................................................................. 303 Table 15 Cervical by Country ....................................................................................................... 305 Table 16 Lung by Country ............................................................................................................. 307 Table 17 Prostate by Country ....................................................................................................... 309 Table 18 Other by Country............................................................................................................ 311 Table 19 Screening by Country ................................................................................................... 314 Table 20 Diagnostic by Country ................................................................................................... 316 Table 21 Therapy by Country....................................................................................................... 318

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Table 22 Monitor by Country ....................................................................................................... 320 Table 23 2020 Clinical Lab Fee Schedule .................................................................................... 322 Table 24 COVID -19 Approved Assays......................................................................................... 370

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Table of Figures
Figure 1 Medicare Clinical Lab Expenditures 2014 to 2024 ($Million).......................................... 34 Figure 2 Comparison of Liquid Biopsy Classes............................................................................... 49 Figure 3 Characteristics of Different Vesicle Types ....................................................................... 60 Figure 4 Percentage of World Population Over 65....................................................................... 77 Figure 5 Global Market Density Chart......................................................................................... 287 Figure 6 Global Market by Cancer - Base vs. Final ..................................................................... 289 Figure 7 Global Market by Cancer Base Year ............................................................................ 290 Figure 8 Global Market by Cancer End Year .............................................................................. 291 Figure 9 Cancer Share by Year .................................................................................................... 292 Figure 10 Cancer Segments Growth............................................................................................ 293 Figure 11 Global Market by Usage - Base vs. Final...................................................................... 295 Figure 12 Global Market by Usage Base Year............................................................................. 296 Figure 13 Global Market by Usage End Year .............................................................................. 297 Figure 14 Usage Share by Year..................................................................................................... 298 Figure 15 Usage Segments Growth .............................................................................................. 299 Figure 16 Breast Growth ................................................................................................................ 302 Figure 17 Colorectal Diagnostics Growth .................................................................................... 304 Figure 18 Cervical Growth ............................................................................................................ 306 Figure 19 Lung Growth .................................................................................................................. 308 Figure 20 Prostate Growth............................................................................................................. 310 Figure 21 Other Growth................................................................................................................. 312

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Figure 22 Screening Growth ......................................................................................................... 315 Figure 23 Diagnostic Growth ........................................................................................................ 317 Figure 24 Therapy Growth............................................................................................................. 319 Figure 25 Monitor Growth.............................................................................................................. 321