Frontier Pharma: Versatile Innovation in Immunology - Large Therapy Area Pipeline with a High Degree of Repositioning Potential

1 Table of Contents

1.1 List of Tables

1.2 List of Figures

2 Executive Summary

2.1 Large Therapy Area Characterized by a High Degree of Pathophysiological Crossover

2.2 Strong Pipeline Shows High Level of Versatile Innovation

2.3 Substantial Deal Making Activity Observed over the Past Decade

3 The Case for Innovation in the Immunology Market

3.1 Growing Opportunities for Biologic Products

3.2 Diversification of Molecular Targets

3.3 Innovative First-in-Class Product Developments Remain Attractive

3.4 Regulatory and Reimbursement Policy Shifts Favor First-in-Class Product Innovation

3.5 Sustained Innovation

4 Introduction

4.1 Therapy Area Introduction

4.2 Symptoms

4.3 Etiology and Pathophysiology

4.3.1 Innate Immunity

4.3.2 Adaptive Immunity

4.3.3 The Role of Cytokines

4.3.4 Autoimmunity

4.3.5 Etiologic Factors for Autoimmunity and Allergies

4.3.6 Conclusion

4.4 Co-morbidities and Complications

4.5 Epidemiology

4.6 Treatment

4.6.1 Non-Biologic Disease-Modifying Anti-Rheumatic Drugs

4.6.2 Glucocorticoids

4.6.3 Biologics and Targeted Therapies

5 Pipeline Landscape Assessment

5.1 Overview

5.2 Pipeline Development Landscape

5.3 Molecular Targets in the Pipeline

5.4 Comparative Distribution of Programs between the Oncology Market and Pipeline by Therapeutic Target Family

5.5 First-in-Class and Versatile Pipeline Programs

5.6 First-in-Class Immunology Products by Phase, Molecule Type and Molecular Target

5.7 Versatility of First-in-Class Pipeline Products

6 Immunology Signaling Network, Disease Causation and Innovation Alignment

6.1 Complexity of Signaling Networks

6.2 Signaling Pathways and First-in-Class Molecular Target Integration

6.3 First-in-Class Matrix Assessment

7 First-in-Class Target and Pipeline Program Evaluation

7.1 Pipeline Programs Targeting Toll-Like Receptors 3, 6 and 8

7.2 Pipeline Programs Targeting Spleen Tyrosine Kinase

7.3 Pipeline Programs Targeting IL-7R

7.4 Pipeline Programs Targeting C-C Chemokine Receptor Type 6

7.5 Pipeline Programs Targeting P2RX7

7.6 Pipeline Programs Targeting ITK

7.7 Pipeline Programs Targeting IRAK4

7.8 Pipeline Programs Targeting Orai1

7.9 Pipeline Programs Targeting Tumor Necrosis Factor Receptor Superfamily Member 5

7.10 Conclusion

8 Strategic Consolidations

8.1 Industry-Wide First-in-Class Deals

8.2 Licensing Deals

8.2.1 Deals by Region, Year and Value

8.2.2 Deals by Stage of Development and Value

8.2.3 Deals by Molecule Type and Value

8.2.4 Deals by Molecular Target and Value

8.3 Co-development Deals

8.3.1 Deals by Region, Year and Value

8.3.2 Deals by Stage of Development and Value

8.3.3 Deals by Molecule Type and Value

8.3.4 Deals by Molecular Target and Value

8.4 List of First-in-Class Pipeline Products with and Without Prior Deal Involvement

9 Appendix

9.1 Abbreviations

9.2 References

9.3 Research Methodology

9.3.1 Data integrity

9.3.2 Innovative and meaningful analytical techniques and frameworks

9.3.3 Evidence based analysis and insight

9.4 Secondary Research

9.4.1 Market Analysis

9.4.2 Pipeline Analysis

9.4.3 Licensing and Co-development Deals

9.5 Contact Us

9.6 Disclaimer

1.1 List of Tables

Table 1: Versatile Innovation in Immunology, Global, Epidemiology of Inflammatory Immunological Disorders, 2015

Table 2: Versatile Innovation in Immunology, Global, Toll-Like Receptors and their Known Ligands, 2016

Table 3: Versatile Innovation in Immunology, Global, Key Features of TLR3, 2016

Table 4: Versatile Innovation in Immunology, Global, Key Features of TLR6, 2016

Table 5 Versatile Innovation in Immunology, Global, Key Features of TLR8, 2016

Table 6: Versatile Innovation in Immunology, Global, Key Features of Syk, 2016

Table 7: Versatile Innovation in Immunology, Global, Key Features of IL-7R, 2016

Table 8: Versatile Innovation in Immunology, Global, Key Features of C-C Chemokine Receptor Type 6, 2016

Table 9: Versatile Innovation in Immunology, Global, Key Features of P2RX7, 2016

Table 10: Versatile Innovation in Immunology, Global, Key Features of ITK, 2016

Table 11: Versatile Innovation in Immunology, Global, Key Features of IRAK4, 2016

Table 12: Versatile Innovation in Immunology, Global, Key Features of Orai1, 2016

Table 13: Versatile Innovation in Immunology, Global, Key Features of Tumor Necrosis Factor Receptor Superfamily Member 5 , 2016

1.2 List of Figures

Figure 1: Versatile Innovation in Immunology, US, Innovation Trends in Product Approvals, 1987–2014

Figure 2: Versatile Innovation in Immunology, US, Sales Performance of First-in-Class and Non-First-in-Class Products Post Marketing Approval, 2006–2013

Figure 3: Versatile Innovation in Immunology, Global, Overall Pharmaceutical Industry Pipeline by Therapy Area and Breakdown of Immunology Pipeline by Indication, 2016

Figure 4: Versatile Innovation in Immunology, Global, Pipeline for Immunology by Stage of Development and Molecule Type, 2016

Figure 5: Versatile Innovation in Immunology, Global, Pipeline for Immunology by Molecular Target, 2016

Figure 6: Versatile Innovation in Immunology, Global, Pipeline and Marketed Products for Immunology by Molecular Target Category, 2016

Figure 7: Versatile Innovation in Immunology, Global, Overall Pharmaceutical Industry First-in-Class Pipeline by Therapy Area and Breakdown of Immunology First-in-Class Pipeline by Indication, 2016

Figure 8: Versatile Innovation in Immunology Therapeutics Market, Global, First-in-Class Pipeline for Immunology by Stage of Development and Molecule Type, 2016

Figure 9: Versatile Innovation in Immunology, Global, First-in-Class Pipeline for Immunology by Molecular Target, 2016

Figure 10: Versatile Innovation in Immunology, Global, Pipeline for Immunology by First-in-Class Status and Molecular Target Class, 2016

Figure 11: Versatile Innovation in Immunology, Global, Distribution of First-in-Class and Established Products by Stage of Development (%), 2016

Figure 12: Versatile Innovation in Immunology, Global, Distribution of First-in-Class and Established Products by Molecular Target Class (%), 2016

Figure 13: Versatile Innovation in Immunology, Global, First-in-Class Immunology Pipeline Products by Number of Indications, 2016

Figure 14: Versatile Innovation in Immunology, Global, Pipeline for Key Immunology Indications by Molecular Target, 2016

Figure 15: Versatile Innovation in Immunology, Global, Versatile Pipeline for Immunology by Stage of Development and Molecule Type, 2016

Figure 16: Versatile Innovation in Immunology, Global, Versatile First-in-Class Pipeline Immunology by Molecular Target, 2015

Figure 17: Versatile Innovation in Immunology, Global, First-in-Class Pipeline for Immunology by Versatile Status and Molecular Target Class, 2016

Figure 18: Versatile Innovation in Immunology, Global, First-in-class Pipeline for Immunology Indications (Part 1), 2016

Figure 19: Versatile Innovation in Immunology, Global, First-in-class Pipeline for Immunology Indications (Part 2), 2016

Figure 20: Versatile Innovation in Immunology, Global, First-in-class Pipeline for Immunology Indications (Part 3), 2016

Figure 21: Versatile Innovation in Immunology, Global, First-in-class Pipeline for Immunology Indications (Part 4), 2016

Figure 22: Versatile Innovation in Immunology, Global, First-in-Class Matrix, 2016 (part 1)

Figure 23: Versatile Innovation in Immunology, Global, First-in-Class Matrix, 2016 (part 2)

Figure 24: Versatile Innovation in Immunology, Global, First-in-Class Matrix, 2016 (part 3)

Figure 25: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting TLR3, 2016

Figure 26: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting TLR6, 2016

Figure 27: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting TLR8, 2016

Figure 28: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting Syk, 2016

Figure 29: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting IL-7R, 2016

Figure 30: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting C-C Chemokine Receptor Type 6, 2016

Figure 31: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting P2RX7, 2016

Figure 32: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting ITK, 2016

Figure 33: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting IRAK4, 2016

Figure 34: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting Orai1, 2016

Figure 35: Versatile Innovation in Immunology, Global, Pipeline Programs Targeting Tumor necrosis factor receptor superfamily member 5 , 2016

Figure 36: Versatile Innovation in Immunology, Global, Licensing Deals by Stage of Development, 2006–2015

Figure 37: Versatile Innovation in Immunology, Global, Industry-Wide Licensing Deals by Deal Value, Upfront Payment Value, Stage of Development and First-in-Class Status ($m), 2006–2015

Figure 38: Versatile Innovation in Immunology, Global, Licensing Deals by Region, Value and Year, 2006–2016

Figure 39: Versatile Innovation immunology, Global, Licensing Deals by Stage of Development, Deal Value and Upfront Payment Value, 2006–2016

Figure 40: Versatile Innovation in Immunology, Global, Licensing Deals by Molecule Type, 2006–2016

Figure 41: Immunology, Global, Licensing Deals by Molecular Target, 2006–2016

Figure 42: Versatile Innovation in Immunology, Global, Licensing Deals Valued Above $100m, 2006–2016

Figure 43: Versatile Innovation in Immunology, Global, Co-development Deals by Region, Value and Year, 2006–2016

Figure 44: Immunology, Global, Co-development Deals by Stage of Development, Deal Value and Upfront Payment Value, 2006–2016

Figure 45: Versatile Innovation in Immunology, Global, Co-development Deals by Molecule Type, 2006–2016

Figure 46: Versatile Innovation in Immunology, Global, Co-development Deals by Molecular Target, 2006–2016

Figure 47: Versatile Innovation in Immunology, Global, Co-development Deals Valued Above $100m, 2006–2016

Figure 48: Versatile Innovation in Immunology, Global, List of First-in-Class Pipeline Products with and Without Prior Deal Involvement, 2016

Figure 49: Versatile Innovation in Immunology, Global, List of First-in-Class Pipeline Products with and Without Prior Deal Involvement, 2016

Figure 50: Versatile Innovation in Immunology, Global, List of First-in-Class Pipeline Products with and Without Prior Deal Involvement, 2016

Figure 51: Versatile Innovation in Immunology, Global, List of First-in-Class Pipeline Products with and Without Prior Deal Involvement, 2016

Frontier Pharma: Versatile Innovation in Immunology - Large Therapy Area Pipeline with a High Degree of Repositioning Potential

Summary

Immunology is a large therapy area characterized by disorders of the immune system – specifically an aberrant immune response against healthy tissues present in the body, leading to chronic or acute inflammation. Depending on the specific site affected, this can lead to various types of chronic pain and loss of mobility, and have a negative impact on quality of life.

This disease area has a total of 2,145 products in active development, trailing only oncology, infectious diseases and central nervous system disorders in terms of pipeline size. There are a total of 529 immunology pipeline products that act on first-in-class molecular targets, representing approximately 40% of the total immunology pipeline for which the molecular target was disclosed.

Due to a degree of crossover between immunology indications in terms of their underlying pathophysiology, it is not uncommon for products being developed for this therapy area to have developmental programs testing them across multiple indications.

Approximately one-fifth of first-in-class pipeline products are in development for two or more indications within the therapy area. This presents an opportunity for companies to develop innovative products across multiple immune disorders, and therefore reach a larger pool of patients than products developed for single indications.

Scope

• What are the key points of overlap in the pathophysiology of immune disorders?
• What is the current standard of treatment across these markets, and what lessons can be learned by companies seeking to innovate and build on these products?
• Which molecule types and molecular targets are most prominent within the pipeline?
• Which first-in-class targets are most promising?
• Do immunology products attract high deal values, and which specific product types are able to attract the highest values?
• Which molecule types and molecular targets dominate the deals landscape?

• Appreciate the current clinical and commercial landscapes by considering disease pathogenesis, etiology, epidemiology, symptoms, co-morbidities and complications, and treatment options.
• Identify leading products and companies within the market, as well as key unmet needs, in order to gain a competitive understanding of gaps in the market.
Review key pipeline trends by analyzing therapies by stage of development, molecule type and molecular target, and identify key trends regarding innovation within each segment.
• Assess the therapeutic potential of first-in-class targets. Using a proprietary matrix, all first-in-class targets in the immunology pipeline have been assessed and ranked according to clinical potential, and the most promising early-stage targets have been further reviewed in greater detail.
• Identify promising first-in-class pipeline assets that have had no prior involvement in licensing or co-development deals, and are therefore potentially suitable for in-licensing.