Global CAR-TCell TherapyMarket –Market Size, Forecasts, Trials & Trends | BioInformant.com

Global CAR-TCell TherapyMarket –Market Size, Forecasts, Trials & Trends | BioInformant.com

TABLE OF CONTENTS

1. REPORT OVERVIEW 111.1 Statement of the Report 111.2 Executive Summary 131.3 INTRODUCTION 152. SIXTY YEAR HISTORY OF CAR-T CELL THERAPY 172.1 Timeline of CAR-T Cell Therapy Development 183. CAR-T MANUFACTURING PROCESSES 193.1 Manufacturing Autologous CAR-T Cells 193.2 T-CellSource 193.3 T-Cell Activation203.3.1 Beads-Based T-Cell Activation 213.3.2 Antibody-Coated Magnetic Beads 213.3.3 Antibody-Coated Nanobeads 213.3.4 Expamer Technology 213.3.5 Activation with Anti-CD3 Antibodies 223.4 Genetic Modification of T-Cells 223.5 Expansion of CAR-T Cells 233.5.1 Expansion of CAR-T Cells using GE Bioreactors 233.5.2 Expansion of CAR-T Cells using G-Rex Bioreactors 233.5.3 Expansion of CAR-T Cells using Prodigy 243.5.4 Expansion of CAR-T Cells through Recursive AAPC Stimulation 243.6 Clinical CAR-T Cell Manufacturing Quality Checkpoints 243.6.1 Qualification of Manufacturing Facilities 243.6.2 Qualification of Ancillary Components 253.6.3 Qualification of Manufacturing Process 253.7 In-Process Testing and Release Testing of Cellular Products 263.8 Allogeneic CAR-T Cells 264. STRUCTURE OF A CAR-T CELL 284.1 First Generation CAR-T Cells 284.2 Second Generation CAR-T Cells294.3 Third Generation CAR-T Cells 304.4 Fourth Generation CAR-T Cells 304.5 Mechanism of Action 324.6 New CAR Models and Concepts 334.6.1 Truck CAR 334.6.2 Universal CAR 334.6.3 Self-driving CAR 334.6.4 Armored CAR 344.6.5 Self-destruct CAR 344.6.6 Conditional CAR 344.6.7 TanCAR 344.6.8 Dual CAR 354.6.9 Safety CAR )sCAR) 354.7 Basic Components of CAR 364.7.1 Common Deigns of CAR-T Constructs 364.7.1.1 Single Chain Fv Fragments (scFv) 374.7.1.2 4-1BB, CD28, OX40, FcεRIγ and CD3ξ 384.7.1.3 Vectors for Transfection385. NUMBER OF CAR-T COMPANIES, THEIR RECENT ACTIVITIES 395.1 Geographical Distribution of CAR-T Cell Therapeutic Companies 395.2 Immunocellular Therapy Companies by Cell Type405.3 Market Leaders in CAR-T Cell Therapy and their Recent Activities415.3.1 AbbVie 41

Global CAR-TCell TherapyMarket –Market Size, Forecasts, Trials & Trends | BioInformant.com

5.3.2 Allogene Therapeutics 415.3.3 Amgen 425.3.4 Agios Pharmaceutical 425.3.5 Atara Biotherapeutics 425.3.6 Autolus Limited 425.3.7 Bellicum Pharmaceuticals 435.3.8 bluebird bio 435.3.9 Calibr 435.3.10 Carina Biotech 435.3.11 CARsgen Therapeutics 445.3.12 Celgene Corporation 445.3.13 Cellectis 445.3.14 Cell Medica 445.3.15 Cell Design Labs 455.3.16 Celularity 455.3.17 Celyad 455.3.18 Fate Therapeutics 455.3.19 Fortress Bio 465.3.20 Gilead Sciences 465.3.21 Janssen Biotech 465.3.22 Juno Therapeutics 465.3.23 JW Therapeutics 475.3.24 Kite Pharma 475.3.25 Medisix Therapeutics 475.3.26 Mustang Bio 475.3.27 Nanjing Legend Biotech485.3.28 Novartis 485.3.29 Pfizer 485.3.30 Precision Biosciences 485.3.31 Posedia Therapeutics 495.3.32 Shire 495.3.33 Sorrento Therapeutics 495.3.34 Ziopharm 496. TUMOR-ASSOCIATED TARGET ANTIGENS 506.1 Antigens on Solid Tumors 506.1.1 Epidermal Growth Factor Receptor (EGFR) 516.1.2 Epidermal Growth Factor Receptor Variant III (EGFRvIII) 516.1.3 Human Epidermal Growth Factor Receptor-2 (HER2) 516.1.4 Mesothelin (MSLN) 516.1.5 Prostate-Specific Membrane Antigen (PSMA) 526.1.6 Disialoganglioside 2 (GD2) 526.1.7 Interleukin-13Rα2 (IL13Rα2) 526.1.8 Glypican-3 (GPC3) 526.1.9 Carbonic Anhydrase IX (CAIX) 536.1.10 L1 Cell Adhesion Molecule (L1-CAM) 536.1.11 Cancer Antigen 125 (CA125) (MUC16) 536.1.12 Prominin-1 (CD133) 536.1.13 Fibroblast Protein-α (FAP-α) 546.1.14 Cancer/Testis Antigen 1B (CTAG1B) 546.1.15 Mucin 1 (MUC1) 546.1.16 Folate Receptor-α (FR-α) 546.2 CAR-T Targets in Hematologic Malignancies 546.2.1 CD19 556.2.2 CD20 556.2.3 CD22 56

Global CAR-TCell TherapyMarket –Market Size, Forecasts, Trials & Trends | BioInformant.com

6.2.4 ROR1 566.2.5 CD30 566.2.6 CD138 566.2.7 CD123 576.2.8 NKG2D-L 576.2.9 BCMA 576.2.10 CD174 576.3 CAR-T Cell Trials Targeting CD19 576.3.1 Positive CR Rates in CD19 Targeted Studies in Hematological Malignancies 586.3.2 Outcome of CAR-T Cell Therapy Trials Targeting Antigens other than CD19 596.3.3 Targets other than CD19 in Hematological Cancers 606.3.4 CD30 vs. BCMA Targets for Multiple Myeloma 616.4 CAR-T Cell Therapy for Solid Tumors 626.4.1 CAR-T Cell Targets in Solid Malignancies 637. TARGET DISEASES FOR CAR-T CELL THERAPY 657.1 Acute Lymphoblastic Leukemia (ALL) 657.2 Chronic lymphocytic leukemia (CLL) 667.3 Non-Hodgkin lymphoma 667.4 Acute myeloid leukemia (AML) 677.5 Neuroblastoma 677.6 Multiple myeloma (MM) 688. PRICING AND PAYMENT MODELS FOR CAR-T THERAPIES 698.1 Controversies over CAR-T Pricing 698.2 Hospital Mark-up Costs for Kymriah and Yescarta 708.3 Cost Effectiveness of Tisagenlecleucel and Axicabtagene718.4 Value-Based Price Benchmarks 728.5 Unit Prices Needed to Reach Cost-Effectiveness Thresholds 738.6 Alternate Payment Strategies 739. MEDICAL FACILITIES OFFERING CAR-T THERAPIES 749.1 CAR-T Recommended in Europe 769.2 CAR-T Cell Therapy in Chinese Hospital 769.3 Canada Joins the CAR-T Club 7710. CAR-T THERAPY PATENT LANDSCAPE 7810.1 Number of CAR-T Cell Patents, 2013-2018 7810.2 CAR-T Patent Types 7910.3 A Brief Snapshot of CAR-T Patent Landscape 8010.3.1 Patents for Anti-CD19 CAR-T 8010.3.2 Patents for Anti-BCMA CAR-T 8010.3.3 Patents for Regulatable CAR-T 8110.3.4 Patents for CAR-T for Solid Tumors 8110.4 Major CAR-T Patent Applicants 8211. DEALS, FUNDINGS, PARTNERSHIPS AND COLLABORATIONS8311.1 Funding for CAR-T 8311.2 CAR-T Deals 8311.3 Initial Public Offering (IPO) 8511.4 Key CAR-T Technology Deals 8511.4.1 Deal between Juno Therapeutics and Eureka for a Fully Human ScFv Binding Domain 8611.4.2 Acquisition of Stage Cell Therapeutics by Juno Therapeutics 8611.4.3 Collaboration between Juno Therapeutics and Editas Medicine 8711.4.5 Kite and Alpine in Research and License Agreement 8711.4.6 Johnson & Johnson Gets PiggyBac Technology from Transposagen 8711.4.7 Johnson & Johnson and Posedia in a Technology Deal 8711.4.8 Partnership between Baxalta and Precision Biosciences 8811.4.9 Novartis, Intellia and Caribou 8811.4.10 Trends in Oncology Licensing, Joint Venture and Research Deals 88

Global CAR-TCell TherapyMarket –Market Size, Forecasts, Trials & Trends | BioInformant.com

12. THE LANDSCAPE OF CAR-T CELL THERAPY CLINICAL TRIALS 9012.1 The Surge in Number of CAR-T Clinical Trials 9012.2 Percentage (%) of Total CAR-T Clinical Trials by Target 9112.3 Research Focus on CAR-T Trials by Indication 9212.4 Clinical Trials using CAR-T Cells by Country as of 2018 9312.5 CAR-T Clinical Trials to Watch 9312.6 CAR-T Projects with Commercial Licensees 9412.7 Clinical CAR-T Constructs with Sole Involvement from Academicia 9612.8 Anti-CD19 CAR-T Studies 9712.9 CAR-T Studies in Multiple Myeloma and Acute Myeloid Leukemia 10011.10 CAR-T Cell Therapy for Solid Tumors 10112.11 Studies of CAR-T Projects Transfected using mRNA Electroporation 10312.12 CAR-T Projects Incorporating Suicide Genes 10312.13 Early Stage CAR-T Assets 10412.14 Anti-CD22 CAR-T Projects 10512.15 Cytokine Release Syndrome (CRS) with CART19 Therapy 10612.16 CAR-T Therapy Pipeline Distribution by Indication 10612.17 CAR-T Therapy Pipeline Distribution by Target Antigen 10812.18 Distribution of CAR-T Clinical Trials in China 10912.18.1 CD19-Directed CAR-T Clinical Trials in China 10912.18.2 Chinese Trials Targeting Non-CD19 Antigens 11112.18.3 Chinese Trials on Solid Tumors 11112.18.4 Chinese Trials Using Fourth Generation CAR Constructs 11312.18.5 Clinical Stage CAR-T Projects in China 11313. CAR-T CELL PRODUCTS IN THE MARKET 11513.1 Tisagenlecleucel (Kymriah) 11513.1.1 Evidences Supporting Effectiveness of Tisagenlecleucel (Kymriah) 11613.1.2 Medical Necessities for Tisagenlecleucel (Kymriah) 11713.1.3 Overall Remission Rates in Patients Treated with Kymriah 11713.1.4 Overall Event-Free Survival Rate with Tisagenlecleucel (Kymriah) 11813.1.5 Key Adverse Events in ELIANA Trial 11913.1.6 Key Adverse Events in JULIET Trial 11913.1.7 Budget Impact for Tisagenlecleucel 12013.1.8 Overall Adverse Events with Tisagenlecleucel 12113.1.9 Per-Patient Potential Budget Impact of Tisagenlecleucel 12213.2 Axicabtagene Ciloleucel (Yescarta) 12213.2.1 Evidences to Support the Effectiveness of Axicabtagene Ciloleucel 12313.2.2 Medical Necessities for Axicabtagene Ciloleucel (Yescarta) 12313.2.3 Clinical Benefits of Axicabtagene Ciloleucel (Yescarta) 12413.2.4 Objective Response Rates (ORR) for Axicabtagene Ciloleucel 12413.2.5 CRR for Axicabtagene Ciloleucel 12513.2.6 Adverse Events in ZUMA-Trial 12513.2.7 Base-Case Results 12613.2.8 Value-Based Benchmark Prices 12613.2.9 Per-Patient Budget Impact of Axicabtagene Ciloleucel 12713.2.10 Unit Cost for Healthcare Utilization in CAR-T Therapy 12813.2.10.1 Costs Associated with Adverse Events 12814. INSURANCE COVERAGE FOR CAR-T THERAPY 13014.2 Coverage Policies for Tisagenlecleucel – B-ALL Patients 13014.2 Coverage for Stem Cell Transplantation (SCT) – B-Cell ALL Patients 13014.3 Coverage for Axicabtagene Ciloleucel – B-Cell NHL Patients 13114.4 Coverage for Stem Cell Plantation (SCT) in B-Cell NHL Patients 13114.5 Insurance Coverage by Medicare and Medicaid 13215. COMMERCIAL THREATS FOR CAR-T INDUSTRY 13315.1 Competition in a Narrow Field 133

Global CAR-TCell TherapyMarket –Market Size, Forecasts, Trials & Trends | BioInformant.com

15.2 Competition from other Technologies 13315.3 Threat from TCRs 13315.4 Threat of Litigation 13316. CHALLENGES TO OVERCOME13416.1 Lack of Persistence 13416.2 Inadequate Activation 13416.3 Transfection Method 13416.4 Humanized Binding Domains 13416.5 Antigen Escape 13516.6 Lineage Switching 13516.7 Lack of Safety 13516.8 Benefits of CAR-T Cell Therapy 13516.9 CAR-T Cell Therapy: Only the Beginning of the Story 13516.10 A New Standard13617. MARKET ANALYSIS 13717.1 Global Market for CAR-T Therapy by Geography 13817.2 Global Market for CAR-T Therapy by Country 13917.3 Global Market for CAR-T Cell Therapy by Targeted Antigens 14117.4 Competitive Landscape 14118. COMPANY PROFILES 14318.1 AbbVie Inc. 14318.1.1 Collaboration with Calibr 14318.2 Adaptimmune Therapeutics PLC14418.2.1 Pipeline 14418.3 Amgen, Inc. 14518.3.1 Amgen’s Collaboration with Kite Pharma14618.3.2 Amgen’s Collaboration with MD Anderson Cancer Center 14618.4 Atara Biotherapeutics, Inc. 14618.4.1 Technology 14718.4.2 Atara tab-cel™ 14818.4.3 Atara ATA188 14818.4.4 Atara ATA230 14818.5 Aurora Biopharma, Inc. 14918.5.1 CAR-T for Glioblastoma14918.6 Autolus Therapeutics PLC 14918.6.1 Technology 15018.7 Bellicum Pharmaceuticals, Inc. 15018.7.1 GoCAR Technology 15018.7.2 BPX-501 15118.7.3 BPX-601 15118.7.4 BPX-701 15118.8 BioAtla LLC 15218.8.1 Conditionally Active Biologics (CABs) 15218.8.2 Agreement with Pfizer 15218.8.3 Agreement with Sinobioway 15318.9 bluebird bio 15318.9.1 Technology 15318.10 Carina Biotech 15418.10.1 Technology 15418.11 CARsgen Therapeutics, Ltd. 15518.12 CARTherics 15618.13 Cellectis 15618.13.1 Products 15718.14 Celularity 15718.15 Celyad SA 158

Global CAR-TCell TherapyMarket –Market Size, Forecasts, Trials & Trends | BioInformant.com

18.16 Creative Biolabs15918.17 DiaCarta, Inc. 16118.17.1 Personalized CAR-T Immunotherapy Platform 16118.18 Endocyte, Inc. 16218.18.1 LU-PSMA-617 16218.18.2 Adaptor-Controlled CAR-T Therapy 16218.19 F1 Oncology, Inc. 16318.19.1 Conditionally Active Biologics (CAB) Technology 16318.20 Fate Therapeutics Inc. 16418.21 Humanigen, Inc.16518.21.1 Ifabotuzumab 16518.22 Immune Therapeutics, Inc. 16618.22.1 CAR-T from Immune Therapeutics 16618.23 Intrexon, Corp. 16718.24 Juno Therapeutics, Inc. 16818.25 Kite Pharma, Inc. 16918.25.1 Product 16918.25.1.1 Yescarta (Axicabtagene ciloleucel) 16918.26 Lion TCR Pte Ltd. 17018.26.1 Technology 17018.26.1.2 Virus-Related Cancers 17018.27 MaxCyte, Inc. 17118.27.1 CARMA Platform 17118.28 Mesoblast, Ltd. 17218.28.1 Partnership with Cartherics 17218.29 Minerva Biotechnologies Corp. 17318.29.1 Solid Tumor Cancer Portfolio 17318.29.2 Antibody Therapeutic for MUC1* Positive Cancers 17318.29.3 Anti-Metastasis Antibody 17418.29.4 MUC1*17418.30 Mustang Bio, Inc. 17518.31 Novartis AG 17618.31.1 Kymriah (Tisagenlecleucel) 17618.32 Oxford BioMedica PLC. 17718.32.1 LentiVector Platform 17718.33 PeproMene Bio Inc. 17818.33.1 BAFFR R CAR-Cell 17918.34 Pfizer, Inc. 17918.34.1 Asset Contribution Agreement with Allogene Therapeutics 18018.35 Posedia Therapeutics Inc. 18018.36 Precision Biosciences, Inc. 18118.36.1 Precision Biosciences’ Cancer Immunotherapy 18118.37 ProMab Biotechnologies Inc. 18118.38 Servier Oncology 18318.39 Sorrento Therapeutics, Inc. 18418.40 TC Biopharm Ltd. 18418.40.1 ImmuniCAR 18518.40.2 OmniCAR 18518.40.3 OmnImmune 18518.41 Tessa Therapeutics Pte Ltd. 18518.41.1 TT10 EBVSTs 18618.41.2 TT12 Armored HPVSTs 18618.41.3 TT14 GPC3-CAR VSTs 18618.41.4 TT16 HER2-CAR VSTs 18618.42 TILT Biotherapeutics Ltd. 187

Global CAR-TCell TherapyMarket –Market Size, Forecasts, Trials & Trends | BioInformant.com

18.42.1 Technology 18718.43 Tmunity Therapeutics Inc. 18818.43.1 Technology 18818.44 TrakCel Ltd. 18918.45 Xyphos 18918.45.1 ConvertibleCAR Technology 18918.46 ZIOPHARM Oncology, Inc. 19018.46.1 IL-12 Platform 19118.46.2 Sleeping Beauty 191

INDEX OF FIGURES

FIGURE 1.1: Diagrammatic Representation of the Binding of CAR-T with Antigen of Malignant Cell 16FIGURE 3.1: Stages from Apheresis to Patient Administration of CAR-T Cells 19FIGURE 3.2: The Process of CAR-T Cell Manufacturing 20FIGURE 4.1: Building a CAR-T Cell and its Binding to Tumor Antigen 28FIGURE 4.2: First Generation CAR-T Cells 29FIGURE 4.3: Second Generation CAR-T Cells 29FIGURE 4.4: Third Generation CAR-T Cells 30FIGURE 4.5: Fourth Generation CAR-T Cells 31FIGURE 4.6: Recognition and Killing of Tumor Cell by CAR-T Cell 32FIGURE 4.7: New CAR Models and Concepts 35FIGURE 4.8: Components of a Chimeric Antigen Receptor 36FIGURE 4.9: Schematic Representation of scFv Fragment 37FIGURE 5.1: Global Distribution of CAR-T Cell Therapeutic Companies 40FIGURE 5.2: Number of Immunocellular Therapy Companies by Cell Type41FIGURE 6.1: Percent (%) Share of CAR-T Cell Trials Targeting CD19 58FIGURE 6.2: Outcome of CAR-T Cell Therapy Trials in Liquid Malignancies, Targeting CD19 59FIGURE 6.3: Outcome of CAR-T Cell Therapy Trials in Liquid Malignancies, Except CD19 60FIGURE 6.4: Most Frequent CAR-T Cell Targets in Liquid Malignancies (Except CD19) 61FIGURE 6.5: Trend in Number of CAR-T Cell Therapy Clinical Trials: CD30 vs. BCMA 62FIGURE 6.6: Clinical Outcome of CAR-T Cell Therapy Trials in Solid Malignancies 63FIGURE 6.7: Most Frequent CAR-T Cell Targets in Solid Malignancies 64FIGURE 10.1: Number of CAR-T Cell Patents, 2013-2018 78FIGURE 10.2: Major CAR-T Patent Applicants 82FIGURE 11.1: Licensing, Joint Venture and Research Only Oncology Deals from 2013-2017 89FIGURE 12.1: Number of Initiated CAR-T Cell Therapy Clinical Trials, 2007-2017 90FIGURE 12.2: Percentage (%) of Total CAR-T Clinical Trials by Target 91FIGURE 12.3: Research Focus on CAR-T Trials by Indication 92FIGURE 12.4: Engineered CD19-CAR-T Cell Targeting CD19 Antigen on the Malignant Cell 97FIGURE 12.5: CAR-T Cells Targeting Solid Tumor Antigen 101FIGURE 12.6: CAR-T Therapy Pipeline Distribution by Indication 107FIGURE 12.7: CAR-T Therapy Pipeline Distribution by Target Antigen 108FIGURE 17.1: Global Market for CAR-T Cell Therapies, 2018-2023 137FIGURE 17.2: Global Market for CAR-T Therapy by Geography, 2024 138FIGURE 17.3: Global Market for CAR-T Therapy by Country, 2024 140FIGURE 17.4: Global Market for CAR-T Cell Therapies by Targeted Antigen, 2018 141

Global CAR-TCell TherapyMarket –Market Size, Forecasts, Trials & Trends | BioInformant.com

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