MESENCHYMAL STEM CELLS ADVANCES & APPLICATIONS TABLE OF CONTENTS

Transcription

1 MESENCHYMAL STEM CELLS ADVANCES & APPLICATIONS TABLE OF CONTENTS 1. REPORT OVERVIEW Statement of the Report Executive Summary INTRODUCTION Regenerative Medicine (RM) and Advanced Therapies Industry: A Brief Overview Global Breakdown of Major RM Industries by Region Breakdown of Global RM Companies by Type Number of Therapeutic Companies, Approved Products and Clinical Trials in RM Sector Number of RM Clinical Trials by Phase of Development Number of RM Companies by Disease Focus Area Major Financial Events in RM Industry Major Partnerships and Acquisitions in RM Industry Total Financings in RM Industry by Segment Type of Financing for RM Industry Major Regulatory Milestones in RM Industry Major Data and Technology Events in RM Industry Major Pharma and Biotech Companies Active in Advanced Therapies Major Corporate Partnerships in RM Industry Anticipated Major RM Clinical Events Notable Deals and Acquisitions in RM, Cell and Gene Therapy Space Big Pharma s Perception of RM Major Therapeutic Opportunities for Big Pharma in Cell Therapy and RM Current Opportunities Near-Term Opportunities Long-Term Opportunities CELL THERAPY INDUSTRY: A BRIEF OVERVIEW Types of Stem Cells Used in Cell Therapy Human Embryonic Stem Cells (hescs) Induced Pluripotent Stem Cells (ipscs) Hematopoietic Stem Cells (HSCs) Mesenchymal Stem Cells (MSCs) Adipose Stem Cells (ASCs) Neural Stem Cells (NSCs) Cell Therapy Product Candidates in Late-Stage Clinical Development Cell Therapy Product Candidates in Early-Stage Clinical Development Cell Therapy Products Being Developed for Cardiovascular Indication Cell Therapy Products Being Developed for Central Nervous System Indication Cell Therapy Products Developed and Being Developed for Wound Care Cell Therapy Products Developed and Being Developed for Spine and Orthopedics Cell Therapy Products Being Developed for Diabetes Cell Therapy Products Being Developed for Autoimmune Diseases Combination of Cell and Gene Therapy Products in Development Cancer Programs Utilizing the Combination of Cell and Immunotherapy Major Commercially Available Cell Therapy Products Cell Therapy Products Approved in South Korea Cell Therapy Clinical Trials: An Overview Cell Therapy Clinical Trials by Geography Top Eight Countries in Cell Therapy Clinical Trials Major Cell Types in Cell Therapy Clinical Trials Major Disease Indications Addresses by Cell Therapy Clinical Trials Fifteen Major Cell Therapies in Phase III... 55

2 Prochymal Mesenchymal Precursor Cell (MPC) MyoCell Ixmyelocel-T ELAD HP StemEx (Carlecortemcel-L) LaViv GSK Renew NT-501 (Renexus) Neocart DeNovo ET MACI Clinical Trial Failures in Cell Therapy in Failure of Phase II for MultiStem Failure of Cardio 133 Trial Termination of AlloCure s ACT-AKI Trial Failed Stroke Trial in India Failure of HeartiCellGram-AMI Trial Failure of Adipose MSCs in ARDS CD133+ in CLI Not Feasible Failed MSC Trial for Multiple Sclerosis Failure of Chinese Diabetes Trial Failed Efficacy Trial in AMI by Stempeucel A Sampling of Stem and Progenitor Cell-Based Trials with 2014 Clinical Readouts Major Cell Therapy Companies and their Locations Involvement of Multinational Companies (MNCs) in Cell Therapy Sector MESENCHYMAL STEM CELLS (MSCs): AN OVERVIEW Biological Properties of MSCs Contributing to their Therapeutic Effects MSCs Capacity to Migrate and Engraft MSCs Differentiation Potential MSCs Potential to Secrete Multiple Bioactive Molecules MSCs Potential for Immunomodulatory Functions Variable Immunophenotype of MSCs Factors Impacting MSCs Acquisition Major Clinical Sources of MSCs Bone Marrow-Derived Mesenchymal Stem Cells (BMMSCs) BMMSCs and Kidney BMMSCs and Pancreas BMMSCs and Heart BMMSCs and Liver BMMSCs and Brain BMMSCs and Intestine BMMSCs and Bone Adipose-Derived Mesenchymal Stem Cells Selected ADSC Secretomes and their Functions Mesenchymal Stem Cells (MSCs) Derived from Wharton s Jelly Clinical Application Properties of WJ-MSCs Immunoprivileged Status of WJ-MSCs Clinical Applications of WJ-MSCs Umbilical Cord Blood-Derived MSCs (UCBMSCs) Dominance of MSCs in Cell Therapy Clinical Trials Major Diseases Addressed by MSCs in Current Clinical Trials MSCs for Treating Liver Diseases MSCs for Neurodegenerative Diseases... 88

3 4.5.3 Clinical Trials Using MSCs for Autoimmune Diseases Clinical Trials Using MSCs for Diabetes MSCs for Cardiovascular Repair MSCs for Musculoskeletal Diseases Studies Using MSCs for Musculoskeletal Indications by Leading Countries Application of MSCs in Joint Diseases MSCs in Neuron/Spinal Cord Diseases MSC Infusion for GvHD MSCs for Crohn s Disease MSCs in Wound Healing Increasing Focus on Immunological Properties of MSCs Percentage of MSCs Clinical Trials by Different Phases Selected MSCs Late-Stage Pipeline Cell Therapies A BRIEF OVERVIEW OF THE MARKET FOR STEM CELLS Global Market for Stem Cells by Disease Indication SELECTED COMPANY PROFILES American Type Culture Collection Inc. (ATCC) Anterogen Co., Ltd Cupistem Injection Queencell Apceth GmbH & Co. KG Apceth s Research Areas BioCardia Inc BioRestorative Therapies Inc brtxdisc ThermoStem Bone Therapeutics SA PREOB ALLOB BrainStorm Cell Therapeutics Inc NurOwn CellGenix Technologie Transfer GmbH Celprogen Inc CellTherapies P/L Services Product Cesca Therapeutics Inc Surgwerks Cellwerks AutoXress (AXP) MarrowXpress (MXP) Res-Q BMC Cyagen Biosciences Inc Mesenchymal Stem Cells from Cyagen Adipose-Derived Mesenchymal Stem Cells from Cyagen Mesenchymal Stem Cells with GFP from Cyagen Adipose-Derived Mesenchymal Cells with GFP from Cyagen Stem Cell Culture Media from Cyagen Stem Cell Differentiation Media from Cynagen Primary Cells from Cynagen Cyagen s Cryopreservation Media Cyagen s Primary Cell Culture Media General Cell Culture Supplements and Specialty Reagents from Cyagen Cynata Therapeutics Ltd Cymerus Platform Technology Cytori Therapeutics Inc

4 Clinical Trial for Scleroderma Clinical Trials for Osteoarthritis Escape Therapeutics Genlantis Kite Pharma Inc Engineered Autologous Cell Therapy (eact) DC-Ad GM-CAIX Life Technologies Corporation Lonza Group Ltd Selected Products Medipost Co. Ltd Cartistem Neurostem Pneumostem Mesoblast Ltd Mesoblast s Product Pipeline Overview NuVasive Inc Osteocel Octa Therapeutics Inc Organogenesis Inc Apligraf Dermagraft Orthofix International N.V Trinity Elite Trinity Evolution Osiris Therapeutics Inc Grafix OvationOS Cartiform Pluristem Therapeutics Inc PLX Cells PromoCell Regeneus Ltd Products ScienCell Research Laboratories Stemcell Technologies Inc Stemedica Cell Technologies Inc Stemedyne MSC Stemedyne NSC Stemedyne RPE Stempeutics Research Pvt. Ltd Stempeucel Stempeutron Stempeucare TiGenix N.V Cx Cx Cx Vericel Corporation

5 INDEX OF FIGURES FIGURE 3.1: Number of Cell Therapy Clinical Trials, FIGURE 3.2: Cell Therapy Clinical Trials (%) by Geography in FIGURE 3.3: Top Eight Countries in Cell Therapy Clinical Trials (%) in FIGURE 3.4: Major Cell Types in Cell Therapy Clinical Trials (Numbers) in FIGURE 3.5: Major Cell Therapy Clinical Trials (Numbers) by Indication in FIGURE 4.1: Schematic of Factors Impacting MSC Acquisition FIGURE 4.2: Number of Clinical Trials Using MSCs, FIGURE 4.3: Increasing Focus on the Immunological Properties of MSCs FIGURE 4.4: Percentage of MSCs Clinical Trials by Different Phases FIGURE 5.1: Global Market for Stem Cells, Stem Cell Services, Cord Blood Banking, Stem Cell Therapies and Bone Marrow Transplants, Through FIGURE 5.2: Global Market for Stem Cells by Disease Indication, Through INDEX OF TABLES TABLE 2.1: Global Breakdown of Major RM Industries by Region..17 TABLE 2.2: Global Breakdown of RM Companies by Type, TABLE 2.3: Number of Therapeutic Companies, Approved Products and Clinical Trials, TABLE 2.4: Number of RM Clinical Trials by Phase in TABLE 2.5: Number of RM Companies by Disease Focus Area. 20 TABLE:2.6: Major Financial Events in RM Industry in TABLE 2.7: Major Partnerships and Acquisitions in RM Industry in TABLE 2.8: Total Financings in RM Industry by Segment in TABLE 2.9: Type of Financing for RM Industry in 2013 and TABLE 2.10: Major Regulatory Milestones in RM Industry in TABLE 2.11: Major Data and Technology Events in RM Industry in TABLE 2.12: Major Pharma and Biotech Companies Active in Advanced Therapies in TABLE 2.13: Major Corporate Partnerships in RM Industry in TABLE 2.14: Anticipated Major RM Clinical Events in TABLE 2.15: Notable Deals and Acquisitions in RM, Cell and Gene Therapy.29 TABLE 2.16: Big Pharma's Interest on Investing in RM by Sector.31 TABLE 2.17: Most Promising Areas in RM for Big Pharma.32 TABLE 3.1: Different Types of Stem Cells Used in Cell Therapy and their Characteristics...35 TABLE 3.2: Cell Therapy Product Candidates in Late-Stage Clinical Development 36 TABLE 3.3: Cell Therapy Product Candidates in Early-Stage Clinical Development..37 TABLE 3.4: Cell Therapy Products Being Developed for Cardiovascular Indication...39 TABLE 3.5: Cell Therapy Products Being Developed for Central Nervous System.40 TABLE 3.6: Cell Therapy Products Developed and Being Developed for Wound Care..41 TABLE 3.7: Cell Therapy Products for Spine and Orthopedics...43 TABLE 3.8: Cell Therapy Products Being Developed for Diabetes 45 TABLE 3.9: Cell Therapy Products Being Developed for Autoimmune Diseases 46 TABLE 3.10: Combination of Cell and Gene Therapy Products in Development.47 TABLE 3.11: Cancer Programs Utilizing the Combination of Cell and Immunotherapy..48 TABLE 3.12: Major Commercially Available Cell Therapy Products..50 TABLE 3.13: Cell Therapy Products Approved in South Korea..51 TABLE 3.14: A Sampling of Stem and Progenitor Cell-Based Trials with 2014 Readouts.62 TABLE 3.15: Major Cell Therapy Companies in the World..63 TABLE 3.15: Major Cell Therapy Companies in the World (Continued) 64 TABLE 3.15: Major Cell Therapy Companies in the World (Continued) 65 TABLE 3.15: Major Cell Therapy Companies in the World (Continued) 66 TABLE 3.15: Major Cell Therapy Companies in the World (Continued) 67 TABLE 3.16: Major Companies and Products in Development in Cell Therapy Sector TABLE 3.16: Major Companies and Products in Development in Cell Therapy (Continued....68

6 TABLE 4.1: Origin and Cell Typed Derived from MSCs TABLE 4.2: Important Bioactive Molecules Secreted by MSCs and Their Functions...71 TABLE 4.3: Immunomodulatory Effects of MSCs on Immune Cells TABLE 4.4: Cell Surface Antigen Expressions of MSCs Isolaed from Different Sources TABLE 4.5: Major Clinical Sources of MSCs...74 TABLE 4.6: A Sample of Clinical Trials Using BMMSCs for Kidney Diseases TABLE 4.7: A Sample of Clinical Trials Using BMMSCs for Diabetes TABLE 4.8: A Sample of Clinical Trials Using BMMSCs for Heart Diseases TABLE 4.9: A Sample of Clinical Trials Using BMMSCs for Liver Diseases TABLE 4.10: Clinical and Experimental Therapies Using MSCs for Neural Diseases TABLE 4.11: A Sample of Clinical Trials Using MSCs for Intestinal Diseases...78 TABLE 4.12: A Sample of Clinical Trials Using BMMSCs for Musculoskeletal Diseases TABLE 4.13: ADSCs Transplantation in Clinical Trials by Region in Phase III, TABLE 4.14: Selected ADSC Secretomes and their Functions TABLE 4.15: A Summary of Clinical Trials Using WJ-MSCs.82 TABLE 4.15: A Summary of Clinical Trials Using WJ-MSCs (Continued)..83 TABLE 4.16: Clinical Trials Using UCBMSCs and Targeted Diseases...84 TABLE 4.17: Dominance of MSCs in 2014 Stem Cells Clinical Trials. 85 TABLE 4.18: Clinical Trials Using MSCs by Disease Type, TABLE 4.19: A Sample of Clinical Trials Using MSCs for Liver Diseases..87 TABLE 4.20: A Sample of Clinical Trials Using MSCs for Neurodegenerative Diseases. 88 TABLE 4.21: A Sample of Phase I and II Clinical Trials for Autoimmune Diseases..89 TABLE 4.22: A Sample of Clinical Trials Using MSCs for Diabetes TABLE 4.23: A Sample of Clinical Trials Using MSCs for Cardiovascular Diseases TABLE 4.24: Clinical Trials Involving MSCs for Bone and Cartilage Repair...91 TABLE 4.25: Studies Using MSCs for Musculoskeletal Indications by Countries in TABLE 4.26: A Sample of Current Clinical Trials Using MSCs for Osteoarthritis.. 93 TABLE 4.27: A Sample of Clinical Trials Involving MSCs for Bone and Cartilage Repair TABLE 4.28: Clinical Trials Using MSCs for Neuron and Spinal Cord Diseases TABLE 4.29: Clinical Experience of MSCs in GvHD Treatment 96 TABLE 4.30: A Sample of Clinical Trials Using MSCs for Crohn's Disease 97 TABLE 4.31: Clinical Studies Using MSCs for Wound Healing TABLE 4.32: Selected MSCs Late-Stage Pipeline Therapies TABLE 5.1: Global Market for Stem Cells, Through TABLE 5.2: Global Market for Stem Cells by Disease Indication, Through TABLE 6.1: BioCardia's Product Pipeline Overview. 110 TABLE 6.2: Bone Therapeutics' Product Pipeline TABLE 6.3: Cyagen's Mesenchymal Cells TABLE 6.4: Cyagen's Adipose-Derived MSCs..120 TABLE 6.5: Cyagen's MSCs with GFP TABLE 6.6: Cyagen's Adipose-Derived MSCs with GFP TABLE 6.7: Cyagen's Stem Cell Culture Media TABLE 6.8: Cyagen's Stem Cell Differentiation Media TABLE 6.9: Primary Cells from Cyagen TABLE 6.10: Cyagen's Cryopreservation Media TABLE 6.11: Cyagen's Primary Cell Culture Media TABLE 6.12: General Cell Culture Supplements and Specialty Reagents from Cyagen TABLE 6.13: Escape Therapeutics' Pipeline Products TABLE 6.14: Kite Pharma's Pipeline and Clinical Trials..130 TABLE 6.15: Mesoblast's Product Pipeline Overview..135 TABLE 6.16: Octa's Pipeline of Therapeutic Programs TABLE 6.17: Regeneus' Product Pipeline TABLE 6.18: Stempeucel in Clinical Trials by Indication TABLE 6.19: Vericel Corporation's Product Portfolio TABLE 6.20: Summary Table for the Companies and Their Product Types