Large and Diverse Pipeline

The liver cancer pipeline contains 238 products in active development, approximately 47% of which are first-in-class. The percentage of the pipeline devoted to innovative products is considerably larger than both the industry and oncology average, which is a promising sign for novel therapeutics reaching the liver cancer market.

The contrast between the market and pipeline is vast. Analysis showed that the market contains 70 products, the majority of which are generic formulations of chemotherapies that are not frequently used in treatment, particularly in advanced-stage patients. Nexavar (sorafenib) is the dominant therapeutic on the market, and is also the only targeted therapy that is in regular use for advanced-stage liver cancer patients. However, pipeline analysis revealed that targeted therapies aimed at the underlying oncogenic signaling pathways are under much greater focus in the pipeline than in the market. The success of targeted therapies across the oncology market as a whole implies that the diversity and innovation in the pipeline is a promising sign, with products currently in development having the potential to transform and improve the relatively open liver cancer market.

Alignment of First-in-Class Molecular Targets with Disease Causation

The liver cancer pipeline is showing signs of adapting to the increasing understanding of aberrant signaling pathways and causes of liver cancer. A large portion of pipeline products target components of known dysfunctional signaling pathways, such as Wnt/ß-catenin signaling, which is commonly mutated in liver cancer tumor samples. By aligning the treatment with specific disease-causing features, the damaging off-target cytotoxic effects of treatment can be reduced, resulting in safer and more efficacious therapies.

GBI Research’s analysis identified substantial variation in the alignment of first-in-class products to underlying dysfunctional signaling at protein and genetic level. The first-in-class products were compared in an in-depth analysis using various parameters to measure the potential of each target, with the most promising targets being further substantiated by published clinical and scientific evidence. Results of the analysis suggested that first-in-class status is not a feature that, in its own right, will create a successful product. However, there are a large number of first-in-class products backed by clinical and Preclinical data that are exciting future prospects for the liver cancer market.

Analysis of Patent Data

The report features an analysis of granted patent applications in the liver cancer market, which was used as an indication of innovation at the earliest stage of product development. Patent analysis provides an insight into the pre-developmental landscape, and identifies long-term future trends within a disease market. In liver cancer, the trend in patent applications in terms of predominant molecular targets reflects the pipeline landscape, suggesting that liver cancer therapeutics will continue to target key oncogenic signaling pathways in the long term.

The frequency at which companies apply for patents within the market helps to identify companies that are trying to establish themselves or increase their liver cancer market share. This information identifies not only potential competitors, but also companies that may seek strategic partnerships to enter drug development.

First-in-Class Products in Licensing and Co-Development Deals

The deals landscape for liver cancer has been relatively active in recent years, with 62 licensing deals and 23 co-development deals between 2006 and 2014. However, the number pertaining to first-in-class products is very low.

A comparative analysis of the deals revealed that first-in-class products have the potential to command substantially higher deal values than non-first-in-class products, which is a reflection of their market potential and importance. A total of 68 first-in-class products that are currently in development have not yet been entered into a licensing or co-development deal. In a transforming market that will favor innovative, targeted therapies with a strong clinical record, there are numerous opportunities for strategic alliances to bolster a first-in-class portfolio or fund clinical development. Although not all are aligned to disease-causing signaling pathways, many are supported by robust scientific and clinical data, making them attractive prospects as both therapeutics and investment opportunities.

Scope

The report includes –

• A brief introduction to liver cancer, including symptoms, pathophysiology, and an overview of pharmacotherapy and treatment algorithms
• Coverage of the changing molecular target landscape and particular points of innovation in the pipeline
• A comprehensive review of the pipeline for first-in-class therapies, analyzed by stage of development, molecule type and molecular target
• Analysis of patent trends and patent families in liver cancer
• Identification and assessment of first-in-class molecular targets, with a particular focus on early-stage programs of which clinical utility has yet to be evaluated, as well as literature reviews of novel molecular targets
• Industry-wide analysis of first-in-class deals compared to non-first-in-class deals
• An assessment of the licensing and co-development deal landscape for liver cancer therapies, and benchmarking of deals comparing first-in-class and non-first-in-class-products

Reasons to buy

The report will enable business development and enable marketing executives to strategize their product launches by allowing them to –

• Understand the focal shifts in molecular targets in the liver cancer pipeline
• Understand the distribution of pipeline programs by phase of development, molecule type and molecular target
• Understand the patent trends in liver cancer and what this means for long-term innovation
• Access a scientific and clinical analysis of first-in-class developmental programs for liver cancer, benchmarked against non-first-in-class targets
• Assess the valuations of licensed and co-developed liver cancer treatments
• Access a list of the first-in-class therapies potentially open to deal-making opportunities

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 Unmet Needs and Limited Market Drive an Innovative Pipeline 4
2.2 Targeted Therapies Segment to Expand over the Coming Decade 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 6
3.4 Regulatory and Reimbursement Policy Shifts Favor First-in-Class Product Innovation 7
3.5 Sustained Innovation 7
3.6 GBI Research Report Guidance 8

4 Clinical and Commercial Landscape 9
4.1 Disease Overview 9
4.2 Symptoms 9
4.3 Epidemiology and Etiology 9
4.4 Pathophysiology 10
4.4.1 Hepatocellular Carcinoma 11
4.4.2 Cholangiocarcinoma 13
4.4.3 Conclusion 14
4.5 Diagnosis 14
4.5.1 Clinical Presentation 14
4.5.2 Alpha-Fetoprotein 14
4.5.3 Diagnostic Imaging and Scans 14
4.5.4 Screening 15
4.5.5 Biopsy 15
4.5.6 Classification 15
4.6 Treatment Options 15
4.7 Treatment Algorithm 15
4.7.1 First Line 16
4.8 Overview of Marketed Products for Liver Cancer 17
4.8.1 Molecular Type and Target Analysis 17
4.8.2 Innovative Products in the Liver Cancer Market 18
4.8.3 Unmet Needs 19

5 Assessment of Pipeline Product Innovation 20
5.1 Liver Cancer Pipeline by Molecule Type, Phase and Therapeutic Target 20
5.2 Comparative Distribution of Programs between the Liver Cancer Market and Pipeline by Therapeutic Target Family 24
5.3 First-in-Class Pipeline Programs Targeting Novel Molecular Targets 25

6 Liver Cancer Patent Family Analysis 29

7 Signaling Network, Disease Causation and Innovation Alignment 37
7.1 The Complexity of Signaling Networks in Oncology 37
7.2 Signaling Pathways Disease-Causing Mutations and First-in-Class Molecular Target Integration 38
7.3 First-in-Class Target Matrix Assessment 41

8 First-in-Class Target Evaluation 47
8.1 Pipeline Programs Targeting ?-Catenin 47
8.2 Pipeline Programs Targeting FGFR4 49
8.3 Pipeline Programs Targeting GPR55 50
8.4 Pipeline Programs Targeting Protein Disulfide Isomerase 52
8.5 Pipeline Programs Targeting Telomerase 53
8.6 Pipeline Programs Targeting Delta-Like 1 Homolog 55
8.7 Pipeline Programs Targeting eIF5A 56
8.8 Pipeline Programs Targeting FAK 58
8.9 Pipeline Programs Targeting TGF? Receptor 60
8.10 Conclusion 62

9 Deals and Strategic Consolidations 63
9.1 Industry-wide First-in-Class Deals 63
9.2 Liver Cancer Deals Landscape 65
9.3 Licensing Deals 65
9.3.1 Molecule Types 68
9.3.2 Mechanism of Action 69
9.4 Co-Development Deals 70
9.4.1 Molecule Types 72
9.4.2 Mechanism of Action 73
9.5 First-In-Class Programs Not Involved in Licensing or Co-Development Deals 73

10 Appendix 76
10.1 References 76
10.2 Abbreviations 78
10.3 Contact Us 79
10.4 Disclaimer 79

List of Tables
Table 1: Liver Cancer, Organizations Frequently Applying for Chemical Entity Patent Families, (2008-2012) 30

List of Figures
Figure 1: Innovation Trends in Product Approvals 5
Figure 2: Sales Performance of First-in-Class and Non-First-in-Class Product Post Marketing Approval 7
Figure 3: Overview of Marketed Products 18
Figure 4: Overview of Pipeline Products 21
Figure 5: Breakdown of Pipeline Molecular Targets 23
Figure 6: Pipeline Molecular Targets by Stage of Development 24
Figure 7: Molecular Target Category Comparison, Pipeline and Marketed Products 25
Figure 8: Molecular Target Category Comparison, Pipeline First-in-Class and Established Molecular Targets 26
Figure 9: List of First-in-Class Pipeline Products (Part 1) 27
Figure 10: List of First-in-Class Pipeline Products (Part 2) 28
Figure 11: Liver Cancer, US and EU, Patent Families Filed and Granted by Year, 2008-2012 29
Figure 12: Liver Cancer, US and EU, Granted Patent Families by Molecular Target, 2008-2012 31
Figure 13: Liver Cancer, US and EU, Granted Patent Families by Molecular Target Family, 2008-2012 32
Figure 14: Liver Cancer, US and EU, Molecular Targets Identified in Patents (Part 1), 2008-2012 34
Figure 15: Liver Cancer, US and EU, Molecular Targets Identified in Patents (Part 2), 2008-2012 35
Figure 16: Signaling Networks of Functional Families in Liver Cancer 40
Figure 17: Target Matrix Assessment (Part 1) 42
Figure 18: Target Matrix Assessment (Part 2) 43
Figure 19: Target Matrix Assessment (Part 3) 44
Figure 20: Target Matrix Assessment (Part 4) 45
Figure 21: Target Matrix Assessment (Part 5) 46
Figure 22: Data and Evidence for ?-Catenin as a Therapeutic Target 48
Figure 23: Pipeline Products Targeting ?-Catenin 49
Figure 24: Data and Evidence for FGFR4 as a Therapeutic Target 50
Figure 25: Pipeline Products Targeting FGFR4 50
Figure 26: Data and Evidence for GPR55 as a Therapeutic Target 51
Figure 27: Pipeline Products Targeting GPR55 52
Figure 28: Data and Evidence for PDI as a Therapeutic Target 53
Figure 29: Pipeline Products Targeting PDI 53
Figure 30: Data and Evidence for Telomerase as a Therapeutic Target 54
Figure 31: Pipeline Products Targeting Telomerase 54
Figure 32: Data and Evidence for DLK1 as a Therapeutic Target 56
Figure 33: Pipeline Products Targeting DLK1 56
Figure 34: Data and Evidence for eIF5A as a Therapeutic Target 57
Figure 35: Pipeline Products Targeting eIF5A 57
Figure 36: Data and Evidence for FAK as a Therapeutic Target 59
Figure 37: Pipeline Products Targeting FAK 59
Figure 38: Data and Evidence for TGF?R1 as a Therapeutic Target 61
Figure 39: Pipeline Products Targeting TGF?R1 61
Figure 40: Industry Wide Deals by Stage of Development, 2006-2014 63
Figure 41: Industry Licensing Deal Values by Stage of Development, 2006-2014 64
Figure 42: Licensing Agreements, 2006-2014 66
Figure 43: Licensing Agreements by Phase, 2006-2014 67
Figure 44: Licensing Agreements by Territory, 2006-2014 68
Figure 45: Licensing Agreements by Molecule Type, 2006-2014 69
Figure 46: Licensing Agreements by Molecular Target, 2006-2014 70
Figure 47: Co-development Agreements, 2006-2014 71
Figure 48: Co-development Agreements by Territory, 2006-2014 72
Figure 49: Co-development Agreements by Molecule Type, 2006-2014 72
Figure 50: Co-development Agreements by Molecular Target, 2006-2014 73
Figure 51: List of First-in-Class Pipeline Products Not Involved in Deals (Part 1) 74
Figure 52: List of First-in-Class Pipeline Products Not Involved in Deals (Part 2) 75