CONTENTS

7 OVERVIEW

8 INTRODUCTION TO GENE THERAPY
8 Datamonitor Healthcare insights and recommendations
8 Gene therapy is the most active modality in regenerative medicine
10 Historically, gene therapy has been riddled with setbacks
10 Gene therapy involves in vivo and ex vivo approaches
11 Bibliography

13 INNOVATIONS IN GENE DELIVERY TECHNOLOGIES
13 Datamonitor Healthcare insights and recommendations
13 Gene therapy is enabled by viral and non-viral methods
21 Bibliography

26 REGULATORY ISSUES
26 Datamonitor Healthcare insights and recommendations
26 Regulatory pathways are providing incentives for gene therapy development
38 Bibliography

41 KEY COMPANIES IN GENE THERAPY
41 Datamonitor Healthcare insights and recommendations
41 Hundreds of companies are involved in gene therapy development
43 REGENXBIO is building its internal pipeline and out-licensing its NAV platform
46 Now owned by Celgene, Juno is pushing ahead with a third-to-market CAR-T
49 Kite Pharma’s cell therapy pipeline will become the foundation of Gilead’s oncology offering
51 CAR-T therapy and directly administered gene therapy are both focuses for Novartis
54 Sarepta targets gene therapies for muscular dystrophies
56 Through collaborations and in-house development, bluebird bio is moving forward with ex vivo gene therapies in multiple diseases
57 Bibliography

60 TRENDS IN APPROVED GENE THERAPIES
60 Datamonitor Healthcare insig
60 A dozen gene therapies are approved worldwide
65 Key gene therapy approvals
68 Bibliography

72 GENE THERAPY PIPELINE TRENDS
72 Datamonitor Healthcare insights and recommendations
72 After plateauing, the gene therapy pipeline is picking up speed
74 The US leads ongoing clinical trial activity in gene therapies
75 Completed gene therapy trials have high success rates
76 Most terminated gene therapy trials are those that were planned but never initiated
77 Both gene therapy and cell and gene therapy approaches are on fairly equal ground
78 Across phases, in vivo and ex vivo therapies are split fairly equally
80 Viral vectors are used more than non-viral vectors for delivery
87 Most gene therapies in development aim to attack rare diseases and cancer
97 Outside of oncology, different diseases emerge in the lead among in vivo and ex vivo therapies
99 Bibliography

100 ONCOLOGY GENE THERAPY TRENDS
100 Datamonitor Healthcare insights and recommendations
100 The majority of gene therapies in the pipeline are for solid tumors
104 CAR therapies are dominant in ex vivo development

108 APPENDIX
108 Scope
108 Methodology

LIST OF FIGURES
9 Figure 1: Gene therapy defined: EMA and FDA definitions
11 Figure 2: Gene therapy delivery approaches, in vivo versus ex vivo
14 Figure 3: Viral and non-viral vectors – advantages and disadvantages
15 Figure 4: Key viral vector types – advantages and disadvantages
27 Figure 5: Product class inclusions in EU and US specialized regenerative medicine regulatory pathways
43 Figure 6: Most active gene therapy companies, by pipeline size
65 Figure 7: Most approved or launched gene therapies are available in Europe
73 Figure 8: Gene therapy pipeline volume, preclinical through pre-registration phase, 1995–2018
74 Figure 9: Gene therapy pipeline volume by phase, 1995–2018
75 Figure 10: Most gene therapy clinical trial activity is in the US
76 Figure 11: Completed gene therapy trials are largely successful; trials by outcomes
77 Figure 12: Top reasons why gene therapy trials are terminated
78 Figure 13: Gene therapy versus cell and gene therapy: breakdown of pipeline
79 Figure 14: Gene therapy pipeline, by in vivo or ex vivo approach and phase
80 Figure 15: Ex vivo gene therapy pipeline, by cell type and phase
81 Figure 16: Viral vector delivery is most prominent in gene therapy
82 Figure 17: In viral vector gene delivery, AAVs are most often used
83 Figure 18: Viral vector gene therapy pipeline, by vector and phase
84 Figure 19: In vivo gene therapies, viral versus non-viral delivery
85 Figure 20: In vivo gene therapies, by vector type
86 Figure 21: Ex vivo gene therapies, viral versus non-viral delivery
87 Figure 22: Ex vivo gene therapies, by vector type
88 Figure 23: Rare disease and oncology dominate gene therapy drug development
89 Figure 24: Gene therapy pipeline, by therapy area and phase
90 Figure 25: Cancer and non-oncologic rare disease diverge in ex vivo versus in vivo delivery
91 Figure 26: Viral vectors are largely used in both cancer and rare non-oncologic gene therapies
92 Figure 27: Other therapy areas are mostly being addressed by in vivo therapy
93 Figure 28: Viral vectors are also most prominent in other therapy areas
94 Figure 29: In vivo gene therapies, by therapy area and viral vector
95 Figure 30: Ex vivo gene therapies, by therapy area and viral vector
96 Figure 31: Lead molecular targets among in vivo therapies
97 Figure 32: Lead molecular targets among ex vivo therapies
98 Figure 33: Lead indications among non-oncology in vivo therapies
99 Figure 34: Lead indications among non-oncology ex vivo therapies
101 Figure 35: Oncology gene therapies are mainly addressing solid tumors
102 Figure 36: Developers focus on ex vivo therapy in cancer
103 Figure 37: Tumor type distribution between in vivo and ex vivo therapies in oncology
104 Figure 38: Top 20 oncology indications in gene therapy development, by approach
105 Figure 39: CAR therapies dominate: oncology ex vivo gene therapies, by approach
106 Figure 40: Ex vivo oncology approaches, by phase
107 Figure 41: Autologous versus allogeneic delivery in oncology ex vivo CAR therapies

LIST OF TABLES
33 Table 1: Summary of FDA guidance on cell and gene therapy
45 Table 2: REGENXBIO gene therapy pipeline
48 Table 3: Juno Therapeutics/Celgene gene therapy pipeline
51 Table 4: Kite Pharma/Gilead gene therapy pipeline
53 Table 5: Novartis gene therapy pipeline
55 Table 6: Sarepta gene therapy pipeline
57 Table 7: Bluebird bio gene therapy pipeline
62 Table 8: Approved gene therapies worldwide, as of Q1 2019