CONTENTS

6 OVERVIEW

7 KEY TAKEAWAYS

8 DISEASE BACKGROUND
8 Definition
8 Subtypes
13 Risk factors
13 Diagnosis

15 TREATMENT
15 Enzyme replacement therapy
15 Hematopoietic stem cell transplantation
16 Substrate reduction therapy
16 Chaperone therapy
16 Gene therapy

17 EPIDEMIOLOGY
17 Lysosomal storage disorders epidemiology

23 MARKETED DRUGS

29 PIPELINE DRUGS

40 RECENT EVENTS AND ANALYST OPINION
40 Miplyffa for Niemann-Pick Disease (June 18, 2021)
41 Pegunigalsidase alfa for Fabry’s Disease (June 2, 2021)
42 Pegunigalsidase alfa for Fabry’s Disease (April 28, 2021)
43 AT-GAA for Pompe Disease (February 11, 2021)
44 AXO-AAV-GM1 for GM1 Gangliosidosis (December 15, 2020)
46 IB1001 for Niemann-Pick Disease (September 30, 2020)
48 Avalglucosidase Alfa for Pompe Disease (June 16, 2020)

51 KEY REGULATORY EVENTS
51 Pompe Candidate AT-GAA Accepted For FDA Review
51 Scottish Funding No For Two Orphans As SMC Tries To Catch Up After COVID-19 Backlog
51 Sanofi Challenges EMA’s Refusal Of New Active Substance Status For Nexviadyme
52 Sanofi Nexviazyme Aims To Take Pompe Disease Therapy To Next Level
52 Orphan Drugs Dominate EU Fast-Track Request Decisions In July
52 Sanofi Genzyme’s Treatment For Pompe Disease On Track For EU Approval
53 Orchard To Work On Reversing English Funding Refusal For Libmeldy Gene Therapy
53 Orphazyme Tumbles Back To Earth As FDA Rejects Arimoclomol
53 Chiesi’s Commercial Hopes In US Hit By FDA Letter
54 Latest Japan Approvals Include World-First For Pabinafusp
54 Latest EU Filings
54 Sanofi Nabs Priority Review For New Pompe Drug
55 Positive On Brineura
55 Gene Therapies Dominate New Crop Of EU PRIME Recipients

56 PROBABILITY OF SUCCESS

57 LICENSING AND ASSET ACQUISITION DEALS
57 Amicus Spins Out Rare Disease Gene Therapy Pipeline, Raises $200m
57 Asia Deal Watch: CANbridge Licenses Orphan Disease Candidates From Mirum, LogicBio

58 CLINICAL TRIALS
58 Denali Sees Some Early Progress With Fusion Protein For Hunter Syndrome
58 Amicus Pompe Disease Combo’s Approvability In Question As Key Trial Misses Mark

59 BIBLIOGRAPHY

61 APPENDIX

LIST OF FIGURES
17 Figure 1: Relative frequencies of lysosomal storage disorders
48 Figure 2: IB1001 for Niemann-Pick Disease (September 30, 2020): Phase II – 201
50 Figure 3: Avalglucosidase Alfa for Pompe Disease (June 16, 2020): Phase III – COMET
56 Figure 4: Probability of success in the inborn errors of metabolism pipeline

LIST OF TABLES
18 Table 1: Prevalence proportions of mucopolysaccharidosis subtypes
19 Table 2: Prevalence proportions of Gaucher disease
20 Table 3: Prevalence proportions of Fabry disease
21 Table 4: Prevalence proportions of Krabbe disease
22 Table 5: Prevalence proportions of Pompe disease
24 Table 6: Marketed drugs for lysosomal storage disorders
30 Table 7: Pipeline drugs for lysosomal storage disorders in the US
40 Table 8: Miplyffa for Niemann-Pick Disease (June 18, 2021)
41 Table 9: Pegunigalsidase alfa for Fabry’s Disease (June 2, 2021)
42 Table 10: Pegunigalsidase alfa for Fabry’s Disease (April 28, 2021)
43 Table 11: AT-GAA for Pompe Disease (February 11, 2021)
45 Table 12: AXO-AAV-GM1 for GM1 Gangliosidosis (December 15, 2020)
46 Table 13: IB1001 for Niemann-Pick Disease (September 30, 2020)
49 Table 14: Avalglucosidase Alfa for Pompe Disease (June 16, 2020)