1 Table of Contents 1 Table of Contents 5 1.1 List of Tables 7 1.2 List of Figures 7 2 Introduction 9 2.1 Disease Introduction 9 2.2 Symptoms 9 2.3 Etiology 10 2.3.1 Genetic Factors 10 2.3.2 Environmental Factors 11 2.3.3 Aging 11 2.4 Pathophysiology 12 2.5 Epidemiology 13 2.6 Disease Stages 14 2.7 Co-morbidities and Complications 15 2.8 Diagnosis 15 2.9 Assessment of Disease Severity 16 2.9.1 Hoehn and Yahr scale 16 2.9.2 Unified Parkinson’s Disease Rating Scale 16 2.10 Treatment 17 2.10.1 Pharmacological Therapies 18 2.10.2 Non-pharmacological Treatments 20 2.11 Treatment Algorithm 21 2.11.1 Early Parkinson’s Disease 21 2.11.2 Advanced Parkinson’s Disease 22 3 Marketed Products 25 3.1 Overview 25 3.1.1 Dopamine Replacement Therapies 25 3.1.2 MAO-B Inhibitors 28 3.1.3 Dopamine Agonists 30 3.1.4 COMT Inhibitors 35 3.1.5 Other Drugs Targeting Non-motor Symptoms of PD 39 3.2 Comparative Efficacy and Safety 40 4 Pipeline for Parkinson’s Disease 44 4.1 Overview 44 4.2 Pipeline Distribution by Mechanism of Action/Molecular Target 46 4.3 Clinical Trials 49 4.3.1 Failure Rate 49 4.3.2 Clinical Trial Duration 51 4.3.3 Clinical Trial Size 53 4.3.4 Comparison of Average Trial Metrics by Phase and Mechanism of Action 55 4.4 Promising Pipeline Molecules 56 4.4.1 Opicapone – Bial 56 4.4.2 Nuplazid (pimavanserin) – Acadia Pharmaceuticals 58 4.4.3 Nurelin (Amantadine Hydrochloride Extended-Release) – Adamas Pharmaceuticals 59 4.4.4 Tozadenant – Biotie Therapies 60 4.4.5 APL-130277 (apomorphine hydrochloride) – Cynapsus Therapeutics 61 4.4.6 P2B001 (pramipexole dihydrochloride + rasagiline mesylate) – Pharma Two B 63 4.4.7 DM-1992 (levodopa + carbidopa extended release) – Depomed 63 4.4.8 CVT-301 (levodopa) – Acorda Therapeutics 65 4.4.9 Dipraglurant Immediate-Release– Addex Therapeutics 65 4.4.10 Accordion Pill (levodopa and carbidopa) – Intec Pharma 66 4.4.11 ND-0612L (levodopa and carbidopa) – NeuroDerm 67 4.5 Heatmaps of Safety and Efficacy for Parkinson’s Disease Pipeline and Marketed Products 69 4.6 Pipeline Product Heat Map and Product Competitiveness Framework 73 5 Market Forecast to 2021 74 5.1 Geographical Markets 74 5.1.1 Global Market 74 5.1.2 North America 76 5.1.3 Top Five European Markets 79 5.1.4 Japan 84 5.2 Drivers and Barriers 85 5.2.1 Drivers 85 5.2.2 Barriers 86 6 Strategic Consolidations 88 6.1 Major Co-Development Deals 88 6.1.1 TechnoPhage Enters into Co-Development Agreement with University of Macau 90 6.1.2 Dainippon Sumitomo Pharma Enters into Research Agreement with CiRA and Hitachi 90 6.1.3 MJFF Enters into Agreement with Prothena 90 6.1.4 Ubiquigent Enters into Co-Development Agreement with UbiQ 91 6.1.5 23andMe Partners with Genentech 91 6.2 Major Licensing Deals 91 6.2.1 Cephalon Enters Into Licensing Agreement With Mesoblast For Regenerative Medicine 93 6.2.2 Dexcel Pharma Enters into Licensing Agreement with Ramot at Tel Aviv University 94 6.2.3 Neuropore Therapies Enters into Licensing Agreement with UCB 94 6.2.4 Catalent Pharma Solutions Enters into Licensing Agreement with Sellas Life Sciences 94 6.2.5 MedGenesis Therapeutix Enters into Licensing Agreement with Pfizer 95 7 Appendix 96 7.1 All Pipeline Drugs by Stage of Development 96 7.1.1 Discovery 96 7.1.2 Preclinical 100 7.1.3 IND/CTA-filed 112 7.1.4 Phase I 113 7.1.5 Phase II 115 7.1.6 Phase III 117 7.1.7 Pre-registration 118 7.2 Market Forecasts to 2021 118 7.2.1 Global 118 7.2.2 US 118 7.2.3 Canada 119 7.2.4 UK 119 7.2.5 France 119 7.2.6 Germany 120 7.2.7 Italy 120 7.2.8 Spain 120 7.2.9 Japan 121 7.3 References 121 7.4 Abbreviations 129 7.5 Research Methodology 132 7.6 Secondary Research 133 7.7 Marketed Product Profiles 133 7.8 Late-Stage Pipeline Candidates 133 7.9 Comparative Efficacy and Safety Heat Map for Marketed and Pipeline Products 134 7.10 Product Competitiveness Framework 134 7.11 Pipeline Analysis 134 7.11.1 Overall Pipeline 134 7.11.2 Clinical Trials 134 7.11.3 Failure Rate 134 7.11.4 Clinical Trial Size 135 7.11.5 Clinical Trial Duration 135 7.11.6 Forecasting Model 135 7.12 Deals Data Analysis 136 7.13 Expert Panel Validation 136 7.14 Contact Us 136 7.15 Disclaimer 136

1.1 List of Tables Table 1: Gene Mutations Related to Parkinson’s Disease and Corresponding Clinical Phenotypes 12 Table 2: Hoehn and Yahr Scale and the Definition of Disability Stages 16 Table 3: Unified Parkinson’s Disease Rating Scale 16 Table 4: All Pipeline Products by Phase, Discovery 96 Table 5: All Pipeline Products by Phase, Preclinical 100 Table 6: All Pipeline Products by Phase, IND/CTA-filed 112 Table 7: All Pipeline Products by Phase, Phase I 113 Table 8: All Pipeline Products by Phase, Phase II 115 Table 9: All Pipeline Products by Phase, Phase III 117 Table 10: All Pipeline Products by Phase, Phase III and Pre-registration 118 Table 11: Global, Parkinson's Disease Market Forecast, 2014–2021 118 Table 12: US, Parkinson's Disease Market Forecast, 2014–2021 118 Table 13: Canada, Parkinson's Disease Market Forecast, 2014–2021 119 Table 14: UK, Parkinson's Disease Market Forecast, 2014–2021 119 Table 15: France, Parkinson's Disease Market Forecast, 2014–2021 119 Table 16: Germany, Parkinson's Disease Market Forecast, 2014–2021 120 Table 17: Italy, Parkinson's Disease Market Forecast, 2014–2021 120 Table 18 : Spain, Parkinson's Disease Market Forecast, 2014–2021 120 Table 19: Japan, Parkinson's Disease Market Forecast, 2014–2021 121 1.2 List of Figures Figure 1: Overview of the Basal Ganglia in the Normal State and Parkinson’s Disease State 13 Figure 2: Parkinson’s Disease Market, Global, Efficacy Heat Map for Marketed Products (Part 1) 41 Figure 3: Parkinson’s Disease Market, Global, Efficacy Heat Map for Marketed Products (Part 2) 42 Figure 4: Pipeline for Parkinson’s Disease, Global, 2015 45 Figure 5: Pipeline for Parkinson’s Disease by Molecular Target, Global, 2015 46 Figure 6: Pipeline for Parkinson’s Disease by Mechanism of Action, Global, 2015 47 Figure 7: Parkinson’s Disease, Global, Average Clinical Trial Failure Rate (%), 2006–2015 49 Figure 8 : Parkinson’s Disease, Global, Clinical Trial Failure Rates for Small Molecules (%), 2006–2015 50 Figure 9: Parkinson’s Disease, Global, Clinical Trial Failure Rates by Mechanism of Action (%), 2006–2015 51 Figure 10: Parkinson’s Disease, Global, Clinical Trial Duration by Molecule Type, 2006–2015 52 Figure 11: Parkinson’s Disease, Global, Clinical Trial Duration by Mechanism of Action, 2006–2015 53 Figure 12: Parkinson’s Disease, Global, Clinical Trial Size by Molecule Type, 2006–2015 54 Figure 13: Parkinson’s Disease, Global, Clinical Trial Size by Mechanism of Action, 2006–2015 55 Figure 14: Pipeline for Parkinson’s Disease, Global, Comparison of Average Trial Metrics by Phase and Mechanism of Action, 2006–2015 56 Figure 15: Parkinson’s Disease Market, Global, Annual Sales of Opicapone ($m), 2015–2021 57 Figure 16: Parkinson’s Disease Market, Global, Annual Sales of Nuplazid ($m), 2016–2021 59 Figure 17 : Parkinson’s Disease Market, Global, Annual Sales of Nurelin ($m), 2016–2021 60 Figure 18: Parkinson’s Disease Market, Global, Annual Sales of Tozadenant ($m), 2018–2021 61 Figure 19: Parkinson’s Disease Market, Global, Annual Sales of APL-130277 ($m), 2017–2021 62 Figure 20: Parkinson’s Disease Market, Global, Annual Sales of P2B001 ($m), 2016–2021 63 Figure 21: Parkinson’s Disease Market, Global, Annual Sales of DM-1992 ($m), 2018–2021 64 Figure 22: Parkinson’s Disease Market, Global, Annual Sales of CVT-301 ($m), 2016–2021 65 Figure 23: Parkinson’s Disease Market, Global, Annual Sales of Dipraglurant IR ($m), 2019–2021 66 Figure 24: Parkinson’s Disease Market, Global, Annual Sales of the Accordion Pill ($m) 2018–2021 67 Figure 25: Parkinson’s Disease Market, Global, Annual Sales of ND-0612L ($m) 2019–2021 68 Figure 26: Parkinson’s Disease Market, Global, Efficacy Heat Map for Pipeline Products 70 Figure 27: Parkinson’s Disease Market, Global, Efficacy Heat Map for Pipeline Products 70 Figure 28: Parkinson’s Disease Market, Global, Efficacy Heat Map for Marketed Products 71 Figure 29: Parkinson’s Disease Market, Global, Efficacy Heat Map for Marketed Products 72 Figure 30: Parkinson’s Disease Market, Global, Product Competitiveness Early Parkinson’s Disease 73 Figure 31: Parkinson’s Disease Market, Global, Product Competitiveness Advanced Parkinson’s Disease 73 Figure 32: Parkinson’s Disease Market, Global, Treatment Patterns by Number of Patients (‘000), 2014–2021 75 Figure 33: Parkinson’s Disease Market, Global, Market Size ($m), 2014–2021 75 Figure 34: Parkinson’s Disease Market, US and Canada, Treatment Patterns by Number of Patients (‘000), 2014–2021 76 Figure 35: Parkinson’s Disease Market, US and Canada, Annual Cost of Therapy ($), 2014–2021 78 Figure 36: Parkinson’s Disease Market, US and Canada, Market Size ($), 2014–2021 79 Figure 37: Parkinson’s Disease Market, Top Five EU Countries, Treatment Patterns by Number of Patients (‘000), 2014–2021 80 Figure 38: Parkinson’s Disease Market, Tope Five EU Countries, Annual Cost of Therapy ($m), 2014–2021 82 Figure 39: Parkinson’s Disease Market, Top Five EU Countries, Market Size ($m), 2014–2021 83 Figure 40: Parkinson’s Disease Market, Japan, Treatment Patterns by Number of Patients (‘000) and the Annual Cost of Therapy ($), 2014–2021 84 Figure 41: Parkinson’s Disease Market, Japan, Market Size ($m), 2014–2021 85 Figure 42: Parkinson’s Disease Market, Global, Co-development Deals, 2006–2015 88 Figure 43: Parkinson’s Disease Market, Global, Co-development Deals by Molecule type and Stage of Development, 2006–2015 89 Figure 44: Parkinson’s Disease Market, Global, Co-development Deals by Mechanism of Action, 2006–2015 90 Figure 45: Parkinson’s Disease Market, Global, Licensing Deals, 2006–2015 92 Figure 46: Parkinson’s Disease Market, Global, Licensing Deals by Molecule Type and Stage of Development, 2006–2015 93 Figure 47: Parkinson’s Disease Market, Global, Licensing Deals by Molecular Targets and Aggregate Deal Value ($), 2006–2015 93