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 A Crowded, Competitive Market, with Significant Unmet Needs Remaining 5 2.2 Early-Stage Pipeline Offers Greatest Promise for First-in-Class Innovation 5 2.3 Cytokine and Cytokine Receptors, as well as Protein Kinases, Largely Dominate First-in-Class Pipeline Products 5 3 The Case for Innovation 6 3.1 Growing Opportunities for Biologic Products 7 3.2 Diversification of Molecular Targets 7 3.3 Innovative First-in-Class Development Remains Attractive 8 3.4 Regulatory and Reimbursement Policy Shifts Favor First-in-Class Product Innovation 8 3.5 Sustained Innovation 8 3.6 GBI Research Report Guidance 9 4 Clinical and Commercial Landscape 10 4.1 Disease Overview 10 4.2 Disease Symptoms 10 4.3 Epidemiology 11 4.4 Etiology 11 4.5 Pathophysiology 11 4.6 Co-morbidities and Complications 12 4.7 Diagnosis 12 4.7.1 Blood Tests 12 4.7.2 1987 Rheumatoid Arthritis Classification 13 4.7.3 2010 ACR-EULAR Classification Criteria for Rheumatoid Arthritis 13 4.8 Disease Progression 13 4.9 Treatment Options and Treatment Algorithm 14 4.10 Overview of Marketed Products in Rheumatoid Arthritis 15 4.10.1 Molecule Type and Molecular Target Analysis 15 5 Assessment of Pipeline Product Innovation 17 5.1 Rheumatoid Arthritis Pipeline by Stage of Development, Molecule Type and Molecular Target 17 5.2 Comparative Distribution of Programs between the Rheumatoid Arthritis Market and Pipeline by Therapeutic Target Family 21 5.3 First-in-Class Programs Targeting Novel Molecular Targets 21 6 Signaling Network, Disease Causation and Innovation Alignment 32 6.1 Complexity of Signaling Networks in Rheumatoid Arthritis 32 6.2 Signaling Pathways, Disease-Causing Mutations and First-in-Class Molecular Target Integration 33 6.3 First-in-Class Matrix Assessment 33 7 First-in-Class Target Evaluation 37 7.1 Pipeline Programs Targeting Tumor Necrosis Factor Receptor Superfamily Member 5 (CD40) 37 7.2 Pipeline Programs Targeting Non-Receptor Tyrosine-Protein Kinase TYK2 (TYK2) 38 7.3 Pipeline Programs Targeting IL-10 and IL-18 39 7.4 Pipeline Programs Targeting 72 kDa Type IV Collagenase (MMP2) 41 7.5 Pipeline Programs Targeting P2X Purinoceptor 7 (P2RX7) 42 7.6 Pipeline Programs Targeting Protein Kinase C Theta Type (PRKCQ) 43 7.7 Pipeline Programs Targeting C-C Motif Chemokine 4 (CCL4) and C-C Motif Chemokine 5 (CCL5) 44 7.8 Pipeline Programs Targeting C-X-C Motif Chemokine 10 (CXCL10) and C-X-C Motif Chemokine 13 (CXCL13) 46 8 Strategic Consolidations 48 8.1 Industry-Wide First-in-Class Deals 48 8.2 Licensing Deals 49 8.3 Co-development Deals 52 8.4 First-in-Class Programs Not Involved in Licensing or Co-development Deals 56 9 Appendix 59 9.1 References 59 9.2 Abbreviations 63 9.3 Research Methodology 64 9.4 Secondary Research 64 9.4.1 Market Analysis 64 9.4.2 Pipeline Analysis 65 9.4.3 First-in-Class Matrix Assessment 65 9.4.4 First-in-Class Target Profiles 65 9.4.5 Licensing and Co-Development Deals 66 9.5 Contact Us 66 9.6 Disclaimer 66

1.1 List of Tables Table 1: 2010 ACR-EULAR Classification Criteria for Rheumatoid Arthritis, 2010 13 Table 2: Rheumatoid Arthritis, Global, Key Features and Pipeline Activity of Tumor Necrosis Factor Receptor Superfamily Member 5 (CD40), 2016 37 Table 3: Rheumatoid Arthritis, Global, Pipeline Programs Targeting Tumor Necrosis Factor Receptor Superfamily Member 5 (CD40), 2016 38 Table 4: Rheumatoid Arthritis, Global, Key Features and Pipeline Activity of Tyrosine-Protein Kinase TYK2 (TYK2), 2016 39 Table 5: Rheumatoid Arthritis, Global, Pipeline Programs Targeting Tyrosine-Protein Kinase TYK2 (TYK2), 2016 39 Table 6: Rheumatoid Arthritis, Global, Key Features and Pipeline Activity of Interleukin 18, 2016 40 Table 7: Rheumatoid Arthritis, Global, Pipeline Programs Targeting Interleukin 18, 2016 40 Table 8: Rheumatoid Arthritis, Global, Key Features and Pipeline Activity of Interleukin 10, 2016 41 Table 9: Rheumatoid Arthritis, Global, Pipeline Programs Targeting Interleukin 10, 2016 41 Table 10: Rheumatoid Arthritis, Global, Key Features and Pipeline Activity of 72 kDa type IV collagenase (MMP2), 2016 42 Table 11: Rheumatoid Arthritis, Global, Pipeline Programs Targeting 72 kDa type IV collagenase (MMP2), 2016 42 Table 12: Rheumatoid Arthritis, Global, Key Features and Pipeline Activity of P2X Purinoceptor 7 (P2RX7), 2016 43 Table 13: Rheumatoid Arthritis, Global, Pipeline Programs Targeting P2X Purinoceptor 7 (P2RX7), 2016 43 Table 14: Rheumatoid Arthritis, Global, Key Features and Pipeline Activity of Protein Kinase C Theta Type (PRKCQ), 2016 44 Table 15: Rheumatoid Arthritis, Global, Rheumatoid Arthritis, Global, Pipeline Programs Targeting Protein Kinase C Theta Type (PRKCQ), 2016 44 Table 16: Rheumatoid Arthritis, Global, Rheumatoid Arthritis, Global, Pipeline Programs Targeting C-C Motif Chemokine 4 (CCL4), 2016 45 Table 17: Rheumatoid Arthritis, Global, Rheumatoid Arthritis, Global, Pipeline Programs Targeting C-C Motif Chemokine 5 (CCL5), 2016 45 Table 18: Rheumatoid Arthritis, Global, Rheumatoid Arthritis, Global, Pipeline Programs Targeting C-C Motif Chemokine 4 (CCL4) and C-C Motif Chemokine 5 (CCL5), 2016 45 Table 19: Rheumatoid Arthritis, Global, Key Features and Pipeline Activity of C-X-C Motif Chemokine 10, 2016 46 Table 20: Rheumatoid Arthritis, Global, Pipeline Programs Targeting C-X-C Motif Chemokine 10, 2016 47 Table 21: Rheumatoid Arthritis, Global, Key Features and Pipeline Activity of C-X-C Motif Chemokine 13, 2016 47 Table 22: Rheumatoid Arthritis, Global, Pipeline Programs Targeting C-X-C Motif Chemokine 13 (CXCL13), 2016 47 1.2 List of Figures Figure 1: Rheumatoid Arthritis, US, Innovation Trends in Product Approvals, Number of Product Approvals by FDA and Five-Year Moving Average of Product Approvals, 1987-2012 7 Figure 2: Rheumatoid Arthritis, Sales Performance of First-in-Class and Non-First-in-Class Products Post Marketing Approval ($m), 2006-2013 8 Figure 3: Rheumatoid Arthritis, Global, Marketed Products by Molecule Type and Molecular Target, 2016 16 Figure 4: Rheumatoid Arthritis, Global, Pipeline by Stage of Development and Molecule Type, 2016 18 Figure 5: Rheumatoid Arthritis, Global, Pipeline by Molecular Target and Stage of Development, 2016 19 Figure 6: Rheumatoid Arthritis, Global, Pipeline by Key Molecular Target Groups, 2016 20 Figure 7: Rheumatoid Arthritis, Global, Distribution of Molecular Targets Across Pipeline and Marketed Products, 2016 21 Figure 8: Rheumatoid Arthritis, Global, Distribution of Pipeline First-in-Class and Established Molecular Targets, 2016 22 Figure 9: Rheumatoid Arthritis, Global, Percentage Distribution of First-in-Class and Established Pipeline Products by Stage of Development (%), 2016 22 Figure 10: Rheumatoid Arthritis, Global, Percentage Distribution of First-in-Class and Established Pipeline Products by Molecular Target (%), 2016 22 Figure 11: Rheumatoid Arthritis, Global, Pipeline Products, 2016 (part 1) 24 Figure 12: Rheumatoid Arthritis, Global, Pipeline Products, 2016 (part 2) 25 Figure 13: Rheumatoid Arthritis, Global, Pipeline Products, 2016 (part 3) 26 Figure 14: Rheumatoid Arthritis, Global, Pipeline Products, 2016 (part 4) 27 Figure 15: Rheumatoid Arthritis, Global, Pipeline Products, 2016 (part 5) 28 Figure 16: Rheumatoid Arthritis, Global, Pipeline Products, 2016 (part 6) 29 Figure 17: Rheumatoid Arthritis, Global, Pipeline Products, 2016 (part 7) 30 Figure 18: Rheumatoid Arthritis, Global, Pipeline Products, 2016 (part 8) 31 Figure 19: Rheumatoid Arthritis, Global, First-in-Class Molecular Target Matrix Assessment, 2016 (part 1) 34 Figure 20: Rheumatoid Arthritis, Global, First-in-Class Molecular Target Matrix Assessment, 2016 (part 2) 35 Figure 21: Rheumatoid Arthritis, Global, First-in-Class Molecular Target Matrix Assessment, 2016 (part 3) 36 Figure 22: Rheumatoid Arthritis, Global, Industry-Wide Deals by Stage of Development, 2006-2014 48 Figure 23: Rheumatoid Arthritis, Global, Industry-Wide Licensing Deals by Deal Value ($m), Upfront Payment Value ($m) and Stage of Development, 2006-2014 49 Figure 24: Rheumatoid Arthritis, Global, Licensing Deals by Region and Deal Value ($m), 2006-2016 50 Figure 25: Rheumatoid Arthritis, Global, Disclosed and Undisclosed Licensing Deals by Year, Total Disclosed Deal Value ($m) and Total Upfront Payment Value ($m), 2006-2015 50 Figure 26: Rheumatoid Arthritis, Global, Licensing Deals by Stage of Development, Deal Value ($m) and Upfront Payment Value ($m), 2006-2016 51 Figure 27: Rheumatoid Arthritis, Frequency and Aggregate Deal Value of Licensing Deals by Molecule Type and Molecular Target, Global, 2006-2016 52 Figure 28: Rheumatoid Arthritis, Global, Co-development Deals by Region and Deal Value ($m), 2006-2016 53 Figure 29: Rheumatoid Arthritis, Global, Disclosed and Undisclosed Co-development Deals by Year, Total Disclosed Deal Value ($m) and Total Upfront Payment Value ($m), 2006-2015 53 Figure 30: Rheumatoid Arthritis, Global, Co-development Deals by Stage of Development, Deal Value ($m) and Upfront Payment Value ($m), 2006-2016 54 Figure 31: Rheumatoid Arthritis, Global, Frequency and Aggregate Deal Value of Co-development Deals by Molecule Type and Molecular Target, 2006-2016 55 Figure 32: Rheumatoid Arthritis, Global, First-in-Class Programs with No Recorded Prior Deal Involvement, 2016 (part 1) 57 Figure 33: Rheumatoid Arthritis, Global, First-in-Class Programs with No Recorded Prior Deal Involvement, 2016 (part 2) 58