The Guard1 Trial, an Open-Label, Multinational Phase 1/2 Study of the Safety and Efficacy of Ex Vivo, Lentiviral Vector-Mediated Gene Therapy AVR-RD-02 for Subjects With Type 1 Gaucher Disease
Phase: PHASE1
Conditions: Gaucher Disease
Sponsor: AVROBIO



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INVESTIGATOR’S AGREEMENT
I have read the AVRO-RD-02-201 study protocol and agree to conduct the study in accordance 
with this protocol, all applicable government regulations, the principles of the International 
Council for Harmonisation (ICH) E6 Guidelines for Good Clinical Practice (GCP), and the 
principles of the World Medical Association Declaration of Helsinki. I also agree to maintain the 
confidentiality of all information received or developed in connection with this protocol.  
Printed Name of Investigator
Signature of Investigator 
Date
Site Number

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2
TABLE OF CONTENTS
SPONSOR SIGNATURE PAGE .................................................................................................. 2 
INVESTIGATOR’S AGREEMENT ............................................................................................. 3 
1
SYNOPSIS ......................................................................................................................... 4 
2
TABLE OF CONTENTS ................................................................................................. 12 
3
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .................................. 17 
4
INTRODUCTION ........................................................................................................... 20 
5
STUDY OBJECTIVES AND ENDPOINTS ................................................................... 22 
5.1
Study Objectives ........................................................................................................... 22 
5.1.1
Primary Objectives ..................................................................................................... 22 
5.1.2
Secondary Objectives ................................................................................................. 22 
5.1.3
Exploratory Objectives .............................................................................................. 22 
5.2
Endpoints ...................................................................................................................... 23 
5.2.1
Primary Endpoints ..................................................................................................... 23 
5.2.2
Secondary Endpoints ................................................................................................. 23 
5.2.3
Exploratory Endpoints ............................................................................................... 23 
6
INVESTIGATIONAL PLAN .......................................................................................... 25 
6.1
Summary of Study Design ............................................................................................ 25 
6.2
Discussion of Design and Control ................................................................................ 30 
6.2.1
Overall Study Design and Study Population ............................................................. 30 
6.2.2
Stem Cell Mobilization and Conditioning Regimens ................................................ 31 
6.2.2.1 
Stem Cell Mobilization ........................................................................................... 31 
6.2.2.2 
Conditioning ........................................................................................................... 32 
6.2.3
Efficacy and Safety Measures .................................................................................... 35 
7
STUDY POPULATION .................................................................................................. 36 
7.1
Inclusion Criteria .......................................................................................................... 36 
7.2
Exclusion Criteria ......................................................................................................... 38 
7.3
Rationale for Inclusion or Exclusion of Certain Study Candidates .............................. 39 
7.4
Discontinuations ........................................................................................................... 41 
7.4.1
Discontinuation of Subjects ....................................................................................... 41 
7.4.2
Discontinuation of Study Sites/Site Terminated by Sponsor ..................................... 41 
7.4.3
Discontinuation of the Study/Study Terminated by Sponsor .................................... 41 

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7.4.4
Stopping Rules ........................................................................................................... 42 
7.4.4.1 
Stopping Rules for AVR-RD-02 ............................................................................. 42 
7.4.4.2 
Enrollment Pause Criteria ....................................................................................... 42 
7.4.5
Engraftment Failure ................................................................................................... 42 
7.4.6
Enzyme Replacement Therapy .................................................................................. 43 
7.4.6.1 
Enzyme Replacement Therapy Initiation Rules for Switch-Stable Subjects 
Only: 0-5 Months After Gene Therapy Infusion .................................................... 43 
7.4.6.2 
Enzyme Replacement Therapy Starting Rules: 6-12 Months After Gene 
Therapy Infusion ..................................................................................................... 43 
8
TREATMENT ................................................................................................................. 46 
8.1
Treatments Administered .............................................................................................. 46 
8.1.1
Pre-gene Therapy Infusion Period (Approximately 8 Weeks to 10 Weeks) ............. 46 
8.1.1.1 
Mobilization and Apheresis .................................................................................... 46 
8.1.1.2 
Investigational Product Preparation/Testing for Release ........................................ 47 
8.1.1.3 
Conditioning ........................................................................................................... 48 
8.1.2
Gene Therapy Infusion Period (1 Day) ...................................................................... 50 
8.1.3
Post-gene Therapy Infusion Follow-up Period (Approximately 52 Weeks) ............. 50 
8.2
Materials and Supplies .................................................................................................. 50 
8.3
Dosing Considerations .................................................................................................. 51 
8.3.1
Rationale for Selection of Dose in the Study ............................................................. 51 
8.3.2
Other Important Treatment Considerations ............................................................... 51 
8.4
Blinding......................................................................................................................... 52 
9
STUDY ASSESSMENTS ............................................................................................... 53 
9.1
Safety Assessments ....................................................................................................... 53 
9.1.1
Physical Examinations ............................................................................................... 53 
9.1.2
Vital Signs .................................................................................................................. 53 
9.1.3
Serum Chemistry, Hematology, and Urinalysis ........................................................ 53 
9.1.4
Electrocardiograms .................................................................................................... 54 
9.1.5
Reproductive Potential ............................................................................................... 54 
9.1.6
Immunogenicity ......................................................................................................... 55 
9.1.7
Replication-Competent Lentivirus ............................................................................. 55 
9.1.8
Insertional Site Analysis ............................................................................................ 55 
9.1.9
Samples to be Archived for Possible Future Testing ................................................. 55 

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9.1.10 
COVID-19 Guidance: Sign and Symptom Assessment............................................. 56 
9.2
Safety Monitoring ......................................................................................................... 56 
9.2.1
Adverse Events .......................................................................................................... 56 
9.2.1.1 
Exemptions to Adverse Event Recording/Reporting .............................................. 57 
9.2.1.2 
Severity Assessment ............................................................................................... 58 
9.2.1.3 
Causality Assessment.............................................................................................. 58 
9.2.1.4 
Outcome Assessment .............................................................................................. 59 
9.2.1.5 
Serious Adverse Events .......................................................................................... 60 
9.2.1.6 
Suspected Unexpected Serious Adverse Reactions ................................................ 60 
9.2.1.7 
Reporting Adverse Events ...................................................................................... 61 
9.2.1.8 
Sponsor Reporting Requirements ........................................................................... 61 
9.2.1.9 
Investigator Reporting Requirements ..................................................................... 61 
9.2.2
Exposure During Pregnancy and/or Lactation ........................................................... 61 
9.3
Engraftment and Efficacy Measures ............................................................................. 62 
9.3.1
Vector Copy Number ................................................................................................. 62 
9.3.2
GCase Enzyme Activity in Peripheral Blood ............................................................ 62 
9.3.3
Enzyme Replacement Therapy .................................................................................. 62 
9.3.4
Primary Efficacy Measures ........................................................................................ 63 
9.3.5
Secondary Efficacy Measures .................................................................................... 63 
9.3.6
Exploratory Efficacy Measures .................................................................................. 63 
9.4
Appropriateness of Measurements ................................................................................ 64 
10
DATA QUALITY ASSURANCE ................................................................................... 65 
10.1
Data Collection and Storage ......................................................................................... 65 
11
STATISTICAL METHODS AND PLANNED ANALYSES ......................................... 66 
11.1
General Considerations ................................................................................................. 66 
11.2
Determination of Sample Size ...................................................................................... 66 
11.3
Analysis Sets ................................................................................................................. 67 
11.4
Demographics and Baseline Characteristics ................................................................. 67 
11.5
Subject Disposition ....................................................................................................... 67 
11.6
Concomitant Medications and Non-Pharmacologic Therapies and Procedures ........... 67 
11.6.1 
Prophylaxis ................................................................................................................ 68 
11.6.2 
Re-Vaccination .......................................................................................................... 68 
11.7
Treatment Compliance .................................................................................................. 68 

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11.8
Safety Analyses ............................................................................................................. 68 
11.8.1 
Physical Examination and Vital Signs ....................................................................... 68 
11.8.2 
Clinical Laboratory Tests ........................................................................................... 68 
11.8.3 
Adverse Events .......................................................................................................... 68 
11.8.4 
Reproductive Potential ............................................................................................... 69 
11.8.5 
Other Safety Assessments .......................................................................................... 70 
11.9
Analysis of Immunogenicity ......................................................................................... 70 
11.10 
Analysis of Engraftment ............................................................................................... 70 
11.11 
Analysis of Enzyme Activity ........................................................................................ 70 
11.12 
Analysis of Standard of Care ERT................................................................................ 70 
11.13 
Efficacy Analyses ......................................................................................................... 70 
11.13.1 
Secondary Efficacy Analysis ..................................................................................... 70 
11.13.2 
Exploratory Efficacy Analyses .................................................................................. 71 
11.14 
Subgroup Analyses ....................................................................................................... 71 
11.15 
Missing or Invalid Data ................................................................................................ 71 
12
DATA COLLECTION AND QUALITY CONTROL .................................................... 72 
12.1
Database Management and Data Quality Control ........................................................ 72 
12.2
Data Monitoring Committee ......................................................................................... 72 
12.3
Subject Confidentiality and Data Privacy ..................................................................... 72 
12.4
Study Record Retention ................................................................................................ 73 
13
ADMINISTRATIVE, ETHICAL, AND REGULATORY CONSIDERATIONS .......... 74 
13.1
Informed Consent.......................................................................................................... 74 
13.2
Ethical Conduct of the Study ........................................................................................ 74 
13.3
Regulatory Considerations ............................................................................................ 74 
13.3.1 
Investigator Information ............................................................................................ 75 
13.3.2 
Protocol Signatures .................................................................................................... 75 
13.3.3 
Final Report Signature ............................................................................................... 75 
13.4
Publication Policy ......................................................................................................... 75 
14
LIST OF REFERENCES ................................................................................................. 76 
15
APPENDICES ................................................................................................................. 85 
15.1
Schedules of Assessments: Screening through the Apheresis Period ........................... 86 
15.2
Schedules of Assessments: Investigational Product Preparation and Testing 
through End of Gene Therapy Infusion ........................................................................ 92 

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15.3
Schedules of Assessments: Post-gene Therapy Infusion Follow-up Period 
(Study Week 1 [Day 1] through Study Week 52 [Day 365]) ....................................... 99 
15.4
Enrollment (and Data Monitoring Committee Review) Schedule .............................. 105 
LIST OF TABLES
Table 1: 
PK- and Weight-Based Guided Busulfan Conditioning Regimen for Sites 
Using LC-MS to Perform Busulfan TDM ........................................................... 48 
Table 2: 
PK- and Weight-Based Guided Busulfan Conditioning Regimen for Sites 
Using the Immunoassay Kit to Perform Busulfan TDM ..................................... 49 
Table 3: 
Causality Definitions ........................................................................................... 58 
Table 4: 
Schedule of Assessments from Screening through the Apheresis Period ............ 86 
Table 5: 
Schedule of Assessments from Investigational Product Preparation and 
Testing through End of Gene Therapy Infusion .................................................. 92 
Table 6: 
Schedule of Assessments for the Post-gene Therapy Infusion Follow-up 
Period (Study Week 1 [Day 1] through Study Week 52 [Day 365]) ................... 99 
Table 7: 
Enrollment (and DMC Review) Schedule ......................................................... 105 
LIST OF FIGURES
Figure 1: 
Clinical Study Design for AVRO-RD-02-201 ..................................................... 26 
Figure 2: 
Overall Study Design for AVRO-RD-02-201 ..................................................... 28 
Figure 3: 
Overview of the Pre-gene Therapy Infusion and Gene Therapy Infusion 
Periods of Study AVRO-RD-02-201 ................................................................... 29 

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3
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Abbreviation
Definition
ADA
Anti-drug antibodies
ADL
Activities of daily living
AE
Adverse event(s)
AESI
Adverse event of special interest
ALP 
Alkaline phosphatase
ALT 
Alanine aminotransferase
AMH
Anti-Müllerian hormone
AML
Acute myeloid leukemia
ANC
Absolute neutrophil count
AST
Aspartate aminotransferase
ATC 
Anatomical Therapeutic Chemical (classification)
AUC
Area-under-the curve
BID
Twice a day
BMB
Bone marrow burden
BMD
Bone mineral density
BMI
Body mass index
BMT
Bone marrow transplant
BPI-SF
Brief Pain Inventory-Short Form
BUN
Blood urea nitrogen
CBER
Center for Biologics Evaluation and Research
cDNA
Complementary deoxyribonucleic acid
CIOMS
Council for International Organizations of Medical Sciences
CFR
Code of Federal Regulations
cGMP
current Good Manufacturing Practice
CMIA
Chemiluminescent microplate immunoassay
CMP
Common myeloid progenitors
COVID-19
Coronavirus disease 2019
CS
Clinically significant
CSR
Clinical Study Report
CTCAE
Common Terminology Criteria for Adverse Events
ddPCR
Droplet digital polymerase chain reaction
DBS
Dried blood spot
DHHS 
Department of Health and Human Services
DMC
Data Monitoring Committee
DNA
Deoxyribonucleic acid
DXA
Dual-energy X-ray absorptiometry
ECG
Electrocardiogram
eCRF
Electronic case report form

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Abbreviation
Definition
EIA 
Enzyme immunosorbent assay
EMA
European Medicines Agency
ERT
Enzyme replacement therapy
FDA
Food and Drug Administration
FSFV
First subject first visit
FSH
Follicle-stimulating hormone
GBA  
Glucosylceramidase beta gene
GCase
Glucocerebrosidase
GCP
Good Clinical Practice
G-CSF
Granulocyte-colony stimulating factor
GGT
Gamma-glutamyl transferase
GLP 
Good Laboratory Practice
GluCer
Glucosylceramide
GMP
Granulocytes/monocytes progenitors
HBV
Hepatitis B virus
HCV
Hepatitis C virus
HCT
Hematopoietic cell transplant
HIV
Human immunodeficiency virus
HSC
Hematopoietic stem cell
HSCT
Hematopoietic stem cell transplantation
HTLV
Human T-cell lymphotropic virus
ICF
Informed consent form
ICH
International Council for Harmonisation
IEC 
Independent Ethics Committee
IRB
Institutional Review Board
ISA
Insertional site analysis
ITP 
Idiopathic thrombocytopenic purpura
IV
Intravenous(ly)
LC-MS
Liquid chromatography-mass spectrometry
LDH 
Lactate dehydrogenase
LH 
Luteinizing hormone
LLN 
Lower limit of normal
LSLV 
Last subject last visit
LSD 
Lysosomal storage disorder
LV 
Lentiviral vector
lyso-Gb1
Glucosylsphingosine 
MDS 
Myelodysplastic Syndrome
MedDRA
Medical Dictionary for Regulatory Activities
MEP
Megakaryocyte/erythroid progenitors

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Abbreviation
Definition
MGUS
Monoclonal gammopathy of undetermined significance
MLD
Metachromatic leukodystrophy
MLP
Multilymphoid progenitors
MPP
Multipotent progenitors
MRI
Magnetic resonance imaging
NCS
Not clinically significant
NK
Natural killer
PBL
Peripheral blood leukocyte
PCR
Polymerase chain reaction
PI
Principal Investigator
PK
Pharmacokinetics
QD
Once daily
QoL
Quality of Life 
qPCR
Quantitative polymerase chain reaction
RBC
Red blood cell
RCL
Replication-competent lentivirus
RNA
Ribonucleic acid
SAE
Serious adverse event(s)
SAP
Statistical analysis plan
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2
SC
Subcutaneous
SCD
Sickle cell disease
SCID-Xl
X-linked severe combined immunodeficiency
SF-36
36-Item Short Form Health Survey
SRT
Substrate reduction therapy
SUSAR
Suspected unexpected serious adverse reaction(s)
TDM 
Therapeutic drug monitoring
TDT 
Transfusion-dependent beta-thalassemia
TEAE 
Treatment-emergent adverse event
t-MDS
Therapy-related myelodysplastic syndrome
TTP 
Thrombotic thrombocytopenic purpura
UK
United Kingdom
US
United States
VCN
Vector copy number
VDRL
Venereal Disease Research Laboratory
WBC
White blood cell
WHO
World Health Organization 

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4
INTRODUCTION
Gaucher disease is a rare, autosomal recessive lysosomal storage disorder (LSD) caused by 
mutations in the glucosylceramidase beta (GBA) gene, leading to deficiency of the lysosomal 
enzyme glucocerebrosidase (GCase). Diagnosis of Gaucher disease is made by GBA gene 
mutation analysis and documented GCase enzyme activity deficiency in whole blood, peripheral 
blood leukocytes (PBLs) or mononuclear cells, or in cultured fibroblasts (Pastores and Hughes 
2020). Deficiency of GCase enzyme activity leads to accumulation of its major substrate, 
glucosylceramide (GluCer), primarily within the lysosomes of macrophages. These pathologic 
macrophages (called Gaucher cells) infiltrate various organs, including the liver, spleen, and 
bone marrow, causing disease-related manifestations and complications. 
Gaucher disease is classified into three major subtypes (Types 1, 2, and 3). Type 1 disease is 
considered the most common form, representing 90% to 95% of all Gaucher disease in North 
America and Europe (Stirnemann 2017). In Type 1 Gaucher disease (non-neuronopathic), organ 
involvement is generally limited to the viscera and bone; Types 2 and 3 Gaucher disease 
(neuronopathic) are also associated with neurological involvement. Although there is significant 
heterogeneity in clinical presentation, common clinical features of Gaucher disease include 
splenomegaly (in more than 90% of patients), hepatomegaly (in 60% to 80% of patients), and 
cytopenias, including thrombocytopenia (in 60% to 90% of patients) and anemia (in 20% to 50% 
of patients). Spleno- and hepatomegaly may be associated with infarction and abdominal pain 
and/or distension. Bone manifestations of the disease include acute bone crises, primarily in the 
pelvis and lower extremities, which have clinical features consistent with osteomyelitis, bone 
infarcts, avascular necrosis, pathologic fractures, and chronic pain. Rarely, pulmonary 
involvement, manifested as pulmonary fibrosis, restrictive lung disease, and/or pulmonary 
arterial hypertension, may also be observed. Fatigue is a common complaint of Gaucher patients 
(50%) that can limit participation in academic, professional, and social activities (Stirnemann 
2017). Taken together, these Gaucher disease-related manifestations and complications are 
associated with significant morbidity and have an adverse impact on Quality of Life (QoL). 
Currently, five therapies are available for treatment of Gaucher disease: three intravenously (IV) 
administered enzyme replacement therapies (ERTs) (Cerezyme® [imiglucerase]; VPRIV®
[velaglucerase alpha], most recently being offered as 10-minute home infusion (Becker-Cohen 
2022); and ELELYSO® [taliglucerase alpha]) and two orally administered substrate reduction 
therapies (SRTs) intended to inhibit GluCer biosynthesis (Zavesca® [miglustat] and Cerdelga®
[eliglustat]). Although these therapeutic options for patients with Gaucher disease are currently 
available, there are inherent limitations associated with each. 
Despite availability of ERT and clinical improvements, some patients have achieved only a sub-
optimal response to ERT after years on treatment (Biffi 2016; Charrow and Scott 2015; Bennett 
2018; Weinreb 2021). This may be due, in part, to ERTs very short half-life and biweekly 
delivery by IV infusion, which provide a very high level of enzyme activity for less than 24 
hours followed by a return to pre-treatment levels (CEREZYME PI; ELELYSO PI; VPRIV PI). 
In a long-term study on hematologic, visceral, bone pain, bone crisis, height, weight, and body 
mass index (BMI) outcomes in Gaucher disease Type 1 patients, with subset analysis based on 
pre-treatment severity, genotype, and age at treatment initiation, improvements seen during early 
treatment years are sustained by continuing treatment for 20 years, except for bone pain in 
non-splenectomized patients (Weinreb 2021). In addition, although ERTs are generally well 
tolerated, a small fraction of patients treated with ERT have also experienced hypersensitivity 

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reactions, anaphylactic reactions, and/or anaphylactoid reactions, and some have also developed 
anti-drug antibodies (ADA). The rates by which these immune-mediated reactions occur vary by 
product but appear less frequently among patients receiving the ERT formulation derived from 
the wild-type gene (ie, velaglucerase alfa).
Of the available SRTs, eliglustat is considered a first-line therapy for adults with Type 1 Gaucher 
disease; however, miglustat is only recommended as a second-line therapy for adult patients for 
whom ERT is not suitable. Furthermore, there are safety considerations with both eliglustat and 
miglustat administration. Eliglustat is contraindicated in patients with pre-existing cardiac 
disease, electrolyte disturbances (or conditions that lead to electrolyte disturbances), and/or who 
are receiving certain classes of anti-arrhythmic medications due to the propensity to cause 
concentration-related increases in electrocardiogram (ECG) intervals. Eliglustat is also 
contraindicated in patients with specific P450 metabolizer status (CERDELGA PI). Miglustat 
administration is associated with significant gastrointestinal symptoms, including diarrhea (in 
more than 80% of patients) and neurologic symptoms, including tremors and peripheral 
neuropathy, for which periodic neurologic assessment on an ongoing basis is recommended 
(ZAVESCA PI). 
Considering the limitations of the currently approved ERTs and SRTs for Gaucher disease, 
AVROBIO is developing an ex vivo lentiviral vector (LV)-mediated, gene modified, autologous 
cell therapy for the treatment of Gaucher disease. This gene therapy aims to provide autologous 
gene therapy infusion of CD34+ enriched hematopoietic stem cells (HSCs) transduced with an 
LV that inserts codon-optimized, human GBA complementary deoxyribonucleic acid (cDNA) 
into the cells’ genomes. Autologous CD34+ HSCs obtained from the subject’s mobilized 
peripheral blood will be genetically modified ex vivo with an LV containing a ribonucleic acid 
(RNA) transcript that, after reverse transcription, results in codon-optimized cDNA that, upon its 
integration into the human genome, encodes for functional human GCase. After the subject has 
undergone a conditioning regimen and washout period, the genetically-modified cells will be 
returned to the subject by IV infusion. Progeny of these genetically modified CD34+ enriched 
cells are expected to produce functional human, wild type GCase, thus, restoring the cell’s 
missing enzymatic activity. This replacement GCase is expected to physiologically break down 
and prevent the accumulation of GluCer and its deacetylated form, glucosylsphingosine 
(lyso-Gb1), primarily in the lysosomes of cells of the reticuloendothelial system, especially 
monocytes and macrophages. In a mouse model of Gaucher disease, early or late ex vivo,
LV-mediated gene therapy of hematopoietic stem and progenitor cells prevented or reversed 
Gaucher disease manifestations in bone marrow, liver, and spleen (Dahl 2015). Given the close 
similarities between the mammalian lysosomal systems, it is reasonable to expect a similar 
outcome in human Gaucher patients. 
Unlike ERTs and SRTs, this LV gene therapy is intended for single administration, having the 
potential to provide sustained therapeutic levels of functional GCase over the patient’s lifetime, 
thus eliminating the need for biweekly IV infusions and resulting in a beneficial effect on the 
disease manifestations, patient QoL, and healthcare burden associated with Gaucher disease. In 
support of this approach, a review of approximately 50 cases of allogeneic HSC transplantations 
(HSCTs) for the treatment of Types 2 and 3 Gaucher disease found that HSCT can completely 
correct visceral and bony changes (Ito and Barrett 2013).
Information about the known and expected benefits, risks, and reasonably anticipated adverse 
events (AEs) of AVR-RD-02 may be found in the current edition of the Investigator’s Brochure. 

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5
STUDY OBJECTIVES AND ENDPOINTS
Study objectives and associated endpoints are presented in Sections 5.1 and 5.2, respectively. 
The frequency and timing of study measurements are provided in the Schedule of Assessments 
(Section 15). Information regarding sample and data collection are presented in Section 9.
5.1
Study Objectives
5.1.1
Primary Objectives
The primary objectives of this study are to: 
Evaluate the safety and tolerability of AVR-RD-02 investigational product 
Assess measures of engraftment of gene-augmented HSCs by determining average vector 
copy number (VCN) in peripheral blood and bone marrow aspirates using quantitative 
polymerase chain reaction (qPCR) and/or droplet digital polymerase chain reaction 
(ddPCR) analysis 
Evaluate the effect of AVR-RD-02 investigational product on clinical and biomarker 
indices of Type 1 Gaucher disease, including: 
Spleen volume assessed by abdominal magnetic resonance imaging (MRI)
Liver volume assessed by abdominal MRI
Hemoglobin concentration 
Platelet count
Lyso-Gb1 plasma levels
5.1.2
Secondary Objectives
The secondary objectives of the study are to:
Evaluate GCase enzyme activity in peripheral blood 
Evaluate the need for ERT following treatment with AVR-RD-02 investigational product 
Assess the immunogenicity of AVR-RD-02 investigational product 
Evaluate the effect of AVR-RD-02 investigational product on clinical and biomarker 
indices of Type 1 Gaucher disease, including: 
Chitotriosidase enzyme activity in plasma  
Bone marrow burden (BMB) scoring by bone MRI
Bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA) 
5.1.3
Exploratory Objectives 
The exploratory objectives are to:  
Evaluate the effect of AVR-RD-02 investigational product on QoL assessed by the 
36-Item Short Form Health Survey (SF-36) 
Evaluate the effect of AVR-RD-02 investigational product on pain assessed by the Brief 
Pain Inventory-Short Form (BPI-SF)
Assess exploratory biomarkers for Gaucher disease in serum, plasma, PBLs, and urine 
Assess the impact of the conditioning regimen on reproductive potential 

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5.2
Endpoints
5.2.1
Primary Endpoints
Primary endpoints include the following: 
Safety endpoints 
Incidence and severity of AEs, incidence of serious adverse events (SAEs), and incidence 
and severity of AEs of interest, including drug-product related AEs, infections, and 
malignancy 
Change from Baseline in clinical laboratory values relevant to safety
Change from Baseline in vital signs 
Change from Baseline in ECG findings at Weeks 26 and 52 
Engraftment endpoints 
Average VCN assessed by qPCR and/or ddPCR in peripheral blood at Baseline and 
Weeks 13, 26, 39, and 52 and in bone marrow aspirate at Baseline and Weeks 26 and 52 
Efficacy endpoints 
Change from Baseline in spleen volume assessed by abdominal MRI at Weeks 26, 39, 
and 52 
Change from Baseline in liver volume assessed by abdominal MRI at Weeks 26, 39, 
and 52 
Change from Baseline in hemoglobin concentration at Weeks 13, 26, 39, and 52  
Change from Baseline in platelet count at Weeks 13, 26, 39, and 52 
Change from Baseline in lyso-Gb1 plasma levels at Weeks 13, 26, 39, and 52 
5.2.2
Secondary Endpoints
Secondary efficacy endpoints include: 
Change from the Baseline in GCase enzyme activity level in peripheral blood at Weeks 
13, 26, 39, and 52  
ERT frequency and dosing between Weeks 26 through 52, inclusive
Change from Baseline in anti-GCase total antibodies, and subsequent titers and isotypes 
at Weeks 5, 13, 26, 39, and 52 
Change from Baseline in BMD assessed by DXA at Week 52 
Change from Baseline in clinical and biomarker indices of Type 1 Gaucher disease, 
including the following: 
Chitotriosidase enzyme activity levels in plasma at Weeks 13, 26, 39, and 52  
BMB score as assessed by bone MRI at Weeks 26, 39, and 52 
5.2.3
Exploratory Endpoints 
Exploratory efficacy endpoints include: 
Change from Baseline in QoL as assessed by SF-36 at Week 52 
Change from Baseline in pain as assessed by BPI-SF at Weeks 13, 26, 39, and 52 
Change from Baseline in exploratory biomarkers for Gaucher disease in serum, plasma, 
urine, and whole blood derived leukocytes or subpopulations at Weeks 13, 26, 39, and 52 

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Evaluate exploratory genomic biomarkers for Gaucher disease in whole blood at 
Screening (ie, CHIT1, gene encoding chitotrioside)  
Average VCN and ISA results in whole blood and bone marrow cells at specified time 
points. 
Exploratory safety endpoints include: 
Change from Baseline in ovarian reserve as assessed by anti-Müllerian hormone (AMH), 
follicle-stimulating hormone (FSH), and luteinizing hormone (LH) (female subjects only) 
at Weeks 26 and 52 
Change from Baseline in menstrual cycle (female subjects only) monthly through 
Week 52 
Change from Baseline in sperm count, volume, sperm concentration, total motility, 
progressive motility, and morphology (male subjects only) at Week 52 

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6
INVESTIGATIONAL PLAN
6.1
Summary of Study Design 
This is a Phase 1/2 multinational, open-label study to assess the safety and efficacy of 
AVR-RD-02 in approximately 8 to 16 
 50 years of age and postpubertal at Screening with a confirmed diagnosis of Type 1 Gaucher 
disease (based on clinical phenotype and deficient GCase enzyme activity in peripheral blood). 
The planned study may consist of 2 arms that are to be enrolled sequentially: 
Switch-
other week (or equivalent; ie, any combination of infusions resulting in a total monthly 
disease at the time of Screening. Switch-stable subjects must discontinue ERT at least 
2 weeks before the scheduled gene therapy infusion day. Subjects must not have been on 
SRT within 12 months of Screening. 
Treatment-naïve arm: Subjects with Type 1 Gaucher disease who have never received 
either ERT or SRT for Gaucher disease or have not received either ERT or SRT for 
Gaucher disease within 12 months of Screening (ie, treatment-naïve subjects). Enrollment 
will follow a similar scheme as for the switch-stable subjects. For any subject who is 
treatment-naïve, ERT peri-procedurally (from the Screening Period throughout 2 weeks 
prior to Gene Therapy Infusion Period) will be considered in consultation with the PI and 
Sponsor Medical Monitor.
Initially, 1 switch-stable subject will undergo treatment with AVR-RD-02. Following Week 5 
(Day 30) post-gene therapy infusion data review by an independent Data Monitoring Committee 
(DMC), if it is determined that study enrollment may proceed, a second safety cohort of 1 adult 
switch-stable subject may undergo conditioning. If DMC data review of these initial 2 subjects 
indicates no significant safety concerns, enrollment may be expanded to enroll switch-stable 
subjects in an unrestricted manner. In addition, the treatment-naïve study arm may be open to 
enrollment and will follow the same gated enrollment scheme as outlined above for the 
switch-stable arm. Neither switch-stable subjects nor treatment-naïve subjects will receive ERT 
following gene therapy, unless clinically warranted by prespecified criteria (see Section 7.4.6 for 
post-transplant ERT initiation criteria).
An overview of the clinical study design can be found in Figure 1. 

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Visit delays due to the global pandemic (coronavirus disease 2019 [COVID-19]) or other 
unforeseen reasons may necessitate that some procedures/assessments be performed locally, 
performed out of the window, or repeated if performed outside the acceptable timelines for this 
study. Under such circumstances and in consultation with the Sponsor, remote visits (eg, 
telemedicine, home nursing visits, etc.) may be considered, and may replace some protocol 
procedures/assessments, when possible. If required, COVID-19 testing will be performed per the 
institutional guidelines prior to protocol procedures/assessments. To facilitate detection of AEs, 
other suitable healthcare providers of study subjects (eg, primary care physician, physician’s 
assistant, nurse practitioner, or equivalent) may be engaged in notifying participating 
Investigators of AEs being collected for the study. Similarly, blood collection on dried blood 
spot (DBS) cards for GCase activity measurement may occur at the indicated study time points 
in mitigation of unforeseen logistic delays. 
Individuals may be allowed to re-screen based on discussions with the Principal Investigator (PI) 
and the Sponsor’s medical representative or designee’s review and approval. Subjects who 
discontinue from the study prior to gene therapy infusion of AVR-RD-02 may be replaced. 
An independent DMC will be established for the study to review safety and efficacy information 
during the Pre-gene Therapy Infusion, Gene Therapy Infusion, and Post-gene Therapy Infusion 
Follow-up Periods of the study to assess for signals that may preclude continued study 
enrollment and/or necessitate changes to the protocol.  
Details on the DMC including meeting frequency will be outlined in a DMC Charter for the 
study, which outlines that the DMC will review data from the safety and efficacy assessments 
periodically throughout the study to ensure the ongoing safety of subjects. 
An overview of the overall study design can be found in Figure 2. A detailed overview of the 
Pre-gene Therapy Infusion and Gene Therapy Infusion Periods is provided in Figure 3.

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Tabular overviews of the required assessments for the study (including the timing of each) can 
be found in Section 15. The Schedule of Assessments from Screening through the Apheresis 
Period is in Table 4, the Schedule of Assessments from Investigational Product Preparation and 
Testing through End of Gene Therapy Infusion is in Table 5, and the Schedule of Assessments 
for the Post-gene Therapy Infusion Follow-up Period (Study Week 1 [Day 1] through Study 
Week 52 [Day 365]) is in Table 6. 
After study completion, consenting subjects will continue periodic safety and efficacy 
assessments for approximately 14 additional years (for a total of approximately 15 years 
post-gene therapy infusion follow-up) in a long-term follow-up study to AVRO-RD-02-201.  
6.2
Discussion of Design and Control
6.2.1
Overall Study Design and Study Population
The open-label design was deemed appropriate for the early phase nature of the study. 
Approximately 8 to 16 switch-stable and treatment-naïve subjects with Type 1 Gaucher disease 
will be enrolled sequentially in this study to assess the safety and change-from-baseline efficacy 
of AVR-RD-02 in both subjects who have previously been on a stable ERT regimen and those 
who have not received ERT or SRT. This approach will allow for an early-phase assessment of 
engraftment in these two important populations, may allow for a greater understanding of the 
potential clinical benefit in these populations, and thereby may help inform future clinical 
development. 
The study is designed to enable an assessment of safety and efficacy, in a risk-stratified manner, 
among adult subjects who have been stable on ERT and those naïve to ERT. Based on stopping 
rules and data collected from initial safety cohorts, an independent DMC review at pre-specified 
intervals will assess the appropriateness of the progressive introduction of additional cohorts and 
subjects.  
Subjects with Type 1 Gaucher disease will be the focus of this Study AVRO-RD-02-201, as this 
is the most common form of Gaucher disease (Grabowski 2015). As this will be a study with no 
control arm, only an assessment of treatment response relative to baseline in Type 1 Gaucher 
disease will be performed. To facilitate the comparison to baseline, previous medical records will 
be requested for study subjects in order to establish a more robust estimate of pre-treatment 
measures of disease. The exclusion of subjects with neuronopathic forms of Gaucher disease (ie, 
Types 2 and 3 Gaucher disease) should prevent the potential introduction of confounding signals 
associated with these conditions, thereby allowing a better understanding and interpretability of 
this study’s outcomes in relation to previous clinical study observations in Type 1 Gaucher 
disease (see Section 7.3). 
In clinical studies of wild type GCase, velaglucerase alfa, immunogenicity was low for both 
switch-stable and treatment-naïve subjects (Pastores 2014; VPRIV PI).  
Given the overall comparability of safety profiles among switch-stable and treatment-naïve 
subjects in these studies, AVRO-RD-02-201 aims to include both switch-stable and treatment-
naïve subjects. 

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Once DMC review of the available data from a total of 2 safety cohorts of switch-stable subjects 
occurs, the DMC may determine that enrollment may expand to include additional switch-stable 
subjects in an unrestricted manner. In addition, the treatment-naïve study arm may be open to 
enrollment and will follow the same gated enrollment scheme as outlined above for the switch-
stable arm (see Section 6.1).
The inclusion of subjects with ages ranging from 
18 years to 
50 years is based on several 
considerations. The age of onset/diagnosis of Type 1 Gaucher disease has been reported to range 
from the first to the ninth decade of life, is influenced by genotype, and varies among geographic 
regions. Diagnosis of Type 1 Gaucher disease has been initially reported prenatally and as late as 
the ninth decade (Charrow 2000). The median age of onset of Type 1 Gaucher disease is 
approximately 30 years among N370S homozygotes, with an earlier age of onset (75th percentile 
before the age of 30) observed with other genotypes. Age at diagnosis of younger than 10 years 
was reported in patients with N370S/84GG, L444P homozygotes, L444P/?, and N370S/IVS2+1 
genotypes, all of which are often associated with severe symptomatology (Charrow 2000). All
subjects will be required to be postpubertal, defined as having Tanner Stage 5 genital 
development and pubic hair distribution in males and breast development in females at the time 
of Screening. The requirement to have adult male (Tanner Stage 5) genital development or 
Tanner Stage 5 breast development was included as part of study eligibility to ensure subjects 
aged 18 years to 21 years are not continuing to undergo the metabolic and other physical changes 
50 years of age at Screening was 
included as rates of engraftment may decrease with increasing age. Therefore, safety and 
efficacy can best be assessed by capturing an age range in which most Type 1 Gaucher disease 
patients are diagnosed and limiting the age of the study population to individuals most likely to 
 50 years).  
The Screening through Pre-gene Therapy Infusion Period could be as long as 21 weeks. To avoid 
any significant interruption of enzyme replacement for switch-stable subjects, ERT will be 
continued up to 2 weeks before the scheduled gene therapy infusion day. This 2-week timeframe 
should serve as an adequate washout period for the replacement enzyme before gene therapy 
infusion is initiated. This timeframe is based on the pharmacokinetics (PK) and clearance of 
commercially available ERTs and the corresponding dosing frequency recommendations (see the 
package inserts for imiglucerase, velaglucerase alfa, and taliglucerase alfa).
6.2.2
Stem Cell Mobilization and Conditioning Regimens
6.2.2.1
Stem Cell Mobilization
Both granulocyte-colony stimulating factor (G-CSF) and plerixafor are being used in the study 
for stem cell mobilization. Superiority of G-CSF and plerixafor over G-CSF alone in stem cell 
mobilization of subjects has been demonstrated (Baiamonte 2015; Goker 2015; Yannaki 2013); 
in combination with G-CSF, plerixafor has been shown to increase peripheral blood CD34+ cell 
counts, including increased frequency of more primitive CD34+ cell subtypes and capacity to 
produce colonies. 

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6.2.2.2
Conditioning
A 4-day conditioning regimen of IV busulfan once daily (QD) will be used in the study. Before 
the 4-day conditioning regimen begins, a weight-based test dose of busulfan 0.8 mg/kg IV will 
be administered on Day -6 to determine PK and the initial doses that will be given on Day -4 and 
Day -3 of the Conditioning phase. Busulfan PK samples may be drawn daily during the 
conditioning phase. The myeloablative cumulative target for busulfan exposure will be an 
area-under-the curve (AUC) of 90(day 0-4) ± 2% mg•hr/L. The United States Food and Drug 
Administration (US FDA), European Medicines Agency (EMA), and Health Canada recommend 
an initial IV busulfan weight-based dose of 0.8 mg/kg IV every 6 hours or 3.2 mg/kg IV daily for 
conditioning, with consideration for modified dosing strategies for patients with less than ideal 
body weight (Busulfan PI; Busulfan Product Monograph; Busulfan SmPC). However, Bartelink 
et al. (Bartelink 2012) investigated the covariates related to the PK of busulfan and determined 
that body weight was the most predictive covariate that explained variability in busulfan 
exposure between patients. The relationship between body weight and clearance was 
characterized by an allometric equation with a scaling component (Bartelink 2012). The scaling 
range for adolescents and adults was from 2.7 mg/kg/day to 4.1 mg/kg/day and allowed for 
individualized initial dosing based on body weight. However, further studies evaluating the PK 
of busulfan by Davis et al. (Davis 2019) and Weil et al. (Weil 2017) determined that 
administration of a busulfan test dose given before the 4-day myeloablative conditioning regimen 
allowed for the use of a personalized PK-guided dosing strategy based on the PK from the test 
dose and the patient’s body weight, which resulted in significant improvement in target AUC 
attainment and less interpatient variability compared to using the weight-based dosing regimen 
alone as described by Bartelink et al. The personalized PK- and weight-based guided dosing 
strategy as suggested by Weil et al. and Davis et al. in addition therapeutic drug monitoring 
(TDM) of the PK of the test dose and during conditioning has resulted in more accurate 
cumulative AUC outcomes versus our previous weight-based and TDM-guided dosing without 
test dose.
This PK- and weight-based guided individualized dosing regimen of busulfan defines a 
once-daily regimen for myeloablative conditioning at an AUC(day 0-4) of 90 mg•hr/L
(5,400 µmol•min/day). Because busulfan PK display large interpatient and intrapatient 
variability and exposure, TDM of busulfan is routinely performed as standard clinical care in 
patients undergoing HSCT (Long-Boyle 2015).
The timing of the busulfan test dose and the approach to busulfan TDM at each site will be 
determined by the method used to perform TDM. The 2 options for performing busulfan TDM 
are as follows:
Liquid chromatography-mass spectrometry (LC-MS): Busulfan TDM will be performed 
on the test dose on Conditioning Day -6 to inform the dose on Conditioning Days -4 
and -3. The PK sampling may also be performed on Day -5 to support optimization of 
busulfan exposure. Busulfan TDM will also be performed on Conditioning Days -4 
and -3 to inform the doses on Days -2 and -1, respectively. Collective information from 
TDM on all days during Conditioning (Day -4 to Day -1) will be used to calculate the 
cumulative AUC in Study AVRO-RD-02-201, with plasma samples taken at periodic 
intervals post-busulfan administration as described in Section 8.1.1.3 and in the Schedule 

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of Assessments (Table 5). All laboratories performing TDM will use validated methods 
to quantify busulfan in plasma, according to Good Laboratory Practice (GLP).  
An investigational, validated automated nanoparticle immunoassay kit (Saladax 
Biomedical, Inc.): Busulfan TDM will be performed on the test dose on Conditioning 
Day -5 to inform the dose on Conditioning Day -4. Busulfan TDM will be performed on 
Conditioning Day -4, and TDM PK results will be used to inform the dose on 
Conditioning Day -3 together with the TDM PK results from the test dose. Busulfan 
TDM will be performed on Conditioning Day -3, and TDM PK results will be used to 
inform the dose on Conditioning Day -2 together with the results from the test dose and 
Conditioning Day -4. Busulfan TDM will be performed on Conditioning Day -2, and 
TDM PK results will be used to inform the dose of Conditioning Day -1 together with the 
results from the test dose and Conditioning Days -4 and -3. Collective information from 
TDM on all days during Conditioning (Day -4 to Day -1) will be used to calculate the 
cumulative AUC in Study AVRO-RD-02-201, with plasma samples taken at periodic 
intervals post-busulfan administration as described in Section 8.1.1.3 and in the Schedule 
of Assessments (Table 5).
Further information regarding assessment of busulfan exposure can be found in the Laboratory 
Manual. 
The busulfan dose-versus-concentration relationship over time will be evaluated to obtain an 
individualized dosing strategy that optimizes efficacy and minimizes toxicity. Optimizing the 
target for cumulative busulfan exposure has a significant impact on outcomes (Bartelink 2016). 
In transfusion-dependent beta-thalassemia (TDT) patients who underwent autologous HSCT for 
LV-mediated gene therapy, a 4-day myeloablative conditioning regimen, with an average 
busulfan daily dose range of 4,670 µmol•min/L to 5,212 µmol•min/L per day, was used 
(Thompson 2018). In 400 children and young adults who underwent allogeneic HSCT for 
non-oncology indications, a busulfan-AUC of 78 to 101 mg•hr/L was considered to be optimal 
for targeting a balance between acute toxicity and patient outcomes, including graft failure, or 
disease relapse (Bartelink 2016).
In the AVRO-RD-02-201 study, busulfan dosing will be determined using PK modeling 
software, as described in the Study Treatment Manual. Reports in the literature indicate that 
cumulative AUCs are sometimes calculated with methods that vary by institution, and thus, use 
of a PK modeling software program can provide a consistent, standardized approach in dosing 
strategies between sites (Bartelink 2016).  
Busulfan crosses the blood-brain barrier and can cause neurotoxicity, including seizures, when 
administered at higher doses. Therefore, anticonvulsant medication is routinely prescribed for 
patients undergoing myeloablative therapy with busulfan in preparation for bone marrow 
transplant (BMT) or hematopoietic cell transplant (HCT). Consistent with this practice, 
anticonvulsant prophylaxis will be administered concurrent with busulfan administration for 
conditioning in this study. Levetiracetam will be administered in this study as described in 
Section 8.1.1.3. The dosing regimen selected for levetiracetam has been shown in literature to be 
effective at preventing seizures in adults receiving conditioning with busulfan in preparation for 
HSCT, and to have an acceptable safety profile when administered in combination with busulfan 
(Akiyama 2018). For subjects with contraindications to levetiracetam, an alternative anti-

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convulsant medication (eg, benzodiazepines or valproic acid) may be used before and after 
busulfan treatment (Busulfan PI).
Busulfan treatment at the approved dose and schedule produces profound, transient 
myelosuppression in all patients. Hematologic changes have been observed in subjects receiving 
myeloablative busulfan conditioning regimens used in other autologous LV-mediated gene 
therapy studies for TDT, sickle cell disease (SCD), metachromatic leukodystrophy (MLD),
leukocytes adhesion deficiency-1, and X-linked chronic granulomatous disease (Fumagalli 2022;
Sessa 2016; Thompson 2018; Tisdale 2018; Kohn 2020; see also the Investigator’s Brochure for 
AVR-RD-02). Similar outcomes were achieved by Mamcarz et al in LV-mediated gene therapy 
for X-linked severe combined immunodeficiency (SCID-X1) patients, albeit targeted busulfan 
was indicated at low dose (Mamcarz 2019).  
While secondary malignancies have been reported among individuals exposed to busulfan during 
treatment for hematologic cancers, less is known about the magnitude of this risk among 
individuals exposed to short term busulfan conditioning in the management of non-malignant 
disorders (eg, gene therapy or BMT). To address this concern, AVROBIO conducted a literature 
review of busulfan conditioning in conjunction with BMT or HCT for non-malignant conditions 
(literature references available upon request). Similarly, AVROBIO reviewed the literature for 
busulfan conditioning before LV-mediated gene therapy for non-malignant conditions (literature 
references available upon request). With the exception of the one case of post therapy-related
myelodysplastic syndrome (t-MDS) reported in an individual who underwent busulfan 
conditioning before LV-mediated gene therapy for SCD (Hsieh 2020), no other cases of t-MDS, 
leukemia (acute myeloid leukemia [AML]), cancer, or precancerous lesions were reported in 
over 700 exposures to busulfan conditioning for non-malignant conditions. Based on this 
literature review, the risk of t-MDS or leukemia due to busulfan conditioning before 
LV-mediated gene therapy for non-malignant conditions appears to be low. Nevertheless, 
deoxyribonucleic acid (DNA) will be collected from bone marrow aspirate and peripheral blood 
samples at Baseline and stored for subsequent evaluation should t-MDS, leukemia (AML),
hematologic cancer, or a precancerous condition be observed.  
The impact of the busulfan conditioning regimen used in this study on fertility is not fully 
understood. Data from studies of the use of conditioning agents in oncology indications suggest 
that these agents may be associated with transient or persistent infertility with a significant 
impact on QoL of transplanted patients (Faraci 2019; Busulfan PI; Busulfan Product Monograph;
Busulfan SmPC).   
The potential risk of infertility in the study will be mitigated by: 
Males will be offered sperm cryopreservation and females will be offered oocyte 
harvesting and cryopreservation.  
The impact of the conditioning regimen on the subjects’ reproductive potential will be 
assessed during the study by evaluating the change from Baseline in sperm count, 
volume, sperm concentration, total motility, progressive motility, and morphology in 
males, and changes from Baseline in menstrual history, AMH, FSH, and LH (biomarkers 
of ovarian reserve) in females. For female subjects, the use of gonadotrophic-releasing 
hormone agonists (Lupron) for ovarian chemoprotection can be offered prior to 
gonadotoxic therapy such as busulfan. 

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For both male and female subjects, additional assessments of reproductive potential 
and/or referral to a urologist (male subjects) or a reproductive endocrinologist (female 
subjects) is recommended.
Pregnancy outcomes, if any, will be monitored and recorded during this study. 
6.2.3
Efficacy and Safety Measures
Measures of engraftment of gene-augmented HSCs will be evaluated by determining average 
VCN using qPCR and/or ddPCR in peripheral blood and bone marrow. To ensure subject safety, 
a CD34+ stem cell back-up of nontransduced cells will be collected and stored for use as rescue 
treatment in the unlikely event that there is prolonged bone marrow aplasia after AVR-RD-02 
treatment (see Section 8.1.1.1).
Efficacy measures chosen for the planned AVRO-RD-02-201 study have been commonly used to 
measure treatment effects in trials of ERT and SRT for Gaucher disease. Efficacy and safety 
endpoints chosen, and the timing of these assessments, considered the following: the natural 
history of Gaucher disease, the clinical progression of signs/symptoms known to impact 
morbidity and mortality in subjects with the disease, and regulatory guidelines for follow-up of 
subjects receiving gene therapy products (ie, US Department of Health and Human Services
[DHHS], FDA, Center for Biologics Evaluation and Research [CBER], Guidance for Industry, 
Long Term Follow-Up After Administration of Human Gene Therapy Products, January 2020 
[FDA 2020a] US DHHS, FDA, CBER, Guidance for Industry, Testing of Retroviral Vector-
Based Human Gene Therapy Products for Replication Competent Retrovirus During Product 
Manufacture and Patient Follow-up, January 2020 [FDA 2020b] EMA, Guideline on Follow-up 
of Patients Administered with Gene Therapy Medicinal Products, October 2009 [EMA 2009]).

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7
STUDY POPULATION
Individuals may be allowed to re-screen based on discussions with the PI and the Sponsor’s 
medical representative or designee’s review and approval.  
Prospective approval of protocol deviations, but not limited to recruitment and enrollment 
criteria, also known as protocol waivers or exemptions, are not permitted.
7.1
Inclusion Criteria
Common Inclusion Criteria for all Enrolled (Switch-stable and Treatment-naïve) Subjects:
Subjects must meet all of the following inclusion criteria for participation in this study:
1. Subject must be willing and able to provide written informed consent for the study in 
accordance with applicable regulations and guidelines and to comply with all study visits 
and procedures, including the use of any data collection device(s) that may be used to 
directly record subject data.
2.
development and pubic hair distribution in males and breast development in females). 
Guidelines for Tanner staging will be provided in the appropriate Study Manual. 
3. Subject has a confirmed diagnosis of Type 1 Gaucher disease based on deficient GCase 
enzyme in blood (and/or documented historical deficiency of GCase activity, verified by 
the PI) and clinical phenotype (Gary 2018) at Screening. Deficient GCase activity results 
from DBS cards are acceptable for inclusion criteria at Screening (Miyamoto 2021).
a. For switch-stable subjects, documentation of deficient GCase enzyme activity in 
peripheral blood prior to having been started on ERT is required. If GCase levels 
prior to ERT are not available, deficient trough GCase enzyme activity in peripheral 
blood at Screening is required.  
4. Female subjects of reproductive potential will be counseled regarding the risks, benefits, 
limitations, and alternatives associated with female fertility preservation. Oocyte 
harvesting and cryopreservation will be offered. 
5. Male subjects must be willing to refrain from donating sperm any time after receiving 
conditioning therapy. For subjects planning on (or for whom there is a possibility of) 
fathering children in the future, cryopreservation before undergoing conditioning will be 
recommended.  
6. All subjects who have not undergone successful surgical sterilization (ie, vasectomy, 
hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) must agree to remain 
sexually abstinent or use two effective methods of contraception while sexually active 
from the day of conditioning administration until 52 weeks post-gene therapy infusion 
(ie, the Week 52 study visit). Two methods of contraception are required even with 
documented medical assessment of surgical success of sterilization.
a. For male subjects and for male spouses/partners of female subjects, condoms are an 
acceptable method of barrier contraception.
b. For female subjects and for female spouses/partners of male subjects, acceptable 
methods of barrier contraception include diaphragm, cervical cap, or contraceptive 
sponge. 

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7. Male and female subjects must agree to refrain from donating sperm and eggs, 
respectively, after undergoing conditioning.  
8. Subject must be willing to refrain from donating blood, organs, tissues, or cells for gene 
therapy infusion any time after AVR-RD-02 treatment. 
9. Subject must be willing to receive blood or blood products transfusion to manage AEs. 
Additional Inclusion Criteria for Switch-stable Subjects:
In addition to inclusion criteria 1 through 9, switch-stable subjects must meet all of the following 
inclusion criteria for participation in this study: 
10. Subject has undergone a stable dose (within 75% to 125% of the prescribed dose) of ERT 
infusions resulting in a total monthly ERT dose of  30 U/kg and  120 U/kg) for 
 24 consecutive months with no significant interruptions, in the opinion of the 
Investigator, in dosing over the last 6 months prior to Screening. 
11. Subject has normal or near-normal hematologic values at Screening defined as one or 
more of the following: 
a.
b.
 × 109/L
12. Subject has stable Gaucher disease during the 6 months immediately preceding Screening 
defined by: 
a. Stable hemoglobin concentration (ie, within a range of ± 2 g/dL of the Screening 
value) based on documented historical clinical laboratory results  
and
Stable platelet count (within ± 20% of the Screening value) based on documented historical 
clinical laboratory results
13. Subject has not received SRT for Gaucher disease during the 12 months immediately 
preceding Screening.
Additional Inclusion Criteria for Treatment-naïve Subjects:
In addition to inclusion criteria 1 through 9, treatment-naïve subjects must meet the following 
inclusion criteria for participation in this study: 
14. Subject has never received either ERT or SRT for Gaucher disease or has not received 
either ERT or SRT for Gaucher disease within 12 months of Screening. 
15.
2 g/dL below the lower limit of normal (LLN) for age 
and sex at Screening and at least one of the following at Screening:
a. Platelet count < 120 × 109/L
Enlarged liver by palpation, confirmed on abdominal MRI 
Moderate splenomegaly by palpation, confirmed on abdominal MRI 
16. For any subject who is treatment-naïve, ERT peri-procedurally (from the Screening 
Period through to Gene Therapy Infusion Period) will be considered in consultation with 
the PI and Sponsor Medical Monitor. 

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7.2
Exclusion Criteria
Subjects will be excluded from participation in this study if they meet any of the following 
exclusion criteria:
1. Subject has Type 2 or 3 Gaucher disease, has severe neurological signs and symptoms, 
defined as complete ocular paralysis, overt myoclonus or history of seizures, 
characteristic of neuronopathic Gaucher disease, or has a tremor, peripheral neuropathy 
or symptoms of Parkinson’s disease. 
2. Subject has any one of the following: 
a. Hemoglobin value < 9.0 g/dL, or 
b. Platelet count < 70 × 109/L, or  
c. Spleen volume > 10 × normal, or 
d. Pulmonary hypertension 
3. Subject has experienced a prior anaphylactic or anaphylactoid reaction (of any severity) 
to ERT.
4. Treatment-naïve subject has history of clinically significant (CS) anti-GCase antibodies.  
5. Subject has a contraindication to ERT, in the opinion of the Investigator. 
6. Subject has a contraindication to HSC transplantation, in the opinion of the Investigator. 
7. Subject presents with iron, folic acid, and/or vitamin B12 deficiency sustained anemia 
during Screening. 
8. Subject has idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic 
purpura (TTP), thrombocytopenia, anemia, hepatomegaly, splenomegaly, and/or 
osteoporosis unrelated to Gaucher disease, in the opinion of the Investigator. 
9. Subject has a clinical co-morbidity such as neurologic, cardiovascular, pulmonary, 
hepatic, gastrointestinal, renal, hematologic, endocrine, metabolic, genetic, immunologic, 
neoplastic, or psychiatric disease, other medical condition(s), or intercurrent illnesses that 
may confound the study results or, in the opinion of the Investigator, may preclude 
participation in the study.
10. Subject is a pregnant and/or lactating female.
11. Subject is unable to understand the nature, scope, and possible consequences of the study. 
12. Subject has diabetes mellitus (Type 1 or Type 2). 
13. Subject has active, progressive bone necrosis.
14. Subject has an active chronic infection during the Screening, Baseline, or Pre-gene 
Therapy Infusion Period of the study. 
15. Subject has an active uncontrolled acute bacterial, viral, fungal, parasitic, or 
prion-associated infection during the Screening, Baseline, or Pre-gene Therapy Infusion 
Period of the study.  
16. Subject has a history of (or current) tuberculosis.
17. Subject tests positive for hepatitis B virus (HBV), hepatitis C virus (HCV), human 
immunodeficiency virus (HIV, Type 1 or 2), human T-cell lymphotropic virus (HTLV)-1, 
HTLV-2, and/or syphilis on Venereal Disease Research Laboratory (VDRL) test, 
chemiluminescent microplate immunoassay (CMIA), or enzyme immunosorbent assay 
(EIA) at Screening.

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18. Subject has a prior history of (or current) cancer or precancerous lesion or has a known 
genetic predisposition to cancer. The one exception is a prior history of resected 
squamous cell carcinoma.  
19. Subject has any other medical condition that predisposes him/her to (or conveys 
increased risk of) malignancy, in the opinion of the Investigator, including history of (or 
current) monoclonal gammopathy of undetermined significance (MGUS). 
20. Subject has a history of alcohol or illicit drug abuse, according to the Investigator’s 
judgment. 
21. Subject has undergone, or is scheduled to undergo, BMT, HSC, and/or solid organ 
transplant. NOTE: Subjects who are otherwise eligible for the study but are scheduled for 
bone marrow or HSC transplant to treat Type 1 Gaucher disease may be enrolled in the 
study (instead of receiving an allogeneic transplant) and undergo gene therapy infusion 
with AVR-RD-02. 
22. Subject has white blood cell (WBC) count < 3.0 × 109/L and/or uncorrected bleeding 
disorder from enrollment (ie, signing of informed consent at Screening) through the Gene 
Therapy Infusion Period of the study (ie, the day of AVR-RD-02 gene therapy infusion). 
23. Subject has CS immunosuppressive disease or condition, in the opinion of the 
Investigator, at Screening.
24. Subject is on (or requires treatment with) cytotoxic or immunosuppressive agents from 60 
days prior to signing informed consent at Screening (ie, study enrollment) through the 
Week 52 study visit; the one exception is treatment with cytotoxic or immunosuppressive 
agents required per protocol for stem cell transplant.  
25. Subject is on (or requires treatment with) red blood cell (RBC) growth factor (eg, 
erythropoietin) from 6 months prior to enrollment (ie, signing of informed consent at 
Screening) through the Week 52 study visit.  
26. Subject has any condition that makes it impossible to perform MRI studies. 
27. Subject has medical condition(s) and/or is receiving medication(s) that would 
contraindicate ability to undergo mobilization (including contraindication to G-CSF 
and/or plerixafor), apheresis, or conditioning. 
28. Busulfan is contraindicated for the subject. 
29. Subject has previously received treatment with AVR-RD-02 or any other gene therapy. 
30. Subject is participating in (or plans to participate in) any other investigational drug trial, 
or plans to be exposed to any other investigational agent, device, and/or procedure, from 
30 days prior to enrollment (ie, signing of informed consent at Screening) through study 
completion. 
7.3
Rationale for Inclusion or Exclusion of Certain Study Candidates
AVR-RD-02 is an ex vivo LV, autologous gene therapy intended for the durable provision of 
functional GCase in subjects with Gaucher disease. Enrollment is restricted to subjects with Type 
1 Gaucher disease for this Phase 1/2 study to reduce between-subject symptom, and thus, 
endpoint variability. The most robust assessment of safety and efficacy with AVR-RD-02 
treatment would be generated in subjects with Type 1 Gaucher disease who are switch-stable (as 
defined in this protocol) and in treatment-naïve subjects with Type 1 Gaucher disease. While it is 
generally recognized that individuals with Types 2 and 3 Gaucher disease exhibit significant 
neurologic features and markedly reduced life spans, the natural history of these conditions, 

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along with reports of treatment response, are not well understood. Whereas clinical study data on 
the safety and efficacy of treatments for Types 2 and 3 Gaucher disease have not been published, 
there is an extensive body of literature that has arisen from the numerous clinical studies 
conducted in Type 1 Gaucher disease, thereby allowing for more meaningful interpretation of 
outcomes in comparison to previous observations (Barton 1991; Ben Turkia 2013; Cox 2012;
Cox 2015; Elstein 2015; Gonzalez 2013; Grabowski 1995; Mistry 2015; Pastores 2014; Zimran 
2011).
Exclusion of subjects with Types 2 and 3 Gaucher disease prevents the potential introduction of 
confounding safety signals (see Section 6.2). Thus: 
Inclusion criterion 3 identifies the Type 1 Gaucher disease study population; and,  
Exclusion criterion 1 eliminates subjects who have, or are suspected of having, Types 2 
or 3 Gaucher disease.
The requirement that subjects be postpubertal (defined as Tanner Stage 5 genital development 
and pubic hair distribution in males and breast development in females) at Screening was 
included to ensure that subjects 18 years to 21 years of age are not continuing to undergo the 
metabolic and other physical changes associated with puberty. The requirement for subjects to be 
as rates of engraftment may decrease with 
increasing age (see Section 6.2). Thus: 
Inclusion criterion 2
postpubertal, defined as Tanner Stage 5 genital development and pubic hair distribution 
in males and  breast development in females.
As the impact of the planned conditioning regimen on infertility and primary ovarian 
insufficiency in this study population is not fully understood, the entry criteria include items to 
off-set the potential risk of infertility to female and male subjects (see Section 6.2.2):
Inclusion criterion 4 mitigates the female infertility risk associated with this protocol by 
offering reproductive counseling and oocyte harvesting and cryopreservation. 
Inclusion criterion 7 prohibits male and female subjects from donating sperm or egg, 
respectively, after undergoing conditioning, and offers male subjects the option of sperm 
cryopreservation prior to conditioning. 
Inclusion criteria 10 through 13 define the switch-stable subjects, and inclusion criteria 14 and 
15 define the treatment-naïve subjects.
Individuals may be allowed to re-screen based on discussions with the PI and the Sponsor’s 
medical representative or designee’s review and approval. 
Other exclusion criteria are related to the subjects’ fitness for the conditioning regimen and gene 
therapy infusion. In addition, to most accurately assess the effects of AVRO-RD-201, subjects 
with medical conditions that can potentially confound measures of safety and efficacy will also 
be excluded.  

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7.4
Discontinuations
7.4.1
Discontinuation of Subjects
The criteria for enrollment must be followed explicitly. If it is discovered that a subject who did 
not meet entry criteria was inadvertently enrolled prior to AVR-RD-02 gene therapy infusion, the 
subject will be discontinued from the study. If the subject underwent any study-related 
procedures and then experienced an AE, they will be followed for 30 days or until the AE 
resolves, whichever is longer (see Section 9.2). If it is discovered that a subject who did not meet 
entry criteria underwent gene therapy infusion, the subject will not be discontinued and will be 
followed as per protocol.
Subjects who discontinue from the study prior to gene therapy infusion of AVR-RD-02 may be 
replaced.
In addition, subjects may be discontinued from the study in the following circumstances: 
The subject or the subject’s legal representative (ie, legal guardian) requests to be 
withdrawn from the study. 
Sponsor decision 
The Sponsor or its designee discontinues the study or discontinues the subject’s 
participation in the study for medical, safety, regulatory, or other reasons consistent with 
applicable laws, regulations, and Good Clinical Practice (GCP). 
The Sponsor or its designee discontinues the clinical study at a particular 
investigative site.
AE
If the Investigator decides that the subject should be withdrawn because of an SAE or 
a CS laboratory value, study-related procedures are to be discontinued and appropriate 
safety measures taken. The Sponsor or its designee is to be alerted immediately. In cases
where the subject has received gene therapy infusion, the subject will be provided the 
opportunity to participate in the long-term follow-up study. 
7.4.2
Discontinuation of Study Sites/Site Terminated by Sponsor
Study site participation may be discontinued if the Sponsor or its designee, the Investigator, or 
the Institutional Review Board/Independent Ethics Committee (IRB/IEC) of the study site judges 
it necessary for medical, safety, regulatory, or other reasons consistent with applicable laws, 
regulations, and GCP. Subjects would be provided the opportunity to transfer to an eligible site. 
7.4.3
Discontinuation of the Study/Study Terminated by Sponsor
The study will be discontinued if the Sponsor or its designee judges it necessary for medical, 
safety, regulatory, or other reasons consistent with applicable laws, regulations, and GCP. 
Subjects who have received gene therapy infusion will be provided the opportunity to participate 
in the long-term follow-up study. 

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7.4.4
Stopping Rules
7.4.4.1
Stopping Rules for AVR-RD-02 
If the following occurs, gene therapy infusion procedures in additional subjects will be 
temporarily suspended, and a safety review meeting will take place with the DMC and the 
Sponsor: 
Death of a subject that is attributed as possibly, probably, or definitely related to 
AVR-RD-02. 
Gene therapy infusion procedures may resume if appropriate changes to study conduct are 
identified and implemented to reduce any risks to subjects going forward. 
7.4.4.2
Enrollment Pause Criteria
Enrollment in this study may be paused at any time for safety reasons. 
In the event enrollment is paused, subjects who have already been treated with 
AVR-RD-02 Drug Product will continue in the study. 
The following are examples of events that may result in enrollment pause.  
Death of a subject that is attributed as possibly, probably, or definitely related to 
AVR-RD-02. 
Leukemia/lymphoma that is attributed to an AVRO-RD-02-201 study procedure. 
Any individual subject shows no or sub-optimal evidence of engraftment of 
AVR-RD-02 gene modified cells (based on average VCN in blood and bone marrow 
samples or GCase enzyme activity in blood) at or after Week 26 assessments. 
Detection of leukemia/lymphoma due to vector-mediated oncogenesis by insertional 
mutagenesis.
Failure to achieve reconstitution with transduced cells in at least one subject, 
necessitating the use of rescue cells. 
Unexpected, CS, AVRO-RD-02-related Grade 3 or Grade 4 toxicities in > 2 subjects.
If enrollment pause occurs, gene therapy infusion procedures in additional subjects will 
be temporarily paused, and a safety review meeting will take place with the DMC and the 
Sponsor. 
A determination will be made as to whether the trial should continue without change, 
continue with specific changes, or terminate.
The Sponsor will inform the regulatory authorities and the Investigators, and each site’s 
IRB/IEC and other appropriate institutional regulatory bodies will be promptly notified if 
a decision to pause enrollment is made.
Study enrollment may resume if appropriate changes to study conduct are identified and 
implemented to reduce any risks to subjects going forward. 
7.4.5
Engraftment Failure
Engraftment failure is defined as failure to achieve an absolute neutrophil count (ANC) 
 0.5 × 109/L by Day 42 post-gene therapy infusion of AVR-RD-02 Drug Product. In the event 
of an engraftment failure: 

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The subject should receive the back-up rescue cells. 
Based on the Investigator’s discretion, the subject may receive additional evaluations 
and/or treatments that are outside the scope of this protocol to monitor for and manage 
engraftment failure.
7.4.6
Enzyme Replacement Therapy
Subjects will be routinely monitored throughout the post-gene therapy infusion period for 
changes from Baseline values in clinical parameters. Subjects may be started on standard of care 
ERT in accordance with prespecified ERT starting rules that have been established for time 
periods of 0 to 5 months and 6 months to 12 months after gene therapy infusion as outlined 
below. 
7.4.6.1
Enzyme Replacement Therapy Initiation Rules for Switch-Stable Subjects Only: 
0-5 Months After Gene Therapy Infusion 
Between 0 and 5 months after gene therapy infusion, clinical parameters including hemoglobin 
concentration and platelet counts will be monitored monthly between the Week 5 (Day 30) and 
Week 26 (Day 180) visits. Levels of GCase activity will be monitored between the Week 9 (Day 
60) and Week 26 (Day 180) visits. Subjects with GCase activity above the range for Gaucher 
disease (ie, > 15% of the lower limit of the range observed in healthy individuals; Pastores and 
Hughes 2020) in samples collected at 2 months or any of the subsequent months following gene 
therapy infusion will not receive ERT. At Week 13 (Month 3), subjects who have not received 
post-gene therapy infusion ERT and have laboratory values that fall within the following clinical 
parameters: GCase activity in blood > 15% of the lower limit of the range observed in healthy 
individuals and hem
not be required to undergo clinical assessments or GCase activity testing at Week 18 (Month 4) 
or Week 22 (Month 5). These subjects will resume their clinical assessments at the 6-month 
post-gene therapy infusion visit. 
Subjects with GCase activity that falls within the diagnostic range for Gaucher disease (ie, 
GCase activity 
consecutive monthly visits at the Week 9, 13, 18, or 22 visits will be evaluated for starting ERT. 
All subjects whose GCase activity falls below 15% of the lower limit of the range observed in 
healthy individuals at Week 9, 13, 18, or 22 visits will be monitored. The GCase activity value 
will be distributed to the PI and the Sponsor’s medical representative or designee. The 
determination to initiate post-gene therapy infusion ERT and the ERT dose will be based on this 
result and will be at the discretion of the PI and the Sponsor’s medical representative or 
designee. Prior to initiation of ERT and to post-gene therapy infusion discontinuation of ERT 
that was restarted, blood and bone marrow samples will be collected to assist with evaluating the 
impact of restarting ERT.
7.4.6.2
Enzyme Replacement Therapy Starting Rules: 6-12 Months After Gene Therapy 
Infusion 
The following only applies to subjects who have not been started on ERT between post-gene 
therapy infusion Weeks 9 to 26. 

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Switch-stable Subjects
Beginning with the Week 26 (Day 180/Month 6) visit, if two or more of the clinical parameters 
listed below are met over two consecutive visits, and if the observed clinical deterioration is, in 
the Investigator’s judgment, directly related to the subject’s Gaucher disease, the subject may be 
restarted on ERT at a dose of 15 U/kg every other week (or equivalent):  
Decrease from Baseline in hemoglobin concentration of > 2g/dL 
Platelet count of < 35 × 109/L
Increase in liver volume (as indicated by organ palpation) confirmed to be 20% greater 
than baseline (as measured by MRI)
Increase in spleen volume (as indicated by organ palpation) confirmed to be 25% greater 
than baseline (as measured by MRI)
New onset pulmonary hypertension 
If the clinical parameters that prompted ERT dosing do not return to baseline values within 
3 months, the Investigator has the option of increasing the ERT dose by additional increments of 
15 U/kg every other week (or the equivalent). The Investigator will discontinue ERT once the 
affected clinical parameters return to baseline values.
If, after ERT re-initiation, ERT has again been discontinued and any of the clinical parameters 
outlined above are again observed and confirmed, and are, in the Investigator’s judgment, 
directly related to the subject’s Gaucher disease, blood and bone marrow samples will be 
collected to assist with evaluating no or sub-optimal engraftment of AVR-RD-02 gene modified 
cells. Consequently, if any individual subject shows no or sub-optimal evidence of engraftment
of AVR-RD-02 gene modified cells (based on average VCN in blood and bone marrow samples 
or GCase enzyme activity in blood) at or after Week 26 assessments, the subject will continue 
the historical standard of care or the treatment that is recommended by the Investigator. 
Treatment-naïve Subjects
Beginning with the Week 26 visit, if any of the clinical parameters outlined below are observed 
and confirmed, and are, in the Investigator’s judgment, directly related to the subject’s Gaucher 
disease, ERT therapy may be initiated: 
1. Hemoglobin value < 7.0 g/dL
2. Platelet count < 35 × 109/L
3. New onset pulmonary hypertension 
The Investigator will discontinue ERT once the affected clinical parameters return to baseline 
values.  
If, after the initiation of ERT, ERT has been discontinued and any of the clinical parameters 
outlined above are again observed and confirmed, and are, in the Investigator’s judgment, 
directly related to the subject’s Gaucher disease, the subject’s ERT therapy may be 
re-introduced. The Investigator may again discontinue ERT once the affected clinical parameters 
return to baseline values. Prior to initiation of ERT and to post-gene therapy infusion 
discontinuation of ERT that was restarted, blood and bone marrow samples will be collected to 
assist with evaluating the impact of restarting ERT.

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Sponsor intends to follow subjects enrolled in this study for approximately 14 additional years 
(for a total of approximately 15 years post-gene therapy infusion follow-up) by way of a 
follow-up study to AVRO-RD-02-201. 

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8
TREATMENT
8.1
Treatments Administered
The Sponsor identifier for the investigational product is AVR-RD-02. The active substance in 
AVR-RD-02 is autologous CD34+ enriched HSCs that have been genetically modified ex vivo
with an LV containing an RNA transcript that, after reverse transcription, results in 
codon-optimized cDNA that, upon its integration into the human genome, encodes for functional 
human GCase. The finished investigational product is presented as a cryopreserved cell 
suspension in infusion bag(s) in vapor-phase liquid nitrogen, which must be thawed prior to use. 
The investigational product is intended for one-time IV infusion of between 3 × 106/kg and 
10 × 106/kg body weight autologous CD34+ enriched HSCs that have been genetically modified.  
In addition to AVR-RD-02, subjects will receive the following medications as part of the 
autologous transplant procedure in this study: 
Between 4 and 8 G-CSF injections and 2 plerixafor injections for HSC mobilization 
before AVR-RD-02 gene therapy infusion.  
Additional G-CSF injections will be considered beginning Day +30 after treatment 
with AVR-RD-02 gene therapy infusion if subject’s ANC < 0.5 × 109/L. G-CSF may be 
considered earlier if clinically needed in consultation with the PI and Sponsor Medical 
Monitor.  
Five IV infusions of busulfan, including 1 test dose to inform the conditioning dose and 
4 doses for myeloablative conditioning before treatment with AVR-RD-02. 
Anticonvulsant medication administration, in conjunction with busulfan administration, 
for seizure prophylaxis. 
Levetiracetam will be administered. If levetiracetam is contraindicated, an alternative 
anticonvulsant medication (eg, benzodiazepines or valproic acid) may be used.
Further details of treatment administration (including dosing regimens) are described in 
Sections 8.1.1 through 8.1.3. Additional details can also be found in the Study Treatment 
Manual.
8.1.1
Pre-gene Therapy Infusion Period (Approximately 8 Weeks to 10 Weeks) 
In some instances, the Pre-gene Therapy Infusion Period may be extended beyond 10 weeks due 
to subject and/or site availability to initiate conditioning.
8.1.1.1
Mobilization and Apheresis 
Mobilization of the subject’s HSC will take place at the participating investigational site based 
upon standard institutional procedures. On Mobilization Days 1 through 4, subjects meeting 
eligibility criteria for study participation will receive a daily G-CSF dose of 10 µg/kg body 
weight administered IV or subcutaneously (SC) (for sites with only prefilled syringes, a G-CSF 
daily dose from 10 µg/kg body weight up to 12 µg/kg body weight, administered in either a 
single or divided twice a day [BID] dose may be administered). On the evening of Mobilization 

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Day 4, subjects will receive an injection of plerixafor (0.24 mg/kg) 8 hours to 11 hours prior to 
the first apheresis. 
On the morning of Apheresis Day 1, mononuclear cells enriched with CD34+ stem cells will be 
harvested from the subject’s peripheral blood by apheresis 8 hours to 11 hours after the first 
plerixafor administration on Mobilization Day 4, using standard institutional procedures at the 
participating investigational study site. The apheresis unit obtained on Apheresis Day 1 will be 
shipped to the manufacturing site for cell transduction and processing (see Section 8.1.1.2). 
Refer to the Apheresis Day 1 section of the Study Treatment Manual for further details regarding 
Day 1 of apheresis.
On the evening of Apheresis Day 1, subjects will receive another injection of plerixafor 
(0.24 mg/kg) 8 hours to 11 hours prior to the second apheresis. On the morning of Apheresis 
Day 2, subjects will undergo an additional harvest of mononuclear cells enriched with CD34+ 
stem cells from the subject’s peripheral blood by apheresis, using standard institutional 
procedures at the participating investigational study site. Refer to the Apheresis Day 2 section of 
the Study Treatment Manual for further details regarding Day 2 of apheresis. The apheresis unit 
obtained on Apheresis Day 2 will be retained and stored at the investigational site for use as 
rescue treatment in the unlikely event that there is prolonged bone marrow aplasia after treatment 
with AVR-RD-02. 
If plerixafor cannot be administered within 8 hours to 11 hours prior to the first and the second 
apheresis in the outpatient setting, the subject should stay in a facility with night staffing (eg, 
inpatient unit or partial hospital) to ensure that plerixafor is administered within window. If 
hospital admission is not feasible, plerixafor can be administered up to 14 hours prior to 
apheresis to achieve a peak CD34+ cell count (Mozobil PI).
After each apheresis (ie, on Apheresis Days 1 and 2), total cell count (per µL) and CD34+ cell 
enumeration by flow cytometry will be performed at the participating investigational study site 
to ensure an adequate number of cells have been procured for CD34+ cell selection. The target 
number of cells for the Apheresis Day 1 collection is 6.5 × 1010 total cells and 6.5 × 108 CD34+ 
cells (shipped to the manufacturing site for transduction); the target number of cells for the 
Apheresis Day 2 collection is at least 3 × 106 CD34+ cells/kg body weight (retained at the site).
If the quality of the cells is not optimum and affects transduction efficiency, additional round(s) 
of apheresis may be required.  Similarly, if the AVR-RD-02 Drug Product manufactured does 
not meet release criteria for subject infusion, the Sponsor will immediately notify the 
Investigator, and an additional mobilization and apheresis cycle may be considered.   
Details on timing for mobilization and apheresis are outlined in the Schedule of Assessments in 
Table 5, and details on the processes may be found in the Study Treatment Manual and 
Apheresis Operations Manual.
8.1.1.2
Investigational Product Preparation/Testing for Release
Following harvest on Apheresis Day 1, the apheresis unit harvested on that day will be 
transported under temperature-controlled conditions (2°C to 8ºC) to a manufacturing site for 
further processing. The manufacturing for the AVR-RD-02 investigational product is compliant 
with applicable current Good Manufacturing Practice (cGMP).

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AVR-RD-02 will be tested for identity, potency, purity, and safety prior to release for clinical 
use. Once the release testing is complete, AVR-RD-02 investigational product will be 
dispositioned for clinical use and sent to the investigational site in dry shipper with a Certificate 
of Analysis(es), documenting that all release testing specifications for clinical use have been met, 
and that the investigational product can be used in humans. AVR-RD-02 is stable for up to 
12 months when stored in vapor-phase liquid nitrogen. 
8.1.1.3
Conditioning 
After the site receives the investigational product dispositioned for clinical use, the subject will 
enter the Conditioning phase.  
During this phase of the study, subjects will receive a QD, 4-day myeloablative conditioning 
regimen of IV busulfan that is informed by a weight-based test dose of 0.8 mg/kg administered 
on Conditioning Day -6. The test dose will serve to establish the predicted PK for each 
individual subject, as part of the TDM. The test dose of busulfan will be administered on 
Conditioning Day -6 for sites using LC-MS to perform busulfan TDM and on Conditioning 
Day -5 for sites using the immunoassay kit to perform busulfan TDM. 
For Conditioning Days -4, -3, -2, and -1, a dose simulation program will be used to determine the 
busulfan dose required for each subject to achieve the busulfan target AUC, as described in the 
Study Treatment Manual. The myeloablative cumulative target for busulfan exposure in the 
AVRO-RD-02-201 study will be an AUC of 90(day 0-4) ± 2% mg•hr/L.
Once-daily dosing of IV busulfan with TDM will be administered as follows for sites using
LC-MS to perform TDM (also see Table 1):
On Conditioning Days -4 and -3, a PK- and weight-based guided IV busulfan dose, based 
on TDM PK of the test dose on Day -6 and the respective calculated AUC generated from 
the web-based dose simulation program, will be administered.
For Conditioning Day -2, the dose simulation program will be used to determine the 
busulfan dose required for each subject to achieve the busulfan target AUC based on 
TDM PK of the test dose and Day -4. 
For Conditioning Day -1, the dose simulation program will be used to determine the 
busulfan dose required for each subject to achieve the busulfan target AUC based on 
TDM PK of the test dose, Day -4, and Day -3. 
If AUC of the previous dose is outside of the AUCtarget determined by the web-based dose 
simulation program, the busulfan dose will be adjusted accordingly. 
Table 1: 
PK- and Weight-Based Guided Busulfan Conditioning Regimen for Sites 
Using LC-MS to Perform Busulfan TDM
Dosing Day
Busulfan Dose (mg/kg/day)
TDM PK Schedule for Busulfan Dose Determination 
Day -6 
Test dose of 0.8 mg/kg
PK sampling at 1, 3, 5, and 7 hours post dose; TDM PK 
results will be used to inform the dose on Day -4 and 
Day -3 
Day -4 
Dose based on TDM PK of test dose
PK sampling at 1, 3, and 5 hours post dose; TDM PK 
results will be used to inform the dose on Day -2 together 
with TDM PK results from the test dose

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Day -3 
Dose based on TDM PK of test dose
PK sampling at 1, 3, and 5 hours post dose; TDM PK 
results will be used to inform the dose on Day -1 together 
with TDM PK results from the test dose and Day -4
Day -2 
Dose based on TDM PK of test dose 
and Day -4 
PK sampling at 1, 3, and 5 hours post dose; TDM PK 
results will be used to inform the cumulative AUC
Day -1 
Dose based on TDM PK of test 
dose, Day -4, and Day -3 
PK sampling at 1, 3, and 5 hours post dose; TDM PK 
results will be used to inform the cumulative AUC
Abbreviations: AUC = area-under-the curve; LC-MS = liquid chromatography-mass spectrometry; 
PK = pharmacokinetics; TDM = therapeutic drug monitoring.
Once-daily dosing of IV busulfan with TDM will be administered as follows for sites using the 
immunoassay kit to perform TDM (see also Table 2):
On Conditioning Day -4, a PK- and weight-based guided IV busulfan dose, based on 
TDM PK of the test dose on Day -5 and the respective calculated AUC generated from 
the web-based dose simulation program, will be administered.
For Conditioning Day -3, the web-based dose simulation program will be used to 
determine the busulfan dose required for each subject to achieve the busulfan target AUC 
based on TDM PK of the test dose and Day -4. 
For Conditioning Day -2, the web-based dose simulation program will be used to 
determine the busulfan dose required for each subject to achieve the busulfan target AUC 
based on TDM PK of the test dose, Day -4, and Day -3. 
For Conditioning Day -1, the web-based dose simulation program will be used to 
determine the busulfan dose required for each subject to achieve the busulfan target AUC 
based on TDM PK of the test dose, Day -4, Day -3, and Day -2. 
If AUC of the previous dose is outside of the AUCtarget determined by the web-based dose 
simulation program, the busulfan dose will be adjusted accordingly. 
Table 2: 
PK- and Weight-Based Guided Busulfan Conditioning Regimen for Sites 
Using the Immunoassay Kit to Perform Busulfan TDM
Dosing Day
Busulfan Dose (mg/kg/day)
TDM PK Schedule for Busulfan Dose 
Determination 
Day -5 
Test dose of 0.8 mg/kg
PK sampling at 1, 3, 5, and 7 hours post dose; TDM 
PK results will be used to inform the dose on Day -4 
Day -4
Dose based on TDM PK of test dose
PK sampling at 1, 3, and 5 hours post dose; TDM PK 
results will be used to inform the dose on Day -3
together with TDM PK results from the test dose
Day -3
Dose based on TDM PK of test dose 
and Day -4 
PK sampling at 1, 3, and 5 hours post dose; TDM PK 
results will be used to inform the dose on Day -2
together with TDM PK results from the test dose and 
Day -4
Day -2 
Dose based on TDM PK of test 
dose, Day -4, and Day -3 
PK sampling at 1, 3, and 5 hours post dose; TDM PK 
results will be used to inform the dose on Day -1
together with TDM PK results from the test dose, 
Day -4, and Day -3 
Day -1
Dose based on TDM PK of test 
dose, Day -4, Day -3, and Day -2 
PK sampling at 1, 3, and 5 hours post dose; TDM PK 
results will be used to inform the cumulative AUC
Abbreviations: AUC = area-under-the curve; PK = pharmacokinetics; TDM = therapeutic drug monitoring.

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Pharmacokinetic sampling may also be performed on Day -5 to support optimization of busulfan 
exposure. 
Anticonvulsant medication will be administered for seizure prophylaxis in conjunction with 
busulfan administration. Levetiracetam will be administered at a dose of 1,000 mg per day from 
Conditioning Day -8 (ie, 2 days before administration of the busulfan test dose) until 1 day after 
the administration of the 4-day busulfan conditioning regimen. For subjects with contraindication 
to levetiracetam, an alternative anticonvulsant medication (eg, benzodiazepines or valproic acid) 
may be used.
After the 4-day conditioning regimen is administered, a busulfan washout period after the end of 
the last busulfan infusion for a minimum of 24 hours and up to a maximum of 48 hours is 
required prior to AVR-RD-02 administration.  
Timing for the conditioning procedures is outlined in the Schedule of Assessments in Table 5,
with further information included in the Study Treatment Manual.
8.1.2
Gene Therapy Infusion Period (1 Day) 
After completion of the busulfan washout period (ie, a minimum of 24 hours up to a maximum 
of 48 hours after the end of the last busulfan infusion), AVR-RD-02 will be administered once 
by IV infusion. Prior to IV infusion, subject identifiers on AVR-RD-02 investigational product 
must be checked against the intended recipient, and the investigational product must be thawed 
at 37ºC prior to use. Further details on the gene therapy infusion process may be found in the 
Study Treatment Manual. 
8.1.3
Post-gene Therapy Infusion Follow-up Period (Approximately 52 Weeks) 
After AVR-RD-02 infusion, the subject will enter the Post-gene Therapy InfusionFollow-up 
Period, during which time periodic safety and efficacy assessments will be performed to monitor 
safety post-gene therapy infusion, and to assess measures of engraftment and clinical response. 
In particular, safety laboratory assessments will be performed daily for the first 7 days post-gene 
therapy infusion. G-CSF injections will be considered in case a subject’s ANC is < 0.5 × 109/L at 
Day +30 post-gene therapy infusion. G-CSF may be considered earlier if clinically needed in 
consultation with the PI and Sponsor Medical Monitor. 
8.2
Materials and Supplies
AVR-RD-02 
The finished investigational product is presented as a cryopreserved product, which is thawed at 
37°C immediately prior to use. The thawed investigational product is intended for one-time IV 
infusion of between 3 × 106/kg and 10× 106/kg body weight autologous CD34+ enriched HSCs 
that have been genetically modified. 
Upon receipt at the investigational site, cryopreserved investigational product must be 
maintained cryopreserved in infusion bag(s) in vapor-phase liquid nitrogen until ready to thaw 
for clinical use. Thawed investigational product maintained at controlled room temperature in 
cryopreservation media is stable for up to 3 hours. 

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Traceability from the initiation of autologous HSC procurement through the completion of 
AVR-RD-02 gene therapy infusion must be ensured through labeling and documentation control 
at each step. Investigational sites are required to maintain labeling control and documentation to 
support these steps. The exact volume infused, and the time of gene therapy infusion start, and 
completion will be documented in the subject’s electronic case report form (eCRF). 
Any unused AVR-RD-02 investigational product should be disposed of in accordance with local 
biosafety requirements. 
Further details may be found in the Study Treatment Manual. 
Other Study Treatments
For storage requirements, handling, and stability of other study treatments (ie, pre-gene therapy 
infusion injections), see the manufacturers packaging.
8.3
Dosing Considerations 
8.3.1
Rationale for Selection of Dose in the Study
The goal of the gene therapy infusion is to provide as many CD34+ transduced cells as possible. 
Due to variables in individual apheresis results, the actual number of infused transduced cells 
will vary per subject.
The appropriateness of proceeding with myeloablation in any given subject will be based 
on the results of that subject’s corresponding Drug Product release test, including the 
number of cells and cell viability. 
The AVR-RD-02 dose range to be administered (ie, between 3 × 106/kg and 10 × 106/kg 
body weight autologous CD34+ enriched HSCs that have been genetically modified) is 
based upon well-established and accepted safe practices commonly used in autologous 
HSCT and has been shown to safely achieve rapid hematopoietic reconstitution along 
with long-term engraftment. The safety and potential efficacy of dosing using accepted 
autologous HSCT practice is highlighted by the demonstrated safety and benefit of 
autologous HSCT in the treatment of the visceral manifestation of Gaucher disease (Ito 
and Barrett 2013).
The upper dose limit of 10 × 106 CD34+ cells/kg is supported by preclinical safety 
studies that demonstrated tolerability at twice the planned maximum dose. 
There is general consensus that a minimum dose of 2.5 × 106 cells/kg of mobilized 
CD34+ cells is required for favorable engraftment (Jillella and Ustun 2004). However, at 
lower cell counts, recovery of platelet and neutrophil counts may be delayed. Therefore, 
the lowest dose of AVR-RD-02 selected for the study is 3.0 × 106 cells/kg.
Data collected during the course of this trial (eg, Drug Product testing results, cell 
number, cell viability, average VCN per cell, total dose administered along with clinical 
safety, engraftment, % transduction, and efficacy outcomes, etc.) may help inform future 
dosing considerations. 
8.3.2
Other Important Treatment Considerations
As AVR-RD-02 is an autologously-derived product, it is not tested for transmissible infectious 
agents. Healthcare professionals handling AVR-RD-02 should therefore take appropriate 

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precautions per local guidelines to avoid potential transmission of infectious diseases.
Additionally, as this is an autologous drug product pre-medications as mitigation of infusion 
reactions are not required routinely.  
A summary of precautions required and key toxicities associated with G-CSF, plerixafor, 
busulfan, levetiracetam (or other anticonvulsant medication used) can be found in the 
Investigator’s Brochure for AVR-RD-02. Investigators should refer to the most current local 
prescribing information for details regarding precautions required and a complete list of 
toxicities associated with G-CSF, plerixafor, busulfan, levetiracetam (or other anticonvulsant 
medication used). 
Precautions should be taken during apheresis to avoid conditions such as hypotension, electrolyte 
abnormalities, citrate toxicity, thrombocytopenia, and coagulation abnormalities. Stem cell 
infusion can cause tightness in chest, hypotension, coughing, chest pain, decreased urine output, 
weakness, hypersensitivity reactions, electrolyte disturbances, and rarely, engraftment syndrome 
(fever, rash, and non-cardiogenic pulmonary edema). Subjects should be cautioned on these and 
other potential side effects of stem cell infusion.
Complete details regarding study treatments are contained in the Study Treatment Manual.
8.4
Blinding
This is an open-label study. 

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9
STUDY ASSESSMENTS 
Tabular overviews of the required assessments for the study (including the timing of each) can 
be found in Section 15.1. The Schedule of Assessments from Screening through the Apheresis 
Period is in Table 4, the Schedule of Assessments from Investigational Product Preparation and 
Testing through End of Infusion is in Table 5, and the Schedule of Assessments for the 
Post-infusion Follow-up Period (Study Week 1 [Day 1] through Study Week 52 [Day 365]) is in 
Table 6. 
9.1
Safety Assessments
9.1.1
Physical Examinations
A physical examination will be performed at the times specified in Table 4, Table 5, and Table 6.
Each examination will include the following assessments: general appearance; skin; head, ears, 
eyes, nose, mouth, and throat; neck; lymph nodes; chest; heart; abdomen; limbs; central nervous 
system; and musculoskeletal system. 
If CS worsening from Screening are noted for any assessments, the change will be documented 
as an AE in the AE eCRF. Conditions present at the time informed consent is signed and will be 
documented in the Medical History eCRF. Clinical significance is defined as any worsening in 
physical findings that has medical relevance and may result in an alteration in medical care. The 
Investigator will continue to monitor the subject until the parameter returns to baseline or until 
the Investigator determines that follow-up is no longer medically necessary. 
9.1.2
Vital Signs
The following vital signs will be recorded at the times specified in Table 4, Table 5, and Table 6:
heart rate (beats/minute), systolic and diastolic blood pressure (mmHg), respiratory rate 
(breaths/minute), and temperature (°C or °F). Vital signs will be obtained after the subject has 
been supine or seated. On Days 1 and 2 of the Apheresis phase of the Pre-gene Therapy Infusion 
Period, vital signs must be taken prior to apheresis. On Day 0 of the Gene Therapy Infusion 
Period (ie, the day of AVR-RD-02 infusion), vital signs must be taken pre-infusion (window -10 
minutes) and post-infusion (window +10 minutes). Additional vital signs may be taken if 
clinically indicated and/or mandated per local institution practice for gene therapy infusion.  
If CS worsening in vital signs as compared to Screening is noted, the change will be documented 
as an AE in the AE eCRF. Clinical significance is defined as any variation in vital signs that has 
medical relevance and may result in an alteration in medical care. The Investigator will continue 
to monitor the subject until the parameter returns to baseline or until the Investigator determines 
that follow-up is no longer medically necessary. 
9.1.3
Serum Chemistry, Hematology, and Urinalysis 
Serum chemistry, hematology, and urinalysis will be performed at the times specified in Table 4,
Table 5, and Table 6. In particular, safety laboratory assessments will be performed daily for the 
first 7 days post-gene therapy infusion (see Section 8.1.3).
Serum chemistry includes aspartate aminotransferase (AST), alanine aminotransferase (ALT), 
gamma-glutamyl transferase (GGT), amylase, lipase, alkaline phosphatase (ALP), lactate 

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dehydrogenase (LDH), bilirubin, calcium, albumin, phosphate, magnesium, uric acid, and 
glucose. Electrolytes include sodium, potassium, chloride, bicarbonate, blood urea nitrogen 
(BUN), and serum creatinine. Hematology includes hematocrit, hemoglobin, platelet count, 
WBC count (total and differential), RBC count, ANC, and flow cytometric analysis of T and B 
cell counts as well as peripheral blood lymphocyte subsets (CD3, CD4, CD8, CD19, and 
CD16/56). Urinalysis includes blood, glucose, protein, specific gravity, and microscopic 
examination (if clinically indicated).
Laboratory assessments for safety will be tested locally.
It is anticipated that some laboratory values may be outside of the normal value range due to the 
underlying disease or recovery from conditioning. As in routine practice, the Investigators should 
use their medical judgment when assessing clinical significance. Clinical significance is defined 
as any worsening in laboratory measurements which has medical relevance and which results in 
a change in medical care. If any CS laboratory worsening from Baseline is noted, the changes 
will be documented as AEs in the AE eCRF. The Investigator will also assess the relationship to 
study treatment (see Section 9.2.1 for guidance on reporting, recording, and assessing AEs) for 
all CS out of range values. The Investigator will continue to monitor the subject with additional 
laboratory assessments until (1) values have reached normal range and/or baseline, or (2) in the 
judgment of the Investigator, out of range values are not related to the administration of study 
drug or other protocol-specific procedures.
9.1.4
Electrocardiograms
For each subject, 12-lead digital ECGs will be collected at the times specified in Table 4,
Table 5, and Table 6 as single ECGs for over-read. Subjects must be supine for approximately 
5 to 10 minutes before ECG collection and remain supine but awake during ECG collection. 
Electrocardiograms may be obtained at additional times when deemed clinically necessary. 
Collection of more ECGs than expected at a given time point is allowed when needed to ensure 
high quality records.
Electrocardiograms will be interpreted by a qualified physician (the Investigator or qualified 
designee) at the site as soon after the time of ECG collection as possible, and ideally while the 
subject is still present to determine whether the subject meets entry criteria and for immediate 
subject management should any clinically relevant findings be identified. 
9.1.5
Reproductive Potential
For male subjects, sperm samples for volume, sperm count, sperm concentration, total motility, 
progressive motility, and morphology will be collected at the times specified in Table 4, Table 5,
and Table 6 and will be tested locally.
For female subjects, the use of gonadotrophic-releasing hormone agonists (Lupron) for ovarian 
chemoprotection can be offered prior to gonadotoxic therapy such as busulfan. A recall history 
of menstrual cycles for the year preceding enrollment will also be collected at Baseline. Monthly 
menstrual reports will be provided by female subjects for all menstrual cycles beginning at the 
Baseline visit through the end of the study. In addition, a blood sample for AMH, FSH, and LH 
will be collected at the times specified in Table 4, Table 5, and Table 6 and will be tested locally. 

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If test results indicate reduced fertility (eg, oligospermia or azoospermia, decreased sperm 
motility, and/or abnormal sperm morphology in male subjects; abnormal AMH levels in female 
subjects), investigational sites should follow institutional guidelines for further evaluation. For 
both male and female subjects, additional assessments of reproductive potential and/or referral to 
a urologist (male subjects) or a reproductive endocrinologist (female subjects) may be 
recommended.
Reproductive outcomes, if any, will be monitored and recorded during this study. 
9.1.6
Immunogenicity
Blood samples for immunogenicity testing will be collected at the times specified in Table 4,
Table 5, and Table 6 to determine antibody production against GCase. Immunogenicity will be 
assessed by a central laboratory using validated assays designed to detect IgG, IgA, and IgM. 
Blood samples for immunogenicity testing may be obtained at additional times, including when 
an allergic reaction to investigational product is suspected and/or when otherwise deemed 
clinically necessary.
9.1.7
Replication-Competent Lentivirus
Peripheral blood samples for replication-competent lentivirus (RCL) testing will be collected at 
the times specified in Table 4 and Table 6 to detect the emergence of RCL.
Blood samples will be tested centrally. Details on blood sample collection, processing, and 
shipment will be included in the Laboratory Manual. 
9.1.8
Insertional Site Analysis  
For subjects with an average VCN
-positive with an average of 1 copy/diploid 
genome (c/dg), testing for vector ISA will also take place at the times specified in Table 4,
Table 5, and Table 6. 
Blood samples will be tested centrally. Details on blood sample collection, processing, and 
shipment will be included in the Laboratory Manual.
Additional blood sample collection for ISA may also take place at any time, if clinically 
indicated. 
9.1.9
Samples to be Archived for Possible Future Testing
The DNA from peripheral blood and bone marrow aspirate samples will be collected at Baseline, 
as specified in Table 4, and will be archived for possible future testing should a subject develop 
hematologic cancer.  
As knowledge of Type 1 Gaucher disease pathophysiology and related biomarkers continues to 
evolve, back-up plasma and urine samples will be collected and archived for possible future 
non-genomic and genomic biomarker testing either at specialized laboratories or a Biorepository 
site. These samples will be destroyed 5 years after the Clinical Study Report (CSR) is finalized. 

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9.1.10
COVID-19 Guidance: Sign and Symptom Assessment
During the period where there remains transmission risk of coronavirus disease 2019 
(COVID-19), site staff will monitor the subject’s temperature and perform a COVID-19 
symptom assessment prior to study procedures, assessments, and visits per the individual site’s 
guidelines. If there is no institution specific guideline, the site staff will perform a PCR test to 
check for current SARS-CoV-2/COVID-19 infection.  
The COVID-19 test prior to study procedures, including mobilization, apheresis, conditioning 
and AVR-RD-02 gene therapy infusion, will be conducted no later than 5 days prior to the 
planned procedure. 
Most recent updates on COVID-19 infection can be addressed in the latest version of the Public 
Health Surveillance for COVID-19, Interim Guidance (World Health Organization 2020).  
9.2
Safety Monitoring
Investigators are responsible for monitoring the safety of subjects who have entered this study 
and for alerting the Sponsor or its designee to any event that seems unusual, even if this event 
may be considered an unanticipated benefit to the subject. 
The Investigator is responsible for the appropriate medical care of subjects during the study. 
If an SAE that is considered related to a study procedure or the study causes a subject to 
discontinue before completing the study, the Investigator remains responsible for following the 
event through an appropriate health care option. The subject should be followed for 30 days or 
until the event is resolved, whichever is longer. Frequency of follow-up evaluation is left to the 
discretion of the Investigator.
The Sponsor’s medical representative or designee will monitor safety data throughout the course 
of the study. 
The Sponsor’s medical representative or designee will review SAEs within time frames 
mandated by company procedures. The Sponsor’s medical representative or designee will, as 
appropriate, periodically review the following:
Trends in safety data 
Laboratory analytes
AEs, including monitoring of infections and malignancies 
If a subject experiences elevated ALT or AST > 3×the upper limit of the normal range or 
elevated total bilirubin > 2×the upper limit of the normal range, clinical and laboratory 
monitoring should be initiated by the Investigator. Details for hepatic monitoring depend upon 
the severity and persistence of observed laboratory test abnormalities. To ensure subject safety 
and comply with regulatory guidance, the Investigator is to consult with the Sponsor’s medical 
representative or designee regarding collection of specific recommended clinical information and 
follow-up laboratory tests.
9.2.1
Adverse Events
An AE is any untoward medical occurrence in a clinical study subject who has been 
administered a medicinal product and that does not necessarily have a causal relationship with 

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this treatment. An AE can therefore be any unfavorable or unintended sign (for example, an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal product, whether or not considered related to this medicinal product. 
For the purposes of this study, the definition of an AE also covers:  
Medication errors and uses outside of what is foreseen in the protocol, including 
accidental overdose, only if an AE results from the error
Any Grade 3 or higher platelet count, Grade 3 or higher WBC count, and any Grade 2 or 
higher neutrophil count (grade determined by the Common Terminology Criteria for 
Adverse Events [CTCAE] v4.03; see Section 9.2.1.2) regardless of whether considered 
CS by Investigator report 
Fertility-related events, considered an AE of special interest (AESI) for the study 
The following are not considered AEs: 
Situations where an untoward medical occurrence did not occur (eg, planned and/or 
elective admission to a hospital)
Anticipated day-to-day fluctuations of pre-existing disease(s)
Condition(s) present or detected at the start of the study that do not worsen
The Sponsor has standards for reporting AEs that are to be followed regardless of applicable 
regulatory requirements that may be less stringent. 
Lack of drug effect is not an AE in clinical studies because the purpose of the clinical study is to 
establish drug effect.
Cases of pregnancy that occur in female subjects or partners of male subjects during exposure to 
study treatment are to be reported (see Section 9.2.2). Data on fetal outcome and breast-feeding 
are collected for regulatory reporting and drug safety evaluation. 
Study site personnel will record the occurrence and nature of each subject’s pre-existing 
conditions, including CS signs and symptoms of the disease under treatment in the study in 
Medical History eCRF.
After the informed consent form (ICF) is signed, site personnel will record any change in the 
condition(s) and the occurrence and nature of any AEs. Adverse events will be recorded in the 
eCRF according to the study period in which they occurred (ie, Screening, Baseline, Pre-gene 
Therapy Infusion [Mobilization, Apheresis, or Conditioning], Gene Therapy Infusion, or 
Post-gene Therapy Infusion Follow-up). 
9.2.1.1
Exemptions to Adverse Event Recording/Reporting 
For the purposes of this study, the following will not be considered AEs: 
Situations where an untoward medical occurrence did not occur (eg, social and/or 
convenience admission to a hospital, inpatient busulfan conditioning and management, 
etc.), and anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen over the course of the study 
Lack of drug effect (because one of the objectives of this study is to establish the effect of 
AVR-RD-02 treatment)

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9.2.1.2
Severity Assessment
Adverse event severity will be graded using the CTCAE v4.03. The CTCAE is a descriptive 
terminology utilized for AE reporting. A grading (severity) scale is provided for each AE term 
(Each CTCAE v4.03 term is a Medical Dictionary for Regulatory Activities [MedDRA] Lowest 
Level Term). 
Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique 
clinical descriptions of severity for each AE based on this general guideline: 
Grade 1
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.
Grade 2
Moderate; minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living (ADL).a
Grade 3
Severe or medically significant, but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care ADL.b
Grade 4
Life-threatening consequences; urgent intervention indicated.
Grade 5
Death related to AE.
a
Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc.
b
Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, 
and not bedridden. 
Change in severity of an AE should be documented based on specific guidelines in the eCRF 
completion guidelines. 
Severity and seriousness must be differentiated; severity describes the intensity of an AE while 
seriousness refers to an AE that has met the criteria for an SAE (see Section 9.2.1.5).
9.2.1.3
Causality Assessment
Investigators will be instructed to report to the Sponsor or its designee their assessment of the 
potential relatedness of each AE (both serious and non-serious) to protocol procedures and/or 
study treatment. Causality assessments will be provided on the eCRF (and any additional forms 
as appropriate) according to the study period in which it occurred (ie, Screening, Baseline, 
Pre-gene Therapy Infusion [Mobilization, Apheresis, or Conditioning], Gene Therapy Infusion, 
or Post-gene therapy infusion Follow-up). Causality relationship will be classified according to 
the definitions in Table 3.
Table 3: 
Causality Definitions
Definite
Event or laboratory test abnormality with plausible time relationship to drug intake
Cannot be explained by disease or other drugs
Response to withdrawal plausible (pharmacologically, pathologically)
Event definitive pharmacologically or phenomenologically (ie, an objective and 
specific medical disorder or a recognized pharmacological phenomenon)
Rechallenge satisfactory, if necessary

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9.2.1.5
Serious Adverse Events
The SAE collection begins after the subject has signed informed consent. Elective or planned 
procedures and/or hospitalizations that were scheduled or anticipated prior to entry into the study 
should not be reported as SAEs. During the study, elective, anticipated, or planned 
procedures/hospitalizations should not be reported as SAEs unless the underlying medical 
condition has worsened over the course of the study. For SAEs that are due to worsening 
underlying medical conditions, the SAE form should be marked as “due to underlying medical 
condition.” 
Study site personnel must alert the Sponsor or its designee of any SAE within 24 hours of 
Investigator awareness of the event via a Sponsor-approved method. This 24-hour notification 
requirement refers to the initial SAE information.
An SAE is any AE from this study that results in 1 or more of the following outcomes: 
Results in death 
Requires or prolongs hospitalization 
Is life-threatening (that is, immediate risk of dying) 
Persistent or significant disability/incapacity
Congenital anomaly or birth defect 
Other medically important serious event
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered SAEs when, based upon appropriate medical judgment, it may 
jeopardize the subject and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition.
The SAEs occurring up to and including the subject’s last study visit will be collected regardless 
of the Investigator’s opinion of causation. 
If an Investigator becomes aware of SAEs occurring to a subject after the subject’s participation 
in the study has ended (including any protocol-required post-treatment follow-up), the 
Investigator should report the SAEs to the Sponsor regardless of the Investigator’s opinion of 
causation.
Information on SAEs expected in the study population independent of study treatment and that 
will be assessed by the Sponsor in aggregate periodically during the course of the study may be 
found in the Reference Safety Information section of the Investigator’s Brochure.  
9.2.1.6
Suspected Unexpected Serious Adverse Reactions
Suspected unexpected serious adverse reactions (SUSARs) are serious events that are not listed 
in the Investigator’s Brochure and that are identified as related to study treatment. United States 
21 Code of Federal Regulations (CFR) 312.32 and European Union Clinical Trial Directive 
2001/20/EC and the associated detailed guidances or national regulatory requirements in 
participating countries require the reporting of SUSARs. The Sponsor has procedures that will be 
followed for the recording and expedited reporting of SUSARs that are consistent with global 
regulations and the associated detailed guidances.

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9.2.1.7
Reporting Adverse Events 
All non-serious AEs must be recorded in the eCRF upon awareness.  
All SAEs must be reported to the to Sponsor or designee, via the SAE contact in the Safety 
Management Plan, within 24 hours of the Investigator or their staff becoming aware of them. 
The Investigator must complete, sign, and date the SAE pages, verify the accuracy of the 
information recorded on the SAE pages with the corresponding source documents, and send a 
copy via electronic submission to the safety database or e-mail. Facsimile transmission may be 
used in the event of electronic submission or e-mail failure.
When further information becomes available, the SAE Report Form should be updated with the 
new information and reported immediately via the same methods as the initial information. 
Additional follow-up information, if required or available, should be reported to the Sponsor or 
designee within 24 hours of the Investigator or their staff becoming aware of this additional 
information via same manner as above.  
Follow-up information should be recorded on a follow-up SAE Report Form and placed with the 
original SAE information and kept with the appropriate section of the SAE Report Form and/or 
study file.  
These timelines for reporting information to the Sponsor must be followed for all initial SAE 
reports and for all follow-up versions of the initial reports.  
All SAEs (related and unrelated) will be recorded from the signing of informed consent until the 
Week 52 (or Early Termination) Visit. 
For all SAEs the Investigator must provide the following: 
Appropriate and requested follow-up information in the time frame detailed above 
Causality of the SAE(s)
Outcome of the SAE(s)
Redacted medical records and laboratory/diagnostic information
9.2.1.8
Sponsor Reporting Requirements
The Sponsor or its legal representative is responsible for notifying the relevant regulatory 
authorities of SAEs meeting the reporting criteria. This protocol will use the current 
Investigator’s Brochure as the Reference Safety Document. The expectedness and reporting 
criteria of an SAE will be determined by the Sponsor from the Reference Safety Document. 
9.2.1.9
Investigator Reporting Requirements
The Investigator must fulfill all local regulatory obligations required for the study Investigators. 
It is the PI’s responsibility to notify the IRB/IEC of all SAEs that occur at his or her site. 
Investigators will also be notified of all SUSAR events that occur during the clinical study. Each 
site is responsible for notifying its IRB/IEC of these additional SAEs according to local 
requirements.  
9.2.2
Exposure During Pregnancy and/or Lactation
Pregnancy data will be collected during this study for all subjects.  

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Pregnancy is permissible during the study provided that the gestational carrier is not a subject in 
the study and the pregnancy is the result of either: 
a. A fertilization involving the subject’s gametes that occurred before the subject’s 
busulfan exposure, or 
b. A fertilization that involves gametes collected from the subject before busulfan 
exposure, or 
c. A fertilization using donor sperm or egg in lieu of the subject’s gametes. 
Exposure during pregnancy must be recorded and the subject followed until the outcome of the 
pregnancy is known (spontaneous miscarriage, therapeutic abortion, elective termination, normal 
birth, congenital abnormality, or ongoing), even if the subject discontinues from the study. 
If a female subject or a male subject’s partner becomes pregnant while treated or exposed to 
study treatment, the Investigator must submit a pregnancy form to the Sponsor or designee via 
the same method as SAE reporting (see Section 9.2.1.7). When the outcome of the pregnancy 
becomes known (ie, spontaneous miscarriage, elective termination, normal birth, or congenital 
abnormality), the pregnancy form must be completed and returned to the Sponsor or designee. If 
additional follow-up is required, the Investigator will be requested to provide the information.
For any partner pregnancies reported during the study, the pregnancy must be followed until the 
outcome of the pregnancy is known, even if the subject discontinues from the study. 
Pregnancy in itself is not regarded as an AE unless there is a suspicion that study treatment may 
have interfered with the effectiveness of a contraceptive medication. However, complications of 
pregnancy and abnormal outcomes of pregnancy are AEs, and many may meet criteria for an 
SAE (such as ectopic pregnancy, spontaneous abortion, intrauterine fetal demise, neonatal death, 
or congenital anomaly). Elective abortions without complications should not be reported as AEs. 
9.3
Engraftment and Efficacy Measures
9.3.1
Vector Copy Number 
Blood samples for measurement of average VCN in PBLs and bone marrow aspirate by qPCR 
and/or ddPCR analysis will be collected at times shown in Table 4, Table 5, and Table 6.
Samples will be tested at a central laboratory.
9.3.2
GCase Enzyme Activity in Peripheral Blood 
Blood samples for measurement of GCase enzyme activity in peripheral blood will be collected 
at times shown in Table 4, Table 5, and Table 6. Samples will be tested at a central laboratory.
Blood collection on DBS cards for GCase activity measurement will also occur at the indicated 
study time points in mitigation of unforeseen circumstances, which could ruin blood samples 
arriving out of the sample stability period at the central laboratory (Gill 2022; Miyamoto 2021). 
9.3.3
Enzyme Replacement Therapy
Investigators will record the rationale for initiating standard of care ERT as well as gene therapy 
infusion dates and dose. 

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9.3.4
Primary Efficacy Measures
The following primary efficacy measures will be collected at the times shown in Table 4,
Table 5, and Table 6: 
Spleen and liver volumes assessed by abdominal MRI. Scans will be performed locally 
and interpreted by a blinded central reader (local interpretation will be used to determine 
study eligibility). Details will be included in the Imaging (or other relevant) Manual for 
the study. 
Hemoglobin concentration, hematocrit percentage, and platelet count samples collected 
for efficacy measures will be tested at a central laboratory. Details regarding sample 
collection, processing, and shipment will be included in the Laboratory Manual.
Biomarkers for Gaucher disease (ie, chitotriosidase enzyme activity and lyso-Gb1 plasma
levels) will be analyzed in blood samples by a central laboratory. Details regarding 
sample collection, processing, and shipment will be included in the Laboratory Manual.  
9.3.5
Secondary Efficacy Measures
The following secondary efficacy measures will be collected at the times shown in Table 4,
Table 5, and Table 6: 
BMB will be assessed by bone MRI (DeMayo 2008; Maas 2003; Robertson 2007). Scans 
will be performed locally and scored by a blinded central reader. Details will be included 
in the Imaging (or other relevant) Manual for the study. 
BMD assessed by DXA. Scans will be performed and interpreted locally.  
9.3.6
Exploratory Efficacy Measures
The following exploratory efficacy measures will be collected at the times shown in Table 4 and 
Table 6: 
Functional status assessed by the SF-36: The SF-36 is a 36-item, subject-reported 
measure yielding 8 subscale scores (Vitality, Physical Functioning, Bodily Pain, General 
Health Perceptions, Physical Role Functioning, Emotional Role Functioning, Social Role 
Functioning, and Mental Health) and 2 component summary scores (Physical 
Functioning and Mental Functioning).
Pain assessed by the BPI-SF questionnaire: The BPI-SF is a 9-item self-administered 
questionnaire used to evaluate the severity of a subject’s pain and the impact of this pain 
on the subject’s daily functioning on an 11-point scale (ie, 0 = “no pain” to 10 = “pain as 
bad as you can imagine”).
Exploratory biomarkers for Gaucher disease in serum, plasma, PBLs, and urine: As 
knowledge of Gaucher disease pathophysiology and related biomarkers continues to 
evolve, serum, urine, plasma and PBL samples will be collected and archived for possible 
future non-genomic and genomic biomarker testing. Samples will be destroyed 5 years 
after the CSR is finalized.
To assess engraftment dynamics, average VCN will be determined, and ISA performed, 
in whole blood and bone marrow cells at time points specified in Table 4; Table 5; and 
Table 6. Details on whole blood and bone marrow sample collection, processing, and 
shipment will be included in the Laboratory Manual for the study. 

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9.4
Appropriateness of Measurements
Efficacy and safety measures chosen for this study have commonly been used to measure 
treatment effects in studies of Gaucher disease (Barton 1991; Ben Turkia 2013; Elstein 2011;
Elstein 2015; Gonzalez 2013; Grabowski 1995; Kamath 2014; Lukina 2010; Pastores 2016;
Pastores 2004; Rolfs 2013; Zimran 2010; Zimran 2011; Zimran 2013; Zimran 2015; Miyamoto 
2021).

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10
DATA QUALITY ASSURANCE
To ensure accurate, complete, and reliable data, the Sponsor or its representatives will do the 
following: 
Provide instructional material to the study sites, as appropriate 
Provide training to instruct the Investigators and Study Coordinators. This training will 
give instruction on the protocol, the completion of the eCRFs, and the study procedures. 
Conduct monitoring visits at the study site
Be available for consultation and stay in contact with the study site personnel
Review data/data listings on an ongoing basis, and use standard computer edits to detect 
errors in data collection
Conduct a quality review of the database
In addition, the Sponsor or its representatives will periodically check a sample of the subject data 
recorded against source documents at the study site. The study and/or study site may be audited 
by the Sponsor or its representatives and/or regulatory agencies at any time. Investigators will be 
given notice before an audit occurs. 
To ensure the safety of subjects in the study and to ensure accurate, complete, and reliable data, 
the Investigator will keep records of laboratory tests, clinical notes, and subject medical records 
in the subject files as original source documents for the study. If requested, the Investigator will 
provide the Sponsor, applicable regulatory agencies, and applicable IRBs/IECs with direct access 
to original source documents. 
10.1
Data Collection and Storage 
All clinical raw data will be recorded promptly, accurately, and legibly either directly into a data 
capture system as e-source data or indelibly on paper (eg, ECG readings). A detailed list of the 
type (electronic or paper) and location for all source data will be included in the Trial Master 
File. When recorded electronically, CRFs will be electronically generated. All raw data will be 
preserved in order to maintain data integrity. The Investigator or designee will assume the 
responsibility of ensuring the completeness, accuracy, and timeliness of the clinical data.
At each scheduled monitoring visit, the Investigator or designee will cooperate with the 
Sponsor’s representative(s) for the periodic review of study documents to ensure the accuracy 
and completeness of data capture.
The Investigator or designee will prepare and maintain adequate and accurate study documents 
(medical records, ECGs, AE and concomitant medication reporting, and raw data collection 
forms) designed to record all observations and other pertinent data for each subject. 
The Investigator will allow Sponsor representatives, contract designees, authorized regulatory 
authority inspectors, and the IRB/IEC to have direct access to all documents pertaining to the 
study. 

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11
STATISTICAL METHODS AND PLANNED ANALYSES
11.1
General Considerations
This first-in-human study is designed to assess both safety and early efficacy in a limited number 
of switch-stable subjects and treatment-naïve subjects. This is not a pivotal study. The results of 
this Phase 1/2 study will help inform the appropriateness and design of future clinical studies that 
evaluate AVR-RD-02. 
In this open-label study, after AVR-RD-02 gene therapy infusion, measure of engraftment, 
clinical response, and safety are analyzed for each individual subject on an ongoing basis. 
Considering this, a discrete interim analysis of data collected in this study will not be performed. 
Final analysis for the study will be performed after all enrolled subjects complete the Week 52 
assessments (or prematurely discontinue the study). Prior to the analysis of the study data, a 
detailed statistical analysis plan (SAP) will be written describing all analyses to be performed. 
The SAP may contain modifications to the analysis plan described below and will supersede the 
statistical sections of this protocol. Any changes to the statistical plans will be described and 
justified in the CSR. 
The study aims to assess the safety and tolerability of AVR-RD-02 as well as to explore the 
possibility of any indications of an efficacy response signal. As such, all continuous safety, 
tolerability, and efficacy endpoints will be summarized descriptively at each protocol-scheduled 
time point and as change from Baseline. Continuous data will be summarized using descriptive 
summary statistics (number of non-missing observations, mean, standard deviation, median, 
minimum, and maximum). Categorical data will be summarized as frequency counts and 
percentages at each protocol-scheduled time point. 
For all safety endpoints, baseline will be defined as the last available, non-missing observation 
prior to first study treatment administration unless specifically mentioned otherwise. For all 
efficacy endpoints, baseline will be defined as the last available, non-missing observation prior 
to AVR-RD-02 administration. In general, Unknown, Not Done, Not Applicable, and other 
classifications of missing data will not be considered when calculating baseline observations. 
However, valid categorical observations will be considered for baseline calculations. In addition, 
non-missing results from unscheduled assessments prior to first study drug administration may 
also be considered in the calculation of baseline observations.
Only data from nominal protocol-scheduled visits will be included in summary tables. Data from 
unscheduled visits will be included in listings. 
No formal hypothesis tests or statistical models are planned.
11.2
Determination of Sample Size
The sample size of approximately 8 to 16 subjects chosen for this study was selected without 
statistical considerations but was determined based on prior Phase 1/2 study designs in Gaucher 
disease (Barton 1991; Zimran 2010). Because this study is designed to minimize risk, the study 
size may be adjusted based on safety and/or efficacy assessments performed during the course of 
the study and/or recommendations of the independent DMC and/or regulatory agencies. 

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11.3
Analysis Sets
Subject inclusion into each population defined below will be determined. 
Intent-to-Treat (ITT) Population: All enrolled subjects who initiate any study procedures, 
beginning with mobilization by G-CSF and plerixafor. This is the primary safety and efficacy 
population. 
Treatment Population (TP): All enrolled subjects who receive AVR-RD-XX gene therapy 
infusion.  
Per Protocol Population: All enrolled subjects who complete the study without major (ie, 
important) protocol deviations.
11.4
Demographics and Baseline Characteristics
Demographic (age, race, ethnicity, height, weight, and BMI) and baseline data, including disease 
history and characteristics will be summarized. Medical and surgical history will be coded using 
the most current MedDRA and summarized by System Organ Class and Preferred Term. All 
other data recorded at the Screening assessment will be listed only.
11.5
Subject Disposition
The total number of subjects enrolled and treated in each analysis population will be 
summarized. The number of subjects discontinuing the study early, along with the reason for 
early study discontinuation, will also be summarized. 
11.6
Concomitant Medications and Non-Pharmacologic Therapies and Procedures 
Medications used in this study will be coded by using the most current World Health 
Organization (WHO) Drug Dictionary Enhanced.  
The start dates of medications will be used to assign medications into the following categories: 
Prior medication: any medication that started before initial dosing of study treatment 
regardless of when it ended
Concomitant medication: medication continued or newly received at or after initial 
dosing of study treatment  
Medications will be classified as a prior medication and/or a concomitant medication. If a 
medication has a missing or partial missing start/end date or time and it cannot be determined 
whether it was taken before initial treatment or concomitantly, it will be considered as prior and 
concomitant. Prior and concomitant medications will be summarized by Anatomical Therapeutic 
Chemical (ATC) classification and drug preferred term; the summary tables will show the 
number and percentage of subjects taking each medication by ATC classification and preferred
term. Subjects who take the same medication (in terms of the ATC classification and preferred 
term) more than once will be counted only once for that medication. 
Prior medication and concomitant medication will be listed and summarized separately.

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11.6.1
Prophylaxis 
Medications routinely administered as prophylaxis against infectious disease should be 
administered per institutional guidelines. 
11.6.2
Re-Vaccination 
Re-vaccination schedule after AVR-RD-02 gene therapy infusion will occur upon at least the 
partial reconstitution of the subject’s adaptive immunity after busulfan myeloablative 
conditioning regimen. Investigational sites therefore are encouraged to follow their current 
internal bone marrow transplantation re-vaccination guidelines in alignment with the study 
Investigator and the Transplant Physician.  
11.7
Treatment Compliance 
All study treatment administration data will be listed. As all study treatment will be administered 
at the investigational site, treatment compliance will not be determined for this study.
11.8
Safety Analyses  
All safety analyses will be conducted on the Safety Population.
11.8.1
Physical Examination and Vital Signs
All individual vital signs results will be presented in data listings. Observed vital signs parameter 
values and changes from Baseline will be summarized at each protocol-scheduled time point. 
Physical examination data will be listed only. 
11.8.2
Clinical Laboratory Tests
All individual clinical laboratory results will be presented in data listings. Values outside the 
laboratory reference range will be flagged (low-L, high-H).
Observed values and changes from Baseline in clinical laboratory data will be summarized at 
each protocol-scheduled time point. Frequency tabulations of the number of normal and 
abnormal (low and high) records, as well as the number of CS and not clinically significant 
(NCS) records, will also be summarized at each protocol-scheduled time point. Urinalysis results 
will be summarized at each protocol-scheduled time point using frequency tabulations, and any 
available microscopic urinalysis results will be listed. 
In addition, shift tables will be produced per CTCAE grading. 
11.8.3
Adverse Events
Adverse events will be coded using MedDRA. Adverse events will be grouped by System Organ 
Class and Preferred Term and summarized. The summary tables will present the frequency and 
percentage of total subjects by System Organ Class and Preferred Term.
For the summaries of AEs, subjects who experience the same AE (in terms of the MedDRA 
Preferred Term) more than once will be counted only once for that event in the number of 
subjects; however, all occurrences of the same event will be counted in the number of events.

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Adverse event summaries will be restricted to treatment-emergent AEs (TEAEs) only. 
Treatment-emergent adverse events are defined as AEs that commence on or after the time of 
first study treatment administration. AEs without an onset date or time will be defined as TEAEs 
except where an incomplete date (eg, month and year) clearly indicates that the event started 
prior to start of first study treatment administration or if the AE stop date indicates that the event 
started and/or stopped prior to start of first study treatment administration. 
Incidence of TEAEs as well as duration, severity, relationship to study treatment, outcome, and 
actions taken will be listed for each subject. In addition, listings of TEAEs leading to 
discontinuation of the study, SAEs, and deaths will be provided if applicable. 
The following TEAE summaries will be provided: 
Overall summary of TEAEs:
Any TEAE
Any severe / 
CTCAE Grade 3 TEAE
Any TEAE considered as related to any study treatment (assessed by the Investigator 
as being possibly related, probably related, or definitely related) 
Any TEAE leading to discontinuation from the study 
Any serious TEAE
Any life-threatening TEAE 
Any TEAE leading to death 
TEAEs overall and by System Organ Class and Preferred Term
TEAEs related to any study treatment overall and by System Organ Class and Preferred 
Term (a TEAE related to study treatment is defined as any TEAE assessed by the 
Investigator as being possibly related, probably related, or definitely related to any study 
treatment)
TEAEs by severity/CTCAE Grade overall and by System Organ Class and Preferred 
Term
TEAEs leading to study discontinuation overall and by System Organ Class and Preferred 
Term
Serious TEAEs overall and by System Organ Class and Preferred Term
TEAEs of interest (related TEAEs, infections, infertility, and malignancies)
Treatment-emergent adverse events will be presented by decreasing frequency across all 
subjects, broken out by switch-stable and treatment-naïve study arms. 
11.8.4
Reproductive Potential
Reproductive potential for male subjects will be evaluated based on sperm count, volume, sperm 
concentration, total motility, progressive motility, and morphology. Reproductive potential for 
female subjects will be evaluated based on changes in menstrual history and ovarian reserve 
(based on AMH, FSH, and LH levels). 
All individual results will be presented in data listings. Values outside the laboratory reference 
range will be flagged (low-L, high-H).

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Observed values and changes from Baseline in reproductive endpoints will be summarized at 
each protocol-scheduled time point. Frequency tabulations of the number of normal and 
abnormal (low and high) records, as well as the number of CS and NCS records, will also be 
summarized at each protocol-scheduled time point.  
Pregnancy outcomes, if any, will be monitored and recorded during this study. 
11.8.5
Other Safety Assessments
All individual ECG parameter results and the clinical assessment of the ECG will be presented in 
data listings. Observed ECG parameter values and changes from Baseline will be summarized at 
each protocol-scheduled time point. Clinical assessment of the ECG (Normal, Abnormal NCS, 
Abnormal CS) will be summarized using frequency tabulations. 
The anti-GCase antibody data will also be summarized. All other safety data will be listed only. 
11.9
Analysis of Immunogenicity
Immunogenicity testing will be conducted in enrolled subjects at Baseline and Weeks 5, 13, 26, 
39, and 52. Change from Baseline in anti-GCase antibody isotypes and titers will be 
summarized.
11.10 Analysis of Engraftment
All engraftment analyses will be conducted on the Engraftment Population. Measurement of
average VCN in peripheral blood at Baseline and Weeks 13, 26, 39, and 52, and bone marrow 
aspirates at Baseline and Weeks 26 and 52, will be summarized. Changes from Baseline will also 
be summarized.
11.11 Analysis of Enzyme Activity
All GCase enzyme activity analyses will be conducted on the Enzyme Activity Population. 
Observed values and changes from Baseline in anti-GCase enzyme activity level at Weeks 13, 
26, 39, and 52 will be summarized. 
11.12 Analysis of Standard of Care ERT 
The analyses for standard of care ERT will be conducted on the Enzyme Activity Population. 
The rationale, frequency, and dose of ERT between Weeks 26 through 52, inclusive, will be 
summarized. Changes from Baseline will also be summarized. 
11.13 Efficacy Analyses 
All efficacy analyses will be conducted on the Efficacy Population. All raw and derived efficacy 
data will be listed.
11.13.1
Secondary Efficacy Analysis  
For categorical endpoints, the number and percentage of subjects will be summarized using 
frequency tabulations. For continuous endpoints, observed values and changes from Baseline 
will be summarized at each protocol-scheduled time point.  

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11.13.2
Exploratory Efficacy Analyses
For categorical endpoints, the number and percentage of subjects will be summarized using 
frequency tabulations. For continuous endpoints, observed values and changes from Baseline 
will be summarized at each protocol-scheduled time point.  
For questionnaire data, the appropriate scores will be calculated, and data will be summarized 
overall and for each domain where relevant. 
11.14 Subgroup Analyses 
Subgroups will be defined in the SAP for this study. 
11.15 Missing or Invalid Data 
For subjects who are withdrawn from the study prior to study completion, all data compiled up to 
the point of discontinuation will be used for analysis. All withdrawals will be included in all 
analyses up to the time of withdrawal. Any imputations for missing data will be detailed in the 
SAP.

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12
DATA COLLECTION AND QUALITY CONTROL
Data collection is the responsibility of the staff at the study site under the supervision of the 
Investigator. Permission must be secured to obtain retrospective and prospective data 
corresponding to endpoints/data collected in this trial from the medical charts of the subjects. 
The designated study site staff will enter the data required by the protocol into the eCRFs. The 
eCRF is the primary data collection instrument for the study. The eCRFs have been built using a 
fully validated, secure, web-enabled software that conforms to CFR Title 21 Part 11 
requirements. The Investigator should ensure the accuracy, completeness, legibility, and 
timeliness of the data reported in the eCRFs and all other required reports. Data reported on the 
eCRF that are derived from source documents should be consistent with the source documents, 
or the discrepancies should be explained. All data requested on the eCRF must be recorded. Any 
missing data must be explained. For eCRFs, an audit trail will be maintained by the system to 
capture data changes. Study site staff will not be given access to the electronic data capture 
system until they have been trained. Automatic validation programs check for data discrepancies 
in the eCRFs and allow modification or verification of the entered data by the study site staff. 
The Investigator is responsible for assuring that the data recorded on eCRFs are complete, 
accurate, and that the entry and updates are performed in a timely manner.
12.1
Database Management and Data Quality Control 
The Sponsor’s medical representative or designee will review the data entered by the 
investigational staff for completeness and accuracy. Electronic data queries stating the nature of 
the problem and requesting clarification will be created for discrepancies and missing values by 
generating appropriate error messages. In addition, the outsourced vendor data management staff 
will review the data using validation programs and database listings and will enter electronic data 
queries for discrepancies allowing modification or verification of the entered data by the 
designated study staff. 
12.2
Data Monitoring Committee 
An independent DMC will be established for the study. The DMC will consist of clinical study 
experts in stem cell transplantation, gene therapy, and Gaucher disease independent of the study. 
The DMC will monitor the safety aspects of the trial, including review of all SAEs and data, 
after subjects complete the Week 5 (Day 30) follow-up visit. The proposed DMC schedule as 
subjects are enrolled in the study is shown in Table 7. Additional meetings may be scheduled as 
necessary. 
The specific responsibilities of the DMC are described in the DMC Charter, which is maintained 
as a separate document. 
12.3
Subject Confidentiality and Data Privacy
In order to maintain subject confidentiality, each subject will be assigned a unique subject 
identifier. This subject identifier will be used in place of the subject’s name and initials for the 
purpose of data analysis and reporting. Medical record number or other local reference identifiers 
will not be collected as part of the study database. The subject’s date of birth will be requested; 

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however, only the subject’s birth year will be collected in the study database to document age 
eligibility requirements.
All parties will ensure protection of subject personal data and will not include subject names or 
initials on any study forms, reports, publications, or in any other documents, except where 
required by law. An exception to this will be any identifying information required by the site and 
the manufacturer for purposes of traceability of apheresed stem cells throughout the extraction, 
transportation, manufacturing and re-delivery process to ensure that the correct stem cells are 
administered to the study subject.  
In accordance with local regulations in each of the study countries, subjects will be informed 
about data handling procedures (including, as applicable, the lawful basis for the processing of 
data) and asked for their consent. All parties will conduct the study in accordance with applicable 
laws and regulations governing privacy and data protection, such as the Health Insurance 
Portability and Accountability Act of 1996, the General Data Protection Regulation, and the 
United Kingdom Data Protection Act of 2018. Data protection and privacy regulations will be 
observed in capturing, forwarding, processing, and storing subject data. Every effort will be 
made to protect subject confidentiality in accordance with local regulations. 
12.4
Study Record Retention
Study documentation includes, but is not limited to, all eCRFs, data correction forms or queries, 
images, laboratory reports, source documents, monitoring logs/letters, training records, 
curriculum vitaes, and regulatory documents (eg, protocol and amendments, IRB/IEC 
correspondence and approval, and signed participant consent/permission/assent forms).  
Government agency regulations and directives require that the study Investigator must retain all 
study documentation pertaining to the conduct of a clinical study. It is expected that all study 
documentation will be retained for 2 years following the last anticipated regulatory approval or 
up to 25 years from study completion, whichever is longer. However, the length of storage of 
study documentation varies by country and stage of clinical development in any region in the 
world. Therefore, no study documentation will be destroyed or moved to a new location without 
prior written approval from the Sponsor. If offsite archiving is used, all records must be readily 
retrievable and made available for review at the time of an audit or regulatory authority 
inspection.  

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13
ADMINISTRATIVE, ETHICAL, AND REGULATORY 
CONSIDERATIONS
13.1
Informed Consent
The Investigator is responsible for ensuring that the subject understands the potential risks, 
benefits, limitations, and alternatives to participating in the study, including answering any 
questions the subject may have throughout the study and sharing in a timely manner any new 
information that may be relevant to the subject’s willingness to continue his or her participation 
in the study. 
The ICF will be used to explain the potential risks and benefits of study participation to the 
subject in simple terms before the subject is entered into the study, and to document that the 
subject is satisfied with his or her understanding of the risks, benefits, limitations, and 
alternatives to participating in the study and desires to participate in the study. 
The Investigator is responsible for ensuring that informed consent is given by each subject or 
legal representative. This includes obtaining the appropriate signatures and dates on the ICF prior 
to the performance of any protocol procedures and prior to the administration of investigational 
product. 
As used in this protocol, the term “informed consent” includes all consent given by subjects or 
their legal representatives.
13.2
Ethical Conduct of the Study
The Sponsor or its representatives must approve all ICFs before they are used at investigative 
site(s). All ICFs must be compliant with the International Council for Harmonisation (ICH) 
guideline on GCP.  
Documentation of IRB/IEC approval of the protocol and the ICF must be provided to the 
Sponsor before the study may begin at the investigative site(s). The IRBs/IECs will review the 
protocol as required. 
13.3
Regulatory Considerations
This study will be conducted in accordance with: 
1. US CFR
2. The ICH GCP Guideline (E6 [R2])
3. Declaration of Helsinki (“Recommendations Guiding Physicians in Biomedical Research 
Involving Human Patients”) and all its accepted amendments to date concerning medical 
research in humans
4. Consensus ethics principles derived from international ethics guidelines, including the 
Council for International Organizations of Medical Sciences (CIOMS) International 
Ethical Guidelines
5. Applicable laws and regulations 

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13.3.1
Investigator Information
One PI will oversee the trial at each investigative site. The PI undertakes to perform the study in 
accordance with this clinical study protocol, the ICH GCP guidelines, and the applicable national 
regulations and local IRB/IEC requirements.
The PI may appoint other individuals as he/she deems appropriate to assist in the conduct of the 
study. All appointed designees will be listed in the site delegation log. The appointed designates 
will perform their duties in accordance with ICH GCP guidelines and will be supervised by and 
under the responsibility of the PI. 
13.3.2
Protocol Signatures 
The Sponsor’s medical representative or designee will approve the protocol, confirming that, to 
the best of his or her knowledge, the protocol accurately describes the planned design and 
conduct of the study.  
After reading the protocol, each PI will sign the protocol signature page and send a copy of the 
signed page to a Sponsor representative. 
13.3.3
Final Report Signature
The CSR-coordinating Investigator will sign the final CSR for this study, indicating agreement 
that, to the best of his or her knowledge, the report accurately describes the conduct and results 
of the study. 
The Sponsor’s medical representative or designee and statistician will approve the final CSR for 
this study, confirming that, to the best of his or her knowledge, the report accurately describes 
the conduct and results of the study. 
13.4
Publication Policy
The full terms for publication are included in the clinical study agreement between the Sponsor 
and the Investigator. 

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14
LIST OF REFERENCES
Akiyama 2018 
Akiyama K, Kume T, Fukaya M, Shiki I, Enami T, Tatara R, et al. Comparison of levetiracetam 
with phenytoin for the prevention of intravenous busulfan-induced seizures in hematopoietic cell 
transplantation recipients. Cancer Chemother Pharmacol. 2018;82(4):717-21. 
Baiamonte 2015
Baiamonte E, Barone R, Di Stefano R, Lo Iacono M, Spina B, Contino F, et al. Hematopoietic 
Stem Cell Mobilization for Gene Therapy: The Combination of G-CSF+Plerixafor in Patients 
with Beta-Thalassemia Major Provides High Yields of CD34+ Cells with Primitive Signatures. 
Blood. 2015;126(23):4412. 
Bartelink 2016 
Bartelink IH, Lalmohamed A, van Reij EM, Dvorak CC, Savic RM, Zwaveling J, et al. 
Association of busulfan exposure with survival and toxicity after haemopoietic cell 
transplantation in children and young adults: a multicentre, retrospective cohort analysis. Lancet 
Haematol. 2016;3(11):e526-e536. 
Bartelink 2012 
Bartelink IH, van Kesteren C, Boelens JJ, Egberts TC, Bierings MB, Cuvelier GD, et al. 
Predictive performance of a busulfan pharmacokinetic model in children and young adults. Ther 
Drug Monit. 2012;34(5):574-83. 
Barton 1991 
Barton NW, Brady RO, Dambrosia JM, Di Bisceglie AM, Doppelt SH, Hill SC, et al. 
Replacement therapy for inherited enzyme deficiency--macrophage-targeted glucocerebrosidase 
for Gaucher's disease. N Engl J Med. 1991;324(21):1464-70. 
Becker-Cohen 2022
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Ben Turkia 2013 
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alfa enzyme replacement therapy compared with imiglucerase in patients with Gaucher disease. 
Am J Hematol. 2013;88(3):179-84. 
Bennett 2018 
Bennett L and Fellner C. Pharmacotherapy of Gaucher Disease: current and future options. P&T.
2018;43:274-309. 

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Biffi 2016 
Biffi A. Gene therapy for lysosomal storage disorders: a good start. Hum Mol Genet.
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Busulfan PI
Busulfan. Prescribing Information: Available at: 
https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=busulfan.
Busulfan Product Monograph
Busulfan. Product Monograph: BC Cancer Drug Manual; 2018 http://www.bccancer.bc.ca/drug-
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Busulfan SmPC
Busulfan. SmPC: Accord Healthcare Limited, North Harrow, Middlesex, UK; 2018 
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CERDELGA PI
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CEREZYME PI
Cerezyme. Prescribing Information: Sanofi Genzyme. Available at: 
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prospective, open-label non-inferiority study. Orphanet J Rare Dis. 2012;7:102. 

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Cox 2015 
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ELELYSO PI
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Faraci M, Diesch T, Labopin M, Dalissier A, Lankaster A, Gennery A, et al. Gonadal function 
after busulfan compared with treosulfan in children and adolescents undergoing allogeneic 
hematopoietic stem cell transplant. Biol Blood Marrow Transplant. 2019; 25: 1786 – 91. 

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EMA 2009 
EMA. Guideline on Follow-up of Patients Administered with Gene Therapy Medicinal Products. 
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FDA 2020a 
FDA. Guidance for Industry: Long Term Follow-Up After Administration of Human Gene 
Therapy Products. 2020a. https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/long-term-follow-after-administration-human-gene-therapy-products. 
FDA 2020b 
FDA. Guidance for Industry: Testing of Retroviral Vector-Based Human Gene Therapy Products 
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Fumagalli 2022 
Fumagalli, F, Calbi V, Sora M, Baldoli C, Rancolta P, Ciotti F, et al. Lentiviral haematopoietic 
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Gary 2018 
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Goker 2015 
Goker H, Etgul S, and Buyukasik Y. Optimizing mobilization strategies in difficult-to-mobilize 
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Gonzalez 2013 
Gonzalez DE, Turkia HB, Lukina EA, Kisinovsky I, Dridi MF, Elstein D, et al. Enzyme 
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Grabowski 2015 
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Hsieh 2020 
Hsieh MM, Bonner M, Pierciey FJ, Uchida N, Rottman J, Demopoulos L, et al. Myelodysplastic 
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Ito and Barrett 2013 
Ito S and Barrett AJ. Gauchers disease—A Reappraisal of Hematopoietic Stem Cell 
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Jillella and Ustun 2004 
Jillella AP and Ustun C. What is the optimum number of CD34+ peripheral blood stem cells for 
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Kamath 2014 
Kamath RS, Lukina E, Watman N, Dragosky M, Pastores GM, Arreguin EA, et al. Skeletal 
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Kohn 2020 
Kohn DB, Booth C, Kang EM, Pai SY, Shaw KL, Santilli G, et al. Lentiviral gene therapy for 
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Long-Boyle 2015 
Long-Boyle JR, Savic R, Yan S, Bartelink I, Musick L, French D, et al. Population 
pharmacokinetics of busulfan in pediatric and young adult patients undergoing hematopoietic 
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into routine clinical use. Ther Drug Monit. 2015;37(2):236-45.

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Lukina 2010
Lukina E, Watman N, Arreguin EA, Banikazemi M, Dragosky M, Iastrebner M, et al. A phase 2 
study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher 
disease type 1. Blood. 2010;116(6):893-9. 
Maas 2003 
Maas M, van Kuijk C, Stoker J, Hollak CE, Akkerman EM, Aerts JF, et al. Quantification of 
bone involvement in Gaucher disease: MR imaging bone marrow burden score as an alternative 
to Dixon quantitative chemical shift MR imaging--initial experience. Radiology.
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Mamcarz 2019 
Mamcarz E, Zhou S, Lockey T, Abdelsamed H, Cross S, Kang G, et al. Lentiviral Gene Therapy 
Combined with Low-Dose Busulfan in Infants with SCID-X1. N Engl J Med. 2019;380:1525-34.
Mistry 2015 
Mistry PK, Lukina E, Ben Turkia H, Amato D, Baris H, Dasouki M, et al. Effect of oral 
eliglustat on splenomegaly in patients with Gaucher disease type 1: the ENGAGE randomized 
clinical trial. JAMA. 2015;313(7):695-706. 
Miyamoto 2021
Miyamoto T, Iino M, Komorizome Y, Kiguchi T, Furukawa M, Otsuka M, et al. Screening for 
Gaucher Disease using dried blood spots tests: A Japanese multicenter, cross-sectional survey. 
Intern. Med. 2021;60:699-707. 
Mozobil PI
Mozobil. Prescribing Information: Sanofi. Available at: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022311s001lbl.pdf. Accessed 
13 May 2022. 
Pastores and Hughes 2020 
Pastores GM, and Hughes DA. Gaucher Disease. In: Adam MP, Ardinger HH, Pagon RA, et al., 
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2019. URL: https://www.ncbi.nlm.nih.gov/books/NBK1269/.
Pastores 2016 
Pastores GM, Turkia HB, Gonzalez DE, Ida H, Tantawy AA, Qin Y, et al. Development of anti-
velaglucerase alfa antibodies in clinical trial-treated patients with Gaucher disease. Blood Cells 
Mol Dis. 2016;59:37-43.

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Pastores 2014 
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2014;16(5):359-66. 
Pastores 2004 
Pastores GM, Weinreb NJ, Aerts H, Andria G, Cox TM, Giralt M, et al. Therapeutic goals in the 
treatment of Gaucher disease. Semin Hematol. 2004;41(4 Suppl 5):4-14. 
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Robertson PL, Maas M, and Goldblatt J. Semiquantitative assessment of skeletal response to 
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VPRIV PI
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Weil E, Zook F, Oxencis C, Canadeo A, Urmanski A, Waggoner M, et al. Evaluation of the 
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Hematopoietic stem cell mobilization for gene therapy: superior mobilization by the combination 
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Hum Gene Ther. 2013;24(10):852-60. 
ZAVESCA PI
ZAVESCA. Prescribing Information: Actelion Pharmaceuticals US, Inc. Available at: 
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=817892d1-ee12-4632-85fc-
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Zimran 2011 
Zimran A, Brill-Almon E, Chertkoff R, Petakov M, Blanco-Favela F, Munoz ET, et al. Pivotal 
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15
APPENDICES

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SRT = substrate reduction therapy; VCN = vector copy number; VDRL = Venereal Disease Research Laboratory; VSV = vesicular stomatitis virus; W = week; 
WBC = white blood cell.
a
Screening assessments must be performed within 60 days prior to the Baseline visit.
b
The Baseline visit may be conducted over the course of up to 7 days.
c
Mobilization is to be initiated the day following the last Baseline assessment.
d
Assessments required for those subjects who prematurely discontinue the study after initiation of the Pre-gene Therapy Infusion Period. Assessments should 
be completed as soon as feasible after the decision to discontinue the study has been made. If logistic or medical constraints result in delays, the assessments 
must be completed within 3 months following the decision to discontinue. After discontinuation, every effort should be made to continue to follow the 
subject for safety monitoring (including any indication[s] of loss of gene therapy effect). 
e
Medical history will include retrospective collection from medical records of Gaucher disease-specific medical and surgical history, including historical 
results of GCase enzyme activity testing and previous use of ERT and SRTs. Copies of medical records will be retained in the source documents.
f
Transmittable disease testing includes serological analysis for HIV Ag/Ab, HIV NAT, HBsAg, anti-HBc, HBV NAT, anti-HCV antibody, HCV NAT, 
syphilis test (VDRL, CMIA, or EIA), CMV IgG Ab, CMV IgM Ab, HTLV-1 Ab, HTLV-2 Ab, HSV-1 IgG Ab, HSV-2 IgG Ab, and, if applicable, VSV IgG 
Ab. If applicable, testing for West Nile virus by PCR must also be performed. To determine if a viral test is applicable to the subject, investigational clinical 
sites should consult the CDC website for up-to-date guidance. Subjects who test positive for HBV, HCV, HIV (Type 1 or 2), HTLV-1, HTLV-2, and/or 
syphilis on VDRL, CMIA, or EIA will be screen failures. Consult the Study Treatment Manual for a list of applicable testing for your region. Similarly, to
determine if a viral test is applicable for the region, investigational clinical sites should consult the CDC website for up-to-date guidance. Testing should be 
completed within 30 days prior to apheresis.
g
Blood sample(s) and bone marrow aspirate will be analyzed by a central laboratory. Additional blood sample and bone marrow aspirate must also be 
collected before initiation and cessation of ERT, when applicable. Additional blood samples will be used for the following tests: GCase enzyme activity, 
biomarkers for Gaucher disease, VCN, ISA, immunogenicity, and RCL. Details on collection, processing, and shipment will be included in the Laboratory 
Manual for the study. 
h
Abdominal and bone MRI scans will be performed locally and will be interpreted by a blinded central reader. The abdominal MRI performed at Screening 
will also be interpreted locally to determine study eligibility. Blinded central reader interpretation will be used for final efficacy analysis. Details on 
collection, processing, and shipment will be included in an Imaging (or other relevant) Manual for the study.
i
Hemoglobin, hematocrit, and platelet assessments collected for efficacy analysis will be tested at a central laboratory. Details on collection, processing, and 
shipment will be included in the Laboratory Manual for the study.
j
Two tubes for GCase in PBLs. 
k
DXA will be performed and interpreted locally. 
l
Samples to be collected and stored for possible future testing. Details on collection, processing, and shipment will be included in the Laboratory Manual for 
the study.
m
The SF-36 and BPI-SF should be completed prior to any other required assessments at the study visit.
n
Vital signs include heart rate, blood pressure, respiratory rate, and temperature. Vital signs will be obtained with the subject supine or seated. On Days 1 and 
2 of the Apheresis phase of the Pre-gene therapy infusion Period, vital signs must be taken prior to apheresis. On Day 0 of the Gene Therapy Infusion Period 
(ie, the day of AVR-RD-02 gene therapy infusion), vital signs must be taken pre-gene therapy infusion (window -10 minutes) and post-gene therapy infusion 
(window +10 minutes). Additional vital signs may be taken if clinically indicated and/or mandated per local institution practice for gene therapy infusion. 
o
CBC with differential performed locally includes the following: hemoglobin, hematocrit, platelet count, WBC count (total and differential), RBC count, and 
ANC count. 
p
Assessment will include routine flow cytometric analysis of T and B cell counts as well as peripheral blood lymphocyte subsets. Panel will include CD3, 
CD4, CD8, CD19, and CD16/56. Performed locally.

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q
Serum chemistry includes AST, ALT, GGT, amylase, lipase, ALP, LDH, bilirubin, calcium, albumin, phosphate, magnesium, uric acid, and glucose. 
Electrolytes include sodium, potassium, chloride, bicarbonate, BUN, and serum creatinine. Performed locally.
r
Urinalysis includes blood, glucose, protein, specific gravity, and microscopic examination (if clinically indicated). Performed locally.
s
Additional blood sample collection for immunogenicity testing, RCL testing, and ISA may also take place at any time, if clinically indicated. 
t
Screening samples are to be collected for treatment-naïve subjects only. All subsequent samples are to be collected from all treatment-naïve and 
switch-stable subjects.
u
Samples will be collected and stored for possible future testing should hematologic cancer develop. Details on collection, processing, and shipment will be 
included in the Laboratory Manual for the study.
v
For measures of reproductive potential in male subjects, sperm samples for sperm count, volume, sperm concentration, total motility, progressive motility, 
and morphology will be collected. Samples should be collected after at least 5 days to 7 days of abstinence. Samples will be tested locally. For samples that 
yield abnormal results, an additional sample must be collected and tested to confirm the initial results. Percutaneous epidydimal sperm aspiration and 
hormonal laboratory assessments (eg, testosterone) will also be offered to male subjects (optional assessments), which will be analyzed locally. If test results 
indicate reduced fertility (eg, oligospermia or azoospermia, decreased sperm motility, and/or abnormal sperm morphology), investigational sites should 
follow institutional guidelines for further evaluation. Additional assessments of reproductive potential and/or referral to a urologist may be recommended. 
Early termination assessments of measures of reproductive potential are not required for male subjects who have had a vasectomy and sterility confirmed at 
the Baseline assessment.
w
Results of the serum pregnancy test to be obtained at Screening (exclusion criterion) and prior to starting mobilization drugs and apheresis procedure (FACT 
Eigth Edition). 
x
For females, monthly menstrual calendar (for all menstrual cycles beginning at the Baseline visit) by subject report will be collected at the specified study 
visits. At Baseline, a recall of menstrual history over the previous 12 months will be collected.
y
Measures of reproductive potential in females include AMH, FSH, and LH for assessment of ovarian reserve, which will be assessed locally. Early 
termination assessments of measures of reproductive potential are not required for female subjects who are confirmed as not of child-bearing potential at 
Baseline assessment. 
z
On Mobilization Days 1 through 4 of the Pre-gene Therapy Infusion Period, a daily G-CSF dose of 10 µg/kg body weight will be administered (for sites with 
only prefilled syringes, a G-CSF daily dose from 10 µg/kg body weight up to 12 µg/kg body weight administered in either a single or divided BID dose may 
be administered). The G-CSF dose may be administered SC or IV.
aa
On the evening of Mobilization Day 4 and on the evening of Apheresis Day 1, plerixafor (0.24 mg/kg) will be administered SC. 
bb
On the morning of Apheresis Day 1 (ie, between 8 hours and 11 hours after the first plerixafor administration on Mobilization Day 4), cells will be harvested 
from the subject’s peripheral blood; this apheresis unit will be shipped to the manufacturing site for cell transduction and processing. On the morning of 
Apheresis Day 2 (ie, between 8 hours and 11 hours after plerixafor administration on Apheresis Day 1), an additional harvest of cells will occur; cells 
harvested from this apheresis (nontransduced cells) will be retained and stored at the investigational site for use as rescue treatment (if needed). Standard 
institutional procedures at the participating investigational study site will be used for both apheresis procedures. If the quality of the cells is not optimum and 
affects transduction efficiency, additional round(s) of apheresis may be required.
cc
Prior and concomitant medications and therapies will be recorded from the time of signing of informed consent until completion of the Week 52 assessments 
for the study. 
dd
All AEs (including SAEs and AEs of interest) will be recorded from the time of signing of informed consent until completion of the Week 52 assessments 
for the study. 
ee
The COVID-19 test prior to study procedures, including mobilization, apheresis, conditioning and AVR-RD-02 gene therapy infusion, will be conducted no 
later than 5 days prior to the planned procedure.

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must be completed within 3 months following the decision to discontinue. After discontinuation, every effort should be made to continue to follow the 
subject for safety monitoring (including any indication[s] of loss of gene therapy effect). 
e
Blood sample(s) will be analyzed by a central laboratory. Details on collection, processing, and shipment will be included in the Laboratory Manual for the 
study. 
f
Hemoglobin, hematocrit, and platelet assessments for the efficacy analysis will be tested at a central laboratory. Details on collection, processing, and 
shipment will be included in the Laboratory Manual for the study.
g
Vital signs include heart rate, blood pressure, respiratory rate, and temperature. Vital signs will be obtained with the subject supine or seated. On Day 0 of 
the Gene Therapy Infusion Period (ie, the day of AVR-RD-02 gene therapy infusion), vital signs must be taken pre-gene therapy infusion (window -10 
minutes) and post-gene therapy infusion (window +10 minutes). Additional vital signs may be taken if clinically indicated and/or mandated per local 
institution practice for gene therapy infusion. 
h
The CBC with differential, performed locally, includes the following: hemoglobin, hematocrit, platelet count, WBC count (total and differential), RBC 
count, and ANC. During the Conditioning washout period, testing should be performed daily. Samples will be tested locally.
i
Assessment will include routine flow cytometric analysis of T and B cell counts as well as peripheral blood lymphocyte subsets. Panel will include: CD3, 
CD4, CD8, CD19, and CD16/56. Performed locally.
j
Serum chemistry includes AST, ALT, GGT, amylase, lipase, ALP, LDH, bilirubin, calcium, albumin, phosphate, magnesium, uric acid, and glucose. 
Electrolytes include sodium, potassium, chloride, bicarbonate, BUN, and serum creatinine. During the Conditioning washout period, testing should be 
performed daily. Samples will be tested locally.
k
Urinalysis includes blood, glucose, protein, specific gravity, and microscopic examination (if clinically indicated). Performed locally.
l
Additional blood sample collection for immunogenicity testing, RCL testing, and ISA may also take place at any time, if clinically indicated. 
m
For measures of reproductive potential in male subjects, sperm samples for sperm count, volume, sperm concentration, total motility, progressive motility, 
and morphology will be collected. Samples should be collected after at least 5 days to 7 days of abstinence. Samples will be tested locally. For samples that 
yield abnormal results, an additional sample must be collected and tested to confirm the initial results. Percutaneous epidydimal sperm aspiration and 
hormonal laboratory assessments (eg. testosterone) will also be offered to male subjects (optional assessments), which will be analyzed locally. If test results 
indicate reduced fertility (eg, oligospermia or azoospermia, decreased sperm motility, and/or abnormal sperm morphology), investigational sites should 
follow institutional guidelines for further evaluation. Additional assessments of reproductive potential and/or referral to a urologist is recommended. Early 
termination assessments of measures of reproductive potential are not required for male subjects who have had a vasectomy and sterility confirmed at the 
Baseline assessment.
n
For female subjects, results of the serum pregnancy test on Conditioning Day -8 must be confirmed negative prior to the administration of the test dose of 
busulfan on Conditioning Day -6.
o
For females, monthly menstrual calendar (for all menstrual cycles beginning at the Baseline visit) by subject report will be collected at the specified study 
visits. 
p
Measures of reproductive potential in females include AMH, FSH, and LH for assessment of ovarian reserve, which will be assessed locally. If test results 
indicate reduced ovarian reserve during the study, investigational sites should follow institutional guidelines for further evaluation of female subjects. 
Additional assessments of reproductive potential and/or referral to an endocrinologist is recommended.
q
Levetiracetam will be administered at a dose of 1,000 mg per day beginning 2 days before administration of the busulfan test dose (ie, on Conditioning 
Day -8) and continuing until 1 day after administration of the 4-day busulfan administration conditioning regimen (ie, until 1 day into the Conditioning 
washout period). For subjects with a contraindication to levetiracetam, an alternative anticonvulsant medication (eg, benzodiazepines or valproic acid) may 
be used. Details on medication administered must be captured in the eCRF.  
r
A conditioning regimen of IV busulfan including a test dose of 0.8 mg/kg on Day -6 will be administered. For sites using LC-MS to perform busulfan TDM, 
the busulfan test dose will be administered on Day -6. The Day -4 and Day -3 busulfan dose will be PK and weight-guided based on the test dose and the 

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respective calculated AUC using a web-based dose simulation program. The busulfan doses for Conditioning Days -2 and -1 will be based on an AUC 
calculation generated from a web-based dose simulation program that uses measurements of busulfan in serial blood samples drawn over several hours (see 
footnote ‘s’) on Conditioning Days -6 (test dose), -4 (for the Day -2 dose), and -3 (for the Day -1 dose). For sites using the investigational automated 
nanoparticle immunoassay kit (Saladax Biomedical, Inc.) to perform busulfan TDM, the busulfan test dose will be administered on Day -5. The Day -4
busulfan dose will be PK- and weight-guided based on the test dose and the respective calculated AUC using a web-based dosing simulation program. The 
busulfan doses for Day -3, Day -2, and Day -1 will be based on an AUC calculation generated from a web-based dose simulation program that will use 
measurements of busulfan in serial blood samples over several hours (see footnote ‘t’) on Conditioning Day -5 (test dose) and all subsequent Conditioning 
days prior to that day’s dose. If the AUCprevious dose is outside of ± 0% of the AUCtarget determined by the program, the busulfan dose will be adjusted 
accordingly. See Section 8.1.1.3 (and the Study Treatment Manual) for further details on busulfan dose determination.
s
Blood samples are to be collected 1, 3, 5, and 7 hours after busulfan test dose administration for busulfan TDM and dose determination (see footnote ‘r’). 
Blood samples will be collected 1, 3, and 5 hours after busulfan dose administration on Days -4, -3, -2, and -1 for busulfan TDM for dose determination (ie, 
Days -4 and -3) and actual cumulative AUC calculations (ie, Days -4, -3, -2 and -1; see also footnote ‘r’). Laboratories performing TDM must use validated 
methods to quantify busulfan in plasma according to GLP. 
t
For sites using LC-MS to perform busulfan TDM, PK sampling may also be performed on Day -5 to support optimization of busulfan exposure. 
u
Prior and concomitant medications and therapies will be recorded from the time of signing of informed consent until completion of the Week 52 assessments 
for the study.
v
All AEs (including SAEs and AEs of special interest) will be recorded from the time of signing of informed consent until completion of the Week 52 
assessments for the study.
w
Additional samples for determination of busulfan exposure may be collected.
x
The COVID-19 test prior to study procedures, including mobilization, apheresis, conditioning and AVR-RD-02 gene therapy infusion, will be conducted no 
later than 5 days prior to the planned procedure.

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b
During the Post-gene Therapy Infusion Follow-up Period, additional assessments may be performed at any time for clinical management or safety concerns 
at the discretion of the Investigator.
c
The Week 52 (End of Study; Day 365) visit may be conducted over the course of up to 3 days.
d
Assessments required for those subjects who prematurely discontinue the study. Assessments should be completed as soon as feasible after the decision to 
discontinue the study has been made. If logistic or medical constraints result in delays, the assessments must be completed within 3 months following the 
decision to discontinue. After discontinuation, every effort should be made to continue to follow the subject for safety monitoring (including any 
indication[s] of loss of gene therapy effect).
e
Blood sample(s) and bone marrow aspirate will be analyzed by a central laboratory. Additional blood sample and bone marrow aspirate must also be 
collected before initiation and cessation of ERT, when applicable. Additional blood samples will be used for the following tests: GCase enzyme activity, 
biomarkers for Gaucher disease, VCN, ISA, when applicable, immunogenicity, and RCL. Details on collection, processing, and shipment will be included in 
the Laboratory Manual for the study. 
f
Abdominal and bone MRI scans will be performed locally and interpreted by a blinded central reader. Details on collection, processing, and shipment will be 
included in an Imaging (or other relevant) Manual for the study.
g
Hemoglobin, hematocrit, and platelet assessments for efficacy analysis will be tested at a central laboratory. Details on collection, processing, and shipment 
will be included in the Laboratory Manual for the study.
h
All subjects whose GCase activity falls 15% of the lower limit of the range observed in healthy individuals at Week 9 (Day 60 / Month 2), Week 13 (Day 90 
/ Month 3), Week 18 (Day 120 / Month 4), and Week 22 (Day 150 / Month 5) (see Section 7.4.6) will be monitored. At Week 13 (Month 3), subjects who 
have not restarted ERT and meet the following clinical parameters: blood GCase activity > 15% and hemoglobin concentration and platelet c
80% of 
the baseline value, will not be required to undergo clinical assessments at Week 18 (Month 4) or Week 22 (Month 5). These subjects will resume their 
clinical assessments with the 6-month post-gene therapy infusion visit.
i
The DXA will be performed and interpreted locally. 
j
Samples to be collected and stored for possible future testing. Details on collection, processing, and shipment will be included in the Laboratory Manual for 
the study.
k
The SF-36 and BPI-SF should be completed prior to any other required assessments at the study visit.
l
At a minimum, physical examinations, vital signs collection, and blood sample collection for CBC with differential and electrolytes must occur daily through 
a minimum of 7 days post-gene therapy infusion (ie, until Day 7 of the Post-gene Therapy Infusion Follow-up Period). If clinically indicated and/or 
mandated per local institution practice post-gene therapy infusion, additional physical examinations, vital signs collection, and blood sample collection for 
CBC with differential and electrolytes should also take place.
m
Vital signs include heart rate, blood pressure, respiratory rate, and temperature, and will be obtained with the subject supine or seated. 
n
CBC with differential performed locally includes the following: hematocrit, hemoglobin, platelet count, WBC count (total and differential), RBC count, and 
ANC count. If ANC is 1.5 × 109/L on Day 5 of the Post-gene Therapy Infusion Follow-up Period, blood sample for ANC should continue to be collected 
(and G-CSF injection administered daily [see footnote ‘o’]) until the subject achieves an ANC > 1.5 × 109/L. During and after completion of daily testing for 
ANC post-gene therapy infusion, blood sample for hemoglobin and platelet count must continue to be collected in accordance with the Schedule of 
Assessments for these clinical laboratories collected for efficacy.
o
A G-CSF injection of 5 µg/kg body weight (for sites with only prefilled syringes, a G-CSF dose from 4 µg/kg body weight up to 6 µg/kg body weight, 
administered in either a single or divided BID dose) will be considered in case a subject’s ANC is < 0.5 × 109/L at Day +30 post-gene therapy infusion and 
onwards. G-CSF may be considered earlier if clinically needed in consultation with the PI and Sponsor Medical Monitor.
p
Assessment will include routine flow cytometric analysis of T and B cell counts as well as peripheral blood lymphocyte subsets. Panel will include: CD3, 
CD4, CD8, CD19, and CD16/56. Performed locally.
q
Serum chemistry includes AST, ALT, GGT, amylase, lipase, ALP, LDH, bilirubin, calcium, albumin, phosphate, magnesium, uric acid, and glucose. 
Electrolytes include sodium, potassium, chloride, bicarbonate, BUN, and serum creatinine. Performed locally.
r
Urinalysis includes blood, glucose, protein, specific gravity, and microscopic examination (if clinically indicated). Performed locally.

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s
Additional blood sample collection for immunogenicity testing, RCL testing, and ISA may also take place at any time, if clinically indicated. 
t
For measures of reproductive potential in male subjects, sperm samples for sperm count, volume, sperm concentration, total motility, progressive motility, 
and morphology will be collected. Samples should be collected after at least 5 days to 7 days of abstinence. Samples will be tested locally. For samples that 
yield abnormal results, an additional sample must be collected and tested to confirm the initial results. Percutaneous epidydimal sperm aspiration and 
hormonal laboratory assessments (eg, testosterone) will also be offered to male subjects (optional assessments), which will be analyzed locally. If test results 
indicate reduced fertility (eg, oligospermia or azoospermia, decreased sperm motility, and/or abnormal sperm morphology), investigational sites should 
follow institutional guidelines for further evaluation. Additional assessments of reproductive potential and/or referral to a urologist may be recommended. 
End-of-treatment/early termination assessments of measures of reproductive potential are not required for male subjects who have had a vasectomy and 
sterility confirmed at the Baseline assessment.
u
For females, monthly menstrual calendar (for all menstrual cycles beginning at the Baseline visit) by subject-report will be collected at the specified study 
visits.
v
Measures of reproductive potential in females include AMH, FSH, and LH for assessment of ovarian reserve, which will be assessed locally. If test results 
indicate reduced ovarian reserve during the study, investigational sites should follow institutional guidelines for further evaluation of female subjects. 
Additional assessments of reproductive potential and/or referral to an endocrinologist is recommended.
w
Prior and concomitant medications and therapies will be recorded from the time of signing of informed consent until completion of the Week 52 assessments 
for the study. 
x
All AEs (including SAEs and AEs of interest) will be recorded from the time of signing of informed consent until completion of the Week 52 assessments 
for the study.
y
Remote visits may be conducted in lieu of clinic visits for the following protocol-scheduled visits: Week 18 (Day 120) and Week 22 (Day 150). The site will 
coordinate the collection of blood samples. If protocol-scheduled clinic visits are no longer possible, the Investigator must consult with the Sponsor Medical 
Monitor to determine the best course of action which could include remote visits.

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15.4
Enrollment (and Data Monitoring Committee Review) Schedule
Table 7: 
Enrollment (and DMC Review) Schedule
Dosing 
Cohorta
No. of 
Subjects
Safety 
Review by 
DMC?b
Safety Data Reviewed by 
DMC
DMC Review Outcome and Study Impact
Switch-stable Subjects
1
1
Yes
Safety data through the 
Week 5 (Day 30) follow-up 
assessments for 1 subject
If review of safety data by the DMC determines that enrollment may proceed, the 
mobilization therapy for a switch-stable subject enrolled in dosing cohort 2 may 
begin. If safety concerns are identified by the DMC, the DMC will provide 
recommendations to AVROBIO. Dosing and enrollment may proceed on the basis 
of these recommendations or following remediation as set forth in the DMC 
Charter. 
2 
1 
Yes
Safety data through the 
Week 5 (Day 30) follow-up 
assessments for the subject in 
safety cohort 2 (all available 
data from the subject enrolled 
in dosing cohort 1 will also be 
provided)
If review of safety data by the DMC determines that enrollment may proceed, the 
mobilization therapy for switch-stable subjects enrolled in dosing in cohort 3 may 
begin without further restriction. 
In addition, mobilization therapy for a treatment-naïve subject enrolled in dosing 
cohort 4 may begin. 
If safety concerns are identified by the DMC, the DMC will provide 
recommendations to AVROBIO. Dosing and enrollment may proceed on the basis 
of these recommendations or following remediation as set forth in the DMC 
Charter.
Treatment-naïve Subjects
4 
1 
Yes
Safety data through the 
Week 5 (Day 30) follow-up 
assessments for 1 subject
If review of safety data by the DMC determines that enrollment may proceed, the 
mobilization therapy for a treatment-naïve subject enrolled in dosing cohort 5 may 
begin. 
If safety concerns are identified by the DMC, the DMC will provide 
recommendations to AVROBIO. Dosing and enrollment may proceed on the basis 
of these recommendations or following remediation as set forth in the DMC 
Charter.

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Dosing 
Cohorta
No. of 
Subjects
Safety 
Review by 
DMC?b
Safety Data Reviewed by 
DMC
DMC Review Outcome and Study Impact
5 
1 
Yes
Safety data through the 
Week 5 (Day 30) follow-up 
assessments for the subject in 
safety cohort 5 (all available 
data from the subject enrolled 
in dosing cohort 4 will also be 
provided)
If review of safety data by the DMC determines that enrollment may proceed, the 
mobilization therapy for treatment-naïve subjects enrolled in dosing in cohort 6 
may begin without further restriction.
If safety concerns are identified by the DMC, the DMC will provide 
recommendations to AVROBIO. Dosing and enrollment may proceed on the basis 
of these recommendations or following remediation as set forth in the DMC 
Charter.
Abbreviation: DMC = Data Monitoring Committee.
a
Enrollment will continue up to the maximum planned enrollment for the study that considers both switch-stable and treatment-naïve subjects.
b
The DMC reviews included are those planned for making continued dosing and study enrollment decisions. Additional DMC reviews may also take place in 
accordance with the protocol and DMC Charter established for the study.