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 Exceptionally Large and Innovative Pipeline 6 2.2 Alignment of First-in-Class Molecular Target with Disease Causation 6 2.3 Highly Active Deals Landscape with Numerous Investment Opportunities 6 3 The Case for Innovation 7 3.1 Growing Opportunities for Biologic Products 7 3.2 Diversification of Molecular Targets 8 3.3 Innovative First-in-Class Product Developments Remain Attractive 8 3.4 Regulatory and Reimbursement Policy Shifts Favor First-in-Class Innovation 9 3.5 Sustained Innovation in Breast Cancer 9 3.6 Report Guidance 9 4 Clinical and Commercial Landscape 11 4.1 Overview of Breast Cancer 11 4.2 Symptoms 11 4.3 Diagnosis 11 4.4 Etiology 12 4.4.1 Age and Gender 12 4.4.2 Genetics 12 4.4.3 Environmental 13 4.5 Pathophysiology 13 4.5.1 Tumor Initiation and Aberrant Cell Proliferation and Survival 13 4.5.2 Tumor Metabolic Shift 14 4.5.3 Tumor Progression, Micro-environment Alteration and Angiogenesis 15 4.5.4 Cancer Stem Cells 16 4.6 Epidemiology 16 4.7 Complications 17 4.8 Prognosis and Disease Staging 18 4.8.1 Classification 19 4.9 Introduction to Breast Cancer Treatments 20 4.9.1 Treatment Algorithm 20 4.9.2 Treatment Options for Breast Cancer 22 4.10 Overview of Marketed Products in Breast Cancer 26 4.11 Current Unmet Needs in the Breast Cancer Market 27 5 Assessment of Pipeline Product Innovation 29 5.1 Overview 29 5.2 Breast Cancer Pipeline by Phase of Development and Molecule Type 29 5.3 Pipeline by Molecular Target 30 5.4 Comparative Distribution of Programs between the Market and Pipeline by Molecular Target Class 32 5.5 Comparative Distribution of First-in-Class and Non-First-in-Class Pipeline Programs by Molecular Target Class 32 5.5.1 Percentage Distribution of First-in-Class and Non-First-in-Class Pipeline Programs 35 5.6 Ratio of First-In-Class Programs to First-in-Class Molecular Targets within the Pipeline 36 5.7 List of All First-in-Class Pipeline Programs 38 6 Signaling Network, Disease Causation and Innovation Alignment 62 6.1 Complexity of Signaling Networks in Breast Cancer 62 6.2 Signaling Pathways, Disease-Causing Mutations and First-in-Class Molecular Target Integration 62 6.3 First-in-Class Molecular Target Matrix Assessment 63 7 First-in-Class Target Evaluation 70 7.1 Pipeline Programs Targeting PI3K Catalytic Subunit Alpha Isoform (PI3KCA) 70 7.2 Pipeline Programs Targeting GTPase KRAS (K-ras) 71 7.3 Pipeline Programs Targeting Cluster of Differentiation 47 (CD47) 72 7.4 Pipeline Programs Targeting CD278 (ICOS gene product) 74 7.5 Pipeline Programs Targeting Stimulator of Interferon Genes (TMEM173 gene product) 74 7.6 Pipeline Programs Targeting Receptor Tyrosine Protein Kinase ERBB 3 (HER3) 76 7.7 Pipeline Programs Targeting Neuregulin-1 (NRG1) 79 7.8 Pipeline Programs Targeting Calcium Release-Activated Calcium Channel Protein 1 (ORAI1) 80 7.9 Conclusion 81 8 Strategic Consolidations 83 8.1 Industry-Wide First-in-Class Deals 83 8.2 Breast Cancer Deals Landscape 84 8.3 Licensing Deals 85 8.3.1 Deals by Region, Value and Year 85 8.3.2 Deals by Stage of Development and Value 86 8.3.3 Deals by Molecule Type and Molecular Target 87 8.3.4 List of Deals with Disclosed Deal Values 88 8.4 Co-development Deals 92 8.4.1 Deals by Region, Value and Year 92 8.4.2 Deals by Stage of Development and Value 93 8.4.3 Deals by Molecule Type and Molecular Target 94 8.4.4 List of Deals with Disclosed Deal Values 95 8.5 First-In-Class Programs with and without Prior Licensing or Co-development Deal Involvement 96 9 Appendix 105 9.1 Abbreviations 105 9.2 References 106 9.3 Methodology 120 9.3.1 Data integrity 120 9.3.2 Innovative and Meaningful Analytical Techniques and Frameworks 120 9.3.3 Evidence Based Analysis and Insight 120 9.4 Secondary Research 120 9.4.1 Market Analysis 121 9.4.2 Pipeline Analysis 121 9.4.3 Licensing and Co-development Deals 121 9.5 Contact Us 122 9.6 Disclaimer 122

1.1 List of Tables Table 1: Breast Cancer, Global, Tumor, Regional Lymph Node and Metastasis Staging, 2010-2013 18 Table 2: Breast Cancer, Global, US, Disease Stage at Diagnosis and Five-year Relative Survival (%), 2013 18 Table 3: Breast Cancer, Global, Breast Cancer Histopathological and Molecular Classification, 2018 19 Table 4: Breast Cancer, Global, Key Features of Phosphoinositide 3-kinase Catalytic Subunit Alpha Isoform (PI3K), 2018 70 Table 5: Breast Cancer, Global, Pipeline Programs Targeting Phosphoinositide 3-kinase Catalytic Subunit Alpha Isoform (PI3K), 2018 71 Table 6: Breast Cancer, Global, Key Features of GTPase KRAS (K-ras), 2018 72 Table 7: Breast Cancer, Global, Pipeline Programs Targeting GTPase KRAS (K-ras), 2018 72 Table 8: Breast Cancer, Global, Key Features of Cluster of Differentiation 47 (CD47), 2018 73 Table 9: Breast Cancer, Global, Pipeline Programs Targeting Cluster of Differentiation 47 (CD47), 2018 73 Table 10: Breast Cancer, Global, Key Features of Cluster of Differentiation 278 (CD278), 2018 74 Table 11: Breast Cancer, Global, Pipeline Programs Targeting Cluster of Differentiation 278 (CD278), 2018 74 Table 12: Breast Cancer, Global, Key Features of Stimulator of Interferon Genes (STING), 2018 75 Table 13: Breast Cancer, Global, Pipeline Programs Targeting Stimulator of Interferon Genes (STING), 2018 76 Table 14: Breast Cancer, Global, Key Features of Tyrosine Protein Kinase ERBB3 (HER3), 2018 77 Table 15: Breast Cancer, Global, Pipeline Programs Targeting Tyrosine Protein Kinase ERBB3 (HER3), 2018 78 Table 16: Breast Cancer, Global, Key Features of Neuregulin-1 (NRG-1), 2018 80 Table 17: Breast Cancer, Global, Pipeline Programs Targeting Neuregulin-1 (NRG-1), 2018 80 Table 18: Breast Cancer, Global, Key Features of Calcium Release Activated Calcium Channel Protein 1 (ORAI1), 2018 81 Table 19: Breast Cancer, Global, Pipeline Programs Targeting Calcium Release Activated Calcium Channel Protein 1 (ORAI1), 2018 811.2 List of Figures Figure 1: Breast Cancer, Global, Innovation Trends in Product Approvals Across the Pharmaceutical Market, 1987-2014 7 Figure 2: Breast Cancer, Global, Post-Marketing-Approval Sales Performance of First-in-Class Products Across the Pharmaceutical Industry ($m), 2006-2013 8 Figure 3: Breast Cancer, Global, Treatment Algorithm for Cancer Diagnosed at Stages I to III, 2018 21 Figure 4: Breast Cancer, Global, Treatment Algorithm for Cancer Diagnosed at Stage IV, 2018 22 Figure 5: Breast Cancer, Global, Market by Molecule Type and Molecular Target, 2018 27 Figure 6: Breast Cancer, Global, Pipeline Size by Therapy Area, 2018 29 Figure 7: Breast Cancer, Global, Pipeline by Stage of Development and Molecule Type, 2018 30 Figure 8: Breast Cancer, Global, Pipeline by Molecular Target and Breakdown of Growth Factor Antagonist Molecular Target Class, 2018 31 Figure 9: Breast cancer, Global, Distribution of Pipeline and Marketed Products by Molecular Target Class, 2018 32 Figure 10: Breast Cancer, Global, Distribution of Pipeline Products by First-in-Class Status and Molecular Target Class, 2018 34 Figure 11: Breast Cancer, Global, Percentage Distribution of First-in-Class and Non-First-in-Class Products by Stage of Development and Molecular Target Class, 2018 36 Figure 12: Breast Cancer, Global, Ratio of First-in-Class Products to First-in-Class Targets by Stage of Development and Molecular Target Class, 2018 37 Figure 37: Breast Cancer, Global, First-in-Class Molecular Target Matrix Assessment for Breast Cancer, 2018 (part 1) 64 Figure 44: Breast Cancer, Global, Industry-Wide Licensing Deals by First-in-Class Status and Stage of Development, 2006-2015 83 Figure 45: Breast Cancer, Global, Industry-Wide Licensing Deals by First-in-Class Status, Deal Value, Upfront Payment Value and Stage of Development, 2006-2014 84 Figure 46: Breast Cancer, Global, Licensing Deals by Region, Value and Year, 2006-2018 86 Figure 47: Breast Cancer, Global, Licensing Deals by Deal Value, Upfront Payment Value and Stage of Development, 2006-2018 87 Figure 48: Breast Cancer, Global, Number and Aggregate Deal Value of Licensing Deals by Molecule Type and Molecular Target Class, 2006-2018 88 Figure 52: Breast Cancer, Global, Co-development Deals by Region, Value and Year, 2006-2018 92 Figure 53: Breast Cancer, Global, Number and Aggregate Deal Value of Co-development Deals by Stage of Development and Year, 2006-2018 93 Figure 54: Breast Cancer, Global, Number and Aggregate Deal Value of Co-development Deals by Molecule Type and Molecular Target Class, 2006-2018 94 Figure 55: Breast Cancer, Global, Number and Aggregate Deal Value of Co-development Deals by Molecule Type and Molecular Target Class, 2006-2018 95