1 Table of Contents
1 Table of Contents 2
1.1 List of Tables 4
1.2 List of Figures 4
2 Executive Summary 6
2.1 Limited Treatment Options despite Large Market Opportunity 6
2.2 Exceptionally High Level of First-in-Class Innovation within Alzheimer’s Disease Pipeline 6
2.3 Active Deals Landscape Dominated by GPCR-Targeting Products 6
3 The Case for Innovation 7
3.1 Growing Opportunities for Biologic Products 8
3.2 Diversification of Molecular Targets 8
3.3 Innovative First-in-Class Product Developments Remain Attractive 9
3.4 Regulatory and Reimbursement Policy Shifts Favor First-in-Class Product Innovation 9
3.5 Sustained Innovation in Alzheimer’s Disease 10
3.6 GBI Research Report Guidance 10
4 Clinical and Commercial Landscape 12
4.1 Disease Overview 12
4.2 Classification of Dementia and Mild Cognitive Impairment 12
4.3 Symptoms, Disease Staging and Prognosis 13
4.4 Diagnosis 14
4.4.1 Mini Mental State Exam 15
4.4.2 Alzheimer’s Disease Assessment Scale – Cognitive 15
4.4.3 Alzheimer’s Disease Co-operative Study – Activities of Daily Living Inventory 16
4.4.4 Imaging Techniques 16
4.4.5 Lumbar Puncture 17
4.4.6 Blood Tests 17
4.5 Epidemiology 17
4.6 Etiology and Pathophysiology 17
4.6.1 Etiological Risk Factors 17
4.6.2 Pathophysiology 18
4.7 Management and Treatment of Alzheimer’s Disease 21
4.7.1 Pharmacological Intervention 21
4.7.2 Non-pharmacological Intervention 22
4.8 Overview of Marketed Products 23
4.9 Indications Associated with Alzheimer’s Disease 26
4.9.1 Anxiety 26
4.9.2 Depression 27
4.9.3 Psychosis 28
4.9.4 Insomnia 29
5 Assessment of Pipeline Product Innovation 30
5.1 Overview 30
5.2 Pipeline by Stage of Development and Molecule Type 30
5.2.1 Alzheimer’s Disease 30
5.2.2 Alzheimer’s-Disease-Associated Indications 31
5.3 Pipeline by Molecular Target 33
5.3.1 Alzheimer’s Disease 33
5.3.2 Alzheimer’s-Disease-Associated Indications 35
5.4 Comparative Distribution of Programs between the Market and Pipeline by Molecular Target Class 36
5.4.1 Alzheimer’s Disease 36
5.4.2 Alzheimer’s-Disease-Associated Indications 37
5.5 First-in-Class Programs Targeting Novel Molecular Targets 37
5.5.1 Alzheimer’s Disease 37
5.5.2 Alzheimer’s-Disease-Associated Indications 41
5.6 Ratio of First-in-Class Products to First-in-Class Targets 44
5.6.1 Alzheimer’s Disease 44
5.6.2 Alzheimer’s-Disease-Associated Indications 46
5.7 List of All First-in-Class Pipeline Programs 48
6 Signaling Network, Disease Causation and Innovation Alignment 58
6.1 Complexity of Signaling Networks 58
6.2 Signaling Pathways and First-in-Class Molecular Target Integration 58
6.3 First-in-Class Matrix Assessment 59
7 First-in-Class Target Profiles 64
7.1 Pipeline Programs Targeting Presenilin 1 for Alzheimer’s Disease 64
7.2 Pipeline Programs Targeting Apolipoprotein E for Alzheimer’s Disease 65
7.3 Pipeline Programs Targeting Apoptosis Regulator BAX for Alzheimer’s Disease 66
7.4 Pipeline Programs Targeting Sortilin for Alzheimer’s Disease 69
7.5 Pipeline Programs Targeting Metabotropic Glutamate Receptors 1, 2, 3, 4, 5 and 7 for Alzheimer’s Disease, Anxiety, Depression and Psychosis 70
7.6 Pipeline Programs Targeting Sodium Dependent Neutral Amino Acid Transporter B(0) AT2 for Depression and Anxiety 76
7.7 Pipeline Programs Targeting Cytochrome P450 1A2 for Insomnia and Anxiety 78
8 Strategic Consolidations 80
8.1 Industry-Wide First-in-Class Deals 80
8.2 Licensing Deals 82
8.2.1 Deals by Region, Value and Year 82
8.2.2 Deals by Indication 83
8.2.3 Deals by Stage of Development and Value 83
8.2.4 Deals by Molecule Type, Molecular Target and Value 84
8.2.5 List of Deals with Deal Values Exceeding $100m 86
8.3 Co-development Deals 87
8.3.1 Deals by Region, Value and Year 87
8.3.2 Deals by Indication 88
8.3.3 Deals by Stage of Development and Value 88
8.3.4 Deals by Molecule Type, Molecular Target and Value 89
8.3.5 List of Deals with Deal Values Exceeding $100m 90
8.4 First-in-Class Programs with and without Prior Involvement in Licensing and Co-development Deals 90
9 Appendix 91
9.1 References 91
9.2 Abbreviations 98
9.3 Research Methodology 99
9.3.1 Data integrity 99
9.3.2 Innovative and meaningful analytical techniques and frameworks: 99
9.3.3 Evidence based analysis and insight: 99
9.4 Secondary Research 99
9.4.1 Market Analysis 99
9.4.2 Pipeline Analysis 99
9.4.3 First-in-Class Matrix Assessment 100
9.4.4 First-in-Class Target Profiles 100
9.4.5 Licensing and Co-Development Deals 101
9.5 Contact Us 101
9.6 Disclaimer 101
Table 1: Alzheimer’s Disease and Associated Indications, Global, Common Forms of Dementia, 2017 13
Table 2: Alzheimer’s Disease and Associated Indications, Global, Common Alzheimer’s Disease Symptoms by Disease Stage, 2017 14
Table 3: Alzheimer’s Disease and Associated Indications, Global, Scoring for Mini-Mental State Exam, 2017 15
Table 4: Alzheimer’s Disease and Associated Indications, Global, Scoring for the Alzheimer’s Disease Assessment Scale-Cognitive , 2017 16
Table 5: Alzheimer’s Disease and Associated Indications, Global, Common Physical and Psychological Symptoms Associated with Anxiety Disorders, 2017 26
Table 6: Alzheimer’s Disease and Associated Indications, Global, Common Forms of Depression, 2017 28
Table 7: Alzheimer’s Disease and Associated Indications, Global, Key Features of Presenilin 1, 2017 64
Table 8: Alzheimer’s Disease and Associated Indications, Global, Pipeline Programs Targeting Presenilin 1, 2017 65
Table 9: Alzheimer’s Disease and Associated Indications, Global, Key Features of Apolipoprotein E, 2017 66
Table 10: Alzheimer’s Disease and Associated Indications, Global, Pipeline Programs Targeting Apolipoprotein E, 2017 66
Table 11: Alzheimer’s Disease and Associated Indications, Global, Key Features of Apoptosis Regulator BAX, 2017 68
Table 12: Alzheimer’s Disease and Associated Indications, Global, Pipeline Programs Targeting Apoptosis Regulator BAX, 2017 68
Table 13: Alzheimer’s Disease and Associated Indications, Global, Key Features of Sortilin, 2017 69
Table 14: Alzheimer’s Disease and Associated Indications, Global, Pipeline Programs Targeting Sortilin, 2017 70
Table 15: Alzheimer’s Disease and Associated Indications, Global, Key Features of Metabotropic Glutamate Receptor 1, 2017 71
Table 16: Alzheimer’s Disease and Associated Indications, Pipeline Programs Targeting Metabotropic Glutamate Receptor 1, 2017 71
Table 17: Alzheimer’s Disease and Associated Indications, Global, Key Features of Metabotropic Glutamate Receptor 2, 2017 72
Table 18: Alzheimer’s Disease and Associated Indications, Pipeline Programs Targeting Metabotropic Glutamate Receptor 2, 2017 72
Table 19: Alzheimer’s Disease and Associated Indications, Global, Key Features of Metabotropic Glutamate Receptor 3, 2017 73
Table 20: Alzheimer’s Disease and Associated Indications, Pipeline Programs Targeting Metabotropic Glutamate Receptor 3, 2017 73
Table 21: Alzheimer’s Disease and Associated Indications, Global, Key Features of Metabotropic Glutamate Receptor 4, 2017 74
Table 22: Alzheimer’s Disease and Associated Indications, Pipeline Programs Targeting Metabotropic Glutamate Receptor 4 (GRM4), 2017 74
Table 23: Alzheimer’s Disease and Associated Indications, Global, Key Features of Metabotropic Glutamate Receptor 5, 2017 75
Table 24: Alzheimer’s Disease and Associated Indications, Pipeline Programs Targeting Metabotropic Glutamate Receptor 5, 2017 75
Table 25: Alzheimer’s Disease and Associated Indications, Global, Key Features of Metabotropic Glutamate Receptor 7 (GRM7), 2017 76
Table 26: Alzheimer’s Disease and Associated Indications, Pipeline Programs Targeting Metabotropic Glutamate Receptor 7 (GRM7), 2017 76
Table 27: Alzheimer’s Disease and Associated Indications, Global, Sodium Dependent Neutral Amino Acid Transporter B0 AT2, 2017 77
Table 28: Alzheimer’s Disease and Associated Indications, Global, Pipeline Programs Targeting Sodium Dependent Neutral Amino Acid Transporter B0 AT2, 2017 78
Table 29: Alzheimer’s Disease and Associated Indications, Global, Key Features of Cytochrome P450 1A2, 2017 79
Table 30: Alzheimer’s Disease and Associated Indications, Global, Pipeline Programs Targeting Cytochrome P450 1A2, 2017 79
1.2 List of Figures
Figure 1: Alzheimer’s Disease and Associated Indications, Global, US, Innovation Trends in Product Approvals, 1987-2014 8
Figure 2: Alzheimer’s Disease and Associated Indications, US, Sales Performance of First-in-Class and Non-First-in-Class Products Post Marketing Approval, 2006-2013 9
Figure 3: Alzheimer’s Disease and Associated Indications, Global, Alzheimer’s Disease Market by Molecular Target, 2017 24
Figure 4: Alzheimer’s Disease and Associated Indications, Global, Alzheimer’s Disease Associated Indications Market by Molecular Target, 2017 25
Figure 5: Alzheimer’s Disease and Associated Indications, Global, Pipeline by Therapy Area, 2017 30
Figure 6: Alzheimer’s Disease, Global, Pipeline by Stage of Development and Molecule Type, 2017 31
Figure 7: Anxiety, Depression, Psychosis and Insomnia, Global, Pipelines by Stage of Development, 2017 32
Figure 8: Anxiety, Depression, Psychosis and Insomnia, Global, Pipelines by Molecule Type, 2017 33
Figure 9: Alzheimer’s Disease, Global, Pipeline by Molecular Target, 2017 34
Figure 10: Anxiety, Depression, Psychosis and Insomnia, Global, Pipelines by Molecular Target, 2017 36
Figure 11: Alzheimer’s Disease, Global, Pipeline and Marketed Products by Molecular Target Class, 2017 37
Figure 12: Alzheimer’s-Disease-Associated Indications, Global, Pipeline and Marketed Products by Molecular Target Class, 2017 37
Figure 13: Alzheimer’s Disease, Global, Pipeline by Molecular Target Class, First-in-Class Status and Stage of Development, 2017 39
Figure 14: Alzheimer’s Disease, Global, Percentage Distribution of First-in-Class and Non-First-in-Class Pipeline Products by Stage of Development and Molecular Target Class, 2017 40
Figure 15: Alzheimer’s-Disease-Associated Indications, Global, Pipeline by Molecular Target Class, First-in-Class Status and Stage of Development, 2017 42
Figure 16: Alzheimer’s-Disease-Associated Indications, Global, Percentage Distribution of First-in-Class and Non-First-in-Class Pipeline Products by Stage of Development and Molecular Target Class, 2017 43
Figure 17: Alzheimer’s Disease, Global, Ratio of First-in-Class Products to First-in-Class Targets for Pipeline Products by Stage of Development and Molecular Target Class, 2017 45
Figure 18: Alzheimer’s-Disease-Associated Indications, Global, Ratio of First-in-Class Products to First-in-Class Targets for Pipeline Products by Stage of Development and Molecular Target Class, 2017 47
Figure 19: Alzheimer’s Disease and Associated Indications, Global, List of All First-in-Class Pipeline Programs, 2017 (part 1) 48
Figure 20: Alzheimer’s Disease and Associated Indications, Global, List of All First-in-Class Pipeline Programs, 2017 (part 2) 49
Figure 21: Alzheimer’s Disease and Associated Indications, Global, List of All First-in-Class Pipeline Programs, 2017 (part 3) 50
Figure 22: Alzheimer’s Disease and Associated Indications, Global, List of All First-in-Class Pipeline Programs, 2017 (part 4) 51
Figure 23: Alzheimer’s Disease and Associated Indications, Global, List of All First-in-Class Pipeline Programs, 2017 (part 5) 52
Figure 24: Alzheimer’s Disease and Associated Indications, Global, List of All First-in-Class Pipeline Programs, 2017 (part 6) 53
Figure 25: Alzheimer’s Disease and Associated Indications, Global, List of All First-in-Class Pipeline Programs, 2017 (part 7) 54
Figure 26: Alzheimer’s Disease and Associated Indications, Global, List of All First-in-Class Pipeline Programs, 2017 (part 8) 55
Figure 27: Alzheimer’s Disease and Associated Indications, Global, List of All First-in-Class Pipeline Programs, 2017 (part 9) 56
Figure 28: Alzheimer’s Disease and Associated Indications, Global, List of All Pipeline Programs, 2017 (part 10) 57
Figure 29: Alzheimer’s Disease and Associated Indications, Global, First-in-Class Matrix Assessment for Alzheimer’s Disease Products, 2017 60
Figure 30: Alzheimer’s Disease and Associated Indications, Global, First-in-Class Matrix Assessment for Anxiety Products, 2017 61
Figure 31: Alzheimer’s Disease and Associated Indications, Global, First-in-Class Matrix Assessment for Depression Products, 2017 62
Figure 32: Alzheimer’s Disease and Associated Indications, Global, First-in-Class Matrix Assessment for Psychosis Products, 2017 62
Figure 33: Alzheimer’s Disease and Associated Indications, Global, First-in-Class Matrix Assessment for Insomnia Products, 2017 63
Figure 34: Alzheimer’s Disease and Associated Indications, Global, Industry-Wide Licensing Deals by First-in-Class Status and Stage of Development, 2006-2014 80
Figure 35: Alzheimer’s Disease and Associated Indications, Global, Industry-Wide Licensing Deals by Deal Value, Upfront Payment Value, Stage of Development and First-in-Class Status, 2006-2014 81
Figure 36: Alzheimer’s Disease and Associated Indications, Global, Licensing Deals by Region, Value and Year, 2006-2017 82
Figure 37: Alzheimer’s Disease and Associated Indications, Global, Licensing Deals by Indication and Deal Value, 2006-2017 83
Figure 38: Alzheimer’s Disease and Associated Indications, Global, Licensing Deals by Deal Value, Upfront Payment Value and Stage of Development, 2006-2017 84
Figure 39: Alzheimer’s Disease and Associated Indications, Global, Number and Aggregate Deal Value of Licensing Deals by Molecule Type, 2006-2017 84
Figure 40: Alzheimer’s Disease and Associated Indications, Global, Number and Aggregate Deal Value of Licensing Deals by Molecular Target, 2006-2017 85
Figure 41: Alzheimer’s Disease and Associated Indications, Global, Licensing Deals Exceeding $100m in Value, 2006-2017 86
Figure 42: Alzheimer’s Disease and Associated Indications, Global, Co-development Deals by Region, Value and Year, 2006-2017 87
Figure 43: Alzheimer’s Disease and Associated Indications, Global, Co-development Deals by Indication and Deal Value, 2006-2017 88
Figure 44: Alzheimer’s Disease and Associated Indications, Global, Co-development Deals by Stage of Development, Deal Value and Upfront Payment Value, 2006-2017 88
Figure 45: Alzheimer’s Disease and Associated Indications, Global, Number and Aggregate Deal Value of Co-development Deals by Molecule Type, 2006-2017 89
Figure 46: Alzheimer’s Disease and Associated Indications, Global, Number and Aggregate Deal Value of Co-development Deals by Molecular Target, 2006-2017 89
Figure 47: Alzheimer’s Disease and Associated Indications, Global, Co-development Deals Exceeding $100m in Value, 2006-2017 90
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