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 Lucerastat for Fabry’s Disease (October 11, 2021)
41 Pegunigalsidase alfa for Fabry’s Disease (October 8, 2021)
42 Miplyffa for Niemann-Pick Disease (June 18, 2021)
43 Pegunigalsidase alfa for Fabry’s Disease (June 2, 2021)
45 Pegunigalsidase alfa for Fabry’s Disease (April 28, 2021)
46 AT-GAA for Pompe Disease (February 11, 2021)
47 AXO-AAV-GM1 for GM1 Gangliosidosis (December 15, 2020)

50 KEY REGULATORY EVENTS
50 World-First For Sanofi ASMD Drug
50 Orphazyme Teeters On The Brink As Arimoclomol EU Filing Is Pulled
50 Pricing Deals Spell Good News For Exkivity & Vimizin In England
51 New EU Filings Include Tibsovo Resubmission, Pegunigalsidase & Daprodustat
51 Gene Therapy Libmeldy Undergoes Cross-Country HTA In Europe
51 Uncertain Future For Orphazyme After Arimoclomol Snub In Europe
52 Sanofi ‘Strongly Disagrees’ With EMA Rejection Of NAS Status For Nexviadyme
52 Rare EU Fast-Track Nod For Sanofi Genzyme’s Olipudase Alfa
53 PRIME: EMA Says Yes To Only Three Of Twenty Hopefuls
53 Orphazyme Wants More Time To Deal With Late-Stage Issues For Arimoclomol In EU
53 Pompe Candidate AT-GAA Accepted For FDA Review
54 Scottish Funding No For Two Orphans As SMC Tries To Catch Up After COVID-19 Backlog
54 Sanofi Challenges EMA’s Refusal Of New Active Substance Status For Nexviadyme
54 Sanofi Nexviazyme Aims To Take Pompe Disease Therapy To Next Level
55 Orphan Drugs Dominate EU Fast-Track Request Decisions In July
55 Sanofi Genzyme’s Treatment For Pompe Disease On Track For EU Approval
56 Orchard To Work On Reversing English Funding Refusal For Libmeldy Gene Therapy
56 Orphazyme Tumbles Back To Earth As FDA Rejects Arimoclomol
56 Chiesi’s Commercial Hopes In US Hit By FDA Letter

58 PROBABILITY OF SUCCESS

59 LICENSING AND ASSET ACQUISITION DEALS
59 Cyclo Therapeutics Announces Collaboration With University of The Witwatersrand
59 Lysogene Licenses Gene Therapy Candidate From Yeda Research
59 Centogene And Insilico Announce Research And Development Collaboration
59 Libmeldy: ‘Significant Discount’ For World’s Most Expensive Drug Secures English Funding
60 Lysogene Terminates Partnership With Sarepta
60 Takeda Will Commercialize JCR’s Hunter Syndrome Drug
60 Takeda Continues Recent Gene Therapy Partnering Spree With Poseida Pact
61 Amicus Spins Out Rare Disease Gene Therapy Pipeline, Raises $200m
61 Asia Deal Watch: CANbridge Licenses Orphan Disease Candidates From Mirum, LogicBio

62 CLINICAL TRIALS
62 Protalix Plans US Resubmission For ERT For Fabry After Positive Phase III Trial Results
62 Sanofi Posts More Positive Olipudase Alfa Data As Approval Decisions Loom
63 Avrobio Plots Plan B After Fabry Disease Gene Therapy Problems
63 Sangamo’s Fabry Gene Therapy May Be A STAAR In The Making
64 Idorsia’s Fabry Drug Flounders In Phase III
64 Denali Sees Some Early Progress With Fusion Protein For Hunter Syndrome

65 BIBLIOGRAPHY

67 APPENDIX

LIST OF FIGURES
17 Figure 1: Relative frequencies of lysosomal storage disorders
58 Figure 2: 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: Lucerastat for Fabry’s Disease (October 11, 2021)
42 Table 9: Pegunigalsidase alfa for Fabry’s Disease (October 8, 2021)
43 Table 10: Miplyffa for Niemann-Pick Disease (June 18, 2021)
44 Table 11: Pegunigalsidase alfa for Fabry’s Disease (June 2, 2021)
45 Table 12: Pegunigalsidase alfa for Fabry’s Disease (April 28, 2021)
46 Table 13: AT-GAA for Pompe Disease (February 11, 2021)
48 Table 14: AXO-AAV-GM1 for GM1 Gangliosidosis (December 15, 2020)