1 Table of Contents 1 Table of Contents 2 1.1 List of Tables 3 1.2 List of Figures 3 2 Executive Summary 4 2.1 High Unmet Need and a Limited Number of Marketed Options 4 2.2 Large, Diverse and Highly Innovative Pipeline 4 2.3 Active Deals Landscape Reflects the Dynamic Pipeline 4 3 The Case for Innovation 5 3.1 Growing Opportunities for Biologic Products 6 3.2 Diversification of Molecular Targets 6 3.3 Innovative First-in-Class Product Developments Remain Attractive 7 3.4 Regulatory and Reimbursement Policy Shifts Favor First-in-Class Product Innovation 7 3.5 Sustained Innovation 8 3.6 GBI Research Report Guidance 8 4 Clinical and Commercial Landscape 9 4.1 Disease Overview 9 4.2 Symptoms 9 4.3 Diagnosis 10 4.3.1 Clinical Presentation 10 4.3.2 Alpha-Fetoprotein 10 4.3.3 Diagnostic Imaging and Scans 10 4.3.4 Screening 10 4.3.5 Biopsy 11 4.3.6 Staging, Classification and Prognosis 11 4.4 Epidemiology and Etiology 11 4.5 Pathophysiology 13 4.6 Risk Factors and Co-Morbidities 17 4.7 Treatment Options 17 4.8 Treatment Algorithm 18 4.9 Overview of Marketed Products for Liver Cancer 19 4.9.1 Innovative Products in the Liver Cancer Market 20 4.9.2 Unmet Needs 21 5 Assessment of Pipeline Product Innovation 22 5.1 Liver Cancer Pipeline by Molecule Type, Phase and Therapeutic Target 22 5.2 Comparative Distribution of Programs between the Liver Cancer Market and Pipeline by Therapeutic Target Family 26 5.3 First-in-Class Pipeline Programs 26 6 Signaling Network, Disease Causation and Innovation Alignment 34 6.1 The Complexity of Signaling Networks in Oncology 34 6.2 Signaling Pathways Disease-Causing Mutations and First-in-Class Molecular Target Integration 35 6.3 First-in-Class Target Matrix Assessment 35 7 First-in-Class Target Evaluation 38 7.1 Pipeline Programs Targeting PIK3CA, PIK3CB and PIK3CG 38 7.2 Pipeline Programs Targeting Protein Kinase C Delta 39 7.3 Pipeline Programs Targeting AKT1 40 7.4 Pipeline Programs Targeting HER3/ERBB3 42 7.5 Pipeline Programs Targeting ROR1 43 7.6 Pipeline Programs Targeting PRKACA fusions 44 7.7 Pipeline Programs Targeting Frizzled 2 44 7.8 Pipeline Programs Targeting CDK1 and 2 45 7.9 Pipeline Programs Targeting PTK2/FAK 46 7.10 Conclusion 47 8 Deals and Strategic Consolidations 48 8.1 Industry-Wide First-in-Class Deals 48 8.2 Liver Cancer Deals Landscape 49 8.3 Licensing Deals 50 8.3.1 Molecule Type 52 8.3.2 Molecular Target 52 8.4 Co-development Deals 55 8.4.1 Molecule Type 56 8.4.2 Molecular Target 56 8.5 First-in-Class Programs Not Involved in Licensing or Co-development Deals 58 9 Appendix 64 9.1 Abbreviations 64 9.2 References 65 9.3 Research Methodology 68 9.4 Secondary Research 69 9.4.1 Market Analysis 69 9.4.2 Pipeline Analysis 69 9.4.3 First-in-Class Matrix Assessment 69 9.4.4 First-in-Class Target Profiles 70 9.4.5 Licensing and Co-development Deals 70 9.5 Contact Us 70 9.6 Disclaimer 70

1.1 List of Tables Table 1: Symptoms of Liver Cancer 10 Table 2: Tumor, Regional Lymph Node and Metastasis Staging 11 Table 3: Risk Factors and Comorbidities for Liver Cancer 17 Table 4: Liver Cancer, Key Features and Pipeline Activity of PIK3CA/PIK3CB/PIK3CG 39 Table 5: Liver Cancer Key Features and Pipeline Activity of PRCKD 40 Table 6: Liver Cancer, Key Features and Pipeline Activity of AKT1 42 Table 7: Liver Cancer, Key Features and Pipeline Activity of HER3 43 Table 8: Liver Cancer, Key Features and Pipeline Activity of ROR1 43 Table 9: Liver Cancer, Key Features and Pipeline Activity of PRKACA Fusions 44 Table 10: Liver Cancer, Key Features and Pipeline Activity of FZD2 45 Table 11: Liver Cancer, Key Features and Pipeline Activity of CDK1/2 46 Table 12: Liver Cancer, Key Features and Pipeline Activity of PTK2/FAK 47 1.2 List of Figures Figure 1: Innovation Trends in Product Approvals, Number of Product Approvals by FDA and Five-Year Moving Average of Products Approvals (%), 1987-2015 6 Figure 2: Sales Performance After Marketing Approval of First-in-Class and Non-First-in-Class Products, 2006-2013 ($m) 7 Figure 3: Liver Cancer, Marketed Product Overview, 2017 19 Figure 4: Liver Cancer, Pipeline Products by Therapy Area, 2017 22 Figure 5: Liver Cancer, Developmental Pipeline Overview, 2017 23 Figure 6: Liver Cancer, Developmental Pipeline Overview, 2017 25 Figure 7: Liver Cancer, Molecular Target Category Comparison, Pipeline and Marketed Products, 2017 26 Figure 8: Liver Cancer Drug Market, Global, Percentage Distribution of First-in-Class Products in Pipeline by Stage of Development (%), 2017 27 Figure 9: Liver Cancer Drug Market, Global, Distribution of First-in-Class Products in Pipeline by Molecular Target (%), 2017 27 Figure 10: Liver Cancer, Products in the Pipeline (Part 1), 2017 28 Figure 11: Liver Cancer, Products in the Pipeline Part 2, 2017 29 Figure 12: Liver Cancer, Products in the Pipeline Part 3, 2017 30 Figure 13: Liver Cancer, Products in the Pipeline Part 4, 2017 31 Figure 14: Liver Cancer, Products in the Pipeline Part 5, 2017 32 Figure 15: Liver Cancer, Products in the Pipeline Part 6, 2017 33 Figure 16: Liver Cancer, First-in-Class Molecular Target Analysis Matrix, Part 1 2017 36 Figure 17: Liver Cancer, First-in-Class Molecular Target Analysis Matrix, Part 2 2017 37 Figure 18: Liver Cancer, First-in-Class Molecular Target Analysis Matrix, Part 3 2017 37 Figure 19: Liver Cancer, PIK3CA/PIK3CB/PIK3CG Targeting Products, 2017 39 Figure 20: Liver Cancer, PRKCD Targeting Products 40 Figure 21: Liver Cancer, AKT1 Targeting Products, 2017 41 Figure 22: Liver Cancer, HER3 Targeting Products, 2017 42 Figure 23: Liver Cancer, ROR1 Targeting Products, 2017 43 Figure 24: Liver Cancer, PRKACA Fusion Targeting Products, 2017 44 Figure 25: Liver Cancer, FZD2 Targeting Products, 2017 45 Figure 26: Liver Cancer, CDK1/2 Targeting Products, 2017 46 Figure 27: Liver Cancer, PTK2/FAK Targeting Products, 2017 47 Figure 28: Pharmaceutical Market, Global, Industry-Wide Deals by Stage of Development, 2006-2014 48 Figure 29: Pharmaceutical Market, Global, Industry Licensing Deal Values by Stage of Development, 2006-2014 49 Figure 30: Liver Cancer, Global, Licensing Deals by Region and Value, 2006-Q1 2017 51 Figure 31: Liver Cancer, Global, Licensing Deals by Stage and Value, 2006-Q1 2017 52 Figure 32: Liver Cancer, Licensing Deals by Molecular Type, 2006-Q1 2017 52 Figure 33: Liver Cancer, Licensing Deals by Molecular Target, 2006-Q1 2017 53 Figure 34: Liver Cancer, Licensing Deals with Disclosed Values, 2006-Q1 2017 54 Figure 35: Liver Cancer Drug Market, Global, Co-development Deals by Region, Value and Year, 2006-Q1 2017 55 Figure 36: Liver Cancer, Co-development Deals by Stage and Value, 2006-Q1 2017 56 Figure 37: Liver Cancer, Co-development Deals by Molecule Type, 2006-Q1 2017 56 Figure 38: Liver Cancer, Co-development Deals by Molecular Target, 2006-Q1 2017 57 Figure 39: Liver Cancer, Co-development Deals with Disclosed Values, 2006-Q1 2017 57 Figure 40: Liver Cancer Market, Global, Pipeline Programs in Active Development Involved in Previous Deals, 2017 58 Figure 41: Liver Cancer Market, Global, Pipeline Programs in Active Development Without Recorded Prior Deal Involvement, 2016 (Part 1) 59 Figure 42: Liver Cancer Market, Global, Pipeline Programs in Active Development Without Recorded Prior Deal Involvement, 2016 (Part 2) 60 Figure 43: Liver Cancer Market, Global, Pipeline Programs in Active Development Without Recorded Prior Deal Involvement, 2016 (Part 3) 61 Figure 44: Liver Cancer Market, Global, Pipeline Programs in Active Development Without Recorded Prior Deal Involvement, 2016 (Part 4) 62 Figure 45: Liver Cancer Market, Global, Pipeline Programs in Active Development Without Recorded Prior Deal Involvement, 2016 (Part 5) 63