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 LYS-SAF302 for Mucopolysaccharidosis IIIA (MPS IIIA; Sanfilippo A Syndrome) (November 18, 2022)
42 Lucerastat for Fabry’s Disease (October 11, 2021)
43 Pegunigalsidase alfa for Fabry’s Disease (October 8, 2021)
44 Miplyffa for Niemann-Pick Disease (June 18, 2021)
45 Pegunigalsidase alfa for Fabry’s Disease (June 2, 2021)

48 KEY REGULATORY EVENTS
48 FDA Action On AT-GAA Delayed By China COVID-19 Policy
48 Gene Therapy For Lethal Glycogen Storage Disease Wins EMA PRIME Designation
49 Chiesi Seeks US Debut For Velmanase Alfa
49 Xenpozyme Earns Sanofi A Priority Review Voucher
49 Sanofi’s Xenpozyme Is First Drug Approved For Rare Genetic Disease ASMD
50 NICE Recommends Nexviadyme Despite Uncertainties
50 Sanofi Bags EU Approvals But Fumes At Regulator
51 Sanofi Closes In On A Pair Of Approval Firsts
51 World-First For Sanofi ASMD Drug
51 Orphazyme Teeters On The Brink As Arimoclomol EU Filing Is Pulled
52 Pricing Deals Spell Good News For Exkivity & Vimizin In England
52 New EU Filings Include Tibsovo Resubmission, Pegunigalsidase & Daprodustat
52 Gene Therapy Libmeldy Undergoes Cross-Country HTA In Europe
53 Uncertain Future For Orphazyme After Arimoclomol Snub In Europe

54 PROBABILITY OF SUCCESS

55 LICENSING AND ASSET ACQUISITION DEALS
55 Kyorin To Use CellGenTech’s Platform In Fabry Disease
55 Sio Gene Ends Gene Therapy Collaboration With Umass
55 Orphazyme’s Sorry Story Ends In Fire Sale
56 Abeona Settles For Ultragenyx Deal
56 Orchard Secures New Libmeldy Price In Germany
56 Kriya Therapeutics Acquires Warden Bio
56 Cyclo Therapeutics Announces Collaboration With University of The Witwatersrand
57 Lysogene Licenses Gene Therapy Candidate From Yeda Research
57 Centogene And Insilico Announce Research And Development Collaboration
57 Libmeldy: ‘Significant Discount’ For World’s Most Expensive Drug Secures English Funding
58 Lysogene Terminates Partnership With Sarepta

59 CLINICAL TRIALS
59 Clinical Update From Phase II/III AAVance Study Of LYS-SAF302
59 Protalix Plans US Resubmission For ERT For Fabry After Positive Phase III Trial Results
60 Sanofi Posts More Positive Olipudase Alfa Data As Approval Decisions Loom
60 Avrobio Plots Plan B After Fabry Disease Gene Therapy Problems

62 BIBLIOGRAPHY

64 APPENDIX

LIST OF FIGURES
17 Figure 1: Relative frequencies of lysosomal storage disorders
54 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: LYS-SAF302 for Mucopolysaccharidosis IIIA (MPS IIIA; Sanfilippo A Syndrome) (November 18, 2022)
42 Table 9: Lucerastat for Fabry’s Disease (October 11, 2021)
44 Table 10: Pegunigalsidase alfa for Fabry’s Disease (October 8, 2021)
45 Table 11: Miplyffa for Niemann-Pick Disease (June 18, 2021)
46 Table 12: Pegunigalsidase alfa for Fabry’s Disease (June 2, 2021)