1 Table of Contents 1 Table of Contents 2 1.1 List of Tables 3 1.2 List of Figures 3 2 Executive Summary 5 2.1 Large Therapy Area Characterized by a High Degree of Pathophysiological Crossover 5 2.2 Strong Pipeline Shows High Level of Versatile Innovation 5 2.3 Substantial Deal Making Activity Observed over the Past Decade 5 3 The Case for Innovation in the Immunology Market 6 3.1 Growing Opportunities for Biologic Products 7 3.2 Diversification of Molecular Targets 7 3.3 Innovative First-in-Class Product Developments Remain Attractive 7 3.4 Regulatory and Reimbursement Policy Shifts Favor First-in-Class Product Innovation 8 3.5 Sustained Innovation 8 4 Introduction 9 4.1 Therapy Area Introduction 9 4.2 Symptoms 9 4.3 Etiology and Pathophysiology 9 4.3.1 Innate Immunity 9 4.3.2 Adaptive Immunity 10 4.3.3 The Role of Cytokines 11 4.3.4 Autoimmunity 11 4.3.5 Etiologic Factors for Autoimmunity and Allergies 12 4.3.6 Conclusion 12 4.4 Co-morbidities and Complications 13 4.5 Epidemiology 13 4.6 Treatment 14 4.6.1 Non-Biologic Disease-Modifying Anti-Rheumatic Drugs 15 4.6.2 Glucocorticoids 15 4.6.3 Biologics and Targeted Therapies 15 5 Pipeline Landscape Assessment 17 5.1 Overview 17 5.2 Pipeline Development Landscape 18 5.3 Molecular Targets in the Pipeline 19 5.4 Comparative Distribution of Programs between the Oncology Market and Pipeline by Therapeutic Target Family 20 5.5 First-in-Class and Versatile Pipeline Programs 21 5.6 First-in-Class Immunology Products by Phase, Molecule Type and Molecular Target 23 5.7 Versatility of First-in-Class Pipeline Products 26 6 Immunology Signaling Network, Disease Causation and Innovation Alignment 35 6.1 Complexity of Signaling Networks 35 6.2 Signaling Pathways and First-in-Class Molecular Target Integration 35 6.3 First-in-Class Matrix Assessment 35 7 First-in-Class Target and Pipeline Program Evaluation 40 7.1 Pipeline Programs Targeting Toll-Like Receptors 3, 6 and 8 40 7.2 Pipeline Programs Targeting Spleen Tyrosine Kinase 44 7.3 Pipeline Programs Targeting IL-7R 46 7.4 Pipeline Programs Targeting C-C Chemokine Receptor Type 6 47 7.5 Pipeline Programs Targeting P2RX7 48 7.6 Pipeline Programs Targeting ITK 50 7.7 Pipeline Programs Targeting IRAK4 51 7.8 Pipeline Programs Targeting Orai1 52 7.9 Pipeline Programs Targeting Tumor Necrosis Factor Receptor Superfamily Member 5 54 7.10 Conclusion 55 8 Strategic Consolidations 56 8.1 Industry-Wide First-in-Class Deals 56 8.2 Licensing Deals 57 8.2.1 Deals by Region, Year and Value 58 8.2.2 Deals by Stage of Development and Value 59 8.2.3 Deals by Molecule Type and Value 60 8.2.4 Deals by Molecular Target and Value 61 8.3 Co-development Deals 62 8.3.1 Deals by Region, Year and Value 62 8.3.2 Deals by Stage of Development and Value 64 8.3.3 Deals by Molecule Type and Value 65 8.3.4 Deals by Molecular Target and Value 66 8.4 List of First-in-Class Pipeline Products with and Without Prior Deal Involvement 67 9 Appendix 72 9.1 Abbreviations 72 9.2 References 72 9.3 Research Methodology 78 9.3.1 Data integrity 78 9.3.2 Innovative and meaningful analytical techniques and frameworks 78 9.3.3 Evidence based analysis and insight 78 9.4 Secondary Research 79 9.4.1 Market Analysis 79 9.4.2 Pipeline Analysis 79 9.4.3 Licensing and Co-development Deals 80 9.5 Contact Us 80 9.6 Disclaimer 80

1.1 List of Tables Table 1: Versatile Innovation in Immunology, Global, Epidemiology of Inflammatory Immunological Disorders, 2015 13 Table 2: Versatile Innovation in Immunology, Global, Toll-Like Receptors and their Known Ligands, 2016 40 Table 3: Versatile Innovation in Immunology, Global, Key Features of TLR3, 2016 42 Table 4: Versatile Innovation in Immunology, Global, Key Features of TLR6, 2016 42 Table 5 Versatile Innovation in Immunology, Global, Key Features of TLR8, 2016 43 Table 6: Versatile Innovation in Immunology, Global, Key Features of Syk, 2016 45 Table 7: Versatile Innovation in Immunology, Global, Key Features of IL-7R, 2016 46 Table 8: Versatile Innovation in Immunology, Global, Key Features of C-C Chemokine Receptor Type 6, 2016 48 Table 9: Versatile Innovation in Immunology, Global, Key Features of P2RX7, 2016 49 Table 10: Versatile Innovation in Immunology, Global, Key Features of ITK, 2016 51 Table 11: Versatile Innovation in Immunology, Global, Key Features of IRAK4, 2016 52 Table 12: Versatile Innovation in Immunology, Global, Key Features of Orai1, 2016 53 Table 13: Versatile Innovation in Immunology, Global, Key Features of Tumor Necrosis Factor Receptor Superfamily Member 5 , 2016 551.2 List of Figures Figure 1: Versatile Innovation in Immunology, US, Innovation Trends in Product Approvals, 1987–2014 6 Figure 2: Versatile Innovation in Immunology, US, Sales Performance of First-in-Class and Non-First-in-Class Products Post Marketing Approval, 2006–2013 8 Figure 3: Versatile Innovation in Immunology, Global, Overall Pharmaceutical Industry Pipeline by Therapy Area and Breakdown of Immunology Pipeline by Indication, 2016 17 Figure 4: Versatile Innovation in Immunology, Global, Pipeline for Immunology by Stage of Development and Molecule Type, 2016 18 Figure 5: Versatile Innovation in Immunology, Global, Pipeline for Immunology by Molecular Target, 2016 20 Figure 6: Versatile Innovation in Immunology, Global, Pipeline and Marketed Products for Immunology by Molecular Target Category, 2016 21 Figure 7: Versatile Innovation in Immunology, Global, Overall Pharmaceutical Industry First-in-Class Pipeline by Therapy Area and Breakdown of Immunology First-in-Class Pipeline by Indication, 2016 22 Figure 8: Versatile Innovation in Immunology Therapeutics Market, Global, First-in-Class Pipeline for Immunology by Stage of Development and Molecule Type, 2016 23 Figure 9: Versatile Innovation in Immunology, Global, First-in-Class Pipeline for Immunology by Molecular Target, 2016 24 Figure 10: Versatile Innovation in Immunology, Global, Pipeline for Immunology by First-in-Class Status and Molecular Target Class, 2016 25 Figure 11: Versatile Innovation in Immunology, Global, Distribution of First-in-Class and Established Products by Stage of Development (%), 2016 26 Figure 12: Versatile Innovation in Immunology, Global, Distribution of First-in-Class and Established Products by Molecular Target Class (%), 2016 26 Figure 13: Versatile Innovation in Immunology, Global, First-in-Class Immunology Pipeline Products by Number of Indications, 2016 26 Figure 14: Versatile Innovation in Immunology, Global, Pipeline for Key Immunology Indications by Molecular Target, 2016 27 Figure 15: Versatile Innovation in Immunology, Global, Versatile Pipeline for Immunology by Stage of Development and Molecule Type, 2016 28 Figure 16: Versatile Innovation in Immunology, Global, Versatile First-in-Class Pipeline Immunology by Molecular Target, 2015 29 Figure 17: Versatile Innovation in Immunology, Global, First-in-Class Pipeline for Immunology by Versatile Status and Molecular Target Class, 2016 30 Figure 18: Versatile Innovation in Immunology, Global, First-in-class Pipeline for Immunology Indications (Part 1), 2016 31 Figure 19: Versatile Innovation in Immunology, Global, First-in-class Pipeline for Immunology Indications (Part 2), 2016 32 Figure 20: Versatile Innovation in Immunology, Global, First-in-class Pipeline for Immunology Indications (Part 3), 2016 33 Figure 21: Versatile Innovation in Immunology, Global, First-in-class Pipeline for Immunology Indications (Part 4), 2016 34 Figure 22: Versatile Innovation in Immunology, Global, First-in-Class Matrix, 2016 (part 1) 37 Figure 23: Versatile Innovation in Immunology, Global, First-in-Class Matrix, 2016 (part 2) 38 Figure 24: Versatile Innovation in Immunology, Global, First-in-Class Matrix, 2016 (part 3) 39 Figure 25: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting TLR3, 2016 43 Figure 26: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting TLR6, 2016 43 Figure 27: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting TLR8, 2016 43 Figure 28: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting Syk, 2016 45 Figure 29: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting IL-7R, 2016 47 Figure 30: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting C-C Chemokine Receptor Type 6, 2016 48 Figure 31: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting P2RX7, 2016 50 Figure 32: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting ITK, 2016 51 Figure 33: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting IRAK4, 2016 52 Figure 34: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting Orai1, 2016 54 Figure 35: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting Tumor necrosis factor receptor superfamily member 5 , 2016 55 Figure 36: Versatile Innovation in Immunology, Global, Licensing Deals by Stage of Development, 2006–2015 56 Figure 37: Versatile Innovation in Immunology, Global, Industry-Wide Licensing Deals by Deal Value, Upfront Payment Value, Stage of Development and First-in-Class Status ($m), 2006–2015 57 Figure 38: Versatile Innovation in Immunology, Global, Licensing Deals by Region, Value and Year, 2006–2016 58 Figure 39: Versatile Innovation immunology, Global, Licensing Deals by Stage of Development, Deal Value and Upfront Payment Value, 2006–2016 59 Figure 40: Versatile Innovation in Immunology, Global, Licensing Deals by Molecule Type, 2006–2016 60 Figure 41: Immunology, Global, Licensing Deals by Molecular Target, 2006–2016 61 Figure 42: Versatile Innovation in Immunology, Global, Licensing Deals Valued Above $100m, 2006–2016 62 Figure 43: Versatile Innovation in Immunology, Global, Co-development Deals by Region, Value and Year, 2006–2016 63 Figure 44: Immunology, Global, Co-development Deals by Stage of Development, Deal Value and Upfront Payment Value, 2006–2016 64 Figure 45: Versatile Innovation in Immunology, Global, Co-development Deals by Molecule Type, 2006–2016 65 Figure 46: Versatile Innovation in Immunology, Global, Co-development Deals by Molecular Target, 2006–2016 66 Figure 47: Versatile Innovation in Immunology, Global, Co-development Deals Valued Above $100m, 2006–2016 67 Figure 48: Versatile Innovation in Immunology, Global, List of First-in-Class Pipeline Products with and Without Prior Deal Involvement, 2016 68 Figure 49: Versatile Innovation in Immunology, Global, List of First-in-Class Pipeline Products with and Without Prior Deal Involvement, 2016 69 Figure 50: Versatile Innovation in Immunology, Global, List of First-in-Class Pipeline Products with and Without Prior Deal Involvement, 2016 70 Figure 51: Versatile Innovation in Immunology, Global, List of First-in-Class Pipeline Products with and Without Prior Deal Involvement, 2016 71