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 Significant Unmet Needs in Diabetic Complications Market 5
2.2 High Proportion of First-in-Class Innovation Offers Promise in Diabetic Complications 5
2.3 Deal Activity Varies with First-in-Class Status 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 Product Development Remains Attractive 7
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 8
4 Clinical and Commercial Landscape 10
4.1 Diabetes Mellitus Overview 10
4.2 Diabetic Neuropathies 11
4.2.1 Disease Overview 11
4.2.2 Signs and Symptoms 11
4.2.3 Epidemiology and Etiology 12
4.2.4 Pathophysiology 12
4.2.5 Diagnosis and Staging 12
4.2.6 Prognosis 13
4.2.7 Treatment Options 13
4.3 Diabetic Nephropathy 14
4.3.1 Disease Overview 14
4.3.2 Sign and Symptoms 14
4.3.3 Epidemiology and Etiology 14
4.3.4 Pathophysiology 14
4.3.5 Diagnosis and Staging 14
4.3.6 Prognosis 15
4.3.7 Treatment Options 15
4.4 Diabetic Retinopathies 16
4.4.1 Disease Overview 16
4.4.2 Signs and Symptoms 16
4.4.3 Epidemiology and Etiology 16
4.4.4 Pathophysiology 16
4.4.5 Diagnosis and Staging 17
4.4.6 Prognosis 17
4.4.7 Treatment Options 17
4.5 Overview of Marketed Products in Diabetic Complications 18
4.5.1 Overview of Marketed Products in Diabetic Neuropathies 18
4.5.2 Overview of Marketed Products in Diabetic Nephropathy 20
4.5.3 Overview of Marketed Products in Diabetic Retinopathies 20
5 Assessment of Pipeline Product Innovation 22
5.1 Diabetic Neuropathies by Molecule Type, Phase and Therapeutic Target 22
5.1.1 Comparative Distribution of Programs between Diabetic Neuropathy Market and Pipeline by Therapeutic Target Family 24
5.1.2 First-in-Class Pipeline Programs Targeting Novel Molecular Targets 25
5.2 Diabetic Nephropathy by Molecule Type, Phase and Therapeutic Target 27
5.2.1 Comparative Distribution of Programs between the Diabetic Nephropathy Market and Pipeline by Therapeutic Target Family 29
5.2.2 First-in-Class Pipeline Programs Targeting Novel Molecular Targets 30
5.3 Diabetic Retinopathies by Molecule Type, Phase and Therapeutic Target 32
5.3.1 Comparative Distribution of Programs between the Diabetic Retinopathy Market and Pipeline by Therapeutic Target Family 34
5.3.2 First-in-Class Pipeline Programs Targeting Novel Molecular Targets 35
5.3.3 Pipeline Products in Diabetic Complications 38
6 Signaling Network, Disease Causation and Innovation Alignment 41
6.1 Complexity of Signaling Networks in Metabolic Disorders 41
6.2 First-in-Class Matrix Assessment 42
7 First-in-Class Target Evaluation 44
7.1 Pipeline Programs Targeting NADPH Oxidase 4 44
7.2 Pipeline Programs Targeting Glutamate Decarboxylase 45
7.3 Pipeline Programs Targeting Growth Hormone Secretagogue Receptor Type 1 46
7.4 Pipeline Programs Targeting Motilin Receptor 47
7.5 Pipeline Programs Targeting Lysophosphatidic Acid Receptor 1 48
7.6 Pipeline Programs Targeting Leukotriene B4 Receptor 1 50
7.7 Pipeline Programs Targeting Integrin Alpha V 51
7.8 Pipeline Programs Targeting Signal Transducer and Activator of Transcription 4 53
8 Deals and Strategic Consolidations 54
8.1 Industry-Wide First-in-Class Deals 54
8.2 Licensing Deals 55
8.2.1 Licensing Deals by Molecule Type 57
8.2.2 Licensing Deals by Molecular Target 57
8.3 Co-development Deals 59
8.3.1 Co-development Deals by Molecule Type 60
8.3.2 Co-development Deals by Molecular Target 60
8.4 First-in-Class Programs Not Involved in Licensing or Co-development Deals 62
9 Appendix 66
9.1 References 66
9.2 Abbreviations 71
9.3 Research Methodology 71
9.4 Secondary Research 72
9.4.1 Market Analysis 72
9.4.2 Pipeline Analysis 72
9.4.3 First-in-Class Matrix Assessment 72
9.4.4 First-in-Class Target Profiles 73
9.4.5 Licensing and Co-Development Deals 73
9.5 Contact Us 73
9.6 Disclaimer 73

1.1 List of Tables
Table 1: Natural Development of Diabetic Nephropathy 15
Table 2: Diabetic Complications, Global, Data for NADPH Oxidase 4 as Therapeutic Target, 2016 44
Table 3: Diabetic Complications, Global, Data for Glutamate Decarboxylase as Therapeutic Target, 2016 46
Table 4: Diabetic Complications, Global, Data for Growth Hormone Secretagogue Receptor Type 1 as Therapeutic Target, 2016 47
Table 5: Diabetic Complications, Global, Data for Motilin Receptor as Therapeutic Target, 2016 48
Table 6: Diabetic Complications, Global, Data for Lysophosphatidic Acid Receptor 1 as Therapeutic Target, 2016 49
Table 7: Diabetic Complications, Global, Data for Leukotriene B4 Receptor 1 as Therapeutic Target, 2016 50
Table 8: Diabetic Complications, Global, Data for Integrin Alpha V as Therapeutic Target, 2016 52
Table 9: Diabetic Complications, Global, Data for Signal Transducer and Activator of Transcription 4 as Therapeutic Target, 2016 53
Table 10: Abbreviations 71

1.2 List of Figures
Figure 1: Diabetic Complications, Global, Number of Product Approvals by FDA and Five-Year Moving Average of Product Approvals (%), 1987–2012 6
Figure 2: Global, Sales Performance of First-in-Class and Non-First-in-Class Products after Marketing Approval ($m), 2016 8
Figure3: Diabetic Neuropathies, Global, Overview of Marketed Products, 2016 19
Figure 4: Diabetic Nephropathy, Global, Overview of Marketed Products, 2016 20
Figure 5: Diabetic Retinopathies, Global, Overview of Marketed Products, 2016 21
Figure 6: Diabetic Neuropathies, Global, Overview of Pipeline Products, 2016 23
Figure 7: Diabetic Neuropathies, Global, Molecular Targets in Pipeline, 2016 24
Figure 8: Diabetic Neuropathies, Global, Pipeline by Molecular Targets and Stage of Development, 2016 24
Figure 9: Diabetic Neuropathies, Global, Molecular Target Family Comparison, Pipeline and Marketed Products, 2016 25
Figure 10: Diabetic Neuropathies, Global, Molecular Target Family Comparison, Pipeline First-in-Class and Established Molecular Targets, 2016 26
Figure 11: Diabetic Neuropathies, Global, Percentage of First-in-Class Products in Pipeline by Molecular Target Family (%), 2016 27
Figure 12: Diabetic Neuropathies, Global, Percentage of First-in-Class Products in Pipeline by Stage of Development (%), 2016 27
Figure 13: Diabetic Nephropathy, Global, Overview of Pipeline Products, 2016 28
Figure 14: Diabetic Nephropathy, Global, Molecular Targets in Pipeline, 2016 29
Figure 15: Diabetic Nephropathy, Global, Pipeline by Molecular Targets and Stage of Development, 2016 29
Figure 16: Diabetic Nephropathy, Global, Molecular Target Family Comparison, Pipeline and Marketed Products, 2016 30
Figure 17: Diabetic Nephropathy, Global, Molecular Target Family Comparison, Pipeline First-in-Class and Established Molecular Targets, 2016 31
Figure 18: Diabetic Nephropathy, Global, Percentage of First-in-Class Products in Pipeline by Molecular Target Family (%), 2016 32
Figure 19: Diabetic Nephropathy, Global, Percentage of First-in-Class Products in Pipeline by Stage of Development (%), 2016 32
Figure 20: Diabetic Retinopathies, Global, Overview of Pipeline Products, 2016 33
Figure 21: Diabetic Retinopathies, Global, Molecular Targets in Pipeline, 2016 34
Figure 22: Diabetic Retinopathies, Global, Pipeline by Molecular Targets and Stage of Development, 2016 34
Figure 23: Diabetic Retinopathies, Global, Complications, Molecular Target Family Comparison, Pipeline and Marketed Products, 2016 35
Figure 24: Diabetic Retinopathies, Global, Molecular Target Family Comparison, Pipeline First-in-Class and Established Molecular Targets, 2016 36
Figure 25: Diabetic Retinopathies, Global, Percentage of First-in-Class Products in Pipeline by Molecular Target Family (%), 2016 37
Figure 26: Diabetic Retinopathies, Global, Percentage of First-in-Class Products in Pipeline by Stage of Development (%), 2016 37
Figure 27: Diabetic Complications, Global, First-in-Class Products in Pipeline (Part 1), 2016 38
Figure 28: Diabetic Complications, Global, First-in-Class Products in Pipeline (Part 2), 2016 39
Figure 29: Diabetic Complications, Global, First-in-Class Products in Pipeline (Part 3), 2016 40
Figure 30: Diabetic Complications, Global, Gastric Cancer, Target Matrix, 2016 43
Figure 31: Diabetic Complications, Global, Pipeline Programs Targeting NADPH Oxidase 4, 2016 45
Figure 32: Diabetic Complications, Global, Pipeline Programs Targeting Glutamate Decarboxylase, 2016 46
Figure 33: Diabetic Complications, Global, Pipeline Programs Targeting Growth Hormone Secretagogue Receptor Type 1, 2016 47
Figure 34: Diabetic Complications, Global, Pipeline Programs Targeting Motilin Receptor, 2016 48
Figure 35: Diabetic Complications, Global, Pipeline Programs Targeting Lysophosphatidic Acid Receptor 1, 2016 49
Figure 36: Diabetic Complications, Global, Pipeline Programs Targeting Leukotriene B4 Receptor 1, 2016 51
Figure 37: Diabetic Complications, Global, Pipeline Programs Targeting Integrin Alpha V, 2016 52
Figure 38: Diabetic Complications, Global, Pipeline Programs Targeting Signal Transducer and Activator of Transcription 4, 2016 53
Figure 39: Diabetic Complications, Global, Deals by Stage of Development, 2006–2014 54
Figure 40: Diabetic Complications, Global, Licensing Deal Values by Stage of Development ($m), 2006–2014 55
Figure 41: Diabetic Complications, Global, Licensing Deal Value, 2006–2016 56
Figure 42: Diabetic Complications, Global, Licensing Deals by Year, 2006–2016 56
Figure 43: Diabetic Complications, Global, Licensing Deals by Stage of Development, 2006–2016 56
Figure 44: Diabetic Complications, Global, Licensing Deal Value by Stage of Development and Molecule Type, 2006–2016 57
Figure 45: Diabetic Complications, Global, Licensing Deal Value by Molecular Target, 2006–2016 57
Figure 46: Diabetic Complications, Global, Summary of Licensing Deals, 2006–2016 58
Figure 47: Diabetic Complications, Global, Co-development Deal Value, 2006–2016 59
Figure 48: Diabetic Complications, Global, Co-development Deals, 2006–2016 59
Figure 49: Diabetic Complications, Global, Co-development Deals by Stage of Development, 2006–2016 60
Figure 50: Diabetic Complications, Global, Co-development by Stage of Development and Molecule Type, 2006–2015 60
Figure 51: Diabetic Complications, Global, Co-development by Stage of Development and Molecular Target, 2006–2015 61
Figure 52: Diabetic Complications, Global, Summary of Co-development Deals, 2006-2016 62
Figure 53: Diabetic Complications, Global, First-in-Class Therapies Not Involved in Deals (Part 1), 2016 63
Figure 54: Diabetic Complications, Global, First-in-Class Therapies Not Involved in Deals (Part 2), 2016 64
Figure 55: Diabetic Complications, Global, First-in-Class Therapies Not Involved in Deals (Part 3), 2016 65