Frontier Pharma: Non-Small Cell Lung Cancer - Identifying and Commercializing First-in-Class Innovation

Non-Small Cell Lung Cancer - Identifying and Commercializing First-in-Class Innovation

Summary

Large Degree of Innovation in NSCLC Pipeline

The NSCLC pipeline currently has 389 products in active development across all stages, but a stark contrast between the mechanisms of action employed in the current market and the pipeline is evident. Where the market comprises primarily ineffective chemotherapies that target tubulin or DNA replication, the pipeline shows an incredibly diverse range of therapies targeting multiple signaling pathways and molecules integral to cancer development. This diversity is partially due to the presence of 122 first-in-class products, which accounts for 38% of the overall pipeline therapies that disclosed their target. In an industry, market and development landscape that favors first-in-class over non-first-in-class development in many ways, such as through faster approval or greater revenue, this finding has strategic implications for a wide array of market participants, both large and small. Despite a high attrition rate in NSCLC, first-in-class therapies that reach the market have the potential to transform and improve the NSCLC treatment landscape.

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

The method of characterizing NSCLC tumors is currently shifting from the traditional histology-based characterization to a more specific molecule-based method of characterization. This has resulted in the identification of key oncogenic mutations in NSCLC and has coincided with the rise of targeted pipeline therapies, which are designed to target proteins in signaling pathways that are frequently mutated, amplified or overexpressed in NSCLC. Aligning the molecular target with disease-causing signaling pathways and frequently mutated pathways therapies can benefit from reduced systemic cytotoxic effects while still inhibiting tumor-promoting signaling. Therefore, targeted therapies often display superior safety and efficacy to chemotherapies.

GBI Research’s proprietary analysis showed substantial variation in how well NSCLC first-in-class targets align to frequent gene mutations. Further in-depth analysis identified the most promising first-in-class targets based on various scientific and clinical parameters. Examining scientific and clinical data of promising first-in-class targets showed that first-in-class status is not, in its own right, enough for a successful product; however, the first-in-class products substantiated by scientific and clinical evidence will be exciting future prospects with the potential to transform the NSCLC market.

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

The NSCLC deals landscape appears relatively quiet for such a large indication. However, analysis showed that of the therapies with disclosed deal values there is significant range in the value of NSCLC deals. Concerning first-in-class specifically, only five licensing or co-development deals have been made since 2006. Despite the low sample size, it is clear that the first-in-class NSCLC products offer an attractive investment prospect as they command much higher deal values and, on average, deals occur earlier in development compared to non-first-in-class counterparts. Both trends were substantiated by industry-wide data that showed that, particularly in Phase I, first-in-class products would attract larger mean and median total deal values. The data highlight that the first-in-class deals landscape is different and indicates a greater chance of becoming much more lucrative than the deals landscape for addition-to-class or advance-in-class therapies.

A total of 117 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 analyzes innovation in NSCLC in the context of the overall pipeline and current market landscape. It also analyzes the deals landscape surrounding first-in-class products and pinpoints in-licensing opportunities.The report includes -
- A brief introduction to NSCLC, including symptoms, pathophysiology, and an overview of pharmacotherapy and treatment algorithms
- Extensive categorization of histological and molecular features of NSCLC tumors
- 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
- 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 NSCLC 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 NSCLC pipeline
- Understand 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 NSCLC, benchmarked against non-first-in-class targets
- Assess the valuations of licensed and co-developed NSCLC treatments
- Access a list of the first-in-class therapies potentially open to deal-making opportunities

1 Table of Contents
1 Table of Contents 2
1.1 List of Tables 2
1.2 List of Figures 2
2 Executive Summary 4
2.1 A High Degree of First-In-Class Innovation in an Active Pipeline 4
2.2 Increasing Molecular Characterization of Tumors with Concomitant First-in-Class Innovation Alignment 4
2.3 Stagnant Deals Landscape Higlights Numerous Investment Opportunities 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 6
3.5 Sustained Innovation 7
3.6 GBI Research Report Guidance 8
4 Clinical and Commercial Landscape 9
4.1 Disease Symptoms 9
4.2 Disease Etiology and Pathophysiology 10
4.2.1 Adenocarcinoma 10
4.2.2 Squamous Cell Carcinoma 12
4.2.3 Large Cell Carcinoma 14
4.2.4 Diagnosis 15
4.2.5 Prognosis 15
4.3 Introduction to NSCLC Treatment 15
4.4 Surgery and Radiation Therapy 16
4.5 Treatment Algorithm 16
4.5.1 First-Line Treatment 18
4.5.2 Maintenance Therapy 23
4.5.3 Second-Line Therapy 25
4.5.4 Third-Line Therapy 27
4.5.5 Adjuvant Therapy 27
4.6 Overview of Marketed Products for NSCLC 28
4.6.1 Molecular Type Analysis 28
4.6.2 Molecular Target Analysis 29
4.6.3 Innovative Products in the NSCLC Market 29
4.6.4 Efficacy and Safety of Marketed Products 30
4.6.5 Current Unmet Needs 31
5 Assessment of Pipeline Product Innovation 32
5.1 NSCLC Pipeline by Molecule Type, Phase and Therapeutic Target 32
5.2 Comparative Distribution of Programs between the NSCLC Market and Pipeline by Therapeutic Target Family 37
5.3 First-in-class Pipeline Programs Targeting Novel Molecule Targets 38
6 Signaling Network, Disease Causation and Innovation Alignment 42
6.1 The Complexity of Signaling Networks in Oncology 42
6.2 Signaling Pathways, Disease-Causing Mutations and First-In-Class Molecular Target Integration 43
6.3 First-in-Class Target Matrix Assessment 47
7 First-in-Class Target Evaluation 50
7.1 Pipeline Programs Targeting PTK2 50
7.2 Pipeline Programs Targeting Erbb3 51
7.3 Pipeline Programs Targeting TP53 52
7.4 Pipeline Programs Targeting CD274 54
7.5 Pipeline Programs Targeting Akt2 56
7.6 Pipeline Programs Targeting STAT3 58
7.7 Pipeline Programs Targeting FGF1 59
7.8 Pipeline Programs Targeting CDK4 60
7.9 Pipeline Programs Targeting AURKB 62
7.10 Pipeline Programs Targeting FNTA 63
7.11 Pipeline Programs Targeting CHEK1 65
7.12 Pipeline Programs Targeting HIF1A 67
7.13 Pipeline Programs Targeting DKK1 69
7.14 Conclusion 70
8 Deals and Strategic Consolidations 72
8.1 Industry-wide First-in-Class Deals 72
8.2 NSCLC Deals Landscape 74
8.3 Licensing Deals 74
8.4 Co-development Deals 81
8.5 First-in-Class Programs Not Involved in Licensing or Co-Development Deals 84
9 Appendix 87
9.1 References 87
9.2 Abbreviations 92
9.3 References for Heat Map 93
9.4 Contact Us 93
9.5 Disclaimer 93

1.1 List of Tables
Table 1: Tumor Node Metastasis Classification 15
Table 2: Stage I-IV Treatment Options - All Histologies 16
Table 3: Stage IIIB–IV Treatment Options – All Histologies 18
Table 4: Chemotherapy Treatment in Late-stage NSCLC Patients with Varied Histologies 19
Table 5: Chemotherapy Treatment in Stage IIIB/IV NSCLC Patients by Regimen 19
Table 6: References for Heat Map 93

1.2 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: Molecular Characteristic Frequency (%) 10
Figure 4: Non-Squamous Stage IIIB/IV Treatment Algorithm 17
Figure 5: Squamous Stage IIIB/IV Treatment Algorithm 17
Figure 6: Molecule Types in Marketed Products 29
Figure 7: Targets in Marketed Products 29
Figure 8: DNA Synthesis/Repair Targets 29
Figure 9: Efficacy and Safety Heatmap of Marketed Products 31
Figure 10: Developmental Pipeline Overview 33
Figure 11: Receptor Tyrosine Kinase Molecular Targets 35
Figure 12: Molecular Target Category Comparison, Pipeline and Marketed Products 38
Figure 13: Molecular Target Category Comparison, Pipeline First-in-Class and Established Molecular Targets 39
Figure 14: First-in-Class Products in the Pipeline, Part 1 40
Figure 15: First-in-Class Products in the Pipeline, Part 2 41
Figure 16: Signaling networks of functional families in NSCLC 45
Figure 17: Signaling network of multi-process functional proteins in NSCLC 46
Figure 18: First-in-Class Molecular Target Analysis Matrix (Part 1) 48
Figure 19: First-in-Class Molecular Target Analysis Matrix (Part 2) 49
Figure 20: Data and Evidence for PTK2 as a Therapeutic Target 50
Figure 21: Pipeline Programs Targeting PTK2 51
Figure 22: Data and Evidence for Erbb3 as a Therapeutic Target 52
Figure 23: Pipeline Programs Targeting ErbB3 52
Figure 24: Data and Evidence for TP53 as a Therapeutic Target 54
Figure 25: Pipeline Programs Targeting P53 54
Figure 26: Data and Evidence for CD274 as a Therapeutic Target 55
Figure 27: Pipeline Programs Targeting CD274 55
Figure 28: Data and Evidence for Akt2 as a Therapeutic Target, 57
Figure 29: e Programs Targeting Akt2 57
Figure 30: Data and Evidence for STAT3 as a Therapeutic Target 59
Figure 31: Pipeline Programs Targeting STAT3 59
Figure 32: Data and Evidence for FGF1 as a Therapeutic Target 60
Figure 33: Pipeline Programs Targeting FGF1 60
Figure 34: Data and Evidence for CDK4 as a Therapeutic Target 61
Figure 35: Pipeline Programs Targeting CDK4 62
Figure 36: Data and Evidence for AURKB as a Therapeutic Target 63
Figure 37: Pipeline Programs Targeting AURKB 63
Figure 38: Data and Evidence for FNTA as a Therapeutic Target 65
Figure 39: Pipeline Programs Targeting FNTA 65
Figure 40: Data and Evidence for CHEK1 as a Therapeutic Target 67
Figure 41: Pipeline Programs Targeting CHEK1 67
Figure 42: Data and Evidence for HIF1A as a Therapeutic Target 68
Figure 43: Pipeline Programs Targeting HIF1A 68
Figure 44: Data and Evidence for DKK1 as a Therapeutic Target 70
Figure 45: Pipeline Programs Targeting DKK1 70
Figure 46: Industry Wide Deals by Stage of Development, 2006–2014 72
Figure 47: Industry Licensing Deal Values by Stage of Development, 2006-2014 73
Figure 48: Licensing Agreements, 2006–2014 75
Figure 49: First-in-Class and Non-First-in-Class Deals Comparison, 2006–2014 76
Figure 50: Regional Network of Licensing Agreements, 2006–2014 76
Figure 51: Licensing Agreements by Molecule Type, 2006–2014 78
Figure 52: Licensing Agreements by Mechanism of Action, 2006–2014 79
Figure 53: Summary of Licensing Deals, 2006–2014 80
Figure 54: Co-development Deals by Year and Phase, 2006–2014 81
Figure 55: Regional Network of Co-development Deals, 2006–2014 82
Figure 56: Co-development Deals by Molecule Type, 2006–2014 82
Figure 57: Co-development Deals by Mechanism of Action, 2006–2014 82
Figure 58: Summary of Co-development Deals, 2006–2014 83
Figure 59: First-in-class Programs with no Recorded Prior Deal Involvement, 2006–2014 (Part 1) 85
Figure 60: First-in-class Programs with no Recorded Prior Deal Involvement, 2006–2014 (Part 2) 86