1 Table of Contents 1 Table of Contents 4 1.1 List of Tables 6 1.2 List of Figures 7 2 Introduction 9 2.1 Disease Introduction 9 2.2 Epidemiology 9 2.3 Symptoms 10 2.4 Etiology 12 2.5 Pathophysiology 12 2.6 Disease Stages 13 2.7 Diagnosis 14 2.8 Prognosis 17 2.9 Treatment 18 2.9.1 Treatment Algorithm 18 2.9.2 Mild-to-Moderate AD 20 2.9.3 Moderate-to-Severe AD 21 3 Marketed Products 22 3.1 Aricept (donepezil) - Eisai 22 3.2 Exelon (rivastigimine) - Novartis 22 3.3 Razadyne (galanatamine) - Janssen 23 3.4 Namenda/Ebixa/Axura/Abixa (memantine), Merz Pharma/Lundbeck/Forest/Daiichi Sankyo 23 3.5 Cognex (tacrine) - Shiniogi 24 3.6 Namzaric (memantine ER + donepezil), Actavis-Adamas 24 4 Heat Map - Marketed Products Overview 25 5 Pipeline Product Developments 26 5.1 The Pipeline Development Landscape 26 5.2 Mechanisms of Action in the Pipeline 27 5.3 Clinical Trials 31 5.3.1 Failure Rate 31 5.3.2 Clinical Trial Duration 32 5.3.3 Clinical Trial Size 34 5.3.4 Competitive Clinical Trials Metric Analysis 38 5.4 Promising Pipeline Molecules 39 5.4.1 MK-8931 - Merck & Co. 39 5.4.2 LMTX (methylthioninium chloride) - TauRX Therapeutics 40 5.4.3 AZD3293 - AstraZeneca 41 5.4.4 AB1010 - AB Science 42 5.4.5 BIIB037 - Biogen 43 5.4.6 TP488 - vTv Therapeutics 44 5.4.7 EVP-6124 - FORUM Pharmaceuticals 45 5.4.8 LuAE58054 - Lundbeck 46 5.4.9 Gantenerumab (R-1540/RG-1450) - Roche 47 6 Heat Map - Pipeline Products Overview 50 7 Market Forecast to 2021 51 7.1 Geographical Markets 51 7.1.1 Global Market 51 7.1.2 North America 55 7.1.3 European Union Five 61 7.1.4 Japan 68 8 Drivers and Barriers 74 8.1 Drivers 74 8.1.1 Rising Prevalence 74 8.1.2 Increasing Public and Policy-Maker Awareness 74 8.1.3 Innovation in Pipeline 74 8.1.4 Growing Understanding of AD Pathophysiology 74 8.2 Barriers 74 8.2.1 Sales Erosion by Generics 74 8.2.2 High Clinical Failure RatesAD has a particularly high clinical trial failure rate. 75 8.2.3 Drug Testing in Patients with Established AD and Advanced Neurodegeneration 75 8.2.4 Low Diagnosis and Treatment Rate 75 9 Strategic Consolidations 76 9.1 Licensing Deals 76 9.1.1 Cephalon Enters into Licensing Agreement with Mesoblast 80 9.1.2 Lundbeck Enters into Licensing Agreement with Otsuka 80 9.1.3 Roche Enters into Licensing Agreement with Prothera 80 9.1.4 GlaxoSmithKline Enters into Licensing Agreement with AFFiRiS 81 9.2 Major Co-development Deals 81 9.2.1 Lundbeck Enters into Co-development Agreement with Otsuka 85 9.2.2 GlaxoSmithKline Enters into Agreement with EPIX Pharma 85 9.2.3 Evotec Enters into Co-development Agreement with Roche 86 9.2.4 Pfizer Enters into Co-development Agreement with Medivation 86 10 Appendix 87 10.1 All Pipeline Drugs by Phase 87 10.1.1 Discovery 87 10.1.2 Preclinical 96 10.1.3 Phase I 116 10.1.4 Phase II 119 10.1.5 Phase III 122 10.1.6 Market Forecasts to 2021 124 10.2 Bibliography 133 10.3 Abbreviations 139 10.4 Research Methodology 140 10.4.1 Secondary Research 141 10.4.2 Marketed Product Profiles 141 10.4.3 Late-Stage Pipeline Candidates 141 10.4.4 Comparative Efficacy and Safety Heat Map for Marketed and Pipeline Products 141 10.4.5 Product Competitiveness Framework 142 10.4.6 Pipeline Analysis 142 10.4.7 Forecasting Model 143 10.4.8 Deals Data Analysis 144 10.5 Contact Us 144 10.6 Disclaimer 144

1.1 List of Tables Table 1: Alzheimer’s Disease Therapeutics Market, Symptoms of Alzheimer’s Disease at Different Stages of Disease 11 Table 2: Alzheimer’s Disease Therapeutics Market, Symptoms of Mild Cognitive Impairment 11 Table 3: Alzheimer’s Disease Therapeutics Market, Global Deterioration Scale for Alzheimer’s Disease 14 Table 4: Alzheimer’s Disease Therapeutics Market, Mini-Mental State Exam 15 Table 5: Alzheimer’s Disease Therapeutics Market, Alzheimer’s Disease Assessment Scale Cognitive Subscale 16 Table 6: Alzheimer’s Disease Therapeutics Market, Mild Cognitive Impairment Diagnosis Guidelines 17 Table 7: Management of AD Symptoms 20 Table 8: AD Market, Global, Pipeline Products, Discovery, 2016 87 Table 9: AD Market, Global, Pipeline Products, Preclinical, 2016 96 Table 10: AD Market, Global, Pipeline Products, Phase I, 2016 116 Table 11: AD Market, Global, Pipeline Products, Phase II, 2016 119 Table 12: AD Market, Global, Pipeline Products, Phase III, 2016 122 Table 13: MCI Market, Global, Market Forecast, 2014-2021 124 Table 14: AD Market, Global, Market Forecast, 2014-2021 124 Table 15: MCI & AD Combined Market, Global, Market Forecast, 2014-2021 124 Table 16: MCI Market, US, Market Forecast, 2014-2021 125 Table 17: AD Market, US, Market Forecast, 2014-2021 125 Table 18: MCI & AD Market, US, Market Forecast, 2014-2021 125 Table 19: MCI Market, Canada, Market Forecast, 2014-2021 126 Table 20: AD Market, Canada, Market Forecast, 2014-2021 126 Table 21: MCI & AD Combined Market, Canada, Market Forecast, 2014-2021 126 Table 22: MCI Market, UK, Market Forecast, 2014-2021 127 Table 23: AD Market, UK, Market Forecast, 2014-2021 127 Table 24: MCI & AD Combined Market, UK, Market Forecast, 2014-2021 127 Table 25: MCI Market, France, Market Forecast, 2014-2021 128 Table 26: AD Market, France, Market Forecast, 2014-2021 128 Table 27: MCI & AD Market Combined, France, Market Forecast, 2014-2021 128 Table 28: MCI Market, Germany, Market Forecast, 2014-2021 129 Table 29: AD Market, Germany, Market Forecast, 2014-2021 129 Table 30: MCI & AD Combined Market, Germany, Market Forecast, 2014-2021 129 Table 31: MCI Market, Italy, Market Forecast, 2014-2021 130 Table 32: AD Market, Italy, Market Forecast, 2014-2021 130 Table 33: MCI & AD Combined Market, Italy, Market Forecast, 2014-2021 130 Table 34: MCI Market, Spain, Market Forecast, 2014-2021 131 Table 35: AD Market, Spain, Market Forecast, 2014-2021 131 Table 36: MCI & AD Combined Market, Spain, Market Forecast, 2014-2021 131 Table 37: MCI Market, Japan, Market Forecast, 2014-2021 132 Table 38: AD Market, Japan, Market Forecast, 2014-2021 132 Table 39: MCI & AD Combined Market, Japan, Market Forecast, 2014-2021 132
1.2 List of Figures Figure 1: Alzheimer’s Disease Therapeutics Market, Treatment Algorithm of Alzheimer’s Disease 19 Figure 2: Alzheimer’s Disease Therapeutics Market, Heat Map for Marketed Products 25 Figure 3: Alzheimer’s Disease Therapeutics Market, Overall Pipeline 27 Figure 4: Alzheimer’s Disease Therapeutics Market, Pipeline by Mechanism of Action (%) 30 Figure 5: Alzheimer’s Disease Therapeutics Market, Clinical Trial Failure Rates by Phase (%) 31 Figure 6: Alzheimer’s Disease Therapeutics Market, Clinical Trial Failure Rates by Mechanism of Action, (%) 32 Figure 7: Alzheimer’s Disease Therapeutics Market, Clinical Trial Duration by Molecule Type (months) 33 Figure 8: Alzheimer’s Disease Therapeutics Market, Clinical Trial Duration by Mechanism of Action (months) 34 Figure 9: Alzheimer’s Disease Therapeutics Market, Clinical Trial Size per Product by Molecule Type (participants) 35 Figure 10: Alzheimer’s Disease Therapeutics Market, Clinical Trial Size per Product by Mechanism of Action (participants) 36 Figure 11: Alzheimer’s Disease Therapeutics Market, Clinical Trial Size per Trial by Molecule Type (participants) 37 Figure 12: Alzheimer’s Disease Therapeutics Market, Clinical Trial Size per Trial by Mechanism of Action (participants) 38 Figure 13: Alzheimer’s Disease Therapeutics Market, Global, Comparison of Average Trial Metrics by Phase and Molecule Type 38 Figure 14: Alzheimer’s Disease Therapeutics Market, Global, Comparison of Average Trial Metrics by Phase and Mechanism of Action 39 Figure 15: Alzheimer’s Disease Therapeutics Market, Global, Verubecestat Market Forecast ($m), 2018-2021 40 Figure 16: Alzheimer’s Disease Therapeutics Market, Global, LMTX Market Forecast ($m), 2017-2021 41 Figure 17: Alzheimer’s Disease Market, Global, AZD3293 Market Forecast ($m), 2019-2021 42 Figure 18: Alzheimer’s Disease Therapeutics Market, Global, Masitinib Market Forecast ($m), 2017-2021 43 Figure 19: Alzheimer’s Disease Therapeutics Market, Global, Aducanumab Market Forecast ($m), 2019-2021 44 Figure 20: Alzheimer’s Disease Therapeutics Market, Global, Azeliragon Market Forecast ($m), 2017-2021 45 Figure 21: Alzheimer’s Disease Therapeutics Market, Global, Encenicline Hydrochloride Market Forecast ($m), 2017-2021 46 Figure 22: Alzheimer’s Disease Therapeutics Market, Global, Idalopirdine Market Forecast ($m), 2017-2021 47 Figure 23: Alzheimer’s Disease Therapeutics Market, Global, Gantenerumab Market Forecast ($m), 2020-2021 49 Figure 24: Alzheimer’s Disease Therapeutics Market, Heat Map for Marketed Products 50 Figure 25: Alzheimer’s Disease and Mild Cognitive Impairment Therapeutics Markets, Global, Treatment Patterns (‘000), 2014-2021 52 Figure 26: Alzheimer’s Disease and Mild Cognitive Impairment Aggregate Therapeutics Market, Global, Treatment Patterns (‘000), 2014-2021 53 Figure 27: Alzheimer’s Disease and Mild Cognitive Impairment Therapeutics Markets, Global, Market Size ($bn), 2014-2021 54 Figure 28: Alzheimer’s Disease and Mild Cognitive Impairment Aggregate Therapeutics Market, Global, Market Size ($bn), 2014-2021 55 Figure 29: Alzheimer’s Disease and Mild Cognitive Impairment Therapeutics Markets, North America, Treatment Patterns (‘000), 2014-2021 56 Figure 30: Alzheimer’s Disease and Mild Cognitive Impairment Aggregate Therapeutics Market, North America, Treatment Patterns (‘000), 2014-2021 57 Figure 31: Alzheimer’s Disease Therapeutics Market, North America, Annual Cost of Therapy ($), 2014-2021 58 Figure 32: Alzheimer’s Disease Therapeutics Market, North America, Market Size ($m), 2014-2021 59 Figure 33: Alzheimer’s Disease and Mild Cognitive Impairment Aggregate Therapeutics Market, North America, Market Size, 2014-2021 60 Figure 34: Mild Cognitive Impairment Therapeutics Market, EU5, Treatment Patterns (‘000), 2014-2021 61 Figure 35: Alzheimer’s Disease Therapeutics Market, EU5, Treatment Patterns (‘000), 2014-2021 62 Figure 36: Alzheimer’s Disease and Mild Cognitive Impairment Aggregate Therapeutics Market, EU5, Treatment Patterns (‘000), 2014-2021 63 Figure 37: Mild Cognitive Impairment Therapeutics Market, EU5, Annual Cost of Therapy ($), 2014-2021 64 Figure 38: Alzheimer’s Disease Therapeutics Market, EU5, Annual Cost of Therapy ($), 2014-2021 65 Figure 39: Mild Cognitive Impairment Therapeutics Market, EU5, Market Size ($m), 2014-2021 66 Figure 40: Alzheimer’s Disease Therapeutics Market, EU5, Market Size ($m), 2014-2021 67 Figure 41: Alzheimer’s Disease and Mild Cognitive Impairment Aggregate Therapeutics Market, EU5, Market Size ($m), 2014-2021 68 Figure 42: Alzheimer’s Disease and Mild Cognitive Impairment Therapeutics Markets, Japan, Treatment Patterns (‘000), 2014-2021 69 Figure 43: Alzheimer’s Disease and Mild Cognitive Impairment Aggregate Therapeutics Market, Japan, Treatment Patterns (‘000), 2014-2021 70 Figure 44: Mild Cognitive Impairment Therapeutics Market, Japan, Annual Cost of Therapy ($), 2014-2021 70 Figure 45: Alzheimer’s Disease Therapeutics Market, Japan, Annual Cost of Therapy ($), 2014-2021 71 Figure 46: Mild Cognitive Impairment Therapeutics Market, Japan, Market Size ($bn), 2014-2021 72 Figure 47: Alzheimer’s Disease Therapeutics Market, Japan, Market Size ($m), 2014-2021 72 Figure 48: Alzheimer’s Disease and Mild Cognitive Impairment Aggregate Therapeutics Market, Japan, Market Size ($bn), 2014-2021 73 Figure 49: Alzheimer’s Disease Therapeutics Market, Licensing Deals by Value, 2006-2015 76 Figure 50: Alzheimer’s Disease Therapeutics Market, Global, Number of Disclosed and Undisclosed Licensing Deals by Year, Aggregate Deal Value ($bn) and Aggregate Upfront Payment Value ($bn), 2006-2015 77 Figure 51: Alzheimer’s Disease Therapeutics Market, Global, Licensing Deals by Stage of Development, Deal Value ($m) and Upfront Payment Value ($m), 2006-2015 78 Figure 52: Alzheimer’s Disease Therapeutics Market, Global, Licensing Deals by Molecule Type and Value ($), 2006-2015 79 Figure 53: Alzheimer’s Disease Therapeutics Market, Global, Licensing Deals by Molecular Target and Aggregate Value ($bn), 2006-2015 80 Figure 54: Alzheimer’s Disease Therapeutics Market, Global, Co-development Deals by Value, 2006-2015 81 Figure 55: Alzheimer’s Disease Therapeutics Market, Global, Number of Disclosed and Undisclosed Co-development Deals by Year, Aggregate Deal Value ($m) and Aggregate Upfront Payment Value ($m), 2006-2015 82 Figure 56: Alzheimer’s Disease Therapeutics Market, Global, Co-development Deals by Stage of Development, Deal Value ($) and Upfront Payment Value ($m), 2006-2015 83 Figure 57: Alzheimer’s Disease Therapeutics Market, Global, Co-development Deals by Molecule Type and Value ($), 2006-2015 84 Figure 58: Alzheimer’s Disease Therapeutics Market, Global, Licensing Deals by Molecular Target and Aggregate Value ($bn), 2006-2015 85