A Platform Study Evaluating the Efficacy and Safety of Investigational Therapies in Participants With Chronic Hepatitis B Infection (PREVAIL)
Phase: PHASE1
Conditions: Hepatitis B, Chronic
Sponsor: Vir Biotechnology, Inc.

Official Title: A Phase 2 Study Evaluating the Efficacy and Safety of VIR-3434 and/or VIR-2218 Containing 
Regimens in Participants with Chronic Hepatitis B Infection (STRIVE) 
NCT Number: NCT05612581
Document Date: 14 December 2023, Version 1.0

PREVAIL PLATFORM CLINICAL STUDY 
SUB-PROTOCOL A (STRIVE) 
PROTOCOL AMENDMENT 3 
This sub-protocol should be read and conducted in conjunction with the 
PREVAIL Master Protocol 
Study Title 
A Phase 2 Study Evaluating the Efficacy and Safety of VIR-3434 and/or 
VIR-2218 Containing Regimens in Participants with Chronic Hepatitis 
B Infection (STRIVE) 
Brief Title 
A Phase 2 Study to Evaluate VIR-3434 and/or VIR-2218 Containing 
Regimens for Treatment of Chronic Hepatitis B Infection 
Master Study Number 
VIR-MHB1-V200 
Sub-Study Number 
VIR-SHB1-V201 
Compounds 
VIR-3434 (tobevibart), VIR-2218 (elebsiran), tenofovir disoproxil 
fumarate (TDF) and pegylated interferon alfa-2a (PEG-IFNα) 
Indication 
Chronic Hepatitis B Infection 
Study Phase 
2 
Study Sponsor 
Vir Biotechnology, Inc. 
1800 Owens Street, Suite 900 
San Francisco, CA 94158, USA 
Regulatory Agency 
Identifying Numbers 
IND: TBD 
EudraCT: 2022-002014-16 (under Master Protocol) 
NCT: 05612581 (under Master Protocol) 
Protocol Date 
14 December 2023, Version 1.0 
This study will be conducted in compliance with International Council for Harmonisation (ICH) Good Clinical 
Practice (GCP), including the archiving of essential documents 
CONFIDENTIALITY STATEMENT  
This document contains confidential information that is the property of Vir Biotechnology, Inc. This confidential 
information is being provided to you, your staff, the applicable Institutional Review Board/Independent Ethics 
Committee, and applicable regulatory authorities solely for the purpose of evaluating or conducting this clinical 
study. This confidential information will be protected by you and your staff against disclosure to or use by third 
parties, except as necessary for the evaluation or conduct of the study. 

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INVESTIGATOR SIGNATURE PAGE 
VIR BIOTECHNOLOGY, INC 
1800 OWENS STREET, SUITE 900 
SAN FRANCISCO, CA 94158 
STUDY ACKNOWLEDGMENT 
A Phase 2 Study Evaluating the Efficacy and Safety of VIR-3434 and/or VIR-2218 
Containing Regimens in Participants with Chronic Hepatitis B Infection (STRIVE) 
This sub-protocol has been approved by Vir Biotechnology, Inc. The following signature 
documents this approval.  
Printed Name 
Signature and Date 
INVESTIGATOR STATEMENT 
I have read the Master Protocol, current sub-protocol, including all appendices, and I agree that it 
contains all necessary details for me and my staff to conduct this study as described. I will 
conduct this study as outlined herein and will make a reasonable effort to complete the study 
within the time designated.  
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Vir Biotechnology, Inc. I will discuss this material with them to ensure 
they are fully informed about the drugs and the study. 
Principal Investigator Printed Name 
Signature 
Date 
PPD

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PROTOCOL AMENDMENT 3 (14 DECEMBER 2023) SUMMARY OF CHANGES TABLE 
Table 1: 
Protocol Document History 
Summaries of changes for Amendment 1 are provided in Section 10.5. 
Table 2: 
Protocol Amendment 3 Summary of Changes 
Section # and Name 
Description of Change 
Brief Rationale 
1.1. Synopsis (Number of 
Participants), 4.1.1. Number of 
Participants, 9.2. Sample Size 
Determination, 9.5. Interim Analysis 
Clarified that floater participants may be added at 
any time at Sponsor’s discretion. As a result of 
this clarification, language in Section 9.5 
(Interim Analysis) was updated for consistency 
To clarify when floater participants can be added 
during the study 
1.1. Synopsis (Intervention Groups 
and Duration), 4.1.3. NRTI 
Discontinuation 
Changed one of the NRTI discontinuation 
criteria from participants discontinue NRTI after 
EOT (in addition to other criteria) if HBsAg 
< 100 IU/mL and ≥1 log10 IU/mL reduction 
from baseline HBsAg to participants discontinue 
NRTI after EOT (in addition to other criteria) if 
HBsAg < LLOQ  
Based on emerging literature, requiring HBsAg 
levels < LLOQ to discontinue NRTI therapy is a 
conservative threshold to lower the risk of viral 
relapse after NRTI discontinuation (Pavlovic 2023). 
4.1.4. NRTI Retreatment 
Clarified that confirmatory test for HBV DNA > 
20,000 IU/mL should occur no later than 7 
calendar days after initial result is received. Also 
clarified that central laboratory testing is 
preferred, but local laboratory results will be 
accepted if it is not feasible to collect central 
laboratory results in time  
To ensure re-testing is done promptly for safety 
management of participants who may be 
recommended to restart their NRTI therapy 
Document 
Date 
Amendment 3 
14 December 2023 
Amendment 2 
11 October 2022 
Amendment 1 
16 May 2022 
Original Protocol 
01 April 2022 

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Section # and Name 
Description of Change 
Brief Rationale 
Section 7.2. Discontinuation of 
Study Intervention(s) 
Added the following additional treatment 
discontinuation criteria:  
Serum ALT or aspartate aminotransferase (AST) 
> 3 × ULN with:
•
serum albumin <3.0g/dL or
•
ascites, hepatic encephalopathy, or liver-
related symptoms (eg, severe fatigue, nausea,
vomiting, right upper quadrant pain in the
absence of an alternative medical
explanation)
Also added study intervention may be 
discontinued in the occurrence of a condition that 
in the opinion of the Investigator significantly 
jeopardizes the wellbeing and safety of the 
participant. Investigator must promptly inform 
the Sponsor Medical Monitor if any such 
condition arises. 
This change was made to include additional criteria 
for treatment discontinuation and clarification for 
when the Investigator may stop study intervention. 
This change was previously made in Addendum 
France-1 of VIR-SHB1-V201 (STRIVE) 
Amendment 2, Version 3.0 in response to a request 
made by ANSM of France and is being added to 
VIR-SHB1-V201 (STRIVE) Amendment 3 to 
harmonize into a single global protocol. 
8.8. Pharmacokinetic Assessments 
Clarified that PK assessments are exploratory 
and may or may not be analyzed, and specific 
assays used for these assessments may be 
changed at the Sponsor’s discretion based on 
emerging data 
To allow for appropriate analyses of exploratory PK 
assessments based on emerging data 
10.2. Appendix 2: Clinical 
Laboratory Tests, 10.7. Appendix 7: 
Additional Assessments in 
Participants That Experience ALT 
Elevation Meeting ECI Criteria  
Added serum phosphate to the protocol-required 
safety laboratory tests  
To align with renal monitoring guidance in the 
Viread® SmPC. This change was previously made 
in Addendum-1 and Addendum France-1 of VIR-
SHB1-V201 (STRIVE) Amendment 2, Version 3.0 
and is being added to VIR-SHB1-V201 (STRIVE) 
Amendment 3 to harmonize into a single global 
protocol. 

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Section # and Name 
Description of Change 
Brief Rationale 
10.2. Appendix 2: Clinical 
Laboratory Tests 
Added footnote to clarify creatinine clearance 
calculation for study visits where weight is not 
measured (creatinine clearance will be calculated 
using the value measured from the most recent 
study visit) 
To provide further guidance for creatinine clearance 
calculation. This clarification was described in 
Protocol Administrative Letter 1 for VIR-SHBV1-
V201 Amendment 2, Version 3.0 and is being added 
to VIR-SHB1-V201 (STRIVE) Amendment 3 to 
harmonize into a single global protocol. 
Entire document 
Other administrative, formatting, and other minor 
changes 
These changes were made to clarify, ensure 
consistency, provide up-to-date information, or 
rectify typographical errors.  
 

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TABLE OF CONTENTS 
INVESTIGATOR SIGNATURE PAGE .........................................................................................2
1.
PROTOCOL SUMMARY ..........................................................................................11
1.1.
Synopsis ......................................................................................................................11
1.2.
Study Schema .............................................................................................................15
1.3.
Schedule of Activities .................................................................................................16
2.
INTRODUCTION ......................................................................................................17
2.1.
Background .................................................................................................................17
2.2.
Study Rationale ...........................................................................................................18
2.3.
Benefit/Risk Assessment ............................................................................................19
2.3.1.
Risk Assessment .........................................................................................................19
2.3.2.
Benefit Assessment .....................................................................................................23
2.3.3.
Overall Benefit Risk Conclusion ................................................................................23
3.
OBJECTIVES AND ENDPOINTS ............................................................................24
4.
STUDY DESIGN .......................................................................................................26
4.1.
Overall Study Design ..................................................................................................26
4.1.1.
Number of Participants ...............................................................................................26
4.1.2.
Intervention Groups and Duration ..............................................................................26
4.1.2.1.
Intervention Groups ....................................................................................................26
4.1.2.2.
Cohort Initiation and VIR-3434 Dosing Selection .....................................................27
4.1.2.3.
Duration ......................................................................................................................28
4.1.3.
NRTI Discontinuation ................................................................................................28
4.1.4.
NRTI Retreatment ......................................................................................................29
4.1.5.
Long-Term and Follow-Up Care ................................................................................29
4.2.
Scientific Rationale for Study Design ........................................................................30
4.2.1.
Rationale for VIR-3434 for the Treatment of Chronic HBV Infection ......................30
4.2.2.
Rationale for VIR-2218 for the Treatment of Chronic HBV Infection ......................31
4.2.3.
Rationale for VIR-3434 + VIR-2218 + TDF for the Treatment of Chronic 
HBV Infection ............................................................................................................32
4.2.4.
Rationale for VIR-3434 + VIR-2218 + PEG-IFNα + TDF for the Treatment 
of Chronic HBV Infection ..........................................................................................33
4.3.
Justification for Dose ..................................................................................................34
4.3.1.
VIR-3434 Dose Selection ...........................................................................................34

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4.3.2.
VIR-2218 Dose Selection ...........................................................................................36
4.3.3.
PEG-IFNα Dose Selection ..........................................................................................37
4.3.4.
TDF Dose Selection ....................................................................................................37
4.4.
End of Study Definition ..............................................................................................37
5.
STUDY POPULATION .............................................................................................38
5.1.
Inclusion Criteria ........................................................................................................38
5.2.
Exclusion Criteria .......................................................................................................39
5.3.
Lifestyle Considerations .............................................................................................41
5.3.1.
Meals and Dietary Restrictions ...................................................................................41
5.3.2.
Caffeine, Alcohol, and Tobacco .................................................................................41
5.3.3.
Activity .......................................................................................................................41
5.4.
Screen Failures ............................................................................................................41
6.
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY ........................42
6.1.
Study Intervention(s) Administered ...........................................................................42
6.2.
Preparation, Handling, Storage, and Accountability ..................................................43
6.3.
Randomization and Blinding ......................................................................................43
6.4.
Study Intervention Compliance ..................................................................................44
6.5.
Dose Modification ......................................................................................................44
6.5.1.
Dose Modifications for PEG-IFNα .............................................................................44
6.5.2.
Dose Modifications for TDF ......................................................................................44
6.6.
Concomitant Therapy .................................................................................................44
6.6.1.
Concomitant Therapy Not Permitted During the Study .............................................44
7.
DISCONTINUATION OF STUDY, STUDY INTERVENTION AND
PARTICIPANT DISCONTINUATION/WITHDRAWAL .......................................45
7.1.
Study Stopping Rules .................................................................................................45
7.2.
Discontinuation of Study Intervention(s) ...................................................................46
7.3.
Participant Discontinuation/Withdrawal from the Study ...........................................46
7.4.
Replacement of Participants .......................................................................................46
7.5.
Lost to Follow-up .......................................................................................................46
8.
STUDY ASSESSMENTS AND PROCEDURES ......................................................47
8.1.
Screening Period .........................................................................................................47
8.2.
Efficacy Assessments .................................................................................................47
8.3.
Safety Assessments .....................................................................................................47

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8.3.1.
Physical Examinations ................................................................................................47
8.3.2.
Vital Signs ..................................................................................................................47
8.3.3.
Clinical Safety Laboratory Tests ................................................................................47
8.3.4.
Pregnancy Testing ......................................................................................................47
8.3.5.
Local Tolerability .......................................................................................................48
8.4.
Assessment of Viral Parameters, Antiviral Activity, and Resistance 
Surveillance ................................................................................................................48
8.5.
48
8.6.
Exploratory Assessments ............................................................................................48
8.6.1.
Exploratory Analysis Samples ....................................................................................48
8.6.2.
48
8.6.2.1.
48
8.6.2.2.
49
8.6.2.3.
49
8.6.3.
49
8.7.
Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Safety 
Reporting ....................................................................................................................49
8.7.1.
Time Period and Frequency for Collecting AE and SAE Information .......................49
8.7.2.
Follow-up of AEs and SAEs .......................................................................................49
8.7.3.
Regulatory Reporting Requirements for SAEs ...........................................................49
8.7.4.
Adverse Events of Interest ..........................................................................................49
8.7.5.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as AEs 
or SAEs .......................................................................................................................49
8.7.6.
Laboratory Event of Clinical Interest .........................................................................50
8.7.7.
Special Situation Reports ............................................................................................50
8.7.7.1.
Pregnancy ...................................................................................................................50
8.8.
Pharmacokinetic Assessments ....................................................................................50
8.8.1.
Optional Sub-Study: VIR-3434 PK ............................................................................50
8.9.
Immunogenicity Assessments ....................................................................................51
8.10.
Electrocardiogram .......................................................................................................51
8.11.
Liver Elastography (eg, FibroScan) ............................................................................51
9.
STATISTICAL CONSIDERATIONS .......................................................................51
9.1.
Statistical Hypotheses .................................................................................................51
CCI
CCI
CCI
CCI
CCI
CCI

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9.2.
Sample Size Determination ........................................................................................51
9.3.
Analysis Sets ...............................................................................................................52
9.4.
Statistical Analyses .....................................................................................................52
9.4.1.
General Considerations ...............................................................................................52
9.4.2.
Primary Endpoint Analysis .........................................................................................52
9.4.2.1.
Target Population ........................................................................................................52
9.4.2.2.
Population Level Summary ........................................................................................52
9.4.3.
Secondary Endpoint(s) Analysis.................................................................................53
9.4.4.
Exploratory Endpoint(s) Analysis ..............................................................................53
9.4.5.
Missing Data ...............................................................................................................53
9.4.6.
Other Safety Analyses ................................................................................................53
9.5.
Interim Analysis ..........................................................................................................53
9.6.
Pharmacokinetics Analyses ........................................................................................54
9.7.
Immunogenicity Analyses ..........................................................................................54
10.
SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS ..................................................................................................55
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ....................55
10.1.1.
Regulatory and Ethical Considerations ......................................................................55
10.1.2.
Financial Disclosure ...................................................................................................55
10.1.3.
Informed Consent Process ..........................................................................................55
10.1.4.
Data Protection ...........................................................................................................55
10.1.5.
Confidentiality ............................................................................................................55
10.1.6.
Committees Structure .................................................................................................55
10.1.6.1.
Liver Flare Adjudication Committee (LFAC) ............................................................55
10.1.7.
Dissemination of Clinical Study Data ........................................................................55
10.1.8.
Data Quality Assurance ..............................................................................................55
10.1.9.
Source Documents ......................................................................................................55
10.1.10.
Electronic Case Report Forms (eCRF) .......................................................................55
10.1.11.
Study and Site Start and Closure ................................................................................56
10.1.12.
Publication Policy .......................................................................................................56
10.2.
Appendix 2: Clinical Laboratory Tests .......................................................................57
10.3.
Appendix 3: AEs, SAEs, SSRs and AEIs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .....................................................59

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10.4.
Appendix 4: List of Abbreviations and Definitions of Terms ....................................60
10.5.
Appendix 5: Summary of Changes for Previous Protocol Amendment .....................62
10.6.
Appendix 6: Contraceptive and Barrier Guidance ......................................................69
10.7.
Appendix 7: Additional Assessments in Participants That Experience ALT 
Elevation Meeting ECI Criteria ..................................................................................71
10.8.
Appendix 8: Anaphylaxis, Cytokine Release Syndrome, And Immune 
Complex Disease Supportive Measures .....................................................................73
10.9.
Appendix 9: Schedule of Activities ............................................................................75
10.10.
Appendix 10: Schedule of Sample Collection for Optional VIR-3434 PK 
Sub-study ....................................................................................................................99
11.
REFERENCES .........................................................................................................100
LIST OF TABLES 
Table 1:
Protocol Document History ..........................................................................................3
Table 2:
Protocol Amendment 3 Summary of Changes .............................................................3
Table 3:
Intervention Groups ....................................................................................................27
Table 4:
Study Intervention (s) Administered ..........................................................................42
Table 5:
Study Arm(s) ..............................................................................................................43
Table 6:
Protocol-Required Safety Laboratory Tests ...............................................................57
Table 7:
Assessments in Participants That Experience ALT Elevation Meeting ECI 
Criteria ........................................................................................................................71
Table 8:
Schedule of Activities: Cohort 1a/2a (PBMC- Qualified Sites Only) ........................75
Table 9:
Schedule of Activities: Cohort 3a (PBMC- Qualified Sites Only) .............................80
Table 10:
Schedule of Activities: Cohort 4a ...............................................................................85
Table 11:
Schedule of Activities: Cohort 5a ...............................................................................90
Table 12:
Schedule of Activities: Follow-Up Period for all Cohorts .........................................95
LIST OF FIGURES 
Figure 1:
Study Schema .............................................................................................................15
Figure 2:
Dosing Scheme by Cohort ..........................................................................................16
Figure 3:
Stages of Chronic HBV Infection ...............................................................................17
Figure 4:
VIR-3434 Observed and Projected Mean Concentration Profile in Healthy 
Volunteers in the Absence of HBsAg .........................................................................35

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1.
PROTOCOL SUMMARY
1.1. 
Synopsis
Study Title 
A Phase 2 Study Evaluating the Efficacy and Safety of VIR-3434 and/or VIR-2218 Containing 
Regimens in Participants with Chronic Hepatitis B Infection (STRIVE) 
Brief Title 
A Phase 2 Study to Evaluate VIR-3434 and/or VIR-2218 Containing Regimens for Treatment of 
Chronic Hepatitis B Infection  
Background and Rationale 
Chronic hepatitis B virus (HBV) infection remains an important global public health problem 
with significant morbidity and mortality (Trepo 2014). Chronic HBV infection is a dynamic 
process characterized by the interplay of viral replication and the host immune response. Patients 
can be divided into different stages of the disease based on the levels of Hepatitis B e antigen 
(HBeAg), HBV DNA, alanine aminotransferase (ALT), and liver inflammation (EASL 2017; 
Sarin 2015; Terrault 2018). 
Among non-cirrhotic patients with chronic HBV infection, treatment is only recommended for 
the subset that have high levels of viremia (HBV DNA) and elevated levels of alanine 
aminotransferase (ALT) (EASL 2017; Sarin 2015; Terrault 2018). Current treatment options for 
chronic HBV infection are limited to nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and 
peginterferon-alfa-2a (PEG-IFNα) (Liang 2015). Long-term therapy NRTI therapy can suppress 
HBV DNA but does not eliminate the cccDNA or integrated DNA. In contrast to NRTIs, 
PEG-IFNα can induce long-term viral control, but only in a small percentage of patients (< 10%) 
and after 48 weeks of therapy (Konerman 2016). Therefore, there exists an unmet need for better 
treatment options that can achieve functional cure. 
VIR-3434 is a monoclonal antibody targeting Hepatitis B surface antigen (HBsAg) with multiple 
potential mechanisms of action including strong neutralizing activity and enhanced immunologic 
activity due to Fc domain engineering. VIR-2218 is a small interfering RNA (siRNA) that is 
associated with substantial reductions in HBsAg in patients with chronic HBV infection. 
VIR-3434, either alone, in combination with VIR-2218, or in combination with both VIR-2218 
and PEG-IFNα, has the potential to achieve a functional cure of chronic HBV infection. 

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Primary and Secondary Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
•
To evaluate the efficacy of VIR-3434 and
tenofovir disoproxil fumarate (TDF) with or
without VIR-2218, or VIR-2218 and
PEG-IFNα
•
Proportion of participants achieving
suppression of HBV DNA (< LLOQ [lower
limit of quantitation]) with HBsAg loss
(< 0.05 IU/mL) at the end of treatmenta
Secondary 
In addition to the Master Protocol, 
•
To assess the effect of VIR-3434 and TDF
with or without VIR-2218, or VIR-2218 and
PEG-IFNα on HBsAg
•
To assess the effect of VIR-3434 and TDF
with or without VIR-2218, or VIR-2218 and
PEG-IFNα on HBV DNA
•
To assess the effect of VIR-3434 and TDF
with or without VIR-2218, or VIR-2218 and
PEG-IFNα on HBeAg and anti-HBe
•
To assess the immunogenicity of VIR-3434
•
To assess the effect of VIR-3434 and TDF
with or without VIR-2218, or VIR-2218 and
PEG-IFNα on ALT levels
In addition to the Master Protocol secondary 
endpoints 1-8, 
9.
Proportion of participants achieving sustained
suppression of HBV DNA (< LLOQ) with
HBsAg loss (< 0.05 IU/mL) after
discontinuation of all treatment
a.
at 24 weeks
b.
at the F48 Follow-Up visit
10. Proportion of participants achieving HBsAg
loss (< 0.05 IU/mL)
a.
at end of treatmenta
b.
at 24 weeks post-end of treatmenta
11. Proportion of participants achieving sustained
suppression of HBV DNA (< LLOQ) after
discontinuation of all treatment
a.
at 24 weeks
b.
at the F48 Follow-Up visit
12. For HBeAg-positive participants: proportion
of participants with HBeAg loss (undetectable
HBeAg) and/or anti-HBe seroconversion
13. Incidence and titers of anti-drug antibodies
(ADA; if applicable) to VIR-3434
14. Mean change in serum HBsAg level from
baseline across timepoints in the study
15. Proportion of participants achieving HBV
DNA < LLOQ across timepoints in the study
16. Proportion of participants achieving ALT
≤ ULN across timepoints in the study
a End of treatment as defined in SOA 

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Overall Study Design 
This sub-protocol (STRIVE) should be read and conducted in conjunction with the PREVAIL 
Master Protocol. The Master Protocol provides a study framework: study outline, populations, 
common objectives and endpoints, common inclusion and exclusion criteria, statistical 
methodology, assessments and planned analyses for all sub-protocols. This sub-protocol is a 
Phase 2, multi-center, open-label study designed to evaluate the safety and efficacy of regimens 
containing VIR-3434, VIR-2218, PEG-IFNα, and an NRTI in non-cirrhotic adult participants 
with chronic HBV infection that have not received prior NRTI or PEG-IFNα treatment. 
Brief Summary 
This sub-protocol is intended to evaluate combinations of VIR-3434 and NRTI (TDF) with or 
without VIR-2218, and VIR-3434 and TDF in combination with both VIR-2218 and PEG-IFNα 
in participants with chronic HBV infection. Study populations II and III as defined in the Master 
Protocol (and table) will be included in this sub-protocol. Participants that have not received any 
prior NRTI or PEG-IFNα treatment will be eligible for enrollment into this study. 
Master Protocol Population 
HBeAg Status 
HBV DNA Level 
ALT Level 
II 
Positive 
> 2,000 IU/mL
> ULN and ≤ 5x ULN
III 
Negative 
> 2,000 IU/mL
> ULN and ≤ 5x ULN
Number of Participants 
Up to 90 participants are planned to be enrolled in this sub-protocol. Cohorts 1a, 2a, and 3a will 
each enroll approximately 10 participants. Cohorts 4a and 5a will each enroll approximately 
15 participants. Additionally, up to 30 floater participants may be added to any cohort in the 
sub-protocol at any time at Sponsor’s discretion. 

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Intervention Groups and Duration 
Cohort 
Study Drug 
Dose 
Route 
Number of 
Doses 
Frequency of Dosing 
1a 
VIR-3434 
300 mg 
SC 
12 
Every 4 weeks 
TDF 
300 mgb 
Oral 
≥ 308c 
Every day 
2a 
VIR-3434 
Up to 300 mga 
SC 
12 
Every 4 weeks 
TDF 
300 mgb 
Oral 
≥ 308c 
Every day 
3a 
VIR-3434 
300 mg 
SC 
4-6d
Every 8-12 weeksd 
TDF 
300 mgb 
Oral 
≥ 252c 
Every day 
4a 
VIR-3434 
300 mg 
SC 
12 
Every 4 weeks 
VIR-2218 
200 mg 
SC 
12 
Every 4 weeks 
TDF 
300 mgb 
Oral 
≥ 308c 
Every day 
5a 
VIR-3434 
300 mg 
SC 
13 
Every 4 weeks 
VIR-2218 
200 mg 
SC 
13 
Every 4 weeks 
PEG-IFNα 
180 mcg 
SC 
48 
Every week 
TDF 
300 mgb 
Oral 
≥ 336c 
Every day 
a The dose of VIR-3434 will be determined before participants are enrolled in the cohort 
b Tenofovir disoproxil fumarate dose (TDF) will be 300 mg as approved by the FDA. Supply outside the United 
States may be Tenofovir disoproxil (TD) 245 mg. 
c The minimum number of doses received by participant. Participants will continue receiving additional doses of 
TDF until they qualify for NRTI discontinuation (Section 4.1.3).  
d The dosing regimen will be finalized before participants are enrolled in the cohort. See Section 4.1.2.2. 
The total duration in the study for participants will be up to 100 weeks in Cohorts 1a, 2a and 
Cohort 4a, 92-96 weeks for Cohort 3a and 104 weeks for Cohort 5a. This includes a Screening 
Period (up to 56 days or 8 weeks), Treatment Period (44 weeks for Cohorts 1a and 2a, 36 or 
40 weeks for Cohort 3a, 44 weeks for Cohort 4a, and 48 weeks for Cohort 5a) and a 
Follow-Up-Period (up to 48 weeks) for all cohorts.  
Participants will discontinue NRTI at F1 or at F12 Follow-Up visits based on most recent data 
available if they meet all of the following criteria (Section 4.1.3): 
•
HBsAg < LLOQ
•
Suppressed HBV DNA (defined as < LLOQ)
•
Undetectable HBeAg (based on quantitative HBeAg)
•
ALT ≤ 2 times the upper limit of normal (ULN)
Participants that meet the criteria to discontinue NRTI treatment will continue per the Follow-Up 
Period Schedule of Activities (SOA).  

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Participants that do not qualify for NRTI discontinuation will continue taking the NRTI until the 
end of the Follow-Up Period. Once participant has completed the study, long-term care should be 
determined by the Investigator or primary treating physician based on local clinical guidelines. 
Liver Flare Adjudication Committee (LFAC) 
The Liver Flare Adjudication Committee (LFAC) will provide hepatic safety oversight by 
performing periodic reviews of data pertaining to participants who meet certain prespecified 
criteria for alanine transaminase elevations (Section 8.7.6). The LFAC membership composition, 
laboratory criteria to trigger patient case evaluation by the LFAC, and data review requirements 
are described in detail in the LFAC Charter (Section 10.1.6.1). 
1.2.
Study Schema 
Eligible participants will be assigned via Interactive Response Technology (IRT) to one of the 
open cohorts. If a participant is ineligible to receive PEG-IFNα (Cohort 5a), they will be 
assigned to one of the other open cohorts. 
The overall study scheme is presented in Figure 1 and the dosing scheme for all the cohorts are 
shown in Figure 2.  
The SOAs for Cohorts 1a/2a, 3a, 4a, and 5a are provided in Table 8, Table 9, Table 10 and 
Table 11. Table 12 shows the SOA for the Follow-Up Period.  
Figure 1: 
Study Schema 

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Figure 2: 
Dosing Scheme by Cohort 
FU = Follow-Up; EOT = end of treatment; QW = every week; Q4W = every 4 weeks; Q8W = every 8 weeks; 
Q12W = every 12 weeks; PEG-IFNα = pegylated interferon alfa-2a; TDF = Tenofovir disoproxil fumarate (or 
Tenofovir disoproxil where applicable); F1 = Follow Up Visit 1; F12 = Follow-Up visit 12 
See Section 4.1 for more details.  
1.3.
Schedule of Activities 
Schedules of activities are provided in Section 10.9. 

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2.
INTRODUCTION
This sub-protocol should be read and conducted in conjunction with the PREVAIL Master 
Protocol (VIR-MHB1-V200). 
2.1.
Background 
Chronic HBV infection remains an important global public health problem with significant 
morbidity and mortality (Trepo 2014). Chronic HBV infection is a dynamic process and depends 
on the relationship between viral replication and host immune responses. Patients may oscillate 
between different phases of the disease, and serial monitoring of biomarkers such as HBV DNA, 
alanine aminotransferase (ALT) and HBV antigens helps determine the natural history of the 
disease (Figure 3). Following infection, the HBV virus may replicate as a stealth virus without a 
host immune response. After years of viral replication (high HBV DNA), the immune system 
mounts a response against infected hepatocytes leading to elevated ALT in Hepatitis B e antigen 
(HBeAg)-positive patients. During this stage of the disease, patients are also characterized by 
moderate to severe inflammation in the liver and accelerated progression of fibrosis. Patients 
infected perinatally may reach this stage of chronic HBV infection following 10-30 years after 
infection, whereas those infected as adults or in childhood progress faster or may even skip this 
stage altogether. The outcomes are also variable for this population. Among patients that are 
HBeAg-positive, some patients become HBeAg-negative rapidly, and others take much longer 
with or without treatment to become HBeAg-negative and positive for anti-HBe (EASL 2017; 
Fattovich 2008; Terrault 2018; Wang 2021).  
Figure 3: 
Stages of Chronic HBV Infection 
Patients with elevated ALT who are HBeAg positive with HBV DNA > 20,000 IU/mL or 
HBeAg negative with HBV DNA > 2,000 IU/mL are eligible for treatment with nucleos(t)ide 
reverse transcriptase inhibitors (NRTIs) and/or peginterferon-alfa-2a (PEG-IFNα) (Liang 2015). 
NRTIs can suppress HBV DNA with long-term therapy but do not eliminate cccDNA or 
integrated DNA. In contrast to NRTIs, PEG-IFNα can induce long-term viral control, but only in 
a small percentage of patients (< 10%) and after 48 weeks of therapy (Konerman 2016). 
Therefore, there exists an unmet need for better treatment options that can achieve functional 
cure. 
Immune 
Tolerant
Immune 
active
Inactive 
carrier
Reactivation
HBV DNA
ALT

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2.2.
Study Rationale 
VIR-3434 is a monoclonal antibody (mAb) targeting HBsAg with multiple potential mechanisms 
of action, including strong neutralizing activity and enhanced immunologic activity due to Fc 
domain engineering. VIR-2218 is a siRNA targeting all HBV RNA transcripts that is associated 
with substantial reductions in HBsAg in patients with chronic HBV infection. VIR-3434 and an 
NRTI (TDF [tenofovir disoproxil fumarate]), in combination with VIR-2218, or in combination 
with both VIR-2218 and PEG-IFNα, have the potential to achieve a functional cure of chronic 
HBV infection. 
See Section 4.2 for additional scientific rationale for the different investigational regimens in this 
sub-protocol.

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2.3.
Benefit/Risk Assessment 
Detailed information about the known and potential benefits and risks of VIR-2218 and VIR-3434 may be found in the respective 
Investigator’s Brochures (IBs). 
2.3.1.
Risk Assessment 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Study Intervention: VIR-2218 
Injection site reactions (ISRs) 
Based on available preliminary clinical data 
from studies VIR-2218-1001 and VIR-
2218-1006, ISRs are a recognized risk of 
subcutaneous (SC) administered siRNA 
therapies and are typically transient. 
Participants are monitored for local tolerability after 
injection and all AEs will be collected to reflect any 
ISRs that may be reported. Routine safety 
monitoring and reporting procedures are in place to 
provide safety overview. 
Immunogenicity: Immunogenicity is a 
potential risk associated with siRNA 
molecules. In general, the development of 
anti-drug antibodies (ADA) may impact 
safety, efficacy, or both. 
Immunogenicity data from Parts B/C of the 
VIR-2218-1001 study indicated a low 
immunogenicity risk based on all confirmed 
subjects yielding negative titers. 
While there were no apparent clinical consequences 
related to the presence of VIR-2218 ADA, 
immunogenicity will continue to be assessed in 
Parts D/F of study VIR-2218-1001. 
Liver function test abnormalities: 
VIR-2218 is targeted for delivery to the 
liver, and transient transaminase 
elevations have been observed with SC 
administration with other 
GalNAc-conjugated siRNA therapeutics. 
Based on available preliminary clinical data 
from studies VIR-2218-1001 and VIR-
2218-1006, minor ALT elevations (Grade 1 
or Grade 2) have been observed in 
participants receiving VIR-2218 
monotherapy. However, none of the 
participants met Hy’s law and the majority 
resolved the ALT elevations by the end of 
treatment. 
Monitoring of liver function is recommended. In 
addition, ALT flares in chronic HBV patients may 
be a sign of restoration of HBV-targeted immunity, 
therefore close monitoring of liver function and 
HBV-viral parameters may be warranted. 
Low probability: Events of Clinical Interest (ECI) 
defined as ALT elevations ≥ 5X and > 2X baseline 
must be reported within 5 business days of 
Investigator notification. The Sponsor will monitor 
ECI and an independent Liver Flare Adjudication 
Committee (LFAC) reviews the liver safety and 
assesses etiology to recommend changes in study 
conduct. 

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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Study Intervention: VIR-3434 
Probability of significant non-target 
mediated toxicity:  
Hypersensitivity reactions (including 
infusion related reactions [IRRs]/injection 
site reactions [ISRs], and anaphylaxis): 
Hypersensitivity reactions (including 
IRRs/ISRs and anaphylaxis), which may 
be severe or life-threatening, are a 
potential risk associated with the mAb 
class. The distinct risk of developing such 
conditions after dosing with VIR-3434 is 
unknown. 
Two clinical studies with VIR-3434 are 
ongoing. In VIR-3434-1002, Parts A and 
B/C, VIR-3434 has been generally well 
tolerated in healthy subjects and in subjects 
with chronic HBV infection. ISRs occurred 
in 20% of subjects in Part A and 10.7% in 
Part B/C; all ISRs were Grade 1 or 2, 
considered related to VIR-3434, and 
resolved without sequelae. In 
VIR-2218-1006 (VIR-2218 + VIR-3434) 
most AEs were Grade 1 or 2 in severity, and 
most were considered not related to VIR-
2218 and/or VIR-3434. No ISRs were 
considered related to VIR-3434. 
Low probability: participants will be closely 
monitored to evaluate any patterns of non-target 
mediated toxicity. 
Participants are monitored for local tolerability after 
injection and all AEs will be collected to reflect any 
hypersensitivity reactions that may be reported. 
Routine safety monitoring and reporting procedures 
are in place to provide safety overview. 
Immunogenicity: Immunogenicity is a 
potential risk associated with the mAb 
class. VIR-3434 is a human 
immunoglobulin G (IgG) mAb; therefore, 
the development of ADA may impact its 
safety, efficacy, or both. 
Immunogenicity data for VIR-3434 is not 
available at this time. An appropriate 
risk-based bioanalytical strategy is being 
used to assess immunogenicity in the study. 
Immunogenicity data will be assessed in relation to 
associated VIR-3434 PK and clinical safety 
measures. 

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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Potential target-mediated risks: immune 
complex disease and hepatotoxicity due to 
the elimination of infected hepatocytes 
via cytotoxic T-cells induced via a 
vaccinal effect. As no or only low levels 
of HBsAg is detected on the surface of 
infected hepatocytes, antibody-dependent 
cellular cytotoxicity (ADCC)/ antibody-
dependent cellular phagocytosis (ADCP)-
mediated elimination of hepatocytes is 
possible but unlikely to occur. 
In Part B/C of study VIR-3434-1002, single 
doses up to 300 mg were well tolerated. No 
clinically significant changes in laboratory 
parameters were observed, and no 
participant developed clinical or laboratory 
evidence of immune complex disease. 
These preliminary results are consistent 
with prior clinical experience supporting the 
safety of anti-HBsAg monoclonal 
antibodies. HBV-ABXTL, a mixture of two 
anti-HBsAg monoclonal antibodies, was 
evaluated at doses up to 80 mg administered 
weekly for 4 doses in patients with baseline 
HBsAg ranging from approximately 20 to 
80,000 IU/mL, and no signs of immune 
complex disease or hepatotoxicity were 
observed (Galun 2002). Additionally, 
several studies have evaluated the use of 
hepatitis B immune globulin (HBIG) in 
patients with chronic HBV infection and 
reported favorable safety and tolerability  
(Perrillo 2013; Reed 1973; Tsuge 2016). In 
the largest study, 64 patients with baseline 
HBsAg ranging from 0.09 to 11,214 IU/mL 
(mean 1,965 IU/mL) received HBIG 
therapy for multiple weeks, and no clinical 
manifestations of immune complex disease 
or other safety concerns were observed 
(Perrillo 2013).  
Low probability: participants will be closely 
monitored to evaluate any patterns of non-target 
mediated toxicity 

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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Study Intervention: VIR-3434 + VIR-2218 + TDF +/- PEG-IFNα 
Hepatotoxicity 
Combination of these study interventions 
may result in hepatotoxicity (eg, elevated 
ALT). Based on available preliminary 
clinical data from VIR-2218-1001, VIR-
2218-1006 and VIR-3434-1002, VIR-2218 
or VIR-3434 monotherapy in virally 
suppressed participants have resulted in 
minor ALT elevations (Grade 1 or Grade 2). 
Combination of VIR-2218 with PEG-IFNα 
resulted in up to Grade 3 elevations in ALT. 
However, none of the participants met Hy’s 
law and majority have resolved the ALT 
elevations after the end of treatment. 
Addition of NRTI (TDF) to the treatment regimen 
to suppress viral replication 
Excluding patients with significant fibrosis or 
cirrhosis, significant chronic liver disease (except 
HBV infection), history of hepatic decompensation. 
Routine safety monitoring and reporting procedures 
ECI defined as ALT elevations ≥ 5X and > 2X 
baseline must be reported within 5 business days of 
Investigator notification. Sponsor monitors ECI and 
an independent LFAC reviews the liver safety and 
assesses etiology to recommend changes in study 
conduct. 
Stopping criteria for study interventions have been 
provided in Section 7.1 
Injection site reactions 
Combination of VIR-3434 +/- VIR-2218 +/- 
PEG-IFNα may result in injection site 
reactions (ISRs) such as injection site pain, 
bruising, itching, rash. In the ongoing 
VIR-3434-1002, VIR-2218-1001 and 
VIR-2218-1006 studies, these interventions 
alone on or in combination have resulted in 
ISRs Grade 1 or 2 in severity that usually 
resolve within a few days to weeks. There is 
no potential cumulative risk for the 
combination intervention of VIR-3434 + 
VIR-2218. 
Participants are monitored for local tolerability after 
injection and all AEs will be collected to reflect any 
ISRs that may be reported. Routine safety 
monitoring and reporting procedures are in place to 
provide safety overview. 

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2.3.2.
Benefit Assessment 
Single doses of VIR-2218 up to 900 mg in healthy volunteers and up to 6 doses of up to 200 mg 
administered every 4 weeks (ie, the highest dose tested) were well tolerated and exhibited safety 
profiles supportive of continued clinical development (VIR-2218 Investigator’s Brochure) in 
participants with chronic HBV infection. Regardless of HBeAg status, VIR-2218 was associated 
with a -1.96 log10 IU/mL mean decrease in HBsAg after 6 every 4-week (Q4W) doses 
(Lim 2022). 
VIR-3434 has the potential to further reduce HBsAg, inhibit infection of new hepatocytes via 
entry inhibition, eliminate infected hepatocytes, and stimulate an adaptive immune response 
against HBV. Lower HBsAg levels may be achieved by lead-in or concomitant administration of 
VIR-2218 and has the potential to augment the effects of VIR-3434 and achieve a functional 
cure of chronic HBV infection. Additionally, multiple-dose regimens of VIR-3434 may produce 
rapid and sustained reductions of HBsAg in the absence of VIR-2218 and potentially achieve 
functional cure of chronic HBV infection as monotherapy.  
PEG-IFNα 180 μg administered weekly for 48-52 weeks results in HBsAg loss in approximately 
≤ 10% of patients overall (Konerman 2016). This duration of therapy is associated with poor 
tolerability and safety concerns that resulted in treatment discontinuation in approximately 5% of 
patients in Phase 3 clinical trials for chronic HBV infection 
(PEGASYS® Prescribing Information). Shorter durations of PEG-IFNα therapy may ameliorate 
these effects while still providing antiviral and immunomodulatory activity, particularly when 
combined with VIR-2218 and VIR-3434.  
In the ongoing VIR-2218-1001 study, multiple regimens of VIR-2218 and PEG-IFNα 
combination therapy are being evaluated in virally suppressed (on NRTIs) participants with 
chronic HBV infection. Preliminary safety and tolerability data suggest that the addition of 
VIR-2218 does not result in additional risks beyond those associated with PEG-IFNα alone 
(Yuen 2021). Additionally, substantial reductions in HBsAg were observed, but few participants 
achieved HBsAg loss. In this study, it is hypothesized that the addition of VIR-3434 to 
VIR-2218 and PEG-IFNα will lead to higher rates of HBsAg loss and functional cure.  
2.3.3.
Overall Benefit Risk Conclusion 
This study will provide information on the safety, tolerability, and efficacy of VIR-3434 and 
NRTI (TDF) in combination with VIR-2218 and/or PEG-IFNα. The study is designed to test the 
hypothesis that regimens containing VIR-3434, TDF and/or VIR-2218, and/or PEG-IFNα may 
lead to a functional cure of chronic HBV infection by reducing HBsAg and stimulating a host 
immune response. Compared to the current standard of care, the regimens in this study offer the 
potential benefits of finite duration, pangenotypic activity, and the potential to achieve functional 
cure, which may be associated with a reduction in serious HBV-associated sequelae such as 
cirrhosis, liver failure, hepatocellular carcinoma, or death.  
The mechanistic rationale, together with available clinical data, supports a favorable risk-benefit 
profile for evaluation of regimens containing VIR-3434 and TDF with or without VIR-2218, and 
with or without VIR-2218 and PEG-IFNα in patients with chronic HBV infection. 

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3.
OBJECTIVES AND ENDPOINTS
Objectives 
Endpoints 
Primary 
•
To evaluate the efficacy of VIR-3434 and
TDF with or without VIR-2218, or VIR-2218
and PEG-IFNα
•
Proportion of participants achieving
suppression of HBV DNA (< LLOQ) with
HBsAg loss (< 0.05 IU/mL) at the end of
treatmenta
Secondary 
In addition to the Master Protocol, 
•
To assess the effect of VIR-3434 and TDF
with or without VIR-2218, or VIR-2218 and
PEG-IFNα on HBsAg
•
To assess the effect of VIR-3434 and TDF
with or without VIR-2218, or VIR-2218 and
PEG-IFNα on HBV DNA
•
To assess the effect of VIR-3434 and TDF
with or without VIR-2218, or VIR-2218 and
PEG-IFNα on HBeAg and anti-HBe
•
To assess the immunogenicity of VIR-3434
•
To assess the effect of VIR-3434 and TDF
with or without VIR-2218, or VIR-2218 and
PEG-IFNα on ALT levels
In addition to the Master Protocol secondary 
endpoints 1-8, 
9.
Proportion of participants achieving sustained
suppression of HBV DNA (< LLOQ) with
HBsAg loss (< 0.05 IU/mL) after
discontinuation of all treatment
a.
at 24 weeks
b.
at the F48 Follow-Up visit
10. Proportion of participants achieving HBsAg
loss (< 0.05 IU/mL)
a.
at end of treatmenta
b.
at 24 weeks post-end of treatmenta
11. Proportion of participants achieving sustained
suppression of HBV DNA (< LLOQ) after
discontinuation of all treatment
a.
at 24 weeks
b.
at the F48 Follow-Up visit
12. For HBeAg-positive participants: proportion
of participants with HBeAg loss
(undetectable HBeAg) and/or anti-HBe
seroconversion
13. Incidence and titers of ADA (if applicable) to
VIR-3434
14. Mean change in serum HBsAg level from
baseline across timepoints in the study
15. Proportion of participants achieving HBV
DNA (< LLOQ) across timepoints in the
study
16. Proportion of participants achieving ALT
≤ ULN across timepoints in the study

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Objectives 
Endpoints 
Exploratory 
In addition to the Master Protocol objectives, 
•
To assess the effect of VIR-3434 and TDF
with or without VIR-2218, or VIR-2218 and
PEG-IFNα on HBeAg and anti-HBe
•
To evaluate proportion of participants meeting
criteria for nucleos(t)ide reverse transcriptase
inhibitor (NRTI) discontinuation or
retreatment
•
To assess the effect of VIR-3434 and TDF
with or without VIR-2218, or VIR-2218 and
PEG-IFNα on HBV DNA
•
To characterize the pharmacokinetics (PK) of
VIR-3434
•
To characterize the PK of VIR-2218 (for
cohorts with VIR-2218)
•
To assess the immunogenicity of VIR-2218
(for cohorts with VIR-2218)
•
To assess the effect of duration of treatment of
VIR-3434 and TDF with or without VIR-
2218, or VIR-2218 and PEG-IFNα
•
To assess potential virological relapse
In addition to the Master Protocol exploratory 
endpoints 1-6, 
7.
For HBeAg-positive participants: time to
achieve HBeAg loss (undetectable HBeAg)
and/or anti-HBe seroconversion
8.
Proportion of participants meeting criteria for
NRTI discontinuation or retreatment in the
study
9.
HBV DNA levels and change from baseline
across timepoints in the study
10. Nadir and maximum change of HBV DNA
level from baseline in the study
11. VIR-3434 PK parameters
12. VIR-2218 PK parameters (for cohorts with
VIR-2218)
13. Incidence and titers of ADA (if applicable) to
VIR-2218 (for cohorts with VIR-2218)
14. Proportion of participants with virological
relapse (defined as either (1) an increase of ≥
1 log10 HBV DNA IU/mL above nadir for at
least 2 consecutive visits OR (2) quantifiable
HBV DNA of ≥ 1 log10 IU/mL above LLOQ
for at least 2 consecutive visits after being <
LLOQ)
a End of Treatment as defined in SOA 

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4.
STUDY DESIGN
4.1.
Overall Study Design 
The STRIVE sub-protocol should be read and conducted in conjunction with the PREVAIL 
Master Protocol. The Master Protocol provides a study framework: study outline, populations, 
common objectives and endpoints, common inclusion and exclusion criteria, statistical 
methodology, assessments and planned analyses for all sub-protocols. STRIVE is a Phase 2, 
multi-center, open-label study designed to evaluate the safety and efficacy of regimens 
containing VIR-3434, VIR-2218, PEG-IFNα, and NRTI in non-cirrhotic adult participants with 
chronic HBV infection that have not received prior NRTI or PEG-IFNα treatment. The study is 
planned to be conducted at multiple clinical investigative sites globally.  
The STRIVE sub-protocol is intended to evaluate up to 48-week regimens of VIR-3434 and 
NRTI, VIR-3434 and NRTI in combination with VIR-2218, and VIR-3434 and NRTI in 
combination with both VIR-2218 and PEG-IFNα in participants with chronic HBV infection. 
Study populations II and III as defined in the Master Protocol (and table) will be included in this 
sub-protocol. Participants that have not received any prior NRTI treatment will be eligible for 
enrollment into this sub-protocol. 
Master Protocol Population 
HBeAg Status 
HBV DNA Level 
ALT Level 
II 
Positive 
> 2,000 IU/mL
> ULN and ≤ 5x ULN
III 
Negative 
> 2,000 IU/mL
> ULN and ≤ 5x ULN
4.1.1.
Number of Participants 
Up to 90 participants are planned to enroll in this sub-protocol. Cohorts 1a, 2a, and 3a will each 
enroll approximately 10 participants. Cohorts 4a and 5a will each enroll approximately 
15 participants. Additionally, up to 30 floater participants may be added to any cohort in this 
sub-protocol at any time at Sponsor’s discretion. 
4.1.2.
Intervention Groups and Duration 
4.1.2.1. 
Intervention Groups  
There are 5 cohorts planned in this sub-protocol (Table 3). 

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Table 3: 
Intervention Groups 
Cohort 
Study Drug 
Dose 
Route 
Number of 
Doses 
Frequency of Dosing 
1a 
VIR-3434 
300 mg 
SC 
12 
Every 4 weeks 
TDF 
300 mgb 
Oral 
≥ 308c 
Every day 
2a 
VIR-3434 
Up to 300 mga 
SC 
12 
Every 4 weeks 
TDF 
300 mgb 
Oral 
≥ 308c 
Every day 
3a 
VIR-3434 
300 mg 
SC 
4-6d
Every 8-12 weeksd 
TDF 
300 mgb 
Oral 
≥ 252c 
Every day 
4a 
VIR-3434 
300 mg 
SC 
12 
Every 4 weeks 
VIR-2218 
200 mg 
SC 
12 
Every 4 weeks 
TDF 
300 mgb 
Oral 
≥ 308c 
Every day 
5a 
VIR-3434 
300 mg 
SC 
13 
Every 4 weeks 
VIR-2218 
200 mg 
SC 
13 
Every 4 weeks 
PEG-IFNα 
180 mcg 
SC 
48 
Every week 
TDF 
300 mgb 
Oral 
≥ 336c 
Every day 
a The dose of VIR-3434 will be determined before participants are enrolled in the cohort 
b Tenofovir disoproxil fumarate dose (TDF) will be 300 mg as approved by the FDA. Supply outside the United 
States may be Tenofovir disoproxil (TD) 245 mg. 
c The minimum number of doses received by participant. Participants will continue receiving additional doses of 
TDF until they qualify for NRTI discontinuation (Section 4.1.3).  
d The dosing regimen will be finalized before participants are enrolled in the cohort. See Section 4.1.2.2. 
4.1.2.2. 
Cohort Initiation and VIR-3434 Dosing Selection 
Cohorts in this study may be enrolled in parallel. Cohorts may be opened, closed, or discontinued 
at the Sponsor’s discretion.  
Information regarding cohort initiation will be provided in communications to the study sites. 
Initially, Cohorts 1a, 4a and 5a will be opened for enrollment. For cohorts in which a VIR-3434 
range of dose or duration is specified in the protocol in lieu of an exact dose or duration, the 
Sponsor will provide communication to study sites regarding the VIR-3434 dose or duration 
prior to initiation of the cohort based on safety, PK, and efficacy data generated in the ongoing 
clinical studies, VIR-2218-1006 and VIR-3434-1002 (see Section 4.3.1 for dose rationale).  
The dose level for Cohort 2a and the frequency of dosing for Cohort 3a will be decided based on 
the efficacy and safety data obtained from Cohort 1a in the current sub-protocol and other 
VIR-3434 monotherapy cohort(s) in the VIR-2218-1006 study. As more data (eg, PK, efficacy, 
safety) are available from ongoing studies in which VIR-3434 is dosed every 4 weeks, an 
alternative dosing regimen (every 8 week or every 12 weeks) may be explored in Cohort 3a. 

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4.1.2.3. 
Duration 
The total duration in the study for participants will be up to 100 weeks in Cohorts 1a, 2a, and 
Cohort 4a, 92-96 weeks for Cohort 3a, and 104 weeks for Cohort 5a. This includes a Screening 
Period (up to 56 days or 8 weeks), Treatment Period (44 weeks for Cohorts 1a and 2a, 36 or 
40 weeks for Cohort 3a, 44 weeks for Cohort 4a, and 48 weeks for Cohort 5a) and a 
Follow-Up-Period (up to 48 weeks) for all cohorts.  
4.1.2.3.1. Screening Period  
The Screening Period for all participants will be up to 56 days (8 weeks). 
4.1.2.3.2. Treatment Period 
The Treatment Period will be 44 weeks for Cohorts 1a and 2a, 36 or 40 weeks for Cohort 3a, 
44 weeks for Cohort 4a, and 48 weeks for Cohort 5a. 
4.1.2.3.3. Follow-Up Period 
Once participants complete the Treatment Period per their respective cohort, they will enter the 
Follow-Up Period. The maximum duration of the Follow-Up Period is 48 weeks after the last 
dose of the study intervention(s). Participants will discontinue the NRTI at the F1 or F12 visit in 
the Follow-Up Period if they meet the criteria to discontinue NRTI (Section 4.1.3) based on the 
data available. Additional study visits are required for participants that discontinue NRTI in the 
Follow-Up Period as indicated in the SOA (see Table 12). Participants that discontinue NRTI at 
F1 visit will be required to return to the site for additional visits at F2, F6, F10, F28, F32, F40 
and F44. Participants that discontinue NRTI at F12 visit will be required to return to the site for 
additional visits F14, F18, F22, F28, F32, F40 and F44. 
4.1.3.
NRTI Discontinuation 
Participants will discontinue NRTI at F1 or at F12 Follow-Up visits based on data available, if 
they meet all of the following criteria: 
•
HBsAg < LLOQ
•
Suppressed HBV DNA (< LLOQ)
•
Undetectable HBeAg (based on quantitative HBeAg)
•
ALT ≤ 2 times the upper limit of normal (ULN)
Participants that meet the criteria to discontinue NRTI treatment will continue per the Follow-Up 
Period Schedule of Activities (SOA). Participants that meet NRTI discontinuation criteria but are 
not appropriate for NRTI discontinuation due to other reasons, based on the opinion of the 
Investigator, may continue on NRTI treatment following discussion with Sponsor Medical 
Monitor to document the rationale for continuing NRTI. 
Participants that do not qualify for NRTI discontinuation will continue taking the NRTI until the 
end of the Follow-Up Period. Once participant has completed the study, long-term care should be 
determined by the Investigator or primary treating physician based on local clinical guidelines. 

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4.1.4.
NRTI Retreatment 
It is recommended that NRTI therapy be reinitiated in participants during the Follow-Up Period 
if they meet any of the follow criteria:  
•
HBV DNA increase ≥ 2 log10 IU/mL within a 2-week period
•
HBV DNA > 100,000 IU/mL at any Follow-Up Period visit (regardless of other biochemical
parameters or ALT values)
•
Confirmed increase of HBV DNA > 20,000 IU/mL (ie, at 2 consecutive collections,
regardless of other biochemical parameters or ALT values)
−
Note: The repeat HBV DNA test should be performed as soon as possible and no later
than 7 calendar days after the initial result is received. Central laboratory testing is
preferred, but local laboratory results will be accepted if it is not feasible to collect central
laboratory results in time.
•
HBV DNA > 2,000 IU/mL concurrent with any of the following criteria at the same visit:
−
Confirmed total bilirubin > 2x ULN and ALT > ULN
−
Any sign of hepatic decompensation (including, but not limited to, confirmed increase in
prothrombin time [PT] ≥ 2 or international normalized ratio [INR] ≥ 0.5 from baseline,
jaundice, ascites, encephalopathy, etc.)
−
ALT > 10x ULN
−
ALT > 2x ULN persisting for ≥ 12 consecutive weeks
−
ALT > 5x ULN persisting for ≥ 4 consecutive weeks
•
Confirmed HBeAg seroreversion (ie, HBeAg positive after being HBeAg negative at NRTI
discontinuation)
•
Any other clinically significant event(s) warranting initiation of NRTI therapy in the opinion
of the investigator after discussion with Sponsor
Participants who are retreated with NRTI therapy should continue to be followed per the SOA 
for the Follow-Up Period (Table 12) through the Week 48 visit. Participants with HBV DNA 
increase ≥ 2 log10 IU/mL within a 2-week period should:  
•
return to the site for an unscheduled visit to measure HBV DNA levels and liver function
tests as soon as possible after the investigator becoming aware of the HBV DNA increase
•
continue returning weekly until HBV DNA levels stabilize (do not increase ≥ 1 log10 IU/mL
over 4-week period or start decreasing for at least 2 consecutive visits) after which they
should continue per the SOA for the Follow-Up Period
If any unscheduled visits needed as outlined above coincide with an existing visit per the 
Follow-Up Period SOA then the Follow-Up visit assessments should be conducted. 
4.1.5.
Long-Term and Follow-Up Care 
Once a participant has completed the study, long-term care should be determined by the 
Investigator or primary treating physician based on local clinical guidelines. 

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4.2.
Scientific Rationale for Study Design 
4.2.1.
Rationale for VIR-3434 for the Treatment of Chronic HBV Infection 
VIR-3434 offers a novel strategy for the treatment of chronic HBV infection by neutralizing 
HBV viral and subviral particles through the targeting of HBsAg and inhibition of viral entry 
into hepatocytes. Additionally, the Fc region of VIR-3434 is engineered to increase binding 
affinity to the neonatal Fc receptor (FcRn) and promote the Fc-gamma receptor (FcγR) binding 
profile towards the activating receptors. These modifications may prolong serum half-life, 
increase potency, and induce a ‘vaccinal’ effect (the induction of antigen-specific T cell 
responses).  
The normal serum half-life of IgG is approximately 21 days and regulated by a balance of 
FcRn-mediated endocytosis and recycling versus endosomal degradation. The well characterized 
LS modification (M428L and N434S) (Gaudinski 2018; Ko 2014; Zalevsky 2010) was included 
in the Fc region of VIR-3434 to have sustained activity against HBV. The LS modification 
increases IgG1 binding to FcRn only at the acidic pH of the endosomal compartment thereby 
increasing IgG recycling back into circulation. Monoclonal antibodies containing the LS 
mutation have previously been studied in humans (Gaudinski 2018). For example, VRC01LS, a 
mAb against the CD4 binding site of the HIV-1 glycoprotein, was deemed safe and well 
tolerated at doses of 5 to 40 mg/kg IV and 5 mg/kg SC in healthy volunteers. No ADAs were 
detected out to 48 weeks. VIR-3434 is similarly anticipated to have an extended half-life in 
humans, resulting in a prolonged duration of exposure. In vitro data for VIR-3434 suggests that 
the LS mutation is not anticipated to interfere with the additional Fc modifications described 
below.  
The Fc region of VIR-3434 was also engineered to include a modification which modulates 
binding to human FcγRs by enhancing binding to the activating receptors FcγRIIa and FcγRIIIa, 
while diminishing binding to the inhibitory receptor FcγRIIb. This Fc modification is designed to 
enhance ADCP of HBsAg and HBV virions and antigen presentation and, as a result, promote 
the induction of T cell responses (“vaccinal effect”). The impact of similar modifications on 
mAb efficacy have been studied in a FcγR-humanized lymphoma mouse model. In this model, 
anti-CD20 antibodies promoted direct killing of tumor cells via engagement of FcγRIIIa on 
macrophages and monocytes. In addition, anti-CD20-immune complexes induced CD8+ T cell 
responses via FcγRIIa-dependent presentation of tumor antigens by dendritic cells. Overall, 
Fc-engineering of anti-CD20 antibodies to increase FcγRIIa and FcγRIIIa binding (GASDALIE 
mutation) had superior therapeutic activity (DiLillo 2015). Parallel reduction of binding to the 
inhibitory FcγRIIb has the potential to further augment this vaccinal effect (DiLillo 2015). 
Available data regarding the use of HBsAg-directed antibodies in the treatment of patients with 
chronic HBV infection suggest that these molecules have the potential to reduce HBsAg levels 
while maintaining an acceptable safety and tolerability profile. GC1102, a fully human 
anti-HBsAg mAb in development for chronic HBV infection and prevention of recurrent HBV 
following liver transplantation, effectively lowered HBsAg by 2-3 log10 IU/mL and was well 
tolerated in a Phase 1 study in patients with chronic HBV infection, with no evidence of serious 
sequelae such as immune complex disease (Lee 2018). HBV-ABXTL (HepeX-B), a mixture of 
two human anti-HBsAg mAbs, was administered to 27 patients with levels of HBsAg ranging 
from approximately 20 to 85,000 IU/mL. HBV-ABXTL was found to have a favorable safety and 

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tolerability profile at doses up to 80 mg administered weekly for 4 doses, and no signs of 
immune complex disease or hepatotoxicity were reported (Galun 2002). Similarly, no adverse 
events were reported in two studies of chronic HBV patients receiving high doses of HBIG to 
prevent re-infection following liver transplantation (Reed 1973; Tsuge 2016).  
Clinical data from the oncology setting suggests that Fc engineering designed to enhance 
ADCC/ADCP, and antigen presentation may improve efficacy without compromising safety or 
tolerability (Im 2018). Margetuximab is a modified version of trastuzumab that is approved by 
the FDA for the treatment of HER2-positive carcinomas. Margetuximab contains modifications 
designed to enhance ADCC/ADCP and antigen presentation. Margetuximab was well tolerated 
in a first-in-human (FIH) Phase 1 study in patients with HER-2 positive carcinomas. Common 
toxicities were primarily ≤ Grade 2, including no evidence of cardiotoxicity (Bang 2017), which 
has been observed with the non-Fc modified parent mAb, trastuzumab, in late-stage clinical trials 
(Ponde 2016; Riccio 2016).  
Taken together, these data suggest that mAbs that are Fc engineered to prolong serum half-life 
and optimize immune effector cell activity have the potential to improve the efficacy of 
therapeutic mAbs without compromising safety. VIR-3434 is predicted to decrease serum 
HBsAg, inhibit intrahepatic viral spread, eliminate infected hepatocytes, and stimulate 
HBV-specific immune responses. Therefore, VIR-3434 has the potential to achieve a functional 
cure of chronic HBV infection, with or without other agents such as VIR-2218, PEG-IFNα and 
an NRTI (TDF). 
VIR-3434 is being evaluated in VIR-3434-1002 and VIR-2218-1006 studies in participants with 
chronic HBV. Cohorts 1a, 2a and 3a will assess the contribution of VIR-3434 to combination 
therapies and its potential to achieve functional cure in the absence of any other investigational 
agents. To assess patient responses and a potential vaccinal effect from VIR-3434, peripheral 
blood mononuclear cells (PBMCs) will be collected to perform evaluation of host cellular 
immune responses (eg, T cells) against HBV antigens. Cohorts 1a and 2a will evaluate 2 dose 
levels of 12 doses of VIR-3434 given every 4 weeks. Depending on the data observed in the 
currently ongoing VIR-3434-1002 and VIR-2218-1006 studies, Cohort 3a may be initiated to 
study the effect of a different dosing regimen of 4-6 doses of VIR-3434, given every 8 or 
12 weeks. 
4.2.2. 
Rationale for VIR-2218 for the Treatment of Chronic HBV Infection  
The use of siRNA offers a novel strategy for the treatment of chronic HBV infection. siRNAs are 
19-21 base-pair RNA duplexes that exploit the endogenous RNA-interference pathway to enable
sequence-specific RNA cleavage and degradation. One siRNA can have multiple antiviral
effects, including degradation of the pgRNA, thus inhibiting viral replication, and degradation of
all viral messenger RNA (mRNA) transcripts, thereby preventing expression of viral proteins.
Removal of viral antigens thought to be tolerogenic may result in the return of a functional
immune response directed against HBV, either alone or in combination with other therapies.

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By contrast, NRTIs act at a distinct part of the viral life cycle and have a different mechanism of 
action than VIR-2218. NRTIs inhibit the HBV polymerase, blocking the reverse transcription of 
the viral pgRNA to viral DNA and preventing the production of infectious virions. NRTIs, 
however, do not directly impact the production of viral proteins such as HBsAg. Reduction of 
HBsAg-containing noninfectious subviral particles by VIR-2218 is considered an important 
differentiator from current treatments. In this sub-protocol, VIR-2218 will be evaluated in 
combination regimens containing VIR-3434 and NRTI (TDF) in the presence (Cohort 5a) and 
absence (Cohort 4a) of PEG-IFNα. 
4.2.3.
Rationale for VIR-3434 + VIR-2218 + TDF for the Treatment of Chronic HBV 
Infection  
Emerging clinical data suggests that a combination of multiple therapeutic modalities may be 
necessary to achieve functional cure in the majority of chronic HBV patients (Revill 2019; 
Zoulim 2015). The massive secretion of HBsAg in chronic HBV infection is thought to 
contribute to T and B cell dysfunction and to impair the host’s ability to clear or control the virus 
(Bertoletti 2016; Burton 2018; Maini 2016). Therefore, development of functional cure is likely 
to require a reduction or elimination of HBsAg in conjunction with the induction of host 
immunity against the infection.  
When administered individually, VIR-2218 and VIR-3434 are associated with substantial 
reductions in HBsAg in patients with chronic HBV infection (Gane 2021; Yuen 2021). The 
combination of VIR-2218 and VIR-3434 is thus anticipated to result in deep, sustained 
reductions in HBsAg. This is supported by AAV-HBV mouse model of chronic HBV infection, 
in which combination treatment with VIR-2218 and VIR-3434 was associated with marked 
reductions in HBsAg. Additionally, lower HBsAg levels achieved by prior or concomitant 
treatment with VIR-2218 may augment the effect of VIR-3434.  
Reduction in HBsAg may also augment the potential immunologic effects of VIR-3434. The Fc 
modifications of VIR-3434 are designed to enhance ADCP of HBsAg and HBV virions and 
antigen presentation and, as a result, promote the induction of T cell responses. Given the 
putative impact of HBsAg on immune function, these potential effects of VIR-3434 may be 
enhanced in the setting of lower HBsAg, which can be achieved with lead-in and/or concurrent 
treatment with VIR-2218. Longer durations of VIR-3434 dosing may also enhance these effects. 
In the VIR-2218-1006 study, combination regimens of VIR-2218 (up to 3 doses of 200 mg 
administered every 4 weeks) and VIR-3434 (up to 12 doses of up to 75 mg administered weekly) 
have been evaluated in participants with chronic HBV infection who are on NRTIs. No 
significant safety concerns have been identified to date, and the study is ongoing.  
The patient population included in this sub-protocol have a high viral burden and elevated ALT, 
therefore are indicated for treatment with an NRTI. NRTIs such as TDF help reduce viral 
replication and thereby reduce the HBV DNA levels. Therefore, they are included as part of all 
regimens in this sub-protocol in addition to VIR-3434.  

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Because the optimal timing and duration of VIR-3434 and TDF in combination with or without 
VIR-2218 to achieve functional cure is unknown, a response-guided approach will be evaluated 
in this sub-protocol. In Cohort 4a, VIR-3434 and VIR-2218 will be administered every 4 weeks 
starting on Day 1 along with TDF administered daily. TDF will be administered daily starting on 
Day 1 and end when the NRTI discontinuation criteria are met up to Week 12 in the Follow-Up 
Period. 
4.2.4.
Rationale for VIR-3434 + VIR-2218 + PEG-IFNα + TDF for the Treatment of 
Chronic HBV Infection  
In patients with chronic HBV infection, PEG-IFNα 180 μg administered weekly for 48-52 weeks 
generally results in HBsAg loss in approximately ≤ 10% of patients overall (Konerman 2016). 
However, in the subset of patients with baseline HBsAg values less than approximately 
1,000-1,500 IU/mL, the rate of HBsAg loss following receipt of PEG-IFNα with or without an 
NRTI is approximately 20-40% (He 2016; Huang 2017; Lee 2020; Li 2016; Ning 2014; 
Takkenberg 2009). This suggests that a reduction in HBsAg during or prior to PEG-IFNα 
therapy may substantially increase the rate of HBsAg loss. Therefore, it is hypothesized that a 
regimen consisting of VIR-2218 and VIR-3434, both of which are associated with substantial 
reductions in HBsAg, plus PEG-IFNα could increase the rate of functional cure beyond that 
associated with PEG-IFNα monotherapy. 
The combination of VIR-2218 and PEG-IFNα is associated with substantial reductions in 
HBsAg beyond those associated with either agent alone. In participants receiving VIR-2218 
200 mg for 6 doses, the mean HBsAg reduction at Week 24 was 1.89 log10 IU/mL (Section 
2.2.3). In a study of PEG-IFNα add-on therapy, the mean HBsAg reduction at Week 24 was 
0.57 log10 IU/mL (Farag 2019). By contrast, in participants receiving both VIR-2218 and 
PEG-IFNα in Cohort 1f of the VIR-2218-1001 study, the mean HBsAg reduction at Week 24 
was 2.55 log10 IU/mL (Yuen 2021). However, few events of HBsAg loss were observed. It is 
hypothesized that the addition of VIR-3434 may lead to greater reductions in HBsAg, higher 
rates of HBsAg loss, and functional cure.  
In the VIR-2218-1006 study, combination regimens of VIR-2218 (up to 3 doses of 200 mg 
administered every 4 weeks) and VIR-3434 (up to 12 doses of up to 75 mg administered weekly) 
have been evaluated in participants with chronic HBV infection who are on NRTIs. No 
significant safety concerns have been identified to date, and the study is ongoing.  
Furthermore, PEG-IFNα has important effects on the immune system which may augment the 
potential development of HBV-specific immunity following administration of VIR-3434. Type I 
interferons regulate antiviral T cells both directly and indirectly via effects on accessory cells, 
such as antigen presenting cells (Crouse 2015) and infiltrating or liver resident immune cells 
(Dill 2014). Liver resident immune cells such as Kupffer cells play an important role in priming 
robust HBV-specific T cell responses, as recently described (De Simone 2021). These effects 
may further increase the likelihood of inducing a durable T cell response (“vaccinal effect”) 
following VIR-3434-containing combination therapies.  

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Because the optimal timing and duration of VIR-3434 and TDF in combination with or without 
VIR-2218 and PEG-IFNα to achieve functional cure is unknown, a response-guided approach 
will be evaluated in this sub-protocol. In Cohort 5a, VIR-3434 and VIR-2218 will be 
administered every 4 weeks starting on Day 1 along with TDF administered daily and PEG-IFNα 
weekly till Week 48. TDF will be administered daily starting on Day 1 and may end when the 
NRTI discontinuation criteria are met at Week 1 or Week 12 in the Follow-Up Period.  
4.3.
Justification for Dose 
4.3.1.
VIR-3434 Dose Selection 
Available PK, safety, and antiviral activity from the ongoing VIR-3434-1002 and 
VIR-2218-1006 studies were considered for selection of the VIR-3434 dosing regimens. 
VIR-3434 has a half-life (t1/2) of approximately 25 days, with measurable concentrations up to 
24 weeks after a single SC dose of 90-900 mg in healthy volunteers (Gupta 2021). 
Dose-proportional increases in Cmax and AUCinf were observed across the SC dose range 
evaluated. A similar t1/2 was observed following a single IV injection of 3,000 mg. 
Nonparametric superposition was employed to predict the concentration time profile and PK 
exposures following 13 SC doses of VIR-3434 300 mg administered every 4 weeks. As seen in 
Figure 4, the projected Cmax of 50 µg/mL for this regimen would not exceed the observed Cmax of 
a single 3,000 mg IV dose of 1,076 µg/mL. Similarly, the projected AUCinf associated with this 
regimen (5,148 day*µg/mL) does not exceed the observed mean AUCinf of the 3,000 mg IV dose 
(11,842 day*µg/mL). Additionally, due to target-mediated drug disposition, the PK exposure in 
healthy volunteers is anticipated to be an overestimate compared to participants with chronic 
HBV infection, as VIR-3434 is expected to be eliminated more rapidly in the presence of 
HBsAg. 
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Figure 4: 
VIR-3434 Observed and Projected Mean Concentration Profile in Healthy 
Volunteers in the Absence of HBsAg 
Mean concentration of VIR-3434 observed over time in healthy volunteers in VIR-3434-1002 administered single 
dose of VIR-3434 either 300 mg SC (green solid line) or 3,000 mg IV (red solid line). The projected mean 
concentration profile of VIR-3434 following 13 doses of 300 mg SC administered every 4 weeks in the absence of 
HBsAg and assuming a 25-day half-life is depicted in blue.  
Data from VIR-3434-1002 demonstrated that single doses of up to 300 mg VIR-3434 were 
generally well tolerated with no safety concerns in participants with chronic HBV infection. The 
majority of AEs were Grade 1 or 2. There were no study discontinuations due to AEs. In the 
ongoing VIR-2218-1006 study, combination regimens of VIR-3434 are being evaluated in 
participants with chronic HBV infection who are on NRTIs. No significant safety concerns have 
been identified to date for VIR-3434 up to 12 doses of up to 75 mg administered weekly. The 
cumulative exposure following 13 SC doses of VIR-3434 every 4 weeks at 300 mg is not 
anticipated to exceed the maximum exposure associated with a single dose of 3,000 mg 
administered IV in healthy volunteers.  
Based on preliminary antiviral data in the ongoing study VIR-3434-1002, VIR-3434 is 
associated with HBsAg reductions > 1 log10 IU/mL in the majority of study participants 
following a single SC dose of 6 to 300 mg in a dose dependent manner (Agarwal 2021; 
Agarwal 2022). The 300 mg dose level was associated with the largest and most durable HBsAg 
reductions, with mean reductions from baseline of >2 log10 at Week 4 and > 1.5 log10 at Week 8. 
Repeat administration of VIR-3434 may enhance the reduction of HBsAg, increase the 
likelihood of eliciting the potential immunomodulatory effects of its Fc domain modifications, 
and prolong the duration of viral entry inhibition.  
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In summary, the observed PK, HBsAg kinetics, and absence of safety signals in the ongoing 
single dose and multiple dose studies, along with the potential for multiple doses of VIR-3434 to 
further lower HBsAg, support the dose level, frequency, and duration of VIR-3434 regimens 
selected for this sub-protocol. 
4.3.2.
VIR-2218 Dose Selection 
Available safety, tolerability, antiviral activity, and pharmacokinetic data from Parts A-F of 
study VIR-2218-1001 were considered when selecting dose regimens for VIR-2218.  
In Part A of the VIR-2218-1001 study, a single SC dose of VIR-2218 was administered to 
healthy volunteers over the dose range of 50 to 900 mg. In Parts B and C of the study, 2 doses of 
VIR-2218 given 4 weeks apart, ranging from 20 to 200 mg were administered to participants 
with chronic HBV infection. In healthy volunteers, VIR-2218 was absorbed after SC injection 
with a median Tmax of 4-7 hours and was not measurable in plasma beyond 48 hours for any 
participant (Gupta 2021). Available PK data from HBV participants were similar to healthy 
adults. No accumulation of VIR-2218 in plasma was evident following a second dose of 
VIR-2218 administered 4 weeks apart in participants with chronic HBV infection.  
In the current sub-study, regimens containing varying durations up to 13 doses of 200 mg 
VIR-2218 administered every 4 weeks will be evaluated to assess the impact of more sustained 
HBsAg suppression on the outcome of functional cure. The duration of VIR-2218 administration 
in each cohort was selected to ensure suppression of HBsAg by VIR-2218 for the entire duration 
of concomitant administration with VIR-3434 with or without PEG-IFNα.  
The VIR-2218 dose level of 200 mg was selected based on results from Parts B and C of the 
VIR-2218-1001 study. In participants with chronic HBV infection, 2 doses of VIR-2218 
administered 4 weeks apart was associated with dose-dependent reductions in HBsAg across a 
dose range of 20-200 mg (Gane 2021; Lim 2022). The largest reductions in HBsAg were 
observed in the 200 mg cohort.  
The VIR-2218 regimens selected for this study are supported by the safety profile of VIR-2218 
in the ongoing VIR-2218-1001 (Yuen 2021) and VIR-2218-1006 studies. In VIR-2218-1001 
Cohorts 1d, 2d, 1f, and 2f, up to 6 doses of 200 mg VIR-2218 administered every 4 weeks either 
as monotherapy or in combination with PEG-IFNα was well tolerated and associated with deep, 
sustained reductions in HBsAg in patients with chronic HBV infection. In both the 
VIR-2218-1001 and VIR-2218-1006 studies, regimens of up to 13 doses of VIR-2218 200 mg 
administered every 4 weeks in combination with PEG-IFNα and/or VIR-3434 are being 
evaluated.  
In summary, PK, safety, and antiviral activity support the VIR-2218 regimens selected for this 
study. 
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4.3.3.
PEG-IFNα Dose Selection 
PEG-IFNα will be administered via subcutaneous injection at a dose of 180 μg given weekly, the 
FDA-approved dose level and frequency for the treatment of chronic HBV infection. This study 
will evaluate the safety and efficacy of a 48-week regimen of PEG-IFNα in combination with 
VIR-3434 and VIR-2218 in Cohort 5a.  
Based on the emerging data from the VIR-2218-1001 study, the combination of VIR-2218 and 
PEG-IFNα provides substantially greater declines in HBsAg (~0.5 log10 IU/mL greater reduction 
at Week 24) compared to VIR-2218 monotherapy (Yuen 2021). T
. All 
participants who have achieved HBsAg loss during the VIR-2218-1001 study, to date, have 
received the combination including PEG-IFNα, while no patients receiving VIR-2218 
monotherapy have achieved HBsAg loss. Preliminary results from this study are consistent with 
findings from clinical studies in which HBV-targeting siRNA monotherapy has not been 
associated with HBsAg loss or functional cure (Yuen 2021). 
4.3.4.
TDF Dose Selection 
TDF will be administered at a dose of 300 mg (or TD at 245 mg) daily, the FDA-approved dose 
level and frequency for the treatment of chronic HBV infection. The optimal duration of TDF 
treatment is unknown and not reported in the prescribing information 
(VIREAD® Prescribing Information). TDF will be administered daily starting on Day 1 and end 
when the NRTI discontinuation criteria are met in the Follow-Up Period (Section 4.1.3). If 
participants qualify for NRTI discontinuation, they will stop TDF and continue in the Follow-Up 
Period. Additional monitoring visits are required in the Follow-Up Period for participants that 
qualify to discontinue NRTI. 
4.4.
End of Study Definition 
The end of study for this sub-protocol is defined as the date of the last observation of the last 
participant. 
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5.
STUDY POPULATION
Participants that fulfil the following inclusion and exclusion criteria at screening are eligible for 
participation in this sub-protocol. Participants may be re-screened after consultation with the 
Sponsor. C
. To achieve these characteristics, 
screening and/or enrollment may be restricted by the Interactive Response Technology (IRT) at 
any time. 
5.1.
Inclusion Criteria 
Inclusion criteria per Master Protocol, details provided for Sub-protocol A in bold 
1. Age ≥ 18 (or age of legal consent, whichever is older) to < 66 years
2. Chronic HBV infection defined as a positive serum HBsAg, HBV DNA, or HBeAg on
2 occasions at least 6 months apart based on previous or current laboratory
documentation (any combination of these tests performed 6 months apart is acceptable)
In addition, as defined in Table 3 of the Master Protocol for populations II and 
III, the participants must be/have: 
a. HBeAg positive or negative
b. HBV DNA > 2,000 IU/mL
c.
ALT > ULN and ≤ 5x ULN
3.
Besides chronic infection with HBV, must be in good health, determined from medical
history, and no clinically significant findings from physical examination, vital signs,
and laboratory values
4.
Female participants must have a negative pregnancy test or confirmation of
postmenopausal status. Post-menopausal status is defined as 12 months with no menses
without an alternative medical cause (see Section 10.6 for additional details). Women
of child-bearing potential (WOCBP) must have a negative blood pregnancy test at
screening and a negative urine pregnancy test on Day 1, cannot be breast feeding, and
must be willing to use highly effective methods of contraception (Section 10.6) 14 days
before study intervention administration through 48 weeks after the last dose of
VIR-3434, VIR-2218, or PEG-IFNα. Female participants must also agree to refrain
from egg donation and in vitro fertilization from the time of study intervention
administration through 48 weeks after the last dose of VIR-3434, VIR-2218, or
PEG-IFNα.
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5.
Male participants with female partners of child-bearing potential must agree to meet
1 of the following contraception requirements from the time of study intervention
administration through 48 weeks after the last dose of VIR-3434, VIR-2218, or
PEG-IFNα: documentation of vasectomy or azoospermia, or male condom use plus
partner use of 1 of the contraceptive options listed for contraception for WOCBP
(Section 10.6). Male participants must also agree to not donate sperm from the time of
first study intervention administration through 48 weeks after the last dose of
VIR-3434, VIR-2218, or PEG-IFNα.
6.
Able to understand and comply with the study requirements and able to provide written
informed consent
Additional Inclusion Criteria for Sub-Protocol A 
7.
HBsAg > 10 IU/mL
8.
Body Mass Index (BMI) ≥ 18 kg/m2 to ≤ 35 kg/m2
5.2.
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Exclusion Criteria per Master Protocol 
1. History of clinically significant liver disease from non-HBV etiology
2. History or current evidence of hepatic decompensation, including ascites, hepatic
encephalopathy, and/or esophageal or gastric varices
3. History or current suspicion of malignancy diagnosed or treated within 5 years
(localized treatment of squamous or non-invasive basal cell skin cancers is permitted;
cervical carcinoma in situ is allowed if appropriately treated prior to screening);
participants under evaluation for malignancy are not eligible.
4. History of bone marrow or solid organ transplant
5. Known active infection other than chronic HBV infection or any clinically significant
acute condition such as fever (> 38° C) or acute respiratory or GI illness within 7 days
prior to Day 1
6. Co-infection with human immunodeficiency virus (HIV), hepatitis A virus (HAV)
IgM, hepatitis C virus (HCV), hepatitis D virus (HDV) or hepatitis E virus (HEV) IgM.
Participants who are HCV antibody or HDV antibody positive, but have a documented
negative HCV RNA or HDV RNA, respectively, are eligible. Participants with positive
HAV immunoglobulin M (IgM) or HEV IgM but asymptomatic and with a positive
HAV immunoglobulin G (IgG) or HEV IgG are eligible.
7. History or clinical evidence of alcohol or drug abuse within the 12 months before
screening or a positive drug screen at screening unless it can be explained by a
prescribed medication (the diagnosis and prescription must be approved by the
investigator). Note: cannabis use is permitted

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8. Received an investigational agent within 90 days or 5 half-lives (if known), whichever
is longer, before study intervention administration or are active in the follow-up phase
of another clinical study involving interventional treatment. Participants must also
agree not to take part in any other interventional study at any time during their
participation in this study, inclusive of the Follow-Up Period.
9. Any clinically significant medical or psychiatric condition that may interfere with
study intervention, assessment, or compliance with the protocol or otherwise makes the
participant unsuitable for participation in the study, as determined by the investigator.
Additional Exclusion Criteria for Sub-Protocol A 
10. Significant fibrosis or cirrhosis as defined by having either a FibroScan (or sponsor-
approved equivalent) result of > 8.5 kPa at screening or a liver biopsy within 1 year
with METAVIR F3 fibrosis or F4 cirrhosis.
11. History of immune complex disease
12. History of an autoimmune disorder
13. History of HBV-related extrahepatic disease, including but not limited to HBV-related
rash, arthritis, or glomerulonephritis
14. History of allergic reactions, hypersensitivity, or intolerance to monoclonal antibodies,
antibody fragments, or any excipients of VIR-3434
15. Prior NRTI or PEG-IFNα therapy
16. Use of any of the following systemic medications within 14 days before study
intervention administration and throughout the study:
a.
Paracetamol (acetaminophen) ≥ 3 g/day
b. Isoniazid
c. Systemic steroids (prednisone equivalent of > 10 mg/day) or other
immunosuppressive agents (Note: corticosteroid administration for the treatment of
immune-mediated AEs is allowed.)
d. Cohort 5a only: Theophylline
e.
Cohort 5a only: Methadone
17. Receipt of an oligonucleotide (eg, siRNA, antisense oligonucleotide) with activity
against HBV within 48 weeks before study intervention administration
18. Receipt of VIR-3434 within 24 weeks prior to Day 1
19. Participant has the following laboratory parameters at screening by laboratory testing:
a.
Direct bilirubin or INR > 1.5 ULN
b. Total bilirubin > 1.5 times ULN
c.
Platelets < 150,000 cells/L
d. Cohort 5a only: Serum amylase or lipase ≥ 3 times the ULN
e. Cohort 5a only: thyroid stimulating hormone (TSH) and free T4 above the ULN or
below the LLN
f.
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20. Creatinine clearance (CLcr) < 30 mL/min as calculated by the Cockcroft-Gault formula
at screening
21. Cohort 5a only: Known hypersensitivity or contraindication to an interferon product
22. Cohort 5a only: Current or prior history of psychosis, bipolar disorder, schizophrenia,
moderate-severe depression, suicide ideation, attempt, or gesture, or high risk for
suicide
23. Cohort 5a only: Current or prior history of clinically significant retinal disease
24. Cohort 5a only: Current or prior history of chronic uncontrolled hypoglycemia, or
uncontrolled hyperglycemia/diabetes (defined as HbA1c ≥ 8%) at screening
25. Cohort 5a only: Current or prior history of colitis
26. Clinically significant abnormalities on 12-lead ECG at screening (as determined by the
investigator)
5.3.
Lifestyle Considerations 
Lifestyle considerations are not applicable to this sub-protocol. 
5.3.1. 
Meals and Dietary Restrictions  
There are no dietary restrictions in this sub-protocol. 
5.3.2.
Caffeine, Alcohol, and Tobacco 
Participants that regularly consume more than 10 units of alcohol per week (1 unit = 1 glass of 
wine [125 mL] = 1 measure of spirits [30 mL] = one-half pint of beer [284 mL]), or more than 
2 units of alcohol per day are excluded from this sub-protocol. There are no limitations on the 
use of caffeine and tobacco in this sub-protocol.  
5.3.3. 
Activity  
There are no limitations on physical activity in this sub-protocol. 
5.4.
Screen Failures 
Participants that screen fail will not be eligible to enroll in the sub-protocol. Participants may be 
re-screened after discussion with the Sponsor. 

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6.
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY
6.1.
Study Intervention(s) Administered 
Table 4: 
Study Intervention (s) Administered 
Intervention 
Label 
VIR-3434 
VIR-2218 
PEG-IFNα 
TDF /TD 
Intervention 
Name 
VIR-3434 
VIR-2218 
Peginterferon 
alfa-2a 
Tenofovir disoproxil 
fumarate/ Tenofovir 
disoproxil 
Type 
Biologic 
Oligonucleotide Biologic 
Drug 
Dose 
Formulation 
Lyophilized 
powder in vial 
Liquid in vial 
Pre-filled 
syringe 
Tablet 
Unit Dose 
Strength(s) 
300 mg/vial 
200 mg/mL at 
0.5 mL 
180 
mcg/syringe 
300 mg tablet (TDF) 
245 mg tablet (TD) 
Dosage Level(s) 
Up to 300 mg 
Q4W-Q12W 
200 mg Q4W 
180 mcg QW 
300 mg QD (TDF) or 
245 mg QD (TD) based 
on supply source 
Route of 
Administration 
SC 
SC 
SC 
Oral 
Use 
Experimental 
Experimental 
Experimental 
Background 
IMP and 
NIMP/AxMP 
IMP 
IMP 
IMP 
IMP 
Sourcing 
Sponsor 
Sponsor 
Sponsor 
Sponsor 
Packaging and 
Labeling 
Single-use vial 
labeled as 
required by 
country 
requirement. 
Single-use vial 
labeled as 
required by 
country 
requirement. 
Pre-filled 
syringe labeled 
as required per 
country 
requirement. 
Bottle labeled as 
required per country 
requirement. 
Current or trade 
name(s) 
VIR-3434 
VIR-2218 
Pegasys® 
Viread® 

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Table 5: 
Study Arm(s) 
Cohort Title 
Cohort 1a/2a 
Cohort 3a 
Cohort 4a 
Cohort 5a 
Cohort Type 
Experimental 
Experimental 
Experimental 
Experimental 
Cohort 
Description 
Participants will 
receive VIR-3434 
up to 300 mg Q4W 
from Day 1 to 
Week 44 along 
with 300 mg TDF 
(or 245 mg TD) 
QD starting on 
Day 1 until they 
qualify to 
discontinue NRTI 
or end of 
Follow-Up Period, 
whichever is later  
Participants will 
receive VIR-3434 
300 mg Q8W or 
Q12W from Day 1 
to Week 44 along 
with 300 mg TDF 
(or 245 mg TD) 
QD starting on 
Day 1 until they 
qualify to 
discontinue NRTI 
or end of 
Follow-Up Period, 
whichever is later 
Participants will 
receive VIR-3434 
300 mg and 
VIR-2218 200 mg 
Q4W from Day 1 
to Week 44 along 
with 300 mg TDF 
(or 245 mg TD) 
QD starting on 
Day 1 until they 
qualify to 
discontinue NRTI 
or end of 
Follow-Up Period, 
whichever is later 
Participants will 
receive VIR-3434 
300 mg and 
VIR-2218 200 mg 
Q4W from Day 1 
to Week 48, 
PEG-IFNα 
180 mcg QW from 
Day 1 to Week 48 
along with 300 mg 
TDF (or 245 mg 
TD) QD starting 
on Day 1 until they 
qualify to 
discontinue NRTI 
or end of 
Follow-Up Period, 
whichever is later 
Associated 
Intervention 
Labels 
VIR-3434, 
TDF/TD 
VIR-3434, 
TDF/TD 
VIR-3434, 
VIR-2218, 
TDF/TD 
VIR-3434, 
VIR-2218, 
PEG-IFNα, 
TDF/TD 
6.2.
Preparation, Handling, Storage, and Accountability 
Detailed instructions for all study interventions will be provided in the Pharmacy Manual. 
6.3.
Randomization and Blinding 
This is an open-label study. Participants will be enrolled to one of the open cohorts in the 
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6.4.
Study Intervention Compliance 
Participants are expected to comply with the dosing schedule of the investigational therapies. 
TDF and PEG-IFNα may be taken home by the participant to be administered daily and weekly 
respectively per this sub-protocol. Participants will be asked to keep a treatment diary noting the 
day and date they take their study intervention and any adverse events. They will be asked to
bring their treatment diary to each study visit along with all used and unused study intervention 
containers. The investigator is responsible for assessing participant compliance. 
6.5.
Dose Modification 
6.5.1.
Dose Modifications for PEG-IFNα 
Dose modifications of PEG-IFNα in response to PEG-IFNα-related adverse reactions are 
permitted at the discretion of the investigator. It is recommended that PEG-IFNα dose 
modifications be performed in accordance with the PEGASYS® approved local product label. 
Alternative dose modification strategies based on local treatment guidelines or institutional 
standards of care are allowed following approval from the Sponsor Medical Monitor. 
Participants enrolled in Cohort 5a who discontinue PEG-IFNα treatment due to 
PEG-IFNα-related adverse reactions may continue treatment with VIR-3434, TDF, and 
VIR-2218 (unless the stopping rules outlined in Section 7.1 are met). These participants will 
follow the schedule of assessments as provided for their cohort with the exception of PEG-IFNα 
administration.  
6.5.2.
Dose Modifications for TDF 
It is recommended that TDF dose modifications be performed in accordance with the VIREAD® 
approved local product label.  
6.6.
Concomitant Therapy 
6.6.1.
Concomitant Therapy Not Permitted During the Study 
Use of NRTIs before Day 1 is prohibited. While on the study, participants will receive TDF per 
this sub-protocol. No other NRTIs are permitted during this study. 
Use of any of the following systemic medications is prohibited within 14 days before study 
intervention administration and throughout the study: 
•
Systemic steroids (prednisone equivalent of > 10 mg/day) or other immunosuppressive
agents (Note: corticosteroid administration for the treatment of immune-mediated AEs is
allowed.)
•
Paracetamol (acetaminophen) ≥ 3 g/day
•
Isoniazid
•
Cohort 5a only: theophylline
•
Cohort 5a only: methadone

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Additionally, the administration of any potentially hepatotoxic medications during the study 
should be considered only if no therapeutic alternative can be identified and after a careful 
consideration of the potential risks and benefits for the participant. Medications that are 
potentially hepatotoxic or associated with drug-induced liver injury include, but are not limited 
to, the following (Björnsson 2016): 
•
Aspirin > 3 g/day or ibuprofen ≥ 1.2 g/day
•
Tricyclic antidepressants
•
Valproate
•
Phenytoin
•
Amiodarone
•
Anabolic steroids
•
Allopurinol
•
Amoxicillin-clavulanate
•
Minocycline
•
Nitrofurantoin
•
Sulfamethoxazole/trimethoprim
•
Erythromycin
•
Rifampin
•
Azole antifungals
•
Herbal or natural remedies
7.
DISCONTINUATION OF STUDY, STUDY INTERVENTION AND
PARTICIPANT DISCONTINUATION/WITHDRAWAL
7.1.
Study Stopping Rules
If either of the following criteria as met, dosing will be paused, and an ad hoc medical 
monitoring meeting will be convened with the study investigator, or their representative and/or 
LFAC (if related to an ECI): 
•
3 or more participants experience Grade 3 or higher study intervention-related AEs in the
same System Organ Class (SOC)
•
2 or more participants experience Grade 4 or higher study intervention-related AEs in the
same SOC
Following an assessment of all available safety data, the committee will vote to discontinue, 
modify (including discontinuation of one or more cohorts), or continue the study. 

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7.2.
Discontinuation of Study Intervention(s) 
Participants that have received at least 1 dose of VIR-3434, VIR-2218 or PEG-IFNα will not 
receive additional doses of either study intervention if any the following criteria are met:  
•
Any clinical manifestations of hepatic decompensation
•
Grade 3 or higher study intervention-related AE of anaphylaxis, cytokine release syndrome,
or immune complex disease
•
Serum ALT > 10 × ULN
•
Serum ALT or aspartate aminotransferase (AST) > 3 × ULN with any of the following
laboratory results or clinical symptoms:
−
total bilirubin > 2 × ULN or
−
INR > 1.5 × ULN (erroneously elevated INR due to incorrect blood volume collection
should be ruled out) or
−
serum albumin < 3.0g/dL or
−
ascites, hepatic encephalopathy, or liver-related symptoms (eg, severe fatigue, nausea,
vomiting, right upper quadrant pain in the absence of an alternative medical explanation)
The investigator should notify the medical monitor immediately in the event that any of the 
above criteria are met. Upon documented agreement with the investigator and the Sponsor 
Medical Monitor, the participant may be considered to continue receiving study intervention. 
Study intervention may be discontinued in the occurrence of a condition that in the opinion of the 
Investigator significantly jeopardizes the wellbeing and safety of the participant. Investigator 
must promptly inform the Sponsor Medical Monitor if any such condition arises.  
Female participants who become pregnant during the Treatment Period will not receive 
additional doses of study intervention. See Master Protocol for additional details.  
Participants receiving PEG-IFNα may discontinue treatment if they meet the criteria outlined in 
the PEGASYS® approved local product label and in Section 6.5.1. 
Participants who discontinue all study interventions (excluding NRTI) prematurely (eg, due to 
meeting a stopping rule) will undergo assessments for the EOT visit at the time of 
discontinuation. These participants will continue to the Follow-Up Period SOA.  
7.3.
Participant Discontinuation/Withdrawal from the Study 
Refer to Master Protocol. 
7.4.
Replacement of Participants 
Refer to Master Protocol. 
7.5.
Lost to Follow-up 
Refer to Master Protocol. 

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8.
STUDY ASSESSMENTS AND PROCEDURES
Study procedures and their timing are summarized in SOA (Section 10.9). Refer to Master 
Protocol for additional details 
8.1.
Screening Period 
Refer to Master Protocol. 
8.2.
Efficacy Assessments 
 Refer to Master Protocol. 
8.3.
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SOA. 
8.3.1. 
Physical Examinations  
Refer to Master Protocol. In addition to the Master Protocol: 
•
At screening, body weight and height will be measured, and BMI will be calculated.
•
Body weight will also be measured at study visits as indicated in the SOA.
•
A dilated fundoscopic retinal examination must be performed during screening for all
participants in this sub-protocol. The participant may be referred to a specialist for
performance of the retinal exam.
8.3.2. 
Vital Signs  
Refer to Master Protocol. 
8.3.3.
Clinical Safety Laboratory Tests 
Clinical laboratory tests that will be performed in this study are presented in Section 10.2. In the 
event of an unexplained clinically relevant (in the opinion of the investigator) abnormal 
laboratory test occurring after study intervention administration, the test may be repeated and 
followed up at the discretion of the investigator until it has returned to the normal range or 
stabilized, and/or a diagnosis is made to adequately explain the abnormality. 
8.3.4. 
Pregnancy Testing  
Please refer to Master Protocol. 

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8.3.5.
Local Tolerability 
If a local reaction around the injection site occurs, photographs may be obtained. Participants 
should be instructed to monitor for local and systemic ISRs, including signs and symptoms of 
anaphylaxis and instructed to seek emergency medical care, if needed. Oral analgesics may be 
used to manage mild to moderate local pain or tenderness. More extensive or severe symptoms 
(eg, suspected anaphylaxis, cytokine release syndrome, or immune complex disease) should be 
evaluated by the study investigator and treated as deemed appropriate by the investigator and per 
local standards of care. See Section 10.8 for additional details.  
8.4.
Assessment of Viral Parameters, Antiviral Activity, and Resistance 
Surveillance  
In addition to the Master Protocol, assessments of antiviral activity performed after screening 
will include: HBsAg (quantitative), antiHBs (quantitative), HBeAg (qualitative or quantitative as 
specified in the SOA), anti-HBe, and HBV DNA. 
Assessments of exploratory viral markers or other viral analyses may also be performed after 
screening; refer to Master Protocol.  
Resistance surveillance to monitor for the potential development of resistance to NRTI (TDF), 
VIR-3434, or VIR-2218 will be conducted for all participants who receive study intervention. 
HBV genome sequencing will be attempted in participants with HBV DNA rebound as defined 
by HBV DNA ≥ 500 IU/mL. As it will not be known at the time of visit if a participant has 
virologic rebound, samples for resistance surveillance will be collected at all study visits noted in 
the SOA. Samples collected for resistance surveillance may be used to perform additional viral 
analyses, including but not limited to viral sequencing. 
Details regarding the processing and shipping of the samples are provided in the Laboratory 
Manual. 
8.5.
 Time points for assessments are 
provided in the SOA for each applicable cohort. 
8.6.
Exploratory Assessments 
8.6.1.
Exploratory Analysis Samples 
Refer to Master Protocol. 
8.6.2.
Details regarding the processing, shipping, and analysis of these samples are provided in the 
Laboratory Manual. 
8.6.2.1.
Refer to Master Protocol. 
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8.6.2.2.
Refer to Master Protocol. 
8.6.2.3.
Refer to Master Protocol. 
8.6.3.
T
h
PEG-IFNα. Samples will be collected at certain time points per the SOA for a given cohort. 
Details regarding sample processing, shipping, and storage are provided in the Laboratory 
Manual and Vir Immunology Sample Manual (if applicable). 
Based on emerging safety and efficacy data, the Sponsor may restrict enrollment to certain sites 
or cohorts.  
8.7.
Adverse Events (AEs), Serious Adverse Events (SAEs), and Other 
Safety Reporting  
Refer to Master Protocol. 
8.7.1.
Time Period and Frequency for Collecting AE and SAE Information 
Refer to Master Protocol. 
8.7.2.
Follow-up of AEs and SAEs 
Refer to Master Protocol. 
8.7.3.
Regulatory Reporting Requirements for SAEs 
Refer to Master Protocol. 
8.7.4.
Adverse Events of Interest 
Not applicable 
8.7.5.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as AEs or 
SAEs  
Refer to Master Protocol. 
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8.7.6.
Laboratory Event of Clinical Interest 
Laboratory events of clinical interest (ECI) for this study are defined as instances of 
ALT > 5x ULN and > 2x baseline.  
An ECI is considered resolved when ALT returns to ≤ Day 1 baseline value. All ECIs must be 
reported to the Sponsor Medical Monitor within 5 business days of the investigator becoming 
aware of the ECI. In addition, the assessments outlined in Section 10.7 of current sub-protocol 
should be performed as soon as possible and no later than two weeks after the initial ALT value 
meeting criteria for a laboratory ECI.  
8.7.7.
Special Situation Reports 
Refer to Master Protocol. 
8.7.7.1. 
Pregnancy  
Refer to Master Protocol. 
8.8.
Pharmacokinetic Assessments 
Blood samples will be collected to assess concentrations of VIR-3434 and VIR-2218 (for cohorts 
receiving VIR-2218). Timepoints for the collection of samples for VIR-3434 and VIR-2218 PK 
analysis are provided in the SOA. Concentrations of VIR-3434 and VIR-2218 PK will be 
quantified using a validated bioanalytical assay. These assessments are exploratory and may or 
may not be analyzed. Specific assays used for these assessments may be changed at the 
Sponsor’s discretion based on emerging data. Details regarding the processing, shipping, and 
analysis of the samples are provided in the Laboratory Manual. 
8.8.1.
Optional Sub-Study: VIR-3434 PK 
Participants with baseline HBsAg > 3,000 IU/mL may consent to the optional VIR-3434 PK 
sub-study to allow better characterization of VIR-3434 PK. Participants in this sub-study will 
have up to two additional study visits during the treatment period to collect VIR-3434 PK 
samples.  
•
PK sub-study visit 1 will occur 5 to 7 days following either the 3rd, 4th, or 5th dose of
VIR-3434.
•
PK sub-study visit 2 (optional) will occur 5 to 7 days following either the 7th, 8th, or 9th dose
of VIR-3434.
Detailed schedule of sample collection for the optional VIR-3434 PK sub-study is provided in 
Section 10.10. In addition to samples for PK, samples for HBsAg, HBV DNA and liver function 
tests will also be collected at the same visits. Participants enrolled in Cohort 3a are excluded 
from the optional VIR-3434 PK sub-study. All other study-specific PK assessments are specified 
in the SOAs for the respective cohorts and will remain unchanged. Details regarding sample 
processing, shipping, and storage are provided in the Laboratory Manual. 

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8.9.
Immunogenicity Assessments 
Blood samples will be collected for analysis of immunogenic responses to determine 
presence/absence and titers of ADA as applicable, according to the timepoints defined in the 
SOA. Samples may also be characterized for neutralizing potential of anti-VIR-3434 antibody 
(NAb), as appropriate. Details regarding the processing, shipping, and analysis of the samples 
are provided in the Laboratory Manual.  
8.10. 
Electrocardiogram 
12-lead safety ECGs will be recorded and reviewed on-site by the investigator. ECGs will be
obtained using an ECG machine that automatically calculates the heart rate and measures PR,
QRS, QT, and QTc intervals. All ECGs should be measured in the supine position after the
participant has rested comfortably for approximately 10 minutes. ECG should be measured
before blood sample collection and administration of study intervention(s), where applicable.
8.11. 
Liver Elastography (eg, FibroScan) 
To exclude the presence of cirrhosis, participants will have a liver elastography (eg, FibroScan or 
other sponsor-approved method) evaluation. This is not required to be performed if the 
participant has had a liver elastography in the 6 months prior to screening or liver biopsy in the 
year prior to screening that confirmed the absence of Metavir F3 fibrosis or F4 cirrhosis. 
9.
STATISTICAL CONSIDERATIONS
This section provides a summary of the planned statistical analyses. Details of the statistical 
analyses will be provided in the Statistical Analysis Plan (SAP), which will be finalized prior to 
the first interim analysis and database lock. 
Any change to the data analysis methods described in the protocol will require an amendment 
only if it changes a principal feature of the protocol. Any other change to the data analysis 
methods described in the protocol and the justification for making the change will be described 
in the SAP and/or the clinical study report. Additional exploratory analyses of the data will be 
conducted as deemed appropriate. 
9.1.
Statistical Hypotheses 
The null hypothesis is that the response rate, defined as the proportion of participants achieving 
suppression of HBV DNA (< LLOQ) with HBsAg loss (< 0.05 IU/mL) at EOT, is ≤ 2%, which 
is the assumed rate of HBsAg loss in NRTI-suppressed patients. The alternative hypothesis is 
that the response rate is greater than 2%. 
This study is exploratory in nature and no multiplicity adjustment will be made. 
9.2.
Sample Size Determination 
A sample size of 10 or 15 in each cohort will provide > 70% statistical power for each cohort to 
reject the null hypothesis, if the true proportion of participants that achieve HBsAg loss is 25%, 
using a 1-sided exact binomial test with a significance level of 2.5%.  

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Up to 60 participants will be enrolled in this sub-protocol initially. Additionally, up to 30 floater 
participants may be added to the cohorts at any time at Sponsor’s discretion. As described in 
Section 9.5, this addition may be based on the data from interim analysis. No more than 
90 participants will be enrolled.  
9.3.
Analysis Sets 
In addition to the master protocol, the following analysis sets will apply to this sub-protocol: 
Analysis Sets 
Description 
PK Analysis Set 
The PK Analysis Set includes all participants in the Full Analysis Set 
who had at least one measurable post-dose concentration.  
The PK Analysis Set will be used for all PK analyses. 
Immunogenicity Analysis Set 
The Immunogenicity Analysis Set includes all participants in the Full 
Analysis Set who had at least 1 post-dose measurement of 
immunogenicity, including screening, titer, or neutralizing 
characterization, as applicable.  
The Immunogenicity Analysis Set will be used for analyses of the 
immunogenicity endpoints. 
Details of immunogenicity analyses will be provided in the SAP. 
9.4.
Statistical Analyses 
9.4.1.
General Considerations 
Refer to the Master Protocol. 
TEAE definition for this sub-protocol: An AE that is reported with an onset date on or after the 
start of study intervention(s) until end of Follow-Up Period. 
Prior to the final analysis, interim analyses will be conducted, and the analyses may be submitted 
for publication or to regulatory agencies to seek guidance for the overall clinical development 
program. 
9.4.2.
Primary Endpoint Analysis 
The primary efficacy endpoint is the proportion of participants achieving suppression of HBV 
DNA (< LLOQ) with HBsAg loss (< 0.05 IU/mL) at EOT.  
9.4.2.1. 
Target Population  
All eligible participants with chronic HBV infection, as defined in the Full Analysis Set. 
9.4.2.2. 
Population Level Summary 
The proportion of participants achieving suppression of HBV DNA (< LLOQ) with HBsAg loss 
(< 0.05 IU/mL) at EOT and the two-sided 95% exact Clopper-Pearson confidence intervals will 
be calculated for each cohort.  

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9.4.3. 
Secondary Endpoint(s) Analysis  
Refer to the Master Protocol for the safety data analysis. 
The key secondary efficacy endpoints (see Section 3 in this sub-protocol and the Master 
protocol) including the effect of the study intervention on HBsAg, anti-HBs, HBeAg, and HBV 
DNA in the Full Analysis Set will be summarized.  
9.4.4.
Exploratory Endpoint(s) Analysis 
Missing data due to withdrawal or all other events will not be imputed. 
9.4.5.
Missing Data 
Values for missing safety laboratory data will not be imputed. However, a missing baseline result 
(defined as predose Day 1) will be replaced with a screening result, if available.  
If no pre-treatment laboratory value is available, the baseline value will be assumed to be normal 
(ie, no grade [Grade 0]) for the summary of graded laboratory abnormalities. If safety laboratory 
results for a participant are missing for any reason at a time point, the participant will be 
excluded from the calculation of summary statistics for that time point. 
9.4.6. 
Other Safety Analyses  
Refer to the Master Protocol for other safety data analyses. 
9.5.
Interim Analysis 
CCI
CCI

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9.6.
Pharmacokinetics Analyses 
VIR-2218 and VIR-3434 concentration data from all sparse samples may be pooled with data 
from other studies and may be used for estimation of population PK parameters. 
PK/pharmacodynamic analyses will be conducted to explore exposure-response relationships 
between PK parameters and selected antiviral variables. These analyses may include graphical 
plots, tabular summaries, and various linear and/or nonlinear analyses. Details of the analysis 
will be provided in a separate analysis plan. 
9.7.
Immunogenicity Analyses 
For all study parts, immunogenicity data will be listed and summarized using descriptive 
statistics, including incidence, titers, and neutralization data, as applicable. 
Correlations between immunogenicity data and safety, efficacy, and PK data will be explored. 
These analyses may include graphical plots, tabular summaries, and various linear and/or 
nonlinear analyses. Details of immunogenicity analyses will be provided in the SAP. 
CCI

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10.
SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations  
10.1.1.
Regulatory and Ethical Considerations 
Refer to Master Protocol. 
10.1.2.
Financial Disclosure 
Refer to Master Protocol. 
10.1.3.
Informed Consent Process 
Refer to Master Protocol. 
10.1.4.
Data Protection 
Refer to Master Protocol. 
10.1.5.
Confidentiality 
Refer to Master Protocol. 
10.1.6.
Committees Structure 
10.1.6.1.
Liver Flare Adjudication Committee (LFAC) 
The Liver Flare Adjudication Committee will provide hepatic safety oversight by performing 
periodic reviews of data pertaining to participants who meet certain prespecified criteria for 
transaminase elevations (Section 8.7.6). Additionally, the Sponsor may request LFAC evaluation 
of specific patient data at any time. The LFAC will be governed by an LFAC Charter that will be 
finalized prior to screening the first participant. The LFAC membership composition, laboratory 
criteria to trigger patient case evaluation by the LFAC, and data review requirements are 
described in detail in the LFAC Charter. 
10.1.7.
Dissemination of Clinical Study Data 
Refer to Master Protocol. 
10.1.8.
Data Quality Assurance 
Refer to Master Protocol. 
10.1.9.
Source Documents 
Refer to Master Protocol. 
10.1.10.
Electronic Case Report Forms (eCRF) 
Refer to Master Protocol 

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10.1.11. 
Study and Site Start and Closure 
Refer to Master Protocol. 
10.1.12. 
Publication Policy 
Refer to Master Protocol. 

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10.2. 
Appendix 2: Clinical Laboratory Tests  
Table 6: 
Protocol-Required Safety Laboratory Tests  
Chemistry 
Hematology 
Albumin 
Blood urea nitrogen (BUN) 
Calcium 
Bicarbonate 
Chloride 
Creatine kinasea 
Creatinine 
Creatinine clearance (calculated)b 
Gammaglutamyltransferase (GGT) 
Glucose (non-fasting) 
Lactate dehydrogenase (LDH) 
Phosphate 
Potassium 
Sodium 
Liver Function Tests: Alkaline phosphatase 
(ALP), alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), bilirubin (total and 
direct)  
Complement (C3, C4, CH50)c 
Platelet count 
Red blood cell (RBC) count 
Hemoglobin 
Hematocrit 
White blood cell (WBC) count with 
differential: neutrophils, lymphocytes, monocytes, 
eosinophils, basophils 
RBC indices: mean corpuscular volume (MCV), 
mean corpuscular hemoglobin (MCH), 
%reticulocytes 
Coagulation Parameters 
Pregnancy Testing 
International normalized ratio (INR)  
Prothrombin time (PT) 
Highly sensitive (serum/plasma or urine) human 
chorionic gonadotropin (hCG) pregnancy test (as 
needed for women of childbearing potential) 
Urinalysis 
Additional Screening Tests 
Bilirubin 
Glucose 
Ketones 
Leukocytes 
Microscopy (if blood or protein is abnormal) 
Nitrite 
pH 
Proteins 
RBCs 
Specific gravity 
Urobilinogen 
Visual inspection for appearance and color 
Urine drug screen (to include at minimum: 
amphetamines, barbiturates, cocaine, opiates, 
cannabinoids, and benzodiazepines) 
Serology:  
Hepatitis Ad, B, Ce, Df and Ed  
Human immunodeficiency virus I and II 
Lipase 
Amylase 
Follicle stimulating hormone (FSH) g  
Hemoglobin A1c (HbA1c) 
Thyroid stimulating hormone (TSH) h  
Free T4h 
HBV genotyping 
a Only required if ALT and/or AST is elevated > 2x the predose Day 1 baseline value 
b Please note the following clarification for the creatinine clearance calculation: for study visits where weight is not 
measured, creatinine clearance will be calculated using the value measured from the most recent study visit 

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c As indicated in the Schedule of Activities (Section 10.9)  
d Participants with positive HAV IgM or HEV IgM but asymptomatic and with a positive HAV IgG or HEV IgG are 
eligible. 
e Participants with positive HCV screening serology may have HCV RT-PCR performed to determine eligibility. 
f Participants with positive HDV screening serology may have HDV RNA performed to determine eligibility. 
g Required for confirmation of menopause only as applicable 
h Required at Screening. For Cohort 5a, TSH and free T4 are also required on Day 1, Week 12, Week 24, Week 36, 
Week 48, F16 and F48. 

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10.3. 
Appendix 3: AEs, SAEs, SSRs and AEIs: Definitions and Procedures 
for Recording, Evaluating, Follow-up, and Reporting 
Refer to Master Protocol. 

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10.4. 
Appendix 4: List of Abbreviations and Definitions of Terms 
ADA 
anti-drug antibodies 
ADCC/ADCP 
antibody-dependent cellular cytotoxicity/ antibody-dependent cellular 
phagocytosis 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BMI 
body mass index 
BUN 
blood urea nitrogen 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
ECI 
events of clinical interest 
EOT 
end of treatment 
FcγR 
Fc-gamma receptor 
FcRn 
Fc receptor 
FSH 
follicle stimulating hormone 
GGT 
gammaglutamyltransferase 
HBIG 
hepatitis B immune globulin 
HBeAg 
Hepatitis B e antigen 
HBsAg 
Hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HDV 
hepatitis D virus 
HEV 
hepatitis E virus 
HIV 
human immunodeficiency virus 
IB 
Investigator’s Brochure 
IgG 
immunoglobulin G 
IgM 
immunoglobulin M 
INR 
international normalized ratio 
IRR 
infusion related reaction 
IRT 
Interactive Response Technology 
ISR 
injection site reaction 
IV 
intravenous 
CCI

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LDH 
lactate dehydrogenase 
LFAC 
Liver Flare Adjudication Committee 
LLOQ 
lower limit of quantitation 
mAb 
monoclonal antibody 
MCH 
mean corpuscular hemoglobin 
MCV 
mean corpuscular volume 
NAb 
neutralizing antibodies 
NRTI 
nucleos(t)ide reverse transcriptase inhibitors 
NSAID 
non-steroidal anti-inflammatory drug 
PBMC 
peripheral blood mononuclear cells 
PEG-IFNα 
peginterferon-alfa-2a 
PK 
pharmacokinetics 
PT 
prothrombin time 
QD 
once a day 
QW 
every week 
Q4W 
every 4 weeks 
Q8W 
every 8 weeks 
Q12W 
every 12 weeks 
RBC 
red blood cell 
SAP 
Statistical Analysis Plan 
SC 
subcutaneous 
siRNA 
small interfering ribonucleic acid 
SRC 
Safety Review Committee 
SOA 
Schedule of Activities 
TD 
tenofovir disoproxil 
TDF 
tenofovir disoproxil fumarate 
TND 
target not detected 
TSH 
thyroid stimulating hormone 
ULN 
upper limit of normal 
WBC 
white blood cell 
WOCBP 
women of child-bearing potential 

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10.5. 
Appendix 5: Summary of Changes for Previous Protocol Amendment 
Protocol Amendment 2 (11 October 2022) Summary of Changes Table 
Section # and Name 
Description of Change 
Brief Rationale 
1.1. Synopsis 
3. Objectives and Endpoints
9.1. Statistical Hypotheses
9.4.2. Primary Endpoint 
Analysis 
9.4.2.2 Population Level 
Summary 
Modified primary endpoint to include achieving 
hepatitis B virus (HBV) DNA suppression (<lower limit 
of quantitation [LLOQ]) in addition to Hepatitis B 
surface antigen (HBsAg) loss (< 0.05 IU/mL) at the end 
of treatment. 
Added proportion of participants achieving HBsAg loss 
(< 0.05 IU/mL) at the end of treatment to the secondary 
endpoints. 
The prior primary endpoint to evaluate proportion of 
participants achieving HBsAg loss (<0.05 IU/mL) at 
the end of treatment was moved to be secondary 
endpoint and the primary endpoint was modified to 
include HBV DNA suppression (<LLOQ) and 
HBsAg loss (<0.05 IU/mL) at the end of treatment 
for better understanding of the effect of the study 
interventions on both viral parameters and better 
align with the FDA HBV clinical guidance 
(FDA 2022).  
1.1. Synopsis 
1.2. Study Schema 
4.1.2.1. Intervention Groups 
4.1.2.3. Duration 
4.1.2.3.2. Treatment Period 
4.2.4. Rationale for VIR-3434 
+ VIR-2218 + PEG-IFNα +
TDF for the Treatment of
Chronic HBV Infection
6.1. Study Arm
9.4.1. General Considerations 
10.9. Appendix 9: Schedule 
of Activities 
Removed option for Cohorts 4a and 5a participants to 
discontinue study intervention (except nucleos(t)ide 
reverse transcriptase inhibitors [NRTI]) after Week 20 if 
they are Hepatitis B e antigen (HBeAg) negative, have 
undetectable HBsAg and HBV DNA < LLOQ at 2 
consecutive visits.  
As a result of this change, dosing of study intervention 
and duration of treatment was updated for Cohorts 4a 
and 5a. In addition, in Section 3 (Objectives and 
Endpoints), the exploratory endpoint assessing the 
proportion of participants with HBsAg loss maintained 
24 weeks post-end of treatment (EOT) of Week 20 (for 
Cohorts 4a and 5a only) was removed.  
Removal of the option to discontinue treatment 
early would allow for all participants within the 
cohort to receive the same duration of treatment and 
thereby allow consistency in analyses evaluating of 
the regimen.  
2.3.1. Risk Assessment 
Updated immunogenicity risks for VIR-2218 and 
VIR-3434. 
Additional edits were made to terminology and 
definitions to align with the most recent VIR-2218 and 
VIR-3434 Investigator’s Brochures (IBs). 
To provide updated risk assessment information for 
VIR-2218 and VIR-3434 per the most recent IBs.  

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Section # and Name 
Description of Change 
Brief Rationale 
4.1.2.3.3. Follow-Up Period 
4.3.4 TDF Dose Selection 
10.9. Appendix 9: Schedule 
of Activities  
Added additional visits in the Follow-up Period at 
Weeks 28, 32, 40, and 44 for participants who 
discontinue NRTI. 
Additional safety monitoring visits were included 
for participants that discontinue NRTI to ensure 
close monitoring of participants off all treatment. 
4.1.4. NRTI Retreatment 
Added the following to the NRTI retreatment criteria for 
participants in the Follow-Up Period: 
HBV DNA > 100,000 IU/mL at any Follow-Up Period 
visit (regardless of other biochemical parameters or 
alanine aminotransferase (ALT) values) 
Confirmed increase of HBV DNA > 20,000 IU/mL (ie, 
at 2 consecutive collections, regardless of other 
biochemical parameters or ALT values) 
Confirmed HBeAg seroreversion (ie, HBeAg positive 
after being HBeAg negative at NRTI discontinuation) 
Additional criteria were added to ensure prompt 
identification of participants that may be at a risk for 
safety complications. Recommendations for 
retreatment with NRTI and additional safety 
monitoring for these participants are outlined in 
Section 4.1.4. 
4.1.5. Long-Term and 
Follow-Up Care 
Added guidance that long-term care should be 
determined by the Investigator or primary treating 
physician based on local clinical guidelines once a 
participant has completed the study. 
Added to provide clarity on long-term care for 
participants after the end of study. 
5.2. Exclusion Criteria 
8.11. Liver Elastography 
(new section)  
10.9. Appendix 9: Schedule 
of Activities 
Clarified that, in addition to FibroScan, liver 
elastography can be assessed with other sponsor-
approved methods.  
Some study sites may not have access to FibroScan 
to measure liver elastography. Sponsor may approve 
alternate methods to determine fibrosis in these 
cases.  
5.2 Exclusion Criteria 
To Exclusion Criterion (EC) #19 added the following 
laboratory parameters: 
•
Total bilirubin > 1.5 times ULN
•
Platelets < 150,000 cells/µL (and removed previous
platelet exclusionary threshold of < 90,000
cells/mm3 for Cohort 5a)
Added total bilirubin and platelet count limits in 
exclusion criteria for clarity. 

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Section # and Name 
Description of Change 
Brief Rationale 
5.2. Exclusion Criteria 
 8.10. Electrocardiogram 
10.9. Appendix 9: Schedule 
of Activities 
Added EC #26: Clinically significant abnormalities on 
12-lead electrocardiogram (ECG) at screening (as
determined by the investigator).
In addition to at screening, added 12-lead safety ECGs 
assessments at Day 8 of the Treatment Period and 
Follow-up Period. 
Screening and post-dose safety ECG assessments 
have been added to assess cardiac safety. 
7.1. Study Stopping Rules 
Added study stopping rules. 
Criteria were added to trigger an ad hoc medical 
monitoring meeting in which a recommendation to 
discontinue, modify, or continue the study will be 
made. 
8.3.1. Physical Examinations 
10.9. Appendix 9: Schedule 
of Activities 
In addition to at screening, body weight measurements 
were also added at study visits as indicated in the 
Schedule of Activities.  
Body weight is required to calculate creatinine 
clearance. 
8.8.1. Optional Sub-Study: 
VIR-3434 PK 
10.10. Appendix 10: 
Schedule of Sample 
Collection for Optional 
VIR-3434 PK Sub-study 
Added optional VIR-3434 pharmacokinetic (PK) 
sub-study. 
To enable characterization of VIR-3434 PK in 
subjects with high levels of HBsAg at baseline. 
9.3. Analysis Sets 
Modified PK Analysis Set to include all participants in 
the Full Analysis Set (previously All Enrolled Set) who 
had at least one measurable postdose concentration. 
Modified Immunogenicity Analysis Set to include all 
participants in the Full Analysis Set (previously Safety 
Analysis Set) who had at least one postdose 
measurement of immunogenicity.  
To align with the updated definition of the Full 
Analysis Set in the master protocol. The Full 
Analysis Set includes all participants who received 
at least one dose of study intervention(s) 
irrespective of post-dose assessments. 
9.6. Pharmacokinetic 
Analyses 
Clarified that VIR-2218 and VIR-3434 concentration 
data from all sparse PK samples may be pooled with 
data from future studies and may be used for estimation 
of population PK parameters 
To provide updated PK analyses plan 

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Section # and Name 
Description of Change 
Brief Rationale 
10.6. Appendix 6: 
Contraceptive and Barrier 
Guidance 
Clarified that an elevated follicle stimulating hormone 
(FSH) in the post-menopausal range should be used to 
confirm a post-menopausal state in women not using 
hormonal contraception or hormone replacement 
therapy. 
To correct FSH criteria used to confirm a post-
menopausal state. 
Entire document 
Other administrative, formatting, and other minor 
changes 
These changes were made to clarify, ensure 
consistency, provide up-to-date information, or 
rectify typographical errors.  
 
Protocol Amendment 1 (16 May 2022) Summary of Changes Table 
Section # and Name 
Description of Change 
Brief Rationale 
Study Title 
Modified study title to “A Phase 2 Study Evaluating the 
Efficacy and Safety of VIR-3434 and/or VIR-2218 
Containing Regimens in Participants with Chronic 
Hepatitis B Infection (STRIVE)” 
Study title was modified to be concise 
1.1 Synopsis 
3. Objectives, endpoints 
and estimands 
9.4.2 Primary Endpoint 
Analysis 
Moved one co-primary endpoint (Proportion of participants 
with HBsAg loss at 24 weeks post-end of treatment) to be a 
secondary endpoint, making “Proportion of participants 
with HBsAg loss (< 0.05 IU/mL) at the end of treatment” 
the only primary endpoint 
This modification was made to focus the primary 
endpoint of the study to evaluate the proportion of 
participants that achieve HBsAg loss on-treatment. 
The sustained HBsAg loss and any additional off-
treatment HBsAg loss will be evaluated as 
secondary endpoints in this study. 
1.1 Synopsis 
3. Objectives, endpoints 
and estimands 
Added secondary endpoints #10 and 11 and modified #16 
# 10 Proportion of participants achieving sustained 
suppression of HBV DNA (< LLOQ) after discontinuation 
of all treatment 
at 24 weeks  
at the F48 Follow-Up visit  
Endpoints 10, and 11 were added/modified to 
conform with the FDA HBV clinical guidance 
(FDA 2022). Endpoint 16 was added for better 
understanding of the change in HBsAg levels 
through the study. (FDA 2022) 

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#11 Proportion of participants achieving sustained 
suppression of HBV DNA (< LLOQ) with HBsAg loss (< 
0.05 IU/mL) after discontinuation of all treatment 
at 24 weeks 
at the F48 Follow-Up visit  
#16 Mean change in serum HBsAg level from baseline 
across timepoints in the study 
1.1 Synopsis 
3. Objectives, endpoints 
and estimands 
Moved these secondary endpoints and the respective 
objectives to exploratory endpoints 
• 
For HBeAg-positive participants: time to achieve 
HBeAg loss (undetectable HBeAg) and/or anti-HBe 
seroconversion  
• 
Proportion of participants meeting criteria for NRTI 
discontinuation or retreatment in the study 
• 
HBV DNA levels and change from baseline across 
timepoints in the study  
• 
Nadir and maximum change of HBV DNA levels from 
baseline in the study 
These endpoints will provide additional 
understanding of the timing of HBeAg loss and 
seroconversion for HBeAg positive patients, the 
changes in the HBV DNA and participants that do 
qualify for NRTI discontinuation or retreatment. 
Therefore, they were better suited as exploratory 
endpoints 
1.1 Synopsis 
3. Objectives, endpoints 
and estimands 
Added exploratory objective and corresponding endpoint 
#11 Proportion of participants with virological relapse 
(defined either as (1) an increase of ≥ 1 log10 HBV DNA 
IU/mL above nadir for at least 2 consecutive visits OR (2) 
quantifiable HBV DNA of ≥ 1 log10 IU/mL above LLOQ 
for at least 2 consecutive visits after being < LLOQ) 
This endpoint was added to conform to the FDA 
HBV clinical guidance to evaluate any virological 
relapse. This will distinguish virological relapse 
from transient increases in HBV DNA that are 
possible after discontinuing NRTI (FDA 2022) 
1.1 Synopsis 
3. Objectives, endpoints 
and estimands 
Other minor clarifications to primary and secondary 
endpoints: 
Defining HBsAg loss as < 0.05 IU/mL 
Modifying TND or undetectable HBV DNA across 
different secondary endpoints as < LLOQ 
These changes were made to provide clarifications 
to the level of viral marker referenced. The HBV 
DNA level was modified from being TND (target 
not detected) to < LLOQ to conform to the FDA 
HBV clinical guidance (FDA 2022) 

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4.1.2.3.2 Treatment Period 
Criteria to stop study interventions at W20 for Cohorts 4a 
and 5a were modified to include HBV DNA < LLOQ in 
addition to undetectable HBeAg and HBsAg 
This criterion was added to ensure that participants 
that stop study interventions have achieved HBV 
DNA suppression and thereby increasing the 
probability of long-term sustained suppression off-
treatment. 
4.1.3 NRTI 
discontinuation 
NRTI discontinuation criterion for HBsAg level was 
modified from < 10 IU/mL to < 100 IU/mL with ≥ 1 log10 
IU/mL reduction from baseline  
There is limited correlation between the sustained 
suppression of HBV DNA and HBsAg loss (< 0.05 
IU/mL). The modified criteria will allow inclusion 
of participants that have achieved HBV DNA 
suppression with ≥ 1 log10 decline in HBsAg from 
baseline and an absolute HBsAg level lower than 
100 IU/mL to be evaluated for sustained 
suppression of HBV DNA. Furthermore, we expect 
a proportion of these participants could achieve 
HBsAg loss during the Follow-Up Period after 
discontinuation of all treatments 
4.1.3 NRTI 
discontinuation 
Timing of NRTI discontinuation was clarified to be either 
at F1 visit based on data available or at F12 visit based on 
data available  
These timings were clarified to ensure that 
participants have adequate monitoring based on 
visits per the Follow-Up Period SOA 
4.1.4 NRTI retreatment 
Added criteria to consider restarting NRTI if participants 
have HBV DNA ≥ 2 log10 IU/mL within a 2-week period or 
any other clinically significant event(s) warranting 
initiation of NRTI therapy in the opinion of the 
investigator. 
In addition, additional monitoring requirements for 
participants that discontinue NRTI and experience an 
increase in HBV DNA plus weekly monitoring of 
participants that experience HBV DNA ≥ 2 log10 IU/mL 
within a 2-week period has been added 
Added to ensure participant safety in case of a 
virological relapse after discontinuation of all study 
treatments.  
5.2 Exclusion criteria 
Added sub-criterion #27, d. Cohort 5a only: Platelets < 
90,000 cells/mm3, absolute neutrophil count (ANC) < 1,500 
cells/mm3 
Added to comply with Pegasys® Prescribing 
Information 

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9.3 Analysis Sets 
Clarified that the PK and immunogenicity analysis sets will 
include all participants from the Safety Analysis Set who 
received at least one dose of study drug and had at least 
one measurable post-dose concentration or at least one 
post-dose immunogenicity measurement respectively.  
Modified to provide clarity 
Table 12 Schedule of 
Activities: Follow-Up 
Period for all cohorts 
Addition of Follow-Up visits for participants that 
discontinue NRTI: 
If discontinuing at F1 visit then additional visits at F2, F6 
and F10  
If discontinuing NRTI at F12 visit then additional visits 
include F14, F18 and F22 
These visits were added to ensure additional 
periodic monitoring of participants after 
discontinuation of all treatments including NRTI 
Entire document 
Other administrative, formatting, and other minor changes 
These changes were made to clarify, ensure 
consistency, or rectify typographical errors. 

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10.6. 
Appendix 6: Contraceptive and Barrier Guidance 
WOCBP may be included in this study and include any female participant who has experienced 
menarche and who is not post-menopausal or permanently sterilized (eg, bilateral tubal 
occlusion, hysterectomy, bilateral oophorectomy, or bilateral salpingectomy). 
WOCBP must be willing to use highly effective methods of contraception from 14 days before 
the first dose of study intervention to 48 weeks after the final dose of VIR-3434, VIR-2218, 
PEG-IFNα. After the end of study, use of TDF in WOCBP should be determined per the 
VIREAD® approved local product label. 
Highly effective methods of birth control are defined as those that result in a low failure rate 
(ie, less than 1% per year). Birth control methods which are considered highly effective include: 
•
Established use of combined (estrogen and progestogen containing) oral, intravaginal, or
transdermal hormonal methods of contraception associated with inhibition of ovulation OR
established use of progestogen-only oral, injectable, or implantable hormonal methods of
contraception associated with inhibition of ovulation. It is not currently known whether
VIR-2218 or VIR-3434 will impact the effectiveness of hormonal contraceptive methods;
therefore, it is recommended to use an additional form of contraception (ie, barrier method)
for 48 weeks after the last administration of VIR-3434, VIR-2218, or PEG-IFNα. After the
end of study, use of TDF in WOCBP should be determined per the VIREAD® approved
local product label.
•
Placement of an intrauterine device
•
Placement of an intrauterine hormone-releasing system
•
Surgical sterilization of male partner (with the appropriate documentation of vasectomy or
the absence of sperm in the ejaculate; for female participants on the study, the vasectomized
male partner should be the sole partner for that participant)
•
True sexual abstinence from heterosexual contact, when in line with the preferred and usual
lifestyle of the participant. Periodic abstinence (eg, calendar, ovulation, symptothermal, post
ovulation methods) and withdrawal are not acceptable methods of contraception. Abstinent
participants must agree to use 1 of the above-mentioned contraceptive methods for 48 weeks
after study intervention administration if they start heterosexual relationships during the
study.
•
Barrier method in combination with hormonal contraceptive, as described above
Post-menopausal status is defined as 12 months with no menses without an alternative medical 
cause. An elevated follicle stimulating hormone (FSH) level in the post-menopausal range 
should be used to confirm a post-menopausal state in women not using hormonal contraception 
or hormone replacement therapy (HRT). In the absence of 12 months of amenorrhea, 
confirmation with more than one FSH measurement is required. 
Females on HRT and whose menopausal status is in doubt must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 

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Female participants must also agree to refrain from egg donation and in vitro fertilization from 
the time of study intervention administration through 48 weeks after the last dose of VIR-3434, 
VIR-2218, or PEG-IFNα. After the end of study, use of TDF in WOCBP should be determined 
per the VIREAD® approved local product label. 
Male participants with female partners of child-bearing potential must agree to meet 1 of the 
following contraception requirements from the time of study intervention administration until 
48 weeks after the last administration of VIR-3434, VIR-2218, or PEG-IFNα. After the end of 
study, use of TDF in males with female partners of child-bearing potential should be determined 
per the VIREAD® approved local product label. 
•
Documentation of azoospermia or vasectomy
•
Male condom plus partner use of 1 of the contraceptive options listed above for contraception
for WOCBP (hormonal contraceptive, intrauterine device)
Male participants must also agree not to donate sperm from the first dose of study intervention 
through 48 weeks after the last dose of VIR-3434, VIR-2218, or PEG-IFNα. After the end of 
study, use of TDF in males donating sperm should be determined per the VIREAD® approved 
local product label. 

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10.7. 
Appendix 7: Additional Assessments in Participants That Experience 
ALT Elevation Meeting ECI Criteria 
Additional assessments will be performed in participants who experience ALT elevations 
meeting ECI criteria as outlined in Section 8.7.6. Following the occurrence of elevated ALT 
meeting ECI criteria per central laboratory, the assessments in Table 7 will be performed as soon 
as possible and no later than 2 weeks after the initial ALT value meeting criteria for a laboratory 
ECI.  
The full panel of assessments should only be performed once per ECI occurrence. An ECI 
occurrence is considered resolved when ALT returns to ≤ Day 1 baseline value. Individual 
assessments may be repeated per investigator discretion, as needed.  
Participants who meet ECI criteria will continue to receive study intervention unless criteria for 
study intervention discontinuation are met. Criteria for individual participation discontinuation 
from further dosing are described in Section 7.1. 
Table 7: 
Assessments in Participants That Experience ALT Elevation Meeting ECI 
Criteria  
Chemistry 
Hematology 
Albumin 
Blood urea nitrogen (BUN) 
Calcium 
Bicarbonate 
Chloride 
Calcium 
Creatine kinase 
Creatinine 
Creatinine clearance (calculated) 
Gammaglutamyltransferase (GGT) 
Glucose  
Lactate dehydrogenase (LDH) 
Phosphate 
Potassium 
Sodium 
Uric acid 
Lipase 
Liver Function Tests: Alkaline phosphatase 
(ALP), alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), bilirubin (total and 
direct) 
Platelet count 
Red blood cell (RBC) count 
Hemoglobin 
Hematocrit 
White blood cell (WBC) count with 
differential: neutrophils, lymphocytes, monocytes, 
eosinophils, basophils 
RBC indices: mean corpuscular volume (MCV), 
mean corpuscular hemoglobin (MCH), 
%reticulocytes 
Coagulation Parameters 
Exploratory testing 
International normalized ratio (INR) 
Prothrombin time (PT) 
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Extended Hepatic Panel 
Imaging 
Quantitative HBsAg 
HBV DNA 
Quantitative HBeAg 
HAV antibody IGM 
HCV antibody  
HCV RNA PCR (qualitative and quantitative) 
HDV antibody or RNA 
HEV antibody IgM 
Epstein-Barr Virus antibodies (IgM and IgG) 
Cytomegalovirus antibodies (IgM and IgG) 
Varicella Zoster Virus antibodies IgG 
HSV-I and II IgG 
IgG 
Phosphatidylethanol 
Aldolase 
Anti-nuclear antibodies 
Anti-Smooth muscle antibodies 
Anti-LKM1 antibody 
Anti-mitochondrial antibodies 
Anti-SLA antibodies 
Ferritin 
Ceruloplasmin 
IgM 
Urinary ethylglucuronide 
Acetaminophen  
Abdominal ultrasound, including doppler flow if 
available (CT or MRI is acceptable in place of 
ultrasound if clinically indicated) 
Focused Medical History 
Use of any potentially hepatotoxic concomitant 
medications, including over the counter 
medications and herbal remedies 
Exposure to other potentially hepatotoxic agents 
including any work-related exposures (eg, 
solvents, pesticides, etc.) 
Alcohol consumption and drugs of abuse 
Travel History 
Exercise History 

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10.8. 
Appendix 8: Anaphylaxis, Cytokine Release Syndrome, And Immune 
Complex Disease Supportive Measures 
The following equipment or agents may be needed in the event of a suspected anaphylactic 
reaction or cytokine release syndrome: 
•
ECG monitor
•
Blood pressure monitor
•
Oxygen saturation monitor
•
Thermometer
•
Tourniquet
•
Oxygen
•
Mechanical ventilator
•
Renal replacement therapy
•
IV infusion solutions, tubing, catheters, and tape
•
Fresh-frozen plasma and/or cryoprecipitate
•
Epinephrine
•
Antihistamines, such as diphenhydramine
•
Corticosteroids, such as hydrocortisone, prednisolone, and methylprednisolone
The following are procedures that may be followed in the event of a suspected anaphylactic 
reaction or cytokine release syndrome: 
•
Maintain an adequate airway
•
Stop study intervention injection (if reaction occurs during injection)
•
Call for additional medical assistance
•
Apply a tourniquet proximal to the injection site to slow systemic absorption of study
intervention (if reaction occurs during injection). Do not obstruct arterial flow in the limb.
•
Ensure appropriate monitoring is in place, such as continuous ECG and pulse oximetry
monitoring
•
Administer epinephrine, antihistamines, corticosteroids or other medications/products as
necessary based on the status of the participant and as directed by the physician
•
Draw local laboratory samples as appropriate, possibly including evaluation of cytokines
•
The following equipment or agents may be needed in the event of suspected immune
complex disease
•
Thermometer
•
Analgesic and antipyretic agents, such as non-steroidal anti-inflammatory drugs (NSAIDs)

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•
Antihistamines, such as diphenhydramine
•
Corticosteroids, such as prednisone and methylprednisolone
•
In extreme cases, equipment for plasmapheresis may be needed
The following are procedures that may be followed in the event of suspected immune complex 
disease: 
•
Though unlikely to occur acutely, stop study intervention injection (if reaction occurs during
injection)
•
Ensure temperature is appropriately monitored
•
Monitor for most common manifestations, including rheumatic (arthralgias) and
dermatologic (pruritic rash) findings
•
Administer NSAIDs, antihistamines, corticosteroids, or other medications/products as
necessary based on the status of the participant and as directed by the physician
•
Draw local laboratory samples as appropriate, possibly including complete blood count,
erythrocyte sedimentation rate, C-reactive protein, urinalysis, serum chemistry, and
evaluation of complement
•
In extreme cases, plasmapheresis may be employed

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10.9. 
Appendix 9: Schedule of Activities 
Assessments in bold are in addition to those listed in the PREVAIL Master protocol. 
Table 8: 
Schedule of Activities: Cohort 1a/2a (PBMC- Qualified Sites Only) 
Study Stage 
Screen-
ing 
Treatment Perioda
Visit Week 
W1 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32 
W36 
W40 
W44/ 
EOTb 
Visit Day ± Visit Window 
D -56 
to -1 
D1 D8±2 D29±2 
D57±2 
D85±2 D113±2 D141±2 D169±2 D197±2 D225±2 D253±2 D281±2 D309±2 
Study Procedures 
Informed consent 
X 
Inclusion/exclusion criteria 
X 
Xc
Demography 
X 
Physical examination d 
X 
X 
Body weight 
X 
Medical history 
X 
Vital signse
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse event review/recordf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Liver elastography (eg, 
Fibroscan) g
X 
12-lead safety ECGh
X 
X 
ECI surveillance i 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VIR-3434 local tolerability j 
X 

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Study Stage 
Screen-
ing 
Treatment Perioda
Visit Week 
W1 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32 
W36 
W40 
W44/ 
EOTb 
Visit Day ± Visit Window 
D -56 
to -1 
D1 D8±2 D29±2 
D57±2 
D85±2 D113±2 D141±2 D169±2 D197±2 D225±2 D253±2 D281±2 D309±2 
Drug Administration 
VIR-3434 administration k 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
TDF administration (QD) l 
X 
Treatment Diary 
X 
Laboratory Assessmentsn 
Pregnancy testo
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Screening viral serologyp 
X 
Liver function testsq 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum chemistryq 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematologyq 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation parameters q 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysisqr
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine for drugs of abuse s 
X 
HBsAg quantitative 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Anti-HBs qualitative 
X 
Anti-HBs quantitative 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HBeAg qualitative 
X 
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Study Stage 
Screen-
ing 
Treatment Perioda
Visit Week 
W1 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32 
W36 
W40 
W44/ 
EOTb 
Visit Day ± Visit Window 
D -56 
to -1 
D1 D8±2 D29±2 
D57±2 
D85±2 D113±2 D141±2 D169±2 D197±2 D225±2 D253±2 D281±2 D309±2 
HBeAg quantitative 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Anti-HBe qualitative 
X 
HBV DNA quantification 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HBV genotyping 
X 
Complement testing r 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VIR-3434 PKt 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VIR-3434 immunogenicityu 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Exploratory Assessments 
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Study Stage 
Screen-
ing 
Treatment Perioda
Visit Week 
W1 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32 
W36 
W40 
W44/ 
EOTb 
Visit Day ± Visit Window 
D -56 
to -1 
D1 D8±2 D29±2 
D57±2 
D85±2 D113±2 D141±2 D169±2 D197±2 D225±2 D253±2 D281±2 D309±2 
D = day; EOT = end of treatment; W = week  
a On days in which study intervention is administered, assessments performed predose unless otherwise specified. 
b If a participant discontinues treatment or withdraws prematurely from the study prior to the Week 44 visit, EOT assessments should be performed. 
c Prior to study intervention administration on Day 1, participant eligibility will be confirmed. 
d See Section 8.3.1 for assessments to be performed during a full physical examination. A dilated fundoscopic retinal examination must be performed during 
Screening. The participant may be referred to a specialist for performance of the retinal exam. 
e Vital signs (blood pressure, pulse rate, respiratory rate, and temperature) should be measured after the participant has rested comfortably for approximately 10 
minutes. 
f After signing of the informed consent form (ICF), but prior to initiation of study intervention, AEs/SAEs related to protocol-mandated procedures will be 
reported. Following initiation of study intervention, all AEs/SAEs, regardless of cause or relationship, will be recorded for the entire duration of the study. 
Further details can be found in Section 8.7.  
g Does not need to be performed if the participant has had a liver elastography (eg, FibroScan or other sponsor-approved method) in the 6 months prior to 
screening or liver biopsy in the year prior to screening that confirmed the absence of Metavir F3 fibrosis or F4 cirrhosis. 
h 12-lead safety ECG will be recorded and should be measured in the supine position after the participant has rested comfortably for approximately 10 minutes. 
Further details can be found in Section 8.10.  
i Participants will be monitored for ECI, and additional assessments may be performed if indicated. Section 8.7.6 and Section 10.7 for more information. 
j On Day 1, local tolerability should be assessed approximately 1 hour after VIR-3434 administration. At the discretion of the investigator, unscheduled visits are 
permitted as needed for follow-up of any unresolved local tolerability symptoms. Local tolerability symptoms occurring at other visits should be reported as 
AEs. 
k VIR-3434 will be administered via SC injection every 4 weeks. Participants will be monitored for at least 1 hour after VIR-3434 administration. 
l TDF will be administered orally every day until the criteria in Section 4.1.3 are met.
.
n Screening laboratory tests may be repeated (eg, for values thought to be erroneous) with Sponsor approval.
o WOCBP are required to have pregnancy tests. A blood pregnancy test will be performed at screening, and a urine pregnancy test will be performed at
subsequent visits. Negative pregnancy test must be confirmed prior to study intervention administration.
p See Section 8.4 for viral serology parameters. 
q Clinical laboratory and urinalysis parameters are described in Section 10.2. 
r Additional samples for urinalysis and complement testing will be collected at any time if fever, rash, or arthralgia are observed in a participant without 
alternative explanation per the assessment of the investigator, or if immune complex disease is suspected by the investigator based on other signs or symptoms 
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consistent with immune complex disease. Other signs and symptoms consistent with immune complex disease include, but are not limited to, decreased 
complement, hematuria, proteinuria, and/or decreased renal function. Urinalysis parameters are described in Section 10.2. 
s Drugs of abuse included in the panel are described in Section 10.2.  
t At all visits during the Treatment Period where PK collection is required, samples will be collected predose only. On Day 8, no VIR-3434 will be dosed, 
therefore PK sample can be collected anytime during visit. VIR-3434 PK sample collection includes samples for free and total PK assays, as applicable. 
Predose samples will be collected within 1 hour prior to dose. Further details can be found in Section 8.8. 
u Includes samples for ADA and neutralizing antibodies (NAb), as applicable for VIR-3434. Samples will be collected prior to dosing and at each indicated
timepoint thereafter. Additional samples for immunogenicity analysis may be collected if a persistent drug related immunologic event is suspected.
v See Section 8.4 for more information. 
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Table 9: 
Schedule of Activities: Cohort 3a (PBMC- Qualified Sites Only) 
Study Stage 
Screen-
ing 
Treatment Perioda
Visit Week 
W1 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32 
W36/ 
EOTbc
W40/ 
EOTbc 
Visit Day ± Visit Window 
D -56 
to -1 
D1 D8±2 D29±2 
D57±2 
D85±2 
D113±2 
D141±2 D169±2 D197±2 
D225±2 D253±2 D281±2 
Study Procedures 
Informed consent 
X 
Inclusion/exclusion criteria 
X 
Xd 
Demography 
X 
Physical examination e
X 
Xf 
Xg 
Body weight 
X 
Medical history 
X 
Vital signsh
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse event review/recordi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Liver elastography (eg, 
Fibroscan) j
X 
12-lead safety ECGk
X 
X 
ECI surveillance l 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VIR-3434 local tolerability m 
X 

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Study Stage 
Screen-
ing 
Treatment Perioda
Visit Week 
W1 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32 
W36/ 
EOTbc
W40/ 
EOTbc 
Visit Day ± Visit Window 
D -56 
to -1 
D1 D8±2 D29±2 
D57±2 
D85±2 
D113±2 
D141±2 D169±2 D197±2 
D225±2 D253±2 D281±2 
Drug administration 
VIR-3434 administration 
(Q8W) n
X 
X 
X 
X 
X 
X 
VIR-3434 administration 
(Q12W) n 
X 
X 
X 
X 
TDF administration (QD)o 
X 
Treatment Diary 
X 
Laboratory Assessmentsq 
Pregnancy testr
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Screening viral serologys 
X 
Liver function tests t 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum chemistry t 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology t 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation parameters t 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis tu 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine for drugs of abuse v 
X 
HBsAg quantitative 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Anti-HBs qualitative 
X 
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Study Stage 
Screen-
ing 
Treatment Perioda
Visit Week 
W1 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32 
W36/ 
EOTbc
W40/ 
EOTbc 
Visit Day ± Visit Window 
D -56 
to -1 
D1 D8±2 D29±2 
D57±2 
D85±2 
D113±2 
D141±2 D169±2 D197±2 
D225±2 D253±2 D281±2 
Anti-HBs quantitative 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HBeAg qualitative 
X 
HBeAg quantitative 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Anti-HBe qualitative 
X 
HBV DNA quantification 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HBV genotyping 
X 
Complement testing u 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VIR-3434 PKw 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VIR-3434 immunogenicityx 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Exploratory Assessments 
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Study Stage 
Screen-
ing 
Treatment Perioda
Visit Week 
W1 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32 
W36/ 
EOTbc
W40/ 
EOTbc 
Visit Day ± Visit Window 
D -56 
to -1 
D1 D8±2 D29±2 
D57±2 
D85±2 
D113±2 
D141±2 D169±2 D197±2 
D225±2 D253±2 D281±2 
D = day; EOT = end of treatment; W = week  
a On days in which study intervention is administered, assessments performed predose unless otherwise specified. 
b If Q8W dosing regimen is chosen, then W40 will be the EOT visit and assessments for EOT should be done at W40. Similarly, if Q12W dosing regimen is 
chosen then W36 will be the EOT and assessments for EOT should be done at W36. 
c If a participant discontinues treatment or withdraws prematurely from the study prior to the Week 36 (Q12W) or Week 40 (Q8W) visit, EOT assessments 
should be performed. 
d Prior to study intervention administration on Day 1, participant eligibility will be confirmed. 
e See Section 8.3.1 for assessments to be performed during a full physical examination. A dilated fundoscopic retinal examination must be performed during 
Screening. The participant may be referred to a specialist for performance of the retinal exam. 
f To be conducted if W36 will be EOT (Q12W dosing regimen). 
g To be conducted if W40 will be EOT (Q8W dosing regimen). 
h Vital signs (blood pressure, pulse rate, respiratory rate, and temperature) should be measured after the participant has rested comfortably for approximately 10 
minutes. 
i After signing of the informed consent form (ICF), but prior to initiation of study intervention, AEs/SAEs related to protocol-mandated procedures will be 
reported. Following initiation of study intervention, all AEs/SAEs, regardless of cause or relationship, will be recorded for the entire duration of the study. 
Further details can be found in Section 8.7  
j Does not need to be performed if the participant has had a liver elastography (eg, FibroScan or other sponsor-approved method) in the 6 months prior to 
screening or liver biopsy in the year prior to screening that confirmed the absence of Metavir F3 fibrosis or F4 cirrhosis. 
k 12-lead safety ECG will be recorded and should be measured in the supine position after the participant has rested comfortably for approximately 10 minutes. 
Further details can be found in Section 8.10. 
l Participants will be monitored for ECI, and additional assessments may be performed if indicated. See Section 8.7.6 and Section 10.7 for more information.
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m On Day 1, local tolerability should be assessed approximately 1 hour after VIR-3434 administration. At the discretion of the investigator, unscheduled visits are 
permitted as needed for follow-up of any unresolved local tolerability symptoms. Local tolerability symptoms occurring at other visits should be reported as 
AEs. 
n VIR-3434 will be administered via SC injection either every 8 weeks or every 12 weeks. Participants will be monitored for at least 1 hour after VIR-3434 
administration. 
o TDF will be administered orally every day until the criteria in Section 4.1.3 are met
q Screening laboratory tests may be repeated (eg, for values thought to be erroneous) with Sponsor approval. 
r WOCBP are required to have pregnancy tests. A blood pregnancy test will be performed at screening, and a urine pregnancy test will be performed at 
subsequent visits. Negative pregnancy test must be confirmed prior to study intervention administration. 
s See Section 8.4 for viral serology parameters. 
t Clinical laboratory and urinalysis parameters are described in Section 10.2. 
u Additional samples for urinalysis and complement testing will be collected at any time if fever, rash, or arthralgia are observed in a participant without
alternative explanation per the assessment of the investigator, or if immune complex disease is suspected by the investigator based on other signs or symptoms
consistent with immune complex disease. Other signs and symptoms consistent with immune complex disease include, but are not limited to, decreased
complement, hematuria, proteinuria, and/or decreased renal function. Urinalysis parameters are described in Section 10.2.
v Drugs of abuse included in the panel are described in Section 10.2.  
w At all visits during the Treatment Period where PK collection is required, samples will be collected predose only. On Day 8, PK sample will be collected 
anytime during visit. VIR-3434 PK sample collection includes samples for free and total PK assays, as applicable. Predose samples will be collected within 1 
hour prior to dose. Further details can be found in Section 8.8  
x Includes samples for ADA and neutralizing antibodies (NAb), as applicable for VIR-3434. Samples will be collected prior to dosing and at each indicated 
timepoint thereafter. Additional samples for immunogenicity analysis may be collected if a persistent drug related immunologic event is suspected. 
y See Section 8.4 for more information. 
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Table 10: 
Schedule of Activities: Cohort 4a 
Study Stage 
Screen-
ing 
Treatment Perioda
Visit Week 
W1 
W4 
W8 
W12 
W16 
W20  
W24 
W28 
W32 
W36 
W40 
W44/ 
EOTb
Visit Day ± Visit Window 
D -56 
to -1 
D1 
D2 
D8 
±2 
D29 
±2 
D57 
±2 
D85 
±2 
D113 
±2 
D141 
±2 
D169 
±2 
D197 
±2 
D225 
±2 
D253 
±2 
D281 
±2 
D309 
±2 
Study Procedures 
Informed consent 
X 
Inclusion/exclusion criteria 
X 
Xc
Demography 
X 
Physical examination d 
X 
X 
Body weight 
X 
Medical history 
X 
Vital signse
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse event review/recordf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication 
review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Liver elastography (eg, 
Fibroscan)g
X 
12-lead safety ECGh
X 
X 
ECI surveillancei 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VIR-3434 local tolerabilityj 
X 
Drug Administration 
VIR-3434 and VIR-2218 
administrationk
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
TDF administration (QD)l 
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Study Stage 
Screen-
ing 
Treatment Perioda
Visit Week 
W1 
W4 
W8 
W12 
W16 
W20  
W24 
W28 
W32 
W36 
W40 
W44/ 
EOTb
Visit Day ± Visit Window 
D -56 
to -1 
D1 
D2 
D8 
±2 
D29 
±2 
D57 
±2 
D85 
±2 
D113 
±2 
D141 
±2 
D169 
±2 
D197 
±2 
D225 
±2 
D253 
±2 
D281 
±2 
D309 
±2 
Treatment Diary 
X 
Laboratory Assessmentsn 
Pregnancy testo
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Screening viral serologyp 
X 
Liver function testsq 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum chemistry q 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology q 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation parameters q 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis qr
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine for drugs of abuse s 
X 
HBsAg quantitative 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Anti-HBs qualitative 
X 
Anti-HBs quantitative 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HBeAg qualitative 
X 
HBeAg quantitative 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Anti-HBe qualitative 
X 
HBV DNA quantification 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
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Study Stage 
Screen-
ing 
Treatment Perioda
Visit Week 
W1 
W4 
W8 
W12 
W16 
W20  
W24 
W28 
W32 
W36 
W40 
W44/ 
EOTb
Visit Day ± Visit Window 
D -56 
to -1 
D1 
D2 
D8 
±2 
D29 
±2 
D57 
±2 
D85 
±2 
D113 
±2 
D141 
±2 
D169 
±2 
D197 
±2 
D225 
±2 
D253 
±2 
D281 
±2 
D309 
±2 
HBV genotyping 
X 
Complement testing r 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VIR-3434 PK predose t 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VIR-3434 PK postdose 
Xu
Xv 
VIR-2218 PK predosew
X 
X 
X 
VIR-2218 PK postdose 
Xx 
Xy 
Xx 
Xx 
VIR-3434 immunogenicity z 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VIR-2218 immunogenicityaa
X 
X 
X 
X 
X 
X 
X 
Exploratory Assessments 
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Study Stage 
Screen-
ing 
Treatment Perioda
Visit Week 
W1 
W4 
W8 
W12 
W16 
W20  
W24 
W28 
W32 
W36 
W40 
W44/ 
EOTb
Visit Day ± Visit Window 
D -56 
to -1 
D1 
D2 
D8 
±2 
D29 
±2 
D57 
±2 
D85 
±2 
D113 
±2 
D141 
±2 
D169 
±2 
D197 
±2 
D225 
±2 
D253 
±2 
D281 
±2 
D309 
±2 
D = day; EOT = end of treatment; W = week  
a On days in which study intervention is administered, assessments performed predose unless otherwise specified. 
aa Includes samples for ADA of VIR-2218. Samples will be collected prior to dosing at each indicated timepoint. Additional samples for immunogenicity analysis 
may be collected if a persistent drug related immunologic event is suspected.  
b If a participant discontinues treatment or withdraws prematurely from the study prior to the Week 44 visit, EOT assessments should be performed. 
bb See Section 8.4 for more information. 
c Prior to study intervention administration on Day 1, participant eligibility will be confirmed. 
cc
d See Section 8.3.1 for assessments to be performed during a full physical examination. A dilated fundoscopic retinal examination must be performed during 
Screening. The participant may be referred to a specialist for performance of the retinal exam. 
e Vital signs (blood pressure, pulse rate, respiratory rate, and temperature) should be measured after the participant has rested comfortably for approximately 10 
minutes. 
f After signing of the informed consent form (ICF), but prior to initiation of study intervention, AEs/SAEs related to protocol-mandated procedures will be 
reported. Following initiation of study intervention, all AEs/SAEs, regardless of cause or relationship, will be recorded for the entire duration of the study. 
Further details can be found in Section 8.7 
g Does not need to be performed if the participant has had a liver elastography (eg, FibroScan or other sponsor-approved method) in the 6 months prior to 
screening or liver biopsy in the year prior to screening that confirmed the absence of METAVIR F3 fibrosis or F4 cirrhosis. 
h 12-lead safety ECG will be recorded and should be measured in the supine position after the participant has rested comfortably for approximately 10 minutes. 
Further details can be found in Section 8.10.  
i Participants will be monitored for ECI, and additional assessments may be performed if indicated. See Section 8.7.6 and Section 10.7 for more information. 
j On Day 1, local tolerability should be assessed approximately 1 hour after VIR-3434 administration. At the discretion of the investigator, unscheduled visits are 
permitted as needed for follow-up of any unresolved local tolerability symptoms. Local tolerability symptoms occurring at other visits should be reported as 
AEs. 
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k VIR-3434 and VIR-2218 will be administered via SC injection every 4 weeks. Participants will be monitored for at least 1 hour after VIR-3434 administration. 
l TDF will be administered orally every day until the criteria in Section 4.1.3 are met.
n Screening laboratory tests may be repeated (eg, for values thought to be erroneous) with Sponsor approval. 
o WOCBP are required to have pregnancy tests. A blood pregnancy test will be performed at screening, and a urine pregnancy test will be performed at
subsequent visits. Negative pregnancy test must be confirmed prior to study intervention administration.
p See Section 8.4 for viral serology parameters. 
q Clinical laboratory and urinalysis parameters are described in Section 10.2.  
r Additional samples for urinalysis and complement testing will be collected at any time if fever, rash, or arthralgia are observed in a participant without 
alternative explanation per the assessment of the investigator, or if immune complex disease is suspected by the investigator based on other signs or symptoms 
consistent with immune complex disease. Other signs and symptoms consistent with immune complex disease include, but are not limited to, decreased 
complement, hematuria, proteinuria, and/or decreased renal function. Urinalysis parameters are described in Section 10.2. 
s Drugs of abuse included in the panel are described in Section 10.2.  
t VIR-3434 PK sample collection includes samples for free and total PK assays, as applicable. Predose samples will be collected within 1 hour prior to dose. 
Further details can be found in Section 8.8. 
u Day 2 VIR-3434 PK postdose sample will be collected between 22 to 28 hours post D1 dose.
v VIR-3434 PK postdose sample can be collected at any time during the D8 visit.
w VIR-2218 PK predose samples will be collected within 1 hour prior to dose. Further details can be found in Section 8.8.
x Day 1, Week 20, and Week 44 VIR-2218 PK postdose samples will be collected between 2 to 6 hours postdose.
y Day 2 VIR-2218 PK samples will be collected between 22 to 28 hours post D1 dose.
z Includes samples for ADA and neutralizing antibodies (NAb), as applicable for VIR-3434. Samples will be collected prior to dosing at each indicated
timepoint. Additional samples for immunogenicity analysis may be collected if a persistent drug related immunologic event is suspected. 
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Table 11: 
Schedule of Activities: Cohort 5a 
Study Stage 
Screen-
ing 
Treatment Perioda
Visit Week 
W1 
W4 
W8 
W12 
W16 
W20  
W24 
W28 
W32 
W36 
W40 
W44 
W48/ 
EOTb 
Visit Day ± Visit Window 
D -56 
to -1 
D1 
D2 
D8 
±2 
D29 
±2 
D57 
±2 
D85 
±2 
D113 
±2 
D141 
±2 
D169 
±2 
D197 
±2 
D225 
±2 
D253 
±2 
D281 
±2 
D309 
±2 
D337 
±2 
Study Procedures 
Informed consent 
X 
Inclusion/exclusion criteria 
X 
Xc
Demography 
X 
Physical examination d 
X 
X 
Body weight 
X 
Medical history 
X 
Vital signse
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse event review/recordf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication 
review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Liver elastography (eg 
Fibroscan)g
X 
12-lead safety ECGh
X 
X 
ECI surveillancei 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VIR-3434 local tolerability j 
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Study Stage 
Screen-
ing 
Treatment Perioda
Visit Week 
W1 
W4 
W8 
W12 
W16 
W20  
W24 
W28 
W32 
W36 
W40 
W44 
W48/ 
EOTb 
Visit Day ± Visit Window 
D -56 
to -1 
D1 
D2 
D8 
±2 
D29 
±2 
D57 
±2 
D85 
±2 
D113 
±2 
D141 
±2 
D169 
±2 
D197 
±2 
D225 
±2 
D253 
±2 
D281 
±2 
D309 
±2 
D337 
±2 
Drug Administration 
VIR-3434 and VIR-2218 
administrationk
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PEG-IFNα administration 
(QW)l
X 
X 
TDF administration (QD)m 
X 
Treatment Diary 
X 
Laboratory Assessmentso 
Pregnancy test p 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Screening viral serology q 
X 
Liver function tests r
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum chemistry r 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology r 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation parameters r 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysisrs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine for drugs of abuse t 
X 
HBsAg quantitative 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Anti-HBs qualitative 
X 
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Study Stage 
Screen-
ing 
Treatment Perioda
Visit Week 
W1 
W4 
W8 
W12 
W16 
W20  
W24 
W28 
W32 
W36 
W40 
W44 
W48/ 
EOTb 
Visit Day ± Visit Window 
D -56 
to -1 
D1 
D2 
D8 
±2 
D29 
±2 
D57 
±2 
D85 
±2 
D113 
±2 
D141 
±2 
D169 
±2 
D197 
±2 
D225 
±2 
D253 
±2 
D281 
±2 
D309 
±2 
D337 
±2 
Anti-HBs quantitative 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HBeAg qualitative 
X 
HBeAg quantitative 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Anti-HBe qualitative 
X 
HBV DNA quantification 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HBV genotyping 
X 
Complement testing s 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VIR-3434 PK predose u 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VIR-3434 PK postdose 
Xv 
Xw 
VIR-2218 PK predosex
X 
X 
X 
VIR-2218 PK postdose 
Xy 
Xz 
Xy 
Xy 
VIR-3434 immunogenicity aa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VIR-2218 immunogenicity bb 
X 
X 
X 
X 
X 
X 
X 
X 
Exploratory Assessments 
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Study Stage 
Screen-
ing 
Treatment Perioda
Visit Week 
W1 
W4 
W8 
W12 
W16 
W20  
W24 
W28 
W32 
W36 
W40 
W44 
W48/ 
EOTb 
Visit Day ± Visit Window 
D -56 
to -1 
D1 
D2 
D8 
±2 
D29 
±2 
D57 
±2 
D85 
±2 
D113 
±2 
D141 
±2 
D169 
±2 
D197 
±2 
D225 
±2 
D253 
±2 
D281 
±2 
D309 
±2 
D337 
±2 
D = day; EOT = end of treatment; W = week  
a On days in which study intervention is administered, assessments performed predose unless otherwise specified. 
aa Includes samples for ADA and neutralizing antibodies (NAb), as applicable for VIR-3434. Samples will be collected prior to dosing and at each indicated 
timepoint thereafter. Additional samples for immunogenicity analysis may be collected if a persistent drug related immunologic event is suspected. 
b If a participant discontinues treatment or withdraws prematurely from the study prior to the Week 48 visit, EOT assessments should be performed. 
bb Includes samples for ADA of VIR-2218. Samples will be collected prior to dosing at each indicated timepoint thereafter. Additional samples for 
immunogenicity analysis may be collected if a persistent drug related immunologic event is suspected.  
c Prior to study intervention administration on Day 1, participant eligibility will be confirmed. 
cc See Section 8.4 for more information. 
d See Section 8.3.1 for assessments to be performed during a full physical examination. A dilated fundoscopic retinal examination must be performed during 
Screening. The participant may be referred to a specialist for performance of the retinal exam. 
e Vital signs (blood pressure, pulse rate, respiratory rate, and temperature) should be measured after the participant has rested comfortably for approximately 10 
minutes. 
e
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f After signing of the informed consent form (ICF), but prior to initiation of study intervention, AEs/SAEs related to protocol-mandated procedures will be 
reported. Following initiation of study intervention, all AEs/SAEs, regardless of cause or relationship, will be recorded for the entire duration of the study. 
Further details can be found in Section 8.7.  
g Does not need to be performed if the participant has had a liver elastography (eg, FibroScan or other sponsor-approved method) in the 6 months prior to 
screening or liver biopsy in the year prior to screening that confirmed the absence of METAVIR F3 fibrosis or F4 cirrhosis. 
h 12-lead safety ECG will be recorded and should be measured in the supine position after the participant has rested comfortably for approximately 10 minutes. 
Further details can be found in Section 8.10.  
i Participants will be monitored for ECI, and additional assessments may be performed if indicated. See Section 8.7.6 and Section 10.7 for more information. 
j On Day 1, local tolerability should be assessed approximately 1 hour after VIR-3434 administration. At the discretion of the investigator, unscheduled visits are 
permitted as needed for follow-up of any unresolved local tolerability symptoms. Local tolerability symptoms occurring at other visits should be reported as 
AEs. 
k VIR-3434 and VIR-2218 will be administered via SC injection every 4 weeks. Participants will be monitored for at least 1 hour after VIR-3434 administration. 
l PEG-IFNα will be administered via SC injection every week.
m TDF will be administered orally every day until the criteria in Section 4.1.3 are met.
o Screening laboratory tests may be repeated (eg, for values thought to be erroneous) with Sponsor approval.
p WOCBP are required to have pregnancy tests. A blood pregnancy test will be performed at screening, and a urine pregnancy test will be performed at
subsequent visits. Negative pregnancy test must be confirmed prior to study intervention administration. 
q See Section 8.4 for viral serology parameters. 
r  Clinical laboratory and urinalysis parameters are described in Section 10.2.  
s Additional samples for urinalysis and complement testing will be collected at any time if fever, rash, or arthralgia are observed in a participant without 
alternative explanation per the assessment of the investigator, or if immune complex disease is suspected by the investigator based on other signs or symptoms 
consistent with immune complex disease. Other signs and symptoms consistent with immune complex disease include, but are not limited to, decreased 
complement, hematuria, proteinuria, and/or decreased renal function. Urinalysis parameters are described in Section 10.2.  
t Drugs of abuse included in the panel are described in Section 10.2. 
u VIR-3434 PK sample collection includes samples for free and total PK assays, as applicable. Predose samples will be collected within 1 hour prior to dose.
Further details can be found in Section 8.8.
v Day 2 VIR-3434 PK postdose sample will be collected between 22 to 28 hours post D1 dose. 
w VIR-3434 PK postdose sample can be collected at any time during the D8 visit. 
x VIR-2218 PK predose samples will be collected within 1 hour prior to dose. Further details can be found in Section 8.8. 
y Day 1, Week 20, and Week 48 VIR-2218 PK post-dose samples will be collected between 2 to 6 hours postdose. 
z Day 2 VIR-2218 PK samples will be collected between 22 to 28 hours post D1 dose. 
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Table 12: 
Schedule of Activities: Follow-Up Period for all Cohorts 
Study Stage 
Follow-Up Period 
Follow up Visit 
F1  
F2a
F4 
F6a
F8 
F10a F12 
F14b 
F16 
F18b 
F20 
F22b 
F24 
F28c F32c 
F36 F40c F44c F48/ 
EOFU 
Visit Day ± Visit 
Window 
D8 
±2 
D15 
±2 
D29 
±7 
D43 
±7 
D57 
±7 
D71 
±7 
D85 
±7 
D99 
±7 
D113 
±7 
D127 
±7 
D141 
±7 
D155 
±7 
D169 
±7 
D197 
±7 
D225 
±7 
D253 
±7 
D281 
±7 
D309 
±7 
D337 
±7 
Study Procedures 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Body weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse event 
review/recordd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication 
review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead safety ECGe
X 
ECI surveillancef
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Drug administration 
TDF administrationg
X 
Treatment Diary 
X 
Laboratory Assessments 
Pregnancy testi 
X 
X 
X 
X 
X 
Liver function testsj 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum chemistryj 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematologyj 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
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Study Stage 
Follow-Up Period 
Follow up Visit 
F1  
F2a
F4 
F6a
F8 
F10a F12 
F14b 
F16 
F18b 
F20 
F22b 
F24 
F28c F32c 
F36 F40c F44c F48/ 
EOFU 
Visit Day ± Visit 
Window 
D8 
±2 
D15 
±2 
D29 
±7 
D43 
±7 
D57 
±7 
D71 
±7 
D85 
±7 
D99 
±7 
D113 
±7 
D127 
±7 
D141 
±7 
D155 
±7 
D169 
±7 
D197 
±7 
D225 
±7 
D253 
±7 
D281 
±7 
D309 
±7 
D337 
±7 
Coagulation parametersj 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysiskj 
X 
X 
X 
X 
HBsAg quantitative 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Anti-HBs quantitative 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HBeAg quantitative 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Anti-HBe qualitative 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HBV DNA quantification 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Complement testingk 
X 
X 
VIR-3434 PK l 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VIR-3434 
immunogenicitym 
X 
X 
X 
X 
X 
X 
X 
VIR-2218 
immunogenicityn 
X 
X 
X 
X 
X 
X 
X 
Exploratory Assessments 
CCI
CCI
CCI
CCI
CCI
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Study Stage 
Follow-Up Period 
Follow up Visit 
F1  
F2a
F4 
F6a
F8 
F10a F12 
F14b 
F16 
F18b 
F20 
F22b 
F24 
F28c F32c 
F36 F40c F44c F48/ 
EOFU 
Visit Day ± Visit 
Window 
D8 
±2 
D15 
±2 
D29 
±7 
D43 
±7 
D57 
±7 
D71 
±7 
D85 
±7 
D99 
±7 
D113 
±7 
D127 
±7 
D141 
±7 
D155 
±7 
D169 
±7 
D197 
±7 
D225 
±7 
D253 
±7 
D281 
±7 
D309 
±7 
D337 
±7 
D = day; E = End of Follow-Up; F= Follow-Up visit week  
a Visits are only required in participants who discontinue NRTI at F1 Follow-Up visit. 
b Visits are only required in participants who discontinue NRTI at F12 Follow-Up visit. 
c Visits are only required in participants who discontinue NRTI. 
d In the Follow-Up Period, all AEs/SAEs, regardless of cause or relationship, will be recorded for the entire duration of the study. Further details can be found in 
Section 8.7. 
e 12-lead safety ECG will be recorded and should be measured in the supine position after the participant has rested comfortably for approximately 10 minutes. 
Further details can be found in Section 8.10. 
f Participants will be monitored for ECI, and additional assessments may be performed if indicated. See Section 8.7.6 and Section 10.7 for more information. 
g TDF will be administered orally every day unless the criteria in Section 4.1.3 are met.  
i WOCBP are required to have pregnancy tests. A urine pregnancy test will be performed.  
j Clinical laboratory and urinalysis parameters are described in Section 10.2.  
k Additional samples for urinalysis and complement testing will be collected at any time if fever, rash, or arthralgia are observed in a participant without 
alternative explanation per the assessment of the investigator, or if immune complex disease is suspected by the investigator based on other signs or symptoms 
consistent with immune complex disease. Other signs and symptoms consistent with immune complex disease include, but are not limited to, decreased 
complement, hematuria, proteinuria, and/or decreased renal function. Urinalysis parameters are described in Section 10.2. 
l VIR-3434 PK sample collection includes samples for free and total PK assays, as applicable. Further details can be found in Section 8.8.
m Includes samples for ADA and neutralizing antibodies (NAb), as applicable for VIR-3434. Additional samples for immunogenicity analysis may be collected if
a persistent drug related immunologic event is suspected. 
CCI
CCI
CCI
CCI
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n (Cohorts 4a and 5a). Includes samples for ADA of VIR-2218. Additional samples for immunogenicity analysis may be collected if a persistent drug related 
immunologic event is suspected. 
CCI
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10.10. 
Appendix 10: Schedule of Sample Collection for Optional VIR-3434 PK Sub-study 
Collection Visit 
PK sub-study visit 1 
any one of the three visits is neededa 
PK sub-study visit 2 (optional) 
any one of the three visits is neededa 
Study Visit 
W9 
W13 
W17 
W25
W29 
W33
Visit Day ± Visit Window 
D64 
-2
D92 
-2
D120 
-2
D176 
-2
D204 
-2
D232 
-2
Laboratory Assessments 
VIR-3434 PKb 
X 
X 
Liver function tests 
X 
X 
HBsAg quantitative 
X 
X 
HBV DNA quantification 
X 
X 
Participants enrolled in Cohort 3a are excluded from the optional VIR-3434 PK sub-study. 
a VIR-3434 PK sample will be collected any time during the visit. VIR-3434 PK sample collection includes samples for free and total PK assays, as applicable. 
b See Sections 8.8 and 8.8.1 for more details. 

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11.
REFERENCES
Agarwal K, Yuen M, Wedemeyer, H, et al. Dose-dependent durability of hepatitis B surface 
antigen reductions following administration of a single dose of VIR-3434, a novel neutralizing 
vaccinal monoclonal antibody. EASL International Liver Congress, June 22-26, 2022. 
Agarwal K, Yuen MF, Wedemeyer H, Arizpe A, et al. Rapid HBsAg Reduction in Chronic 
Hepatitis B Virus Infection: Preliminary Results From a Phase 1 Study Evaluating a Single Dose 
of VIR-3434, a Novel Neutralizing, Vaccinal Monoclonal Antibody. Poster. Presented at 
AASLD: The Liver Meeting (Virtual), November 12-15, 2021. 
Ahn SH, Marcellin P, Ma X, Caruntu FA, Tak WY, Elkhashab M, Chuang WL, Tabak F, Mehta 
R, Petersen J, Guyer W, Jump B, Chan A, Subramanian M, Crans G, Fung S, Buti M, Gaeta GB, 
Hui AJ, Papatheodoridis G, Flisiak R, Chan HLY. Hepatitis B Surface Antigen Loss with 
Tenofovir Disoproxil Fumarate Plus Peginterferon Alfa-2a: Week 120 Analysis. Dig Dis Sci. 
2018 Dec;63(12):3487-3497. doi: 10.1007/s10620-018-5251-9. Epub 2018 Aug 22. Erratum in: 
Dig Dis Sci. 2018 Oct 15: PMID: 30136045; PMCID: PMC6244971. 
Bang YJ, Giaccone G, Im SA, Oh DY, Bauer TM, Nordstrom JL, Li H, Chichili GR, Moore PA, 
Hong S, Stewart SJ, Baughman JE, Lechleider RJ, Burris HA. First-in-human phase 1 study of 
margetuximab (MGAH22), an Fc-modified chimeric monoclonal antibody, in patients with 
HER2-positive advanced solid tumors. Ann Oncol. 2017 Apr 1;28(4):855-861. doi: 
10.1093/annonc/mdx002. PMID: 28119295; PMCID: PMC6246722. 
Bertoletti A, Ferrari C. Adaptive immunity in HBV infection. J Hepatol. 2016 Apr;64(1 
Suppl):S71-S83. doi: 10.1016/j.jhep.2016.01.026. PMID: 27084039. 
Björnsson ES. Hepatotoxicity by Drugs: The Most Common Implicated Agents. Int J Mol Sci. 
2016 Feb 6;17(2):224. doi: 10.3390/ijms17020224. PMID: 26861310; PMCID: PMC4783956. 
Burton AR, Pallett LJ, McCoy L, et al. Dysfunctional surface antigen-specific memory B cells 
accumulate in chronic hepatitis B infection. European Association for the Study of the Liver 
International Liver Congress 2018. Paris, France. 
Crouse J, Kalinke U, Oxenius A. Regulation of antiviral T cell responses by type I interferons. 
Nat Rev Immunol. 2015 Apr;15(4):231-42. doi: 10.1038/nri3806. Epub 2015 Mar 20. PMID: 
25790790. 
De Simone G, Andreata F, Bleriot C, Fumagalli V, Laura C, Garcia-Manteiga JM, Di Lucia P, 
Gilotto S, Ficht X, De Ponti FF, Bono EB, Giustini L, Ambrosi G, Mainetti M, Zordan P, 
Bénéchet AP, Ravà M, Chakarov S, Moalli F, Bajenoff M, Guidotti LG, Ginhoux F, Iannacone 
M. Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by
hepatocellular priming. Immunity. 2021 Sep 14;54(9):2089-2100.e8. doi:
10.1016/j.immuni.2021.05.005. Epub 2021 Aug 31. PMID: 34469774; PMCID: PMC8459394
DiLillo DJ, Ravetch JV. Differential Fc-Receptor Engagement Drives an Anti-tumor Vaccinal 
Effect. Cell. 2015 May 21;161(5):1035-1045. doi: 10.1016/j.cell.2015.04.016. Epub 2015 May 
11. PMID: 25976835; PMCID: PMC4441863.

Master Study VIR-MHB1-V200 
Sub-study VIR-SHB1-V201 
Amendment 3, Version 1.0 
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Page 101 
Dill MT, Makowska Z, Trincucci G, Gruber AJ, Vogt JE, Filipowicz M, Calabrese D, Krol I, 
Lau DT, Terracciano L, van Nimwegen E, Roth V, Heim MH. Pegylated IFN-α regulates hepatic 
gene expression through transient Jak/STAT activation. J Clin Invest. 2014 Apr;124(4):1568-81. 
doi: 10.1172/JCI70408. Epub 2014 Feb 24. PMID: 24569457; PMCID: PMC3973080. 
European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; 
European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the 
management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370-398. doi: 
10.1016/j.jhep.2017.03.021. Epub 2017 Apr 18. PMID: 28427875. 
Farag MS, Fung S, van Campenhour MJH, et al. Addition of Peginterferon Alfa-2a Increases 
HBsAg Decline in HBeAg-negative Chronic Hepatitis B Patients Treated with Long-Term 
Nucleos(t)ide Analogue Therapy. Presented at AASLD The Liver Meeting, November 8-12, 
2019. Boston, MA. 
Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on 
disease progression and prognostic factors. J Hepatol. 2008 Feb;48(2):335-52. doi: 
10.1016/j.jhep.2007.11.011. Epub 2007 Dec 4. PMID: 18096267. 
FDA. Chronic Hepatitis B Virus Infection: Developing Drugs for Treatment. 
https://www.fda.gov/media/117977/download. Apr 2022. 
Galun E, Eren R, Safadi R, Ashour Y, Terrault N, Keeffe EB, Matot E, Mizrachi S, Terkieltaub 
D, Zohar M, Lubin I, Gopher J, Shouval D, Dagan S. Clinical evaluation (phase I) of a 
combination of two human monoclonal antibodies to HBV: safety and antiviral properties. 
Hepatology. 2002 Mar;35(3):673-9. doi: 10.1053/jhep.2002.31867. Erratum in: Hepatology 2002 
Apr;35(4):986. PMID: 11870383. 
Gane E, Lim YS, Cloutier D, Shen L, et al. Safety and Antiviral Activity of VIR-2218, An X-
Targeting RNAi Therapeutic, In Participants With Chronic Hepatitis B Infection: Week 48 
Follow-Up Results. Oral Presentation. Presented at the EASL Digital International Liver 
Conference, June 23-26, 2021. 
Gaudinski MR, Coates EE, Houser KV, Chen GL, Yamshchikov G, Saunders JG, Holman LA, 
Gordon I, Plummer S, Hendel CS, Conan-Cibotti M, Lorenzo MG, Sitar S, Carlton K, Laurencot 
C, Bailer RT, Narpala S, McDermott AB, Namboodiri AM, Pandey JP, Schwartz RM, Hu Z, 
Koup RA, Capparelli E, Graham BS, Mascola JR, Ledgerwood JE; VRC 606 Study Team. 
Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: 
A Phase 1 open-label clinical trial in healthy adults. PLoS Med. 2018 Jan 24;15(1):e1002493. 
doi: 10.1371/journal.pmed.1002493. PMID: 29364886; PMCID: PMC5783347. 
Gupta SV, Arizpe A, Fanget M, Dholakiya SL, et al. Preliminary Pharmacokinetics and Safety in 
Healthy Volunteers of VIR-3434, a Monoclonal Antibody for the Treatment of Chronic Hepatitis 
B Infection. Poster. Presented at the EASL Digital International Liver Conference, June 23–26, 
2021. 
He LT, Ye XG, Zhou XY. Effect of switching from treatment with nucleos(t)ide analogs to 
pegylated interferon α-2a on virological and serological responses in chronic hepatitis B patients. 
World J Gastroenterol. 2016;22(46):10210-10218. 

Master Study VIR-MHB1-V200 
Sub-study VIR-SHB1-V201 
Amendment 3, Version 1.0 
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Confidential 
Page 102 
Huang J, Zhang K, Chen W, Liao J, Luo X, Chen R. Switching to PegIFNα-2b leads to HBsAg 
loss in patients with low HBsAg levels and HBV DNA suppressed by Nas. Sci Rep. 
2017;7(1):13383. 
Im S-A, Bang Y-J, Oh D-Y, Giaccone G., Bauer T, Nordstrom J, Li H, Moore P, Hong S, 
Baughman J, Rock E, BurrisH. Long-term responders to single-agent margetuximab, an Fc-
modified anti-HER2 monoclonal antibody, in metastatic HER2+ breast cancer patients with prior 
anti-HER2 therapy. DOI: 10.1158/1538-7445.SABCS18-P6-18-11 Published February 2019 
Ko SY, Pegu A, Rudicell RS, Yang ZY, Joyce MG, Chen X, Wang K, Bao S, Kraemer TD, Rath 
T, Zeng M, Schmidt SD, Todd JP, Penzak SR, Saunders KO, Nason MC, Haase AT, Rao SS, 
Blumberg RS, Mascola JR, Nabel GJ. Enhanced neonatal Fc receptor function improves 
protection against primate SHIV infection. Nature. 2014 Oct 30;514(7524):642-5. doi: 
10.1038/nature13612. Epub 2014 Aug 13. PMID: 25119033; PMCID: PMC4433741. 
Konerman MA, Lok AS. Interferon Treatment for Hepatitis B. Clin Liver Dis. 2016 
Nov;20(4):645-665. doi: 10.1016/j.cld.2016.06.002. Epub 2016 Aug 8. PMID: 27742005. 
Lee HW, Park JY, Hong T, et al. A prospective, open‐label, dose‐escalation, single‐center, phase 
1 study for GC1102, a recombinant human immunoglobulin for chronic hepatitis B patients. 
American Association for the Study of Liver Diseases. The Liver Meeting 2018. Abstract 453.. 
Li Y, Si L, Zhai Y, Hu Y, Hu Z, Bei JX, Xie B, Ren Q, Cao P, Yang F, Song Q, Bao Z, Zhang H, 
Han Y, Wang Z, Chen X, Xia X, Yan H, Wang R, Zhang Y, Gao C, Meng J, Tu X, Liang X, Cui 
Y, Liu Y, Wu X, Li Z, Wang H, Li Z, Hu B, He M, Gao Z, Xu X, Ji H, Yu C, Sun Y, Xing B, 
Yang X, Zhang H, Tan A, Wu C, Jia W, Li S, Zeng YX, Shen H, He F, Mo Z, Zhang H, Zhou G. 
Genome-wide association study identifies 8p21.3 associated with persistent hepatitis B virus 
infection among Chinese. Nat Commun. 2016 May 31;7:11664. doi: 10.1038/ncomms11664. 
PMID: 27244555; PMCID: PMC4895015. 
Liang TJ, Block TM, McMahon BJ, Ghany MG, Urban S, Guo JT, Locarnini S, Zoulim F, 
Chang KM, Lok AS. Present and future therapies of hepatitis B: From discovery to cure. 
Hepatology. 2015 Dec;62(6):1893-908. doi: 10.1002/hep.28025. Epub 2015 Oct 27. PMID: 
26239691; PMCID: PMC4681668. 
Lim YS, Yuen MF, Cloutier D, Thanawala V, Shen L, Gupta SV, Arizpe A, Cathcart A, Hwang 
C, Gane E. Longer Treatment Duration of Monthly VIR-2218 Results in Deeper and More 
Sustained Reductions in Hepatitis B Surface Antigen in Participants with Chronic Hepatitis B 
Infection. Oral Presentation. Presented at EASL International Liver Conference, June 22-26, 
2022. 
Maini MK, Gehring AJ. The role of innate immunity in the immunopathology and treatment of 
HBV infection. J Hepatol. 2016 Apr;64(1 Suppl):S60-S70. doi: 10.1016/j.jhep.2016.01.028. 
PMID: 27084038. 

Master Study VIR-MHB1-V200 
Sub-study VIR-SHB1-V201 
Amendment 3, Version 1.0 
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Page 103 
Marcellin P, Ahn SH, Ma X, Caruntu FA, Tak WY, Elkashab M, Chuang WL, Lim SG, Tabak F, 
Mehta R, Petersen J, Foster GR, Lou L, Martins EB, Dinh P, Lin L, Corsa A, Charuworn P, 
Subramanian GM, Reiser H, Reesink HW, Fung S, Strasser SI, Trinh H, Buti M, Gaeta GB, Hui 
AJ, Papatheodoridis G, Flisiak R, Chan HL; Study 149 Investigators. Combination of Tenofovir 
Disoproxil Fumarate and Peginterferon α-2a Increases Loss of Hepatitis B Surface Antigen in 
Patients With Chronic Hepatitis B. Gastroenterology. 2016 Jan;150(1):134-144.e10. doi: 
10.1053/j.gastro.2015.09.043. Epub 2015 Oct 8. PMID: 26453773. 
Ning Q, Han M, Sun Y, et al. Switching from entecavir to PegIFN alfa-2a in patients with 
HBeAg-positive chronic hepatitis B: a randomized open-label trial (OSST trial). J Hepatol. 
2014;61(4):777-84. 
Pavlovic V, Gane E, Xie Q, et al. Nucleos(t)ide analogue discontinuation outcomes in chronic 
hepatitis B participants treated with xalnesiran with and without an immunomodulator: Interim 
results from the phase 2, randomized, controlled, adaptive, open-label platform study 
(PIRANGA) (Poster 5045-C). American Association for the Study of Liver Diseases. The Liver 
Meeting (AASLD); November 10-14 2023; Boston, MA; Abstract # 5006. 
PEGASYS® (peginterferon alfa-2a) [US package insert]. South San Francisco, CA: Genentech, 
Inc.; 2021.  
Perrillo R, Buti M, Durand F, Charlton M, Gadano A, Cantisani G, et al. Entecavir and hepatitis 
B immune globulin in patients undergoing liver transplantation for chronic hepatitis B. Liver 
Transpl. 2013 Aug;19(8):887–95. 
Pondé NF, Lambertini M, de Azambuja E. Twenty years of anti-HER2 therapy-associated 
cardiotoxicity. ESMO Open. 2016 Jul 21;1(4):e000073. doi: 10.1136/esmoopen-2016-000073. 
PMID: 27843627; PMCID: PMC5070246. 
Reed WD, Eddleston AL, Cullens H, Williams R, Zuckerman AJ, Peters DK, Williams DG, 
Maycock WA. Infusion of hepatitis-B antibody in antigen-positive active chronic hepatitis. 
Lancet. 1973 Dec 15;2(7842):1347-51. doi: 10.1016/s0140-6736(73)93321-7. PMID: 4128052. 
Revill PA, Penicaud C, Brechot C, Zoulim F. Meeting the Challenge of Eliminating Chronic 
Hepatitis B Infection. Genes (Basel). 2019 Apr 1;10(4):260. doi: 10.3390/genes10040260. 
PMID: 30939846; PMCID: PMC6523454. 
Riccio G, Coppola C, Piscopo G, Capasso I, Maurea C, Esposito E, De Lorenzo C, Maurea N. 
Trastuzumab and target-therapy side effects: Is still valid to differentiate anthracycline Type I 
from Type II cardiomyopathies? Hum Vaccin Immunother. 2016 May 3;12(5):1124-31. doi: 
10.1080/21645515.2015.1125056. Epub 2016 Feb 2. PMID: 26836985; PMCID: PMC4963071. 
Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien 
RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, 
Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, 
Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the 
management of hepatitis B: a 2015 update. Hepatol Int. 2016 Jan;10(1):1-98. doi: 
10.1007/s12072-015-9675-4. Epub 2015 Nov 13. PMID: 26563120; PMCID: PMC4722087. 
Takkenberg B, Zaaijer H, Weegink C, et al. Baseline HBsAg level predict HBsAg loss in chronic 
hepatitis B patients treated with a combination of peginterferon alfa-2a and adefovir: an interim 
analysis. EASL International Liver Congress. Copengahen, Denmark. 2009. 

Master Study VIR-MHB1-V200 
Sub-study VIR-SHB1-V201 
Amendment 3, Version 1.0 
Vir Biotechnology, Inc. 
Confidential 
Page 104 
Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS Jr, Bzowej 
NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 
2018 hepatitis B guidance. Hepatology. 2018 Apr;67(4):1560-1599. doi: 10.1002/hep.29800. 
PMID: 29405329; PMCID: PMC5975958. 
Trepo C. A brief history of hepatitis milestones. Liver Int. 2014 Feb;34 Suppl 1:29-37. doi: 
10.1111/liv.12409. PMID: 24373076. 
Tsuge M, Hiraga N, Uchida T, Kan H, Miyaki E, Masaki K, Ono A, Nakahara T, Abe-Chayama 
H, Zhang Y, Naswa MG, Kawaoka T, Miki D, Imamura M, Kawakami Y, Aikata H, Ochi H, 
Hayes CN, Chayama K. Antiviral effects of anti-HBs immunoglobulin and vaccine on HBs 
antigen seroclearance for chronic hepatitis B infection. J Gastroenterol. 2016 Nov;51(11):1073-
1080. doi: 10.1007/s00535-016-1189-x. Epub 2016 Mar 4. PMID: 26943168. 
VIREAD® (tenofovir disoproxil fumarate) [US package insert]. Foster City, CA: Gilead 
Sciences, Inc.; 2019. 
Wang G, Duan Z. Guidelines for Prevention and Treatment of Chronic Hepatitis B. J Clin Transl 
Hepatol. 2021 Oct 28;9(5):769-791. doi: 10.14218/JCTH.2021.00209. Epub 2021 Sep 28. 
PMID: 34722192; PMCID: PMC8516840. 
Yuen MF, Lim YS, Cloutier D, Thanawala V, et al. Preliminary Results From a Phase 2 Study 
Evaluating VIR-2218 Alone and in Combination With Pegylated Interferon Alfa-2a in 
Participants With Chronic Hepatitis B Infection. Oral Presentation. Presented at AASLD: The 
Liver Meeting (Virtual), November12-15, 2021. 
Zalevsky J, Chamberlain AK, Horton HM, Karki S, Leung IW, Sproule TJ, Lazar GA, 
Roopenian DC, Desjarlais JR. Enhanced antibody half-life improves in vivo activity. Nat 
Biotechnol. 2010 Feb;28(2):157-9. doi: 10.1038/nbt.1601. Epub 2010 Jan 17. PMID: 20081867; 
PMCID: PMC2855492. 
Zoulim F, Durantel D. Antiviral therapies and prospects for a cure of chronic hepatitis B. Cold 
Spring Harb Perspect Med. 2015 Apr 1;5(4):a021501. doi: 10.1101/cshperspect.a021501. PMID: 
25833942; PMCID: PMC4382723. 

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