Frontier Pharma: Type 2 Diabetes Mellitus - Therapies Targeting GPCRs and Protein Kinases Dominate Pipeline, with Strong Repositioning Opportunities into Associated Areas, Including Obesity and Cardiovascular Disease

1 Table of Contents
1 Table of Contents 2
1.1 List of Tables 4
1.2 List of Figures 4
2 Executive Summary 6
2.1 Competitive Market Landscape Driven by Rising Prevalence 6
2.2 Large and Diverse Pipeline Dominated by Products Acting on G Protein Coupled Receptors (GPCR) and Protein Kinases 6
2.3 Strong Opportunities for Investment in First-in-Class Products 6
3 The Case for Innovation 7
3.1 Growing Opportunities for Biologic Products 7
3.2 Diversification of Molecular Targets 8
3.3 Innovative First-in-Class Product Developments Remain Attractive 8
3.4 Regulatory and Reimbursement Policy Shifts Favor First-in-Class Innovation 9
3.5 Sustained Innovation in Type 2 Diabetes Mellitus 9
4 Clinical and Commercial Landscape 10
4.1 Overview of Type 2 Diabetes Mellitus 10
4.2 Disease Classification 10
4.2.1 Type 1 Diabetes Mellitus 10
4.2.2 Type 2 Diabetes Mellitus 11
4.2.3 Type 3 Diabetes Mellitus 11
4.2.4 LADA 11
4.2.5 MODY 11
4.2.6 Gestational 11
4.2.7 Pancreatic diabetes 11
4.2.8 Prediabetes 11
4.3 Symptoms 11
4.4 Diagnosis 12
4.5 Etiology 12
4.6 Pathophysiology 13
4.7 Comorbidities and Complications 14
4.8 Epidemiology 15
4.9 Treatment 16
4.9.1 Non-Insulin T2DM Therapies 17
4.9.2 Insulin-Based T2DM Therapies 19
4.10 Overview of Marketed Products 20
4.11 Unmet Need and Commercial Opportunities in T2DM 22
5 Assessment of Pipeline Product Innovation 23
5.1 Overview 23
5.2 Pipeline by Stage of Development and Molecule Type 23
5.3 Pipeline by Molecular Target 24
5.4 Comparative Distribution of Programs between the Market and Pipeline by Molecular Target Class 26
5.5 Comparative Distribution of First-in-Class and Non-First-in-Class Pipeline Programs by Molecular Target Class 27
5.6 Ratio of First-in-Class Programs to First-in-Class Molecular Targets within the Pipeline 28
5.7 List of All First-in-Class Pipeline Programs 30
6 Signaling Network, Disease Causation and Innovation Alignment 39
6.1 Complexity of Signaling Networks in Type 2 Diabetes Mellitus 39
6.2 Signaling Pathways, Disease-Causing Mutations and First-in-Class Molecular Target Integration 39
6.3 First-in-Class Molecular Target Matrix Assessment 39
7 First-in-Class Molecular Target Evaluation 44
7.1 Pipeline Programs Targeting G Protein Coupled Receptor Kinase 5 (GRK5) 44
7.2 Pipeline Programs Targeting Gastric Inhibitory Polypeptide Receptors (GIPR) 45
7.3 Pipeline Programs Targeting Bone Morphogenetic Protein Receptor Type 1A (BMPR1A), Bone Morphogenetic Protein Receptor Type 1B (BMPR1B) and Bone Morphogenetic Protein Receptor Type 2 (BMPR2) 46
7.4 Pipeline Programs Targeting Solute Carrier Family 13 Member 5 (SLC13A5) 48
7.5 Pipeline Programs Targeting N Formyl Peptide Receptor 3 (FPR3) and N Formyl Peptide Receptor 2 (FPR2) 49
7.6 Pipeline Programs Targeting Neuromedin U receptor 2 (NMUR2) and Neuromedin U receptor 1 (NMUR1) 50
7.7 Pipeline Programs Targeting Peptide YY (PYY) 51
7.8 Pipeline Programs Targeting Apelin Receptor (APLNR) 52
7.9 Pipeline Programs Targeting Insulin Receptor Substrate (IRS1) and Insulin Receptor Substrate (IRS2) 53
7.10 Conclusion 56
8 Strategic Consolidations 57
8.1 Industry-Wide First-in-Class Deals 57
8.2 Licensing Deals 58
8.2.1 Deals by Region, Value and Year 58
8.2.2 Deals by Stage of Development and Value 59
8.2.3 Deals by Molecule Type and Molecular Target 59
8.2.4 List of Deals with Disclosed Deal Values 60
8.3 Co-development Deals 62
8.3.1 Deals by Region, Value and Year 62
8.3.2 Deals by Stage of Development and Value 62
8.3.3 Deals by Molecule Type and Molecular Target 63
8.3.4 List of Deals with Disclosed Deal Values 64
8.4 First-in-Class Programs with and without Prior Licensing or Co-development Deal Involvement 65
9 Appendix 69
9.1 References 69
9.2 Abbreviations 74
9.3 Methodology 75
9.3.1 Data Integrity 75
9.3.2 Innovative and Meaningful Analytical Techniques and Frameworks 75
9.3.3 Evidence Based Analysis and Insight 75
9.4 Secondary Research 75
9.4.1 Market Analysis 76
9.4.2 Pipeline Analysis 76
9.4.3 Licensing and Co-development Deals 77
9.5 Contact Us 77
9.6 Disclaimer 77

List of Tables
1.1 List of Tables
Table 1: Type 2 Diabetes Mellitus, Global, Related Indications of T2DM First-in-Class Products, 2018 40
Table 2: Type 2 Diabetes Mellitus, Global, Key Features of G Protein Coupled Receptor Kinase 5 (GRK5), 2018 44
Table 3: Type 2 Diabetes Mellitus, Global, Pipeline Programs Targeting G Protein Coupled Receptor Kinase 5 (GRK5), 2018 44
Table 4: Type 2 Diabetes Mellitus, Global, Key Features of Gastric Inhibitory Polypeptide Receptor (GIPR), 2018 45
Table 5: Type 2 Diabetes Mellitus, Global, Pipeline Programs Targeting Gastric Inhibitory Polypeptide Receptor (GIPR), 2018 46
Table 6: Type 2 Diabetes Mellitus, Global, Key Features of Bone Morphogenetic Protein Receptor Type 1A (BMPR1A), 2018 47
Table 7: Type 2 Diabetes Mellitus, Global, Key Features of Bone Morphogenetic Protein Receptor Type 1B (BMPR1B), 2018 47
Table 8: Type 2 Diabetes Mellitus, Global, Key Features of Bone Morphogenetic Protein Receptor Type 2 (BMPR2), 2018 47
Table 9: Type 2 Diabetes Mellitus, Global, Pipeline Programs Targeting Bone Morphogenetic Protein Receptor Type 1A (BMPR1A), Bone Morphogenetic Protein Receptor Type 1B (BMPR1B) and Bone Morphogenetic Protein Receptor Type 2 (BMPR2), 2018 48
Table 10: Type 2 Diabetes Mellitus, Global, Key Features of Solute Carrier Family 13 Member 5 (SLC13A5), 2018 48
Table 11: Type 2 Diabetes Mellitus, Global, Pipeline Programs Targeting Solute Carrier Family 13 Member 5 (SLC13A5), 2018 49
Table 12: Type 2 Diabetes Mellitus Drugs Market, Global, Pipeline Programs Targeting N-Formyl Peptide Receptor 2 (FPR2) and N-Formyl Peptide Receptor 3 (FPR3), 2018 49
Table 13: Type 2 Diabetes Mellitus Drugs Market, Global, Pipeline Programs Targeting N-Formyl Peptide Receptor 2 (FPR2) and N-Formyl Peptide Receptor 3 (FPR3) , 2018 50
Table 14: Type 2 Diabetes Mellitus, Global, Key Features of Neuromedin U Receptor 1 (NMUR1), 2018 51
Table 15: Type 2 Diabetes Mellitus, Global, Key Features of Neuromedin U Receptor 2 (NMUR2), 2018 51
Table 16: Type 2 Diabetes Mellitus, Global, Global, Pipeline Programs Targeting Neuromedin U Receptor 2 (NMUR2), 2018 51
Table 17: Type 2 Diabetes Mellitus Drugs Market, Global, Key Features of Targeting Peptide YY (PYY), 2018 52
Table 18: Type 2 Diabetes Mellitus Drugs Market, Global, Pipeline Programs Targeting Peptide YY (PYY), 2018 52
Table 19: Type 2 Diabetes Mellitus, Global, Key Features of Apelin Receptor (APLNR), 2018 53
Table 20: Type 2 Diabetes Mellitus, Global, Pipeline Programs Targeting Apelin Receptor (APLNR), 2018 53
Table 21: Type 2 Diabetes Mellitus, Global, Key Features of Insulin Receptor Substrate 1 (IRS1), 2018 54
Table 22: Type 2 Diabetes Mellitus, Global, Key Features of Insulin Receptor Substrate 2 (IRS2), 2018 55
Table 23: Type 2 Diabetes Mellitus, Global, Pipeline Programs Targeting Insulin Receptor Substrate 1 (IRS1), 2018 55
Table 24: Type 2 Diabetes Mellitus, Global, Pipeline Programs Targeting Insulin Receptor Substrate 2 (IRS2), 2018 55

List of Figures
1.2 List of Figures
Figure 1: Type 2 Diabetes Mellitus, Global, Innovation Trends in Product Approvals Across the Pharmaceutical Market, 1987-2014 7
Figure 2: Type 2 Diabetes Mellitus, Global, Post-Marketing-Approval Sales Performance of First-in-Class and Non-First-in-Class Products Across Pharmaceutical Industry ($m), 2006-2013 8
Figure 3: Type 2 Diabetes Mellitus, Global, Market by Molecule Type and Molecular Target, 2018 21
Figure 4: Type 2 Diabetes Mellitus, Global, Pipeline Size by Therapy Area, 2018 23
Figure 5: Type 2 Diabetes Mellitus, Global, Pipeline by Stage of Development and Molecule Type, 2018 24
Figure 6: Type 2 Diabetes Mellitus, Global Pipeline by Molecular Target and Stage of Development, 2018 25
Figure 7: Type 2 Diabetes Mellitus, Global, Pipeline Breakdown of GPCR and Protein Kinase Molecular Target Class, 2018 25
Figure 8: Type 2 Diabetes Mellitus, Global, Distribution of Pipeline and Marketed Products by Molecular Target Class, 2018 26
Figure 9: Type 2 Diabetes Mellitus, Global, Distribution of Pipeline Products by First-in-Class Status and Molecular Target Class, 2018 27
Figure 10: Type 2 Diabetes Mellitus, Global, Percentage Distribution of First-in-Class and Non-First-in-class Pipeline Programs by Stage of Development and Molecular Target Class, 2018 28
Figure 11: Type 2 Diabetes Mellitus, Global, Ratio of First-in-Class Products to First-in-Class Targets by Stage of Development and Molecular Target Class, 2018 29
Figure 12: Type 2 Diabetes Mellitus, Global, All First-in-Class Pipeline Programs, 2018 (part 1) 30
Figure 13: Type 2 Diabetes Mellitus, Global, All First-in-Class Pipeline Programs, 2018 (part 2) 31
Figure 14: Type 2 Diabetes Mellitus, Global, All First-in-Class Pipeline Programs, 2018 (part 3) 32
Figure 15: Type 2 Diabetes Mellitus, Global, All First-in-Class Pipeline Programs, 2018 (part 4) 33
Figure 16: Type 2 Diabetes Mellitus, Global, All First-in-Class Pipeline Programs, 2018 (part 5) 34
Figure 17: Type 2 Diabetes Mellitus, Global, All First-in-Class Pipeline Programs, 2018 (part 6) 34
Figure 18: Type 2 Diabetes Mellitus, Global, All First-in-Class Pipeline Programs, 2018 (part 7) 35
Figure 19: Type 2 Diabetes Mellitus, Global, All First-in-Class Pipeline Programs, 2018 (part 8) 35
Figure 20: Type 2 Diabetes Mellitus, Global, All First-in-Class Pipeline Programs, 2018 (part 9) 36
Figure 21: Type 2 Diabetes Mellitus, Global, All First-in-Class Pipeline Programs, 2018 (part 10) 36
Figure 22: Type 2 Diabetes Mellitus, Global, All First-in-Class Pipeline Programs, 2018 (part 11) 37
Figure 23: Type 2 Diabetes Mellitus, Global, All First-in-Class Pipeline Programs, 2018 (part 12) 38
Figure 24: Type 2 Diabetes Mellitus, Global, First-in-Class Molecular Target Matrix Assessment for Type 2 Diabetes Mellitus, 2018 (part 1) 41
Figure 25: Type 2 Diabetes Mellitus, Global, First-in-Class Molecular Target Matrix Assessment for Type 2 Diabetes Mellitus, 2018 (part 2) 42
Figure 26: Type 2 Diabetes Mellitus, Global, First-in-Class Molecular Target Matrix Assessment for Type 2 Diabetes Mellitus, 2018 (part 2) 43
Figure 27: Type 2 Diabetes Mellitus, Global, Industry-Wide Licensing Deals by First-in-Class Status and Stage of Development, 2006-2015 57
Figure 28: Type 2 Diabetes Mellitus, Global, Industry-Wide Licensing Deals by First-in-Class Status, Deal Value, Upfront Payment Value and Stage of Development, 2006-2014 58
Figure 29: Type 2 Diabetes Mellitus, Global Licensing Deals by Region, Value and Year 2006-2018 59
Figure 30: Type 2 Diabetes Mellitus, Global, Licensing Deals by Deal Value, Upfront Payment Value and Stage of Development, 2006-2018 59
Figure 31: Type 2 Diabetes Mellitus, Global, Number and Aggregate Deal Value of Licensing Deals by Molecule Type and Molecular Target Class, 2006-2018 60
Figure 32: Type 2 Diabetes Mellitus, Global, Licensing Deals with Disclosed Deal Values, 2006-2018 61
Figure 33: Type 2 Diabetes Mellitus, Global, Co-development Deals by Region, Value and Year 2006-2018 62
Figure 34: Type 2 Diabetes Mellitus, Global, Number and Aggregate Deal Value of Co-development Deals By Stage of Development and Year, 2006-2018 63
Figure 35: Type 2 Diabetes Mellitus, Global, Co-development Deals by Deal Value, Upfront Payment Value and Stage of Development, 2006-2018 64
Figure 36: Type 2 Diabetes Mellitus, Global, Co-development Deals with Disclosed Deal Values, 2006-2018 65
Figure 37: Type 2 Diabetes Mellitus, Global, First-in-Class Programs with and without Prior Involvement in Licensing or Co-development Deals, 2006-2018 (part 1) 66
Figure 38: Type 2 Diabetes Mellitus, Global, First-in-Class Programs with and without Prior Involvement in Licensing or Co-development Deals, 2006-2018 (part 2) 67
Figure 39: Type 2 Diabetes Mellitus, Global, First-in-Class Programs with and without Prior Involvement in Licensing or Co-development Deals, 2006-2018 (part 3) 68