1. REPORT INTRODUCTION 1.1 Objective of the Study 13 1.2 Secondary Research 13 1.3 Scope of the report: 13 2. DISEASE OVERVIEW 14 2.1 Introduction 14 2.2 Classification of MG 15 2.2.1 Congenital MG 15 2.2.2 Ocular MG 15 2.2.3 Generalized MG 15 2.2.4 Transient Neonatal MG 15 2.2.5 Juvenile MG 16 2.3 Clinical Classification 18 2.4 Signs and Symptoms 20 2.5 Causes 22 2.6 Pathogenesis 23 2.7 Pathophysiology 25 2.7.1 Presynaptic Surface 25 2.7.2 Synaptic Cleft 26 2.7.3 Postsynaptic Surface 27 2.7.4 The Acetylcholine Receptor 28 2.7.5 Neuromuscular Junction Formation and Muscle-Specific Kinase 29 2.7.6 Safety Factor for Neuromuscular Transmission 29 2.7.7 Immunopathology 30 2.7.8 Autoantibodies in MG 30 2.7.9 Cellular Autoimmunity 31 2.7.10 Cytokine Influences 32 2.7.11 The Thymus in MG Pathogenesis 33 2.7.12 The Differential Involvement of Muscle Groups by MG 34 2.8 Diagnosis 35 2.8.1 Differential Diagnosis 37 2.9 Treatment 39 2.9.1 International Consensus guidance for management of Myasthenia Gravis 40 2.9.1.1 Development of guidance treatment statements 40 2.9.2 Myasthenia gravis: Association of British Neurologists’ Management Guidelines 46 2.9.2.1 International Consensus Guidance for Management of Myasthenia Gravis 46 2.9.2.2 Treatment of Generalized Myasthenia Gravis 48 2.9.2.3 Management of side effects: Propantheline or mebeverine can help cholinergic side effects 48 2.9.2.4 Assessment and Management of the relapsing patient with Myasthenia 51 2.9.3 Japanese Clinical Guidelines for Myasthenia Gravis 54 2.9.3.1 Recommendations 55 2.9.3.2 Thymectomy for non-thymomatous patients 56 2.9.3.2.1 Recommendations 56 2.9.3.3 Oral immunosuppressive therapy 56 2.9.3.3.1 Recommendations 56 2.9.3.4 High-dose Intravenous Methylprednisolone treatment 58 2.9.3.4.1 Recommendations 58 2.9.3.5 IVIg treatment 58 2.9.3.5.1 Recommendations 58 2.9.3.6 PE/PP 59 2.9.3.6.1 Recommendations 59 2.9.3.7 Treatment for anti-AChR antibody-negative patients (including MuSK-MG) 59 2.9.3.7.1 Recommendations 59 2.9.3.8 Treatment strategies for ocular MG 59 2.9.3.8.1 Recommendations 59 2.9.3.9 Treatment Strategies for LOMG and elderly MG patients 60 2.9.3.9.1 Recommendations 60 2.10 Treatment Algorithm 61 3. PRODUCTS ANALYSIS BY TECHNOLOGY 62 3.1 Product Analysis of the Technology 62 4. PRODUCTS ANALYSIS BY DESIGNATION 63 4.1 Comparative Analysis 63 5. TOTAL NUMBER OF MARKETED AND EMERGING PRODUCTS 64 5.1 Comparative Analysis 64 6. LIST OF MARKETED PRODUCTS 65 6.1 List of Marketed Products 65 6.2 Eculizumab: Alexion Pharmaceuticals 65 6.2.1 Product Description 65 6.2.2 Regulatory Milestones 66 6.2.2.1 Approval 66 6.2.3 Research and Development 67 6.2.3.1 Clinical Studies 67 6.2.3.1.1 Phase III 67 6.2.3.1.2 Results of Analysis 67 6.2.3.2 Current Pipeline Activity 69 6.2.3.2.1 Phase III 69 6.2.4 Product Development Activities 69 6.2.4.1 Patent Dispute 69 6.2.4.2 Acquisition 69 6.2.4.3 Designation 70 6.2.4.4 Patent 70 6.3 Tacrolimus: Astellas 71 6.3.1 Product Description 71 6.3.2 Regulatory Milestones 72 6.3.2.1 Approval 72 6.3.3 Research and Development 72 6.3.3.1 Clinical Studies 72 6.3.4 Product Development Activities 73 6.3.4.1 Designation 73 6.4 Venoglobulin IH: Mitsubishi Tanabe Pharma Corporation 74 6.4.1 Product Description 74 6.4.2 Regulatory Milestones 74 6.4.2.1 Approval 74 6.4.2.2 Clinical Studies 74 6.4.2.2.1 Results of Analysis 75 6.4.3 Product Development Activities 75 6.4.3.1 Merger 75 6.4.3.2 Designation 75 7. PIPELINE THERAPEUTICS AT A GLANCE 77 7.1 Pipeline Therapeutics at a Glance 77 8. COMPARATIVE ANALYSIS 78 8.1 Total Number of Emerging Products in Myasthenia Gravis 78 9. LATE PHASE PRODUCTS (PHASE III) 79 9.1 Comparative Analysis 79 9.2 Amifampridine Phosphate: Catalyst Pharmaceuticals 79 9.2.1 Product Description 79 9.2.2 Research and Development 80 9.2.2.1 Clinical Studies 80 9.2.2.1.1 Phase III 80 9.2.2.1.2 Phase II 80 9.2.2.1.3 Results of Analysis 81 9.2.3 Product Development Activities 82 9.2.3.1 Agreement 82 9.2.3.2 Designation 83 9.3 Efgartigimod: Argenx 84 9.3.1 Product Description 84 9.3.2 Research and Development 84 9.3.2.1 Clinical Studies 84 9.3.2.1.1 Phase III 84 9.3.2.1.2 Results of Analysis 85 9.3.3 Product Development Activities 86 9.3.3.1 Designation 86 9.3.3.2 Grant 86 9.3.3.3 Technology 86 9.4 Human normal immunoglobulin G (IgG): CSL Behring 87 9.4.1 Product Description 87 9.4.2 Research and Development 88 9.4.2.1 Clinical Studies 88 9.4.2.1.1 Phase III 88 9.4.2.1.2 Phase II 88 9.5 IGIV-C: Grifols Therapeutics 89 9.5.1 Product Description 89 9.5.2 Research and Development 90 9.5.2.1 Clinical Studies 90 9.5.2.1.1 Phase III 90 9.5.2.1.2 Phase II 90 10. MID PHASE PRODUCTS (PHASE II) 92 10.1 Comparative Analysis 92 10.2 Iscalimab: Novartis 92 10.2.1 Product Description 92 10.2.2 Research and Development 93 10.2.2.1 Pre-clinical Studies 93 10.2.2.2 Clinical Studies 94 10.2.2.2.1 Phase II 94 10.2.2.2.2 Results of Analysis 94 10.3 M281: Momenta Pharmaceuticals 95 10.3.1 Product Description 95 10.3.2 Research and Development 96 10.3.2.1 Clinical Studies 96 10.3.2.1.1 Phase II 96 10.3.2.1.2 Phase I 96 10.3.2.1.3 Results of Analysis 96 10.4 Rozanolixizumab: UCB Pharma 98 10.4.1 Product Description 98 10.4.2 Research and Development 98 10.4.2.1 Clinical Studies 98 10.4.2.1.1 Phase II 98 10.4.2.1.2 Results of Analysis 98 10.5 RVT-1401: Immunovant (Roivant Sciences) 100 10.5.1 Product Description 100 10.5.2 Research and Development 100 10.5.2.1 Clinical Studies 100 10.5.2.1.1 Phase II 100 10.5.3 Product Development Activities 101 10.5.3.1 Licensing Agreement 101 10.6 Zilucoplan: Ra Pharmaceuticals 102 10.6.1 Product Description 102 10.6.2 Research and Development 102 10.6.2.1 Clinical Studies 102 10.6.2.1.1 Phase II 102 10.6.2.1.2 Results of Analysis 102 10.6.3 Product Development Activities 104 10.6.3.1 Technology 104 10.6.3.2 Patent 104 10.7 Myasterix: CuraVac 105 10.7.1 Product Description 105 10.7.2 Research and Development 105 10.7.2.1 Clinical Studies 105 10.7.2.1.1 Phase I/II 105 10.7.2.1.2 Results of Analysis 106 10.7.3 Product Development Activities 106 10.7.3.1 Designation 106 10.7.3.2 Grant 106 11. EARLY STAGE PRODUCTS (PHASE I) 108 11.1 Comparative Analysis 108 11.2 GTP-004: GT Biopharma 108 11.2.1 Product Description 108 11.2.2 Research and Development 108 11.2.2.1 Clinical Studies 108 11.2.2.1.1 Phase I 108 11.2.2.1.2 Results of Analysis 109 11.2.3 Product Development Activities 109 11.2.3.1 Patents 109 12. PRE-CLINICAL AND DISCOVERY STAGE PRODUCTS 111 12.1 Comparative Analysis 111 12.2 ACT-101: Alpha Cancer Technologies 111 12.2.1 Product Description 111 12.2.2 Research and Development 112 12.2.2.1 Pre-clinical Studies 112 12.2.3 Product Development Activities 112 12.2.3.1 Designation 112 12.3 HBN-1 (IV): Hibernaid 113 12.3.1 Product Description 113 12.4 Myasthenia Gravis-Tolerogen: Toleranzia 114 12.4.1 Product Description 114 12.5 Pre-clinical Program: AnTolRx 115 12.5.1 Product Description 115 12.5.2 Product Development Activities 115 12.5.2.1 Financing 115 12.5.2.2 Technology 115 12.6 PRTX-100: Protalex 116 12.6.1 Product Description 116 12.6.2 Research and Development 116 12.6.2.1 Pre-clinical Studies 116 12.6.3 Product Development Activities 116 12.6.3.1 Patent 116 12.7 TOL 3034: Tolerion 117 12.7.1 Product Description 117 12.7.2 Product Development Activities 117 12.7.2.1 Technology 117 12.8 Coversin: Akari Therapeutics 118 12.8.1 Product Description 118 12.8.2 Product Development Activities 119 12.8.2.1 Patent 119 12.8.2.2 Financing 119 12.8.2.3 Merger Agreement 119 12.9 HBN-100: Hibernaid 120 12.9.1 Product Description 120 13. THERAPEUTIC ASSESSMENT 122 13.1 Assessment by Product Type 122 13.2 Assessment by Stage and Product Type 122 13.3 Assessment by Route of Administration 123 13.4 Assessment by Stage and Route of Administration 124 13.5 Assessment by Molecule Type 125 13.6 Assessment by Stage and Molecule Type 126 14. APPROVAL TIMELINES 127 14.1 Approval Timelines for Clinical Products 127 15. ANALYST INSIGHTS 129 16. INACTIVE PRODUCTS 130 16.1 Comparative Analysis 130 16.2 Belimumab: GlaxoSmithKline 130 16.2.1 Product Description 130 16.2.2 Research and Development 131 16.2.2.1 Clinical Studies 131 16.2.2.1.1 Results of Analysis 131 16.3 EN101: Amarin Corporation 133 16.3.1 Product Description 133 16.3.2 Research and Development 133 16.3.2.1 Clinical Studies 133 16.3.2.1.1 Phase IIa 133 16.3.2.1.2 Results of Analysis 133 16.3.3 Product Development Activities 134 16.3.3.1 Designation 134 16.3.3.2 Agreement 134 16.4 Tirasemtiv: Cytokinetics 135 16.4.1 Product Description 135 16.4.2 Research and Development 135 16.4.2.1 Clinical Studies 135 16.4.2.1.1 Phase II 135 16.4.2.1.2 Results of Analysis 135 16.4.3 Product Development Activities 136 16.4.3.1 Collaboration Agreement 136

Figure 1: Total Number of Products in Myasthenia Gravis 27 Figure 2: Products Analysis by Designation 63 Figure 3: Total Number of Marketed and Emerging Products 64 Figure 4: Total Number of Emerging Products in Myasthenia Gravis 78 Figure 5: Late Stage Products (Phase III) 79 Figure 6: Mid Stage Products (Phase II) 92 Figure 7: Early Stage Products (Phase I) 108 Figure 8: Pre-clinical and Discovery Stage Products 111 Figure 9: Assessment by Product Type 122 Figure 10: Assessment by Stage and Product Type 122 Figure 11: Assessment by Route of Administration 123 Figure 12: Assessment by Stage and Route of Administration 124 Figure 13: Assessment by Molecule Type 125 Figure 14: Assessment by Stage and Molecule Type 126 Figure 15: Approval Timelines for Clinical Products 127 Figure 16: Inactive Products 130Table 1: Clinical subtypes of MG 16 Table 2: Features of different subtypes of MG 17 Table 3: Osserman und Genkins classification of myasthenia gravis, modified by the MGFA/Task Force 37 Table 4: Definition of QMG score 38 Table 5: MG-MMT scores 39 Table 6: Proposed Diagnostic Criteria for Myasthenia Gravis 54 Table 7: Products Analysis by Technology 62 Table 8: Products Analysis by Designation 63 Table 9: Total Number of Marketed and Emerging Products 64 Table 10: List of Marketed Products 65 Table 11: Clinical Trial Description: Eculizumab 69 Table 12: General Description: Eculizumab 70 Table 13: Clinical Trial Description: Tacrolimus 73 Table 14: General Description: Tacrolimus 73 Table 15: Clinical Trial Description: Venoglobulin IH 5% 75 Table 16: General Description: Venoglobulin IH 5% 75 Table 17: Total Number of Emerging Products in Myasthenia Gravis 78 Table 18: Late Stage Products (Phase III) 79 Table 19: Clinical Trial Description: Amifampridine Phosphate 82 Table 20: General Description: Amifampridine Phosphate 83 Table 21: Clinical Trial Description: Efgartigimod 86 Table 22: General Description: Efgartigimod 87 Table 23: Clinical Trial Description: Hizentra 88 Table 24: General Description: Human normal immunoglobulin G (IgG) 89 Table 25: Clinical Trial Description: IGIV-C 90 Table 26: General Description: IGIV-C 90 Table 27: Mid Stage Products (Phase II) 92 Table 28: Clinical Trial Description: Iscalimab 95 Table 29: General Description: Iscalimab 95 Table 30: Clinical Trial Description: M281 97 Table 31: General Description: M281 97 Table 32: Clinical Trial Description: Rozanolixizumab 99 Table 33: General Description: Rozanolixizumab 99 Table 34: Clinical Trial Description: RVT-1401 100 Table 35: General Description: RVT-1401 101 Table 36: Clinical Trial Description: Zilucoplan 103 Table 37: General Description: Zilucoplan 104 Table 38: Clinical Trial Description: Myasterix 106 Table 39: General Description: Myasterix 106 Table 40: Early Stage Products (Phase I) 108 Table 41: Clinical Trial Description: GTP-004 109 Table 42: Patents: GTP-004 109 Table 43: General Description: GTP-004 110 Table 44: Pre-clinical and Discovery Stage Products 111 Table 45: General Description: ACT-101 112 Table 46: General Description: HBN-1 (IV) 113 Table 47: General Description: Myasthenia Gravis-Tolerogen 114 Table 48: General Description: Pre-clinical Program 115 Table 49: General Description: PRTX-100 117 Table 50: General Description: TOL 3034 118 Table 51: General Description: Coversin 119 Table 52: General Description: HBN-100 120 Table 53: Assessment by Product Type 122 Table 54: Assessment by Stage and Product Type 123 Table 55: Assessment by Route of Administration 123 Table 56: Assessment by Stage and Route of Administration 124 Table 57: Assessment by Molecule Type 125 Table 58: Assessment by Stage and Molecule Type 126 Table 59: Approval Timelines for Clinical Products 127 Table 60: Inactive Products 130 Table 61: Clinical Trial Description: Belimumab 132 Table 62: General Description: Belimumab 132 Table 63: Clinical Trial Description: EN101 133 Table 64: General Description: EN101 134 Table 65: Clinical Trial Description: Tirasemtiv 136 Table 66: General Description: Tirasemtiv 137

Akari Therapeutics Alexion Pharmaceuticals Alpha Cancer Technologies Amarin Corporation AnTolRx Argenx Astellas Catalyst Pharmaceuticals CSL Behring CuraVac Cytokinetics Grifols Therapeutics GSK GT Biopharma Hibernaid Immunovant (Roivant Sciences) Mitsubishi Tanabe Pharma Corporation Momenta Pharmaceuticals Novartis Protalex Ra Pharmaceuticals Toleranzia Tolerion UCB Pharma