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 Neglected Therapy Area with High Levels of Genericization 6 2.2 Diverse Pipeline Demonstrates Potential to Address Unmet Needs 6 2.3 Increase in Strategic Consolidations in Recent Years 6 3 The Case for Innovation 7 3.1 Growing Opportunities for Biologic Products 8 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 Orphan and Rare Dermatological Diseases 9 3.6 GBI Research Report Guidance 9 4 Clinical and Commercial Landscape 11 4.1 Overview of the Dermatology Market 11 4.2 Overview of Orphan and Rare Diseases 11 4.2.1 Overview of Systemic Sclerosis (Scleroderma) 12 4.2.2 Overview of Alopecia 12 4.2.3 Overview of Epidermolysis Bullosa 12 4.2.4 Overview of Pemphigus Vulgaris 13 4.2.5 Overview of Vitiligo 13 4.2.6 Overview of Cutaneous Lupus Erythematosus 13 4.3 Symptoms 13 4.3.1 Systemic sclerosis 13 4.3.2 Alopecia 14 4.3.3 Epidermolysis bullosa 14 4.3.4 Pemphigus Vulgaris 14 4.3.5 Vitiligo 14 4.3.6 Cutaneous Lupus Erythematosus 14 4.4 Diagnosis 14 4.4.1 Systemic sclerosis 15 4.4.2 Alopecia 15 4.4.3 Epidermolysis bullosa 16 4.4.4 Pemphigus Vulgaris 16 4.4.5 Vitiligo 16 4.4.6 Cutaneous Lupus Erythematosus 16 4.5 Etiology 16 4.5.1 Systemic Sclerosis 16 4.5.2 Alopecia 16 4.5.3 Epidermolysis Bullosa 17 4.5.4 Pemphigus Vulgaris 17 4.5.5 Vitiligo 17 4.5.6 Cutaneous Lupus Erythematosus 18 4.6 Pathophysiology 18 4.6.1 Systemic Sclerosis 19 4.6.2 Alopecia 19 4.6.3 Epidermolysis Bullosa 19 4.6.4 Pemphigus Vulgaris 19 4.6.5 Vitiligo 19 4.6.6 Cutaneous Lupus Erythematosus 20 4.7 Epidemiology 20 4.7.1 Systemic sclerosis 20 4.7.2 Alopecia 20 4.7.3 Epidermolysis Bullosa 21 4.7.4 Pemphigus Vulgaris 21 4.7.5 Vitiligo 21 4.7.6 Cutaneous Lupus Erythematosus 21 4.8 Co-morbidities and Complications 21 4.8.1 Systemic Sclerosis 22 4.8.2 Alopecia 22 4.8.3 Epidermolysis Bullosa 22 4.8.4 Pemphigus Vulgaris 22 4.8.5 Vitiligo 22 4.8.6 Cutaneous Lupus Erythematosus 22 4.9 Treatment 22 4.9.1 Systemic Sclerosis 23 4.9.2 Alopecia 24 4.9.3 Epidermolysis Bullosa 24 4.9.4 Pemphigus Vulgaris 24 4.9.5 Vitiligo 25 4.9.6 Cutaneous Lupus Erythematosus 25 4.10 Overview of Marketed Products 25 5 Assessment of Pipeline Product Innovation 27 5.1 Overview 27 5.2 Pipeline by Stage of Development and Molecule Type 27 5.2.1 Overall Pipeline 27 5.2.2 Pipeline by Key Indications 28 5.3 Pipeline by Molecular Target 32 5.3.1 Overall Pipeline 32 5.3.2 Pipeline for Key Indications 33 5.4 Comparative Distribution of Programs between the Market and Pipeline by Molecular Target Class 35 5.5 Comparative Distribution of First-in-Class and Non-First-in-Class Pipeline Programs by Molecular Target Class 35 5.6 Percentage Distribution of First-in-Class and Non-First-in-Class Pipeline Programs by Stage of Development, Molecule Type and Molecular Target Class 37 5.7 Ratio of First-in-Class Programs to First-in-Class Molecular Targets by Stage of Development, Molecule Type and Molecular Target Class 38 5.8 List of All Pipeline Programs 40 6 Signaling Network, Disease Causation and Innovation Alignment 47 6.1 Complexity of Signaling Networks in Orphan and Rare Dermatological Diseases 47 6.2 Signaling Pathways and First-in-Class Molecular Target Integration 47 6.3 First-in-Class Molecular Target Matrix Assessment 47 7 First-in-Class Molecular Target Evaluation 52 7.1 Pipeline Programs Targeting Collagen type XVII (COL17A1) 52 7.2 Pipeline Programs Targeting Collagen type VII, alpha 1 (COL7A1) 52 7.3 Pipeline Programs Targeting Interleukin 2 Receptor Subunit Beta (IL2RB) 54 7.4 Pipeline Programs Targeting Desmoglein 1 (DSG1) 55 7.5 Pipeline Programs Targeting Nacht LRR and PYD Domains Containing Protein 3 (NLRP3) 56 7.6 Pipeline Programs Targeting Interleukin 3 Receptor Subunit Alpha (IL3RA) 58 7.7 Pipeline Programs Targeting Non-Receptor Tyrosine Protein Kinase TYK2 (TYK2) 59 7.8 Pipeline Programs Targeting Interleukin 6 Receptor Subunit Beta (IL6ST) 61 7.9 Pipeline Programs Targeting Potassium Voltage-Gated Channel Subfamily A Member 3 (KCNA3) 62 7.10 Pipeline Programs Targeting Kallikrein 7 (KLK7) 63 7.11 Pipeline Programs Targeting Eotaxin (CCL11) 64 7.12 Pipeline Programs Targeting Interleukin 2 (IL2) 65 8 Strategic Consolidations 67 8.1 Industry-wide First-in-Class Deals 67 8.2 Licensing Deals 68 8.2.1 Deals by Region, Value and Year 68 8.2.2 Deals by Key Indication and Value 69 8.2.3 Deals by Stage of Development and Value 70 8.2.4 Deals by Molecule Type and Molecular Target 71 8.2.5 List of Deals with Disclosed Deal Values 72 8.3 Co-development Deals 73 8.3.1 Deals by Region, Value and Year 73 8.3.2 Deals by Indication and Value 74 8.3.3 Deals by Stage of Development and Value 74 8.3.4 Deals by Molecule Type and Molecular Target 74 8.3.5 List of Deals with Disclosed Deal Values 76 8.4 First-in-Class Programs with and without Prior Licensing or Co-development Deal Involvement 76 9 Appendix 79 9.1 References 79 9.2 Abbreviations 83 9.3 Pipeline Disease List 84 9.4 Methodology 84 9.4.1 Data Integrity 84 9.4.2 Innovative and Meaningful Analytical Techniques and Frameworks 85 9.4.3 Evidence Based Analysis and Insight 85 9.5 Secondary Research 85 9.5.1 Market Analysis 85 9.5.2 Pipeline Analysis 85 9.5.3 Licensing and Co-development Deals 86 9.6 Contact Us 86 9.7 Disclaimer 86

1.1 List of Tables Table 1: Orphan and Rare Dermatological Diseases, Global, Key Features of Collagen Type XVII (COL17A1), 2018 52 Table 2: Orphan and Rare Dermatological Diseases, Global, Pipeline Programs Targeting Collagen Type XVII (COL17A1), 2018 52 Table 3: Orphan and Rare Dermatological Diseases, Global, Key Features of Collagen Type VII, Alpha 1 (COL7A1), 2018 53 Table 4: Orphan and Rare Dermatological Diseases, Global, Pipeline Programs Targeting Collagen Type VII, Alpha 1 (COL7A1), 2018 54 Table 5: Orphan and Rare Dermatological Diseases, Global, Key Features of Interleukin 2 Receptor Subunit Beta (IL2RB), 2018 55 Table 6: Orphan and Rare Dermatological Diseases, Global, Pipeline Programs Targeting Interleukin 2 Receptor Subunit Beta (IL2RB), 2018 55 Table 7: Orphan and Rare Dermatological Diseases, Global, Key Features of Desmoglein 1 (DSG1), 2018 56 Table 8: Orphan and Rare Dermatological Diseases, Global, Pipeline Programs Targeting Desmoglein 1 (DSG1), 2018 56 Table 9: Orphan and Rare Dermatological Diseases, Global, Key Features of Nacht LRR and PYD Domains Containing Protein 3 (NLRP3), 2018 57 Table 10: Orphan and Rare Dermatological Diseases, Global, Pipeline Programs Targeting Nacht LRR and PYD Domains Containing Protein 3 (NLRP3), 2018 58 Table 11: Orphan and Rare Dermatological Diseases, Global, Key Features of Interleukin 3 Receptor Subunit Alpha (IL3RA), 2018 59 Table 12: Pipeline Programs Targeting Interleukin 3 Receptor Subunit Alpha (IL3RA), 2018 59 Table 13: Orphan and Rare Dermatological Diseases, Global, Key Features of Non-receptor Tyrosine Protein Kinase TYK2, 2018 60 Table 14: Orphan and Rare Dermatological Diseases, Global, Pipeline Programs Targeting Non-receptor Tyrosine Protein Kinase TYK2, 2018 61 Table 15: Orphan and Rare Dermatological Diseases, Global, Key Features of Interleukin 6 Receptor Subunit Beta (IL6ST), 2018 62 Table 16: Orphan and Rare Dermatological Diseases, Global, Pipeline Programs Targeting Interleukin 6 Receptor Subunit Beta (IL6ST), 2018 62 Table 17: Orphan and Rare Dermatological Diseases, Global, Key Features of Potassium Voltage Gated Subfamily A Member 3 (KCNA3), 2018 63 Table 18: Orphan and Rare Dermatological Diseases, Global, Pipeline Programs Targeting Potassium Voltage Gated Channel Subfamily A Member 3 (KCNA3), 2018 63 Table 19: Orphan and Rare Dermatological Diseases, Global, Key Features of Kallikrein 7 (KLK7), 2018 64 Table 20: Orphan and Rare Dermatological Disease, Global, Pipeline Programs Targeting Kallikrein 7 (KLK7), 2018 64 Table 21: Orphan and Rare Dermatological Diseases, Global, Key Features of Eotaxin (CCL11), 2018 65 Table 22: Orphan and Rare Dermatological Diseases, Global, Pipeline Programs Targeting Key Features of Eotaxin (CCL11), 2018 65 Table 23: Orphan and Rare Dermatological Diseases, Global, Key Features of Interleukin 2 (IL2), 2018 66 Table 24: Orphan and Rare Dermatological Diseases, Global, Pipeline Programs Targeting Interleukin 2 (IL2), 2018 661.2 List of Figures Figure 1: Orphan and Rare Dermatological Diseases, US, Innovation Trends in Products Approvals, 1987-2014 7 Figure 2: Orphan and Rare Dermatological Diseases, US, Sales Performance of First-in-Class and Non-First-in-Class Products Post Marketing Approval, 2006-2013 9 Figure 3: Orphan and Rare Dermatological Diseases Global, Market by Molecule Type and Molecular Target Class, 2018 26 Figure 4: Orphan and Rare Dermatological Diseases, Global, Overall Pharmaceutical Pipeline by Therapy Area, 2018 27 Figure 5: Orphan and Rare Dermatological Diseases, Global, Overall Pipeline by Stage of Development and Molecule Type, 2018 28 Figure 6: Orphan and Rare Dermatological Diseases, Global, Pipeline for Key Indications by Stage of Development, 2018 29 Figure 7: Orphan and Rare Dermatological Diseases, Global, Pipeline for Key Indications by Molecule Type, 2018 31 Figure 8: Orphan and Rare Dermatological Diseases, Global, Overall Pipeline by Molecular Target and Stage of Development, 2018 33 Figure 9: Orphan and Rare Dermatological Diseases, Global, Pipeline for Key Indications by Molecular Target Class, 2018 34 Figure 10: Orphan and Rare Dermatological Diseases, Global, Pipeline and Marketed Programs by Molecular Target Class, 2018 35 Figure 11: Orphan and Rare Dermatological Diseases, Global, First-in-Class and Non-First-in-Class Pipeline Programs by Molecular Target Class and Stage of Development, 2018 36 Figure 12: Orphan and Rare Dermatological Diseases, Global, Percentage Distribution of First-in-Class and Non-First-in-Class Pipeline Programs by Stage of Development and Molecular Target Class, 2018 38 Figure 13: Orphan and Rare Dermatological Diseases, Global, Ratio of First-in-Class Programs to First-in-Class Targets by Stage of Development and Molecular Target Class, 2018 39 Figure 14: Orphan and Rare Dermatological Diseases, Global, All First-in-Class Pipeline Programs, 2018 (part 1) 40 Figure 15: Orphan and Rare Dermatological Diseases, Global, All First-in-Class Pipeline Programs, 2018 (part 2) 41 Figure 16: Orphan and Rare Dermatological Diseases, Global, All First-in-Class Pipeline Programs, 2018 (part 3) 42 Figure 17: Orphan and Rare Dermatological Diseases, Global, All First-in-Class Pipeline Programs, 2018 (part 4) 43 Figure 18: Orphan and Rare Dermatological Diseases, Global, All First-in-Class Pipeline Programs, 2018 (part 5) 44 Figure 19: Orphan and Rare Dermatological Diseases, Global, All First-in-Class Pipeline Programs, 2018 (part 6) 45 Figure 20: Orphan and Rare Dermatological Diseases, Global, All First-in-Class Pipeline Programs, 2018 (part 7) 46 Figure 21: Orphan and Rare Dermatological Diseases, Global, First-in-Class Molecular Target Matrix Assessment, 2018 (part 1) 49 Figure 22: Orphan and Rare Dermatological Diseases, Global, First-in-Class Molecular Target Matrix Assessment, 2018 (part 2) 50 Figure 23: Orphan and Rare Dermatological Diseases, Global, First-in-Class Molecular Target Matrix Assessment, 2018 (part 3) 51 Figure 24: Orphan Dermatological Disease, Global, Industry-Wide Licensing Deals by First-in-Class Status and Stage of Development, 2006-2015 67 Figure 25: Orphan Dermatological Diseases, Global, Industry-Wide Licensing Deals by First-in-Class Status, Deal Value, Upfront Payment Value and Stage of Development, 2006-2014 68 Figure 26: Orphan and Rare Dermatological Diseases, Global, Licensing Deals by Region, Value and Year, 2006-2018 69 Figure 27: Orphan and Rare Dermatological Diseases, Global, Number and Aggregate Deal Value of Licensing Deals for Systemic Sclerosis, Alopecia and Epidermolysis Bullosa, 2018 70 Figure 28: Orphan and Rare Dermatological Diseases, Global, Licensing Deals by Deal Value, Upfront Payment Value and Stage of Development, 2006-2018 70 Figure 29: Orphan and Rare Dermatological Diseases, Global, Number and Aggregate Deal Value of Licensing Deals by Molecule Type, 2006-2018 71 Figure 30: Orphan and Rare Dermatological Diseases Global, Licensing Deals with Disclosed Deal Values, 2006-2018 72 Figure 31: Orphan and Rare Dermatological Diseases, Global, Co-development Deals by Region, Value and Year, 2006-2018 73 Figure 32: Orphan and Rare Dermatological Diseases, Global, Number and Aggregate Deal Value of Co-development Deals for Systemic Sclerosis, Alopecia and Epidermolysis Bullosa, 2018 74 Figure 33: Orphan Dermatological Diseases, Co-development Deals by Deal Value, Upfront Payment Value and Stage of Development, 2006-2018 74 Figure 34: Orphan Dermatological Diseases, Global, Number and Aggregate Deal Value of Co-development Deals by Molecule Type and Molecular Target Class, 2006-2018 75 Figure 35: Orphan and Rare Dermatological Disease, Global, Co-development Deals with Disclosed Deal Values, 2006-2018 76 Figure 36: Orphan and Rare Dermatological Diseases, Global, First-in-Class Programs with and without Prior Involvement in Licensing or Co-development Deals, 2018 (part 1) 77 Figure 37: Orphan and Rare Dermatological Diseases, Global, First-in-Class Programs with and without Prior Involvement in Licensing or Co-development Deals, 2018 (part 2) 78