Exceptionally Large and Innovative Pipeline

The prostate cancer pipeline is among the largest in the pharmaceutical industry with 484 products in active development across all stages. The range of mechanisms of action employed by these compounds is also highly diverse, especially in comparison to the existing market landscape. More pertinently, the degree and proportion of breakthrough innovations in this pipeline is exceptional; GBI Research analysis identified 174 first-in-class programs in the prostate cancer pipeline, acting on 122 first-in-class molecular targets. This accounts for some 36% of all products with a disclosed molecular target and is reflective of the high degree of innovation in this indication. This has far-reaching strategic implications for all market participants, as, despite the high attrition rate in prostate cancer, it is highly likely many of the first-in-class technologies will reach the market over the coming decade and may transform the clinical and commercial landscape.

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

One of the key trends in oncology and in prostate cancer in particular over the last decade is the clinical and commercial impact of targeted therapies designed to target proteins in signaling pathways that are strongly associated with disease progression. By aligning the molecular targets for therapeutic intervention with disease causation and/or propagation, these therapies limit the systemic cytotoxic effects whilst inhibiting tumor-promoting signaling pathways. Such strategies thereby typically achieve superior efficacy and safety profiles.

Our proprietary analyses demonstrate significant levels of differentiation as to how well the first-in-class products and their respective molecular targets align to underlying gene and protein level mutations and dysfunction. More advanced analytics further substantiated these findings as strong levels of differentiation in the scientific and clinical rationale for first-in-class molecular targets emerged. Furthermore, clear frontrunners were identified by integrating analyses to assess the accessibility of molecular targets for therapeutic compounds, the size of the target patient population that would benefit from therapeutic intervention, and the expected positioning of the first-in-class products based on the molecular targets and mechanisms of action of currently marketed products.

These insights and a detailed review of the available evidence from scientific studies substantiate the perspective that first-in-class-product technology in its own right is not sufficient to offer a compelling scientific and clinical rationale. However, a range of products offer very significant scientific and clinical promise and could therefore result in a strong commercial proposition with the prospect of clinically and commercially transformative products in the future.

A Deals Landscape with Numerous Investment Opportunities

Analysis has confirmed that 169 of the 174 first-in-class products have not been involved in a licensing or co-development deal. Although many act on targets that are not yet strongly substantiated in terms of their therapeutic potential in prostate cancer in clinical studies, there are many which are supported by promising in vivo and in vitro preclinical evidence, and as such are highly promising prostate cancer therapies. Indeed, breakthrough innovations are highly desirable as an investment option.

However, most deals involving first-in-class products were either preclinical or Phase I development, whereas advance-in-class and addition-to-class product deals were typically made in Phases II and III, therefore showing significant differentiation. These findings have significant strategic implications for both biotech companies seeking to out-license products and firms with an interest in in-licensing first-in-class products with strong clinical and commercial prospects.

Scope

The report analyzes innovation in prostate cancer, in the context of the overall pipeline and current market landscape. In addition, it analyzed the deals landscape surrounding first-in-class products in prostate cancer, and pinpoints opportunities for in-licensing. The report covers and includes –

• A brief introduction to prostate cancer, including symptoms, pathophysiology, and overview of pharmacotherapy and treatment algorithms.
• The changing molecular target landscape between market and pipeline and particular focal points of innovation in the pipeline.
• Comprehensive review of the pipeline for first-in-class therapies, analyzed on the basis of stage of development, molecule type and molecular target.
• 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 on novel molecular targets.
• Assessment of the licensing and co-development deal landscape for prostate cancer therapies and benchmarking of deals involving first-in-class versus non-first-in-class-products.

Reasons to buy

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

• Understanding of the focal shifts in molecular targets in the prostate cancer pipeline.
• Understanding of the distribution of pipeline programs by phase of development, molecule type and molecular target.
• Access a scientific and clinical analysis of first-in-class developmental programs for prostate cancer, benchmarked against non-first-in-class targets.
• 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 Active Pipeline Reflects Large Market with Significant Unmet Needs 4
2.2 Market Landscape to Grow in Diversity over Coming Decade 4
2.3 Deals Landscape Presents Significant Investment Opportunities for First-in-Class Products 4

3 The Case for Innovation in Prostate Cancer 6
3.1 Growing Opportunities for Biologic Products 7
3.2 Diversification of Molecular Targets 7
3.3 Innovative First-in-Class Product Developments Remain Attractive 7
3.4 Regulatory and Reimbursement Policy Shifts Favor First-in-Class Product Innovation 8
3.5 Sustained Innovation 8
3.6 GBI Research Report Guidance 9

4 Clinical and Commercial Landscape 10
4.1 Disease Overview 10
4.1.1 Epidemiology 10
4.1.2 Etiology 11
4.1.3 Disease Pathophysiology 12
4.1.4 Disease Symptoms 14
4.1.5 Disease Staging and Diagnosis 14
4.1.6 Treatment 16
4.2 Overview of Marketed Products 19
4.2.1 Hormonal Therapies 19
4.2.2 Chemotherapy 20
4.2.3 Therapeutic Vaccines 20
4.2.4 Targeted Therapies (Second Generation Anti-androgens) 21
4.2.5 Bone Metastasis Treatments 21

5 Assessment of Pipeline Product Innovation 22
5.1 Prostate Cancer Pipeline by Molecule Type, Phase and Therapeutic Target 22
5.2 Comparative Distribution of Programs between the Prostate Cancer Market and Pipeline by Molecular Target 28
5.3 First-in-Class Pipeline Programs Targeting Novel Molecule Targets 28

6 Signaling Network, Disease Causation and Innovation Alignment 35
6.1 The Complexity of Signaling Networks in Oncology 35
6.2 Signaling Pathways, Disease-Causing Mutations and First-in-Class Molecular Target Integration 36
6.3 First-in-class Target Matrix Assessment 38

7 First-in-Class Target and Pipeline Program Evaluation 42
7.1 Pipeline Programs Targeting Human Double Minute 2 42
7.1.1 Overview of Pipeline Programs Targeting MDM2 44
7.2 Pipeline Programs Targeting AKT1 44
7.2.1 Overview of Pipeline Programs Targeting AKT1 46
7.3 Pipeline Programs Targeting Tumor Protein p53 46
7.3.1 Overview of Pipeline Programs Targeting p53 47
7.4 Pipeline Programs Targeting Mitogen-Activated Protein Kinase 47
7.4.1 Overview of Pipeline Programs Targeting MAPK 49
7.5 Pipeline Programs Targeting Specificity Protein 1 49
7.5.1 Overview of Pipeline Programs Targeting Specificity Protein 1 52
7.6 Pipeline Programs Targeting X-linked Inhibitor of Apoptosis Protein 52
7.6.1 Overview of Pipeline Programs Targeting X-linked Inhibitor of Apoptosis Protein 53
7.7 Pipeline Programs Targeting Hypoxia-Inducible Factor 1 53
7.7.1 Overview of Pipeline Programs Targeting Hypoxia-Inducible Factor 1 55
7.8 Pipeline Programs Targeting Galectin-3 55
7.8.1 Overview of Pipeline Programs Targeting Galectin-3 56
7.9 Pipeline Programs Targeting Prostate Specific Membrane Antigen 57
7.9.1 Overview of Pipeline Programs Targeting Prostate Specific Membrane Antigen 59
7.10 Pipeline Programs Targeting Aurora Kinase 59
7.10.1 Overview of Pipeline Programs Targeting Aurora Kinase 61
7.11 Conclusion 62

8 Deals and Strategic Consolidations 63
8.1 Industry-wide First-in-Class Deals 63
8.2 Licensing Deals 65
8.3 Co-developments 68
8.4 First-in-Class Programs not Involved in Licensing or Co-Development Deals 70

9 Appendix 75
9.1 References 75
9.2 Signaling Pathways, Disease-Causing Mutations and First-in-Class Molecular Target Integration Tables 82
9.3 Abbreviations 89
9.4 Expert Panel Validation 90
9.5 Contact Us 91
9.6 Disclaimer 91

List of Tables

Table 1: Prostate Cancer Risk Factors 12
Table 2: Prostate Cancer, Disease Stage Classification 14

List of Figures

Figure 1: Innovation Trends in Product Approvals 6
Figure 2: Sales Performance of First-in-Class and Non-First-in-Class Product Post Marketing Approval 8
Figure 3: Percentage of Men Diagnosed with Prostate Cancer in the US by Age (%), 2005–2009 10
Figure 4: Average Number of New Cases and Age-Specific Incidence Rates per 100,000 Population in the UK, 2008–2010 11
Figure 5: Prostate Cancer Treatment Algorithm (Stages I and II) 16
Figure 6: Prostate Cancer Treatment Algorithm (Stages III) 17
Figure 7: Prostate Cancer Treatment Algorithm (Stages IV) 18
Figure 8: Global Pipeline Overview 23
Figure 9: Molecular Target Classes of Pipeline Products 24
Figure 10 : Prostate Cancer, Molecular Targets 25
Figure 11: Molecular Target Category Comparison, Pipeline and Marketed Products 28
Figure 12: First-in-Class and Non-First-in-Class Pipeline Product Comparison 29
Figure 13: Prostate Cancer, First-in-Class Products in the Prostate Cancer Pipeline, Part 1 30
Figure 14: Prostate Cancer, First-in-Class Products in the Prostate Cancer Pipeline, Part 2 31
Figure 15: Prostate Cancer, First-in-Class Products in the Prostate Cancer Pipeline, Part 3 32
Figure 16: Prostate Cancer, First-in-Class Products in the Prostate Cancer Pipeline, Part 4 33
Figure 17: Signaling Networks of Functional Families in Prostate Cancer 37
Figure 18: First-in-Class Molecular Target Analysis Matrix (Part 1) 39
Figure 19: First-in-Class Molecular Target Analysis Matrix (Part 2) 40
Figure 20: First-in-Class Molecular Target Analysis Matrix (Part 3) 41
Figure 21: MDM2 as a Therapeutic Target 43
Figure 22: Pipeline Programs Targeting MDM2 44
Figure 23: AKT as a Therapeutic Target 45
Figure 24: Pipeline Programs Targeting AKT1 46
Figure 25: TP53 as a Therapeutic Target 47
Figure 26: Pipeline Programs Targeting p53 47
Figure 27: MAPK8 as a Therapeutic Target 49
Figure 28: Pipeline Programs Targeting MAPK 49
Figure 29: Sp1 as a Therapeutic Target 51
Figure 30: Pipeline Programs Targeting Specificity Protein 1 52
Figure 31: XIAP as a Therapeutic Target 53
Figure 32: Pipeline Programs Targeting X-linked Inhibitor or Apoptosis Protein 53
Figure 33: HIF1A as a Therapeutic Target 55
Figure 34: Pipeline Programs Targeting Hypoxia-Inducible Factor 1 55
Figure 35: Galectin–3 as a Therapeutic Target 56
Figure 36: Pipeline Programs Targeting Galectin-3 56
Figure 37: PSMA as a Therapeutic Target 58
Figure 38: Pipeline Programs Targeting PSMA 59
Figure 39: Aurora Kinase as a Therapeutic Target 61
Figure 40: Pipeline Programs Targeting Aurora Kinase 61
Figure 41: Industry-wide Deals by Stage of Development, 2006–2014 63
Figure 42: Industry-wide Deals by Stage of Development, 2006–2014 64
Figure 43: Licensing Deals by Region, 2006–2014 65
Figure 44: Licensing Deals, 2006–2014 66
Figure 45: First-in-Class and Non-First-in-Class Comparison, 2006–2014 67
Figure 46: Market for Prostate Cancer, Global, Licensing Deals by Mechanism of Action, 2006–2014 67
Figure 47: Co-development Deals by Region, 2006–2014 68
Figure 48: Co-development Deals, 2006–2014 69
Figure 49: Co-developments by Mechanism of Action, 2006–2014 69
Figure 50: First-in-class Programs with no Recorded Prior Deal Involvement, 2006–2014 (Part 1) 71
Figure 51: First-in-class Programs with no Recorded Prior Deal Involvement, 2006–2014 (Part 2) 72
Figure 52: First-in-class Programs with no Recorded Prior Deal Involvement, 2006–2014 (Part 3) 73
Figure 53: Signaling Networks of Functional Families in Prostate Cancer, Table 1 82
Figure 54: Signaling Networks of Functional Families in Prostate Cancer, Table 2 83
Figure 55: Signaling Networks of Functional Families in Prostate Cancer, Table 3 84
Figure 56: Signaling Networks of Functional Families in Prostate Cancer, Table 4 85
Figure 57: Signaling Networks of Functional Families in Prostate Cancer, Table 5 86
Figure 58: Signaling Networks of Functional Families in Prostate Cancer, Table 6 87
Figure 59: Signaling Networks of Functional Families in Prostate Cancer, Table 7 88
Figure 60: Signaling Networks of Functional Families in Prostate Cancer, Table 8 89