A Phase I/II, Multicenter, Open-Label, Single-Dose, Dose-Ranging Study to Assess the Safety and Tolerability of ST-920, an AAV2/6 Human Alpha Galactosidase A Gene Therapy, in Subjects With Fabry Disease (STAAR)
Phase: PHASE1
Conditions: Fabry Disease
Sponsor: Sangamo Therapeutics

Sangamo Therapeutics, Inc. 
 
 
 
 
 
 
 
 
 
ST-920-201                     
CONFIDENTIAL 
Clinical Study Protocol Amendment 7 08June2022 
Page 1 of 92 
 
 
 
 
 
 
 
Clinical Study Protocol 
 
A Phase I/II, Multicenter, Open-Label, Single-Dose, Dose-Ranging 
Study to Assess the Safety and Tolerability of ST-920, an AAV2/6 
Human Alpha Galactosidase A Gene Therapy in Subjects with 
Fabry Disease 
 
 
 
 
 
 
 
 
Protocol Number: ST-920-201 
BB-IND: 18733 
EudraCT: 2019-000667-24 
Sponsor: Sangamo Therapeutics, Inc. 
7000 Marina Blvd. 
Brisbane, CA 94005 
(628) 252-7545 
 

Sangamo Therapeutics, Inc. 
 
 
 
 
 
 
 
 
 
ST-920-201                     
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Clinical Study Protocol Amendment 7 08June2022 
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Clinical Study Protocol 
A Phase I/II, Multicenter, Open-Label, Single-Dose, Dose-Ranging 
Study to Assess the Safety and Tolerability of ST-920, an AAV2/6 
Human Alpha Galactosidase A Gene Therapy in Subjects with 
Fabry Disease 
Protocol Number: ST-920-201 
BB-IND: 18733 
EudraCT: 2019-000667-24 
Sponsor: Sangamo Therapeutics, Inc. 
7000 Marina Blvd. 
Brisbane, CA 94005 
+1 628 252 7545  
Medical Monitor:  Cristobal Passalacqua, M.D. 
Phone: +1 917 322 9524  
CPassalacqua@sangamo.com 
Original Version: December 12, 2018 
Amendment 1: March 01, 2019 
Amendment 2: July 02, 2019 
Amendment 3: December 20, 2019 
Amendment 4: February 20, 2020 
Amendment 5: October 26, 2020 
Amendment 6: February 11, 2021 
Amendment 7:  June 08, 2022 
PROPERTY OF SANGAMO THERAPEUTICS, INC. 
Confidential and Proprietary 
This document contains confidential and proprietary information. It is intended solely for the use 
of the Investigator, Co-Investigators, staff, appropriate institutional review boards or ethical 
committees, and other required regulatory bodies. The information in this document may not be 
disclosed, divulged, or published externally without written approval from Sangamo 
Therapeutics, Inc. 
This study will be conducted in compliance with the protocol, the International Conference on 
Harmonisation (ICH) Guidelines, Good Clinical Practices, and applicable regulatory 
requirements, including the U.S. Code of Federal Regulations. 

Sangamo Therapeutics, Inc. 
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Sangamo Therapeutics, Inc. 
 
 
Clinical Approval Signature Page 
 
 
 
 
Protocol Number: ST-920-201 
BB-IND: 18733 
EudraCT: 2019-000667-24 
Protocol Title: A Phase I/II, Multicenter, Open-Label, Single-
Dose, Dose-Ranging Study to Assess the 
Safety and Tolerability of ST-920, an AAV2/6 
Human Alpha Galactosidase A Gene Therapy 
in Subjects with Fabry Disease 
 
 
 
 
 
 
 
__________________________________               _______________________________ 
Cristobal Passalacqua, M.D. 
Date 
Medical Monitor 
Senior Medical Director, Clinical Sciences 
Sangamo Therapeutics, Inc. 
 
 
 
 
 
 
 
__________________________________               _______________________________ 
Bettina Cockroft, M.D., M.B.A 
Date 
Protocol Review Committee Chairperson 
Senior Vice President & Chief Medical Officer 
Sangamo Therapeutics, Inc. 
 
 
6/8/2022 | 10:48 PDT
6/8/2022 | 08:45 PDT

Sangamo Therapeutics, Inc. 
ST-920-201 
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Clinical Study Protocol Amendment 7 08June2022 
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Sangamo Therapeutics, Inc. 
 
 
Investigator Agreement Page 
 
 
 
Protocol Number: ST-920-201 
BB-IND: 18733 
EudraCT: 2019-000667-24 
Protocol Title: A Phase I/II, Multicenter, Open-Label, Single-
Dose, Dose-Ranging Study to Assess the 
Safety and Tolerability of ST-920, an AAV2/6 
Human Alpha Galactosidase A Gene Therapy 
in Subjects with Fabry Disease 
 
 
 
 
I have read all pages of this clinical study protocol for which Sangamo Therapeutics, Inc. is the 
Sponsor. I agree to conduct the study as outlined in the protocol, and to comply with all terms 
and conditions set out therein. I confirm that I will conduct the study in accordance with ICH 
guidelines and applicable local regulations. I will ensure that Sub-Investigator(s) and other 
relevant members of my staff have access to copies of this protocol and the ICH guidelines to 
enable them to work in accordance with the provisions of these documents. 
 
 
___________________________________ 
________________ 
Investigator Signature  
  
 
 
 
 
 
Date 
 
 
___________________________________ 
 
Investigator Printed Name 
  
 
 
 
 
 
 
 
 
___________________________________ 
 
Site Name 
 
 
  
 
 
 
 
 
 
 
 
________________________________________________________________________ 
 
Site Address 
 
 

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TABLE OF CONTENTS 
CLINICAL STUDY PROTOCOL .............................................................................................. 2 
CLINICAL APPROVAL SIGNATURE PAGE ........................................................................ 3 
INVESTIGATOR AGREEMENT PAGE .................................................................................. 4 
TABLE OF CONTENTS ............................................................................................................. 5 
LIST OF FIGURES ...................................................................................................................... 8 
LIST OF TABLES ........................................................................................................................ 8 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS .............................................. 9 
PROTOCOL SYNOPSIS ........................................................................................................... 12 
1. 
INTRODUCTION............................................................................................................... 26 
1.1 
Fabry disease ............................................................................................................................. 26 
1.2 
ST-920 Molecular Design and Construction ............................................................................. 27 
1.3 
Nonclinical Studies .................................................................................................................... 28 
1.3.1 
Pharmacology ........................................................................................................................ 28 
1.3.1.1 
In Vitro Pharmacology ................................................................................................. 28 
1.3.1.2 
In Vivo Pharmacology Studies ...................................................................................... 29 
1.3.2 
Pharmacokinetics .................................................................................................................. 31 
1.3.3 
Toxicology ............................................................................................................................ 32 
1.3.4 
Nonclinical Conclusion ......................................................................................................... 32 
1.4 
Clinical Experience with AAV Gene Therapy and AAV2/6 Serotype ..................................... 33 
1.5 
Rationale for ST-920 Dose Selection ........................................................................................ 33 
1.6 
Targeted Patient Population ....................................................................................................... 34 
1.7 
Benefit-Risk Assessment and Study Hypothesis ....................................................................... 34 
1.7.1 
Vertical and Horizontal Transmission ................................................................................... 35 
1.7.2 
Off-Target Effects ................................................................................................................. 35 
1.7.3 
Humoral Immune Response to AAV .................................................................................... 35 
1.7.4 
Development of Neutralising Anti-Human α-Gal A Antibodies ........................................... 36 
1.7.5 
Vector-induced Hepatitis and Loss of α-Gal A Expression .................................................. 36 
1.7.6 
Transduction of Extra-Hepatic Tissues ................................................................................. 36 
1.7.7 
Corticosteroids to Suppress Immune Hepatitis ..................................................................... 36 
1.7.8 
Insertional Mutagenesis and/or Tumorigenesis ..................................................................... 36 
1.7.9 
Exposure to Supraphysiological Levels of α-Gal A .............................................................. 37 
1.7.10 Risks of Kidney Biopsy......................................................................................................... 37 
1.7.11 Risks of Skin Biopsy ............................................................................................................. 37 
1.7.11.1 
Risks of Incisional Skin Biopsy.................................................................................... 38 
1.7.11.2 
Risks of Punch Biopsy .................................................................................................. 38 
1.7.12 Risks of Liver Biopsy ............................................................................................................ 38 
1.7.13 Risks Associated with DNA Impurities ................................................................................ 38 
1.7.13 Risks Associated with Replication Competent AAV ............................................................ 39 
2. 
STUDY OBJECTIVES AND ENDPOINTS ..................................................................... 40 
2.1 
Objectives and Endpoints .......................................................................................................... 40 
3 
STUDY DESIGN ................................................................................................................. 42 
3.1 
Overview and Rationale ............................................................................................................ 42 
3.2 
Screening Period ........................................................................................................................ 46 
3.3 
Baseline Period .......................................................................................................................... 47 
3.4 
Treatment Period and Dose Escalation Rules ............................................................................ 47 
3.5 
Study Stopping Rules ................................................................................................................ 49 

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3.6 
Enzyme Replacement Therapy Withdrawal (any time after Week 4) ....................................... 50 
3.6.1 
ERT Withdrawal Monitoring ................................................................................................ 51 
3.6.2 
ERT Withdrawal Follow-Up ................................................................................................. 51 
3.7 
End of Study Visit and Long-Term Follow-up Study ............................................................... 52 
4. 
SUBJECT SELECTION .................................................................................................... 52 
4.1 
Inclusion Criteria ....................................................................................................................... 52 
4.2 
Exclusion Criteria ...................................................................................................................... 54 
5. 
INFORMED CONSENT .................................................................................................... 55 
6 
STUDY ASSESSMENTS AND PROCEDURES ............................................................. 55 
6.1 
Demographic/Medical History Assessments ............................................................................. 56 
6.1.1 
Medical History ..................................................................................................................... 56 
6.1.2 
Demographics ....................................................................................................................... 56 
6.1.3 
Fabry Gene Sequencing ........................................................................................................ 57 
6.1.4 
Infectious Disease Screening ................................................................................................ 57 
6.1.5 
Neutralizing Antibodies to AAV6 and Immune Response to α-Gal A ................................. 57 
6.1.6 
Concomitant Medications ..................................................................................................... 57 
6.1.6.1 
Vaccines ....................................................................................................................... 57 
6.1.7 
ERT Clinical Assessment ...................................................................................................... 58 
6.1.8 
ERT Administration Log ....................................................................................................... 58 
6.1.9 
Diagnostic α-Gal A Activity ................................................................................................. 58 
6.2 
Safety/Tolerability Assessments ................................................................................................ 58 
6.2.1 
Physical Examination ............................................................................................................ 58 
6.2.2 
Vital Signs ............................................................................................................................. 58 
6.2.3 
Clinical Laboratory ............................................................................................................... 59 
6.2.4 
Adverse Events ...................................................................................................................... 59 
6.2.5 
Liver Panel ............................................................................................................................ 59 
6.2.6 
12-Lead Electrocardiogram ................................................................................................... 59 
6.2.7 
Echocardiogram .................................................................................................................... 59 
6.2.8 
Magnetic Resonance Imaging (MRI) of Liver ...................................................................... 60 
6.2.9 
Circulating AFP Level .......................................................................................................... 60 
6.2.10 Vector Genome Polymerase Chain Reaction ........................................................................ 60 
6.2.11 COVID-19 Assessments ....................................................................................................... 60 
6.2.12 Pregnancy Testing ................................................................................................................. 61 
6.3 
Pharmacodynamic Assessments ................................................................................................ 61 
6.3.1 
α-Gal A Testing in Blood ...................................................................................................... 61 
6.3.2 
Gb3 Testing ........................................................................................................................... 61 
6.3.3 
Lyso-Gb3 Testing .................................................................................................................. 61 
6.4 
Fabry Disease Clinical Impact Assessments ............................................................................. 61 
6.4.1 
Glomerular Filtration Rate, and Total Protein and Albumin to Creatinine Ratios ................ 61 
6.4.2 
Kidney biopsy ....................................................................................................................... 62 
6.4.3 
Cardiac MRI .......................................................................................................................... 62 
6.4.4 
Cardiac Biomarkers ............................................................................................................... 62 
6.4.5 
Minnesota Living With Heart Failure Questionnaire (MLHF-Q) Summary Score .............. 62 
6.4.6 
Skin Biopsy ........................................................................................................................... 63 
6.4.7 
Pain Assessments: Frequency of Pain Medication Use and Short Form Brief Pain Inventory .  
 
 ............................................................................................................................................... 63 
6.4.8 
Quality of Life ....................................................................................................................... 63 
6.4.9 
Gastrointestinal Symptoms Rating Scale .............................................................................. 63 
6.4.10 Mainz Severity Score Index (MSSI) ..................................................................................... 63 
6.4.11 Pulmonary Function Tests ..................................................................................................... 64 

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6.4.12 Audiologic Evaluation .......................................................................................................... 64 
6.5 
Immunogenicity ......................................................................................................................... 64 
6.6 
Future Research ......................................................................................................................... 64 
7 
INVESTIGATIONAL PRODUCT AND OTHER STUDY MEDICATIONS .............. 64 
7.1 
ST-920 ....................................................................................................................................... 64 
7.1.1 
Inventory, Storage, and Handling of the Drug Product ......................................................... 65 
7.1.2 
ST-920 Administration .......................................................................................................... 65 
7.1.3 
Precautions ............................................................................................................................ 65 
7.1.4 
Dose Modifications ............................................................................................................... 66 
7.2 
Concomitant Medication and Supportive Care .......................................................................... 66 
8 
SAFETY AND POTENTIAL RISKS ............................................................................... 66 
9 
SAFETY MONITORING AND ADVERSE EVENTS ................................................... 67 
9.1 
Definitions ................................................................................................................................. 67 
9.1.1 
Adverse Event ....................................................................................................................... 67 
9.1.2 
Serious Adverse Event .......................................................................................................... 67 
9.1.3 
Suspected Unexpected Serious Adverse Reaction ................................................................ 68 
9.2 
Adverse Event Reporting Period ............................................................................................... 68 
9.3 
Recording of an Adverse Event ................................................................................................. 68 
9.4 
Serious Adverse Event Reporting .............................................................................................. 69 
9.5 
Suspected Unexpected Serious Adverse Reaction Reporting Obligations ................................ 70 
9.6 
Pregnancy Reporting ................................................................................................................. 70 
9.7 
Overdose Reporting ................................................................................................................... 71 
10 SUBJECT WITHDRAWAL/DISCONTINUATION, AND SAFETY MONITORING 
COMMITTEE ............................................................................................................................. 71 
10.1 
Subject Withdrawal and Discontinuation from Study ............................................................... 71 
10.2 
Safety Monitoring and Mitigation Plan ..................................................................................... 71 
10.3 
Safety Monitoring Committee ................................................................................................... 72 
11 STATISTICAL ANALYSES ............................................................................................. 73 
11.1 
Determination of Sample Size ................................................................................................... 73 
11.2 
Statistical Analyses .................................................................................................................... 73 
11.2.1 Analysis of the Conduct of the Study .................................................................................... 73 
11.2.2 Primary Safety Analyses ....................................................................................................... 73 
11.2.3 Secondary Analyses .............................................................................................................. 74 
11.2.4 Exploratory Analyses ............................................................................................................ 74 
12 REFERENCES .................................................................................................................... 76 
APPENDIX 1: SCHEDULE OF EVENTS ............................................................................... 78 
APPENDIX 2: ERT WITHDRAWAL SCHEDULE OF EVENTS ....................................... 82 
APPENDIX 3: CORTICOSTEROID REGIMEN ................................................................... 83 
APPENDIX 4: INSTRUCTION FOR LIVER BIOPSY SAMPLE COLLECTION AND 
TISSUE PREPARATION .......................................................................................................... 84 
APPENDIX 5: INVESTIGATOR OBLIGATIONS ................................................................ 85 
APPENDIX 6: ADMINISTRATIVE CONSIDERATIONS ................................................... 87 
APPENDIX 7: COVID-19 GUIDANCE: SCREENING ASSESSMENTS AND REMOTE 
VISITS ......................................................................................................................................... 90 
APPENDIX 8: REMOTE VISITS ............................................................................................. 92 

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LIST OF FIGURES 
 
FIGURE 1: 
SCHEMATIC OF THE ST-920 HGLA AAV CASSETTE ................................................. 28 
FIGURE 2: 
SCHEMA OF STUDY ENROLLMENT: DOSE ESCALATION AND EXPANSION ................... 44 
FIGURE 3: 
SCHEMATIC OF COVID-19 INFECTION TESTING REQUIREMENTS .............................. 91 
 
 
LIST OF TABLES 
 
TABLE 1: 
DOSE BY COHORT ...................................................................................................... 48 
TABLE 2: 
CLINICAL LABORATORY TESTS .................................................................................. 59 
 
 

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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
α-Gal A 
Alpha-galactosidase A 
AAV 
Adeno-associated virus 
ACE 
Angiotensin converting enzyme 
AE 
Adverse event 
AFP 
Alpha fetoprotein  
ALP 
Alkaline phosphatase 
ALT 
Alanine transaminase 
ApoE 
Apolipoprotein E 
ARB 
Angiotensin receptor blocker 
AST 
Aspartate transaminase 
BPI 
Brief Pain Inventory 
BSC 
BioSafety Committee 
CCoA 
Clinical Certificate of Analysis 
cDNA 
Complementary deoxyribonucleic acid 
CMR 
Cardiovascular magnetic resonance 
CRF 
Case report form 
CTCAE 
Common Terminology Criteria for Adverse Events 
ddPCR 
Droplet digital polymerase chain reaction 
DNA 
Deoxyribonucleic acid 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
ECHO 
Echocardiogram 
eGFR 
Estimated glomerular filtration rate 
EMA 
European Medicines Agency 
EOS 
End of study 
ERT 
Enzyme replacement therapy 
ETV 
Early termination visit 
FDA 
Food and Drug Administration 
Gb3 
Globotriaosylceramide 
GC 
Genome copy 
GFR 
Glomerular filtration rate 
GGT 
Gamma-glutamyl transferase  
GI 
Gastrointestinal 
GLA 
The gene Galactosidase alpha 
GLAKO 
GLA knockout 
GLAKO/Gb3Stg GLA knockout with overexpression of Gb3 synthase 
GLP 
Good laboratory practice 
hAAT 
Human α-1-antitrypsin 
HAV 
Hepatitis A virus 
HBV 
Hepatitis B virus 
HCC 
Hepatocellular carcinoma 
HCV 
Hepatitis C virus 
HEENT 
Head, eyes, ears, nose, and throat 

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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS (CONT.) 
hGLA 
Human GLA  
HIV 
Human immunodeficiency virus 
IATA 
International Air Transport Association 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent ethics committee 
IND 
Investigational New Drug 
IRB 
Institutional review board 
IUD 
Intrauterine device 
IUS 
Intrauterine hormone-releasing system 
IV 
Intravenous  
LDH 
Lactate dehydrogenase 
LGE 
Late gadolinium enhancement 
LVH 
Left ventricular hypertrophy 
LVMI 
Left ventricular mass index 
Lyso-Gb3 
Globotriaosylsphingosine 
LTFU 
Long-term follow-up 
MedDRA 
Medical Dictionary for Regulatory Activities 
MHRA 
Medicines and Healthcare products Regulatory Agency 
MLHF-Q 
Minnesota Living With Heart Failure Questionnaire 
MPS 
Mucopolysaccharidosis 
MRI 
Magnetic resonance imaging 
mRNA 
Messenger RNA 
MSSI 
Mainz Severity Score Index 
NASH 
Non-alcoholic steatohepatitis 
NHP 
Non-human primate 
NIH 
National Institutes of Health 
NOAEL 
No-observed-adverse-effect level 
NT-proBNP 
N-terminal pro-hormone B-type natriuretic peptide 
NYHA 
New York Heart Association  
OHR 
Office for Human Research 
PBS 
Phosphate buffered saline 
PCR 
Polymerase chain reaction 
PFT 
Pulmonary function test 
QOL 
Quality of life 
qPCR 
Quantitative polymerase chain reaction 
RNA 
Ribonucleic acid 
RSI 
Reference safety information 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
Sf9/rBV 
Sf9 insect cell/recombinant baculovirus 
SFN 
Small fiber neuropathy 
SMC 
Safety Monitoring Committee 
ST-920PC 
ST-920 parent construct 

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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS (CONT.) 
SUSAR 
Suspected unexpected serious adverse reaction 
TB 
Tuberculosis 
TEAE 
Treatment-emergent adverse event 
UACR 
Urine albumin to creatinine ratio 
ULN 
Upper limit of normal 
UPCR 
Urine protein to creatinine ratio  
vg 
Vector genome 
WHV 
Woodchuck hepatitis virus 
WPRE 
Woodchuck hepatitis virus posttranscriptional regulatory element 
WT 
Wild type 

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PROTOCOL SYNOPSIS 
ST-920-201 Study Protocol Synopsis 
A Phase I/II, Multicenter, Open-Label, Single-Dose, Dose-Ranging Study to Assess the Safety and 
Tolerability of ST-920, an AAV2/6 Human Alpha Galactosidase A Gene Therapy in Subjects with 
Fabry Disease 
Sponsor 
Sangamo Therapeutics, Inc. 
Investigational 
Product 
ST-920 is an adeno-associated virus (AAV) 2/6 vector that encodes a human alpha 
galactosidase A (α-Gal A; hGLA) cDNA. 
Study Sites 
Approximately 20 to 30 sites worldwide 
Study Design 
Multicenter, open-label, single dose, dose-ranging study 
Study 
Rationale 
Fabry disease is an X-linked lysosomal storage disease caused by mutations in the GLA 
gene, which encodes the lysosomal enzyme alpha galactosidase A (α-Gal A). Deficiency 
of α-Gal A activity results in the progressive, systemic accumulation of its primary 
substrate, globotriaosylceramide (Gb3) and its deacetylated soluble form, 
globotriaosylsphingosine (lyso-Gb3). Long-term accumulation of these substrates leads to 
renal, cardiac, and/or cerebrovascular disease, with reduced life expectancy. Depending 
on the mutation and residual α-Gal A enzyme level, the disease presents as classical 
early-onset Fabry disease in childhood/adolescence or as an attenuated (adult) form later 
in life. 
In both classical and adult forms, the current standard of care is enzyme replacement 
therapy (ERT) using recombinant α-Gal A. Infusion of recombinant α-Gal A into the 
bloodstream allows transfer to secondary tissues via mannose-6-phosphate receptor-
mediated uptake (cross-correction). However, the short half-life of the recombinant 
α-Gal A (<1 hour in plasma) used in ERT necessitates a lifetime of infusions, with 
associated risk of infusion-related reactions. In addition, a significant percentage of 
patients eventually generate antibodies to the recombinant enzyme, which may impact the 
activity of the ERT enzyme, which consequently may not clear all substrate from organs 
such as the kidneys.   
Recombinant α-Gal A products with longer half-lives are being developed which may be 
administered less frequently. However, it is anticipated that these will still require long-
term administration with associated risk of infusion-related reactions, and that α-Gal A 
levels will still fluctuate significantly over time. Thus, there is a need for alternative 
therapies that address the unmet needs in Fabry disease. 
Gene therapy with AAV vectors has shown great promise in both preclinical and clinical 
trials to efficiently and safely deliver therapeutic transgenes to the liver, with reports of 
stable levels of transgene expression out to at least eight years for hemophilia B. 

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The proposed study uses ST-920, a recombinant AAV2/6 vector encoding the cDNA for 
human α-Gal A. The α-Gal A produced by this cDNA has an identical amino acid 
sequence to the native enzyme, and also to recombinant α-Gal A, an approved ERT. The 
ST-920 construct encodes a liver-specific promoter, the human α-1-antitrypsin (hAAT) 
promoter and includes liver-specific regulatory elements.  In addition, AAV2/6 exhibits 
liver tropism thus providing the potential for long-term hepatic production of α-Gal A in 
Fabry disease subjects. Studies of ST-920 in a Fabry disease mouse model administered 
AAV2/6 encoding hGLA cDNA by intravenous (IV) injection show generation of 
therapeutic circulating levels of α-Gal A. The one-time treatment with ST-920 minimizes 
the risk of infusion-related reactions which may be associated with biweekly ERT. The 
goal of ST-920 is to provide stable, long-term production of α-Gal A at therapeutic levels 
in patients with Fabry disease. Importantly, the constant production of α-Gal A in humans 
should enable reduction and potentially clearance of Fabry disease substrates Gb3 and 
lyso-Gb3.  
Objectives 
and Endpoints 
Objectives 
Endpoints 
Primary 
• To assess safety and 
tolerability of ST-920 
• 
Incidence of treatment-emergent adverse 
events (TEAEs) 
Additional safety evaluations will include: 
o Routine hematology, chemistry, and liver 
tests, vital signs, electrocardiogram (ECG) 
and echocardiogram (ECHO) 
o Serial alpha fetoprotein (AFP) testing and 
magnetic resonance imaging (MRI) of liver 
(or equivalent imaging modality) to monitor 
for liver mass 
Secondary 
• To assess α-Gal A activity 
and the presence of its 
substrates in plasma over 
time 
• Change from baseline at specific time points 
over the 1-year study period in: 
o α-Gal A activity in plasma 
o Gb3 and lyso-Gb3 levels in plasma 
• To assess impact of ST-920 
on ERT administration 
required for subjects on 
ERT  
• Change from baseline at specific time points 
over the 1-year study period in: 
o Frequency of ERT infusion 
• To assess the impact of 
ST-920 on renal function  
• Change from baseline at specific time points 
over the 1-year study period in: 
o Estimated glomerular filtration rate (eGFR) 
using the CKD-EPI formula 
• To assess the impact of 
ST-920 on cardiac function 
and left ventricular 
hypertrophy 
• Change from baseline at specific time points 
over the 1-year study period in: 
o Ejection fraction, global longitudinal strain, 
left ventricular mass index (LVMI), left 
ventricular systolic function measured by 
cardiac magnetic resonance imaging (CMR) 

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• To evaluate ST-920 vector 
DNA shedding over time 
• ST-920 vector clearance measured by level of 
vector genome in blood (plasma), saliva, urine, 
stool, and semen (if applicable) 
Exploratory 
 
• To assess clinical impact of 
ST-920 on Fabry disease 
• Change from baseline at specific time points 
over the 1-year study period in: 
o Late gadolinium enhancement (LGE), 
native myocardial T1 values and T2 
mapping measured by cardiac MRI (CMR) 
o High sensitivity troponin T, N-terminal 
pro-hormone B type natriuretic peptide 
(NT-proBNP) and other cardiac biomarkers  
o Minnesota Living With Heart Failure 
Questionnaire (MLHF-Q) summary score  
o Urine protein to creatinine ratio (UPCR) 
and urine albumin to creatinine ratio 
(UACR) 
o Biomarkers of renal function in urine 
o Neuropathic pain measured by the Brief 
Pain Inventory (BPI) 
o Frequency of pain medication use 
o Gastrointestinal (GI) symptoms measured 
by the GI symptoms rating scale 
o Mainz Severity Score Index (MSSI) 
o Quality of life (QOL) patient-reported 
outcome measured by the SF-36 
questionnaire 
o Pulmonary function 
o Audiologic function  
• To assess α-Gal A activity 
over time in skin  
• Change from baseline at specific time points 
over the 1-year study period in: 
o α-Gal A activity measured in skin  
• To assess the presence of 
Gb3 inclusion levels in skin 
in ERT-naïve and ERT-
pseudo-naïve subjects 
(defined as not having 
received ERT treatment 
during the 6 months prior to 
baseline) and selected 
subjects previously on 
migalastat 
• Change from baseline at specific time points 
over the 1-year study period in: 
o Gb3 inclusion levels measured in skin in 
ERT-naïve and ERT-pseudo-naïve subjects 
and selected subjects previously on 
migalastat 
 
• To assess the presence of 
α-Gal A substrates in urine 
for all subjects over time  
• Change from baseline at specific time points 
over the 1-year study period in: 
o Gb3 and lyso-Gb3 levels in urine for all 
subjects over time 

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• To assess immune response 
to AAV2/6  
• Measurement of antibodies to AAV2/6  
• Assessment of cell-mediated immune response 
to AAV2/6 
• To assess immune response 
to α-Gal A  
• Measurement of immune response to α-Gal A  
• To assess the impact of 
ST-920 on Gb3 inclusion in 
the kidney (via kidney 
biopsy) in ERT-naïve and 
ERT-pseudo-naïve subjects 
and selected subjects 
previously on migalastat 
• Percent reduction from baseline at Week 24: Gb3 
inclusion in the kidney (assessed by kidney 
biopsy) in ERT-naïve and ERT-pseudo-naïve 
subjects and selected subjects previously on 
migalastat 
Study 
Population 
Adult male and female subjects who are ≥ 18 years of age with a documented diagnosis 
of Fabry disease based on the established criteria for Fabry disease. 
Number of 
Subjects 
Up to 48 subjects will be enrolled in this study. 
Inclusion & 
Exclusion 
Criteria 
Inclusion Criteria 
1.  ≥18 years of age 
2. Signed, written informed consent  
3. Diagnosis of Fabry disease 
4. One or more of the following symptoms: i) cornea verticillata, ii) acroparesthesia, iii) 
anhidrosis, iv) angiokeratoma  
5. Subjects who are on ERT or are ERT-naïve or are ERT-pseudo-naïve (defined as not 
having received ERT treatment during the 6 months prior to baseline). For subjects 
receiving ERT, ERT must have been administered at a stable dose and regimen for at 
least 6 months (defined as not having missed more than 3 doses of ERT during the 6 
months prior to consent). 
6. Subjects on migalastat (Galafold™) must agree to withdraw migalastat prior to 
Baseline and, if non-responder to migalastat (based on clinical and/or biochemical 
assessments), undergo an incisional skin biopsy and kidney biopsy. 
7. Male subjects must refrain from sperm donation from the time of ST-920 
administration until a minimum of 3 consecutive semen samples are negative for 
AAV2/6 after administration of ST-920 and a minimum of 90 days after ST-920 
administration. 
8. Female subjects must refrain from egg donation from the time of ST-920 
administration until all the samples are negative for AAV2/6 after administration of 
ST-920. 
9. Subjects must agree to use a highly effective form of contraception from the time of 
ST-920 administration until a minimum of 90 days after ST-920 administration and, 
for male subjects, a minimum of 3 consecutive semen samples are negative for 
AAV2/6 after administration of ST-920. Highly effective birth control methods 
include: 
a. a documented vasectomy or permanent sterilization  

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b. condom  
c. combined (estrogen and progestogen containing) hormonal contraception (oral, 
intravaginal or transdermal) 
d. progestogen-only hormonal contraception associated with inhibition of ovulation 
(oral, injectable or implantable) 
e. intrauterine device (IUD) 
f. intrauterine hormone-releasing system (IUS) 
g. sexual abstinence is acceptable only as true abstinence and when in line with the 
preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, 
ovulation, symptothermal, post-ovulation methods) and withdrawal are not 
acceptable methods of contraception 
10. Subject must be fully vaccinated (as per the Centers for Disease Control and 
Prevention (CDC) definition in the US and as per local guidelines in other countries) 
for COVID-19 at least one month prior to dosing 
Additional inclusion criteria for: 
Cohorts 1-4b:  
11. Male subjects with classical Fabry disease as defined by < 5% α-Gal A activity in either 
plasma or leukocytes.  
a. For male subjects who do not have documented diagnostic α-Gal A activity, a 
blood sample will be taken to measure α-Gal A activity (in plasma). For subjects 
who are on ERT, this blood draw must be taken at least 13 days after their last 
ERT infusion (trough). 
b. If the subject’s α-Gal A activity is > 5% and the subject is on ERT, this level of 
enzyme activity may be due to residual α-Gal A activity from the last ERT 
infusion. In this case, the diagnosis of classical Fabry disease may be confirmed 
if the following three criteria are fulfilled:  
i. two or more documented symptomatic characteristics outlined in inclusion 
criterion #4. If there is documented clustered periumbilical angiokeratoma, 
this symptom alone is sufficient as it is a pathognomonic sign of classical 
Fabry disease;  
ii. a mutation that is indicative of classical Fabry (i.e. listed in a database, such 
as http://dbfgp.org); and 
iii. the α-Gal A activity at trough is below the lower limit of the normal range of 
the assay. 
Female cohort:  
12. Female subjects with a documented mutation that is indicative of classical Fabry (i.e., 
listed in a database, such as http://dbfgp.org) and treatment (ERT and/or migalastat) is 
clinically indicated 
Renal and Cardiac cohorts:  
13. Symptomatic Fabry disease defined for male subjects by <30% α-Gal A activity in 
either plasma or leukocytes and for female subjects based on genetic test results 
consistent with Fabry pathogenic mutation, or in the case of novel mutations a first-
degree male family member with Fabry disease with the same mutation 
AND 
Renal cohort: 
14. Screening eGFR value between 40-90 mL/min/1.73 m²  

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15. Linear negative eGFR slope (estimated from at least 3 serum creatinine values within 
18 months, including the value obtained during screening visit) of ≥ 2 mL/min/1.73 
m²/year  
Cardiac cohort: 
16. Left ventricular hypertrophy (LVH) in 2D echocardiography or CMR defined as an 
end diastolic septum and posterior wall thickness ≥12 mm with no other explanation 
for LVH, OR presentation with cardiac changes indicative of disease progression 
such as decreased global longitudinal strain on 2D strain echocardiography or low 
native T1 mapping on CMR 
Exclusion Criteria 
1. Positive neutralizing antibodies to AAV6  
2. Intercurrent illness expected to impair evaluation of safety or efficacy during the 
observation period of the study  
3. eGFR <40 mL/min/1.73m2 
4. Active infection with hepatitis A virus (HAV ribonucleic acid [RNA] positive), active 
or occult hepatitis B virus infection (positive HBV-DNA or anti-HBc positive), active 
infection with hepatitis C virus (HCV RNA positive), infection with the human 
immunodeficiency virus (HIV) as measured by quantitative polymerase chain reaction 
(qPCR), or active or latent infection with tuberculosis (TB) measured by quantiferon 
test 
5. Breastfeeding at screening or breastfeeding during required period of contraception 
6. History of liver disease such as clinically significant steatosis, fibrosis, non-alcoholic 
steatohepatitis (NASH) and cirrhosis, biliary disease within 6 months of informed 
consent; except for Gilbert’s syndrome 
7. Elevated circulating serum AFP  
8. For subjects receiving ERT, recent or recurrent hypersensitivity reaction manifested by 
significant infusion reaction to ERT treatment within 6 months prior to consent 
9. One or more of the following: 
a. Albumin ≤ 3.5 g/dL  
b. Total bilirubin > upper limit of normal (ULN) and direct bilirubin ≥ 0.5 mg/dL 
c. Alkaline phosphatase (ALP) > 2.0 x ULN 
d. Alanine aminotransferase (ALT) > 1.5 x ULN  
10. Current or history of systemic IV or oral immunomodulatory agents, or biologics or 
steroid use in the past 6 months prior to consent (topical and inhaled treatment are 
allowed, [e.g., for asthma or eczema]). Occasional use of systemic steroid may be 
allowed based on discussion and agreement with the Medical Monitor. 
11. Contraindication to use of corticosteroids  
12. History of malignancy, except for non-melanoma skin cancer and localized prostate 
cancer treated with curative intent 
13. Recent history of alcohol or substance abuse. The use of marijuana may be considered 
on an individual basis with discussion and agreement from the Medical Monitor.  
14. Participation in investigational interventional drug or medical device study throughout 
the duration of this study and within the last 3 months prior to consent (with the 
exception of implantable loop recorders as in the RaILRoAD trial) 
15. Prior treatment with a gene therapy product 

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16. Known hypersensitivity to components of ST-920 formulation 
17. Any other reason that, in the opinion of the Site Investigator or Medical Monitor, would 
render the subject unsuitable for participation in the study, including but not limited to 
risk of COVID-19 infection 
Additional exclusion criteria for: 
Cohorts 1- 4, female and renal cohort: 
18. Subjects who meet New York Heart Association (NYHA) Class III and IV  
Renal cohort:  
19. History of renal dialysis or transplantation 
20. History of acute kidney insufficiency in the 6 months prior to screening 
21. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker 
(ARB) therapy initiated within 4 weeks prior to screening or changed ACE inhibitor or 
ARB dose in the 4 weeks prior to screening 
22. Urine protein to creatinine ratio (UPCR) > 0.5 g/g who are not being treated with an 
ACE inhibitor or ARB 
Cardiac cohort: 
23. Significant cardiac fibrosis defined as having more than 3 segments full thickness of 
late gadolinium enhancement on CMR 
24. Any contraindications to CMR as per local hospital/institution guidelines 
25. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker 
(ARB) therapy initiated within 4 weeks prior to screening or changed ACE inhibitor or 
ARB dose in the 4 weeks prior to screening  
26. NHYA Class IV 
Concomitant 
Medications 
All medications are permitted with limited exceptions. The use of potentially hepatotoxic 
agents including herbal supplements may be allowed based on discussion and agreement 
with the Medical Monitor.   
For subjects receiving ERT, ERT must have been administered at a stable dose and 
regimen (defined as not having missed more than 3 doses of ERT during the 6 months 
prior to consent). Subjects should continue to receive ERT at a stable dose and regimen 
(14 days ± 1 day) during the study as per standard of care unless they undergo ERT 
withdrawal. 
Subjects who are ERT-naïve or ERT pseudo-naïve (defined as not having received ERT 
treatment in the 6 months prior to baseline) may not initiate treatment with ERT during 
the study period, unless dictated by clinical circumstances and following discussion with 
the Sponsor Medical Monitor. Subjects may not initiate treatment with migalastat 
(Galafold™) during the study period. 

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Dose and 
Rationale for 
Dose Selection 
The doses being evaluated were selected based on preclinical studies in mice and 
monkeys and cumulative safety data from ongoing Sangamo clinical studies that use the 
same AAV 2/6. Several dose levels may need to be studied to identify a safe and tolerable 
therapeutic dose. The dose levels for this dose escalation study are as noted in Table 1. 
Dose escalation to the next dose level will be decided by the Safety Monitoring 
Committee (SMC) upon review of safety data from the previous cohort. Other data 
derived from other Sangamo-sponsored clinical trials that use in vivo AAV2/6 based 
therapy may be considered as well, and based on the recommendation of the SMC, which 
will comprise external subject matter experts, the study Medical Monitor, Sponsor’s Drug 
Safety Lead, and Site Investigators as appropriate (as described in the SMC charter). 
From preclinical experiments with ST-920 in a mouse model of Fabry disease, it is 
anticipated that supraphysiological levels of enzymatic activity need to be achieved in the 
blood (at least 8 times the normal enzymatic activity), at steady state, in order to lead to a 
full reduction of substrate accumulation in the main target organs (kidneys and heart).  
In addition, depending on the enzyme activity and safety data of the subjects dosed, the 
SMC may recommend a dose escalation to one of the doses listed in Table 1. 
No dose given to subjects will exceed 5.00E+13 vg/kg (by qPCR) without a substantial 
amendment. 
 
Table 1: Dose by Cohort  
Cohort 
AAV1 Dose (vector genomes [vg]/kg) 
 qPCR2  
1 
0.50E+13  
2 
1.00E+13 or 3.00E+13 
3 
3.00E+13 or 5.00E+13 
4 
5.00E+13  
1AAV = adeno-associated virus, 2quantitative PCR  
 
A droplet digital PCR (ddPCR) test method is being developed to determine the level of 
vector genome (vg) titers for ST-920. The nominal genome copies (vg/mL) are not 
changing; a new method (ddPCR) to evaluate the nominal genome copies is being 
implemented and will replace the qPCR method. Once fully implemented, drug product 
released using the initial qPCR assay or the new ddPCR assay will be used in Study 
ST-920-201. See Section 7 for additional details. 
Treatment 
Plan 
Up to 48 subjects may be enrolled in this overall study. Initially, recruitment will be 
limited to male subjects meeting criteria for inclusion during dose escalation. Once a safe 
and tolerable dose is selected, recruitment will be extended via dose expansion to a 
broader patient population. Once cohort expansion is initiated, subjects will undergo 
assessments which will determine the most appropriate expansion cohort for their 
enrollment.  
During dose escalation, treatment of the first 2 subjects will be staggered so that the 
second subject cannot be infused until the first subject has been observed for at least 
2 weeks. After any 2 subjects in a cohort have been dosed, safety data from these 
2 subjects will be reviewed by the SMC. Dose escalation to the next dose cohort and dose 

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expansion cannot occur until at least 4 weeks of safety data are available after the second 
subject in the preceding cohort has been dosed, and safety data from this cohort has been 
reviewed by the SMC. The SMC will recommend whether it is safe to escalate the dose or 
add subjects to the dose cohort at the same dose level. Once a cohort’s data has been 
reviewed and dose escalation has been endorsed, additional subjects may be infused at 
any time in the same cohort, as per protocol.  
Two male subjects with classical Fabry disease will be dosed in Cohort 1. Following the 
SMC recommendation to dose escalate to Cohort 2, which is subdivided into Cohort 2a 
(subjects who are antibody-positive to α-Gal A) and Cohort 2b (subjects who are 
antibody-negative to α-Gal A), 2 male subjects with classical Fabry disease will be dosed 
and safety data from these 2 subjects will be reviewed by the SMC. After SMC review, 
up to an additional 8 (4 subjects in Cohort 2a and 4 subjects in Cohort 2b) subjects may 
be recruited into Cohort 2 and if dose escalation is recommended, recruitment of subjects 
into Cohort 3 may commence. Dosing may continue in Cohort 2 until all 10 subjects have 
been dosed, unless it is concluded during the SMC review that it is more appropriate to 
dose in Cohort 3 rather than continuing dosing at the Cohort 2 dose level. Dosing in 
Cohort 3 and the remainder of Cohort 2 can be concurrent.   
Following the SMC recommendation to dose escalate to Cohort 3, which is subdivided 
into Cohort 3a (subjects who are antibody-positive to α-Gal A) and Cohort 3b (subjects 
who are antibody-negative to α-Gal A), 2 male subjects with classical Fabry disease will 
be dosed and safety data from these 2 subjects will be reviewed by the SMC. After SMC 
review, up to an additional 8 (4 subjects in Cohort 3a and 4 subjects in Cohort 3b) 
subjects may be recruited into Cohort 3 and if dose escalation is recommended, 
recruitment of subjects into Cohort 4 may commence. Dosing may continue in Cohort 3 
until all 10 subjects have been dosed, unless it is concluded during the SMC review that it 
is more appropriate to dose in Cohort 4 rather than continuing dosing at the Cohort 3 dose 
level. Dosing in Cohort 4 and the remainder of Cohort 3 can be concurrent.   
Following the SMC recommendation to dose escalate to Cohort 4, which is subdivided 
into Cohort 4a (subjects who are antibody-positive to α-Gal A) and Cohort 4b (subjects 
who are antibody-negative to α-Gal A), 2 male subjects with classical Fabry disease will 
be dosed and safety data from these 2 subjects will be reviewed by the SMC. After SMC 
review, up to an additional 8 subjects may be recruited into Cohort 4. Dosing may 
continue in Cohort 4 until all 10 subjects have been dosed, unless it is concluded during 
the SMC review that it is more appropriate to select a dose for dose expansion. Dosing in 
dose expansion and the remainder of Cohorts 3 and/or 4 can be concurrent.   
The dose considered to be tolerable and safe will be utilized in the dose expansion 
cohorts. After dose escalation has been completed, dose expansion will commence where 
up to 6 subjects will be enrolled into each of the dose expansion cohorts, which include 
patients with classical Fabry disease who are antibody-positive to α-Gal A, patients with 
classical Fabry disease who are antibody-negative to α-Gal A, female patients (female 
cohort) and patients who meet criteria for the renal (renal cohort) and cardiac (cardiac 
cohort) inclusion and exclusion criteria. The dose for the expansion cohorts may be 
reassessed if there are emerging safety considerations. 

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Anti α-Gal A Ab positive cohort:  Up to 6 male subjects with classical Fabry disease 
who are antibody-positive to α-Gal A will be enrolled. 
Anti α-Gal A Ab negative cohort:  Up to 6 male subjects with classical Fabry disease 
who are antibody-negative to α-Gal A will be enrolled. 
Female cohort: Up to 6 female subjects with classical Fabry disease will be enrolled.  
Renal cohort: Up to 6 male or female subjects with symptomatic Fabry disease with a 
linear negative eGFR slope (estimated from at least 3 historical serum creatinine values 
[within 18 months, including the value obtained during screening visit]) of ≥ 
2 mL/min/1.73 m²/year will be enrolled. 
Cardiac cohort: Up to 6 male or female subjects with symptomatic Fabry disease with 
cardiac involvement, defined as either LVH in 2D echocardiography or CMR (end 
diastolic septum and posterior wall thickness ≥ 12 mm) with no other explanation for 
LVH OR cardiac changes indicative of disease progression such as decreased global 
longitudinal strain on 2D strain echocardiography or low native T1 mapping on CMR will 
be enrolled. Subjects who have had a cardiovascular event in the 6-month period before 
screening may be excluded at the discretion of the Investigator. 
For all dose escalation and dose expansion cohorts, subjects who received ERT prior to 
study participation will continue to receive ERT during the study and remain on their 
current dose and regimen per standard of care unless they undergo ERT withdrawal. For 
subjects on ERT, baseline testing of enzyme and substrate levels will be coordinated such 
that samples will be taken on 2 separate occasions in the morning at trough, defined as 
14 days (± 1 day) after the previous ERT infusion. An additional time point will have 
been taken previously during the screening period, so as to have 3 time points to assess 
the residual activity of α-Gal A at trough prior to the gene therapy administration. These 
3 samples must be taken at trough, and preferably at the same time during the day (e.g. in 
the morning) to minimize the impact of non-specific factors on enzyme activity.  
Based on Sangamo’s prior clinical experience with the AAV2/6 vector, an ALT elevation 
(suggestive of an immune reaction to the viral capsid) may be observed. Subjects will be 
closely monitored for ALT elevation throughout the study and the protocol-defined 
treatment (or treatment at the discretion of the Investigator and agreed upon with the 
Medical Monitor) with corticosteroids may be initiated in response. Dose selection and 
guidance are provided in Appendix 3 of the protocol. 
ST-920 will be administered via IV infusion while the subject is in the healthcare facility, 
where the subject will remain for observation for at least 24 hours after completion of the 
ST-920 infusion. During infusion, only light foods such as jello or apple sauce or liquids 
may be consumed. The subject will be discharged when all vital signs are stable and any 
adverse events (AEs) have resolved or the subject is considered stabilized as per 
Investigator judgment.  
Following the infusion of ST-920, study visits will be conducted on Day 8, Weeks 2, 4, 6, 
8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52. The Week 28, 32, 40, 44, and 48 study 
visits have assessments that do not require evaluation at the clinical site, and therefore 

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may be conducted remotely. Assessments for AEs and concomitant medications may be 
conducted remotely over the phone by the study staff. 
Liver tests will be assessed twice weekly during the first 20 weeks after ST-920 infusion, 
then weekly for four weeks (Weeks 21-24), and monthly thereafter to coincide with study 
visits (Weeks 28-52). Liver tests may be conducted remotely and analyzed locally or 
centrally. Blood samples for liver tests will be drawn 2-4 days apart when possible. For 
the first week they will be drawn on Day 2 and 2-4 days later.  Day 8 visit will be the first 
Week 2 blood draw. If there is a need to initiate treatment with corticosteroids because of 
elevated ALT, liver enzymes will continue to be assessed at least twice a week until 
normalization and then per protocol thereafter analyzed locally or centrally. 
Dose 
Escalation 
For the first 2 subjects in each cohort, treatment will be staggered so that each subsequent 
subject will not be infused until the preceding subject has been observed for at least 
2 weeks. After the first 2 subjects, the subsequent subjects in the same dose cohort can be 
infused at any time if the safety data from the first 2 subjects is deemed satisfactory by the 
SMC. 
A decision to dose escalate to the next dose level will not occur until at least 4 weeks after 
the 2 subjects in the preceding cohort have been dosed and the safety data from the 
2 subjects in the prior cohort has been reviewed by the SMC.  
Dosing and dose escalation will be paused if any of the stopping rules are met. In such an 
event, the SMC will be convened and provide recommendations to dose de-escalate, or 
discontinue the study (refer to the Safety Monitoring Committee & Stopping Rules). No 
further dosing of subjects will be performed at that dose level or higher until a substantial 
amendment is submitted to regulatory authorities for review, and the amendment has been 
approved by the site Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) or equivalent. 
Dose 
Expansion 
The dose deemed to be tolerable and safe will be utilized in the expansion cohorts. 
ERT 
Withdrawal 
The ultimate goal of ST-920 treatment is to abrogate the need for ERT by using an 
AAV2/6 vector encoding cDNA for human α-Gal A, resulting in long-term, liver-specific 
expression of α-Gal A in Fabry disease subjects. Subjects who undergo ERT withdrawal 
will be closely monitored for any AEs, vital signs, any changes in safety laboratory 
evaluations and activity of α-Gal A and substrates (Gb3 and lyso-Gb3) compared to 
baseline. 
During dose escalation, ERT withdrawal is at the discretion of the Site Investigator after 
consultation with the Sponsor, and is only to be considered for subjects who are willing 
and meet all of the following criteria: 
• Are ≥ 4 weeks post-administration of ST-920. 
• Are medically stable and can tolerate temporary discontinuation of ERT in the 
judgment of the Site Investigator. 
• Agree to increased safety monitoring and additional lab testing until ERT Withdrawal 
Follow-Up visit (Appendix 2). 

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Initiation of the dose expansion phase of the study assumes that a safe and tolerable dose 
of ST-920 has been achieved. At this point, ERT withdrawal will be implemented for all 
subjects who are in the expansion cohorts and have achieved supraphysiological (above 
normal range) plasma α-Gal A for 8 weeks ± 2 weeks, at the discretion of the investigator. 
ERT withdrawal assumes a complete stop in ERT administration rather than a 
“dose-down” or dose reduction. 
ERT does not need to be restarted after the ERT Withdrawal Follow-Up visit. However, 
ERT may be re-initiated at any time based on clinical circumstances or at the judgment of 
the Site Investigator. After ERT withdrawal, in order to assess whether a subject has 
received a suboptimal dose, evidence of a lack of response will be primarily based on α-
Gal A activity and lyso-Gb3 substrate levels, which will be tested on a regular basis (refer 
to Appendix 2 for a full list of assessments and schedule of events). Plasma α-Gal A 
activity below the normal range, or plasma lyso-Gb3 levels, will be part of the criteria 
used by the Site Investigators to determine lack of response (and need for reinstitution of 
ERT). 
Study 
Duration 
The duration of study participation will be up to 84 weeks for each subject divided into up 
to 8 weeks for screening, up to 24 weeks for baseline, and 52 weeks follow-up after 
dosing. Accrual is planned for 48 months. Subjects will be encouraged to participate in an 
additional separate long-term follow-up study (of 4 years) for a total of at least 5 years 
from infusion.  
Safety 
Monitoring 
Committee & 
Stopping 
Rules 
An SMC with appropriate medical and scientific expertise was appointed to provide 
safety oversight for the study. The SMC is comprised of external subject matter experts, 
the study Medical Monitor, Sponsor’s Drug Safety Lead, Study Biostatistician, and Site 
Investigators as appropriate. The SMC will periodically meet during the study and 
provide recommendations to the Sponsor concerning dosing. The SMC will also convene 
at any time if an emergent safety issue emerges during the study or one of the stopping 
rules are met. These include:   
• Any one Grade 3 or higher AE with at least a reasonable possibility of a causal 
relationship to the investigational product 
• Serious adverse event (SAE) with at least a reasonable possibility of a causal 
relationship to the investigational product 
• Death of a subject 
• Development of a malignancy, with the exception of non-melanoma skin cancers and 
localized prostate cancer treated with curative intent 
The study may also be stopped for any of the following reasons: 
• Sponsor, in consultation with the SMC or Regulatory Agency, decides for any reason 
that subject safety may be compromised by continuing the study. 
• Sponsor decides to discontinue the development of the investigational product, 
ST-920. 
All data will be evaluated to determine whether changes should be made to the study or if 
accrual should be continued or halted. If stopping criteria are met, no further dosing of 
subjects will be performed at that dose level or higher until a substantial amendment is 
submitted to regulatory authorities for review, and the amendment has been approved by 

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the site Institutional Review Board (IRB)/Independent Ethics Committee (IEC) or 
equivalent. 
Relevant data from other trials sponsored by Sangamo may be shared with the SMC to 
expand the clinical experience, particularly as it relates to safety and dose, and such data 
can be used by the SMC to inform its recommendations for the present study.  
The SMC may also recommend changes to the dose and enrollment of cohorts based on 
cumulative safety data from this and other Sangamo sponsored clinical trials that use in 
vivo AAV2/6 based therapy. When no further enrolling or dosing decisions are required 
of the SMC, the SMC will no longer meet on a regular basis. The Sponsor will continue 
to review the subject safety data on an ongoing basis. 
Safety 
Monitoring 
and 
Mitigation 
Plan 
Elevation of liver enzymes has been observed in other trials using AAV 2/6. Therefore, 
liver tests (aspartate transaminase [AST], alanine transaminase [ALT], bilirubin, alkaline 
phosphatase [ALP], and gamma-glutamyl transferase [GGT]) will be monitored closely 
throughout the study. 
These will be performed twice weekly during the first 20 weeks after ST-920 infusion, 
weekly for four weeks (Weeks 21-24), and then monthly thereafter to coincide with study 
visits (Weeks 28-52) in all subjects, and may be conducted remotely. 
If there is a need to initiate corticosteroid treatment as a result of elevated liver enzymes, 
liver enzymes will continue to be assessed at least twice a week until normalization and 
then per protocol thereafter analyzed locally or centrally. 
Sample Size 
This is a Phase I/II dose-escalation study with up to 48 subjects. The sample size for this 
study was not based on statistical considerations but is considered sufficient to provide a 
preliminary assessment of the safety and tolerability of ST-920 in subjects with Fabry 
disease.  
Subjects who prematurely discontinue the study prior to 52 weeks of study follow-up 
(i.e., subjects who were enrolled but not dosed, were lost to follow-up, or discontinued 
prematurely for another reason) may be replaced with another subject at the discretion of 
the Sponsor. 
Statistical 
Analyses 
The primary objective of this study is to evaluate the safety and tolerability of ST-920. 
All statistical summaries will be descriptive in nature. All subjects who receive any 
portion of the ST-920 infusion will be included in the analyses. All analyses, summaries, 
and listing will be generated using SAS version 9.4 or later. Further analysis details will 
be provided in the statistical analysis plan (SAP). 
Primary Safety Analyses 
TEAEs will be summarized overall and by dose and cohort. For each subject, the 
maximum reported severity of each AE will be used in the summaries by severity grade. 
In addition, summaries of all SAEs and AEs related to study treatment will be provided.  
For other safety evaluations, data will be summarized for each time point. Change from 
baseline values may be calculated for continuous parameters and summarized by time 
point. Shift-tables may also be constructed for selected parameters. 

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Secondary Analyses 
At each sampling time point, the actual value and the change from baseline for α-Gal A, 
Gb3 and lyso-Gb3, eGFR, ejection fraction, global longitudinal strain, LVMI and left 
ventricular systolic function will be summarized by dose and cohort using descriptive 
statistics and plotted over the 1-year study period by dose and cohort. Similar summaries 
will also be provided for ERT naïve/ERT pseudo-naïve subjects, and separately for ERT 
subjects (migalastat subjects will be grouped with either the ERT naïve/ERT 
pseudo-naïve subjects, or with the ERT subject, based on the clinical response determined 
by the Investigator at Screening). 
For subjects who undergo ERT withdrawal, changes from pre- to post- ERT withdrawal 
in the frequency and dose of ERT infusions will be evaluated and summarized using 
annualized total dose and number of infusions. Duration of ERT withdrawal may also be 
analyzed. 
Clearance of ST-920 measured by vector genomes in the different samples (plasma, 
saliva, urine, stool, and semen, if applicable) will be summarized over time by dose and 
cohort. 
Exploratory Analyses 
Data permitting, the following exploratory endpoints and their change from baseline 
summaries by dose and cohort will be provided at each sampling time point over the 
1-year study period: 
• LGE, native myocardial T1 values and T2 mapping measured by CMR 
• High-sensitivity troponin T, NT-proBNP and other cardiac biomarkers  
• MLHF-Q summary score  
• UPCR and UACR 
• Biomarkers of renal function in urine 
• Neuropathic pain measured by the BPI 
• Frequency of pain medication use 
• GI symptoms measured by the GI symptoms rating scale 
• MSSI 
• QOL patient-reported outcome measured by the SF-36 questionnaire 
• α-Gal A activity measured in skin  
• Gb3 inclusion levels measured in skin in ERT-naïve and ERT-pseudo-naïve subjects 
and selected subjects previously on migalastat  
• Gb3 and lyso-Gb3 levels in urine for all subjects over time 
• Pulmonary function over time 
• Audiologic function over time 
Data permitting, summaries of percent reduction from baseline at Week 24 by dose and 
cohort will be provided for:  
• Gb3 inclusion in the kidney (assessed by kidney biopsy) in ERT-naïve and 
ERT-pseudo-naïve subjects and selected subjects previously on migalastat 
Summaries by dose and cohort will be provided for the following exploratory endpoints at 
each sampling time point: 
• Measurement of antibodies to AAV2/6  
• Assessment of cell-mediated immune response to AAV2/6 
• Measurement of immune response to α-Gal A  

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1. 
INTRODUCTION 
1.1 
Fabry disease 
Fabry disease is an X-linked lysosomal storage disease caused by mutations in the GLA gene, 
which encodes the lysosomal enzyme alpha galactosidase A (α-Gal A). Deficiency of α-Gal A 
activity results in the progressive, systemic accumulation of its primary substrate, 
globotriaosylceramide (Gb3), and its deacetylated soluble form, globotriaosylsphingosine 
(lyso-Gb3). Long-term accumulation of these substrates leads to renal, cardiac and/or 
cerebrovascular disease, with reduced life expectancy. Depending on the mutation and residual 
α-Gal A enzyme level, the disease presents as classical early-onset Fabry disease in 
childhood/adolescence or as an attenuated (adult) form later in life. Classical Fabry disease 
occurs when residual enzyme activity is <5% (Arends et al. 2017) and typically occurs in males. 
Early symptoms may include periodic acroparesthesia, angiokeratomas, corneal and lenticular 
opacities, progressive renal insufficiency, cardiac disease, and cerebrovascular events. The 
attenuated or adult form of Fabry disease commonly involves only one organ system, usually 
cardiac or renal.  
 
In both classical and adult forms, the current standard of care is enzyme replacement therapy 
(ERT) using recombinant α-Gal A, or chaperone therapy, which is available only for patients 
whose mutations are amenable to it. Infusion of recombinant α-Gal A into the bloodstream 
allows transfer to secondary tissues via mannose-6-phosphate receptor-mediated uptake 
(cross-correction). However, the short half-life of the recombinant α-Gal A used in ERT 
(approximately 1 hour in plasma) (Clarke et al. 2007) necessitates a lifetime of frequent 
infusions, with associated risk of infusion-related reactions in a significant proportion of patients 
(Clarke et al. 2007), some of which are severe. In addition, a significant percentage of patients 
eventually generate antibodies to the recombinant enzyme, which may impact the activity of the 
ERT enzyme, which consequently may not clear all substrate from organs such as the kidneys 
(Linthorst et al. 2004).  
 
Recombinant α-Gal A products with longer half-lives are being developed which may be 
administered less frequently. However, it is anticipated that these will still require long-term 
administration with associated risk of infusion-related reactions, and that α-Gal A levels will still 
fluctuate significantly over time. Thus, there is a need for alternative therapies that address the 
unmet needs in Fabry disease. 
 
Gene therapy with adeno-associated viral (AAV) vectors has shown great promise in both 
preclinical and clinical trials to efficiently and safely deliver therapeutic transgenes to the liver, 
with reports of stable levels of transgene expression at least out to eight years for hemophilia B  
(Nathwani et al. 2018; Muhuri et al. 2022).  
 
The proposed study uses ST-920, a recombinant AAV2/6 vector encoding the cDNA for human 
α-Gal A. The α-Gal A produced by this cDNA has an identical amino acid sequence to the native 
enzyme, and also to recombinant α-Gal A, an approved ERT. The ST-920 vector encodes a liver 
specific promoter, and AAV2/6 exhibits liver tropism thus providing the potential for long-term 
and stable hepatic production of α-Gal A in Fabry disease subjects. Studies in a Fabry disease 
mouse model administered IV with AAV2/6 encoding hGLA cDNA show generation of 

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therapeutic levels (over 300-fold wild type) of α-Gal A. The one-time treatment with ST-920 
minimizes the incidence of infusion-related reactions which may be associated with biweekly 
ERT. Production of therapeutic levels of α-Gal A in humans could enable reduction and 
potentially clearance of Fabry disease substrates Gb3 and lyso-Gb3 and may reduce the risk of 
antibody development to the enzyme produced because of constant production of the enzyme, 
rather than peak and trough seen with ERT. The goal of ST-920 is to provide stable, long-term 
production of α-Gal A at therapeutic levels in subjects with Fabry disease. Importantly, the 
constant production of α-Gal A in humans should enable reduction and potentially clearance of 
Fabry disease substrates Gb3 and lyso-Gb3. 
 
1.2 
ST-920 Molecular Design and Construction 
ST-920 consists of the ST-920 hGLA expression cassette (3321 bp) that includes liver-specific 
regulatory elements that drive expression of a hGLA transgene (Figure 1). The hGLA transgene 
is under the control of an enhancer and hepatic control region from the human apolipoprotein E 
(ApoE) gene and the human α-1-antitrypsin (hAAT) promoter. The ApoE enhancer and hAAT 
promoter are specifically and highly active in the liver, the intended target tissue, but inactive in 
non-liver cell and tissue types, thus preventing hGLA expression and activity in non-target 
tissues.  A modified chimeric intron (HBB-IGG) has been added as this sequence has been 
shown to increase transgene expression. The hGLA transgene comprises a codon-optimized 
hGLA construct, including the native GLA signal peptide; the secreted α-Gal A has the same 
amino acid sequence as the native protein and an approved recombinant α-Gal A enzyme 
replacement therapy (agalsidase beta, Fabrazyme®)  
 
ST-920 contains a mutated form of the woodchuck hepatitis virus (WHV) posttranscriptional 
regulatory element (WPREmut6). WPREmut6 is a 592-bp DNA sequence containing the 
promoter region of WHV X protein followed by a truncated form of the X protein itself (WPRE, 
Zufferey et al. 1999) with point mutations in the putative promoter region and start codon of the 
X protein open reading frame to prevent X protein expression (mut6, Zanta-Boussif et al. 2009). 
The poly A sequence is a derivative of the bovine growth hormone polyadenylation signal. The 
addition of the WPREmut6 element led to increased α-Gal A protein production. Indeed, greater 
potency was noted with ST-920 compared to ST-920 parent construct (ST-920PC, that lacks the 
WPREmut6 element). 
 
The ST-920 AAV vector is packaged with capsid serotype AAV2/6 using a 
Sf9 insect cell / recombinant baculovirus (Sf9/rBV) expression system. 
 
 

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Figure 1: 
Schematic of the ST-920 hGLA AAV Cassette 
Transcription of the human GLA transgene is driven from a liver-specific regulatory element consisting of an 
enhancer, promoter and intron. The enhancer is a derivative of the human ApoE gene enhancer and hepatic control 
region, the promoter is the human α-1-antitrypsin promoter, and the intron is the chimeric HBB-IGG intron. The 
WPREmut6 is derived from the promoter region and a truncated form of the woodchuck hepatitis virus X protein. 
The poly adenylation signal is derived from the bovine growth hormone polyA sequence. SP refers to the 
endogenous hGLA signal peptide. Sizes of the various elements are shown as is the entire size of the cassette 
(3321 bp). 
 
1.3 
Nonclinical Studies 
The nonclinical evaluation included 3 in vitro and 10 in vivo studies. The in vivo studies were 
conducted as components of combination endpoint studies that included pharmacology, 
pharmacokinetics, AAV vector biodistribution and/or vector shedding, and toxicology. Mouse 
and cynomolgus monkey were selected as relevant species for evaluation. In addition, two mouse 
models of Fabry disease were used to assess potential changes on the biomarkers of the disease.  
 
Some changes implemented during the nonclinical development were the:  
1) introduction of ST-920 which harbors a WPREmut6 element in the cDNA but is otherwise 
identical to ST-920PC. Based on improvements in α-Gal A activity related to the WPREmut6 
element, ST-920 was selected for clinical development. 
2) use of Sf9 cells instead of HEK293 for manufacturing.  
 
These changes were bridged in vitro and in vivo using head to head comparison studies. 
 
Details of all studies are provided in the Investigator Brochure. 
 
1.3.1 
Pharmacology  
1.3.1.1 
In Vitro Pharmacology  
The pharmacological activity of ST-920 and ST-920PC was evaluated in vitro using various 
mouse, cynomolgus monkey and human primary cell and cell lines system.  
 
α-Gal A activity was measured in cell supernatant and hGLA messenger ribonucleic acid 
(mRNA) levels were assessed in cell pellets.  ST-920 and ST-920PC were either produced in 

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HEK293 cells or in a Sf9 baculovirus cell system. Several doses were evaluated (up to 
multiplicities of infection of 2.00E+6 vg/cell). 
 
Overall, dose-dependent, high levels of secreted and pharmacologically active α-Gal A were 
measured. α-Gal A cellular uptake via the mannose-6 -phosphate receptor pathway was 
confirmed. ST-920 had similar or higher activity when compared to ST-920PC (up to 2-fold 
more activity in cynomolgus primary hepatocytes, up to 4-fold more activity in human primary 
hepatocytes and 7-fold more activity in human HepG2 cells), supporting the selection of ST-920 
for clinical development. 
 
The observed lower potency in the Sf9/rBV material can likely be attributed to the differences in 
the VP1:VP2:VP3 capsid ratios for AAV produced in mammalian cells (such as HEK293) and 
insect cells (such as Sf9). 
 
1.3.1.2 
In Vivo Pharmacology Studies 
1.3.1.2.1 Studies Conducted in 2 Mouse Models of Fabry Disease  
Early nonclinical studies evaluated ST-920PC. The pharmacodynamic activity of ST-920PC was 
evaluated in 2 mouse models of Fabry disease including the GLA knockout (GLAKO) and 
GLAKO/Gb3Stg (GLA knockout with overexpression of Gb3 synthase) mouse models, due to 
similarities in natural history between these mice and the human disease. In both models, Gb3 
and lyso-Gb3 (α-Gal A substrates) accumulate in plasma and organs/tissues. In addition, 
GLAKO/Gb3Stg mice display a renal phenotype similar to that seen in patients. 
 
The mice received an IV dose administration of ST-920PC at levels ranging from 2.00E+11 to 
5.00E+13 vg/kg. The animals were monitored for 2 to 3 months. Material was either produced in 
HEK293 cells or in a Sf9 insect cell/rBV expression system.  
 
Overall, in both models, dose-dependent, sustained, supraphysiological levels of plasma human 
(h)GLA activity were measured. Supraphysiological levels of hGLA activity were also achieved 
in the liver, heart and kidney along with a reduction in the tissue levels of disease substrates, Gb3 
and lyso-Gb3.  
 
In GLAKO animals given 5.00E+13 vg/kg dose levels (Sf9 insect cells, comparable to clinical 
material), plasma hGLA activity was up to 700-fold the normal levels. Gb3 levels were generally 
reduced by 80% or more in the liver, heart and kidney compared to untreated animals. 
 
However, in GLAKO/Gb3Stg that display a renal phenotype, this reduction in Gb3 did not lead 
to an improvement in pathology of this organ. Presumably, by the time of dosing (2 to 3 months 
of age), these animals had already developed severe kidney damage. 
 
1.3.1.2.2 Studies Conducted in Wild Type Mice 
Human α-Gal A enzyme expression/activity in plasma and liver was evaluated in five studies 
conducted in wild type (WT) mice. 
 

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Male and female C57BL/6 mice were given an IV dose administration of ST-920 or ST-920PC 
at levels ranging from 5.00E+11 to 1.50E+14 vg/kg. The animals were monitored for up to 90 
days. The material was produced in HEK293 cells or Sf9/rBV insect cells. 
 
In summary, hGLA protein was detected in liver of these mice via a human GLA-specific 
western blot. Dose-related supraphysiological levels of plasma α-Gal A activity (endogenous 
plus human α-Gal A activity) were measured by Day 7 and maintained to Day 90. 
 
Consistent with in vitro data, plasma and liver α-Gal A levels were higher in animals 
administered ST-920PC manufactured in HEK293 cell versus Sf9 cell system (up to 21-fold 
higher). 
 
In addition, the presence of the WPREmut6 element in ST-920 led to greater plasma and liver 
α-Gal A activity compared to ST-920PC. Animals administered ST-920 or ST-920PC at the 
2.00E+12 vg/kg dose level had plasma α-Gal A levels up to 70- and 11-fold of normal, 
respectively. In these animals, liver α-Gal A activity was up to 35- and 8-fold that of normal, 
respectively. 
 
ST-920 and ST-920PC pharmacological activity was evaluated in a head-to-head comparison 
study using Sf9/rBV material. Greater activity was noted with ST-920, up to 7-fold higher 
α-Gal A plasma and liver activity compared to ST-920PC at the 5.00E+13 vg/kg dose level. 
 
In a Good Laboratory Practice (GLP) 3-month toxicology study, plasma α-Gal A activity 
increased in a dose-dependent manner in WT mice treated with ST-920 and remained stable over 
the 3-month study duration. The mean plasma α-Gal A activity was higher (~2- to 5-fold at the 
1.50E+14 vg/kg dose) in male mice compared to female mice, which is consistent with lower 
vector genome copy levels in female mice. The lower level of AAV transduction in female 
mouse liver has been observed in previous Sangamo studies using AAV2/6 vectors and has been 
reported by others (Nietupski et al., 2011; Davidoff et al., 2003). 
 
1.3.1.2.3 Study Conducted in Nonhuman Primates (Cynomolgus Monkeys) 
A GLP 2-month pharmacology and toxicology study was conducted following administration of 
a single IV dose of ST-920PC at 6.00E+12, 1.00E+13, 3.00E+13, or 6.00E+13 vg/kg to male 
cynomolgus monkeys (n=3/group). To mitigate a possible immune response to ST-920PC and/or 
human GLA, animals received rituximab (10 mg/kg; IV) prior to study drug administration and 
methylprednisolone (10 mg/kg; intramuscular) daily throughout the study. An additional group 
received ST-920PC at the highest dose (6.00E+13 vg/kg) but no immunosuppression 
administration. The ST-920PC lot used in this study was manufactured in a GMP clinical 
manufacturing process using the Sf9/rBV cell platform comparable to the manufacturing process 
for the Phase I/II clinical study.  
 
Circulating α-Gal A protein levels and plasma α-Gal A activity were generally detected by 
Day 7, with protein levels and activity peaking between Days 7 and 21, and no clear dose 
response. Animals administered ST-920PC without immunosuppression generally had lower 

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levels of α-Gal A protein and activity than animals administered ST-920PC with 
immunosuppression. The lack of clear dose response and rapid clearance of α-Gal A activity and 
protein levels is likely related to an immune reaction against human α-Gal A in the monkey. 
Despite the reduced levels of human α-Gal A, some animals sustained high levels of human 
α-Gal A (activity and protein). In one high dose animal (6.00E+13 vg/kg, IV) levels of 
193 nmol/hr/mL were measured on Day 56 while levels in vehicle treated animals were 
undetectable (<10 nmol/hr/mL). α-Gal A activity was measured in the liver and spleen tissue of 
all animals at necropsy.  
 
In summary, circulating α-Gal A activity was measured in cynomolgus monkeys following 
administration of ST-920PC. The transient nature of this response in several animals was likely 
related to an expected immune response to the human α-Gal A enzyme (human protein 
administered to an animal).  
 
1.3.2 
Pharmacokinetics 
All 10 in vivo studies conducted in this program included various gene therapy-related 
pharmacokinetics evaluations.   
 
Plasma AAV2/6 pharmacokinetic analysis following ST-920PC IV administration to C57BL/6 
mice and cynomolgus monkeys showed a dose-dependent increase in vector copy numbers. 
Half-life ranged from 19.3 to 31.2 hours for cynomolgus monkeys receiving an 
immunosuppression regimen, 16 hours for cynomolgus monkeys not receiving the 
immunosuppression regimen, and approximately 7 hours in both male and female C57BL/6 
mice. 
 
ST-920 or ST-920PC vector copies were evaluated by quantitative polymerase chain reaction 
(qPCR) in the liver from mouse and monkey studies to gauge liver exposure to test compound 
and/or compare exposure between material manufactured in HEK293 cells at Sangamo or 
Sf9/rBV process at Brammer Bio. Levels of vector copies in the liver increased with dose and 
higher levels were found with HEK293 material compared to Sf9/rBV material. Evaluation of 
vector copies in testes showed no detectable levels in 3-month GLAKO mouse study and very 
low levels in the 2-month monkey study. Evaluation of vector copies in ovaries and testes 
showed low levels in the 3-month C57BL/6 mouse study. 
 
In situ hybridization studies measuring levels of hGLA DNA construct in the liver showed a 
dose-response relationship in mouse and monkey hepatocytes and confirmed transfer of DNA to 
the nuclei. The high dose (5.00E+13 vg/kg) in the mouse yielded a range of 28% to 58% positive 
staining cells, and the high dose (6.00E+13 vg/kg; with immunosuppression) in the monkey 
study yielded a range of 61% to 73% positive staining cells. Another monkey (without 
immunosuppression) yielded 49% positive staining cells. 
 
Samples for vector shedding analysis were evaluated by a qPCR method in the 3-month 
C57BL/6 mouse study and in the 2-month monkey study. There was no measurable amount of 
ST-920 vector at 3 months in any of the urine, semen, and feces samples tested in the mouse 
study. In the monkeys, low levels of hGLA vector were measured in the saliva, urine- and feces 

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of some ST-920 treated animals up to Day 4 (urine) or Day 14 (saliva, feces). At Day 60, no 
hGLA vector levels were detected in these biological fluids. 
 
To supplement ST-920 tissue biodistribution and shedding analysis, data from the Sangamo 
SB-913 IND (BB17006) for mucopolysaccharidosis II (MPS II) were included in ST-920 IND 
since the same AAV6 capsid proteins are present in both compounds and similar manufacturing 
processes were employed. In the GLP 6-month pharmacology and toxicology study evaluating 
SB-913, the following tissues and biological fluids were evaluated for the presence of the vector: 
liver, brain, heart, kidney, lung, spleen, intestines, testes, urine, semen and feces. A qualified 
qPCR analysis method was used. This study showed liver tropism and rapid shedding. No vector 
was detected in semen. 
 
Overall, the PK evaluation confirmed hepatic tropism of ST-920, liver-specific production of 
human α-Gal A, secretion in the blood stream and distribution to secondary tissues. Rapid 
ST-920 clearance from the blood stream and other biological fluids (shedding) was observed.  
No ST-920 vector was detected in semen. 
 
1.3.3 
Toxicology 
Four studies characterized the ST-920/ST-920PC toxicology profile including a 3-month 
single-dose study with ST-920PC in a Fabry disease mouse model (GLAKO mice), a 4-week and 
3-month GLP study with ST-920 in C57BL/6 mice, and a 2-month GLP study with ST-920PC in 
cynomolgus monkeys. All ST-920 and ST-920PC studies administered test compound via a 
single-dose IV administration. 
 
Overall, ST-920 and ST-920PC were well tolerated in a Fabry disease mouse model (GLAKO), 
WT (C56BL/6) mice and cynomolgus monkeys. 
 
In GLAKO mice, there were no adverse findings related to a single IV administration of 
ST-920PC up to 5.00E+13 vg/kg, the highest dose level tested.  In the GLP C57BL/6 mouse 
studies, the no-observed-adverse-effect level (NOAEL) was ≥ 1.50E+14 vg/kg, the highest dose 
tested. In the GLP monkey study, ST-920-related findings were limited to animals that did not 
receive an immunosuppression treatment (6.00E+13 vg/kg). These findings consisted of 
increases in lymphoid cellularity in lymphoid tissues and spleen and were likely consistent with 
an immune response related to hGLA and/ or AAV2/6 administration. In this study, the NOAEL 
was 6.00E+13 vg/kg, with or without the immunosuppressive regimen, the highest dose level 
tested. 
 
1.3.4 
Nonclinical Conclusion 
The studies in the Fabry disease mouse models, WT mice and immunosuppressed cynomolgus 
monkeys, demonstrate the feasibility of safely producing durable and potentially efficacious 
levels of α-Gal A after treatment with ST-920. 
 
No adverse effects were noted in the mice at dose levels up to 1.50E+14 vg/kg and in the 
monkeys at dose levels up to 6.00E+13 vg/kg, the highest dose levels given, respectively. 
 

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Therefore, the clinical starting dose of 0.50E+13 vg/kg is supported by a 30-fold safety dose 
multiple in mice and 12-fold safety dose multiple in monkeys.  
 
Measurable levels of α-Gal A are expected in subjects at a dose of 0.50E+13 vg/kg based on the 
marked pharmacodynamic response noted in the Fabry disease mice given 2.00E+12 vg/kg. 
 
1.4 
Clinical Experience with AAV Gene Therapy and AAV2/6 Serotype 
Several AAV-mediated cDNA gene transfer Phase I and II studies have reported clinical study 
data and are currently enrolling in Phase III studies, using IV administration. Onasemnogene 
abeparvovec-xioi (ZOLGENSMA [AveXis 2019]), an AAV9-based gene therapy treatment, is 
approved in the United States for pediatric patients ≤ 2 years with spinal muscular atrophy with 
bi-allelic mutations in the survival motor neuron 1 (SMN1) and has been found to cause 
aminotransferase (aspartate transaminase [AST]/alanine transaminase [ALT]) elevations. An 
AAV2-based gene therapy product (LUXTURNA [Bennett et al. 2016]), administered sub-
retinally, was recently approved for the treatment of subjects with confirmed biallelic RPE65 
mutation-associated retinal dystrophy.  
 
In all studies, mild immune reactions were observed after gene therapy. In all the hemophilia 
studies reported to date, where the gene therapy is administered via the intravenous route, 
AAV-associated elevation of liver enzymes have been observed at vector doses ranging from 
5.00E+11 vg/kg to 6.00E+13 vg/kg, with variable amount of losses in factor protein expression 
(Manno et al. 2006, Nathwani et al. 2014). Based on Sangamo’s prior clinical experience with 
AAV2/6 vector, an ALT elevation (suggestive of an immune reaction to the viral capsid) may be 
observed. Subjects will be closely monitored for ALT elevation (Appendix 1) throughout the 
study and the protocol-defined treatment (or treatment at the discretion of the Investigator and 
agreed upon with the Medical Monitor) with corticosteroids may be initiated in response. Dose 
selection and guidance are provided in Appendix 3 of the protocol. 
 
As of the data cut on 14 February 2022, six male patients with classic Fabry disease had been 
dosed in study ST-920-201: 2 patients in Cohort 1 (dose 0.50E+13 vg/kg), 2 patients in Cohort 2 
(dose 1.00E+13 vg/kg) and 2 patients in Cohort 3 (dose 3.00E+13 vg/kg). Eleven treatment-
related AEs, all mild, were reported: Cohort 1 Subject 1 anemia, thrombocytosis, rash; Cohort 2 
Subject 1 fever (twice); Cohort 3 Subject 1 fever, frequent bowel movements, abdominal pain, 
fatigue, headache, and myalgia. No treatment-related serious AEs were reported. No subject 
experienced liver enzyme elevations requiring steroid treatment (for further details, refer to the 
Investigator Brochure). 
 
1.5 
Rationale for ST-920 Dose Selection 
The rationale for ST-920 dose selection was based on: 
i. 
Nonclinical pharmacology and safety studies administering AAV2/6 at IV doses ranging 
from 0.50E+13 to 1.50E+14 vg/kg to mice and cynomolgus monkeys with ST-920PC 
(Sangamo Studies TX17-GLA-019 and TX17-GLA-020) and ST-920 (Sangamo Studies 
TX18-GLA-031, TX18-GLA-032, and TX19-GLA-050) resulting in pharmacodynamic 
activity at the lowest dose tested and no adverse events (AEs) related to administration up 

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to the highest dose tested. These studies included concomitant assessments of the 
pharmacology, PK/biodistribution and toxicology. 
ii. 
Cumulative safety data from similar ongoing clinical studies that use the same AAV2/6 
(ClinicalTrials.gov Identifiers: NCT03041324, NCT02702115, and NCT03061201). 
iii. 
Administration of a safe and potentially active starting dose. 
 
Based on the nonclinical safety and pharmacodynamic mouse data, the proposed clinical dose 
range is 0.50E+13 to 5.00E+13 vg/kg, with a starting dose of 0.50E+13 vg/kg. The doses 
proposed were well tolerated in other Sangamo clinical studies. 
 
1.6 
Targeted Patient Population 
Subjects who satisfy all inclusion/exclusion criteria will be enrolled into one of the 4 treatment 
dose cohorts. The targeted patient population of this study will be male and female subjects ≥18 
years of age with a documented diagnosis of Fabry disease (Arends et al. 2017). Cohorts 1, 2, 3, 
and 4 include males with classical Fabry disease defined by plasma and/or leukocyte α-Gal A 
activity and one or more characteristics of classical Fabry disease among cornea verticillata, 
acroparesthesia, anhidrosis and angiokeratoma. Female cohort includes females with classical 
Fabry defined as a documented GLA mutation and one or more characteristics of classical Fabry 
disease among cornea verticillata, acroparesthesia, anhidrosis and angiokeratoma. Renal cohort 
includes both males and females with symptomatic Fabry disease with a linear negative eGFR 
slope (estimated from at least 3 historical serum creatinine values [within 18 months, including 
the value obtained during screening visit]) of ≥ 2 mL/min/1.73 m²/year. Cardiac cohort includes 
both males and females with symptomatic Fabry disease, with cardiac involvement. Due to the 
X-linked nature of this genetic disease, female Fabry patients are heterozygous for the genetic 
defect and have a wide range of residual α-Gal A levels (Winchester & Young 2006). Therefore, 
females will be included in the Female cohort once an appropriate dose is determined in a 
homogeneous population of classical Fabry disease males to mitigate the possibility that 
biochemical or clinical heterogeneity confounds any responses to ST-920, specifically the α-Gal 
A levels produced by the cDNA. 
 
1.7 
Benefit-Risk Assessment and Study Hypothesis 
Fabry disease is an inherited lysosomal storage disorder that results from mutations in the gene 
encoding the enzyme α-Gal A. Decreased levels of α-Gal A result in the accumulation of toxic 
levels of a type of glycosphingolipid, Gb3, in the blood vessels and body tissues. The severity of 
the symptoms varies among individuals depending upon their specific GLA mutation and the 
level of residual α-Gal A activity. Currently, the treatment of choice for this patient population is 
ERT using recombinant α-Gal A or chaperone therapy. 
 
The objective of ST-920 investigational therapy is to provide patients with Fabry disease stable 
therapeutic, liver-specific expression of α-Gal A which may improve on the current clinical 
outcomes of ERT therapy and ultimately replace ERT altogether.  
 
The potential risks of ST-920 include insertion mutagenesis (carcinogenicity), vertical and 
horizontal transmission and off-target effects.  

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Mitigation strategies are in place for each potential risk and are described in the Investigator 
Brochure. Additional risks and related mitigation strategies are listed below.  
 
1.7.1 
Vertical and Horizontal Transmission 
ST-920 employs a replication defective AAV vector and persistence in bodily fluids is not 
anticipated past 60 days based on animal data. No data are available suggesting transmission of 
the AAV vector to the offspring of an exposed male subject. As a precaution to avoid 
transmission to partners of the viral vectors, through shedding, male subjects must agree to use a 
highly effective form of contraception (e.g., true sexual abstinence, documented vasectomy, 
condom) and refrain from sperm donation from the time of ST-920 administration until a 
minimum of 3 consecutive semen samples are negative for AAV2/6 after administration of 
ST-920 and a minimum of 90 days after ST-920 administration. Female subjects must agree to 
use a highly effective form of contraception (described in Inclusion Criteria 9), and they must 
refrain from egg donation from the time of ST-920 administration until all the samples are 
negative for AAV2/6 after administration of ST-920. 
 
ST-920 vector shedding has been shown in animal and human studies and is generally cleared in 
bodily fluids by 2 months post dose administration. Results from the first six subjects of 
ST-920-201 show that the AAV6 vector is not detectable after 2-8 weeks post-dosing. To 
mitigate any potential risks to other individuals or the environment from vector shedding, 
subjects are instructed to avoid the contact of their body fluids or excrements with other 
individuals or the environment, and maintain hygiene and cleanliness of their hands and the 
environment within an appropriate time period after receiving treatment; items to be disposed 
after coming in contact with the body fluids or excrements of subjects should be sealed in 
disposable garbage bags. For details, refer to the Laboratory Manual. 
 
1.7.2 
Off-Target Effects 
Because the viral vector construct includes a liver-specific promoter for the GLA gene and 
liver-specific enhancers, the transgene should only be expressed in the liver, thus limiting the 
risk of off-target effects to the liver. Off-target effects from circulating enzyme are not 
anticipated, as supraphysiological levels of produced enzymes in animal preclinical experiments 
did not reveal any relevant adverse effects. Despite this, subjects will be followed for a total of 
52 weeks (-2 weeks/+ 1 month) post-ST-920 infusion in this study. Subjects will also be 
encouraged to participate in an additional, optional separate long-term follow-up study (of 
4 years) for a total of up to 5 years from infusion to facilitate detection of potential delayed AEs 
associated with ST-920 treatment. 
 
1.7.3 
Humoral Immune Response to AAV 
As described in Section 1.3.3 of this protocol, in the GLP C57BL/6 mouse studies, the 
no-observed-adverse-effect level (NOAEL) was ≥ 1.50E+14 vg/kg, the highest dose tested. In 
the GLP monkey study, ST-920PC-related findings were limited to animals that did not receive 
an immunosuppression treatment (6.00E+13 vg/kg). There were no adverse findings related to a 
single IV administration of ST-920PC up to 5.00E+13 vg/kg, the highest dose level tested, hence 
risk mitigation strategies are not needed. 

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Patients treated with ST-920 are expected to develop a humoral antibody response against the 
AAV capsid. An enzyme-linked immunosorbent assay has been developed to detect anti-AAV6 
total antibodies from patient serum post-dose throughout the study. This anti-AAV6 antibody 
assay has been validated and sample analysis will follow FDA and EMA recommended tiered 
immunogenicity testing approach to confirm a positive response. 
 
1.7.4 
Development of Neutralising Anti-Human α-Gal A Antibodies 
Subjects treated with ST-920 carry a similar risk of developing an antibody response to the 
treatment as with other biologic interventional therapies. Two validated assays following FDA 
and EMA guidelines on immunogenicity assessment, total antibody and neutralizing antibody 
assays, are in place to assess and monitor treatment-elicited antibody response to transgene 
expressed α-Gal A. 
 
1.7.5 
Vector-induced Hepatitis and Loss of α-Gal A Expression 
As described in Section 1.4 of this protocol, based on Sangamo’s prior clinical experience with 
AAV2/6 vector, an ALT elevation (suggestive of an immune reaction to the viral capsid) may be 
observed. Subjects will be closely monitored for ALT elevation throughout the study and the 
protocol-defined treatment (or treatment at the discretion of the Investigator and agreed upon 
with the Medical Monitor) with corticosteroids may be initiated in response. Corticosteroid dose 
selection and guidance are provided in Appendix 3. 
 
1.7.6 
Transduction of Extra-Hepatic Tissues 
As stated in the Investigator Brochure, ST-920 includes a liver-specific promoter for the GLA 
gene and liver-specific enhancers, therefore, the transgene should only be expressed in the liver, 
thus limiting the risk of off-target effects. Off-target effects were not observed in nonclinical 
studies where supraphysiological concentrations of produced enzyme were attained. Subjects 
will be closely followed for up to 5 years after ST-920 administration, with standard safety 
monitoring, described in Protocol ST-920-LT01, Appendix A, Schedule of Events.  
 
1.7.7 
Corticosteroids to Suppress Immune Hepatitis 
Based on Sangamo’s prior clinical experience with AAV2/6 vector, it is possible that an ALT 
elevation (suggestive of an immune reaction to the viral capsid) may be observed. Subjects will 
be closely monitored for ALT elevation throughout the study and the protocol-defined treatment 
(or treatment at the discretion of the Investigator and agreed upon with the Medical Monitor) 
with corticosteroids may be initiated in response. The corticosteroid dosing regimen and tapering 
schedule are provided in Appendix 3.  
 
1.7.8 
Insertional Mutagenesis and/or Tumorigenesis  
The consensus in the gene therapy field is that insertional mutagenesis and carcinogenic risks 
associated with AAV gene therapy vectors is low. AAV vectors predominantly persist 
as episomal structures and integration frequency of AAV is estimated to be very low.  There are 
no attributes of ST-920 that indicate that this AAV6 vector has unique properties that increase 

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oncogenic risk. ST-920 hGLA expression is driven by a liver specific promoter/enhancer and 
lacks the strong viral promoters which are associated with increased carcinogenicity risk. While 
insertional mutagenic risk cannot be completely excluded, the overall weight of the evidence 
indicates the risk is low. 
 
The balance between benefit and (theoretical) risk should be weighed, and long-term 
monitoring for potential hepatocellular carcinogenicity will be key. The clinical plan includes 
monitoring for hepatocellular carcinoma (HCC)/liver masses by magnetic resonance 
imaging (MRI) or equivalent imaging modality at 24 weeks and at 1 year post ST-920 
administration. In addition, the long-term safety of ST-920 will be evaluated as part of the 
long-term follow-up (LTFU, 4 years) study for 5 years from ST-920 infusion. This will include 
serial alpha fetoprotein (AFP) testing and liver imaging to monitor for potential liver masses at 
Months 12, 24, 36, and 48 (± 2 months). 
 
1.7.9 
Exposure to Supraphysiological Levels of α-Gal A  
Nonclinical studies administered ST-920 IV to mice at doses up to 1.50E+14 vg/kg and assessed 
plasma α-Gal A activity over 3 months. Plasma α-Gal A activity increased in a dose-dependent 
manner in mice treated with ST-920 and remained stable over the 3-month study duration.  
Overall, supraphysiological levels of α-Gal A activity (up to ~4,100-fold in male and ~2,200 in 
female mice at 3 months) were observed in plasma, compared to those in vehicle control group. 
No ST-920 treatment-related adverse effects were seen and the NOAEL was considered to be 
≥1.50E+14 vg/kg, the highest dose tested. These results support safety of supraphysiological 
levels of plasma α-Gal A activity. 
 
1.7.10 
Risks of Kidney Biopsy 
For subjects who are ERT-naïve or ERT-pseudo-naïve (defined as not having received ERT 
treatment during the 6 months prior to baseline) and selected subjects previously on migalastat 
who the Principal Investigator, in conversation with the Sponsor Medical Monitor, considers a 
non-responder to migalastat based on clinical and/or biochemical assessments, a kidney biopsy 
will be performed at baseline and after 6 months of dosing. The risks associated with this 
procedure include bleeding and infection. The bleeding is usually minor but can be severe in rare 
cases, requiring surgery to stop the bleeding. Management will be based on local guidelines. 
Infection will be treated based on standard of care. There is a low risk of puncturing adjacent 
organs; to reduce this risk, the procedure is guided by ultrasound. Local anesthesia and pain 
medication during and after the procedure will be based on local guidelines, considering 
potential risks of adverse reactions to such medications. 
 
1.7.11 
Risks of Skin Biopsy 
Skin biopsy will be performed using incisional or punch biopsy techniques. All biopsies will 
result in a scar. Some scars may be raised, which is more likely if the biopsy is taken on the 
upper body. Scars fade gradually. The biopsy will be done in non-exposed areas of the skin such 
as the abdomen. 
 

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1.7.11.1 
Risks of Incisional Skin Biopsy 
Incisional skin biopsy may produce discomfort, which will be mitigated by local anesthesia. A 
minor burning sensation may occur when the freezing is injected, but usually subsides in a few 
seconds. Skin biopsies may also be associated with bleeding, which will be managed by applying 
pressure and a bandage. Complete healing of the wound may take weeks. 
 
In addition to these risks of bleeding and scarring, there can be bruising, infection, and an 
allergic reaction to topical antibiotics. These risks will be mitigated by keeping the area clean 
and covering the site with a breathable bandage. 
 
1.7.11.2 
Risks of Punch Biopsy 
Punch skin biopsy may produce discomfort, which will be mitigated by local anesthesia. A minor 
burning sensation may occur when the freezing is injected, but usually subsides in a few seconds. 
Skin biopsies may also be associated with bleeding, which will be managed by applying pressure 
and a bandage. Complete healing of the wound may take weeks. 
 
In addition to these risks of bleeding and scarring, there can be bruising, infection, and an 
allergic reaction to topical antibiotics. These risks will be mitigated by keeping the area clean 
and covering the site with a breathable bandage. 
 
1.7.12 
Risks of Liver Biopsy 
Liver biopsy will be required in the presence of a liver mass > 2 cm and elevated AFP (described 
in Section 6.2.8). The bleeding is usually minor but can be severe in rare cases, requiring surgery 
to stop the bleeding. Management will be based on local guidelines. Infection will be treated 
based on standard of care. There is a low risk of puncturing adjacent organs; to reduce this risk, 
the procedure is guided by ultrasound. Local anesthesia and pain medication during and after the 
procedure will be based on local guidelines, considering potential risks of adverse reactions to 
such medications. 
 
1.7.13 
Risks Associated with DNA Impurities  
To control for residual host cell DNA in the Sangamo gene therapy manufacturing process, 
benzonase is added to the cell harvest prior to purification as a mitigation strategy to prevent 
residual DNA being larger than 200 base pairs. The benzonase enzyme digests all forms of 
nucleic acid by hydrolyzing with high efficiency (nearly 99.95%) unencapsidated nucleic acid 
oligomers into smaller nucleotide fragments of <10 base pairs in length. Due to high efficiency 
of benzonase treatment, there is a high probability that the total amount of residual host cell 
DNA observed is within the expected size range, thus posing no concern based on current 
regulatory guidance. Finally, Sangamo is characterizing potentially encapsidated DNA with both 
short and long read next generation sequencing for any nucleotides greater than 200 base pairs 
and to date has not found any unexpected areas of concern. All DNA sequences detected are 
process related and found in extremely low percentages of total encapsidated nucleic acids. 
 

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1.7.13 
Risks Associated with Replication Competent AAV  
ST-920 employs a replication defective AAV vector and persistence in bodily fluids is not 
anticipated past 60 days based on animal data. The risk associated with the generation of a 
replication competent AAV in the manufacturing process is very low, based on the presence of 
engineering and analytical controls that are implemented during the manufacture and release of 
the ST-920 drug product. The manufacturing process is designed to make use of two separate 
baculovirus infected insect cells (BIICs), namely Helper and Vector BIICs. The Helper BIIC 
contains a plasmid that provides rep/cap genes while Vector BIIC contains a plasmid that 
provides ITR, transgene and regulatory elements. This strategy allows for separating the ITR 
region from rep/cap elements thereby de-risking the possibility of producing a replication 
competent AAV during the manufacture of the ST-920 drug product. In addition, the control 
strategy includes a lot release test for the detection of a replication competent AAV. A negative 
test result for this assay is required for the lot release, confirming that the AAV drug product is 
replication deficient. 
 
 

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2. 
STUDY OBJECTIVES AND ENDPOINTS 
2.1 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
• To assess safety and tolerability 
of ST-920 
• 
Incidence of treatment-emergent adverse events (TEAEs) 
Additional safety evaluations will include: 
o Routine hematology, chemistry, and liver tests, vital 
signs, electrocardiogram (ECG) and echocardiogram 
(ECHO) 
o Serial alpha fetoprotein (AFP) testing and MRI of liver 
(or equivalent imaging modality) to monitor for liver 
mass 
Secondary 
• To assess α-Gal A activity and 
the presence of its substrates in 
plasma over time 
• Change from baseline at specific time points over the 1-year 
study period in: 
o α-Gal A activity in plasma 
o Gb3 and lyso-Gb3 levels in plasma 
• To assess impact of ST-920 on 
ERT administration required for 
subjects on ERT  
• Change from baseline at specific time points over the 1-year 
study period in: 
o Frequency of ERT infusion 
• To assess the impact of ST-920 
on renal function  
• Change from baseline at specific time points over the 1-year 
study period in: 
o Estimated glomerular filtration rate (eGFR) using the 
CKD-EPI formula 
• To assess the impact of ST-920 
on cardiac function and left 
ventricular hypertrophy 
• Change from baseline at specific time points over the 1-year 
study period in: 
o Ejection fraction, global longitudinal strain, left 
ventricular mass index (LVMI), left ventricular systolic 
function measured by cardiac magnetic resonance 
imaging (CMR) 
• To evaluate ST-920 vector DNA 
shedding over time 
• ST-920 vector clearance measured by level of vector 
genome in blood (plasma), saliva, urine, stool, and semen (if 
applicable) 
Exploratory 
• To assess clinical impact of 
ST-920 on Fabry disease 
• Change from baseline at specific time points over the 1-year 
study period in: 
o Late gadolinium enhancement (LGE), native myocardial 
T1 values and T2 mapping measured by cardiac MRI 
(CMR) 
o High sensitivity troponin T, N-terminal pro-hormone B 
type natriuretic peptide (NT-proBNP) and other cardiac 
biomarkers  

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o Minnesota Living With Heart Failure Questionnaire 
(MLHF-Q) summary score  
o Urine protein to creatinine ratio (UPCR) and urine 
albumin to creatinine ratio (UACR) 
o Biomarkers of renal function in urine 
o Neuropathic pain measured by the Brief Pain Inventory 
(BPI) 
o Frequency of pain medication use 
o Gastrointestinal (GI) symptoms measured by the GI 
symptoms rating scale 
o Mainz Severity Score Index (MSSI) 
o Quality of life (QOL) patient-reported outcome 
measured by the SF-36 questionnaire 
o Pulmonary function 
o Audiologic function 
• To assess α-Gal A activity over 
time in skin   
• Change from baseline at specific time points over the 1-year 
study period in: 
o α-Gal A activity measured in skin  
• To assess the presence of Gb3 
inclusion levels in skin in ERT-
naïve and ERT-pseudo-naïve 
subjects (defined as not having 
received ERT treatment during 
the 6 months prior to baseline) 
and selected subjects previously 
on migalastat 
• Change from baseline at specific time points over the 1-year 
study period in: 
o Gb3 inclusion levels measured in skin in ERT-naïve and 
ERT-pseudo-naïve subjects and selected subjects 
previously on migalastat. 
 
• To assess the presence of α-Gal 
A substrates in urine for all 
subjects over time  
• Change from baseline at specific time points over the 1-year 
study period in: 
o Gb3 and lyso-Gb3 levels in urine for all subjects over 
time 
• To assess immune response to 
AAV2/6  
• Measurement of antibodies to AAV2/6  
• Assessment of cell-mediated immune response to AAV2/6 
• To assess immune response to α-
Gal A  
• Measurement of immune response to α-Gal A  
• To assess the impact of ST-920 
on Gb3 inclusion in the kidney 
(via kidney biopsy) in ERT-
naïve and ERT-pseudo-naïve 
subjects and selected subjects 
previously on migalastat 
• Percent reduction from baseline at Week 24: 
o Gb3 inclusion in the kidney (assessed by kidney 
biopsy) in ERT-naïve and ERT-pseudo-naïve subjects 
and selected subjects previously on migalastat 
 
Any samples collected from consenting subjects may be used for future research objectives. Such 
future research objectives may include analysis of biomarkers of severity of disease, response to 
therapy (e.g., cytokines, soluble cell surface proteins, soluble receptors), additional measures of 

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α-Gal A activity/protein levels, correlation with functional improvements, as well as 
determination of AAV virus inhibition, function, immunogenicity, or pharmacodynamics (e.g., 
antibodies, soluble receptors, AAV viral receptor inhibitors, cytokines, co-existing alternate 
serotype antibodies). For further details, refer to the Study Reference Manual. 
 
3 
STUDY DESIGN 
3.1 
Overview and Rationale 
This is a Phase I/II, multicenter, open-label, single-dose, dose-ranging study with a dose 
escalation phase potentially enrolling 4 cohorts representing 4 dose levels. Up to 48 subjects who 
are ≥ 18 years of age and who satisfy all inclusion/exclusion criteria are eligible to be enrolled in 
the overall study. Initially, recruitment will be limited to male subjects meeting criteria for 
inclusion during dose escalation. Once a safe and tolerable dose is selected, recruitment will be 
extended via dose expansion to a broader patient population. Once dose expansion is initiated, 
subjects will undergo assessments which will determine the most appropriate expansion cohort 
for their enrollment.   
 
During dose escalation, treatment of the first 2 subjects will be staggered so that the subsequent 
subject cannot be infused until the preceding subject has been observed for at least 2 weeks. 
After any 2 subjects in a cohort have been dosed, safety data from these 2 subjects will be 
reviewed by the Safety Monitoring Committee (SMC). Dose escalation to the next dose cohort 
and dose expansion cannot occur until at least 4 weeks of safety data are available after the 
second subject in the preceding cohort has been dosed, and data from this cohort has been 
reviewed by the SMC. The SMC will recommend whether it is safe to escalate the dose or to add 
subjects to the dose cohort at the same dose level. Once a cohort’s data has been reviewed and 
dose escalation has been endorsed, additional subjects may be infused at any time in the same 
cohort, as per protocol.  
 
Two male subjects with classical Fabry disease will be dosed in Cohort 1. Following the SMC 
recommendation to dose escalate to Cohort 2, which is subdivided into Cohort 2a (subjects who 
are antibody-postive to α-Gal A) and Cohort 2b (subjects who are antibody-negative to α-Gal A), 
2 male subjects with classical Fabry disease will be dosed and safety data from these 2 subjects 
will be reviewed by the SMC. After SMC review, up to an additional 8 (4 subjects in Cohort 2a 
and 4 subjects in Cohort 2b) subjects may be recruited into Cohort 2 and if dose escalation is 
recommended, recruitment of subjects into Cohort 3 may commence. Dosing may continue in 
Cohort 2 until all 10 subjects have been dosed, unless it is concluded during the SMC review that 
it is more appropriate to dose in Cohort 3 rather than continuing dosing at the Cohort 2 dose 
level. Dosing in Cohort 3 and the remainder of Cohort 2 can be concurrent. 
 
Following the SMC recommendation to dose escalate to Cohort 3, which is subdivided into 
Cohort 3a (subjects who are antibody-positive to α-Gal A) and Cohort 3b (subjects who are 
antibody-negative to α-Gal A), 2 male subjects with classical Fabry disease will be dosed and 
safety data from these 2 subjects will be reviewed by the SMC. After SMC review, up to an 
additional 8 (4 subjects in Cohort 3a and 4 subjects in Cohort 3b) subjects may be recruited into 
Cohort 3 and if dose escalation is recommended, recruitment of subjects into Cohort 4 may 
commence. Dosing may continue in Cohort 3 until all 10 subjects have been dosed, unless it is 

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concluded during the SMC review that it is more appropriate to dose in Cohort 4 rather than 
continuing dosing at the Cohort 3 dose level. Dosing in Cohort 4 and the remainder of Cohort 3 
can be concurrent. 
 
Following the SMC recommendation to dose escalate to Cohort 4, which is subdivided into 
Cohort 4a (subjects who are antibody-positive to α-Gal A) and Cohort 4b (subjects who are 
antibody-negative to α-Gal A), 2 male subjects with classical Fabry disease will be dosed and 
safety data from these 2 subjects will be reviewed by the SMC. After SMC review, up to an 
additional 8 subjects may be recruited into Cohort 4. Dosing may continue in Cohort 4 until all 
10 subjects have been dosed, unless it is concluded during the SMC review that it is more 
appropriate to select a dose for dose expansion. Dosing in dose expansion and the remainder of 
Cohorts 3 and/or 4 can be concurrent.   
 
The dose considered to be tolerable and safe will be utilized in the dose expansion cohorts. After 
dose escalation has been completed, dose expansion will commence where up to 6 subjects will 
be enrolled into each of the dose expansion cohorts, which include patients with classical Fabry 
disease who are antibody-positive to α-Gal A, patients with classical Fabry disease who are 
antibody-negative to α-Gal A, female patients (female cohort) and patients who meet criteria for 
the renal (renal cohort) and cardiac (cardiac cohort) inclusion and exclusion criteria. The dose for 
the expansion cohorts may be reassessed if there are emerging safety considerations. 
 
Anti α-Gal A Ab positive cohort:  Up to 6 male subjects with classical Fabry disease who are 
antibody-positive to α-Gal A will be enrolled. 
 
Anti α-Gal A Ab negative cohort:  Up to 6 male subjects with classical Fabry disease who are 
antibody-negative to α-Gal A will be enrolled. 
 
Female cohort: Up to 6 female subjects with classical Fabry disease will be enrolled. 
 
Renal cohort: Up to 6 male or female subjects with symptomatic Fabry disease with a linear 
negative eGFR slope (estimated from at least 3 historical serum creatinine values [within 18 
months, including the value obtained during screening visit]) of ≥ 2 mL/min/1.73 m²/year will be 
enrolled. 
 
Cardiac cohort: Up to 6 male or female subjects with symptomatic Fabry disease with cardiac 
involvement, defined as either left ventricular hypertrophy (LVH) in 2D echocardiography or 
CMR (end diastolic septum and posterior wall thickness ≥ 12mm) with no other explanation for 
LVH OR cardiac changes indicative of disease progression such as decreased global longitudinal 
strain on 2D strain echocardiography or low native T1 mapping on CMR will be enrolled. 
Subjects who have had a cardiovascular event in the 6-month period before screening may be 
excluded at the discretion of the Investigator. 

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Figure 2: 
Schema of Study Enrollment: Dose Escalation and Expansion 
For all dose escalation and expansion cohorts, subjects who received ERT prior to study 
participation will continue to receive ERT during the study and remain on their current dose and 
regimen per standard of care unless they undergo ERT withdrawal. For subjects on ERT, 
baseline testing of enzyme and substrate levels will be coordinated such that samples will be 
taken on 2 separate occasions in the morning at trough, defined as 14 days (± 1 day) after the 
previous ERT infusion. An additional time point will have been taken previously during the 
screening period, so as to have 3 time points to assess the residual activity of α-Gal A at trough 
prior to the gene therapy administration. These 3 samples must be taken at trough, and preferably 
at the same time during the day (e.g. in the morning) to minimize the potential impact of 
non-specific factors on enzyme activity. 
 
Based on Sangamo’s prior clinical experience with the AAV2/6 vector, an ALT elevation 
(suggestive of an immune reaction to the viral capsid) may be observed. Subjects will be closely 
monitored for ALT elevation throughout the study and the protocol-defined treatment (or 
treatment at the discretion of the Investigator and agreed upon with the Medical Monitor) with 
corticosteroids may be started in response to ALT elevation. Dose selection and guidance are 
provided in Appendix 3 of the protocol. 
 
For this Phase I/II study, the sample size of 2 subjects prior to a potential dose escalation was 
chosen based on:  
a)  consideration of optimum benefit/risk of the one-time administration of ST-920 to subjects 
due to the known development of an immune response against AAV6, and hence inability to 
treat the same subject again with AAV6 if efficacy is not achieved 
b)  recruitment feasibility in this orphan disease population, Fabry disease being a rare inherited 
X-linked metabolic disease: 

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i)  approximately 30-40% of subjects are expected to screen fail due to the presence of 
AAV6 neutralizing antibodies 
ii)  only male subjects with classical Fabry disease will be recruited during dose escalation 
and, to ensure that any residual enzyme level does not interfere with the measurement of 
enzyme levels produced by the cDNA transgene, either ERT-naïve subjects or subjects 
on a stable dose and regimen (defined as not having missed more than 3 doses of ERT 
during the 6 months prior to consent) or ERT-pseudo-naïve subjects who have previously 
been on ERT but have not received ERT treatment during the 6 months prior to baseline, 
will be allowed in the study 
c)  ability to detect any safety signal 
 
This sample size of 2 subjects per cohort will provide a 28% chance of observing at least one AE 
for events with a ≥15% incidence. In addition, for an expanded cohort of 6 subjects (2 + 4), the 
sample size of 6 subjects will provide a 62% chance of observing at least 1 AE for events with a 
≥15% incidence.  
 
Safety and tolerability of ST-920 infusion in each cohort will be assessed by incidence of TEAEs 
and serious AEs (SAEs). Other safety assessments will include monitoring liver tests for any 
AAV-associated elevation of liver enzymes, clinical laboratory tests (chemistry, hematology, 
urinalysis), vital signs, AAV clearance from tissues including plasma, urine, saliva, stool and 
semen (if applicable). Safety data from 24 subjects treated in the Sponsor’s studies with AAV2/6 
have, to date, not identified any dose limiting safety concerns with treatment of subjects at the 
starting dose proposed in this study. Therefore, 2 subjects per dose during the escalation is 
believed appropriate to limit the number of subjects who may be exposed to a suboptimal dose, 
and to maximize treatment of subjects at the dose that will optimize the benefit risk assessment. 
This is particularly pertinent, considering that it is very unlikely that a subject could be retreated 
with this technology should they not experience efficacy at the dose tested. 
 
The rationale for a two-week staggering interval between the first 2 subjects in a cohort and four 
weeks between dose cohorts is based on the experience that the Sponsor has acquired from other 
gene therapy programs using AAV2/6. There was no evidence of acute or subacute adverse 
effects in preclinical studies with this product or similar products using AAV2/6. Based on safety 
data from preclinical studies using ST-920 and similar products, as well as clinical studies using 
similar products, a two-week staggering interval between first two subjects in a cohort provides 
adequate time to assess any acute or subacute AEs in this study (for further details, refer to the 
Investigator Brochure).  
 
ST-920 will be administered via intravenous infusion while the subject is in the healthcare 
facility, where the subject will remain for observation for at least 24 hours after completion of 
the ST-920 infusion. During infusion, only light foods such as jello or apple sauce or liquids may 
be consumed. The subject will be discharged when all vital signs are stable and any AEs have 
resolved or the subject is considered stabilized as per Investigator judgment.  
 
Following the infusion of ST-920, study visits will be conducted on Day 8, Weeks 2, 4, 6, 8, 12, 
16, 20, 24, 28, 32, 36, 40, 44, 48, and 52. The Week 28, 32, 40, 44, and 48 study visits have 
assessments that do not require evaluation at the clinical site, and therefore may be conducted 

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remotely. Assessments for AEs and concomitant medications may be conducted remotely over 
the phone by the study staff. 
 
Liver tests will be assessed twice weekly during the first 20 weeks after ST-920 infusion, then 
weekly for four weeks (Weeks 21-24), and monthly thereafter to coincide with study visits 
(Weeks 28-52). Liver tests may be conducted remotely and analyzed locally or centrally. Blood 
samples for liver tests will be drawn 2-4 days apart when possible. For the first week they will be 
drawn on Day 2 and 2-4 days later.  Day 8 visit will be the first Week 2 blood draw. If there is a 
need to initiate treatment with corticosteroids because of elevated ALT, liver enzymes will 
continue to be assessed at least twice a week until normalization and then per protocol thereafter 
analyzed locally or centrally (Appendix 3). 
 
A four-week staggering interval between dose cohorts will allow for appropriate time to collect 
safety data for the first two subjects in each cohort for the Safety Monitoring Committee to 
review and make recommendations to the Sponsor as to whether to dose-escalate, dose-de-
escalate or add a cohort. 
 
The duration of study participation will be up to 84 weeks for each subject divided into up to 8 
weeks for screening, up to 24 weeks for baseline, and 52 weeks follow-up after dosing. Accrual 
is planned for 48 months.   
 
The proposed evaluation period in this study is 52 weeks after ST-920 administration. 
This one-year safety evaluation of the study includes physical evaluation, ECG, ECHO, and 
hearing test, in addition to other routine clinical tests and biochemical safety evaluation (for 
further details, refer to Section 6 and Appendix 1). The 52-week period will monitor for 
long-term expression and sustainability of the enzymatic activity produced by the cDNA, and 
may also give some preliminary information on Fabry-relevant parameters, such as renal 
function, cardiac function. In addition, at the end of the study period of 52 weeks, subjects will 
be encouraged to participate in an additional separate long-term follow-up study (of 4 years) for 
a total of at least 5 years from infusion for long term safety and durability of response 
monitoring. 
 
3.2 
Screening Period  
The objective of the screening visit is to identify subjects who meet the stated inclusion and 
exclusion criteria and who are willing and able to participate in the study. After informed 
consent, screening may take up to approximately 8 weeks and may be performed across several 
visits. 
 
During screening, subjects will be assigned a subject number and will receive the screening 
assessments and procedures described in the Schedule of Events (Appendix 1). Subjects who 
complete all screening procedures, satisfy all eligibility criteria and have their eligibility packet 
verified by the site and approved by the Medical Monitor will be considered enrolled in the 
study. 
 

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Subjects may be re-screened for participation in the study at the judgment of the Site Investigator 
and after consultation with Sponsor. See the Schedule of Events (Appendix 1) for a list of 
assessments performed in the previous 6 months that may be used for evaluation of 
inclusion/exclusion criteria at the judgment of the Site Investigator. Genetic marker analysis 
including Fabry disease gene sequencing will not be repeated as this will not change over time. 
In addition, Fabry disease gene sequencing will only be performed at screening if no prior 
documented gene sequencing results are available. The genotyping will only be used to confirm 
that subjects have a mutation in the GLA gene. The diagnosis of classical Fabry disease will be 
made on the basis of enzyme activity and clinical symptoms for male subjects. For females the 
diagnosis will be made based on mutation and clinical symptoms. 
 
A sample will be taken during the screening period to measure baseline levels of enzyme and 
substrate levels. Two more samples for baseline levels of enzyme and substrate will be taken 
during the baseline period (see Section 3.3), so as to have 3 time points to assess the residual 
activity of α-Gal A prior to the gene therapy administration. For subjects on ERT, testing of 
enzyme and substrate levels will be coordinated such that samples will be taken at trough, 
defined as 14 days (± 1 day) after the previous ERT administration, and preferably at the same 
time during the day (e.g. in the morning) to minimize the potential impact of non-specific factors 
on enzyme activity. 
 
3.3 
Baseline Period 
Baseline assessments and procedures outlined in the Schedule of Events (Appendix 1) will be 
performed within 12 weeks prior to ST-920 infusion. The duration may be extended to 24 weeks 
for subjects whose visits are impacted by delays due to COVID-19. In subjects receiving ERT, 
assessments including α-Gal A levels, and Gb3 and lyso-Gb3 and immunogenicity samples will 
be taken at ERT trough levels, defined as 14 days (± 1 day) after the previous ERT 
administration. Two samples will be taken at baseline on 2 different days in the morning. For 
subjects not on ERT, two samples will be taken at baseline on 2 occasions with at least 14 days 
(± 1 day) between the 2 occasions. Documentation of dosing should be recorded in the electronic 
case report form (eCRF) and administration of all ERT should be obtained and recorded in the 
ERT Administration Log. 
 
3.4 
Treatment Period and Dose Escalation Rules 
As this is a multicenter study, it is important that the current status in regard to subjects in 
screening, enrolled and treated, as well as safety data, be up to date and communicated to the 
study sites. All activated sites will be asked to communicate subject status at their site to the 
Sponsor on at least a weekly basis. A summary of subject status across the study will be shared 
with each site at least on a weekly basis. Significant safety information will be communicated to 
sites as described in Section 9.5. This will allow both the Sponsor and the study sites to be 
up -to -date on current potential treatment slots available based on subjects in screening, and on 
safety data.  
 
As an additional assurance that a site cannot dose a subject when they should not, the vials 
required for the treatment are shipped to the study site only after the subject’s baseline 
assessment visit. 

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Subjects who complete all screening procedures, satisfy all eligibility criteria, and have their 
eligibility packet verified by the site and approved by the Medical Monitor may be enrolled into 
the baseline period. Following verification of the eligibility packet, the Medical Monitor will 
confirm which dose level the subject will be assigned to. 
 
The doses being evaluated were selected based on preclinical studies in mice and monkeys and 
cumulative safety data from ongoing Sangamo clinical studies that use the same AAV2/6. 
Several dose levels may need to be studied to identify a safe and tolerable therapeutic dose.  
The dose levels for this dose escalation study are as noted in Table 1. Dose escalation to the next 
dose level will be decided by the SMC upon review of safety data from the previous cohort. 
Other data derived from other Sangamo-sponsored clinical trials that use in vivo AAV2/6-based 
therapy may be considered as well, and based on the recommendation of the Safety Monitoring 
Committee (SMC), which will be composed of external subject matter experts, the study Medical 
Monitors, Sponsor Drug Safety Lead and Site Investigators as appropriate (as described in the 
SMC charter).  
 
From preclinical experiments with ST-920 in a mouse model of Fabry disease, it is anticipated 
that supraphysiological levels of enzymatic activity need to be achieved in the blood (at least 8 
times the normal enzymatic activity), at steady state, in order to lead to a full reduction of the 
substrate accumulation in the main target organs (kidneys and heart). 
 
In addition, depending on the enzyme activity and safety data of the subjects dosed, the SMC 
may recommend a dose escalation to one of the two doses listed in Table 1. However, no dose 
given to subjects will exceed 5.00E+13 vg/kg (by qPCR) without a substantial amendment. 
 
Table 1: 
Dose by Cohort 
Cohort 
AAV1 Dose (vector genomes [vg]/kg) 
 qPCR2  
1 
0.50E+13  
2 
1.00E+13 or 3.00E+13 
3 
3.00E+13 or 5.00E+13 
4 
5.00E+13  
1AAV = adeno-associated virus, 2quantitative PCR 
 
A droplet digital PCR (ddPCR) test method is being developed to determine the level of vector 
genome (vg) titers for ST-920. The nominal genome copies (vg/mL) are not changing; a new 
method (ddPCR) to evaluate the nominal genome copies is being implemented and will replace 
the qPCR method. Once fully implemented, drug product released using the initial qPCR assay 
or the new ddPCR assay will be used in Study ST-920-201. See Section 7 for additional details. 
 
For the first 2 subjects in each cohort, treatment will be staggered so that each subsequent subject 
will not be infused until the preceding subject has been observed for at least 2 weeks. After the 
first 2 subjects, the subsequent subjects in the same dose cohort can be infused at any time if the 
safety data from the first 2 subjects is deemed satisfactory by the SMC.  
 

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A decision to dose escalate to the next dose level will not occur until at least 4 weeks after the 
2 subjects in the preceding cohort have been dosed and the safety data from the 2 subjects in the 
prior cohort has been reviewed by the SMC.  
 
Safety and tolerability of the ST-920 infusion will be assessed by the incidence of TEAEs and 
SAEs. Other safety assessments will include monitoring liver tests for any AAV-associated 
elevation of liver enzymes, clinical laboratory tests (chemistry, hematology, urinalysis), vital 
signs, AAV clearance from tissues including plasma, urine, saliva, stool and semen (if 
applicable). Preliminary bioactivity and efficacy will be assessed by evaluating any change from 
baseline of α-Gal A levels and Gb3 and lyso-Gb3 substrate levels over time. For those subjects 
on ERT, these samples will be taken at trough ERT levels (with trough defined as 14 days [± 1 
day] after the previous ERT administration). In relation to symptomatic efficacy, we will be 
assessing any changes in Fabry-specific symptoms including GI symptoms, neuropathic pain, 
and lack of sweating with exercise which will be informative as markers of efficacy in subjects 
who are treatment naïve and in subjects who withdraw from ERT after ST-920 infusion. 
 
Dosing and dose escalation will be paused if any of the study stopping rules are met (refer to 
Section 3.5). In such an event, the SMC will be convened to provide recommendations to dose 
de-escalate, or to discontinue the study. No further dosing of subjects will be performed at that 
dose level or higher until a substantial amendment is submitted to regulatory authorities for 
review, and the amendment has been approved by the site Institutional Review Board 
(IRB)/Independent Ethics Committee (IEC) or equivalent. 
 
The dose deemed to be tolerable and safe will be utilized in the expansion cohorts.  
All subjects will be asked to return to the study site for a follow-up visit 7 ± 1 days after ST-920 
infusion. See the Schedule of Events (Appendix 1) for a list of assessments and procedures 
performed on Day 8. Thereafter, study visits are scheduled as described in the Schedule of 
Events (Appendix 1).  
 
Subjects will be followed for a total of 52 weeks (-2 weeks/+ 1 month) post-ST-920 infusion in 
this study. Subjects will be encouraged to participate in an additional, optional separate long-
term follow--up study (4 years) for a total of at least 5 years from infusion. 
 
3.5 
Study Stopping Rules 
An SMC with appropriate medical and scientific expertise was appointed to provide safety 
oversight for the study. The SMC is comprised of external subject matter experts, the study 
Medical Monitor, Sponsor’s Drug Safety Lead, Study Biostatistician, and Site Investigators as 
appropriate. The SMC will periodically meet during the study and provide recommendations to 
the Sponsor concerning dosing. The SMC will also convene at any time if an emergent safety 
issue emerges during the study or one of the stopping rules are met. These include: 
• Any one Grade 3 or higher AE with at least a reasonable possibility of a causal relationship 
to the investigational product 
• SAE with at least a reasonable possibility of a causal relationship to the investigational 
product 
• Death of a subject 

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• Development of a malignancy, with the exception of non-melanoma skin cancers and 
localized prostate cancer treated with curative intent 
 
The study may also be stopped for any of the following reasons:  
• Sponsor, in consultation with the SMC or Regulatory Agency, decides for any reason that 
subject safety may be compromised by continuing the study.  
• Sponsor decides to discontinue development of the investigational product, ST-920.  
 
All data will be evaluated to determine whether changes should be made to the study or if 
accrual should be continued or halted. If stopping criteria are met, no further dosing of subjects 
will be performed at that dose level or higher until a substantial amendment is submitted to 
regulatory authorities for review, and the amendment has been approved by the site Institutional 
Review Board (IRB)/Independent Ethics Committee (IEC) or equivalent. 
 
Relevant data from other trials sponsored by Sangamo may be shared with the SMC to expand 
the clinical experience, particularly as it relates to safety and dose, and such data can be used by 
the SMC to inform its recommendations for the present study. 
 
The SMC may also recommend changes to the dose and enrollment of cohorts based on 
cumulative safety data from this and other Sangamo sponsored clinical trials that use in vivo 
AAV2/6-based therapy. When no further enrolling or dosing decisions are required of the SMC, 
the SMC will no longer meet on a regular basis. The Sponsor will continue to review the subject 
safety data on an ongoing basis. 
 
3.6 
Enzyme Replacement Therapy Withdrawal (any time after Week 4) 
The ultimate goal of ST-920 treatment is to abrogate the need for ERT by using an AAV2/6 
vector encoding cDNA for human α-Gal A, resulting in long-term, liver-specific expression of 
α-Gal A in Fabry disease subjects. During dose escalation, subjects on ERT may be considered 
for complete withdrawal of ERT at the discretion of the Principal Investigator following 
consultation with the Sponsor and with agreement from the subject. The ERT withdrawal can 
only be considered after a period of four weeks, in order to allow enough time for transduction of 
the target liver cells.  
 
Subjects who undergo ERT withdrawal will be closely monitored for any AEs, vital signs, any 
changes in safety laboratory evaluations, including liver tests and activity of α-Gal A and 
substrates (Gb3 and lyso-Gb3) compared to baseline (Appendix 2).  
 
During dose escalation, ERT withdrawal is at the discretion of the Site Investigator after 
consultation with the Sponsor, and is only to be considered for subjects who are willing and meet 
all of the following criteria:  
• Are ≥4 weeks post-administration of ST-920. 
• Are medically stable and can tolerate temporary discontinuation of ERT in the judgment of 
the Site Investigator. 

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• Agree to increased safety monitoring and additional lab testing until ERT Withdrawal 
Follow-Up visit (Appendix 2). 
 
Initiation of the dose expansion phase of the study assumes that a safe and tolerable dose of ST-
920 has been achieved. At this point, ERT withdrawal will be implemented for all subjects who 
are in the expansion cohorts and have achieved supraphysiological (above normal range) plasma 
α-Gal A for 8 weeks ± 2 weeks, at the discretion of the investigator. 
 
ERT withdrawal assumes a complete stop in ERT administration rather than a “dose-down” or 
dose reduction. 
 
Study visits associated with ERT withdrawal may occur concurrently or independently of regular 
scheduled study visits, but should be combined with regular scheduled study visits whenever 
possible to reduce study burden. When combined, assessments associated with ERT withdrawal 
(Appendix 2) that are duplicated at the regular scheduled study visits (Appendix 1) should be 
waived. The ERT Withdrawal Follow-Up visit (visit where a clinical assessment is performed by 
the Site Investigator to determine whether ERT should be reinitiated in the subject) will occur at 
Week 12 after ERT withdrawal visit (Appendix 2), but it can occur earlier at the discretion of the 
Site Investigator, if clinically indicated.  
 
ERT does not need to be restarted after the ERT Withdrawal Follow-Up visit. However, ERT 
may be re-initiated at any time based on clinical circumstances or at the judgment of the Site 
Investigator. After ERT withdrawal, in order to assess whether a subject has received a 
suboptimal dose, evidence of a lack of response will be primarily based on α-Gal A activity and 
lyso-Gb3 substrate levels in plasma, which will be tested on a regular basis (refer to Appendix 2 
for a full list of assessments and schedule of events). Plasma α-Gal A activity below the normal 
range, or plasma lyso-Gb3 levels, will be part of the criteria used by the Site Investigators to 
determine lack of response (and need for reinstitution of ERT). 
 
ERT withdrawal may be repeated if previously unsuccessful, provided this is done at least 
12 weeks after the previous attempt if the subject is willing, and at the discretion of the Site 
Investigator and after consultation with the Sponsor. 
 
3.6.1 
ERT Withdrawal Monitoring  
ERT Withdrawal Monitoring visits will take place following the ERT Withdrawal visit. ERT 
Withdrawal Monitoring visits should be combined with regular scheduled visits whenever 
possible to reduce study burden. ERT Withdrawal Monitoring visits may be conducted remotely. 
 
See the ERT Withdrawal Schedule of Events (Appendix 2) for a list of assessments and 
procedures performed during the ERT Withdrawal Monitoring Visits. 
 
3.6.2 
ERT Withdrawal Follow-Up  
The ERT Withdrawal Follow-Up visit will occur at Week 12 ± 2 days after the ERT withdrawal 
visit (Appendix 2), but it can occur earlier at the discretion of the Site Investigator, if clinically 

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indicated. If clinically indicated, ERT may be re-initiated at any time based on clinical 
circumstances or at the judgment of the Site Investigator. 
 
See the ERT Withdrawal Schedule of Events (Appendix 2) for a list of assessments and 
procedures performed during the ERT Withdrawal Follow-up Visit. 
 
3.7 
End of Study Visit and Long-Term Follow-up Study 
An End of Study (EOS) visit will be conducted at Week 52 (-2 weeks/+1 month) for final 
assessments, detailed in the Schedule of Assessments (Appendix 1). At the EOS visit, subjects 
will be encouraged to participate in a separate long-term follow-up study where subjects will be 
followed for at least 4 years. Subjects will be followed for a total of up to 5 years from infusion. 
Informed consent will be obtained prior to participating in the long-term follow-up study. 
 
4. 
SUBJECT SELECTION 
4.1 
Inclusion Criteria 
1. ≥18 years of age 
2. Signed, written informed consent  
3. Diagnosis of Fabry disease 
4. One or more of the following symptoms: i) cornea verticillata, ii) acroparesthesia, iii) 
anhidrosis, iv) angiokeratoma  
5. Subjects who are on ERT or are ERT-naïve or are ERT-pseudo-naïve (defined as not having 
received ERT treatment in the 6 months prior to baseline). For subjects receiving ERT, ERT 
must have been administered at a stable dose and regimen for at least 6 months (defined as 
not having missed more than 3 doses of ERT during the 6 months prior to consent).   
6. Subjects on migalastat (Galafold™) must agree to withdraw migalastat prior to Baseline 
and, if non-responder to migalastat (based on clinical and/or biochemical assessments), 
undergo an incisional skin biopsy and kidney biopsy. 
7. Male subjects must refrain from sperm donation from the time of ST-920 administration 
until a minimum of 3 consecutive semen samples are negative for AAV2/6 after 
administration of ST-920 and a minimum of 90 days after ST-920 administration. 
8. Female subjects must refrain from egg donation from the time of ST-920 administration until 
all the samples are negative for AAV2/6 after administration of ST-920. 
9. Subjects must agree to use a highly effective form of contraception from the time of ST-920 
administration until a minimum of minimum of 90 days after ST-920 administration and, for 
male subjects, 3 consecutive semen samples are negative for AAV2/6 after administration of 
ST-920. Highly effective birth control methods include: 
i. 
a documented vasectomy or permanent sterilization  
ii. 
condom  
iii. 
combined (estrogen and progestogen containing) hormonal contraception (oral, 
intravaginal or transdermal) 
iv. 
progestogen-only hormonal contraception associated with inhibition of ovulation (oral, 
injectable or implantable) 
v. 
intrauterine device (IUD) 
vi. 
intrauterine hormone-releasing system (IUS) 

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vii. 
sexual abstinence is acceptable only as true abstinence and when in line with the 
preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, 
ovulation, symptothermal, post-ovulation methods) and withdrawal are not 
acceptable methods of contraception 
10. Subject must be fully vaccinated (as per the Centers for Disease Control and 
Prevention (CDC) definition in the US and as per local guidelines in other countries) for 
COVID-19 at least one month prior to dosing 
Additional inclusion criteria for: 
Cohorts 1-4b: 
11. Male subjects with classical Fabry disease as defined by < 5% α-Gal A activity in either 
plasma or leukocytes   
a. For male subjects who do not have documented diagnostic α-Gal A activity, a blood 
sample will be taken to measure α-Gal A activity (in plasma). For subjects who are on 
ERT, this blood draw must be taken at least 13 days after their last ERT infusion (trough). 
b. If the subject’s α-Gal A activity is > 5% and the subject is on ERT, this level of enzyme 
activity may be due to residual α-Gal A activity from the last ERT infusion. In this case, 
the diagnosis of classical Fabry disease may be confirmed if the following three criteria 
are fulfilled:  
i. 
two or more documented symptomatic characteristics outlined in inclusion 
criterion #4. If there is documented clustered periumbilicial angiokeratoma, this 
symptom alone is sufficient as it is a pathognomonic sign of classical Fabry 
disease;  
ii. 
a mutation that is indicative of classical Fabry (i.e. listed in a database, such as 
http://dbfgp.org); and 
iii. 
the α-Gal A activity at trough is below the lower limit of the normal range of the 
assay. 
Female cohort:  
12. Female subjects with a documented mutation that is indicative of classical Fabry (i.e., listed 
in a database, such as http://dbfgp.org) and treatment (ERT and/or migalastat) is clinically 
indicated 
Renal and Cardiac cohorts: 
13. Symptomatic Fabry disease defined for male subjects by <30% α-Gal A activity in either 
plasma or leukocytes and for female subjects based on historical genetic test results consistent 
with Fabry pathogenic mutation or in the case of novel mutations a first-degree male family 
member with Fabry disease with the same mutation 
AND 
Renal cohort: 
14. Screening eGFR value between 40-90 mL/min/1.73 m²  
15. Linear negative eGFR slope (estimated from at least 3 historical serum creatinine values 
[within 18 months, including the value obtained during screening visit]) of ≥ 2 mL/min/1.73 
m²/year  

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Cardiac cohort: 
16. LVH in 2D echocardiography or CMR defined as an end diastolic septum and posterior wall 
thickness ≥12 mm with no other explanation for LVH, OR presentation with cardiac changes 
indicative of disease progression such as decreased global longitudinal strain on 2D strain 
echocardiography or low native T1 mapping on CMR 
 
4.2 
Exclusion Criteria 
1. Positive neutralizing antibodies to AAV6 
2. Intercurrent illness expected to impair evaluation of safety or efficacy during the observation 
period of the study 
3. eGFR <40 mL/min/1.73m2 
4. Active infection with hepatitis A virus (HAV RNA positive), active or occult hepatitis B 
virus infection (positive HBV-DNA or anti-HBc positive), active infection with hepatitis C 
virus (HCV RNA positive), infection with the human immunodeficiency virus (HIV) as 
measured by quantitative polymerase chain reaction (qPCR), or active or latent infection 
with tuberculosis (TB) measured by quantiferon test 
5. Breastfeeding at screening or breastfeeding during required period of contraception 
6. History of liver disease such as clinically significant steatosis, fibrosis, non-alcoholic 
steatohepatitis (NASH) and cirrhosis, biliary disease within 6 months of informed consent; 
except for Gilbert’s syndrome 
7. Elevated circulating serum AFP  
8. For subjects receiving ERT, recent or recurrent hypersensitivity reaction manifested by 
significant infusion reaction to ERT treatment within 6 months prior to consent 
9. One or more of the following: 
a. Albumin ≤ 3.5 g/dL  
b. Total bilirubin > upper limit of normal (ULN) and direct bilirubin ≥ 0.5 mg/dL 
c. Alkaline phosphatase (ALP) > 2.0 x ULN 
d. Alanine aminotransferase (ALT) > 1.5 x ULN  
10. Current or history of systemic intravenous (IV) or oral immunomodulatory agents, or 
biologics or steroid use in the past 6 months prior to consent (topical and inhaled treatment 
are allowed, [e.g., for asthma or eczema]). Occasional use of systemic steroid may be 
allowed based on discussion and agreement with the Medical Monitor. 
11. Contraindication to use of corticosteroids  
12. History of malignancy, except for non-melanoma skin cancer and localized prostate cancer 
treated with curative intent 
13. Recent history of alcohol or substance abuse. The use of marijuana may be considered on an 
individual basis with discussion and agreement from the Medical Monitor.  
14. Participation in investigational interventional drug or medical device study throughout the 
duration of this study and within the last 3 months prior to consent (with the exception of 
implantable loop recorders as in the RaILRoAD trial) 
15. Prior treatment with a gene therapy product 
16. Known hypersensitivity to components of ST-920 formulation 
17. Any other reason that, in the opinion of the Site Investigator or Medical Monitor, would 
render the subject unsuitable for participation in the study, including but not limited to risk 
of COVID-19 infection. 

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Additional exclusion criteria for: 
Cohorts 1-4, female, and renal cohort: 
18. New York Heart Association (NYHA) Class III and IV  
Renal cohort:  
19. History of renal dialysis or transplantation 
20. History of acute kidney insufficiency in the 6 months prior to screening 
21. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) 
therapy initiated within 4 weeks prior to screening or changed ACE inhibitor or ARB dose in 
the 4 weeks prior to screening 
22. Urine protein to creatinine ratio (UPCR) > 0.5 g/g who are not being treated with an ACE 
inhibitor or ARB 
Cardiac cohort: 
23. Significant cardiac fibrosis defined as having more than 3 segments full thickness of late 
gadolinium enhancement on CMR  
24. Any contraindications to CMR as per local hospital/institution guidelines 
25. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) 
therapy initiated within 4 weeks prior to screening or changed ACE inhibitor or ARB dose in 
the 4 weeks prior to screening 
26. NYHA Class IV 
 
5. 
INFORMED CONSENT 
Informed consent must be obtained from the subject before any study-related screening activity 
is undertaken. The subject’s legally authorized representative may also provide informed consent 
for subject participation if allowed by the local IRB/IEC or equivalent. The Site Investigator or 
designated personnel will explain to each subject or the subject’s legally authorized 
representative the nature of the study, its purpose, the procedures, the expected duration, 
alternative therapies available, and the benefits and risks of participation. The Site Investigator or 
designated personnel will explain to each subject or the subject’s legally authorized 
representative that the screening process may start with the assessment of AAV6 neutralizing 
activity. The subject or the subject’s legally authorized representative will receive an information 
and consent document, with the opportunity to ask questions, and will be informed that 
participation is voluntary, and that the subject can withdraw from the study at any time without 
any impact upon the subject’s future clinical care. The subject or the subject’s legally authorized 
representative will receive a copy of the signed and dated written informed consent form. Each 
subject will be re-consented at the time of any informed consent amendment, as applicable, and 
will be provided a copy of the signed and dated revised consent form. 
 
6 
STUDY ASSESSMENTS AND PROCEDURES 
Timing of all study evaluations to be performed during this study is outlined in the Schedule of 
Events (Appendix 1, Appendix 2). Prior to initiation of this study, the study site shall be 
approved by the IRB/IEC or equivalent and the appropriate regulatory agency. 
 
Subjects will be admitted to the health care facility for the ST-920 infusion. ST-920 will be 
injected using a peristaltic pump or IV infusion pump (see Study Pharmacy Manual). During 
infusion, only light foods such as jello or apple sauce or liquids may be consumed. Total 

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volumes will be dependent on subject’s cohort assignment and body weight (kg) at baseline. 
ST-920 will be administered through an IV catheter at a controlled speed while monitoring the 
subject’s vital signs (temperature, heart rate, respiratory rate, and blood pressure). Detailed 
instructions for the thaw and administration of the investigational product are in the Study 
Pharmacy Manual.  
 
The subject will remain in the health care facility for at least 24 hours after completion of 
ST-920 infusion for observation and will be discharged when all AEs have resolved or the 
subject is considered stabilized as per Investigator judgment and all vital signs (temperature, 
heart rate, respiratory rate, and blood pressure) are stable. All safety data must be reviewed prior 
to discharge.  See the Schedule of Events (Appendix 1) for a list of assessments and procedures 
performed on Days 1 and 2. 
 
Subjects who received ERT prior to study participation will continue to receive ERT during the 
study and remain on their current dose and regimen per standard of care unless they undergo 
ERT withdrawal (Section 3.6). For subjects on ERT, baseline testing of enzyme and substrate 
levels will be coordinated such that samples will be taken on 2 separate occasions in the morning 
at trough, defined as 14 days (± 1 day) after the previous ERT administration. A third sample 
will have been taken during the screening period to provide α-Gal A trough levels at 3 time 
points to assess the residual levels of α-Gal A prior to the gene therapy administration.  
 
The actual date should be recorded for all procedures and the Site Investigator should make 
every effort to perform procedures at the scheduled nominal dates outlined in the Schedule of 
Events (Appendix 1). Planned safety and laboratory assessments may be collected at additional 
time points following conversation between the Site Investigator and Medical Monitor based on 
emerging clinical events. The change in timing for any planned study assessments must be 
approved and documented by the Sponsor, but this will not constitute a protocol amendment 
where they are considered needed for safety reasons.  The addition of any new study assessments 
to the protocol required for any ongoing and new subjects would constitute an amendment.  
 
6.1 
Demographic/Medical History Assessments 
6.1.1 
Medical History 
A complete medical history, including concomitant medications, will be obtained to assess study 
eligibility. All clinically significant medical conditions, surgeries, and procedures should be 
recorded. Sites should perform a review of the medical records and collect all eGFR values 
within 18 months prior to screening. If the subject is not normally seen at the study center, it may 
be necessary to obtain medical records to confirm study eligibility. For details, refer to the Study 
Reference Manual. 
 
6.1.2 
Demographics 
Demographic data on each subject (e.g., age, sex, race, ethnicity) will be obtained at the 
screening visit. For details, refer to the Study Reference Manual. 
 

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6.1.3 
Fabry Gene Sequencing 
Fabry disease gene sequencing will be performed at screening to confirm that subjects have a 
mutation in the GLA gene. The assay may be performed on blood or saliva samples. If available, 
gene sequencing results obtained prior to the study may be used. For details, refer to the 
Laboratory Manual.  
6.1.4 
Infectious Disease Screening 
Testing for HIV, HAV, HBV, HCV, and TB will be conducted at screening. Subjects with a 
diagnosis of HIV or evidence of active HAV, HBV, HCV, or TB infection are not eligible to 
participate in this study. For details, refer to the Laboratory Manual. 
 
6.1.5 
Neutralizing Antibodies to AAV6 and Immune Response to α-Gal A 
The level of neutralizing antibodies to AAV6 will be measured at screening to assess the 
subject’s pre-existing immune response to AAV6. Subjects who tested positive for neutralizing 
antibodies to AAV6 are not eligible to participate in this study. If dosing is not completed within 
12 weeks of sample collection for neutralizing antibodies to AAV6 the serum neutralization 
assay to AAV6 should be repeated. Immune response to α-Gal A will be measured to assess the 
effect of anti-α-Gal A antibodies on therapy efficacy and outcome. It is important to collect the 
screening and baseline samples for immune response to α-Gal A at trough (14 days ± 1 day) after 
the previous ERT administration) to reduce interference from ERT. For details, refer to the 
Laboratory Manual. 
 
6.1.6 
Concomitant Medications 
Current concomitant medications will be recorded. For details, refer to the Study Reference 
Manual. 
 
6.1.6.1 
Vaccines 
Live attenuated vaccines (for any infection) should not be prescribed within two weeks prior to 
and up to 20 weeks after ST-920 infusion. 
 
6.1.6.1.1 COVID-19 Vaccine 
ST-920 is to be administered no earlier than 4 weeks after any dose of a COVID-19 vaccine 
dose, including booster doses. For subjects who have been dosed with ST-920, the COVID-19 
vaccine booster can be administered as of 4 weeks following ST-920 infusion. 
 
The COVID-19 vaccine should not be administered if the subject is receiving corticosteroids in 
response to an ALT elevation; it may be administered 7 days following discontinuation of the 
corticosteroids.  
 
COVID-19 vaccines using an adenoviral vector are not contraindicated. 
 

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All subjects participating in this study are encouraged to be up to date with their COVID-19 
vaccination status, including boosters.   
 
6.1.7 
ERT Clinical Assessment 
A clinical assessment of the need for ERT must be conducted at the ERT Withdrawal Follow-Up 
visit if a subject withdraws from ERT. The Site Investigator should determine if chronic ERT 
infusions will be resumed or if the subject may continue without ERT, and indicate the decision 
on the appropriate eCRF. The assessment will be made based on the clinical judgment of the Site 
Investigator and in consultation with the Medical Monitor, taking into account all information 
available (which may include but is not limited to AEs, clinical laboratory testing, α-Gal A 
levels, substrate levels, pain assessment, and other available data). The ERT Clinical Assessment 
may be completed again at any time post-ERT withdrawal if there is a clinically significant 
change in the status of the subject’s ERT administration. 
 
6.1.8 
ERT Administration Log 
The frequency of ERT administration will be studied before and after administration of ST-920. 
Each dose of ERT given to the subject from the time of screening will be recorded on the ERT 
Administration Log, including date and time of start and stop of ERT infusion. At each indicated 
visit, documentation of all ERT administration since the last visit must be obtained and 
confirmed. An assumed standing schedule (e.g., every other week) should not be used. 
 
6.1.9 
Diagnostic α-Gal A Activity  
If available, diagnostic α-Gal A activity results in plasma or leukocytes obtained prior to the 
study may be used.  
 
For subjects who do not have a documented diagnostic α-Gal A activity, a blood sample should 
be taken to measure α-Gal A activity in plasma. For those subjects who are on ERT, this blood 
draw must be taken at least 13 days after their last ERT infusion during trough.  
 
For details, refer to the Laboratory Manual. 
 
6.2 
Safety/Tolerability Assessments 
6.2.1 
Physical Examination 
Physical examinations will be conducted on each subject at the specified visit outlined in the 
Schedule of Events (Appendix 1) and will include at minimum: general appearance, head, eyes, 
ears, nose, and throat; as well as cardiovascular, dermatologic, respiratory, GI, musculoskeletal, 
and neurologic systems. For details, refer to the Study Reference Manual. 
 
6.2.2 
Vital Signs 
Vital signs, including height, weight, systolic/diastolic blood pressure, heart rate, respiratory rate, 
and temperature will be recorded. For details, refer to the Study Reference Manual. 
 

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6.2.3 
Clinical Laboratory  
Clinical laboratory tests are summarized in Table 2:  Clinical Laboratory Tests. For details, refer 
to the Laboratory Manual. 
 
Table 2: 
Clinical Laboratory Tests 
Hematology 
Complete blood count with 
differential and platelet 
count 
Urine (with microscopic examination) 
Glucose 
Protein 
Bilirubin 
Blood 
pH 
Specific gravity 
 
Serum Chemistry 
Sodium (Na) 
Potassium (K) 
Chloride (Cl) 
Carbonate (CO32-) 
Calcium (Ca) 
Phosphate (PO43-) 
Blood urea nitrogen 
Creatinine 
Glucose 
Uric acid 
Analyses will be done centrally unless local analyses is necessary with Sponsor agreement.  
 
6.2.4 
Adverse Events 
AEs will be assessed at each study visit beginning at informed consent. Subjects should be 
questioned about AEs at each scheduled clinic visit or during each telephone contact. The type of 
question asked should be open-ended, (e.g., “Have you had any new health problems?”) or a 
similar type of query. For details, refer to Section 9. 
 
6.2.5 
Liver Panel 
Liver panel will include assessment of ALT, AST, gamma-glutamyl transferase (GGT), total and 
direct bilirubin, ALP, lactate dehydrogenase (LDH), albumin, and total protein levels. Since 
monitoring of liver enzymes is important in this study, it is strongly recommended that subjects 
refrain from consuming alcohol during the study. Liver panel testing will be performed as 
described in the Schedule of Events (Appendix 1), may be conducted remotely, and analyzed 
centrally or locally. The liver panel does not need to be drawn as a separate blood sample if 
Clinical Laboratory Tests are obtained at the same visit. For details, refer to the Laboratory 
Manual. 
 
6.2.6 
12-Lead Electrocardiogram  
12-lead ECGs will be obtained to monitor cardiac function/conduction. For details, refer to the 
Study Reference Manual. 
 
6.2.7 
Echocardiogram  
Standard 2-dimensional Doppler ECHOs will be obtained to evaluate cardiac function. The 
measurements will include chamber volumes, ventricular wall thickness, left ventricular ejection 
fraction, regional wall motion, and valvular morphology and function. For details, refer to the 
Study Reference Manual and the Imaging Guidelines. An ECHO taken within 6 months of 

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consent in the study may be used to determine subject eligibility on a case-by-case basis at the 
discretion of the Site Investigator and the Medical Monitor.  
 
6.2.8 
Magnetic Resonance Imaging (MRI) of Liver 
Magnetic Resonance Imaging (MRI) of the liver is commonly used to evaluate liver pathology 
and will be performed in this study as described in the Schedule of Events (Appendix 1) to 
screen and monitor for the potential development of liver masses. An MRI of the liver can be 
replaced by an abdomen CT-scan or any equivalent imaging technology (like ultrasound) in case 
the subject has a contraindication to MRI (for example history of hip replacement). Parameters 
adapted to the search for a liver mass will be applied to any imaging modality.  
 
Any subject with an elevated AFP and MRI mass suspicious for HCC or greater than 2 cm will 
undergo liver biopsy (Appendix 4). For details, refer to the Study Reference Manual and the 
Imaging Guidelines. An MRI, or equivalent imaging technology, taken within 6 months of 
consent in the study may be used to determine subject eligibility on a case-by-case basis at the 
discretion of the Site Investigator and the Medical Monitor. 
 
6.2.9 
Circulating AFP Level 
Clinical laboratory measurement of AFP will be performed to monitor for potential development 
of malignancy. Subjects with elevated abnormal circulating AFP at screening are not eligible to 
participate in this study. Any subject with an elevated AFP and MRI mass suspicious for 
hepatocellular carcinoma (HCC) or greater than 2 cm will undergo liver biopsy (Appendix 4). 
For details, refer to the Laboratory Manual. 
 
6.2.10 
Vector Genome Polymerase Chain Reaction 
Plasma, saliva, urine, stool, and semen (if applicable) samples will be analyzed by qPCR to 
determine clearance of ST-920 vector genomes. Each type of sample (plasma, saliva, urine, 
stool, semen [if applicable]) should be collected until 3 consecutive specimens of that sample 
type are reported as negative or undetectable for vector genome. For details, refer to the 
Laboratory Manual. 
 
6.2.11 
COVID-19 Assessments 
Subjects will be assessed and monitored for COVID-19 as outlined in Appendix 7. Importantly, 
2 negative PCR tests will be required before the subject can be infused with ST-920. The first 
test can be done 10-14 days prior to planned dosing and the second test should be done 2-3 days 
prior to planned dosing. For details, refer to Appendix 7. 
 
In case of a positive result, COVID-19 standard of care according to the individual site’s 
guidelines will be initiated and the next steps will be discussed between the Investigator and the 
Sangamo Medical Monitor.  
 

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6.2.12 
Pregnancy Testing 
Female subjects who are women of childbearing potential will have a pregnancy test performed 
at the timepoints specified in Schedule of Events (Appendix 1, Appendix 2). Serum pregnancy 
tests will be performed at screening and sent to the central laboratory. At other visits, a urine 
pregnancy test should be performed by the local laboratory. A serum pregnancy test will be 
performed by the central laboratory in the event of a positive or equivocal urine pregnancy test 
result.  
 
6.3 
Pharmacodynamic Assessments 
6.3.1 
α-Gal A Testing in Blood  
α-Gal A activity in plasma will be measured to assess whether α-Gal A is being produced and is 
active.  α-Gal A activity measurements may be conducted. For those subjects on ERT, samples 
should be obtained at trough, defined as 14 days (± 1 day) after the previous ERT administration. 
The date and time of last ERT administration should be recorded on the sample collection eCRF 
as well as on the ERT Administration Log. Additional samples will also be obtained throughout 
the study to further our understanding of the pharmacokinetics of the enzyme and ensure that 
samples obtained prior to ERT are at trough. For details, refer to the Laboratory Manual. 
 
6.3.2 
Gb3 Testing  
Gb3 is a type of glycosphingolipid that accumulate within blood vessels, tissues and organs in 
Fabry disease due to a deficiency in α-Gal A. Gb3 levels in plasma, urine, and other tissues may 
be measured throughout this study to evaluate the impact of ST-920 administration and α-Gal A 
levels. For those subjects on ERT, plasma or urine samples should be obtained at trough, defined 
as 14 days (± 1 day) after the previous ERT administration. For details, refer to the Laboratory 
Manual. 
 
6.3.3 
Lyso-Gb3 Testing 
Lyso-Gb3 is a soluble form of the substrate Gb3. Lyso-Gb3 levels in plasma, urine, and other 
tissues may be measured throughout this study to evaluate the impact of ST-920 administration 
and α-Gal A levels. For those subjects on ERT, samples should be obtained at trough, defined as 
14 days (± 1 day) after the previous ERT administration. For details, refer to the Laboratory 
Manual. 
 
6.4 
Fabry Disease Clinical Impact Assessments 
6.4.1 
Glomerular Filtration Rate, and Total Protein and Albumin to Creatinine 
Ratios 
The kidneys are the organs most severely affected over the long-term course of Fabry disease, 
thereby leading to kidney disease as a major complication of Fabry disease. It would be most 
informative to show any reduction in Gb3 inclusion in the kidneys, however it is likely that most 
of the subjects enrolled in this Phase I/II study will be on ERT at baseline, and it may be 
challenging to see a meaningful change in Gb3 inclusion in the kidneys while on ERT or during 
a short period after ERT withdrawal. We also want to reduce subject burden as much as possible. 

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Therefore, we will instead be monitoring for any change in kidney function over time by 
calculating the glomerular filtration rate (eGFR), and total protein and albumin to creatinine 
ratios. For details, refer to the Study Reference Manual. 
 
6.4.2 
Kidney biopsy 
For those subjects who are ERT-naïve or ERT-pseudo-naïve (defined as has not having received 
ERT treatment during the 6 months prior to baseline) and selected subjects previously on 
migalastat who the Principal Investigator, in conversation with the Sponsor Medical Monitor, 
considers a non-responder to migalastat based on clinical and/or biochemical assessments, any 
meaningful reduction in Gb3 inclusion in the kidneys from baseline would be informative and 
potentially indicative of clinical benefit. Kidney biopsies will thus be performed on ERT-naïve 
or ERT-pseudo-naïve subjects and selected subjects previously on migalastat only, which will be 
on a voluntary basis for Cohort 2 and mandatory for subsequent cohorts unless contraindicated 
by a Site Investigator or physician. Kidney biopsies should be performed as per local 
hospital/institution guidelines. For details, refer to the Laboratory Manual. 
 
6.4.3 
Cardiac MRI 
Fabry disease can be associated with significant cardiac complications. Gb3 accumulates in the 
microvasculature, causing ischemic damages that can result in cardiovascular disease. 
Cardiovascular manifestations of Fabry disease include left ventricular hypertrophy (LVH), 
aortic and mitral regurgitation, conduction defects, coronary artery disease, hypertension, and 
aortic root dilation resulting in arrhythmia, palpitation, angina, dyspnea, or syncope. CMR will 
be used in all subjects to assess cardiac function and LVH by measuring ejection fraction, left 
ventricular global longitudinal strain, left ventricular systolic function and LVMI. It will also be 
used to evaluate changes over time in LGE, native myocardial T1 values and T2 mapping.  
Results from CMR performed within 6 months prior to consent can be used for screening or 
baseline if the patient fulfills the requirements within the Imaging Guidelines; for details, refer to 
the Imaging Guidelines. 
 
6.4.4 
Cardiac Biomarkers 
For all subjects, high sensitivity troponin T, N-terminal pro-hormone B-type natriuretic peptide 
(NT-proBNP), and other cardiac biomarkers, will be measured to assess the clinical impact of 
ST-920 on cardiac manifestations of Fabry disease. High-sensitivity troponin T is a biomarker 
for staging cardiomyopathy progression (Seydelmann et al. 2016) and may also be used to 
monitor subjects for transient myocarditis. NT-pro-BNP is a marker of early cardiac involvement 
and cardiomyopathy progression (Coats et al. 2013; Cammarata et al. 2018). For details, refer to 
the Study Reference Manual. 
 
6.4.5 
Minnesota Living With Heart Failure Questionnaire (MLHF-Q) Summary 
Score 
Heart failure is one of the cardiac manifestations of Fabry disease. (Seydelmann et al. 2016) The 
MLHF-Q is a health-related quality of life questionnaire for patients living with heart failure. It 
includes 21 items rated on six-point Likert scales. It provides a summary score (total score with 

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range 0-105, from best to worst quality of life), as well as scores for physical (8 items, 
range 0-40) and emotional (5 items, range 0-25) dimensions of heart failure. (Bilbao et al. 2016) 
For subjects in the Cardiac cohort, the MLHF-Q summary score will be used to measure quality 
of life. For details, refer to the Study Reference Manual.  
 
6.4.6 
Skin Biopsy 
Progressive Gb3 accumulation in dermal fibroblasts can lead to skin lesions and small fiber 
neuropathy (SFN) responsible for paraesthesias of extremities, hypohydrosis, and GI symptoms. 
Skin biopsies will be performed in ERT-naïve and ERT-pseudo-naïve subjects and selected 
subjects previously on migalastat to monitor any changes in substrate accumulation in skin 
tissues to evaluate any potential impact of ST-920 on any substrate reduction in skin tissues. 
α-Gal A may also be measured in skin biopsies to determine any tissue uptake of the enzyme in 
all subjects. Of note is that special considerations may need to be taken into account for female 
patients based on variable patterns of X chromosome inactivation. For details, refer to the Study 
Reference Manual and Laboratory Manual. 
 
6.4.7 
Pain Assessments: Frequency of Pain Medication Use and Short Form Brief 
Pain Inventory  
Fabry disease can cause pain and burning in the hands and feet (acroparesthesia). This study will 
assess the frequency of pain medication use and will use the short form BPI to measure pain. For 
details, refer to the Study Reference Manual. 
 
6.4.8 
Quality of Life 
Patients with Fabry disease have a lower QOL than the general population. The SF-36 v2 
questionnaire will be used to assess QOL in this study. For details, refer to the Study Reference 
Manual. 
 
6.4.9 
Gastrointestinal Symptoms Rating Scale 
Fabry disease frequently causes GI symptoms such as abdominal pain, diarrhea, constipation, 
nausea, and vomiting. The GI Symptom Rating Scale will be used to assess GI symptoms. For 
details, refer to the Study Reference Manual. 
 
6.4.10 
Mainz Severity Score Index (MSSI) 
The MSSI is a clinical scoring system developed to assess overall disease severity in each 
subject by recording which organs or systems are affected and applying a weighting based on 
impact of organ involvement and their contribution to the morbidity of the disease. The MSSI is 
composed of four sections that cover general, neurological, cardiovascular and renal signs and 
symptoms of Fabry disease. MSSI will be recorded to assess any change in Fabry disease 
progression over time. For details, refer to the Study Reference Manual. 
 

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6.4.11 
Pulmonary Function Tests  
Fabry disease may be associated with pulmonary complications such as airway narrowing and 
capillary blockage. Pulmonary function tests (PFTs) are a common method for evaluating 
respiratory function and will be conducted in this study. For details, refer to the Study Reference 
Manual. Pulmonary function tests taken within 6 months of consent in the study may be used to 
determine subject eligibility on a case-by-case basis at the discretion of the Site Investigator and 
the Medical Monitor. 
 
6.4.12 
Audiologic Evaluation 
Patients with Fabry disease may experience audiologic symptoms such as tinnitus, vertigo, and 
progressive hearing loss. Subjects in this study will receive audiologic evaluations to monitor 
any hearing loss. For details, refer to the Study Reference Manual. 
 
6.5 
Immunogenicity 
Immune responses to both the AAV6 capsid and the α-Gal A enzyme will be assessed by 
measuring total antibodies and/or neutralizing antibodies. Samples for cell-mediated 
immunogenicity will also be collected and stored for future analysis. 
 
6.6 
Future Research 
Any samples collected from consenting subjects may be used for future research which may 
include analysis of biomarkers of renal function and severity of disease, response to therapy 
(e.g., cytokines, soluble cell surface proteins, soluble receptors), additional measures of α-Gal A 
activity/protein levels, correlation with functional improvements, as well as determination of 
AAV virus inhibition, function, immunogenicity, or pharmacodynamics (e.g., antibodies, soluble 
receptors, AAV viral receptor inhibitors, cytokines, co-existing alternate serotype antibodies). 
 
7 
INVESTIGATIONAL PRODUCT AND OTHER STUDY MEDICATIONS 
7.1 
ST-920 
ST-920 is a recombinant AAV vector, AAV2 serotype 6 (AAV2/6), encoding human GLA 
cDNA. 
 
Each lot of ST-920 is formulated at approximately 1.00E+13 vg/mL measured by qPCR in 
phosphate buffered saline (PBS) containing CaCl2, MgCl2, NaCl, Sucrose and Kolliphor 
(Poloxamer) P 188, filled at volumes of 5 mL or 10 mL into vials, and stored at ≤-65°C. The 
vials of ST-920 are labeled and have an aluminum seal with a flip-top. 
 
A ddPCR test method is being developed to determine the level of vector genome (vg) titers for 
ST-920 and will replace the current qPCR method once fully implemented. The nominal genome 
copies (vg/mL) in the investigational product are not changing, just the method by which they 
are measured. The Investigational Product tested using the qPCR method that is within the 
approved shelf life will be used in ST-920-201 study until fully depleted. Clinical batches tested 
using ddPCR method will be used to support the ongoing ST-920-201 study. The Quality dossier 

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with the ddPCR data will be submitted for review prior to the introduction of the ddPCR material 
into ST-920-201. 
 
7.1.1 
Inventory, Storage, and Handling of the Drug Product 
The investigational product required for subject treatment will be shipped to the study center 
with dry ice and temperature monitoring device and will be required to be stored at ≤-65°C (with 
temperature monitoring) prior to the scheduled infusion. 
 
A Clinical Certificate of Analysis (CcoA) will accompany each investigational product shipment. 
The vials will have a label affixed containing the following information: vector identity, lot 
number, concentration, volume, storage conditions, manufacturer, date of manufacturing, 
Sponsor, and “Caution: For investigational use only.” 
 
Subject-specific kits, in the quantities required based on the subject’s weight and cohort, will be 
prepared for shipment to the facility where IP infusion will take place. Kit labels will contain the 
following additional information: subject ID number, protocol number, and quantity. 
 
The study center is required to maintain complete records of all study products received during 
the course of this study, as well as of labeled product that is dispensed. At the conclusion or 
termination of this study, return or destruction of all drug supplies must be pre-approved and 
coordinated with the Sponsor (Refer to the Pharmacy Manual for additional details). 
 
The Site Investigator agrees not to supply labeled product to any person other than study 
personnel and subjects in this study. 
 
7.1.2 
ST-920 Administration 
ST-920 will be administered by IV infusion using a peristaltic pump or IV infusion pump. 
ST-920 should be prepared by a research pharmacy at or near the health care facility and will be 
administered through an IV catheter at a controlled speed while monitoring the subject’s vital 
signs (heart rate, blood pressure, respiratory rate, and temperature). Total volumes will be 
dependent on subject’s cohort assignment and body weight (kg) at baseline. Detailed instructions 
for the thaw and administration of ST-920 are provided in the Pharmacy Manual. 
 
Following ST-920 infusion transient fever, chills, and/or nausea may occur. All subjects must be 
pre-medicated with acetaminophen 650 mg and diphenhydramine hydrochloride (Benadryl®) 
25-50 mg by mouth or IV, or equivalent as per site practice, approximately one hour prior to the 
administration of ST-920. Post- infusion fever and/or chills can be treated with antipyretics not 
exceeding the maximum recommended daily dose and following guidance on the applicable 
product label. If fever and/or chills recur or persist for 24 hours, an evaluation to rule out 
infection should be conducted. 
 
7.1.3 
Precautions 
ST-920 is an investigational product, and there is a potential risk of infusion reactions. 
Emergency medical equipment must be available during the infusion in case the subject has a 

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severe infusion reaction. Vital signs (temperature, heart rate, respiratory rate, and blood pressure) 
must be taken before, during, and after infusion (see Appendix 1 and refer to the Study 
Reference Manual).  
 
All dangerous goods materials, including diagnostic specimens and infectious substances, must 
be transported according to the instructions detailed in the International Air Transport 
Association (IATA) Dangerous Goods Regulations. 
 
7.1.4 
Dose Modifications 
No dose modifications are possible within an individual subject since this is a single infusion 
study. 
 
7.2 
Concomitant Medication and Supportive Care 
The Site Investigator or designate will record all concomitant medications, including over-the-
counter medicinal products, dietary supplements, herbal medications, and medications given in 
treatment of AEs, taken by a subject from screening throughout the course of the study on the 
concomitant medications page in the subject’s case report form (CRF).  
 
All medications are permitted with limited exceptions. The use of potentially hepatotoxic agents 
including herbal supplements may be allowed based on discussion and agreement with the 
Medical Monitor. 
 
For subjects receiving ERT, ERT must have been administered at a stable dose and regimen 
(defined as not having missed more than 3 doses of ERT during the 6 months prior to consent). 
Subjects should continue to receive ERT at a stable dose and regimen (14 days ± 1 day) during 
the study as per standard of care unless they undergo ERT withdrawal (Section 3.6). 
Administration of all ERT should be obtained and recorded in the ERT Administration Log. 
 
Subjects who are ERT-naïve or ERT-pseudo-naïve (defined as not having received ERT 
treatment in the 6 months prior to baseline) may not initiate treatment with ERT during the study 
period, unless dictated by clinical circumstances and following discussion with the Sponsor 
Medical Monitor. Subjects may not initiate treatment with migalastat (Galafold™) during the 
study period. 
 
Treatment with prednisone or other equipotent steroid and pre-treatment with acetaminophen and 
diphenhydramine hydrochloride should also be recorded on the concomitant medications page. 
 
8 
SAFETY AND POTENTIAL RISKS 
Study ST-920-201 is planned as the first-in-human study to assess the safety and tolerability of 
ST-920. There are currently no identified risks with ST-920. Potential risks associated with 
ST-920 include immune reaction to the vector and/or transgene, off-target effects, insertional 
mutagenesis (carcinogenesis), and risk of horizontal and vertical transmission. For details refer to 
current version of the Investigator Brochure. 
 

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9 
SAFETY MONITORING AND ADVERSE EVENTS  
9.1 
Definitions 
9.1.1 
Adverse Event  
An AE is any untoward medical occurrence in a patient or a clinical trial subject administered a 
medicinal product. An AE does not necessarily have a causal relationship with the administered 
treatment. The term can include any of the following events that develop or increase in severity 
during the course of the study: 
• Any sign, symptom, or physical examination finding that worsens in nature, severity, or 
frequency compared to baseline, whether thought to be related or unrelated to the condition 
under study. 
• Any laboratory abnormality that is clinically significant or that requires medication or 
hospitalization. 
• All reactions associated with the use of the study treatment, including those occurring as a 
result of an overdose, abuse, withdrawal phenomena, sensitivity, or toxicity to the study 
treatment. 
• Concurrent illness. 
• Injury or accident. 
A pre-existing condition is one that is present prior to or at the start of the study, and is to be 
reported as part of the subject’s medical history. It should be reported as an AE only if the 
frequency, intensity, or the character of the condition worsens during study participation. 
 
9.1.2 
Serious Adverse Event  
An AE is considered “serious” if, in the view of either the Site Investigator or the Sponsor, it 
results in any of the following outcomes: 
• Death. 
• Life-threatening AE (i.e., AE in which the subject is at risk of death at the time of the event; 
it does not refer to an event that hypothetically might have caused death if it were more 
severe). 
• Inpatient hospitalization or prolongation of existing hospitalization. 
• Persistent or significant incapacity or substantial disruption of ability to conduct normal life 
functions. 
• Congenital anomaly/birth defect in the offspring of an exposed subject. 
 
A medically important event (i.e., an AE that may not result in death, be life-threatening, or 
require hospitalization, but may be considered serious when, based upon appropriate medical 
judgment, the AE may jeopardize the subject and may require medical or surgical intervention to 
prevent one of the outcomes listed above; examples of such medical events include but are not 
limited to allergic bronchospasm requiring intensive treatment in an emergency room or at home, 
blood dyscrasias, or convulsions that do not result in inpatient hospitalizations.) 
 

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9.1.3 
Suspected Unexpected Serious Adverse Reaction 
A suspected unexpected serious adverse reaction (SUSAR) is any SAE that is assessed as both 
unexpected and, in the view of either the Site Investigator or the Sponsor, as a suspected adverse 
reaction. The term suspected adverse reaction means that a causal relationship between the 
medicinal product and the event is at least a reasonable possibility (i.e., there are facts [evidence] 
or arguments to suggest a causal relationship). The definition of a suspected adverse reaction 
also covers medication errors and uses outside what is foreseen in the protocol, including misuse 
and abuse of the product. 
 
An SAE is considered unexpected when its nature or severity is not consistent with the reference 
safety information (RSI) for the product. The expectedness of all SAEs will be determined by the 
Sponsor according to the Investigator Brochure. 
 
9.2 
Adverse Event Reporting Period  
AEs will be monitored continuously during the study and reported from the time that the subject 
has provided written informed consent through the subject’s last day of study participation. 
Subjects will be queried and events will be assessed at each clinic visit. Further assessments may 
be done if indicated for evaluating and monitoring the AE(s).  
 
9.3 
Recording of an Adverse Event 
The Site Investigator is responsible for evaluating all AEs, obtaining supporting documents, and 
determining that documentation of the event is adequate. He/she is responsible for determining 
the severity of the AE and its relationship to the investigational drug. The Site Investigator may 
delegate these duties to Sub-Investigators but must assure that these Sub-Investigators are 
qualified to perform these duties under the supervision of the Site Investigator. 
 
All AEs will be recorded in the subject’s CRF. The detailed description of the event will include 
appropriately graded severity of the AE and its relationship to the investigational product. 
 
Severity 
Severity will be categorized by toxicity grade according to the Common Terminology Criteria 
for Adverse Events (CTCAE) Version 5.0. 
 
AEs not listed in the Common Terminology Criteria for Adverse Events version 5.0 will be 
evaluated by using the following criteria:  
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
Grade 2: Moderate; minimal, local or non-invasive intervention indicated; limiting 
age -appropriate instrumental ADL (e.g., preparing meals, shopping for groceries or 
clothes, using the telephone, managing money, etc.). 

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Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self care ADL (e.g., 
bathing, dressing and undressing, feeding self, using the toilet, taking medications, and 
not bedridden). 
Grade 4: Life-threatening consequences; urgent intervention indicated. 
Grade 5: Death related to AE. 
 
Any Grade 3 and 4 clinical laboratory results that represents an increase in severity from baseline 
will be reported as an AE if it is not associated with a diagnosis already reported on the CRF. A 
Grade 1 or 2 clinical laboratory abnormality should be reported as an AE only if it is considered 
clinically significant by the Site Investigator. 
 
In the event of death, the cause of death should be recorded as the AE and reported as a SAE. 
“Death” is an outcome and not an AE. The term “death” should be reported as an SAE only if the 
cause of death is not known and cannot be determined. If an autopsy is performed, a copy of the 
autopsy report should be obtained if possible. The Site Investigator should make every effort to 
obtain and send death certificates and autopsy reports to Sponsor or designee. 
 
Relationship to Study Treatment 
The relationship of the AE to the investigational drug and corticosteroids if administered will be 
determined by the Site Investigator. The following definitions should be considered when 
evaluating the relationship of AEs and SAEs to ST-920 treatment. 
 
Not related: 
 
An AE will be considered “not related” to the use of the investigational product or the 
corticosteroid if there is not a reasonable possibility that the event has been caused by the 
product under investigation or the corticosteroid. Factors pointing toward this assessment 
include but are not limited to the lack of reasonable temporal relationship between 
administration of the product and the AE, the presence of a biologically implausible 
relationship between the product and the AE, or the presence of a more likely alternative 
explanation for the AE. 
 
Related: 
 
An AE will be considered “related” to the use of the investigational product or the 
corticosteroid if there is a reasonable possibility that the event may have been caused by the 
product under investigation. Factors that point toward this assessment include but are not 
limited to a positive rechallenge, a reasonable temporal sequence between administration of 
the product and the AE, a known response pattern of the suspected product, improvement 
following discontinuation or dose reduction, a biologically plausible relationship between the 
product and the AE, or a lack of an alternative explanation for the AE. 
 
9.4 
Serious Adverse Event Reporting 
All SAEs, whether or not considered to be related to the administration of study treatment or the 
corticosteroid, must be reported immediately to Sponsor’s designee, Medpace Clinical Safety, on 
an SAE Report form within 24 hours of the Site Investigator’s awareness.  
 

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Clinical Study Protocol Amendment 7 08June2022 
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MedPace Clinical Safety SAE Report Notification: 
Email: Medpace-safetynotification@medpace.com 
Telephone: +1-800-730-5779, dial 3 or +1-513-579-9911, dial 3 or +49 89 89 55 718 44 
Fax: +1-866-336-5320 or +49 89 89 55 718 104 
 
Completion Guidelines of the SAE Report Form should be referred to when completing the SAE 
Report Form. Medpace Clinical Safety will query the Site Investigator regarding any further 
information or documentation that is required for a complete case report. Follow-up reports must 
be submitted within 24 hours from the time that the additional information becomes available. 
All SAEs must be followed with appropriate medical management until resolved or stabilized. 
 
The reporting period for all SAEs is from subject consent through the last study visit. 
 
The Site Investigator is responsible for promptly notifying the IRB/IEC or equivalent in 
accordance with local regulations of all SAEs. 
 
9.5 
Suspected Unexpected Serious Adverse Reaction Reporting Obligations 
The Sponsor or its designee will submit SUSAR reports to appropriate regulatory authorities 
(including Competent Authorities in all Member States concerned), Ethics Committees, and Site 
Investigators as per local laws and regulations. Fatal and life-threatening SUSARs will be 
submitted no later than 7 calendar days of first knowledge of the event and follow-up 
information submitted within an additional 8 days. All other SUSARs will be submitted within 
15 calendar days of first knowledge of the event.  
 
Site Investigators are required to report any urgent safety matters to Sponsor or its designee 
within 24 hours. Sponsor or its designee will inform the regulatory authorities, ethics 
committees, and Site Investigators of any events (e.g., change to the safety profile of the study 
treatment, major safety findings) that may occur during the clinical trial that do not fall within 
the definition of a SUSAR but may affect the safety of subjects participating in the clinical trials, 
as required, in accordance with applicable laws and regulations. The reporting period for urgent 
safety issues is the period from the signing of the Informed Consent Form (ICF) through the last 
study visit.  
 
The Site Investigator will notify the IRB/IEC or equivalent of SAEs and urgent safety matters, in 
accordance with IRB/IEC or equivalent requirements and local laws and regulations. A copy of 
this notification must be provided to Sponsor or its designee. 
 
9.6 
Pregnancy Reporting  
Pregnancies of female subjects and pregnancies of male subjects’ partners occurring during this 
study are to be reported to Medpace Clinical Safety on the Pregnancy Reporting Form, as per 
reporting details above in Section 9.4. In general, it is expected that pregnancies are reported in 
the same timeframe as SAEs (i.e., within 24 hours of awareness by the site). The course of all 
pregnancies will be followed to partum at minimum. Congenital abnormalities/birth defects in 
the offspring of subjects should be reported as an SAE if conception occurred during this study. 

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Clinical Study Protocol Amendment 7 08June2022 
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Consent will be collected from the pregnant partner as per local country requirements before any 
data is collected. 
 
9.7 
Overdose Reporting 
Overdose refers to the administration of a quantity of a medicinal product given per 
administration or cumulatively (accidentally or intentionally), which is above the maximum 
recommended dose according to the protocol.  For this study, administration of the 
investigational medicinal product, ST-920, in excess of the protocol defined dose is required to 
be reported within 24 hours of awareness, regardless of whether the overdose is associated with 
clinical sequelae.  The Investigator must complete an Overdose Report Form and submit to 
Medpace Clinical Safety, as per Section 9.4 above. 
 
10 
SUBJECT WITHDRAWAL/DISCONTINUATION, AND SAFETY 
MONITORING COMMITTEE 
10.1 
Subject Withdrawal and Discontinuation from Study 
Subjects may withdraw or should be discontinued from study for any of the following reasons: 
• 
Request by the subject to withdraw. 
• 
Request of Sponsor or primary care provider if he or she thinks the study is no longer in the 
best interest of the subject. 
• 
Subject judged by the Site Investigator to be at significant risk of failing to comply with the 
provisions of the protocol as to cause harm to self or seriously interfere with the validity of 
the study results. 
• 
At the discretion of the IRB/IEC or equivalent, Office for Human Research (OHR), 
regulatory authority (e.g. FDA/ Medicines and Healthcare products Regulatory Agency 
[MHRA] or equivalent), Site Investigator, or Sponsor. 
Subjects who, after dosing, discontinue from the study prematurely or are withdrawn from the 
study will be asked to return to the study site for an early termination visit (ETV). Subjects will 
be strongly encouraged to continue and comply with follow-up safety evaluations. If a subject 
withdraws consent or discontinues from the study post-study treatment, a conference between the 
Site Investigator and Medical Monitor will take place to ensure that the subject understands the 
importance of the study follow-up and that the study treatment cannot be reversed even if a 
subject drops out of the study follow-up. If the subject agrees, a reduced follow-up testing 
schedule may be arranged including telephone call and safety labs to assess treatment-related 
AEs and disease status. See the Schedule of Events (Appendix 1) for a list of assessments and 
procedures performed during the ETV. 
 
10.2 
Safety Monitoring and Mitigation Plan 
Elevation of liver enzymes has been observed in other trials using AAV2/6. Therefore, liver tests 
(AST, ALT, bilirubin, alkaline phosphatase, and GGT) will be monitored closely throughout the 
study. 

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Clinical Study Protocol Amendment 7 08June2022 
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These will be performed twice weekly during the first 20 weeks after ST-920 infusion, weekly 
for four weeks (Weeks 21-24), and then monthly thereafter to coincide with study visits (Weeks 
28-52) in all subjects, and may be conducted remotely. 
If there is a need to initiate corticosteroid treatment as a result of elevated liver enzymes, liver 
enzymes will continue to be assessed at least twice a week until normalization and then per 
protocol thereafter analyzed locally or centrally.  
 
10.3 
Safety Monitoring Committee  
An SMC with appropriate medical and scientific expertise was appointed to provide safety 
oversight for the study. The SMC is comprised of external subject matter experts, the study 
Medical Monitor, Sponsor’s Drug Safety Lead, study Biostatistician, and Site Investigators as 
appropriate. The SMC will periodically meet during the study and provide recommendations to 
the Sponsor concerning dosing. The SMC will also convene at any time if an emergent safety 
issue emerges during the study or one of the stopping rules are met. These include:   
 
• Any one Grade 3 or higher AE with at least a reasonable possibility of a causal relationship 
to the investigational product,  
• Any SAE with at least a reasonable possibility of a causal relationship to the investigational 
product 
• Death of a subject 
• Development of a malignancy, with the exception of non-melanoma skin cancers and 
localized prostate cancer treated with curative intent 
 
The study may also be stopped for any of the following reasons: 
• Sponsor, in consultation with the SMC or Regulatory Agency, decides for any reason that 
subject safety may be compromised by continuing the study. 
• Sponsor decides to discontinue the development of the investigational product, ST-920. 
 
All data will be evaluated to determine whether changes should be made to the study or if 
accrual should be continued or halted. If stopping criteria are met, no further dosing of subjects 
will be performed at that dose level or higher until a substantial amendment is submitted to 
regulatory authorities for review, and the amendment has been approved by the site Institutional 
Review Board (IRB)/Independent Ethics Committee (IEC) or equivalent. 
 
Relevant data from other trials sponsored by Sangamo may be shared with the SMC to expand 
the clinical experience, particularly as it relates to safety and dose, and such data can be used by 
the SMC to inform its recommendations for the present study. 
 
The SMC may also recommend changes to the dose and enrollment of cohorts based on 
cumulative safety data from this and other Sangamo sponsored clinical trials that use in vivo 
AAV2/6-based therapy. 
 

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CONFIDENTIAL 
 
Clinical Study Protocol Amendment 7 08June2022 
Page 73 of 92 
After the SMC meetings, the study sites will be informed of any decisions made in regards to the 
study and of any relevant safety data that might be helpful for subject treatment, follow-up and 
safety. 
 
When no further enrolling or dosing decisions are required of the SMC, the SMC will no longer 
meet on a regular basis. The Sponsor will continue to review the subject safety data on an 
ongoing basis. 
 
11 
STATISTICAL ANALYSES 
11.1 
Determination of Sample Size 
This study will enroll up to 48 subjects (2 subjects in each of Cohorts 1, 2, 3, and 4 with potential 
enrollment of 4 additional subjects in Cohorts 1, 2a, 2b, 3a, 3b, 4a, and 4b, plus up to 6 subjects 
in each of the anti α-Gal A Ab positive, anti α-Gal A Ab negative, female, renal, and cardiac 
cohorts). The sample size for this study was not based on statistical considerations but is 
considered sufficient to provide a preliminary assessment of the safety and tolerability of ST-920 
in subjects with Fabry disease. 
 
Subjects who prematurely discontinue the study prior to the 52 weeks of study follow-up (i.e., 
subjects who were enrolled but not dosed, were lost to follow-up, or discontinued prematurely 
for another reason) may be replaced at the discretion of the Sponsor. 
 
11.2 
Statistical Analyses 
The primary objective of this study is to evaluate the safety and tolerability of ST-920. All 
statistical summaries will be descriptive in nature. All subjects who receive any portion of the 
ST-920 infusion will be included in the analyses. All analyses, summaries, and listing will be 
generated using SAS version 9.4 or later. Further analysis details will be provided in the 
statistical analysis plan (SAP). 
 
11.2.1 
Analysis of the Conduct of the Study 
Enrollment, major protocol violations, and discontinuations from the study will be summarized 
by dose and cohort. The number of subjects who were enrolled, dosed, discontinued, and 
completed the study will be summarized. 
 
Demographic and baseline characteristics will be summarized overall and by dose and cohort.  
 
11.2.2 
Primary Safety Analyses  
The primary objective of this study is to evaluate the safety and tolerability of ST-920. Safety 
assessments will be performed on all subjects. All reported AEs will be coded to a standard set of 
terms using the Medical Dictionary for Regulatory Activities (MedDRA).  
 
The incidence of TEAEs will be evaluated to address the primary endpoint of this study. A 
TEAE is any AE with an onset from administration of the study treatment through the last study 
visit, whether or not it is considered causally related to the study treatment. TEAEs will be 

Sangamo Therapeutics, Inc. 
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CONFIDENTIAL 
 
Clinical Study Protocol Amendment 7 08June2022 
Page 74 of 92 
summarized overall and by dose and cohort. For each subject, the maximum reported severity of 
each AE will be used in the summaries by severity grade. In addition, summaries of all SAEs and 
AEs related to study treatment will be provided. 
 
Additional safety evaluations will include: 
• Routine hematology, chemistry, and liver tests, vital signs, ECG and ECHO  
• Serial AFP testing and MRI of liver (or equivalent imaging modality) to monitor for liver 
mass. 
 
For other safety evaluations, data will be summarized for each time point.  Change from baseline 
values may be calculated for continuous parameters and summarized by time point.  Shift-tables 
may also be constructed for selected parameters. 
 
11.2.3 
Secondary Analyses 
At each sampling time point, the actual value and the change from baseline for plasma α-Gal A 
activity, Gb3 and lyso-Gb3, eGFR, ejection fraction, global longitudinal strain, and LVMI and 
left ventricular systolic function will be summarized by dose and cohort using descriptive 
statistics and plotted over the 1-year study period by dose and cohort. Similar summaries will 
also be provided for ERT naïve/ERT pseudo-naïve subjects, and separately for ERT subjects 
(migalastat subjects will be grouped with either the ERT naïve/ERT pseudo-naïve subjects, or 
with the ERT subject, based on the clinical response determined by the Investigator at 
Screening). 
 
For subjects who undergo ERT withdrawal, changes from pre- to post-ERT withdrawal in the 
frequency and dose of ERT infusions will be evaluated and summarized using annualized total 
dose and number of infusions. Duration of ERT withdrawal may also be analyzed.  
 
Clearance of ST-920 measured by vg in the different samples (plasma, saliva, urine, stool, and 
semen, if applicable) will be summarized over time by dose and cohort. 
 
11.2.4 
Exploratory Analyses 
Data permitting, the following exploratory endpoints and their change from baseline summaries 
by dose and cohort will be provided at each sampling time point over the 1-year study period: 
• LGE, native myocardial T1 values and T2 mapping measured by CMR 
• High sensitivity troponin T, NT-proBNP and other cardiac biomarkers  
• MLHF-Q summary score  
• UPCR and UACR 
• Biomarkers of renal function in urine 
• Neuropathic pain measured by the BPI 
• Frequency of pain medication use 
• GI symptoms measured by the GI symptoms rating scale 
• MSSI 
• QOL patient-reported outcome measured by the SF-36 questionnaire 
• α-Gal A activity measured in skin  

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Clinical Study Protocol Amendment 7 08June2022 
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• Gb3 inclusion levels measured in skin in ERT-naïve and ERT-pseudo-naïve subjects and 
selected subjects previously on migalastat 
• Gb3 and lyso-Gb3 urine for all subjects over time 
• Pulmonary function over time 
• Audiologic function over time 
 
Data permitting, summaries of percent reduction from baseline at Week 24 by dose and cohort 
will be provided for:   
• Gb3 inclusion in the kidney (assessed by kidney biopsy) in ERT-naïve and ERT-pseudo-
naïve subjects and selected subjects previously on migalastat 
 
Summaries by dose and cohort will be provided for the following exploratory endpoints at each 
sampling time point: 
• Measurement of antibodies to AAV2/6  
• Assessment of cell-mediated immune response to AAV2/6 
• Measurement of immune response to α-Gal A  
 
 

Sangamo Therapeutics, Inc. 
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CONFIDENTIAL 
 
Clinical Study Protocol Amendment 7 08June2022 
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12 
REFERENCES 
Arends M, Wanner C, Hughes D, Mehta A, Oder D, Watkinson OT, Elliott PM, Linthorst 
GE, Wijburg FA, Biegstraaten M, Hollak CE. Characterization of Classical and 
Nonclassical Fabry Disease: A Multicenter Study. J Am Soc Nephrol 2017;28(5):1631–41. 
AveXis. ZOLGENSMA® (onasemnogene abeparvovec-xioi) Prescribing Information. 2019. 
Bennett J, Wellman J, Marshall KA, McCague S, Ashtari M, DiStefano-Pappas J, Elci OU, 
Chung DC, Sun J, Wright JF, Cross DR, Aravand P, Cyckowski LL, Bennicelli JL, Mingozzi F, 
Auricchio A, Pierce EA, Ruggiero J, Leroy BP, Simonelli F, High KA, Maguire AM. Safety and 
durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with 
childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial. Lancet. 2016 
Aug 13;388(10045):661-72.  
Bilbao A, Escobar A, Garcia-Perez L, et al. The Minnesota living with heart failure 
questionnaire: comparison of different factor structures. Health and Quality of Life Outcomes 
2016;14:23. 
Cammarata G, Scalia S, Colomba P, et al. A pilot study of circulating microRNAs as potential 
biomarkers of Fabry disease. Oncotarget 2018;9(44):27333-27345. 
Clarke J, West ML, Bultas J, Schiffman R. The pharmacology of multiple regimens of agalsidase 
alfa enzyme replacement therapy for Fabry disease. Genet Med. 2007 Aug;9(8):504-9. PubMed 
PMID: 17700388. 
Coats CJ, Parisi V, Ramos M, et al. Role of serum N-terminal pro-brain natriuretic peptide 
measurement in diagnosis of cardiac involvement in patients with Anderson-Fabry disease. The 
American Journal of Cardiology 2013; 111(1):111-117. 
Davidoff AM, et al. Sex significantly influences transduction of murine liver by recombinant 
adeno-associated viral vectors through an androgen-dependent pathway. Blood 2003, 102(2): 
480-488. 
Linthorst GE, Hollak CE, Donker-Koopman WE, Strijland A, Aerts JM. Enzyme therapy for 
Fabry disease: neutralizing antibodies toward agalsidase alpha and beta. Kidney Int 
2004;66:1589–95. 
Manno CS, Pierce GF, Arruda VR, Glader B, Ragni M, Basko JJ, Ozelo MC, Hoots K, Blatt P, 
Konkle B, Dake M, Kaye R, Razavi M, Zaiko A, Zehnder J, Rustagi PK, Nakai H, Chew A, 
Leonard D, Wright JF, Lessard RR, Sommer JM, Tigges M, Sabatino D, Luk Am Jiang H, 
Mingozzi F, Couto L, Ertl HC, High KA, Kay MA. Successful transduction of liver in 
hemophilia by AAV-factor IX and limitations imposed by the host immune response. Nat Med. 
2006 Mar;12(3):342-7. 
Muhuri M, Levy DI, Schulz M, McCarty D, Gao G. Durability of transgene expression after 
rAAV gene therapy. Mol Ther. 2022 Apr 6;30(4):1364-1380. doi: 10.1016/j.ymthe.2022.03.004. 
Epub 2022 Mar 10.  
Nathwani AC, Reiss UM, Tuddenham EG, et al. Long-term safety and efficacy of factor IX gene 
therapy in hemophilia B. N Engl J Med. 2014 Nov 20;371(21):1994-2004. 

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ST-920-201 
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Clinical Study Protocol Amendment 7 08June2022 
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Nathwani AC, Reiss U, Tuddenham E, et al. Adeno-Associated Mediated Gene Transfer for 
Hemophilia B:8 Year Follow up and Impact of Removing "Empty Viral Particles" on Safety and 
Efficacy of Gene Transfer. Blood 2018; 132 (Supplement 1): 491.  
 
Nietupski JB, et al. Systemic Administration of AAV8-α-galactosidase A Induces Humoral 
Tolerance in Nonhuman Primates Despite Low Hepatic Expression. Mol Ther. 2011, 19(11): 
1999-2011. 
Seydelmann N, Liu D, Kramer J, et al. High-sensitivity troponin: A clinical blood biomarker for 
staging cardiomyopathy in Fabry disease. Journal of the American Heart Association 
2016;5:e002839. 
Winchester B, Young E. Fabry disease: perspective from 5 years of FOS. Chapter 18 In Mehta A 
et al editors. Oxford PharmaGenesis 2006. 
Zanta-Boussif MA, et al. Validation of a mutated PRE sequence allowing high and sustained 
transgene expression while abrogating WHV-X protein synthesis: application to the gene therapy 
of WAS. Gene Therapy. 2009 16(5): 605–19. 
Zufferey R., et al. Woodchuck hepatitis virus posttranscriptional regulatory element enhances 
expression of transgenes delivered by retroviral vectors. J Virol. 1999 73(4): 2886-92. 
 
 

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      CONFIDENTIAL 
 
Clinical Study Protocol Amendment 7 08June2022 
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APPENDIX 1: SCHEDULE OF EVENTS 
PROCEDURE 
Screening  
Baseline 
(a) 
Health 
Care 
Facility 
Day 
Week  
ETV  
 
 
8 
2 
4 
6 
8 
12 
16 
20 
24 
28
* 
32
* 
36 
40* 
44
* 
48* 
52 
EOS 
 
 
(w/in 8 
weeks of 
Baseline) 
(w/in 12 
weeks 
prior to 
ST-920 
infusion) 
Day 
1 
Day 
2  
(+/-
1 
day
) 
(+/-2 days) 
(+/-1 week) 
(+/-2 
weeks) 
(+/-1 week) 
(-2 
weeks/+
1 
month) 
 
Informed Consent 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Medical History 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Inclusion/Exclusion 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Demographics 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Fabry Gene 
Sequencing (b, c) 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Infectious Disease 
Screening 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Neutralizing 
Antibodies to AAV2/6 
(d) 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Physical Examination 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
 
 
X 
  
  
X 
  
  
 
X 
X 
Vital Signs (e) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
X 
  
  
 
X 
X 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Laboratory (f) 
X 
X 
X 
(g) 
X 
  
X 
X 
X 
X 
X 
X 
X 
X 
  
  
X 
  
 
 
X 
X 
AE Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ERT Administration 
Log 
X 
X 
X 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Liver Panel (h) 
X 
X (i) 
X 
(g) 
X  
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECG 
X 
X 
  
  
X 
  
  
  
  
  
  
  
X 
  
  
  
  
  
 
X 
X 
ECHO (b) 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
X 
X 
MRI of Liver (b, j) 
X 
  
  
  
  
  
  
  
  
  
  
  
X 
  
  
  
  
  
 
X 
X 
eGFR (k) 
X 
X 
  
  
X 
  
X 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Diagnostic α-Gal A 
Testing (l) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
α-Gal A Testing in 
Blood (m) 
X  
X (n) 
  
 
 
X (o) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Gb3 and lyso-Gb3 
Testing (m) 
X 
X (n) 
  
X (o) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Iron panel (p) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Biomarkers of Renal 
Function in Urine 
X 
X 
  
  
  
  
  
  
 
X 
X 
  
  
X 
  
  
X 
  
  
 
X 
X 
 

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      CONFIDENTIAL 
 
Clinical Study Protocol Amendment 7 08June2022 
Page 79 of 92 
APPENDIX 1: SCHEDULE OF EVENTS (continued) 
PROCEDURE 
Screening  
Baselin
e 
(a)  
Health Care 
Facility 
Day 
Week 
ET
V 
 
 
 
 
 
8 
2 
4 
6 
8 
12 
16 
20 
24 
28
* 
32
* 
36 
40
* 
44
* 
48
* 
52 EOS 
 
 
(w/in 8 
weeks of 
Baseline) 
(w/in 
12 
weeks 
prior to 
ST-920 
infusio
n) 
Day 
1 
Day 2  
(+/-
1 
day) 
(+/-2 days) 
(+/-1 week) 
(+/-2 weeks) 
(+/-1 week) 
(-
2weeks
/+1 
month) 
 
Protein and albumin 
to Creatinine Ratio in 
Urine 
X 
X 
  
  
  
  
  
  
  
X 
  
  
X 
  
  
X 
  
  
 
X 
X 
Cardiac MRI (CMR) 
(q)  
 X 
X 
  
  
  
  
  
  
  
  
  
  
X 
  
  
  
  
  
 
X 
X 
Blood samples for 
high sensitivity 
troponin T, NT-
proBNP,  and other 
cardiac biomarkers 
 
X 
 
 
 
 
 
 
X 
X 
 
 
X 
 
 
X 
 
 
X 
X 
X 
Minnesota Living 
With Heart Failure 
Questionnaire 
(MLHF-Q) (r) 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
Circulating AFP 
X 
 
 
 
 
 
X 
 
X 
X 
 
 
X 
 
 
 
 
 
 
X 
X 
Skin Biopsy (s) 
  
X 
  
  
  
  
  
  
  
  
  
  
X 
  
  
  
  
  
 
X 
X 
PT, PTT & INR (t) 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Kidney biopsy (t) 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Frequency of Pain 
Medication Use 
X 
X 
  
  
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Short Form Brief 
Pain Inventory (BPI) 
  
X 
  
  
  
  
  
  
  
X 
  
  
X 
  
  
X 
  
  
 
X 
X 
QOL (SF-36 
Questionnaire) 
  
X 
  
  
  
  
  
  
  
  
  
  
X 
  
  
  
  
  
 
X 
X 
GI Symptoms Rating 
Scale 
  
X 
  
  
  
  
  
  
  
  
  
  
X 
  
  
  
  
  
 
X 
X 
Mainz Severity Score 
Index 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
PFTs (b) 
X 
X 
  
  
  
  
  
  
  
  
  
  
X 
  
  
  
  
  
 
X 
X 
Audiologic Evaluation 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
X 
X 
Vector Genome PCR 
in Blood (Plasma) 
  
  
  
X (12 
hr 
post-
infusi
on) 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  

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      CONFIDENTIAL 
 
Clinical Study Protocol Amendment 7 08June2022 
Page 80 of 92 
APPENDIX 1: SCHEDULE OF EVENTS (continued) 
Vector Genome PCR 
in Blood (Plasma), 
Saliva, Urine, Stool 
and Semen (u) 
  
X 
  
  
X 
X 
X 
  
X 
X 
X 
X 
X 
  
  
X 
  
  
 
 X 
  
AAV Immunogenicity 
(v) 
X  
  
  
  
  
X 
X 
  
X 
  
  
X 
  
  
X 
  
  
 
X 
  
Immune response to 
α-Gal A (m) 
X 
X 
 
 
 
 
X 
 
X 
X 
X 
 
X 
 
 
X 
 
 
 
X 
X 
Future Research 
(optional) (w) 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ST-920 Infusion 
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
COVID-19 
Assessment (x) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy test (if 
applicable) (y) 
X 
X 
X 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
* 
Week 28, 32, 40, 44, and 48 study visits have assessments that do not require evaluation at the clinical site, and therefore may be conducted remotely. Assessments for AEs and 
concomitant medications may be conducted remotely over the phone by the study staff. 
a) 
For subjects in screening or baseline whose visits are impacted by the COVID-19 situation, the duration of baseline can be extended up to 24 weeks without having to be screen -failed. 
The Investigator will discuss with Sangamo Medical Monitor to decide which tests need to be repeated to continue in the study on a case-by-case basis. 
b) 
Assessments including ECHO, PFTs, and MRI of liver performed within 6 months of consent may be used for evaluation of inclusion/exclusion criteria on a --case-by-case basis at 
the judgment of the Site Investigator. Further, genetic marker analysis including Fabry disease gene sequencing will not be repeated as these will not change over time. 
c) 
The assay will be performed on blood or saliva samples. If available, gene sequencing results obtained prior to the study may be used.  
d) 
If dosing is not completed within 12 weeks of sample collection, the serum neutralization assay to AAV6 should be repeated. 
e) 
Vital signs include height, weight, systolic/diastolic blood pressure, heart rate, respiratory rate, and temperature. For frequency, refer to the Study Reference Manual. Baseline weight 
obtained 2-4 weeks prior to ST-920 infusion should be used for dose calculation. 
f) 
Clinical laboratory tests include hematology, urinalysis, and serum chemistry. 
g) 
On Day 1, clinical laboratory tests and liver panel should be drawn prior to ST-920 infusion. 
h) 
Liver panel does not need to be drawn as a separate sample if Clinical Laboratory Tests are obtained at the same visit. Liver panel (including assessment of AST, ALT, GGT, total 
and direct bilirubin, ALP, LDH and albumin) and total protein levels will be performed twice weekly from Week 1 through Week 20 after ST-920 infusion, weekly for four weeks 
(Weeks 21, 22, 23, 24 [±2 days]) and then monthly thereafter. Samples may be drawn tandemly for ALT, AST, ALP, and total bilirubin at either local or central labs with results to 
be utilized for decision on corticosteroid treatment. Liver tests may be conducted remotely and analyzed locally or centrally. If there is a need to initiate treatment with corticosteroids 
because of elevated ALT, liver enzymes will continue to be assessed at least twice a week until normalization and then per protocol thereafter analyzed locally or centrally. 
i) 
The liver panel test for the baseline visit will be performed within 7-14 days of planned ST-920 dosing. 
j) 
MRI or equivalent imaging modality for detection of liver masses. 
k) 
eGFR calculated by creatinine levels in blood using the CKD-EPI formula.   
l) 
This assay will be performed on plasma. If available, α-Gal A activity documentation obtained prior to the study may be used (plasma and leukocyte results are acceptable). For 
subjects who do not have a documented α-Gal A activity for diagnosis, a blood sample should be taken to measure plasma α-Gal A activity. For those subjects who are on ERT, this 
blood draw must be taken at least 14 days (± 1 day) after their last ERT infusion.  
m) For subjects on ERT, α-Gal A, immune response to α-Gal A, Gb3 and lyso-Gb3 samples should be obtained at trough, defined as 14 days (+/- 1 day) after the previous ERT 
administration, and should be taken at the same time of the day (i.e. morning) as the subsequent enzyme and substrate samples in the study. 

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n) 
2 samples will be taken at baseline on 2 different occasions at least 13 days apart (for subjects on ERT, preferably at the same time during the day [e.g. in the morning] and at ERT 
trough levels, defined as 14 days [± 1 day] after the previous ERT administration). 
o) 
Samples will be taken every 2 weeks during the first 20 weeks after ST-920 infusion. For substrates analysis in urine, whether naive or on ERT, all samples should be collected in 
the morning (morning void). Samples may be collected remotely. 
p) 
Iron panel will include iron, ferritin, total iron binding capacity, transferrin saturation and hepcidin  
q) 
CMR can be done at screening or baseline. Results of a CMR completed within 6 months prior to consent can be used for screening or the baseline measure unless the parameters 
do not meet imaging guidelines. For all subjects, CMR will include LGE, T1 and T2 mapping.   
r) 
These assessments will be performed only for subjects enrolled in cardiac cohort. 
s) 
Unless contraindicated by a Site Investigator or physician.  
t) 
Kidney biopsies will be voluntary for Cohort 2 and mandatory for subsequent cohorts and performed on ERT-naïve or ERT-pseudo-naïve subjects (defined as not having received 
ERT treatment during the 6 months prior to baseline) and selected subjects previously on migalastat who the Principal Investigator, in conversation with the Sponsor Medical Monitor, 
considers a non-responder to migalastat based on clinical and/or biochemical assessments only, unless contraindicated by a Site Investigator or physician. In subjects who will have 
a kidney biopsy, PT, PTT & INR will be done locally prior to kidney biopsy to ensure blood coagulation is normal.  
u) 
Each type of sample (blood, saliva, urine, stool, semen [if applicable]) should be collected until 3 consecutive specimens of that sample type are reported as negative or undetectable 
for vector genome.  
v) 
Samples for AAV immunogenicity will be taken at baseline, and Weeks 4, 12, 24, 36, and 52 to measure total antibodies to AAV6. Additional samples for cell-mediated 
immunogenicity will be collected at baseline, Week 6 and when ALT is elevated or when there is a 50% drop in α-Gal A expression and/or prior to initiation of a corticosteroid 
treatment if possible. 
w) Future research specimens include plasma and serum. 
x) 
Subject must be fully vaccinated at least one month before infusion with ST-920. COVID-19 Assessments will be performed as outlined in Appendix 7.  
y) 
Serum pregnancy test should be performed by the central laboratory at Screening. At other visits, a urine pregnancy test should be performed by the local laboratory or Investigator. 
 

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APPENDIX 2: ERT WITHDRAWAL SCHEDULE OF EVENTS 
 
PROCEDURE* 
ERT 
Withdrawal 
Visit (a) 
ERT Withdrawal Monitoring Visits          
(+/- 2 days) (b) 
ERT Withdrawal Follow-Up 
Visit (+/- 2 days) (c) 
Week 4 
Week 8 
Week 12 
Physical Examination 
X 
  
  
X 
Vital Signs (d) 
X 
  
  
X 
Clinical Laboratory 
X 
  
  
X 
Concomitant Medications 
X 
X 
X 
X 
AE Assessment 
X 
X 
X 
X 
ERT Administration Log 
  
X 
X 
X 
Liver Panel (e) 
X 
X 
X 
X 
α-Gal A Testing (f) 
X 
X 
X 
X 
Gb-3 Testing (f)  
X 
X 
X 
X 
Lyso Gb-3 Testing (f) 
X 
X 
X 
X 
eGFR 
X 
X 
X 
X 
Urine pregnancy test 
X 
X 
X 
X 
ERT Clinical Assessment 
 
 
 
X 
 
* 
Assessments associated with ERT withdrawal that are duplicated at regularly scheduled study visits may be waived if visits are 
combined (Appendix 1).  
a)  ERT Withdrawal visit may occur at any time after the Week 4 visit (refer to Section 3.6 for additional guidance).  
b)  ERT Withdrawal Monitoring visits will occur on Week 4 and Week 8 ± 2 days after the ERT withdrawal visit.  ERT Withdrawal 
Monitoring visits have assessments that do not require evaluation at the clinical site and may therefore be conducted remotely. 
Assessments for AEs and concomitant medications may be conducted by study staff over the phone.  
c)  The ERT Withdrawal Follow-Up visit will occur at Week 12 ± 2 days after the ERT withdrawal visit but can occur earlier at the 
discretion of the Site Investigator, if clinically indicated. However, ERT may be re-initiated at any time based on clinical 
circumstances or at the judgment of the Investigator. 
d)  Vital signs include height, weight, systolic/diastolic blood pressure, heart rate, respiratory rate, and temperature; refer to the Study 
Reference Manual.  
e)  Liver panel (including assessment of AST, ALT, GGT, total and direct bilirubin, ALP, LDH, albumin, and total protein levels) 
does not need to be drawn as a separate sample if Clinical Laboratory Tests are obtained at the same visit.  
f)  
Subjects must be able to provide additional samples for α-Gal A, Gb3, and lyso-Gb3 testing.  
 
 
 

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APPENDIX 3: CORTICOSTEROID REGIMEN 
Corticosteroids may be initiated in response to ALT elevations that meet the criteria listed below at 
the discretion of the Investigator in discussion with the Medical Monitor. 
 
ALT Level 
Action 
ALT ≥ 2x baseline 
but < ULN 
1. Repeat liver panel within 24 hours 
2. Rule out alternative etiology for ALT elevation and discuss with 
Sangamo’s Medical Monitor 
3. If ALT is ≥ 2 x ALT baseline in 2 consecutive assessments, start 
treatment with corticosteroids in consultation with the study 
Medical Monitor 
 
Continue monitoring liver tests twice weekly until ALT trends toward 
normalization and weekly until returns to baseline value 
ALT ≥ 2x baseline 
and > ULN 
1. Rule out alternative etiology for ALT elevation and discuss with 
Sangamo’s Medical Monitor 
Start treatment with corticosteroids in consultation with the study 
Medical Monitor 
 
Liver enzymes will continue to be assessed at least twice a week until 
normalization and then per protocol thereafter analyzed locally or 
centrally. 
 
Start oral prednisone or other equipotent corticosteroid at 60 mg/day for 1 week continuing with the 
following tapering down schedule: 
 
Week 1  
60 mg/day 
Week 2 
40 mg/day 
Week 3 
30 mg/day 
Week 4 
30 mg/day  
Week 5 
20 mg/day 
Week 6 
10 mg/day 
Week 7 
5 mg/day 
 
Continue monitoring ALT throughout treatment. If ALT increases while on corticosteroids, the dose 
of prednisone (or equipotent corticosteroid) may be adjusted to a maximum of 90 mg/day after 
consultation with the study Medical Monitor. 
 
 

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APPENDIX 4: INSTRUCTION FOR LIVER BIOPSY SAMPLE COLLECTION AND 
TISSUE PREPARATION 
Any subject who has an elevated alpha-fetoprotein and MRI mass suspicious for HCC or greater than 
2 cm will undergo liver biopsy. Histopathologic examination and genomic analysis will be performed 
to evaluate the origin and nature of the tumor. 
 
Liver Biopsy Sample Collection and Tissue Preparation for Genomic Analysis 
Details of the histopathological evaluation, including the weight of liver tissue obtained from each 
biopsy sample, will be summarized in a report and sent to the Sponsor. 
 

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APPENDIX 5: INVESTIGATOR OBLIGATIONS 
The Site Investigator will ensure that the study is conducted in compliance with the protocol, 
Declaration of Helsinki, International Council for Harmonisation (ICH) Guidelines for Good Clinical 
Practice (E6), and all regulatory, state, local, federal and other applicable laws and institutional 
requirements, including, but not limited to, those for subject privacy, informed consent, IRB/IEC or 
equivalent approval, and record retention. 
 
Informed Consent 
No Investigator may involve a human being as a subject in research covered by these regulations 
unless the Investigator has obtained the legally effective informed consent of the subject or the 
subject’s legally authorized representative. An Investigator shall seek such consent only under 
circumstances that provide the prospective subject sufficient opportunity to consider whether or not to 
participate, and that minimize the possibility of coercion or undue influence. The information that is 
given to the subject or the representative shall be in language understandable to the subject or the 
representative. 
 
The Sponsor will provide the Site Investigator with a template for the consent form. State and local 
laws and/or institutional requirements may require the disclosure of additional information in the 
informed consent. The proposed consent form must be submitted to the Sponsor prior to submission 
to the IRB/IEC or equivalent to ensure that it meets the Sponsor standards for consent forms. The 
IRB/IEC or equivalent must approve the consent form. A copy of the approved form must be 
submitted to the Sponsor.  
 
Prior to the initiation of any procedures relating to the study, informed consent shall be documented 
with the approved written consent form signed and dated by the subject at the time of consent. A 
copy of the signed informed consent will be given to the person signing the form. The Site 
Investigator must keep each subject’s signed consent form on file for inspection by a regulatory 
authority at any time. 
 
Institutional Review Board/Ethics Committee and BioSafety Committee 
This protocol, informed consent document, and relevant substantive data are to be submitted to the 
appropriate IRB/IEC or equivalent and BioSafety Committee (BSC) or equivalent for review and 
approval before the initiation of the study. Amendments to the protocol will also be submitted to the 
IRB/IEC or equivalent and BSC (as appropriate) prior to implementation of the change. A letter 
documenting the IRB/IEC or equivalent and BSC approval must be received by the Sponsor prior to 
initiation of the study.  
 
Protocol Amendments 
Any substantive changes to this protocol will be initiated by the Sponsor in writing as a protocol 
amendment. The amendment must be submitted to the IRB/IEC or equivalent together with a revised 
informed consent form, if applicable. Written documentation of IRB/IEC or equivalent approval must 
be received before the amendment may take effect. 
 

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Subject Privacy 
Subject medical information obtained for the purposes of this trial is confidential, and disclosure to 
third parties other than those noted below is prohibited. Upon the subject’s request and written 
permission, medical information may be given to the subject’s personal physician or other 
appropriate medical personnel responsible for the subject’s welfare. Data generated for this study 
must be available for inspection on request to representatives of the FDA/MHRA or equivalent, other 
national or local health authorities, the Sponsor, and the associated IRB/IEC or equivalent. 
 
Release of research results or data that reveal subject names or other personal identifiers (which may 
include photographs, audio, or videotapes), must be carried out in accordance with, as applicable, 
(1) Department of Health and Human Services Standards for Privacy of Individual Health 
Information, 45 CFR 164.508, (2) the EU General Data Protection Regulation 2016/679, and (3) any 
other applicable law regarding subject and data privacy. Written authorization must be obtained from 
the subject and IRB/IEC or equivalent prior to use, processing, transfer, disclosure and release of 
such information, as required by applicable law. Identifiable subject data may not be used for 
purposes of promoting the investigational product. 
 
Reporting Obligations 
Sangamo, the sponsor of this study, is required to report to the regulatory authorities (e.g., 
FDA/MHRA/EMA or equivalent) annually on the status of the trial. Status reports must be filed by 
the Site Investigator with his/her IRB/IEC or equivalent on an annual basis. 
 
The Site Investigator is also responsible for informing his/her IRB/IEC or equivalent of the progress 
of the study and for obtaining annual IRB/IEC or equivalent renewal. The IRB/IEC or equivalent 
must be informed at the time of completion of the study. The Site Investigator should provide his/her 
IRB/IEC or equivalent (if required by the institution) with a summary of the results of the study. 
 
 

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APPENDIX 6: ADMINISTRATIVE CONSIDERATIONS 
Study Documentation 
The Site Investigator and study staff are responsible for maintaining a comprehensive and centralized 
filing system containing all study-related documentation. These files must be suitable for inspection 
by the Sponsor or the FDA/MHRA/EMA or equivalent at any time, and should consist of the 
following elements: 
• Subject files containing the completed medical records, supporting source documentation, eCRFs, 
and the IRB/IEC or equivalent approved Informed Consent signed by subjects. 
• Study files containing all versions of the IRB/IEC or equivalent approved protocol with all 
amendments, IRB/IEC or equivalent approved informed consent forms, copies of all pre-study 
documentation, Form FDA 1572, and all correspondence to and from the IRB/IEC or equivalent 
and the Sponsor. 
The Site Investigator should maintain a list of appropriately qualified persons who are delegated to 
perform significant study-related studies. In addition, the Site Investigator should maintain a 
signature sheet to document signatures and initials of all persons authorized to make entries and/or 
corrections on the source documents and eCRFs. 
 
Record Retention 
The Site Investigator shall retain records required to be maintained under this part for a period of 
2 years following the date a marketing application is approved for the drug for the indication for 
which it is being investigated. If no application is to be filed or if the application is not approved for 
such indication, the Site Investigator shall retain these records until 2 years after the investigation is 
discontinued and the FDA/MHRA/EMA or equivalent are notified. Study records shall be kept for at 
least 25 years or the maximum period by applicable policy or regulation (whichever is greater). 
However, these documents should be retained for a longer period if required by the applicable 
regulatory requirements or by an agreement with the Sponsor. It is the responsibility of the Sponsor 
to inform the Site Investigator as to when these documents no longer need to be retained. 
 
Case Report Forms 
The Site Investigator is responsible for the quality of the data recorded on the CRF. The data recorded 
should be a complete and accurate account of the subject’s record collected during the study. 
 
Clinical data will be recorded on eCRFs provided by the Sponsor. All forms must be legible and 
complete. The Site Investigator must review all entries for completeness and correctness. When 
changes or corrections are made on any CRF, an audit trail will be generated to record date and time 
when a change is made, who made the change, and reason for the change as needed. The original 
entry should not be obscured. 
 
The Site Investigator agrees to complete and sign CRFs in a timely fashion at the end of the study, 
and to make them available to the Study Monitor and Auditor for full inspection. In addition, all data 
queries should be resolved promptly. 
 

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Termination of the Study 
The Sponsor retains the right to terminate the study and remove all the study materials from the study 
site at any time for any reason. Some specific instances that may precipitate such termination are as 
follows: 
• Completion of the study at an investigational site. 
• Site Investigator withdrawal from participation in study. 
• Termination of study by the Sponsor. 
Study Monitoring 
Sangamo, as Sponsor of this study, is responsible to regulatory authorities for monitoring the study 
and ensuring that the study is conducted in accordance with the protocol. The Sponsor has therefore 
assigned a Medical Monitor to this study. Their duties are to aid the Site Investigator and, at the same 
time, the Sponsor in the maintenance of complete, legible, well-organized, and easily retrievable data. 
In addition, a Sangamo Study Monitor will help ensure an understanding of the protocol, reporting 
responsibilities, and the validity of the data.  
 
Individual study sites will be monitored by a Sangamo Study Monitor or designee at appropriate 
intervals to review the consenting process, data recording, and protocol adherence. To perform their 
roles well, the Sangamo monitors or designee must be given direct access to primary subject data 
(source documents) that support data entered onto the CRFs. The Site Investigator and staff are 
expected to cooperate and provide all relevant study documentation in detail at each site visit on 
request for review. Each study center will also be routinely monitored by telephone and/or by email 
to keep abreast of subject status and to answer questions. 
 
Regulatory authorities, the IRB/IEC or equivalent, and/or Sangamo’s Clinical Quality Assurance 
group may request access to all source documents, CRFs, and other study documentation for on-site 
audit or inspection. Direct access to these documents must be guaranteed by the Site Investigator, 
who must provide support at all times for these activities. 
 
The Site Investigator or designated person should agree, as a minimum requirement, to record the 
following information in the subject notes: 
• Protocol identification number, brief description, or title of study. 
• Date and statement that subject has given written informed consent. 
• All study follow-up visit dates. 
• AE as described in Section 9 of this protocol. 
Entries in the subject notes must contain the signature or initials of the person making the entries. 
 
The Study Monitor will perform source data verification at each monitoring visit. 
 
Confidential Information and Publication 
All information provided by the Sponsor to the Site Investigator and any data or results generated in 
the performance of this clinical trial are considered confidential and remain the sole property of the 
Sponsor. The Site Investigator shall maintain this information in confidence and use this information 
solely for in the conduct of the study unless otherwise expressly agreed to in writing by the Sponsor. 

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The Site Investigator understands and agrees that the Sponsor shall have the right to use the data or 
results generated in the performance of the study for any purpose, including in registration documents 
for regulatory authorities in the U.S. or abroad, or for public dissemination in the form of papers, 
abstracts, posters, or other informational materials to be presented at scientific meetings, or published 
in professional journals, or as a part of an academic thesis. The Site Investigator further understands 
and agrees that the Sponsor shall have the right to first publication of the data or results of the study, 
which is intended to be a joint, multi-center publication of the study results made by the Sponsor in 
conjunction with the Site Investigators from all appropriate investigational sites contributing data, 
analysis, and comments. Authorship of publications resulting from this study will be based on 
customary standards for attribution of authorship taking into consideration factors such as 
significance of contribution to the design of the study, analysis and interpretation of the data, and 
critical review of the publication. Subsequent to the first publication of the study results by the 
Sponsor, the Site Investigator may publish the Site Investigator’s site-specific data or results. If the 
Site Investigator wishes to publish the Site Investigator’s site-specific data or results, a copy of such 
proposed publications, papers, abstracts, or other written materials, or an outline of any proposed oral 
presentations, shall be submitted to the Sponsor for review at least 60 days prior to submission of 
such written materials for publication, or any proposed oral presentation. The Sponsor shall have the 
right to review and comment on such written material or outline, and to confirm the accuracy of the 
data described therein by comparison with that collected during the course of this study. In addition, 
the Sponsor shall have the right to require the Site Investigator to, and Site Investigator shall, remove 
specifically identified confidential information of the Sponsor (other than the data or results of the 
study) and/or delay the proposed publication for an additional 60 days to enable the Sponsor to file 
patent applications. 
 
Study Funding 
The costs necessary to perform the study will be agreed to by the Site Investigator and/or the 
management of the study facility, and will be documented in a separate clinical trial agreement. All 
clinical trial agreements will be signed by the authorized representatives of the Site and the Sponsor, 
and the Site Investigator must acknowledge his/her responsibilities thereunder. 
 
 

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APPENDIX 7: COVID-19 GUIDANCE: SCREENING ASSESSMENTS AND REMOTE 
VISITS 
 
Screening Assessments and Monitoring for COVID-19 infection 
 
At every study visit the site staff will monitor the subjects for COVID-19 symptoms as per individual 
site’s process.  
 
If there is no site-specific process, the site staff will ask the following questions: 
 
1. Are you experiencing any of the following symptoms? 
a. New or worsening cough - Y/N 
b. Fever or feeling feverish - Y/N 
c. Shortness of breath - Y/N 
d. Sore throat - Y/N 
e. Body and/or muscle aches - Y/N 
f. Nausea, vomiting, and/or diarrhea - Y/N 
g. Loss of smell, and/or taste - Y/N 
(Questions regarding additional symptoms will be asked as per the updated list from CDC and 
WHO)  
2. In the last 14 days, did you have close contact with a suspected or laboratory-confirmed 
COVID-19 patient? Y/N/ Don’t know 
 
If site staff checks yes to any of the above questions, the Investigator will discuss with Sangamo 
Medical Monitor to perform PCR test and the next steps. Serology test may be done during the study 
as per Investigator’s discretion to measure -for SARS-CoV-2 antibodies and check for past infection. 
For details, refer to the Laboratory Manual. 
 
An oral and/or nasal swab test will be done twice prior to study drug dosing to check for current 
COVID-19 infection using Polymerase Chain Reaction (PCR). In the future if a COVID-19 
diagnostic test with similar specificity and sensitivity to PCR become available it may be used after 
discussing with the medical monitor. The first test can be done 10-14 days prior to planned dosing 
and the second test should be done 2-3 days prior to planned dosing. For details, refer to the 
Laboratory Manual.  

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Clinical Study Protocol Amendment 7 08June2022 
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Figure 3: 
Schematic of COVID-19 Infection Testing Requirements  
Subject Disposition in the Context of COVID-19 
If a subject develops an active COVID-19 infection during the course of the study, the Investigator 
will work with the subject and the Sponsor Medical Monitor to determine the best course of action, 
delaying infusion until the COVID-19 infection has resolved. If a subject is withdrawn from the study 
because of COVID-19, the reason for early termination will be captured in the EDC system as such.  
 
If the subject misses scheduled in-clinic visits due to COVID-19, an unscheduled visit will be 
conducted. At a minimum, clinical laboratory tests must be performed at the unscheduled visit. 
Wherever possible, subjects should not go more than 3 months or 2 consecutive scheduled visits 
without clinical laboratory tests being performed. For further information on remote visits, see 
Appendix 8. 
 
For scenarios not delineated here or for further clarification, the Investigator should consult with the 
Sponsor Medical Monitor to determine the best course of action. 
 
 
 
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
- ve  
+ve  
+ve  
-
 
2 or 3 days prior to 
planned dosing 
PCR
Test  
Do not dose and initiate 
COVID -19 S tandard of
C are 
PCR 
Test  
Dose the
subject  
10-14 days prior to 
planned dosing 
 ve 

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APPENDIX 8: REMOTE VISITS 
Some visits to be conducted as remote visits consisting of a combination of telemedicine and/or home 
health visits at the subject’s home, rather than requiring the subject to attend the clinical site for 
certain in-clinic visits. This is acceptable for certain visits according to the type of assessments 
required or under certain special circumstances, such as in response to COVID-19 (see Appendix 7).  
 
A remote visit can only be conducted if the investigator and subject are in agreement, and there are no 
specific health concerns for the subject that require them to attend the clinical site. The Investigator 
should consult with the Sponsor Medical Monitor to determine the best course of action. If in-clinic 
visits are no longer possible, assessments categorised as in-clinic only activities will not be 
conducted. 
 
Remote visits will be conducted by a Home Health Provider engaged by the Sponsor or CRO. The 
Home Health Provider will provide qualified and experienced research nurses who will be selected 
based on appropriate experience and location in relation to the clinical sites. The research nurses will 
undergo study-specific training and will be familiar with this clinical protocol as well as other 
relevant study documentation. The research nurses will be provided with study-specific manuals that 
include guidance on the visit schedule, individual assessments and standard process for conducting 
each visit.   
 
The option of remote visits will be described to the subject during the consenting process and subjects 
will decide whether or not they consent to use this service. 
 
For remote visits, some clinical laboratory assessments may be conducted by a central laboratory 
rather than at the local laboratory for each study site. Please refer to the Laboratory Manual for 
further details.