Frontier Pharma: Diabetic Complications - Innovative and Diverse Neuropathies, Nephropathy and Retinopathies Pipelines Demonstrate Shift Towards Disease Modifying Therapies

1 Table of Contents

1.1 List of Tables

1.2 List of Figures

2 Executive Summary

2.1 Significant Unmet Needs in Diabetic Complications Market

2.2 High Proportion of First-in-Class Innovation Offers Promise in Diabetic Complications

2.3 Deal Activity Varies with First-in-Class Status

3 The Case for Innovation

3.1 Growing Opportunities for Biologic Products

3.2 Diversification of Molecular Targets

3.3 Innovative First-in-Class Product Development Remains Attractive

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

3.5 Sustained Innovation

3.6 GBI Research Report Guidance

4 Clinical and Commercial Landscape

4.1 Diabetes Mellitus Overview

4.2 Diabetic Neuropathies

4.2.1 Disease Overview

4.2.2 Signs and Symptoms

4.2.3 Epidemiology and Etiology

4.2.4 Pathophysiology

4.2.5 Diagnosis and Staging

4.2.6 Prognosis

4.2.7 Treatment Options

4.3 Diabetic Nephropathy

4.3.1 Disease Overview

4.3.2 Sign and Symptoms

4.3.3 Epidemiology and Etiology

4.3.4 Pathophysiology

4.3.5 Diagnosis and Staging

4.3.6 Prognosis

4.3.7 Treatment Options

4.4 Diabetic Retinopathies

4.4.1 Disease Overview

4.4.2 Signs and Symptoms

4.4.3 Epidemiology and Etiology

4.4.4 Pathophysiology

4.4.5 Diagnosis and Staging

4.4.6 Prognosis

4.4.7 Treatment Options

4.5 Overview of Marketed Products in Diabetic Complications

4.5.1 Overview of Marketed Products in Diabetic Neuropathies

4.5.2 Overview of Marketed Products in Diabetic Nephropathy

4.5.3 Overview of Marketed Products in Diabetic Retinopathies

5 Assessment of Pipeline Product Innovation

5.1 Diabetic Neuropathies by Molecule Type, Phase and Therapeutic Target

5.1.1 Comparative Distribution of Programs between Diabetic Neuropathy Market and Pipeline by Therapeutic Target Family

5.1.2 First-in-Class Pipeline Programs Targeting Novel Molecular Targets

5.2 Diabetic Nephropathy by Molecule Type, Phase and Therapeutic Target

5.2.1 Comparative Distribution of Programs between the Diabetic Nephropathy Market and Pipeline by Therapeutic Target Family

5.2.2 First-in-Class Pipeline Programs Targeting Novel Molecular Targets

5.3 Diabetic Retinopathies by Molecule Type, Phase and Therapeutic Target

5.3.1 Comparative Distribution of Programs between the Diabetic Retinopathy Market and Pipeline by Therapeutic Target Family

5.3.2 First-in-Class Pipeline Programs Targeting Novel Molecular Targets

5.3.3 Pipeline Products in Diabetic Complications

6 Signaling Network, Disease Causation and Innovation Alignment

6.1 Complexity of Signaling Networks in Metabolic Disorders

6.2 First-in-Class Matrix Assessment

7 First-in-Class Target Evaluation

7.1 Pipeline Programs Targeting NADPH Oxidase 4

7.2 Pipeline Programs Targeting Glutamate Decarboxylase

7.3 Pipeline Programs Targeting Growth Hormone Secretagogue Receptor Type 1

7.4 Pipeline Programs Targeting Motilin Receptor

7.5 Pipeline Programs Targeting Lysophosphatidic Acid Receptor 1

7.6 Pipeline Programs Targeting Leukotriene B4 Receptor 1

7.7 Pipeline Programs Targeting Integrin Alpha V

7.8 Pipeline Programs Targeting Signal Transducer and Activator of Transcription 4

8 Deals and Strategic Consolidations

8.1 Industry-Wide First-in-Class Deals

8.2 Licensing Deals

8.2.1 Licensing Deals by Molecule Type

8.2.2 Licensing Deals by Molecular Target

8.3 Co-development Deals

8.3.1 Co-development Deals by Molecule Type

8.3.2 Co-development Deals by Molecular Target

8.4 First-in-Class Programs Not Involved in Licensing or Co-development Deals

9 Appendix

9.1 References

9.2 Abbreviations

9.3 Research Methodology

9.4 Secondary Research

9.4.1 Market Analysis

9.4.2 Pipeline Analysis

9.4.3 First-in-Class Matrix Assessment

9.4.4 First-in-Class Target Profiles

9.4.5 Licensing and Co-Development Deals

9.5 Contact Us

9.6 Disclaimer

1.1 List of Tables

Table 1: Natural Development of Diabetic Nephropathy

Table 2: Diabetic Complications, Global, Data for NADPH Oxidase 4 as Therapeutic Target, 2016

Table 3: Diabetic Complications, Global, Data for Glutamate Decarboxylase as Therapeutic Target, 2016

Table 4: Diabetic Complications, Global, Data for Growth Hormone Secretagogue Receptor Type 1 as Therapeutic Target, 2016

Table 5: Diabetic Complications, Global, Data for Motilin Receptor as Therapeutic Target, 2016

Table 6: Diabetic Complications, Global, Data for Lysophosphatidic Acid Receptor 1 as Therapeutic Target, 2016

Table 7: Diabetic Complications, Global, Data for Leukotriene B4 Receptor 1 as Therapeutic Target, 2016

Table 8: Diabetic Complications, Global, Data for Integrin Alpha V as Therapeutic Target, 2016

Table 9: Diabetic Complications, Global, Data for Signal Transducer and Activator of Transcription 4 as Therapeutic Target, 2016

Table 10: Abbreviations

1.2 List of Figures

Figure 1: Diabetic Complications, Global, Number of Product Approvals by FDA and Five-Year Moving Average of Product Approvals (%), 1987–2012

Figure 2: Global, Sales Performance of First-in-Class and Non-First-in-Class Products after Marketing Approval ($m), 2016

Figure3: Diabetic Neuropathies, Global, Overview of Marketed Products, 2016

Figure 4: Diabetic Nephropathy, Global, Overview of Marketed Products, 2016

Figure 5: Diabetic Retinopathies, Global, Overview of Marketed Products, 2016

Figure 6: Diabetic Neuropathies, Global, Overview of Pipeline Products, 2016

Figure 7: Diabetic Neuropathies, Global, Molecular Targets in Pipeline, 2016

Figure 8: Diabetic Neuropathies, Global, Pipeline by Molecular Targets and Stage of Development, 2016

Figure 9: Diabetic Neuropathies, Global, Molecular Target Family Comparison, Pipeline and Marketed Products, 2016

Figure 10: Diabetic Neuropathies, Global, Molecular Target Family Comparison, Pipeline First-in-Class and Established Molecular Targets, 2016

Figure 11: Diabetic Neuropathies, Global, Percentage of First-in-Class Products in Pipeline by Molecular Target Family (%), 2016

Figure 12: Diabetic Neuropathies, Global, Percentage of First-in-Class Products in Pipeline by Stage of Development (%), 2016

Figure 13: Diabetic Nephropathy, Global, Overview of Pipeline Products, 2016

Figure 14: Diabetic Nephropathy, Global, Molecular Targets in Pipeline, 2016

Figure 15: Diabetic Nephropathy, Global, Pipeline by Molecular Targets and Stage of Development, 2016

Figure 16: Diabetic Nephropathy, Global, Molecular Target Family Comparison, Pipeline and Marketed Products, 2016

Figure 17: Diabetic Nephropathy, Global, Molecular Target Family Comparison, Pipeline First-in-Class and Established Molecular Targets, 2016

Figure 18: Diabetic Nephropathy, Global, Percentage of First-in-Class Products in Pipeline by Molecular Target Family (%), 2016

Figure 19: Diabetic Nephropathy, Global, Percentage of First-in-Class Products in Pipeline by Stage of Development (%), 2016

Figure 20: Diabetic Retinopathies, Global, Overview of Pipeline Products, 2016

Figure 21: Diabetic Retinopathies, Global, Molecular Targets in Pipeline, 2016

Figure 22: Diabetic Retinopathies, Global, Pipeline by Molecular Targets and Stage of Development, 2016

Figure 23: Diabetic Retinopathies, Global, Complications, Molecular Target Family Comparison, Pipeline and Marketed Products, 2016

Figure 24: Diabetic Retinopathies, Global, Molecular Target Family Comparison, Pipeline First-in-Class and Established Molecular Targets, 2016

Figure 25: Diabetic Retinopathies, Global, Percentage of First-in-Class Products in Pipeline by Molecular Target Family (%), 2016

Figure 26: Diabetic Retinopathies, Global, Percentage of First-in-Class Products in Pipeline by Stage of Development (%), 2016

Figure 27: Diabetic Complications, Global, First-in-Class Products in Pipeline (Part 1), 2016

Figure 28: Diabetic Complications, Global, First-in-Class Products in Pipeline (Part 2), 2016

Figure 29: Diabetic Complications, Global, First-in-Class Products in Pipeline (Part 3), 2016

Figure 30: Diabetic Complications, Global, Gastric Cancer, Target Matrix, 2016

Figure 31: Diabetic Complications, Global, Pipeline Programs Targeting NADPH Oxidase 4, 2016

Figure 32: Diabetic Complications, Global, Pipeline Programs Targeting Glutamate Decarboxylase, 2016

Figure 33: Diabetic Complications, Global, Pipeline Programs Targeting Growth Hormone Secretagogue Receptor Type 1, 2016

Figure 34: Diabetic Complications, Global, Pipeline Programs Targeting Motilin Receptor, 2016

Figure 35: Diabetic Complications, Global, Pipeline Programs Targeting Lysophosphatidic Acid Receptor 1, 2016

Figure 36: Diabetic Complications, Global, Pipeline Programs Targeting Leukotriene B4 Receptor 1, 2016

Figure 37: Diabetic Complications, Global, Pipeline Programs Targeting Integrin Alpha V, 2016

Figure 38: Diabetic Complications, Global, Pipeline Programs Targeting Signal Transducer and Activator of Transcription 4, 2016

Figure 39: Diabetic Complications, Global, Deals by Stage of Development, 2006–2014

Figure 40: Diabetic Complications, Global, Licensing Deal Values by Stage of Development ($m), 2006–2014

Figure 41: Diabetic Complications, Global, Licensing Deal Value, 2006–2016

Figure 42: Diabetic Complications, Global, Licensing Deals by Year, 2006–2016

Figure 43: Diabetic Complications, Global, Licensing Deals by Stage of Development, 2006–2016

Figure 44: Diabetic Complications, Global, Licensing Deal Value by Stage of Development and Molecule Type, 2006–2016

Figure 45: Diabetic Complications, Global, Licensing Deal Value by Molecular Target, 2006–2016

Figure 46: Diabetic Complications, Global, Summary of Licensing Deals, 2006–2016

Figure 47: Diabetic Complications, Global, Co-development Deal Value, 2006–2016

Figure 48: Diabetic Complications, Global, Co-development Deals, 2006–2016

Figure 49: Diabetic Complications, Global, Co-development Deals by Stage of Development, 2006–2016

Figure 50: Diabetic Complications, Global, Co-development by Stage of Development and Molecule Type, 2006–2015

Figure 51: Diabetic Complications, Global, Co-development by Stage of Development and Molecular Target, 2006–2015

Figure 52: Diabetic Complications, Global, Summary of Co-development Deals, 2006-2016

Figure 53: Diabetic Complications, Global, First-in-Class Therapies Not Involved in Deals (Part 1), 2016

Figure 54: Diabetic Complications, Global, First-in-Class Therapies Not Involved in Deals (Part 2), 2016

Figure 55: Diabetic Complications, Global, First-in-Class Therapies Not Involved in Deals (Part 3), 2016

Frontier Pharma: Diabetic Complications - Innovative and Diverse Neuropathies, Nephropathy and Retinopathies Pipelines Demonstrate Shift Towards Disease Modifying Therapies

Summary

Diabetes is a common long-term condition that can lead to a range of disparate and serious complications. It is a lifelong, multi-systemic condition that affects a number of integral organs. Diabetes has a rapidly increasing prevalence – it currently affects 10% of adults globally, and is estimated to become the seventh-leading cause of death by 2030.0
The lack of absolute treatment for the condition and the difficulty in maintaining constant glycemic control, even following adequate treatment, can result in a range of complications. The three main indication groups are diabetic nephropathy, which is a progressive condition caused by damage to the capillaries and kidneys glomeruli as a result of diabetes; diabetic retinopathy, which is defined as damage to the retina as a result of high blood sugar; and a range of diabetic neuropathies, a group of conditions in which nerve damage is caused as a result of diabetes mellitus.

The need for improved therapeutics within diabetic complications is especially prominent in comparison with other multi-systemic conditions, as the market is currently predominantly composed of therapies that symptomatically treat the condition, or at best slow disease progression. However, as the understanding of disease pathophysiology in both diabetes and its complications increases, new targets are being identified and converted into improved therapeutic options that are better aligned with the underlying disease pathophysiology than their predecessors.

The diabetic complications pipeline consists of 429 products that contain an array of targets not currently in use within the market. The increase in molecular target diversity signifies the high potential for changes and improvements in the diabetic complications market. One innovative therapy is CBX-129801, a promising synthetic peptide that is currently in development for diabetic neuropathy. Innovation can also be seen within diabetic retinopathy, with therapies such as BCN070660, a topical ophthalmologic formulation currently in development.

Scope

• What effect do current market therapies have on disease progression?
• Which drug classes dominate the current market?
• What additional benefits have newly approved therapies brought to the market?
• Can the increasing number of peptides in the pipeline prove useful in diabetic neuropathy?
• Can neuroprotective therapies prove an important addition in diabetic retinopathies?
• Can the diverse range of molecule types and molecular targets within the pipeline help reverse disease progression?
• To what degree is the pipeline penetrated by first-in-class innovation?
• What is the clinical potential of first-in-class products, based on their alignment to disease-causing pathways?
• Which are the most promising first-in-class targets in early-stage development?
• Which of the first-in-class products in development are not currently involved in a licensing or co-development deal, and therefore represent investment opportunities?

Reasons to buy

Understand the current clinical and commercial landscape. It includes a comprehensive study of disease pathogenesis, diagnosis, prognosis and the treatment options available.

Visualize the composition of the market for each diabetic complication individually, in terms of dominant molecule types and targets, highlighting what the current unmet needs are and how they can be addressed. This knowledge allows a competitive understanding of gaps in the current market.

Analyze the pipeline for each diabetic complication individually and stratify by stage of development, molecule type and molecular target. There are strong signs in the pipeline that the industry is seeking more innovative approaches to treating diabetic complications.

Assess the therapeutic potential of first-in-class targets. Using a proprietary matrix, first-in-class products have been assessed and ranked according to clinical potential. Promising early-stage targets have been reviewed in greater detail.

Identify commercial opportunities in the diabetic complications deals landscape by analyzing trends in licensing and co-development deals and producing a curated list of diabetic complications therapies that are not yet involved in deals, and may be potential investment opportunities.