Phase 2, Double-blind, Randomized, Placebo-controlled Study of HepTcell (Adjuvanted FP-02.2) as an Immunotherapeutic Vaccine in Treatment-naïve Patients With Inactive Chronic Hepatitis B (CHB)
Phase: PHASE2
Conditions: Hepatitis B, Chronic
Sponsor: Altimmune, Inc.

Altimmune, Inc.
910 Clopper Road, Suite 201 S
Gaithersburg, MD  20878
USA
Clinical Study Protocol
DRUG:
HepTcell (Adjuvanted FP-02.2)
STUDY NUMBER:
ALT-301-202
PROTOCOL TITLE:
Phase 2, Double-blind, Randomized, Placebo-
controlled Study of HepTcell (Adjuvanted FP-02.2)
as an Immunotherapeutic Vaccine in Treatment-
naïve Patients with Inactive Chronic Hepatitis B 
(CHB)
IND NUMBER
IND 20482
EudraCT Number
2020-002118-42
SPONSOR:
Altimmune, Inc.
Amendment 04 (Version 5.0)
24 July 2022
Confidentiality Statement
The information in this document is confidential, and its contents are the property of 
Altimmune, Inc. and are confidential. Unauthorized copying, distribution, disclosure, 
or use is prohibited.

Altimmune, Inc.
Protocol ALT-301-202 version 5.0
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HepTcell (Adjuvanted FP-02.2)
Page 2 of 81
CLINICAL PROTOCOL APPROVAL FORM
Protocol Title: Phase 2, Double-blind, Randomized, Placebo-controlled Study of 
HepTcell (Adjuvanted FP-02.2) as an Immunotherapeutic Vaccine in Treatment-naïve
Patients with Inactive Chronic Hepatitis B (CHB)
Study No: ALT-301-202
Protocol Version No: 5.0
Protocol Version Date: 24 July 2022
This study protocol was subject to critical review and has been approved by the Sponsor 
representative.
M. Scott Harris
Chief Medical Officer
Altimmune, Inc.
910 Clopper Road
Suite 201S, Gaithersburg, MD 20878
Signature and Date: ___________________________________________
Digitally signed by MATTHEW
SCOTT HARRIS
Date: 2022-07-24 22:41:33-04:00

Altimmune, Inc. 
Protocol ALT-301-202 version 5.0 
Confidential 
HepTcell (Adjuvanted FP-02.2) 
Page 3 of 81 
 
 
 
 
 
 
 
 
 
 
 
 
PROTOCOL ALT-301-202 
Phase 2, Double-blind, Randomized, Placebo-controlled Study of HepTcell 
(Adjuvanted FP-02.2) as an Immunotherapeutic Vaccine in Treatment-naïve 
Patients with Inactive Chronic Hepatitis B (CHB) 
CONFIDENTIALITY AND INVESTIGATOR STATEMENT 
The information contained in this protocol and all other information relevant to HepTcell 
are the confidential and proprietary information of Altimmune, Inc., and except as may 
be required by federal, state or local laws or regulation, may not be disclosed to others 
without prior written permission of Altimmune, Inc. 
I have read the protocol, including all appendices, and I agree that it contains all of the 
necessary information for me and my staff to conduct this study as described. I will 
conduct this study as outlined herein, in accordance with the regulations stated in the 
Federal Code of Regulations for Good Clinical Practice (GCP) and International Council 
for Harmonisation (ICH) guidelines 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 any 
amendments, and access to all information provided by Altimmune, Inc., or specified 
designees. I will discuss the material with them to ensure that they are fully informed 
about HepTcell and the study. 
 
 
______________________________ 
_________________________ 
Principal Investigator Name (printed) 
Signature 
 
 
_________________________ 
__________________ 
Date (dd-mmm-yyyy) 
Site Number 

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HepTcell (Adjuvanted FP-02.2) 
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STUDY SUMMARY 
Sponsor: Altimmune, Inc. 
Study Title: Phase 2, Double-blind, Randomized, Placebo-controlled Study of 
HepTcell (Adjuvanted FP-02.2) as an Immunotherapeutic Vaccine in Treatment-naïve 
Patients with Inactive Chronic Hepatitis B (CHB) 
Study Number: ALT-301-202 
Study Phase: 2 
Study Centers: Approximately 35 study centers in North America, Europe, United 
Kingdom and Asia-Pacific 
Number of Patients Planned: Approximately 80 patients with inactive CHB and low 
hepatitis B surface antigen (HBsAg) levels (10 to 200 IU/mL) randomized 1:1 to 
HepTcell or placebo and stratified by study center 
Duration of Patient Participation: Each patient will participate in the study up to 
approximately 77 weeks (a 5-week Screening Period, a 24-week Treatment Period, 
and a 52-week Follow-Up Period commencing after the last dose of study medication 
at Week 20) 
Enrollment Period: Approximately 24 months 
Test Product: HepTcell (adjuvanted synthetic fluoropeptide hepatitis B 
immunotherapeutic vaccine) 150 μg of each fluoropeptide + IC31® (500/20 nmol 
KLK/ODN1a) administered by intramuscular (IM) injection at intervals of 4 weeks 
for 6 doses 
Study Objectives: 
Primary Objective: To assess virologic response to HepTcell in treatment-naïve 
patients with inactive CHB 
Secondary Objectives: 
x To assess cellular immune response of HepTcell in treatment-naïve 
patients with inactive CHB 
x To assess the safety of HepTcell in treatment-naïve patients with inactive 
CHB 
Study Design: This study is a Phase 2, randomized, double-blind, placebo-controlled, 
multicenter clinical trial to evaluate the antiviral effects, immunogenicity, and safety 
of HepTcell in treatment-naïve patients with inactive CHB and low HBsAg levels (10 
to 200 IU/mL).  
After providing informed consent, patients will undergo a screening period of up to 
35 days. A Fibroscan will be performed in all patients who have not had this 
examination within the previous 12 months before screening, with the exception of 

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patients with a prior history of liver biopsy within the past 2 years demonstrating no 
evidence of significant fibrosis. 
Patients who meet inclusion and exclusion criteria will be randomized in a 1:1 ratio to 
receive 6 IM doses of HepTcell or placebo (normal saline) at study visits 4 weeks 
apart (Days 1, 29, 57, 85, 113, 141). Randomization may occur up to 3 working days 
before the first day of dosing to allow for the possible preparation of study medication 
by a central pharmacy and shipment to the study site. Adverse events (AEs) will be 
monitored, and blood samples will be collected for quantitative HBsAg (qHBsAg), 
anti-HBsAg antibodies (anti-HBs), hepatitis B virus (HBV) DNA, HBV pre-genomic 
RNA (pg-RNA), hepatitis B core-related antigen (HBcrAg), and interferon-gamma 
(IFN-ȖHQ]\PH-linked immunosorbent spot (ELISpot) assay in peripheral blood 
mononuclear cells (PBMCs). Patients will record any reactogenicity events for 7 days 
after each administration of study medication in a diary. A visit consisting of a 
targeted physical examination and safety laboratory tests, including liver panels, will 
be conducted 7±2 days after administration of Doses 1 and 2 of study medication. 
These visits may be conducted at home or workplace or, in part, as a telemedicine 
visit, at the discretion of the Investigator.  
If the patient has experienced an acute illness or temperature > 38°C in the 2 days 
prior to dosing, the administration of study medication and corresponding visit will be 
delayed until the illness or fever has resolved. 
A Safety Committee will conduct regular blinded reviews of all AEs and 
reactogenicity events. The safety of study participants will also be overseen by an 
unblinded Data Monitoring Committee (DMC); its responsibilities will be laid out in a 
DMC charter. 
A sentinel cohort of 12 patients (6 receiving HepTcell and 6 placebo) will undergo 
blinded safety review by the Safety Committee 7 to 10 days after all ongoing patients 
in the sentinel cohort have completed the respective dose of study medication and will 
determine the decision to continue at that dose to the expanded cohort. Safety will be 
assessed in the sentinel cohort before each dose is administered to the expanded 
cohort. If any of the Stopping Rules (below) are met in one or more patients and the 
event(s) is deemed possibly or probably related to HepTcell, dosing will be suspended 
pending DMC review. DMC recommendations may include instituting modifications 
to ensure the safety of continued dosing or discontinuing the study. If none of the 
Stopping Rules are met, randomization and dosing may continue in the expanded 
study cohort. Patients will be unblinded as necessary as to assess the relationship 
between the study medication and events that meet criteria for Stopping Rules. 
Safety laboratory testing (Table 3), including liver panel, for Doses 1 and 2 will be 
obtained during the visits conducted 7±2 days after these doses of study medication. 
Safety laboratory testing following Doses 3, 4 and 5 will be obtained in the interval 
from 7 days after dose administration and before the next dose of study medication is 
administered. Safety labs after Dose 6 will be assessed at the Day 169 visit. 
Investigators will review the eligibility of all patients prior to dosing to determine if 
the next treatment is to be administered. Eligibility for the next treatment will include: 

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1) confirmation that patients did not meet a Stopping Rule (below); 2) confirmation 
that the pre-treatment liver parameters are within acceptable ranges for treatment 
(below); 3) confirmation that patients do not have a new confirmed or suspected 
immune-mediated medical condition (IMC) (Appendix 2). Patients not meeting these 
criteria will not be treated.  
If abnormalities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), 
total bilirubin, direct bilirubin, or international normalized ratio (INR) are reported 
after dosing is commenced, the following monitoring and dosing rules will be applied: 
Toxicity 
Management 
Discontinuation of Study 
Medication 
$/7RU$67îEXWî8/1
and  
7RWDODQGGLUHFWELOLî8/1
and 
,15î8/1 
Continue dosing 
Monitor liver panel weekly 
,I$/7$67IDOOWRî
ULN, stop weekly monitoring 
 
$/7RU$67î8/1and 
7RWDODQGGLUHFWELOLî8/1
and 
,15î8/1 
Interrupt dosing 
Monitor liver panel weekly 
If $/7$67IDOOWRî8/1
restart dosing; if ALT/AST 
IDOOWRî, stop weekly 
monitoring 
If the event does not resolve 
in 4 weeks or recurs, consult 
medical monitor about 
discontinuing study 
medication 
$/7RU$67î8/1and  
7RWDORUGLUHFWELOLî8/1or 
,15î8/1 
 
Discontinue study medication 
$/7RU$67î8/1and  
7RWDORUGLUHFWELOLî8/1or 
,15î8/1 
Interrupt dosing 
Monitor liver panel weekly 
If total and direct bili fall to 
î8/1DQGRU,15IDOOV
WRîRQFRQVHFXWLYH
tests, stop weekly monitoring 
and restart dosing 
If the event does not resolve 
in 4 weeks or recurs, consult 
medical monitor about 
discontinuing study 
medication 
For patients with Gilbert SynGURPHWKHî8/1FULWHULDIRUWRWDODQGGLUHFW
ELOLUXELQZLOOEHUHSODFHGZLWKDî8/1for direct bilirubin and there will be no 
monitoring criteria for total bilirubin [Fontana 2020]. Other etiologies of ALT, AST, 
total and direct bilirubin, and INR elevations, such liver injury induced by other drugs 
and other viral infections, should be ruled out and treated accordingly. 
If a patient prematurely discontinues study medication on or before Day 169, the 
Day 169/Early termination procedures will be performed. Patients who prematurely 
discontinue study medication will remain in the study for follow-on study 
assessments. 
Patients will be followed for 52 weeks after the last dose of study medication 
(504 days beyond Day 1 for patients who complete the 24-week Treatment Period). 

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AEs and concomitant medications will be recorded from the signing of informed 
consent to Day 169, but only medically-attended adverse events (MAEs), new-onset 
chronic illnesses (NCIs), and IMCs, which will be categorized as AEs, will be 
followed subsequently. Likewise, concomitant medications will be recorded through 
Day 169, but only immunosuppressive medications, vaccines, and new HBV 
treatments or medications associated with MAEs, NCIs, SAEs, hepatitis flares, or 
hepatic injury will be recorded beyond this point. At the end of the clinical trial, the 
decision about follow-on treatments and medical care will be made by the patient’s 
medical physician or medical team in accordance with the usual standard of care. 
Patients will be required to limit their alcohol consumptions to no more than moderate 
intake (defined as 2 drinks/day for men and 1 drink/day for women) during their 
participation in the study. 
Risk-factor appropriate surveillance for hepatocellular carcinoma (HCC) may be 
performed at the discretion of the investigator. 
The measures to be taken at each investigative site to minimize the risks of COVID-19 
will be communicated to the patient, along with any changes to the risks of study 
participation that occur as a result of changing local COVID-19 conditions. Study 
participants will not be prevented from receiving COVID-19 vaccines during their 
trial participation and will be advised accordingly. If an authorized COVID-19 
vaccine has been administered in proximity to a scheduled investigational product (IP) 
administration, a ± 3 day window is allowed for IP dosing. 
Stopping Rules: 
In consultation with the DMC, the following Stopping Rules will be applied: 
x ALT or AST îupper limit of normal (ULN) 
x INR  1.3 
x Total bilirubin  1.5î ULN (excluding patients with Gilbert Syndrome) 
x Direct bilirubin  1.5îULN (for patients with Gilbert Syndrome) 
x Serious adverse events (SAEs) 
x Severe systemic reactogenicity event 
Inclusion Criteria: 
Patients who meet all of the following criteria may be included in the study.  
1. Able and willing to provide informed consent 
2. Men and women 18 to 65 years of age, inclusive 
3. Body Mass Index (BMI) 18.0 to 34.9 kg/m2, inclusive 
4. Inactive, treatment-naïve CHB with documented HBsAg positivity for at least 
12 months before Day 1. (The history of HBsAg positivity may be reduced to 
6 months provided HBV anti-core IgM antibodies are negative). 
5. T+%V$J,8P/EXW200 IU/mL in the 12 months prior to screening or 
from informed consent to randomization 

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If a patient has more than one qHBsAg value within 12 months and prior to 
randomization, the patient will be deemed eligible if any one measurement is 
within the eligible range. 
6. AST, ALT, INR, albumin, total bilirubin (excluding patients with Gilbert 
Syndrome, who will only be eligible for study participation if total bilirubin is 
PJG/) and direct bilirubin within normal limits at screening. Note: ALT 
and AST elevations up to 1.5 x ULN are allowed if evidence of hepatic 
steatosis, defined as one of the following criteria: 1) fatty liver on ultrasound, 
or other imaging modality or Fibroscan controlled attenuation parameter 
&$3G%P. To qualify under these conditions, HBV DNA must be 
,8P/, and there must be no history or signs of liver disease other than 
fatty liver and HBV.  
7. Negative drug screen at screening unless prescribed by a medical practitioner 
for medical use (NB, recreational and prescription cannabis is allowed) 
8. For women of childbearing potential (women who are not permanently sterile 
[documented hysterectomy, bilateral tubal ligation, salpingectomy, or 
oophorectomy] or postmenopausal [12 months with no menses without an 
alternative medical cause]): 
a. Negative pregnancy test on Day 1 
b. Willingness to practice a highly effective method of birth control with low 
user dependency from screening through one menstrual cycle after the last 
dose of study medication, which include: 
i. Abstinence 
ii. Sex only with persons of the same sex 
iii. Monogamous relationship with vasectomized partner 
iv. Intrauterine device 
v. Combined estrogen and progestogen containing hormonal 
contraception associated with inhibition of ovulation (oral, intravaginal, 
transdermal) 
vi. Progestogen-only hormonal contraception associated with inhibition of 
ovulation (oral, injectable or implantable) 
vii. Intrauterine hormone-releasing system   
Patients who practice true abstinence or who exclusively have same sex 
partners need not use contraception, provided it is in line with their 
preferred and usual lifestyle. Periodic abstinence (eg, calendar, ovulation, 
symptothermal, post-ovulation methods) and withdrawal are not acceptable 
methods of contraception. Should any such patient stop practicing 
abstinence, they must use contraception as described above. 
9. For men with sexual partners of childbearing potential, as defined above: 
a. Abstinence 
b. History of vasectomy or surgical sterilization 

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c. Monogamous relationship with a postmenopausal or surgically sterilized 
partner 
d. Willingness to practice a highly effective method of contraception, as 
defined above, for 90 days after the last dose of study medication and to 
refrain from sperm donation for this time 
The same criteria pertaining to abstinence and withdrawal methods in women 
of childbearing potential (Inclusion Criterion 8) apply to men with sexual 
partners of childbearing potential 
10. Willingness to comply with all aspects of the study through the entire study 
period 
Patients who fail to meet Inclusion Criteria 5 and/or 6 and otherwise meet the 
requirements for study participation will be permitted one additional blood draw 
during the same screening period to requalify. Patients who screen fail for other 
Inclusion Criteria may undergo rescreening at the discretion of the Investigator and 
Medical Monitor. 
Exclusion Criteria: 
Patients who do not meet any of the following exclusion criteria may be included in 
the study.  
1. Pregnant or lactating women 
2. Positive hepatitis B e antigen (HBeAg) at screening 
3. History of a hepatitis B flare or 1-log increase in HBV DNA or HBsAg in the 
prior 6 months 
4. Prior or current history of active or untreated human immunodeficiency virus 
(HIV), hepatitis C virus (HCV), or hepatitis delta virus (HDV) 
5. Acute COVID-19, a positive test result for SARS-CoV2 infection, or exposure 
within 14 days to an individual with acute COVID-19 
6. )HEULOHLOOQHVVWHPSHUDWXUH&ZLWKLQWKHSDVWGD\V 
7. Prior or current history of any underlying liver disease not related to HBV 
(NB, steatosis, as documented by imaging or Fibroscan CAP, is permitted if 
ALT and AST are [8/1 DQG+%9'1$,8P/ and there is no 
history or signs of liver disease other than fatty liver and HBV)  
8. Fibroscan > 8.5 kPA at screening, or history of hepatic fibrosis or cirrhosis 
(NB, a Fibroscan is not required if an examination is performed within 12 
months before screening, or a liver biopsy was performed within 2 years 
before screening and no fibrosis [F1 or greater] was identified.) 
9. History of cirrhosis or signs of hepatic decompensation, including but not 
limited to variceal bleeding, ascites, or hepatic encephalopathy 
10. :KLWHEORRGFHOOFRXQW/QHXWURSKLOV/
hemoglobin  11 JG/RUSODWHOHWV25,000/μL 
Note: ,QGLYLGXDOVRI$IULFDQGHVFHQWZLWKDZKLWHEORRGFHOOFRXQW/
wLOOQRWEHH[FOXGHGIRUWKLVUHDVRQLIZKLWHEORRGFHOOFRXQWLV/

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SURYLGHGWKDWWKHQHXWURSKLOFRXQWLV/DQGWKHUHLVQRRWKHULGHQWLILHG
cause of leukopenia. 
11. Prior treatment with an approved or investigational agent for HBV. 
12. History of conditions associated with immunocompromise 
13. History of conditions associated with altered immune response, such as 
anaphylaxis, angioedema, or autoimmune disease 
14. Treatments known to affect the immune system, such as corticosteroids (other 
than topical or inhaled preparations), alkylating drugs, antimetabolites, 
cytotoxic drugs, radiation, immune-modulating biologics, allergy injections, 
immunoglobulins, interferons or other immunomodulating therapies, within 30 
days of screening 
15. Uncontrolled diabetes mellitus, defined as Hemoglobin A1C (HbA1&
at screening 
16. Receipt of live-attenuated replicating vaccines within 30 days or receipt of any 
other licensed or authorized vaccines (including vaccines intended to prevent 
COVID-19) within 14 days prior to Day 1 
17. Change in any chronically administered medication or treatment within 
14 days of screening or inability to maintain these medications at the same 
dose through Day 169 (NB, patients chronically using aspirin, non-steroidal 
anti-inflammatory agents, antacids, vitamins, probiotics, and over-the-counter 
medications will maintain their level of intake throughout the study) 
18. Malignancy within 3 years of screening, excluding non-melanoma skin cancers 
and carcinoma in situ cervical cancer (NB, patients who have undergone prior 
screening for HCC by imaging or alpha-fetoprotein levels will have negative 
test results) 
19. Untreated alcohol or drug abuse 
20. Planned elective surgery or hospitalization during the study period 
21. Participation in a prior trial involving HepTcell or FP-02.2 
22. Known allergy to any of the ingredients in HepTcell 
23. Receipt of any investigational drug or treatment within 30 days before Day 1 
or planned use during the study period 
24. Any medical, psychiatric, or social condition or occupational or other 
responsibility that in the judgment of the Investigator would interfere with or 
serve as a contraindication to protocol adherence, assessment of safety 
(including reactogenicity), or a patient’s ability to give informed consent 
Patients who are excluded by Exclusion Criterion 10 but otherwise meet the 
requirements for study participation will be permitted one additional blood draw to 
requalify. Patients who screen fail for other Exclusion Criteria may undergo 
rescreening at the discretion of the Investigator and Medical Monitor. 

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Efficacy Endpoints: 
Primary Efficacy Endpoint: 
The proportion of patients achieving virologic response, defined as a 1.0-log reduction 
in qHBsAg or serologic clearance of HBsAg, Baseline to Day 169 
Secondary Efficacy Endpoints: 
x Proportion of patients achieving serologic clearance of HBsAg on Day 169 
x Proportion of patients achieving serologic clearance of HBV DNA on 
Day 169 
x Changes in qHBsAg, HBV DNA, HBcrAg, and pg-RNA levels, Baseline 
to Days 85 and 169 
x Change in IFN-ȖIUHTXHQF\E\(/,6SRWLQ3%0&V%DVHOLQHWR'D\V
and 169 
Exploratory Efficacy Endpoints: 
x Proportions of patients achieving serologic clearance of HBsAg on 
Day 505 
x Proportions of patients achieving serologic clearance of HBV DNA on 
Day 505 
x Proportion of patients with anti-HBs on Day 505 
x Changes in qHBsAg, HBV DNA, HBcrAg, and pg-RNA levels, Baseline 
to Days 323 and 505 
x Change in IFN-ȖIUHTXHQF\E\(/,6SRWLQ3%0&V%DVHOLQHWR'D\V
and 505 
Safety Endpoints 
x Incidence and severity of AEs, MAEs, NCIs, and IMCs 
x Incidence and severity of local and systemic reactogenicity events 
x Incidence and duration RIKHSDWLWLVIODUHVGHILQHGDV$/7 î ULN and 
> 100 U/L 
x Changes in ALT, AST, alkaline phosphatase [AP], gamma glutamyl 
transferase [GGT], bilirubin total and direct, and INR and other laboratory 
parameters 
Safety endpoints will be assessed separately for the 24-week Treatment Period and 
52-week Follow-Up Period 
Statistical Methods: 
Power and Sample Size Assumptions: 
A study of interferon-D2 in a population with inactive CHB reported a mean 
incremental decrease of 1.3 log-qHBsAg at 24 weeks in those patients completing 
interferon-D2 treatment compared to non-treatment. Mean decrease would translate to 
DSSUR[LPDWHO\RISDWLHQWVFRPSOHWLQJ treatment achieving 1.3 log-qHBsAg 

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response (reduction). To estimate treatment effect in the current study, the proportion 
of patients achieving a 1.0-log reduction in qHBsAg is estimated as one-KDOIRI
patients) who achieve this response. Assuming a UHVSRQVHUDWHRIRQSODFHERDQG
RQ+HS7FHOO patients will be randomized per treatment group to detect a 
difference in the proportion of patients treated with HepTcell achieving the primary 
endpoint compared to patient treated with placebo at a 0.05 level of significance 
(two-VLGHGZLWKDSSUR[LPDWHO\SRZHU 
Statistical Analysis: 
Population definitions: 
Safety Analysis Set: All patients who receive any study medication. 
Modified intent to treat (mITT): All randomized patients who receive any amount of 
study medication, have a baseline and at least one post-baseline efficacy assessment. 
Patients will be analyzed according to the treatment that they receive. This analysis set 
will be used for primary and secondary analyses. 
Per Protocol (PP): All randomized patients who receive the full designated amount of 
study medication according to the correct treatment assignment and who have results 
from HBV serology and viral markers at Day 85.  
General: 
Baseline is defined as data collected closest to randomization prior to any study 
medication dosing. All analyses and summary statistics will be presented by treatment 
group (HepTcell, placebo). 
Descriptive statistics, including the numbers and percentages for categorical variables 
and the numbers, means, standard deviations, medians, minimums and maximums for 
continuous variables will be provided by treatment. 
Patients will be randomized 1:1 to HepTcell or placebo and stratified by study center 
to minimize imbalances between treatment groups. To assure a 1:1 distribution of 
HepTcell and placebo (6 patients each of 12 patients) in the sentinel cohort, 
randomization in this group will not be stratified. 
An interim analysis will be performed after all patients complete 24 weeks (6 doses) 
of treatment or discontinue study medications. 
Efficacy Analyses: 
Descriptive statistics will be used to evaluate differences in demographic and baseline 
characteristics. 
For the primary analysis, proportions of patients with virologic response, defined as a 
1.0-log reduction in HBsAg or serologic clearance of HBsAg, will be compared 
EHWZHHQ+HS7FHOODQGSODFHERJURXSVXVLQJ)LVKHU¶V([DFW7HVWDWDtwo-sided 
level of significance. The same approach will be applied for secondary or exploratory 
endpoints that are categorical in nature. Patients who discontinue prematurely or have 
missing data will be considered non-responders for that endpoint. Linear and logistic 
regression will be employed to examine the effects of baseline factors, such as 
qHBsAg level, HBV DNA levels, hepatitis B genotype on response. 

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Changes from baseline in PBMC ELISpot, HBsAg, HBcrAg, pg-RNA and HBV DNA 
will be analyzed using a mixed model for repeated measures (MMRM) model. The 
model will include the fixed effects of treatment, stratification factor, week, and 
treatment-by-visit interaction as well as the continuous, covariate of baseline level. 
The model will employ an unstructured within patient covariance matrix and a 
restricted maximum likelihood (ReML) estimation method. 
A Kaplan-Meier model will be developed to compare changes between treatment 
groups in HBsAg clearance and a 1-log reduction in HBsAg over time. 
Relationships between hepatitis flares and HBsAg loss and/or decline will be 
evaluated logistic and linear regression. 
No multiplicity adjustments will be made for secondary or exploratory endpoints. 
Safety and Tolerability: 
Quantitative safety data will be summarized using descriptive statistics and frequency 
distributions. Qualitative safety data will be summarized by frequencies and 
percentages. All summaries will be presented by treatment arms. AEs will be coded 
using Medical Dictionary for Regulatory Activities (MedDRA®), Concomitant 
medications will be coded using World Health Organization (WHO) drug dictionary. 
Laboratory evaluations, vital signs assessments and electrocardiogram (ECG) 
parameters will be summarized by treatment group and protocol specified collection 
time point. A summary of change-from-baseline at each protocol specified time-point 
by treatment group will also be presented. 

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TABLE OF CONTENTS 
CLINICAL PROTOCOL APPROVAL FORM .................................................... 2 
CONFIDENTIALITY AND INVESTIGATOR STATEMENT ........................... 3 
STUDY SUMMARY............................................................................................. 4 
TABLE OF CONTENTS ..................................................................................... 14 
TABLE OF TABLES .......................................................................................... 19 
TABLE OF FIGURES ......................................................................................... 19 
LIST OF ABBREVIATIONS .............................................................................. 20 
1. 
INTRODUCTION AND RATIONALE........................................... 22 
1.1. 
Background ....................................................................................... 22 
1.1.1. 
Chronic Hepatitis B .......................................................................... 22 
1.1.2. 
HepTCell........................................................................................... 23 
1.1.3. 
IC31 .................................................................................................. 24 
1.2. 
Nonclinical Studies ........................................................................... 25 
1.3. 
Previous Clinical Study of FP-02.2 .................................................. 25 
1.4. 
Study Rationale ................................................................................. 26 
2. 
STUDY OBJECTIVES .................................................................... 28 
2.1. 
Primary ............................................................................................. 28 
2.2. 
Secondary ......................................................................................... 28 
3. 
STUDY ENDPOINTS ...................................................................... 29 
3.1. 
Primary Efficacy Endpoint ............................................................... 29 
3.2. 
Secondary Efficacy Endpoints .......................................................... 29 
3.3. 
Exploratory Efficacy Endpoints ....................................................... 29 
3.4. 
Safety Endpoints ............................................................................... 29 
4. 
STUDY PLAN.................................................................................. 30 
4.1. 
Study Design ..................................................................................... 30 
4.2. 
Study Schematic ............................................................................... 32 
4.3. 
Rationale for Study Design ............................................................... 33 
4.4. 
Rationale for Study Population ......................................................... 34 
4.5. 
Dose Rationale .................................................................................. 35 

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4.6. 
Schedule of Events ........................................................................... 36 
5. 
POPULATION ................................................................................. 40 
5.1. 
Number of Patients ........................................................................... 40 
5.2. 
Inclusion Criteria .............................................................................. 40 
5.3. 
Exclusion Criteria ............................................................................. 41 
6. 
STUDY MEDICATION ................................................................... 44 
6.1. 
Description ........................................................................................ 44 
6.1.1. 
Formulation....................................................................................... 44 
6.1.2. 
Packaging, Storage, and Handling .................................................... 44 
6.2. 
Randomization .................................................................................. 45 
6.3. 
Dose and Administration .................................................................. 45 
6.4. 
Dosing Modifications ....................................................................... 45 
6.5. 
Blinding and Unblinding .................................................................. 46 
6.6. 
Accountability................................................................................... 46 
6.7. 
Prior and Concomitant Therapy ........................................................ 47 
6.7.1. 
Prohibited Prior and Concomitant Medications ............................... 47 
6.8. 
Contraception .................................................................................... 48 
6.9. 
Compliance ....................................................................................... 48 
7. 
PREMATURE DISCONTINUATION ............................................ 49 
7.1. 
Individual Patients ............................................................................ 49 
7.1.1. 
Stopping Rules .................................................................................. 49 
7.1.2. 
Disease Progression / Need for Active Treatment ............................ 50 
7.2. 
Study as a Whole .............................................................................. 50 
8. 
DESCRIPTION OF STUDY PROCEDURES ................................. 51 
8.1. 
Screening Assessments ..................................................................... 51 
8.1.1. 
Demographics ................................................................................... 51 
8.1.2. 
Medical History ................................................................................ 51 
8.1.3. 
Fibroscan........................................................................................... 51 
8.1.4. 
Hepatitis B Genotyping .................................................................... 51 
8.2. 
Efficacy Assessments ....................................................................... 51 
8.2.1. 
Immunology ...................................................................................... 51 

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8.2.2. 
Virology ............................................................................................ 51 
8.2.3. 
Stored Sample for Future Analyses .................................................. 52 
8.3. 
Safety Assessments ........................................................................... 52 
8.3.1. 
Reactogenicity Assessments ............................................................. 52 
8.3.2. 
Adverse Events ................................................................................. 52 
8.3.3. 
Clinical Laboratory Tests ................................................................. 52 
8.3.4. 
Height, Weight and BMI .................................................................. 54 
8.3.5. 
Physical Examination ....................................................................... 54 
8.3.6. 
Vital Signs ........................................................................................ 54 
8.3.7. 
Electrocardiogram ............................................................................. 55 
9. 
ADVERSE EVENTS........................................................................ 56 
9.1. 
Definitions ........................................................................................ 56 
9.1.1. 
Adverse Event ................................................................................... 56 
9.1.2. 
Adverse Drug Reaction ..................................................................... 56 
9.1.3. 
Unexpected Adverse Drug Reaction ................................................ 56 
9.1.4. 
Medically Attended Adverse Event .................................................. 56 
9.1.5. 
New-Onset Chronic Illness ............................................................... 57 
9.1.6. 
Immune-Mediated Medical Conditions (IMC) ................................. 57 
9.1.7. 
Serious Adverse Event ...................................................................... 57 
9.2. 
Reporting Responsibilities and Periods ............................................ 58 
9.3. 
Assessment of Adverse Events ......................................................... 58 
9.3.1. 
Severity ............................................................................................. 58 
9.3.2. 
Relatedness (Causality) .................................................................... 59 
9.4. 
Safety Laboratory, Physical Examination, Electrocardiogram, and 
Vital Sign Abnormalities .................................................................. 59 
9.5. 
Pregnancy ......................................................................................... 60 
9.6. 
Overdose ........................................................................................... 60 
9.7. 
Procedures for Recording and Reporting Adverse Events ............... 60 
9.7.1. 
Recording Adverse Events ............................................................... 60 
9.7.2. 
Reporting of Serious Adverse Events ............................................... 61 
9.7.3. 
Special Reporting Situations............................................................. 62 
9.7.4. 
Reporting Pregnancies ...................................................................... 62 

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9.8. 
Safety Committee ............................................................................. 62 
9.9. 
Data Monitoring Committee ............................................................. 63 
9.10. 
Medical Monitor ............................................................................... 63 
10. 
STATISTICS .................................................................................... 64 
10.1. 
General Procedures ........................................................................... 64 
10.2. 
Sample Size ...................................................................................... 64 
10.3. 
Analysis Sets ..................................................................................... 64 
10.4. 
Statistical Methods............................................................................ 64 
10.4.1. 
Primary Efficacy Endpoint ............................................................... 64 
10.4.2. 
Secondary and Exploratory Efficacy Endpoints ............................... 65 
10.4.3. 
Analysis of Safety ............................................................................. 65 
10.4.4. 
Demographic and Baseline Characteristics ...................................... 65 
10.5. 
Interim Analysis................................................................................ 65 
10.6. 
Statistical Analysis Plan ................................................................... 66 
11. 
DATA QUALITY ASSURANCE .................................................... 67 
11.1. 
Data Handling ................................................................................... 67 
11.2. 
Computer Systems ............................................................................ 67 
11.3. 
Data Entry ......................................................................................... 67 
11.4. 
Medical Information Coding ............................................................ 67 
11.5. 
Data Validation ................................................................................. 67 
11.6. 
Study Monitoring Requirements....................................................... 68 
11.7. 
Source Document and Case Report Form Completion ..................... 68 
11.8. 
Record Retention .............................................................................. 69 
12. 
ETHICS ............................................................................................ 70 
12.1. 
Good clinical practice ....................................................................... 70 
12.2. 
Institutional Review Board / Independent Ethics Committee .......... 70 
12.3. 
Patient Information and Consent ...................................................... 70 
12.4. 
Patient Confidentiality ...................................................................... 71 
12.5. 
Protocol compliance ......................................................................... 71 
13. 
COMPENSATION, INSURANCE AND INDEMNITY ................. 72 
14. 
STEERING COMMITTEE .............................................................. 73 

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15. 
PUBLICATION POLICY ................................................................ 74 
16. 
REFERENCES ................................................................................. 75 
APPENDICES ..................................................................................................... 78 
Appendix 1 – Reactogenicity Events ................................................................... 78 
Appendix 2 – Immune-Mediated Medical Conditions ........................................ 79 
 
 
 

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TABLE OF TABLES 
Table 1 
Schedule of Events – Screening and Treatment Periods .................. 37 
Table 2 
Schedule of Events – Follow-up Period ........................................... 39 
Table 3: 
Safety Laboratory Tests .................................................................... 53 
 
TABLE OF FIGURES 
Figure 1: 
Study Visits and Treatments ............................................................. 33 
 

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LIST OF ABBREVIATIONS 
AE 
adverse event 
ALT 
alanine aminotransferase 
anti-HBs 
antibodies to hepatitis B surface antigen 
AST 
aspartate aminotransferase 
Bili 
bilirubin 
CAP 
controlled attenuation parameter 
CHB 
chronic hepatitis B 
DMC 
Data Monitoring Committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ELISpot 
enzyme-linked immunosorbent spot 
ET 
early termination 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HBeAg 
hepatitis B e antigen 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HBcrAg 
hepatitis B core-related antigen 
HCC 
hepatocellular carcinoma 
HCV 
hepatitis C virus 
HDV 
hepatitis delta virus 
HIV 
human immunodeficiency virus 
HLA 
human leukocyte antigen 
ICH 
International Council for Harmonization 
IEC 
Independent Ethics Committee 
IFN-Į 
interferon-alpha 
IFN-Ȗ 
interferon-gamma 
IM 
intramuscular 

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IMC 
immune-mediated medical condition 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
IWRS 
Interactive Web Response System 
KLK 
KLKLLLLLKLK (peptide component of IC31) 
MAE 
medically-attended adverse event 
MedDRA 
Medical Dictionary for Regulatory Activities 
NAFLD 
nonalcoholic fatty liver disease 
NB 
nota bene 
NCI 
new-onset chronic illness 
PBMC 
peripheral blood mononuclear cells 
pg-RNA 
pre-genomic RNA 
qHBsAg 
quantitative hepatitis B surface antigen 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
ULN 
upper limit of normal 
WBC 
white blood cells 
WHO 
World Health Organization 
 

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1. 
INTRODUCTION AND RATIONALE 
1.1. 
Background 
1.1.1. 
Chronic Hepatitis B 
Chronic hepatitis B (CHB) affects 292 million people worldwide (3.9RIWKHZRUOG¶V
population), of which 887,000 die annually of complications of the disease 
[Razavi-Shearer 2018, WHO 2019]. Universal childhood vaccination has significantly 
reduced new incidence of hepatitis B [WHO 2019]. Globally the most common cause of 
CHB is mother-to-child transmission at birth or close childhood contact with infected 
body fluids of a CHB carrier in endemic areas with incomplete vaccination programs. 
Most adults newly infected with hepatitis B virus (HBV) achieve spontaneous serologic 
clearance mediated by HBV-specific CD4+ and CD8+ T cells [Gehring 2019]; those that 
do not clear hepatitis B surface antigen (HBsAg) within 6 months are considered 
chronically infected. Individuals with CHB have profound defects in strength and quality 
of anti-HBV T cell immune responses as a result of immune tolerance or exhaustion 
[Ye 2015].  Immune tolerance may be the result of persistently elevated levels of HBV 
antigens including HBsAg secreted by infected hepatocytes. Overcoming immune 
tolerance by eliciting stronger and more functional cellular immunity is a cornerstone of 
novel CHB treatment strategies to achieve functional cure. 
Current standard of care involves therapy with nucleos(t)ide HBV polymerase inhibitors 
(NUCs) or interferon-alpha (IFN-Į to suppress HBV replication, and reduce hepatic 
necroinflammation and risk of end-stage liver disease [Terrault 2018; EASL 2017]. 
Nucleos(t)ide treatments only rarely achieve functional cure because of their inability to 
restore anti-HBV immunity [Tang 2014] and achieve HBsAg loss. Lifelong treatment is 
required for most patients because of viral rebound that occurs when treatment is 
discontinued. Although NUC therapy is well tolerated, long-term costs are substantial 
[Stahmeyer 2017; Tadrous 2018] and risks of hepatocellular carcinoma, cirrhosis, and 
liver failure are not eliminated [Block 2015; Wong 2018]. These complications have also 
been reported to occur in individuals with inactive CHB who might not otherwise be 
deemed candidates for NUC therapy [Chen 2010]. Interferon-based therapies have been 
associated with high variability of response and unfavorable safety profile that severely 
limit their use, and the use of interferon therapies is not recommended in patients with 
normal liver transaminases and low HBV DNA levels [EASL 2017]. 
Inactive CHB represents a condition of low-level viral replication and low or absent 
hepatic inflammation. Current society guidelines do not recommend treatment for these 
patients, because interferon, the only potential therapy for these patients, has toxicity, and 
the benefit risk ratio is low. However, the risk of hepatocellular carcinoma and cirrhosis 
in these patients remains real, and they continue to bear the lifelong stigmata of 
infectivity, including infecting sexual partners. They also are expected to endure the 
inconvenience of lifelong monitoring, including physician visits and blood tests every 
6 to 12 months, and pass these costs onto the healthcare system. As a result, these 
patients are seeking access to effective and better tolerated treatments for their condition. 

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Should an effective therapy emerge that would also be well-tolerated by patients, the 
benefit-risk ratio would favor benefit. The specificity of HepTcell for hepatitis B 
epitopes, the lack of homology with human proteins and expected absence of off-target 
effects, and the safety and tolerability of the immunotherapeutic in the prior Phase 1 trial 
suggest a favorable risk-benefit ratio for subjects who participate in this trial. 
1.1.2. 
HepTCell 
Altimmune is developing HepTcell (adjuvanted FP-02.2), an immunotherapeutic vaccine 
for treatment of CHB, to address the substantial unmet medical need of this patient 
population. 
HepTcell (adjuvanted FP-02.2) is the final reconstituted product for administration, that 
consists of a lyophilized mixture of 9 fluoropeptides and mannitol (FP-02.2 drug 
product), L-histidine buffer, normal saline (to achieve an isotonic, neutral pH), and IC31® 
(developed by Valneva SE). The 9 synthetic peptides (designated P877, P151, P113, 
P856(K), P753(K), P376, P797(K), P277(K), and P1266(K)) are each covalently linked 
to a fluorocarbon moiety on the N-terminus under a controlled process and formulated in 
mannitol. The peptides vary in length from 32 to 40 amino acids and correspond to a 
conserved region of HBV polymerase, core, or surface protein and contains CD4+ and 
CD8+ T cell epitopes. IC31 is a synthetic, 2-component adjuvant solution comprised of 
40 nmol/mL ODN1a, a single stranded oligodeoxynucleotide consisting of dimeric 
repeats of deoxy-inosine/deoxy-cytosine linked by an unmodified phosphodiester 
backboned and of 1000 nmol/mL KLKLLLLLKLK (KLK), comprising an 11 amino acid 
artificial cationic antimicrobial peptide. 
HepTcell is an immunotherapeutic vaccine specifically designed to enhance T cell 
immunity in patients with CHB and achieve durable control of the virus. With this aim, 
HepTcell has been designed to redirect CD4+ and CD8+ T cell immunity against 
multiple HBV targets, considering both human leukocyte antigen (HLA) and viral genetic 
diversity. It is intended to focus the immune system on discrete conserved and 
immunodominant regions of the HBV proteome presumably less subject to immune 
escape. It is envisioned that HepTcell can either be used alone or as an adjunct to one of 
the emerging and newer direct-acting agents, such as a small interfering RNA (siRNA) or 
capsid assembly modulator (CAM) that are designed to suppress HBV antigens to levels 
that allow restoration of T cell immune functions and the response to the vaccine. 
The manufacturing of the 9 fluoropeptides included in HepTcell relies on a 
well-established solid-phase protein synthesis using FMOC (fluorenylmethoxycarbonyl 
protecting group) chemistry and conventional reversed-phase high-performance liquid 
chromatography (RP-HPLC) purification systems for the production of fully 
characterizable drug substances. 
Each of the 9 peptides included in HepTcell is conjugated to a fluorocarbon moiety as 
part of the solid phase synthesis. Fluorocarbon conjugation results in the formation of a 
short-term antigen depot at the site of injection that prolongs the exposure of the antigens 

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to the immune system [Francis 2015a]. The time course for local degradation at the site 
of injection has not been determined. 
HepTcell was designed to bypass HLA restriction; each peptide sequence has been 
selected from the HBV proteome using a bioinformatics platform so that each peptide 
contains high-density clusters of HLA class I- and class II-binding epitopes that can be 
recognized by a broad patient population irrespective of their genetic background. In 
addition, these peptides have been selected to direct the immune system to target the most 
conserved regions of the virus, have the potential to induce immune responses against all 
known HBV genotypes, and impose high viral fitness costs that limit immune escape. 
&ROOHFWLYHO\WKHVHSHSWLGHVUHSUHVHQWLQJRIWKH+%9SURWHRPHFDQVWLPXODWH
peripheral blood mononuclear cells (PBMCs) in patients with CHB with diverse HLA 
backgrounds. By redirecting the immune system toward the conserved sequences, 
HepTcell has the potential to be more efficient than other vaccine strategies comprising 
full-length antigens, which are associated with poorly directed immune response. 
Perfluorocarbon emulsions have been evaluated as artificial oxygen carriers and shown to 
be safe and well tolerated in animal and human studies [Spahn 1999; Noveck 2000]. The 
perfluorocarbon tested in these studies shares strong homology with the fluoropeptides in 
HepTcell. The dose of fluoropeptides in a single dose of HepTcell (2.25 μg 
fluorocarbon/kg) is several log-fold lower than the dose of fluorocarbon (1.8 g/kg) 
employed in these studies. 
A 6-fluoropeptide influenza vaccine (FP-01.1) using the same fluorocarbon moiety was 
also evaluated in 222 healthy volunteers at doses equivalent of 30 to 300 μg of 
fluorocarbon per injection [NCT01701752, NCT01677676, NCT02071329, 
NCT01265914 and Francis 2015b]. Administration of FP-01.1 resulted in an acceptable 
safety profile and induced robust antiviral T cell responses in a high proportion of 
subjects tested. Clinical studies of perfluorocarbon emulsions with related structure to the 
fluorocarbon moiety used in FP-02.2 have shown these compounds to be well tolerated at 
doses much higher than the fluorocarbon dose in HepTcell. 
1.1.3. 
IC31 
IC31 is a synthetic, 2-component adjuvant comprised of ODN1a, a phosphodiester 
backboned single-stranded oligonucleotide with alternating sequences of the nucleic 
acids inosine and cytidine, and KLKLLLLLKLK (KLK), a cationic antimicrobial 
peptide. 
During nonclinical development, the fluoropeptides (FP-02.1 and FP-02.2) were 
administered by intramuscular (IM) injection over a range of doses, both with and 
without adjuvant IC31. Nonclinical immunogenicity was studied in BALB/c mice and the 
addition of IC31 increased the magnitude and breadth of the immune response and 
prolonged its duration. Additionally, IC31 has been used as an adjuvant combined to 
different vaccines in at least 20 Phase 1 and 2 clinical studies and more than 1221 
subjects with an acceptable safety profile and demonstrated adjuvanticity. Details of these 
studies can be found in the Investigator’s Brochure. 

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1.2. 
Nonclinical Studies 
Altimmune evaluated the functional properties of individual HBV peptides in human 
PBMCs to select the peptides to be included in HepTcell and subsequently evaluated the 
immunogenicity of FP-02.2 in the presence or absence of IC31 and earlier formulations 
in mice. The toxicity of FP-02.2 in the presence or absence of IC31 was also assessed in 
in vitro and in vivo studies. 
Immunogenicity studies in mice demonstrated a robust CD8-dominated T cell response, 
with both phenotypic and functional cytotoxic T cell profiles. The addition of IC31 
increased the magnitude and breadth of this response and prolonged its duration in these 
studies. 
Sequence homology analysis showed no significant similarity between the 9 peptides in 
FP-02.2 and human protein sequences, including those related to autoimmune 
manifestations. 
Intramuscular administration of FP-02.2 + IC31 to mice in 4 doses over 6 weeks (Days 1, 
15, 29, and 43) was well tolerated with no test article-related deaths and only minor 
changes in clinical pathology that were likely attributable to immune stimulation. 
Administration of FP-02.2 only, IC31 only, or FP-02.2 + IC31 was associated with a 
number of histopathological changes at the injection sites, particularly evident in females. 
Additionally, increased cellularity within the splenic white pulp was seen in animals 
administered IC31 only and FP-02.2 + IC31 and in female animals administered FP-02.2 
only. All the changes observed were considered to represent the expected local and 
systemic response to injection of a potent immunostimulatory product and were not 
considered to be adverse. Partial or complete reversibility was seen for all changes after a 
4-week recovery period. 
Assessment of mutagenicity of FP-02.2, the fluorocarbon vector, and IC31 by Ames 
testing showed no mutagenic activity. In vitro genotoxic studies of the FP-02.2 and IC31 
showed no induction of chromosomal aberration. 
In a local tolerance study in New Zealand White rabbits, IM injection of FP-02.2 with or 
without IC31 was well tolerated with no evidence of systemic toxicity or local dermal 
intolerance. 
Nonclinical toxicology data provided by Valneva demonstrate a general lack of toxicity 
for IC31 alone or in combination with vaccine antigens. 
Further details of the non-clinical studies can be found in the Investigator’s Brochure. 
1.3. 
Previous Clinical Study of FP-02.2 
Study FP-02.2_CS_01 was a Phase 1, randomized, double-blind, placebo-controlled 
clinical study of the safety, tolerability, and immunogenicity of FP-02.2 with and without 
IC31 conducted in the United Kingdom and South Korea. Sixty-one adult hepatitis B 
e antigen (HBeAg)-negative patients with CHB who were on chronic nucleoside 
analogue therapy were randomized to receive one of the following treatments as 3 IM 

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administrations in 4-week intervals over 12 weeks: low dose FP-02.2 (150 μg/peptide), 
low dose FP-02.2 + IC31, high dose FP-02.2 (500 μg/peptide), high dose FP-02.2 + IC31, 
IC31 alone, or placebo. Immunogenicity was assessed by an interferon-gamma (IFN-Ȗ) 
enzyme-linked immune absorbent spot (ELISpot) assay in PBMCs. 
A robust immunogenicity response was observed in patients treated with FP-02.2 in 
combination with IC31, with the low dose showing responses comparable to high dose 
responses. The magnitude of response increased with each successive dose of FP-02.2 
and suggested that additional doses would result in an even more robust immunologic 
response. 
All dose regimens were generally safe and well tolerated, with no effect of dose level, 
number of doses, or adjuvant was observed for any of the safety parameters. The 
incidences of injection reactions and adverse events (AEs) were similar in the FP-02.2-
treated and placebo groups. A trend to higher incidences of patient-reported injection site 
reactions were noted in the high dose + IC31 group but no severe reactions were reported, 
and reactions resolved by the next day in approximately half the subjects. There were no 
hepatitis flares or drug related serious AEs (SAEs). Laboratory results and vital signs 
measurements in the placebo group were similar to those in the FP-02.2 groups. 
Further details of the prior clinical study can be found in the Investigator’s Brochure. 
1.4. 
Study Rationale 
This Phase 2 study will evaluate the antiviral effects, immunogenicity, and safety of 
HepTcell in treatment-naïve patients with inactive CHB and low HBsAg levels (10 to 
200 IU/mL).  
The findings of Study FP-02.2_CS_01 establish the ability of HepTcell to induce cell-
mediated responses in HBeAg-negative patients under NUC treatment, which is known to 
be characterized by weak and dysfunctional circulating HBV-specific T cells. It also 
supports the superior immunological characteristics of FP-02.2, designed around highly 
selected conserved and immunodominant HBV-derived peptides, compared with other 
products from other companies in the HBV pipeline of full-length antigens. 
HepTcell was also safe and well-tolerated, with incidences of local injection site 
reactions and TEAEs similar to placebo. The results were consistent with the findings of 
nonclinical toxicology studies and the outcomes of other investigational vaccines 
adjuvanted with IC31. The safety of the current study will be enhanced by the use of a 
sentinel cohort and the use of the lower dose of FP-02.2 from Study FP-02.2_CS_01. 
While FP-02.2 did not show any significant impact on HBsAg levels (decline or loss), 
this likely reflects the short duration of the vaccine regimen and the unfavorable 
immunological status of NUC-treated HBeAg-negative patients enrolled in the study. 
With each successive dose of FP-02.2, a trend toward an increase of the immune 
responses was observed in this trial, so it is anticipated that longer treatment will further 
improve the anti-HBV immune response over time, and treatment has thus been extended 
from 3 to 6 doses. Furthermore, the patients in Study FP-02.2_CS_01 achieved low 

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circulating HBV DNA and HBsAg levels as the result of NUC therapy rather than 
spontaneous (intrinsic) immune control. HBeAg-negative patients with CHB on 
long-term NUC therapy often have relatively high and stable levels of serum HBsAg with 
little or no decline on therapy, and rarely achieving treatment induced HBsAg loss.  
High HBV antigen levels are a known cause of T cell exhaustion during chronic viral 
infection, and experts in the field have expressed the viewpoint of targeting HBV mRNA 
with nucleic acid-based products or using capsid assembly as a way to limit the HBV 
antigen production and serum levels and consequently improve HBV-specific T cell 
immune reconstitution in patients with CHB [Fanning 2019]. In this context, HepTcell is 
eventually anticipated to be beneficial in combination with novel direct acting antiviral 
agents (DAAs) to reduce HBsAg expression. 
In Study FP-02.2_CS_01, HepTcell tended to promote T cell responses primarily 
targeting the HBV polymerase antigen. This would indicate that in HBeAg-negative 
patients under NUC treatment, polymerase is less tolerizing than other HBV antigens, a 
hypothesis that is in line with other observations in the field [Rivino 2018; Loggi 2013]. 
Increasing the breadth of the response to other FP-02.2 antigens can be potentially 
achieved with longer treatment duration, combination with novel DAAs, and the 
selection of patients including those with spontaneous decline in HBsAg who tend to 
show better T cell responses [Loggi 2013]. Therefore, the composition of FP-02.2 will 
not be altered until further clinical evaluations are completed. 

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2. 
STUDY OBJECTIVES 
2.1. 
Primary 
The primary objective of the study is to assess virologic response to HepTcell in 
treatment-naïve patients with inactive CHB. 
2.2. 
Secondary 
The secondary objectives of the study are to assess: 
x Cellular immune response of HepTcell in treatment-naïve patients with 
inactive CHB 
x Safety of HepTcell in treatment-naïve patients with inactive CHB 

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3. 
STUDY ENDPOINTS 
3.1. 
Primary Efficacy Endpoint 
The proportion of patients achieving virologic response, defined as a 1.0-log reduction in 
quantitative HBsAg (qHBsAg) or serologic clearance of HBsAg, Baseline to Day 169. 
3.2. 
Secondary Efficacy Endpoints 
x Proportion of patients achieving serologic clearance of HBsAg on Day 169 
x Proportion of patients achieving serologic clearance of HBV DNA on 
Day 169 
x Changes in qHBsAg, HBV DNA, hepatitis B core-related antigen (HBcrAg) 
and pre-genomic RNA (pg-RNA) levels, Baseline to Days 85 and 169 
x Change in IFN-ȖIUHTXHQF\E\(/,6SRt assay in PBMCs, Baseline to Days 85 
and 169 
3.3. 
Exploratory Efficacy Endpoints 
x Proportion of patients achieving serologic clearance of HBsAg on Day 505 
x Proportion of patients achieving serologic clearance of HBV DNA on 
Day 505 
x Proportion of patients with anti-HBsAg antibodies (anti-HBs) on Day 505 
x Changes in qHBsAg, HBV DNA, HBcrAg, and pg-RNA levels, Baseline to 
Days 323 and 505 
x Change in IFN-ȖIUHTXHQF\E\(/,6SRWassay in PBMCs, Baseline to 
Days 323 and 505 
3.4. 
Safety Endpoints 
x Incidence and severity of AEs, medically-attended AEs (MAEs), new-onset 
chronic illnesses (NCIs), and immune-mediated medical conditions (IMCs) 
x Incidence and severity of local and systemic reactogenicity events 
x Incidence and duration of hepatitis flares, defined as alanine aminotransferase 
(ALT)  î upper limit of normal (ULN) and > 100 U/L 
x Changes in ALT, aspartate aminotransferase (AST), alkaline phosphatase 
(AP), gamma glutamyl transferase (GGT), bilirubin total and direct, 
international normalized ratio (INR) and other laboratory parameters 
Safety endpoints will be assessed separately for the 24-week Treatment Period and 
52-week Follow-Up Period. 

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4. 
STUDY PLAN 
4.1. 
Study Design 
This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter clinical trial 
to evaluate the antiviral effects, immunogenicity, and safety of HepTcell in treatment-
naïve patients with inactive CHB and low HBsAg levels (10 to 200 IU/mL). 
After providing written informed consent, patients will undergo a screening period of up 
to 35 days. A Fibroscan will be performed in all patients who have not had this 
examination within the previous 12 months before Screening with the exception of 
patients with a prior history of liver biopsy within the past 2 years demonstrating no 
evidence of significant fibrosis. 
Patients who meet inclusion and exclusion criteria will be randomized in a 1:1 ratio to 
receive 6 IM doses of HepTcell or placebo (normal saline) at study visits 4 weeks apart 
(Days 1, 29, 57, 85, 113, 141). Randomization may occur up to 3 working days before the 
first day of dosing to allow for the possible preparation of study medication by a central 
pharmacy and shipment to the study site. Adverse events (AEs) will be monitored, and 
blood samples will be collected for qHBsAg, anti-HBs, HBV DNA, HBV pg-RNA, 
HBcrAg, and IFN-Ȗ(/,6SRWDVVD\LQ3%0&V3DWLHQWVZLOOUHFRUGDQ\UHDFWRJHQLFLW\
events (see Appendix 1) for 7 days after each administration of study medication in a 
diary. A visit consisting of a targeted physical examination and safety laboratory tests, 
including liver panels, will be conducted 7±2 days after administration of Doses 1 and 2 
of study medication. These visits, per the Schedule of Events (Table 1 and Table 2), may 
be conducted at home or workplace or, in part, as a telemedicine visit, at the discretion of 
the Investigator.  
If the patient has experienced an acute illness or temperature > 38°C in the 2 days prior to 
dosing, the administration of study medication and corresponding visit will be delayed 
until the illness or fever has resolved. 
A Safety Committee will conduct regular blinded reviews of all AEs and reactogenicity 
events. The safety of study participants will also be overseen by an unblinded Data 
Monitoring Committee (DMC); its responsibilities will be laid out in a DMC charter. 
A sentinel cohort of 12 patients (6 receiving HepTcell and 6 placebo) will undergo 
blinded safety review by the Safety Committee 7 to 10 days after all ongoing patients in 
the sentinel cohort have completed the respective dose of study medication and will 
determine the decision to continue at that dose to the expanded cohort. Safety will be 
assessed in the sentinel cohort before each dose is administered to the expanded cohort. If 
any of the Stopping Rules in Section 7.1.1 are met in one or more patients and the 
event(s) is deemed possibly or probably related to HepTcell, dosing will be suspended 
pending DMC review. DMC recommendations may include instituting modifications to 
ensure the safety of continued dosing or discontinuing the study. If none of the Stopping 
Rules are met, randomization and dosing may continue in the expanded study cohort. 
Patients will be unblinded as necessary to assess the relationship between the study 
medication and events that meet criteria for Stopping Rules. 

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Safety laboratory testing (Table 3), including liver panel, for Doses 1 and 2 will be 
obtained during the visits conducted 7±2 days after these doses of study medication. 
Safety laboratory testing following Doses 3, 4 and 5 will be obtained in the interval from 
7 days after dose administration and before the next dose of study medication is 
administered. Safety labs after Dose 6 will be assessed at the Day 169 visit. Investigators 
will review the eligibility of all patients prior to dosing to determine if the next treatment 
is to be administered. Eligibility for the next treatment will include: 1) confirmation that 
patients did not meet a Stopping Rule (Section 7.1.1); 2) confirmation that the 
pre-treatment liver parameters are within acceptable ranges for treatment (below); 
3) confirmation that patients do not have a new confirmed or suspected IMC 
(Appendix 2). Patients not meeting these criteria will not be treated. 
If abnormalities of ALT, AST, total bilirubin, direct bilirubin, or international normalized 
ratio (INR) are reported after dosing is commenced, the following monitoring and dosing 
rules will be applied: 
Toxicity 
Management 
Discontinuation of Study 
Medication 
ALT or $67îEXW î ULN, 
and  
7RWDODQGGLUHFWELOLîULN, 
and 
,15îULN 
Continue dosing 
Monitor liver panel weekly 
If ALT/AST fall to 
îULN, stop weekly 
monitoring 
 
ALT or $67îULN, and 
7RWDODQGGLUHFWELOLîULN, 
and 
,15îULN 
Interrupt dosing 
Monitor liver panel weekly 
,I$/7$67IDOOWRîULN, 
restart dosing; if ALT/AST 
IDOOWRî, stop weekly 
monitoring 
If the event does not resolve 
in 4 weeks or recurs, consult 
medical monitor about 
discontinuing study 
medication 
ALT or $67 5îULN, and  
7RWDORUGLUHFWELOLîULN, or 
,15îULN 
 
Discontinue study medication 
ALT or $67îULN, and  
Total or GLUHFWELOL1.5îULN, or 
,15îULN 
Interrupt dosing 
Monitor liver panel weekly 
If total and direct bili fall to 
îULN and/or INR falls 
WRîon 2 consecutive 
tests, stop weekly monitoring 
and restart dosing 
If the event does not resolve 
in 4 weeks or recurs, consult 
medical monitor about 
discontinuing study 
medication 
FRUSDWLHQWVZLWK*LOEHUW6\QGURPHWKHî8/1FULWHULDIRUWRWDODQGGLUHFWELOLUXELQ
ZLOOEHUHSODFHGZLWKDî8/1for direct bilirubin and there will be no monitoring 
criteria for total bilirubin [Fontana 2020]. Other etiologies of ALT, AST, total and direct 
bilirubin, and INR elevations, such liver injury induced by other drugs and other viral 
infections, should be ruled out and treated accordingly. 

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If a patient prematurely discontinues study medication on or before Day 169, the 
Day 169/Early termination procedures will be performed. Patients who prematurely 
discontinue study medication will remain in the study for follow-on study assessments. 
Patients will be followed for 52 weeks after the last dose of study medication (504 days 
beyond Day 1 for patients who complete the 24-week Treatment Period). AEs and 
concomitant medications will be recorded from the signing of informed consent to 
Day 169, but only MAEs, NCIs, and IMCs, which will be categorized as AEs, will be 
followed subsequently. Likewise, concomitant medications will be recorded through 
Day 169, but only immunosuppressive medications, vaccines, and new HBV treatments 
or medications associated with MAEs, NCIs, SAEs, hepatitis flares, or hepatic injury will 
be recorded beyond this point. At the end of the clinical trial, the decision about follow-
on treatments and medical care will be made by the patient’s medical physician or 
medical team in accordance with the usual standard of care. 
Patients will be required to limit their alcohol consumptions to no more than moderate 
intake (defined as 2 drinks/day for men and 1 drink/day for women) during their 
participation in the study.  
Risk-factor analysis and appropriate surveillance for hepatocellular carcinoma (HCC) 
may be performed at the discretion of the investigator. 
The measures to be taken at each investigative site to minimize the risks of COVID-19 
will be communicated to the patient, along with any changes to the risks of study 
participation that occur as a result of changing local COVID-19 conditions. Study 
participants will not be prevented from receiving COVID-19 vaccines during their trial 
participation and will be advised accordingly. If an authorized COVID-19 vaccine has 
been administered in proximity to a scheduled investigational product (IP) 
administration, a ± 3-day window is allowed for IP dosing (Table 1). 
4.2. 
Study Schematic 
Each patient will participate in the study up to approximately 77 weeks (a 5--week 
Screening Period, a 24-week Treatment Period, and a 52-week Follow-up Period 
commencing after the last dose of study medication at Week 20). 

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Figure 1:
Study Visits and Treatments
4.3.
Rationale for Study Design
The study design replicates the general design of the prior Phase 1 study but extends 
treatment from 3 to 6 doses and the follow-up after the last dose of study medication from 
30 to 52 weeks. These modifications will enhance the effects of study medication and 
provide a more extended follow-up to assess the durability of immunogenicity and AEs. 
Diaries will be collected for reactogenicity events at visits on Days 8 and 36, which 
correspond to 7±2 days after the first and second dose of study medication. A visit 
consisting of a targeted physical examination will be conducted 7±2 days after 
administration of Doses 1 and 2 of study medication. Safety laboratory testing (Table 3), 
including liver panel, for Doses 1 and 2 will be obtained during the visits conducted 7±2 
after these doses of study medication. Safety laboratory for Doses 3, 4 and 5 will be 
obtained in the pre-treatment interval from 7 days after dose administration through the 
time that the next dose of study medication is administered. Safety labs after Dose 6 will 
be assessed at the Day 169 visit. Investigators will review the eligibility of all patients 
prior to dosing to determine if the next treatment is to be administered. Eligibility for the 
next treatment will include: 1) confirmation that patients did not meet a Stopping Rule 
(Section 7.1.1); 2) confirmation that the pre-treatment liver parameters are within 
acceptable ranges for treatment (Section 4.1); 3) confirmation that patients do not have a 
new confirmed or suspected IMC (Appendix 2). If abnormalities of ALT, AST, total 
bilirubin, direct bilirubin, or INR are reported after dosing is commenced, the monitoring 
and dosing rules of Section 4.1 will be applied. These procedures are considered 
sufficient to evaluate reactogenicity events, particularly after Doses 1 and 2, and guard 

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against hepatitis flares and liver function abnormalities that would preclude the scheduled 
administration of the next dose of study medication. 
For most vaccines, reactogenicity is typically experienced within 3 days of vaccination, 
commensurate with the innate immune response. Because distinct and separate antigens 
are targeted, no specific interactions or immunological interferences between COVID-19 
vaccines and HepTcell are otherwise anticipated. Therefore, if an authorized COVID-19 
vaccine has been administered in proximity to a scheduled investigational product (IP) 
administration, a ± 3 day window is allowed for IP dosing (Table 1). A COVID-19 
vaccine given to a trial subject will be considered as a simple concomitant medication. 
The grading of AE severity is described in Section 9.3.1. The US Food and Drug 
Administration Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials [United States Food and Drug 
Administration 2007] will be the primary scale used to grade AE severity. This scale is 
being employed because the study population is anticipated to be relatively healthy and 
the proposed scale is felt to be better reflective of a healthy population that participates in 
vaccine trials. This scale also offers more detailed grading criteria for local reactogenicity 
events, particularly those for which measurement offers better characterization of the 
event 
The study design adheres to the 2020 US Food and Drug Administration (FDA), 
European Medicines Agency (EMA), Health Canada and Medicines Health products 
Regulatory Agency (MHRA) guidances on the conduct of clinical trials during the 
COVID-19 pandemic [United States Food and Drug Administration 2020, European 
Medicines Agency 2020, Health Canada 2020, Medicines and Healthcare products 
Regulatory Agency 2021]. To that end, the minimal number of in-person clinic 
assessments deemed necessary for the safety and protection of patients are being 
undertaken, with home, work and telemedicine visits being conducted whenever possible. 
The risks and methods to minimize the risks of COVID-19 will be discussed with each 
patient, and changes in the risks of clinical trial tasks that occur as a result of changes in 
local circumstances will be assessed during the trial and communicated to patients on an 
ongoing basis. Study participants will not be prevented from receiving COVID-19 
vaccines during their trial participation and will be advised accordingly. 
4.4. 
Rationale for Study Population 
Patients with inactive CHB and low HBsAg are likely to represent a population of 
patients more likely to benefit from immunotherapy than the population in 
Study FP02.2_CS_01, who could only achieve viral suppression through the use of 
nucleoside analogues. Inactive CHB patients have relatively low circulating levels of 
HBV DNA and are already demonstrating intrinsic immune control, albeit incomplete, 
over the virus. T cell responses against HBV antigens have also been shown to be 
inversely associated with serum HBsAg level, with lower levels leading to higher rates of 
spontaneous HBsAg serologic clearance [Loggi 2013]. In two studies of patients with 
inactive CHB treated with IFN-Į therapy, the HBsAg cutoffs predicting HBsAg serologic 
clearance were 71 and 200 IU/mL, respectively [Lim 2019, Cao 2017]. In a metanalysis 

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of effects of patients treated with IFN-Įbaseline qHBsAg levels predicted functional 
cure [Song 2021]. After 48 weeks of therapy, the HBsAg clearance rates were 
CI: - IRU+%V$J,8P/&,- IRU,8P/
&,- IRU,8P/   &,- IRU,8P/DQG
&,- IRU,8P/While it is clear that clearance of HBsAg is 
predicted by baseline levels in these studies, there is minimal change in levels between 
100 and 500 IU/mL , and the most significant drop-off in HBsAg clearance is in 
those with qHBsAg >1000 IU/mL . These observations support the recruitment of a 
well-defined subpopulation of inactive CHB patients with low qHBsAg levels to enhance 
anti-HBV immune responses and increase HBsAg loss rates. The provision for allowing 
the participation of patients with any one HBsAg level within the eligible range (qHBsAg 
,8P/EXW200 IU/mL) within the past 12 months is to account for the variability 
in the quantitative HBsAg assay.  
Patients with inactive CHB and over the age of 65 have also been excluded, as they 
would not be candidates for treatment of their condition in routine clinical practice. There 
is a global epidemic of obesity and those with hepatitis B are at risk for hepatic steatosis 
from nonalcoholic fatty liver disease (NAFLD). The risk and prevalence of NAFLD 
amongst those with HBV appears to be similar as the general population, ranging 17- 
[Shi 2021]. Inclusion of these subjects in the current study is allowed provided there is 
radiologic evidence of fatty liver or a Fibroscan consistent with hepatic steatosis and no 
HYLGHQFHRIDFWLYH&+%LH+%9'1$,8P/ or other forms of liver disease. 
The level of effectiveness and timeframes for contraception use for study eligibility 
comply with the guidelines of the Clinical Trial Facilitations Group recommendation 
related to contraception and pregnancy testing in clinical trials [Clinical Trial Facilitation 
Group 2014]. The fluoropeptides and IC31 of HepTcell are designed to form a local 
depot at the site of injection, and the magnitude and period of systemic exposure are 
anticipated to be limited. The high molecular weight peptides that comprise HepTcell 
present a low risk of passive transmembrane penetration and/or systemic exposure and it 
is unlikely that they will be absorbed vaginally or placentally. Peptides are expected to be 
degraded into smaller peptides and individual amino acids by the protein degradation 
pathways that are well understood. Even if systemic exposure to HepTcell were to occur, 
the fluoropeptides and IC31 adjuvant components would be rapidly metabolized and their 
appearance in semen would be limited, as would their appearance in plasma from semen. 
Any T cells stimulated by HepTcell would also be HBV specific and unable to cross the 
placenta. Therefore, one-month period of pregnancy testing after the last dose of study 
medication is considered sufficient to protect patients or their sexual partners who 
become pregnant after the 6 doses of study medication are administered. 
4.5. 
Dose Rationale 
The lower dose of FP-02.2 fluoropeptides from the Phase 1 study was chosen for this 
study. The immunogenicity of this dose was equal to or greater than the immunogenicity 
of the higher dose in the prior Phase 1 study. The selection of the lower dose is expected 
to further improve on the safety profile of treatment. Furthermore, with each successive 

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dose of FP-02.2, a trend toward an increase of the immune responses was observed in this 
trial. Consequently, treatment has been extended from 3 to 6 doses. It is anticipated that 
longer treatment will further improve the anti-HBV immune response over time. 
4.6. 
Schedule of Events 
The schedule for study activities is presented in Table 1 for the Screening and Treatment 
Periods and in Table 2 for the Follow-up Period. 

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Table 1 
Schedule of Events – Screening and Treatment Periods 
Study Day 
Screening Period 
Treatment Period 
Day -35 to  
Day -4 
Telephone Visit 
(if needed) a 
Day 1 
Day 8, 36 
Day 29 
Day 57 
Day 85 
Day 113 
Day 141 
Day 169 or 
ETb 
Week (s) 
-4 to -1 
0 
7 days after 
prior visit 
4 
8 
12 
16 
20 
24 
Window (days) 
— 
Up to 3 
working days 
before Day 1 
— 
±2 days 
±2 days 
±2 days 
±2 days 
±2days 
±2 days 
±2 days 
Dose of study medication 
 
 
1 
 
2 
3 
4 
5 
6 
 
Visit may be conducted at home or 
work or in part as a telemedicine visit c 
 
 
 
X 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Eligibility criteria check 
X 
X 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
Concomitant medications (including 
immunosuppressive medications, 
vaccines, and new HBV treatments) d 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Complete PE 
X 
 
 
 
 
 
 
 
 
X 
Targeted and symptom-driven PE 
 
 
X 
X 
X 
X 
X 
X 
X 
 
Height, weight, and BMI 
X 
 
 
 
 
 
 
 
 
X 
Vital signs e 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Fibroscan f 
X 
 
 
 
 
 
 
 
 
 
ECG e 
X 
 
 
 
 
 
 
 
 
X 
Urine pregnancy test g 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
Drug and alcohol screen 
X 
 
 
 
 
 
 
 
 
 
Hepatitis B genotype h 
X 
 
 
 
 
 
 
 
 
 
HCV, HDV, and HIV tests 
X 
 
 
 
 
 
 
 
 
 
Safety labs o  
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Liver panel o 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
HBV serology and viral markers i 
X 
 
X 
 
 
 
X 
 
 
X 
Whole blood for PBMC isolation 
 
 
X 
 
 
 
X 
 
 
X 
Randomization 
 
Xa 
X 
 
 
 
 
 
 
 
Study medication administration 
(number) 
 
 
1 
 
2 j,k,l 
3 j,k,l 
4 j,k,l 
5 j,k,l 
6 j,k,l 
 
Diary distribution (D) review (R) p 
 
 
D 
R 
D 
D 
RD 
RD 
RD 
R 

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Study Day 
Screening Period 
Treatment Period 
Day -35 to  
Day -4 
Telephone Visit 
(if needed) a 
Day 1 
Day 8, 36 
Day 29 
Day 57 
Day 85 
Day 113 
Day 141 
Day 169 or 
ETb 
AEs, including MAEs, NCIs and IMCs, 
and reactogenicity (systemic and local) m 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Stored blood sample for future analysesn 
 
 
X 
 
 
 
 
 
 
X 
AE = adverse event; BMI = body mass index; ECG = electrocardiogram; ET = early termination; HBV = hepatitis B virus; HCV = hepatitis C virus; HDV = hepatitis delta virus; 
HIV = human immunodeficiency virus; MAE = medically-attended adverse event; NCI = new-onset chronic illness; IMC = immune-mediated medical condition; PBMC = 
peripheral blood nonnuclear cell; PE = physical examination; UA = urinalysis 
a Randomization may occur up to 3 working days before Day 1 (the day of first dosing) to allow for the possible preparation of study medication by a central pharmacy and 
shipment to the study site. If the patient is to be randomized before Day 1, the eligibility of the patient will be confirmed by a telephone visit prior to randomization. Concomitant 
medications AEs will also be assessed. 
b If a patient prematurely discontinues study medication before Day 169, Day 169/Early termination procedures will be performed. Patients who prematurely discontinue study 
medication will remain in the study for Follow-Up Period study assessments, the dates of visits adjusted to correspond to 13, 26, 39 and 52 weeks after the last dose of study 
medication. 
c A telemedicine visit would include a home visit by appropriate trained personnel to perform a target and symptom-driven physical and obtain vital signs and safety laboratories. 
The remaining portions of the visit may be conducted virtually by the study investigator. 
d After Day 169 or ET, only immunosuppressive medications, vaccines, and new HBV treatments or medications associated with MAEs, NCIs, SAEs, hepatitis flares, or hepatic 
injury will be recorded. 
e Measured before any blood sample collection. 
f Not required if performed within 12 months or if no fibrosis seen on liver biopsy within 2 years before screening. 
g For women of childbearing potential only. A serum pregnancy test will be obtained in lieu of a urine pregnancy test at screening. 
h Hepatitis B genotyping will be performed at screening if it has not been documented in the prior medical record. 
i Serology and viral markers = HBsAg, anti-HBs, HBVDNA, pg-RNA, HBcAg, HBeAg, HBeAg antibody. 
j If the patient has experienced an acute illness or temperature > 38°C in the 2 days prior to dosing, the administration of study medication and corresponding visit will be delayed 
until the illness or fever has resolved. 
k Investigators will review the eligibility of all patients to determine if the next treatment is to be administered. Eligibility for the next treatment will include 1) confirmation that 
patients did not meet a Stopping Rule (Section 7.1.1); 2) confirmation that the pre-treatment liver parameters are within acceptable ranges for treatment (Section 4.1); 
3) confirmation that patients do not have a new confirmed or suspected IMC (Appendix 2). Patients not meeting these criteria will not be treated. 
l If an authorized COVID-19 vaccine has been administered in proximity to a scheduled IP administration, a ± 3 day window is allowed for IP dosing. 
m After Day 169 or ET, only MAEs, NCIs and IMCs will be recorded. 
n A single blood sample will be collected for biobanking at the beginning of the study (prior to dosing on Day 1) and end of the study. This sample will be used for future analyses 
not specified in the protocol. Analysis will be limited to HBV serologic and HBV-specific DNA and RNA and patients’ DNA will not be analyzed. 
o Safety laboratory testing, including liver panel, for Doses 1 and 2 will be obtained during the visits conducted 7±2 days after these doses of study medication. Safety laboratory 
testing following Doses 3, 4 and 5 will be obtained in the interval from 7 days after dose administration and before the next dose of study medication is administered. Safety labs 
after Dose 6 will be assessed at the Day 169 visit. 
p Diaries will also be reviewed at the Day 85, Day 113, Day 141 and Day 169 visits 

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Table 2 
Schedule of Events – Follow-up Period 
Study Visit 
Follow-Up Period 
Day 232 
Day 323 
Day 414 
Day 505 
or ETa 
Completion of Week (number) 
33 
46 
59 
72 
Window (days) 
±10 days 
±10 days 
±10 days 
±10 days 
Visit may be conducted at home or work 
or in part as a telemedicine visitb 
X 
 
X 
 
Immunosuppressive medications, 
vaccines, and new HBV treatments (only)c 
X 
X 
X 
X 
Targeted and symptom-driven PE 
X 
X 
X 
X 
Height and weight 
 
 
 
X 
Vital signsd 
X 
X 
X 
X 
ECGd 
 
 
 
X 
Hematology and serum chemistry 
X 
X 
X 
X 
Liver panel 
X 
X 
X 
X 
HBV serology and viral markerse 
 
X 
 
X 
Whole blood for PBMC isolation 
 
X 
 
X 
MAEs, NCIs and IMCs (only)f 
X 
X 
X 
X 
AE = adverse event; ECG = electrocardiogram; ET = early termination; HBV = hepatitis B virus; HIV = human immunodeficiency virus; MAE = medically-attended adverse 
event; NCI = new-onset chronic illness; IMC = immune-mediated medical condition; PBMC = peripheral blood nonnuclear cell; PE = physical examination. 
a If a patient prematurely discontinues study medication before Day 505, Day 505/Early termination procedures will be performed. 
b A telemedicine visit would include a home visit by appropriate trained personnel to perform a target and symptom-driven physical and obtain vital signs and safety laboratories. 
The remaining portions of the visit may be conducted virtually by the study investigator. 
c After Day 169 or ET, only immunosuppressive medications, vaccines, and new HBV treatments or medications associated with MAEs, NCIs, SAEs, hepatitis flares, or hepatic 
injury will be recorded. 
d Measured before any blood sample collection. 
e Serology and viral markers = HBsAg, anti-HBs, HBVDNA, pg-RNA, HBcAg, HBeAg, HBeAg antibody. 
f After Day 169 or ET, only MAEs, NCIs and IMCs will be recorded. 

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5. 
POPULATION 
5.1. 
Number of Patients 
Approximately 80 patients are planned for enrollment over approximately 24 months at 
approximately 35 study centers in North America, Europe, UK and Asia-Pacific. 
5.2. 
Inclusion Criteria 
Patients who meet all of the following inclusion criteria may be included in the study. 
1. Able and willing to provide informed consent 
2. Men and women 18 to 65 years of age, inclusive 
3. Body Mass Index (BMI) 18.0 to 34.9 kg/m2, inclusive 
4. Inactive, treatment-naïve CHB with documented HBsAg positivity for at least 
12 months before Day 1. (The history of HBsAg positivity may be reduced to 6 
months provided HBV anti-core IgM antibodies are negative). 
5. T+%V$J,8P/EXW200 IU/mL in the 12 months prior to Screening or 
from informed consent to randomization 
If a patient has more than one qHBsAg value within 12 months and prior to 
randomization, the patient will be deemed eligible if any one measurement is 
within the eligible range. 
6. AST, ALT, INR, albumin, total bilirubin (excluding patients with Gilbert 
Syndrome, who will only be eligible for study participation if total bilirubin is 
 3.0 mg/dL) and direct bilirubin within normal limits at screening. Note: ALT 
and AST elevations up to 1.5 x ULN are allowed if evidence of hepatic steatosis, 
defined as one of the following criteria: 1) fatty liver on ultrasound, or other 
imaging modality or Fibroscan controlled attenuation parameter (CAP) 
 260 dB/m. To qualify under these conditions, HBV DNA must be 
 IU/mL, and there must be no history or signs of liver disease other than 
fatty liver and HBV. 
7. Negative drug screen at Screening unless prescribed by a medical practitioner for 
medical use (NB, recreational and prescription cannabis is allowed) 
8. For women of childbearing potential (women who are not permanently sterile 
[documented hysterectomy, bilateral tubal ligation, salpingectomy, or 
oophorectomy] or postmenopausal [12 months with no menses without an 
alternative medical cause]): 
a. Negative pregnancy test on Day 1 
b. Willingness to practice a highly effective method of birth control with low 
user dependency from screening through one menstrual cycle after the last 
dose of study medication, which include: 
i. Abstinence  

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ii. Sex only with persons of the same sex 
iii. Monogamous relationship with vasectomized partner 
iv. Intrauterine device 
v. Combined estrogen and progestogen containing hormonal contraception 
associated with inhibition of ovulation (oral, intravaginal, transdermal) 
vi. Progestogen-only hormonal contraception associated with inhibition of 
ovulation (oral, injectable or implantable) 
vii. Intrauterine hormone-releasing system 
Patients who practice true abstinence or who exclusively have same sex 
partners need not use contraception, provided it is in line with their preferred 
and usual lifestyle. Periodic abstinence (eg, calendar, ovulation, 
symptothermal, post-ovulation methods) and withdrawal are not acceptable 
methods of contraception. Should any such patient stop practicing abstinence, 
they must use contraception as described above. 
9. For men with sexual partners of childbearing potential, as defined above: 
a. Abstinence 
b. History of vasectomy or surgical sterilization 
c. Monogamous relationship with a postmenopausal or surgically sterilized 
partner 
d. Willingness to practice a highly effective method of contraception, as defined 
above, for 90 days after the last dose of study medication and to refrain from 
sperm donation during this time 
The same criteria pertaining to abstinence and withdrawal methods in women of 
childbearing potential (Inclusion Criterion 8) apply to men with sexual partners of 
childbearing potential 
10. Willingness to comply with all aspects of the study through the entire study 
period 
Patients who fail to meet Inclusion Criteria 5 and/or 6 and otherwise meet the 
requirements for study participation will be permitted one additional blood draw during 
the same screening period to requalify. Patients who screen fail for other Inclusion 
Criteria may undergo rescreening at the discretion of the Investigator and Medical 
Monitor. 
5.3. 
Exclusion Criteria 
Patients who do not meet any of the following exclusion criteria may be included in the 
study. 
1. Pregnant or lactating women 
2. Positive HBeAg at Screening 
3. History of a hepatitis B flare or 1-log increase in HBV DNA or HBsAg in the 
prior 6 months 

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4. Prior or current history of active or untreated human immunodeficiency virus 
(HIV), hepatitis C virus (HCV), or hepatitis delta virus (HDV) 
5. Acute COVID-19, a positive test result for SARS-CoV2 infection, or exposure 
within 14 days to an individual with acute COVID-19  
6. )HEULOHLOOQHVV7oC) within the past 14 days 
7. Prior or current history of any underlying liver disease not related to HBV 
(NB, steatosis, as documented by imaging or Fibroscan CAP, is permitted if ALT 
DQG$67DUH[8/1DQG+%9'1$,8P/ and there is no history or 
signs of liver disease other than fatty liver and HBV) 
8. Fibroscan > 8.5 kPA at Screening or history of hepatic fibrosis or cirrhosis (NB, a 
Fibroscan is not required if an examination is performed within 12 months before 
Screening, or a liver biopsy was performed within 2 years before Screening and 
no fibrosis [F1 or greater] was identified.) 
9. History of cirrhosis or signs of hepatic decompensation, including but not limited 
to variceal bleeding, ascites, or hepatic encephalopathy 
10. :KLWHEORRGFHOOFRXQW/QHXWURSKLOV/KHPRJORELQ
 11 JG/RUSODWHOHWV25,000/μL 
Note: ,QGLYLGXDOVRI$IULFDQGHVFHQWZLWKDZKLWHEORRGFHOOFRXQW/
will not be excluded for this reason if white blRRGFHOOFRXQWLV/
SURYLGHGWKDWWKHQHXWURSKLOFRXQWLV/DQGWKHUHLVQRRWKHULGHQWLILHG
cause of leukopenia. 
11. Prior treatment with an approved or investigational agent for HBV  
12. History of conditions associated with immunocompromise 
13. History of conditions associated with altered immune response, such as 
anaphylaxis, angioedema, or autoimmune disease 
14. Treatments known to affect the immune system, such as corticosteroids (other 
than topical or inhaled preparations), alkylating drugs, antimetabolites, cytotoxic 
drugs, radiation, immune-modulating biologics, allergy injections, 
immunoglobulins, interferons, or other immunomodulating therapies within 30 
days of Screening 
15. Uncontrolled diabetes mellitus, defined as hemoglobin A1C (HBA1&at 
Screening 
16. Receipt of live-attenuated replicating vaccines within 30 days or receipt of any 
other licensed or authorized vaccines (including vaccines intended to prevent 
COVID-19) within 14 days prior to Day 1 
17. Change in any chronically administered medication or treatment within 14 days of 
Screening, or inability to maintain these medications at the same dose through 
Day 169 (NB, patients chronically using aspirin, non-steroidal anti-inflammatory 

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agents, antacids, vitamins, probiotics, and over-the-counter medications will 
maintain their level of intake throughout the study) 
18. Malignancy within 3 years of Screening, excluding non-melanoma skin cancers 
and in situ cervical cancer (NB, patients who have undergone prior screening for 
HCC by imaging or alpha-fetoprotein levels will have negative test results) 
19. Untreated alcohol or drug abuse 
20. Planned elective surgery or hospitalization during the study period 
21. Participation in a prior trial involving HepTcell or FP.02-2 
22. Known allergy to any of the ingredients in HepTcell 
23. Receipt of any investigational drug or treatment within 30 days before Day 1 or 
planned use during the study period 
24. Any medical, psychiatric, or social condition or occupational or other 
responsibility that in the judgment of the Investigator would interfere with or 
serve as a contraindication to protocol adherence, assessment of safety (including 
reactogenicity), or a patient’s ability to give informed consent 
Patients who are excluded by Exclusion Criterion 10 but otherwise meet the requirements 
for study participation will be permitted one additional blood draw to requalify. Patients 
who screen fail for other Exclusion Criteria may undergo rescreening at the discretion of 
the Investigator and Medical Monitor. 

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6. 
STUDY MEDICATION 
6.1. 
Description 
6.1.1. 
Formulation 
6.1.1.1. 
HepTcell 
HepTcell (adjuvanted FP-02.2) is the final reconstituted product for administration, that 
consists of a lyophilized mixture of 9 fluoropeptides and mannitol (FP-02.2 drug 
product), L-histidine buffer, normal saline (to achieve an isotonic, neutral pH), and IC31 
(developed by Valneva SE). The 9 synthetic peptides (designated P877, P151, P113, 
P856(K), P753(K), P376, P797(K), P277(K), and P1266(K)) are each covalently linked 
to a fluorocarbon moiety on the N-terminus under a controlled process and formulated in 
mannitol. Each peptide is 32 to 40 amino acids in length and corresponds to a conserved 
region of HBV polymerase, core, or surface protein and contains CD4+ and CD8+ T cell 
epitopes. IC31 is a synthetic, 2-component adjuvant solution comprised of 40 nmol/mL 
ODN1a, a single stranded oligodeoxynucleotide consisting of dimeric repeats of 
deoxy-inosine/deoxy-cytosine linked by an unmodified phosphodiester backboned and of 
1000 nmol/mL KLK, comprising an 11 amino acid artificial cationic antimicrobial 
peptide. 
HepTcell is administered by IM injection. 
6.1.1.2. 
Placebo 
Normal saline for IM injection will be supplied by the site pharmacy. 
6.1.2. 
Packaging, Storage, and Handling 
All supplies are labelled as investigational products (IPs) in accordance with applicable 
legal and regulatory requirements. All IPs will be stored in a secure place under 
appropriate storage conditions. 
FP-02.2 (0.36 mg per vial or each peptide) supplied in 2 mL single-use glass vials is 
stored at -20°C ± 5°C. 
28 mM L-histidine diluent (1.2 mL) supplied in 2 mL single-use glass vials is stored at 
2-8°C. 
IC31 (1000 nmol/mL KLK; 40 nmol/mL ODN1a) (1.6 mL) supplied in 2 mL single-use 
glass vials is stored at 2-8°C. 
All components will be brought to room temperature before dose preparation. 
In the US, Canada, Spain, Thailand, and Italy reconstitution of IP will be performed by 
unblinded staff at the site. In the UK and Germany, reconstitution of IP will be done at a 
centralized location. Please refer to the ALT-301-202 Pharmacy Manual for more 
information. 

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Use of gloves is recommended when removing material from vials or cleaning up spills. 
Broken, damaged, or leaking vials should be handled with protective gloves as is done for 
sharps and infectious material. Take precautions to avoid accidental injection, 
contamination of wounds or skin abrasions, and contact with sharp materials or needles 
contaminated with IPs. 
Full preparation instructions are detailed in a separate pharmacy manual. 
6.2. 
Randomization 
Following completion of the Screening activities, patients who meet the all the inclusion 
and none of the exclusion criteria will be registered by the Interactive Web Response 
System (IWRS). Eligible patients will be randomly assigned in a 1:1 ratio to HepTcell or 
placebo treatment groups. Randomization will be stratified by study center to minimize 
imbalances between treatment groups. 
The first 12 patients (6 HepTcell, 6 placebo) will form the sentinel cohort. To assure a 1:1 
distribution of HepTcell and placebo in the sentinel cohort, randomization in this group 
will not be stratified. 
If none of the Stopping Rules (see Section 7.1.1) are met in one or more patients in the 
sentinel cohort, randomization may continue in the expanded study cohort. 
The randomization list will be drawn up by an independent statistician. 
6.3. 
Dose and Administration 
HepTcell or normal saline placebo will be administered by IM injection at intervals of 
4 weeks for 6 doses. Doses will be administered on Days 1, 29, 57, 85, 113, and 141 
(±2 days for each dose). The 1.0 mL HepTcell injection contains 0.150 mg of each 
FP-02.2 peptide and IC31 at 500 nmol KLK and 20 nmol ODN1a. 
Each dose of HepTcell or placebo will be administered as an IM injection (1.0 mL) in the 
deltoid muscle, where possible, of the non-dominant arm by appropriately trained clinical 
staff members. Patients will stay in the unit for at least 2 hours following administration 
of the first and second doses. Vital signs will be assessed before dosing and every 15 
minutes post dosing over 2 hours at these two visits, and medications and qualified 
medical personnel will be available in case a patient experiences a severe acute allergic 
reaction during the immediate post-vaccination period. 
Refer to ALT-301-202 Pharmacy Manual for specific preparation information and 
country specific procedures (if applicable). 
If an authorized COVID-19 vaccine has been administered in proximity to a scheduled IP 
administration, a ±3 day window is allowed for IP dosing. 
6.4. 
Dosing Modifications 
The sentinel cohort of 12 patients will undergo blinded safety review by the Safety 
Committee 7 to 10 days after all ongoing patients in the sentinel cohort have completed 

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the respective dose of study medication and will determine the decision to continue at 
that dose into the expanded cohort. Safety will be assessed in the sentinel cohort before 
each dose is administered to the expanded cohort. If any of the Stopping Rules in 
Section 7.1.1 are met in one or more patients in the sentinel cohort and the event(s) is 
deemed possibly or probably related to HepTcell, dosing will be suspended pending 
DMC review. DMC recommendations may include instituting modifications to ensure the 
safety of continued dosing or discontinuing the study. If none of the Stopping Rules 
(below) are met, randomization and dosing may continue in the expanded study cohort. 
Patients will be unblinded as necessary to assess the relationship between the study 
medication and events that meet criteria for Stopping Rules. Patients who experience 
events that meet criteria for Stopping Rules will permanently terminate dosing. 
Monitoring and dosing rules for patients who experience liver abnormalities is described 
in Section 4.1. 
6.5. 
Blinding and Unblinding 
The Pharmacy staff at the central or site pharmacy will be unblinded for the purpose of 
final drug preparation. The pharmacist will consult the IWRS for dose allocation and the 
Pharmacy staff will prepare each dose in compliance with the randomization list. 
Due to the fact that formulations cannot be made to look identical, a blinded syringe will 
be used for administration.  
Knowledge of the randomization list will be limited to the persons responsible for 
creation of the randomization list, pharmacy staff who prepare the study medications, 
unblinded site staff who administer the study medication and any unblinded study 
monitors or auditors, until all data has been entered in the electronic Case Report Form 
(eCRF), quality control and verification of the eCRF and assignment of patients to the 
analysis populations has been completed, the database has been locked, and the study 
formally unblinded. 
Data provided to the Safety Committee will be blinded. 
If unblinding is required in the interest of the safety of a patient, an Investigator will 
discuss the matter with the Sponsor before unblinding. In a medical emergency, the 
Investigator or delegate may unblind via the IWRS for that patient without prior 
consultation with the Sponsor. In that event, the Investigator or delegate will notify the 
Sponsor as soon as possible that the randomization code has been broken for the patient. 
If the blind is broken, the date, time, and reason must be recorded. 
Patients may also be unblinded for the processing of SAEs, expedited safety reports, and 
the emergency unblinding of patients, as detailed in a separate Safety Management Plan. 
6.6. 
Accountability 
The Investigator (or designee) will maintain an accurate record of the receipt of each 
study medication as shipped by the Sponsor (or designee), including the date received. In 

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addition, an accurate study medication disposition record will be kept, specifying the 
amount dispensed for each patient and the dates of dispensation and any returns. 
Sponsor approval is required for on-site destruction of all used study medication and 
shipment of all unused study medication back to the Sponsor at the completion of the 
study and once all reconciliation has occurred. 
6.7. 
Prior and Concomitant Therapy 
In the interests of patient safety and acceptable standards of medical care, the Investigator 
will be permitted to prescribe additional treatment(s) at his/her discretion. However, as 
noted below, changes in any chronically administered medications or treatments should 
be avoided during the Treatment Period (through Day 169). 
All medications must be recorded in the patients’ eCRFs from 30 days before the first 
dose through Day 169 or early termination (ET) from the Treatment Period, but only 
immunosuppressive medications, vaccines, and new HBV treatments or medications 
associated with MAEs, NCIs, SAEs, hepatitis flares, or hepatic injury will be recorded 
beyond this point through the end of the Follow-up Period (Day 505 or ET from 
Follow-up). 
6.7.1. 
Prohibited Prior and Concomitant Medications 
Prohibited prior and concomitant medications are as follows: 
x Any prior treatment with an approved or investigational agent for HBV. 
x Treatments known to affect the immune system, such as corticosteroids (other 
than topical preparations), alkylating drugs, antimetabolites, cytotoxic drugs, 
radiation, immune-modulating biologics, allergy injections, immunoglobulins, 
interferons or other immunomodulating therapies are prohibited within 30 
days of Screening and through the course of the trial. 
x Live vaccines (such as live influenza vaccinations or live travel vaccinations) 
are also not permitted with 30 days of Screening and through the course of the 
trial. 
x Receipt of any investigational drug or treatment within 30 days before Day 1 
or planned use during the study period 
x Change in any chronically administered medication or treatment within 
30 days of Screening or inability to maintain these medications at the same 
dose through Day 169 
In case of worsening or disease progression, study medication will be discontinued, and 
the above medications prohibited will be allowed, at the discretion of the investigator and 
Sponsor, if it is in the patient’s best interest to initiate any treatment prohibited in the 
study. 

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Preventive COVID-19 vaccines that have regulatory approval or emergency use 
authorization will be allowed prior to IP dosing on Day 1, provided that their 
administration adheres to Exclusion Criterion 16. COVID-19 vaccination is also 
permitted during study participation. A ± 3 day window is allowed for IP dosing if a 
COVID-19 vaccine is administered in proximity to a scheduled IP administration after 
Day 1. These vaccines will be captured as a concomitant medication. 
6.8. 
Contraception 
All female patients of childbearing potential must practice a highly effective method of 
birth control with low user dependency, as defined in Section 5.2, from Screening 
through one menstrual cycle after the last dose of study medication. Male patients with 
partners of childbearing potential must practice a highly effective method of 
contraception for 90 days after the last dose of study medication and refrain from sperm 
donation during this time. 
6.9. 
Compliance 
The injections will be administered by study personnel and therefore compliance with 
study medication dosing is not a concern. The study personnel will be appropriately 
trained on study medication administration procedures and documentation requirements 
prior to study start. 
Non-compliance with study procedures will be reported to the Sponsor who will decide if 
persistent non-compliant patients should be withdrawn from continued study treatment. 

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7. 
PREMATURE DISCONTINUATION 
7.1. 
Individual Patients 
Patients can choose to discontinue study medication or participation in the study at any 
time, for any reason, without prejudice to their future medical care. Patients could be 
discontinued for any of the following reasons: 
x Patient request/withdrawal of consent 
x Noncompliance with study requirements 
x Loss to follow-up 
x Investigator discretion 
x Sponsor request, including termination of the study by the Sponsor 
In case of worsening or disease progression, study medication will be discontinued, and 
the medications prohibited in Section 6.7.1 will be allowed, at the discretion of the 
investigator and Sponsor, if it is in the patient’s best interest to initiate any treatment 
prohibited in the study. 
If a patient prematurely discontinues study medication before Day 169, Day 169/ET 
procedures will be performed. Patients who prematurely discontinue study medication 
will remain in the study for Follow-up Period study assessments, with the dates of visits 
adjusted to correspond to 13, 26, 39 and 52 weeks after the last dose of study medication. 
Eligible patients who are randomized and withdrawn before their second dose of study 
medication will be replaced. Patients who have received two doses of study medication 
who are subsequently withdrawn from the study will not be replaced. 
In consultation with the DMC, patients in the Sentinel Cohort may be replaced at any 
time to assure that the reliability and integrity of the data from this cohort remains intact. 
7.1.1. 
Stopping Rules 
In consultation with the DMC, the following Stopping Rules will be applied: 
x ALT or AST î8/1 
x INR  1.3 
x Total bilirubin  1.5 î ULN (excluding patients with Gilbert Syndrome) 
x Direct bilirubin  1.5 îULN (for patients with Gilbert Syndrome) 
x SAEs 
x Severe systemic reactogenicity event (see Appendix 1) 
If any of the Stopping Rules are met in one or more patients in the sentinel cohort (ie, the 
first 12 patients dosed) and the event(s) is deemed possibly or probably related to study 
medication, dosing will be suspended pending DMC review. Similar procedures will be 

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applied if 2 or more patients in the sentinel or expanded study cohort together experience 
Stopping Rules deemed possibly or probably related to study medication at any time 
during the 24-week Treatment Period. DMC recommendations may include instituting 
modifications to ensure the safety of continued dosing or discontinuing the study. 
If the study is halted based on a DMC decision or safety concern, the trial will only be 
restarted after notification of the competent authority via a substantial amendment. 
7.1.2. 
Disease Progression / Need for Active Treatment 
At the end of the clinical trial, either due to premature discontinuation or study 
completion, the decision about follow-on treatments and medical care will be made by 
the patient’s physician or medical team in accordance with the usual standard of care. 
This will assure that patients have access to appropriate therapies in case of progression 
or other need for active treatment. Patients in need of active treatment will receive 
treatment based on the recommendations of American Association for the Study of Liver 
Disease [Terrault 2018], the Canadian Association for the Study of the Liver and 
Association of Medical Microbiology and Infectious Disease Canada [Coffin 2018], and 
European Association for the Study of the Liver guidelines [EASL 2017]. 
7.2. 
Study as a Whole 
Both the Sponsor and the Investigator reserve the right to terminate the study at the 
Investigator’s site at any time. Should this be necessary, the Sponsor or a specified 
designee will inform the appropriate regulatory authorities of the termination of the study 
and the reasons for its termination, and the Investigator will inform the IRB/IEC of the 
same. In terminating the study, the Sponsor and the Investigator will assure that adequate 
consideration is given to the protection of the patients’ interests. 
Possible reasons for termination are: 
x Safety reasons – the incidence of AEs in this or any other study using the 
same investigational product(s) indicates a potential health risk for the patients 
x New scientific knowledge becomes known that makes the objectives of the 
study no longer feasible/valid 
x Unsatisfactory enrollment of patients 

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8. 
DESCRIPTION OF STUDY PROCEDURES 
See Section 4.6 for the Schedule of Events for the Screening and Treatment Periods 
(Table 1) and the Follow-up Period (Table 2). 
8.1. 
Screening Assessments 
8.1.1. 
Demographics 
Demographic data and baseline characteristics will be recorded during Screening. 
8.1.2. 
Medical History 
A complete medical history will be obtained and recorded during Screening. Enquiries 
will be made regarding all body systems including allergies/drug sensitivities, past 
surgeries, substance abuse and any other diseases or disorders. 
The medical history will include a history of hepatitis B flares, Fibroscan tests and 
measurements of qHBsAg, HBV DNA, and liver tests in the 24 months prior to 
Screening. 
8.1.3. 
Fibroscan 
A Fibroscan will be performed at Screening. The Fibroscan is not required if an 
examination was performed within 12 months before Screening, or if no fibrosis was seen 
on liver biopsy within 2 years before Screening. 
8.1.4. 
Hepatitis B Genotyping 
Hepatitis B genotyping will be performed at Screening if it has not been documented in 
the prior medical record. 
8.2. 
Efficacy Assessments 
8.2.1. 
Immunology 
Whole blood samples will be collected and processed to isolate, cryopreserve and store 
PBMCs. This will be conducted at designated laboratory, which may include a central 
laboratory or laboratories at Investigator sites. Further details can be found in the 
laboratory manual. 
Cryopreserved PBMC samples will be transferred to a designated laboratory for 
immunological analyses (IFN-Ȗ(/,6SRW7KHPHWKRGVRI(/,6SRWDQDO\VLVZLOOEH
detailed in the laboratory manual. 
8.2.2. 
Virology 
Blood samples will be collected for the assessment of virological parameters (qHBsAg, 
anti-HBsAg antibody, HBV DNA, HBV pg-RNA, HBcrAg, HBeAg, HBeAg antibody) at 
the times indicated in the Schedule of Events (Section 4.6). Isolation of serum or plasma 

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will be performed at the clinical site following methods detailed in the laboratory manual. 
Serum and plasma will be stored at the clinical site under appropriate conditions (as 
described in the laboratory manual) until shipment to a designated laboratory. The 
methods of virologic analysis will be detailed in the laboratory manual. 
8.2.3. 
Stored Sample for Future Analyses 
A single blood sample from patients will be collected for storage at the beginning of the 
study prior to dosing and at the end of the study, as indicated in Table 1. This sample will 
be used for future analyses not specified in the protocol. Analysis will be limited to HBV 
serologic and HBV-specific DNA and RNA; patients’ DNA will not be analyzed. 
8.3. 
Safety Assessments 
8.3.1. 
Reactogenicity Assessments 
Each patient will record local events, systemic events, and oral temperature in a diary 
daily for 7 days after each dose. Diaries will be distributed to patients at each dosing visit 
to record these events. Patients will also be provided thermometers for daily recording of 
temperatures and measuring devices for the recording the size of injection reactions. 
Events will be graded according to the FDA Guidance for Industry: Toxicity Grading 
Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine 
Clinical Trials [United States Food and Drug Administration 2007]. Unsolicited events 
reported by the patients outside of this 7-day reporting period will be recorded as AEs. 
Microscopic hematuria will be assessed by urinalyses performed at the visits 7±2 days 
after Doses 1 and 2 of study medication, and after Doses 3, 4, 5, and 6 as per the 
Schedule of Events (Table 1). 
Reactogenicity events will be categorized separately from AEs unless they are assessed 
as serious, in which case they will be reported as SAEs. A list of solicited reactogenicity 
events is provided in Appendix 1. 
8.3.2. 
Adverse Events 
Adverse events will be assessed by direct observation and patient assessments/interviews 
from Screening through the end of study. All AEs will be recorded through the end of the 
Treatment Period (Day 169 or ET). After that time, only MAEs, NCIs, and IMCs, which 
will be categorized as AEs, will be recorded through the end of the Follow-up Period 
(Day 505 or ET). A list of IMCs is provided in Appendix 2. 
Details on the definitions, reporting, and management of AEs are provided in Section 9. 
8.3.3. 
Clinical Laboratory Tests 
Blood samples for the safety laboratory tests listed in Table 3 will be collected according 
to the Schedule of Events (Section 4.6). 

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Table 3: 
Safety Laboratory Tests 
Hematology 
White blood cells (WBC) 
Red blood cells 
Hemoglobin 
Hematocrit 
Mean corpuscular volume 
Mean corpuscular hemoglobin 
Mean corpuscular hemoglobin concentration 
Platelets 
:%&GLIIHUHQWLDODEVROXWHDQG 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Liver Panel 
Total and direct bilirubin 
Aspartate transaminase (AST) 
Alanine aminotransferase (ALT) 
Total protein 
Albumin 
Gamma-glutamyl transferase (GGT) 
Lactate dehydrogenase 
Alkaline phosphatase (AP)a 
International normalized ratio (INR) 
Serum Chemistry 
Sodium 
Potassium 
Urea 
Creatinine 
Calcium 
Phosphate 
Glucose 
Creatine kinaseb 
 
Urinalysis 
Protein 
Bilirubin 
Urobilinogen 
Ketones 
Glucose 
Leukocyte esterase 
Red blood cells 
pH 
Nitrites 
Specific gravity 
Microscopy (if clinically indicated or 
hemoglobin is detected on dipstick) 
 
For the purpose of reactogenicity reporting, 
hematuria is defined as 3 or more red blood 
cells per high powered field 

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Serology (at Screening only) 
HIV I and II 
HCV antibodies 
HDV antibodies 
Drugs of abuse and alcohol screen (at Screening only)c 
Amphetamine/ecstasy 
Ethanol 
Cannabinoids 
Cocaine 
Opiates 
Benzodiazepines 
Methadone and/or metabolites 
Barbiturates 
Pregnancy testd 
Beta human chorionic gonadotropin 
 
a Alkaline phosphatase iso-enzymes (liver-specific and bile duct specific) will be measured if original 
alkaline phosphatase test result is above the upper limit of normal. 
b Creatine kinase MB or Troponin T will be measured where clinically indicated. 
c Sites may use locally available drugs of abuse panels and alcohol tests. The specific drugs may vary from 
the outlined list. 
d A serum pregnancy test will be performed in all women of childbearing potential at Screening. Urine 
pregnancy tests will be performed at other time points. 
8.3.4. 
Height, Weight and BMI 
Height and weight will be measured and BMI calculated and recorded at Screening. 
Weight and BMI will also be recorded at end of the Treatment Period (Day 169 or ET) 
and at the end of the Follow-up Period (Day 505 or ET). 
8.3.5. 
Physical Examination 
Physical examinations will be performed by trained medical personnel. A complete 
physical examination will be performed at Screening and the end of the Treatment Period 
(Day 169 or ET). Targeted and symptom-driven physical examinations will be performed 
at all other study visits. Any clinically relevant change in physical examination findings 
will be recorded as AEs. 
8.3.6. 
Vital Signs 
Vital signs, including sitting blood pressure, pulse rate (after at least 5 minutes rest), and 
body temperature, will be recorded at every study visit. Patients will stay in the unit for at 
least 2 hours following administration of the first and second doses. Vital signs will be 
assessed before dosing and every 15 minutes post dosing over 2 hours at these two visits. 
At visits with laboratory assessments, vital signs should be measured before any blood 
sample collection. Any clinically relevant change in vital signs will be recorded as AEs. 
Significant changes of vital signs, including the occurrence of tachycardia, bradycardia, 
hypertension, hypotension and fever will categorized and graded according to the FDA 
Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials [United States Food and Drug 
Administration 2007]. 

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8.3.7. 
Electrocardiogram 
A 12-lead electrocardiogram (ECG) will be performed at Screening, the end of the 
Treatment Period (Day 169 or ET), and at the end of the Follow-up Period (Day 505 or 
ET), as indicated in the Schedule of Events (Section 4.6). At visits with laboratory 
assessments, ECGs should be measured before any blood sample collection. Any 
clinically relevant change in physical examination findings will be recorded as AEs. Any 
clinically relevant change in ECG findings will be recorded as AEs. 

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9. 
ADVERSE EVENTS 
9.1. 
Definitions 
9.1.1. 
Adverse Event 
An AE is defined as any untoward medical occurrence associated with the use of a drug 
in humans, whether or not considered drug related. An AE can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, 
or disease temporally associated with the use of the investigational product whether or 
not related to the investigational product. An AE can be any sign, symptom, or diagnosis 
that appears or changes in intensity during the course of the study. 
Unchanged chronic conditions are not AEs and should not be recorded on the AE pages 
of the eCRF. These medical conditions should be adequately documented on the 
appropriate page of the eCRF (medical history or physical examination). However, 
medical conditions present on the first day of treatment that worsen in intensity or 
frequency during the treatment or post-treatment periods in a manner not consistent with 
natural disease progression should be reported and recorded as AEs. The Investigator will 
actively solicit this information and assess the event in terms of severity and relationship 
to the study treatment regimen.  
The term AE is used to include any AE whether serious or not serious. 
9.1.2. 
Adverse Drug Reaction 
All noxious and unintended responses to a medicinal product related to any dose should 
be considered an adverse drug reaction. A reaction means that a causal relationship 
between a medicinal product and an AE is at least a reasonable possibility, i.e., the 
relationship cannot be ruled out. 
9.1.3. 
Unexpected Adverse Drug Reaction 
An unexpected adverse drug reaction is defined as an adverse reaction, the nature or 
severity of which is not consistent with the reference safety information in the 
Investigator’s Brochure.  
For the purpose of expedited reporting of unexpected serious adverse drug reactions 
(ie, Suspected Unexpected Serious Adverse Reactions [SUSARs]), only possibly or 
probably related and unexpected SAEs (Section 9.3.2) will be considered serious adverse 
drug reactions. 
9.1.4. 
Medically Attended Adverse Event 
An MAE is an AE resulting in hospitalization, emergency room visit, or visit to or from 
medical personnel (other than routine health care visits). 

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9.1.5. 
New-Onset Chronic Illness  
An NCI is an AE that is new (ie, not present at baseline) and typically chronic. Because 
of the significance of this designation for the patient’s health and for evaluation of 
vaccine safety, NCIs are expected to be diagnoses, not symptoms, and the Investigator 
should record sufficient data in the source document to support the diagnosis. 
9.1.6. 
Immune-Mediated Medical Conditions (IMC) 
A list of IMCs is provided in Appendix 2. 
9.1.7. 
Serious Adverse Event 
An AE or suspected adverse reaction is considered serious (an SAE) if, in the view of 
either the Investigator or Sponsor, it results in any of the following outcomes: 
x Death 
x Life-threatening (An AE is considered life-threatening if, in the view of either 
the Investigator or Sponsor, its occurrence places the patient or subject at 
immediate risk of death. It does not include an AE that, had it occurred in a 
more severe form, might have caused death.) 
x Inpatient hospitalization or prolongation of existing hospitalization 
x A persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 
x A congenital anomaly/birth defect 
Life-threatening means that the patient or subject was at immediate risk of death at the 
time of the SAE; it does not refer to a serious AE that hypothetically might have caused 
death if it were more severe. Hospitalization does not include same day surgery, elective 
surgery, optional admission not associated with a precipitating AE (ie, elective cosmetic 
surgery), or hospitalization planned before the start of the study for a pre-existing 
condition that has not worsened. Persistent or significant disability or incapacity means 
that there is a substantial disruption of a person’s ability to carry out normal life 
functions. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse. 

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9.2. 
Reporting Responsibilities and Periods 
It is the responsibility of the Investigator or Subinvestigator(s) to perform periodic 
assessment of AEs. AEs spontaneously reported by the patient or reported in response to 
an open question from the study personnel (eg, ‘Have you had any health problems since 
the previous visit/you were last asked?’) or revealed by observation will be recorded. 
AEs and concomitant medications will be recorded from the signing of informed consent 
to Day 169, but only MAEs, NCIs, and IMCs, which will be categorized as AEs, will be 
followed subsequently through Day 505. Concomitant medication collection will align 
with AE collection. The AE term, date of AE onset, date of AE resolution (if applicable), 
severity, causality, action taken for the AE, outcome and whether or not the AE is an 
MAE, NCI, and or SAE will be recorded. 
AEs must be monitored until they are resolved or stabilized, are clearly determined to be 
due to a patient’s stable or chronic condition or intercurrent illness(es), or follow-up is no 
longer possible. Data describing AEs will be recorded in the patient’s medical record and 
as appropriate, an SAE report form. SAEs will be reported to the Sponsor as described in 
Section 9.7. 
Any SAE that the Investigator considers to be possibly or probably related to study 
medication and occurs at any time after completion of the study must be reported to the 
Sponsor or designee. If at the time the Investigator initially reports an SAE, the event has 
not resolved, the Investigator must provide a follow-up report as soon as it resolves (or 
upon receipt of significant information if the event is still ongoing). 
9.3. 
Assessment of Adverse Events 
9.3.1. 
Severity 
The Investigator should assess the severity of each AE. The AE will be recorded at its 
highest severity grade.  
The severity of all AEs, both serious and non-serious, will be assessed by assigning a 
grade according to the FDA Guidance on the Toxicity Grading Scale for Preventive 
Vaccine Clinical Trials [United States Food and Drug Administration 2007]. NCI 
CTCAE, v 5.0 (http://ctep.cancer.gov/protocolDevelopment/electronic 
_applications/ctc.htm) will be used for AEs not described in this guidance. 
When an AE cannot be graded by the aforementioned FDA guidance or CTCAE, the 
following severity grading may be used: 
x Grade 1 (Mild): awareness of sign or symptom, but easily tolerated 
x Grade 2 (Moderate): discomfort enough to cause interference with usual 
activity 
x Grade 3 (Severe): incapacitating with inability to work or do usual activity 

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x Grade 4 (Life-Threatening): refers to an event in which the patient was, in the 
view of the Investigator, at risk of death at the time of the event. (This 
category is not to be used for an event that hypothetically might have caused 
death if it were more severe.) 
x Grade 5 (Fatal): death related to AE 
An AE that is assessed as severe should not be confused with an SAE. Severity is a 
category for rating the intensity of an event, and both non-serious AEs and SAEs can be 
assessed as severe. An event will be defined as serious when it meets one of the criteria 
described in Section 9.1.7. 
9.3.2. 
Relatedness (Causality) 
The assessment of causality will be based on the information available and may be 
changed upon receipt of additional information. 
Causality should be assessed using the following categories: 
x Unrelated/Unlikely Related: clinical event with an incompatible time 
relationship to investigational agent administration, and that could be 
explained by underlying disease or other drugs or chemicals or is 
incontrovertibly not related to the investigational agent 
x Possibly related: clinical event with a reasonable time relationship to 
investigational agent administration, and that is unlikely to be attributed to 
concurrent disease or other drugs or chemicals 
x Probably related: clinical event with plausible time relationship to 
investigational agent administration, and that cannot be explained by 
concurrent disease or other drugs or chemicals 
9.4. 
Safety Laboratory, Physical Examination, Electrocardiogram, 
and Vital Sign Abnormalities 
Any abnormal laboratory result, physical examination finding, ECG interpretation, or 
vital sign measurement considered clinically significant by the Investigator will be 
recorded as an AE. A clinically significant laboratory abnormality is a confirmed 
abnormality (by repeat test) that is changed sufficiently from Screening/Baseline so that 
in the judgment of the Investigator a change in management is warranted. This alteration 
may include monitoring the laboratory test further, initiating other diagnostic tests or 
procedures, changing ongoing treatment, or administering new treatment.  
Whenever possible, the underlying medical diagnosis (eg, anemia) will be recorded as the 
AE term. Repeated additional assessments required to establish the significance and 
etiology of an abnormal result should be obtained when clinically indicated.  

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9.5. 
Pregnancy 
Pregnancy itself is not regarded as an AE unless there is a suspicion that the study 
medication may have interfered with the effectiveness of a contraceptive medication. 
Pregnancy in a patient’s partner is not considered an AE. Congenital abnormalities/birth 
defects and spontaneous miscarriages should be reported and handled as SAEs. Elective 
abortions without complications should not be handled as AEs. The outcome of a 
pregnancy will be followed-up and documented even if the patient was withdrawn from 
the study. See Section 9.7.4 for further information on reporting of pregnancy.  
An induced elective abortion to terminate a pregnancy without medical reason is not 
regarded as an AE. However, an induced therapeutic abortion to terminate a pregnancy 
because of complications or medical reasons must be reported as an SAE. The underlying 
medical diagnosis for this procedure should be reported as the SAE term. A spontaneous 
abortion in a study patient is always considered an SAE. 
9.6. 
Overdose 
Any instance of overdose (suspected or confirmed and irrespective of whether or not it 
involved study medication must be communicated to the Sponsor or a specified designee 
within 24 hours and be fully documented as an SAE. Details of any signs or symptoms 
and their management should be recorded including details of any antidote(s) 
administered. 
An overdose of study medication is not expected, as it is administered via IM injection. 
Should patients receive a higher dose than the allocated dose, this should be reported in 
the eCRF and the Sponsor should be informed. Any deviations from the assigned dose 
will be handled as a protocol deviation. 
9.7. 
Procedures for Recording and Reporting Adverse Events 
9.7.1. 
Recording Adverse Events 
To improve the quality and precision of AE data, Investigators should observe the 
following guidelines: 
x Whenever possible, use recognized medical terms when recording AEs on the 
AE page of the eCRF. Do not use colloquialisms, jargon, or abbreviations. 
x If known, record the diagnosis (i.e., disease or syndrome) rather than 
component signs and symptoms on AE pages of the eCRF (e.g., record 
“congestive heart failure” rather than “dyspnea”, “rales”, and “cyanosis”). 
However, signs and symptoms that are considered unrelated to an encountered 
syndrome or disease should be recorded as individual AEs on the eCRF page. 
For example, if congestive heart failure and severe headache are observed at 
the same time, each event should be recorded as an individual AE. 
x Adverse events occurring secondary to other events (i.e., sequelae) should be 
identified by the primary cause. A primary AE, if clearly identifiable, 

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generally represents the most accurate clinical term to record on the AE page 
of the eCRF. If a primary SAE is recorded on an AE eCRF page, events 
occurring secondary to the primary event should be described in the narrative 
description of the event. 
x Laboratory abnormalities that are identified by the Investigator as clinically 
significant are to be considered AEs and recorded on the AE eCRF page. 
9.7.2. 
Reporting of Serious Adverse Events 
Serious AEs require reporting to the Sponsor or designee within 24 hours, regardless of 
the relationship of the event to the study treatment regimen. Refer to Section 9.1.7 for the 
definition of an SAE. Procedures for recording and reporting SAEs will be detailed in a 
separate Safety Management Plan for processing SAEs, expedited safety reports, and the 
emergency unblinding of patients. 
Within 24 hours of the Investigator’s observation or learning of an SAE, the Investigator 
should notify Pivotal, S.L.U. (Pivotal Pharmacovigilance) by completing the SAE forms 
as thoroughly as possible with all available details of the event, including a determination 
of causality (even if preliminary), and signing them. The Investigator should 
communicate with Pivotal Pharmacovigilance if input is needed to complete the SAE 
assessment. Investigator causality determination and signature MUST be included for all 
SAEs. The completed SAE form and cover sheet should be sent by email or fax to Pivotal 
Pharmacovigilance. 
Pivotal Pharmacovigilance 
North America: 
(Fax) +1 877-853-3275 
 
(Phone) +1 877-412-8673 
Europe/UK/Asia-Pacific: 
(Fax) +34 913 076 047 
 
(Phone) +34 619 085 538 
e-mail: drugsafety@pivotalcr.com 
If not all information regarding an SAE is initially available, the Investigator should not 
wait to receive additional information before completing the AE eCRF and SAE forms. 
For initial SAE reports, the Investigator should record all case details that can be 
garnered on the SAE form and the AE eCRF page. Relevant follow-up information is to 
be submitted on updated SAE forms as soon as it becomes available. 
If there are questions regarding reporting an SAE or if information needs to be 
transmitted that cannot be recorded on the SAE forms (e.g., discharge summaries, 
laboratory reports), the Investigator should contact Pivotal Pharmacovigilance. 
For unexpected serious adverse drug reactions (SUSARs), blinded reports will be 
disseminated and provided to Investigators at each study site. 

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When required and according to local law and regulations, unblinded SUSARs or other 
SAEs will be reported by an unblinded designee to the IRB/EC and regulatory 
authorities. 
9.7.3. 
Special Reporting Situations 
Death 
Death is an outcome of an event. The event that resulted in death should be recorded and 
reported on the SAE form and the AE eCRF page. 
Surgical or Diagnostic Procedures 
The illness leading to a surgical or diagnostic procedure is to be recorded as an AE/SAE, 
not the procedure itself. The procedure is to be captured in the case narrative as part of 
the action taken in response to the illness. 
9.7.4. 
Reporting Pregnancies 
Pregnancy itself is not considered an AE. If a patient becomes pregnant during the 
study or within 1 month of discontinuing any study medication or the partner of a 
patient participating in the study becomes pregnant during the study or within 3 months 
of discontinuing any study medication, the Investigator should report the pregnancy on a 
separate pregnancy report form provided to the sites. Only pregnancies occurring from 
the time of first study medication dose administered to the patient through Day 505 will 
be reported and documented. 
The patient/partner should be followed by the Investigator until completion of the 
pregnancy. If the pregnancy ends for any reason before the anticipated date, the 
Investigator should notify the Sponsor. At the completion of the pregnancy, the 
Investigator will document the outcome of the pregnancy. 
This pregnancy report form must be completed and submitted, either by e-mail or fax, 
immediately but no later than 24 hours of the Investigator’s learning of the event to: 
Pivotal Pharmacovigilance 
North America:  
(Fax) +1 877-853-3275 
Europe/UK/Asia-Pacific:  
(Fax) +34 913 076 047 
e-mail: drugsafety@pivotalcr.com 
However, any pregnancy complication, spontaneous or elective abortion, still birth, 
neonatal death, or congenital anomaly will be recorded as an AE or SAE, and reported, as 
applicable. 
9.8. 
Safety Committee 
A Safety Committee will conduct regular blinded reviews of all AEs and reactogenicity 
events. The Safety Committee will also review blinded safety data from a sentinel cohort 

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of 12 patients before dosing in the expanded cohort of patients. The responsibilities of the 
Safety Committee will be delineated in a Safety Analysis Plan. 
9.9. 
Data Monitoring Committee 
This study will be overseen by an independent DMC, which will have access to 
unblinded data, as needed, for the assessment of patient safety. A charter describing the 
roles, responsibilities, and operating procedures of the DMC will be implemented prior to 
study initiation. 
9.10. 
Medical Monitor 
A Medical Monitor will provide 24-hour/7-day coverage for medical issues pertaining to 
this study. The contact information for the Medical Monitor in the US and Canada is 
provided below: 
Robert Hardi, MD 
Altimmune, Inc. 
910 Clopper Road, Suite 201S 
Gaithersburg, MD 20878 
Telephone: +1 301-461-1084 
For issues arising in Europe/UK/Asia-Pacific, the contact information for the Medical 
Monitor in the EU is provided below: 
Ernesto Estefania, MD 
Pivotal, S.L.U. 
Calle Gobelas 19, la Florida 
28023 Madrid-Spain 
Telephone: + 34 620 844 036 
e-mail address: ernesto.estefania@pivotalcr.com 

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10. 
STATISTICS 
10.1. 
General Procedures 
Baseline is defined as data collected closest to randomization prior to any study 
medication dosing. All analyses and summary statistics will be presented by treatment 
group (HepTcell, placebo). 
Descriptive statistics, including the numbers and percentages for categorical variables 
and the numbers, means, standard deviations, medians, minimums and maximums for 
continuous variables will be provided by treatment. 
10.2. 
Sample Size 
A study of IFN-Į2 in a population with inactive CHB reported a mean incremental 
decrease of 1.3 log-qHBsAg at 24 weeks in those patients completing IFN-Į2 treatment 
compared to non-treatment. Mean decrease would translate to DSSUR[LPDWHO\RI
patients completing treatment achieving 1.3 log-qHBsAg response (reduction). To 
estimate treatment effect in the current study, the proportion of patients achieving a 
1.0-log reduction in qHBsAg is estimated as one-KDOIRISDWLHQWVwho achieve this 
response. Assuming a response rate of 3RQSODFHERDQG5RQ+HS7FHOO40 patients 
will be randomized per treatment group to detect a difference in the proportion of patients 
treated with HepTcell achieving the primary endpoint compared to patient treated with 
placebo at a 0.05 level of significance (two-VLGHGZLWKDSSUR[LPDWHO\SRZHU 
10.3. 
Analysis Sets 
Safety Analysis Set: All patients who receive any study medication. Patients will be 
analyzed according to the treatment that they receive. 
Modified intent to treat (mITT) Analysis Set: All randomized patients who receive any 
amount of study medication, have a baseline and at least one post-baseline efficacy 
assessment. Patients will be analyzed according to the treatment that they receive. This 
analysis set will be used for primary and secondary analyses. 
Per Protocol (PP) Set: All randomized patients who receive the full designated amount of 
study medication according to the correct treatment assignment and who have results 
from HBV serology and viral markers at Day 85. 
10.4. 
Statistical Methods 
10.4.1. 
Primary Efficacy Endpoint 
For the primary analysis, proportions of patients with virologic response, defined as a 
1.0-log reduction in HBsAg or serologic clearance of HBsAg, will be compared between 
+HS7FHOODQGSODFHERJURXSVXVLQJ)LVKHU¶V([DFW7HVWDWDtwo-sided level of 
significance. 

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Patients who discontinue prematurely or have missing data will be considered 
nonresponders for that endpoint. Linear and logistic regression will be employed to 
examine the effects of baseline factors, such as qHBsAg level, HBV DNA levels, and 
hepatitis B genotype on response. 
10.4.2. 
Secondary and Exploratory Efficacy Endpoints 
The same approach as used for the primary efficacy endpoint will be applied for 
secondary and exploratory endpoints that are categorical in nature. 
Changes from baseline in PBMC ELISpot, HBsAg, HBcrAg, pg-RNA, and quantitative 
HBV DNA will be analyzed using a mixed model for repeated measures (MMRM). The 
model will include the fixed effects of treatment, stratification factor, week, and 
treatment-by-visit interaction as well as the continuous, covariate of baseline level. The 
model will employ an unstructured within patient covariance matrix and a restricted 
maximum likelihood (ReML) estimation method. 
Relationships between hepatitis flares and HBsAg loss and/or decline will be evaluated 
logistic and linear regression. 
A Kaplan-Meier model will be developed to compare changes between treatment groups 
in HBsAg clearance and a 1-log reduction in HBsAg over time. 
No multiplicity adjustments will be made for secondary or exploratory endpoints. 
10.4.3. 
Analysis of Safety 
Quantitative safety data will be summarized using descriptive statistics and frequency 
distributions. Qualitative safety data will be summarized by frequencies and percentages. 
All summaries will be presented by treatment arm. AEs will be coded using Medical 
Dictionary for Regulatory Activities (MedDRA) and concomitant medications will be 
coded using WHO drug dictionary. 
Laboratory evaluations, vital signs assessments and ECG parameters will be summarized 
by treatment group and protocol specified collection time point. A summary of change 
from baseline at each protocol specified time point by treatment group will also be 
presented. 
10.4.4. 
Demographic and Baseline Characteristics 
Descriptive statistics will be used to evaluate differences in demographic and baseline 
characteristics. 
10.5. 
Interim Analysis 
An interim analysis will be performed after all patients complete 24 weeks (6 doses) of 
treatment or discontinue study medication. The conduct of the interim analysis will be 
detailed in the statistical analysis plan (SAP). 

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The database will be locked when all patients complete the Day 169 assessments or 
terminate the trial; a second database lock will take place when all patients complete the 
Day 505 assessments or terminate the trial. Efficacy and safety endpoints (as applicable) 
will be reported on all data accrued through these times. With the exception of unblinding 
required to assess Stopping Rules or the relationship of SAEs to study medication for 
expedited safety reporting, patients will not be individually unblinded until the 
completion of the Day 505 database lock. 
10.6. 
Statistical Analysis Plan 
A formal statistical analysis plan (SAP) will be developed and finalized prior to the 
database lock and unblinding of treatment assignment. This plan will confirm the analysis 
sets used in the analysis, outline all data handling conventions, and specify all statistical 
methods to be used for all safety and efficacy analyses. The SAP will be formalized and 
signed-off on prior to the locking of the database and unblinding of the treatment codes. 
The SAP will supersede the protocol with respect to analyses specified, although the 
primary analysis will remain the same. It is anticipated that analyses other than those 
specified in the protocol may be pre-specified in the SAP. 

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11. 
DATA QUALITY ASSURANCE 
Accurate, consistent, and reliable data will be ensured through the use of standard 
practices and procedures. These are described in the following sections. 
11.1. 
Data Handling 
Data will be recorded at the site on source documents and reviewed by the Clinical 
Research Associate (CRA) during monitoring visits. The CRA will verify data recorded 
in the eCRF system with source documents. All corrections or changes made to any study 
data must be appropriately tracked in an audit trail in the eCRF system. The eCRFs will 
be considered complete when all missing, incorrect, and/or inconsistent data have been 
accounted for. 
11.2. 
Computer Systems 
Data will be processed using a validated computer system conforming to regulatory 
requirements. 
11.3. 
Data Entry 
Data must be recorded using the eCRF system as the study is in progress. All study site 
personnel must log into the system using their secure user name and password in order to 
enter, review, or correct study data. These procedures must comply with 21 CFR Part 11 
and other appropriate international regulations. All passwords will be strictly confidential. 
11.4. 
Medical Information Coding 
For medical information the following thesauri will be used: 
x MedDRA v. 23.0 (or subsequent version) for AEs 
x WHO Drug Dictionary June 2017 (or subsequent version) for concomitant 
medications 
11.5. 
Data Validation 
Validation checks programmed within the eCRF system, as well as supplemental 
validation performed via review of the downloaded data, will be applied to the data in 
order to ensure accurate, consistent, and reliable data. Data identified as erroneous, or 
data that are missing, will be referred to the investigative site for resolution through data 
queries. 
The eCRFs must be reviewed and electronically signed by the Investigator who signed 
the protocol. 

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11.6. 
Study Monitoring Requirements 
It is the responsibility of the Investigator to ensure that the study is conducted in 
accordance with the protocol, Declaration of Helsinki, ICH GCP guidelines, and 
applicable regulatory requirements, and that valid data are entered into the eCRFs. 
The Investigator will permit the Sponsor or their designee to monitor the study as 
frequently as deemed necessary to determine that data recording and protocol adherence 
are satisfactory. Monitoring will include on-site review of the eCRFs for completeness 
and clarity, cross-checking with source documents, and clarification of administrative 
matters. The review of medical records will be performed in a manner to ensure that 
patient confidentiality is maintained. All monitoring activities will be reported and 
archived. In addition, monitoring visits will be documented at the investigational site by 
CRA signature and date on the study-specific monitoring log and the completion of a 
detailed monitoring report. 
The CRA will ensure that the investigation is conducted according to protocol design and 
regulatory requirements by frequent communications with the investigational site 
(monitoring visits, letter, telephone, email, and fax). 
All unused study medication and other study materials are to be returned to the Sponsor 
or designee after the clinical phase of the study has been completed. 
Regulatory authorities, the IRB/EC, and/or the Sponsor’s clinical quality assurance group 
may request access to all source documents, eCRFs, and other study documentation for 
on-site audit or inspection. Direct access to these documents must be guaranteed by the 
Investigator, who must provide support at all times for these activities. 
11.7. 
Source Document and Case Report Form Completion 
Source data is defined as all information in original records and certified copies of 
original records of clinical findings, observations, or other activities in a clinical study 
necessary for the evaluation and reconstruction of the clinical study. Source data are 
contained in source documents (i.e., original records or certified copies). Source 
documents and the eCRFs will be completed for each study patient. It is the 
Investigator’s responsibility to ensure the accuracy, completeness, and timeliness of the 
data reported in the patient’s source document/eCRF. The source document/eCRF should 
indicate the patient’s participation in the study and should document the dates and details 
of study procedures, AEs, and patient status. 
The Investigator, or designated representative, should complete the source 
document/eCRF as soon as possible after information is collected, preferably on the same 
day that a study patient is seen for an examination, treatment, or any other study 
procedure. Any outstanding entries must be completed immediately after the final 
examination. An explanation should be given for all missing data. 
The Investigator must sign and date the Investigator’s Statement at the end of the source 
document/eCRF to endorse the recorded data. 

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The Investigator will retain all completed source documents. A site-specific eCRF 
archive and audit trail will be provided at the close of the study to each Investigator. The 
Sponsor or designee will retain the eCRF archive and audit trail for all investigative sites. 
11.8. 
Record Retention 
Records of patients, source documents, monitoring visit logs, eCRFs, inventories of study 
product, regulatory documents, and other correspondence pertaining to the study must be 
kept in the appropriate study files at the site. The Investigator will maintain all study 
records according to ICH GCP and applicable regulatory requirements. Records will be 
retained for at least 2 years after the last marketing application approval or 2 years after 
formal discontinuation of the clinical development of the investigational product or 
according to applicable regulatory requirements. If the Investigator withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person 
willing to accept the responsibility. The Sponsor must be notified in writing if a custodial 
change occurs. 

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12. 
ETHICS 
12.1. 
Good clinical practice 
The study will be conducted in accordance with the protocol, GCP, the relevant ICH 
guidelines, the applicable regulatory requirements, and the ethical principles that have 
their origins in the Declaration of Helsinki. As required by US FDA (21 CFR 56) and the 
Declaration of Helsinki, the study protocol, amendments, and informed consent form will 
be reviewed and approved, according to 21 CFR Parts 50 and 56 (or similar local 
requirements, such as ICH E6, for ex-US sites), respectively, by each study center’s IRB 
or EC. 
12.2. 
Institutional Review Board / Independent Ethics Committee 
The IRB/EC will review all appropriate study documentation in order to safeguard the 
rights, safety, and wellbeing of patients. Federal/local regulations and ICH GCP 
guidelines require that approval be obtained from an IRB/EC prior to participation of 
patients in research studies. The study will only be conducted at sites where IRB/EC 
approval has been obtained. The protocol, Investigator’s Brochure, informed consent 
form, advertisements (if applicable), written information given to the patients, safety 
updates, annual progress reports, and any revisions to these documents will be provided 
to the IRB/EC by the Investigator. 
No drug will be released to the site for dosing until written IRB/EC authorization has 
been received by the Sponsor. 
12.3. 
Patient Information and Consent 
The informed consent form and any changes to the informed consent form made during 
the course of the study must be agreed to by the Sponsor or their designee and the 
IRB/EC prior to its use and must be in compliance with ICH GCP guidelines, local 
regulatory requirements, and legal requirements. 
The Investigator must ensure that each study patient or proxy is fully informed about the 
nature and objectives of the study and possible risks associated with participation and 
must ensure that the patient has been informed of his/her rights to privacy. The 
Investigator will obtain written informed consent from each patient or the patient’s 
legally authorized representative before any study-specific activity is performed and will 
document in the source documentation that consent was obtained prior to enrollment in 
the study. The original signed copy of the informed consent form must be maintained by 
the Investigator and is subject to inspection by the Sponsor, their representatives, 
auditors, the IRB/EC, and/or regulatory agencies. A copy of the signed informed consent 
form will be given to the study patient or proxy. Whenever possible, patients who 
participate based on proxy consent will be re-consented once deemed capable by the 
Investigator of providing consent on their own. 

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If significant new findings are developed during the course of research which may affect 
the willingness of patients to continue study participation, the Sponsor will notify each 
Investigator of the findings via letter or telephone. 
12.4. 
Patient Confidentiality 
In order to maintain patient privacy, all eCRFs, study medication accountability records, 
study reports and communications will identify the patient by initials and the assigned 
patient number. The Investigator will grant monitor(s) and auditor(s) from the Sponsor or 
its designee and regulatory authority(ies) access to the patient’s original medical records 
for verification of data gathered on the eCRFs and to audit the data collection process. 
The patient’s confidentiality will be maintained and will not be made publicly available 
to the extent permitted by the applicable laws and regulations. 
12.5. 
Protocol compliance 
The Investigator will conduct the study in compliance with the protocol provided by the 
Sponsor, the approval/favorable opinion of the IRB/EC and the appropriate regulatory 
authority(ies). Modifications to the protocol should not be made without agreement of 
both the Investigator and the Sponsor. Changes to the protocol will require written 
IRB/EC approval/favorable opinion prior to implementation, except when the 
modification is needed to eliminate an immediate hazard(s) to patients. The IRB/EC may 
provide, if applicable regulatory authority(ies) permits, expedited review and 
approval/favorable opinion for minor change(s) in ongoing studies that have the 
approval/favorable opinion of the IRB/EC. The Sponsor will submit all protocol 
modifications to the regulatory authority(ies) in accordance with the governing 
regulations. 
When immediate deviation from the protocol is required to eliminate an immediate 
hazard(s) to patients, the Investigator will contact the Sponsor, if circumstances permit, to 
discuss the planned course of action. Any departures from the protocol must be fully 
documented in the eCRF and source documentation and reported to the appropriate study 
monitor or staff in a timely fashion. 

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13. 
COMPENSATION, INSURANCE AND INDEMNITY 
The Sponsor has retained an insurance policy covering, in its terms and provisions, its 
legal liability for injuries caused to participating persons and arising out of this research 
performed strictly in accordance with the scientific protocol as well as with applicable 
law and professional standards. The patient will be appropriately treated or compensated, 
or both, for any health or other problems arising from participation in this study. 

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14. 
STEERING COMMITTEE 
In addition to the DMC, a study Steering Committee will be appointed to advise the 
Sponsor on the conduct of the trial. The committee will comprise of the Principal 
Investigator, the Lead Investigators of the individual participating countries, the 
Sponsor’s Chief Medical Officer, and managers from the Sponsor and the CRO 
overseeing study conduct. The committee will provide advice on study endpoints, 
compliance with protocol procedures, recruitment, safety signal detection, and issues that 
could impact data quality or safety. They will also advise on the acceptability of 
Investigators and sites that will participate in the trial. The Steering Committee will 
remain blinded throughout the trial. A charter describing the roles, responsibilities, and 
operating procedures of the Steering Committee will be developed prior to study 
initiation. 

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15. 
PUBLICATION POLICY 
All information provided regarding the study, as well as all information 
collected/documented during the course of the study, will be regarded as confidential. 
The Investigator agrees not to disclose such information in any way without prior written 
permission from the Sponsor. 
Any publication of the results, either in part or in total, including articles in journals or 
newspapers, oral presentations, or abstracts, by the Investigator(s) or their 
representative(s), shall require prior approval, notification, and review within a 
reasonable time frame by the Sponsor and cannot be made in violation of the Sponsor’s 
confidentiality restrictions or to the detriment of the Sponsor’s intellectual property 
rights. 
It is anticipated that the results of this study will be presented at scientific meetings 
and/or published in a peer reviewed scientific or medical journal. A Publications 
Committee, comprising the Investigators participating in the study and representatives 
from the Sponsor, as appropriate, will be formed to oversee the publication of the study 
results, which will reflect the experience of all participating study centers. Subsequently, 
individual Investigators may publish results from the study in compliance with their 
agreement with the Sponsor. A pre-publication manuscript is to be provided to the 
Sponsor at least 60 days prior to the submission of the manuscript to a publisher. 
Similarly, the Sponsor will provide any company prepared manuscript to the 
Investigators for review at least 30 days prior to submission to a publisher. 

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16. 
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Lim SG, Lee GH, Dan YY, et al. HBsAg loss in inactive chronic hepatitis B carriers is 
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APPENDICES 
Appendix 1 – Reactogenicity Events 
The following reactogenicity events will be assessed by patients for 7 days after each 
dose of study medication and recorded in daily diaries. 
Local (injection site) reactogenicity events 
x Pain (pain on pressure) 
x Pain (spontaneous pain without pressure) 
x Erythema/Redness 
x Swelling/hardening 
Systemic reactogenicity events 
x Headache 
x Fatigue 
x Myalgias (muscle aches) 
x Nausea 
x Vomiting 
x Diarrhea 
x Chills 
x Fever 
x Arthralgias (joint aches) 
Note: Microscopic hematuria will be assessed by urinalyses performed at visits 7±2 days 
after each dose of study medication 

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Appendix 2 – Immune-Mediated Medical Conditions 
Any AE assessed by the Investigator as immune-mediated but not appearing in the list 
below will also be reported as an IMC. 
Gastrointestinal disorders 
x Celiac disease 
x Crohn’s disease 
x Ulcerative colitis 
x Ulcerative proctitis 
Liver disorders 
x Autoimmune cholangitis 
x Autoimmune hepatitis 
x Primary biliary cholangitis 
x Primary sclerosing cholangitis 
Metabolic diseases 
x Addison’s disease 
x Autoimmune thyroiditis (including Hashimoto thyroiditis) 
x Diabetes mellitus type I 
x Grave’s or Basedow’s disease 
Musculoskeletal disorders 
x Antisynthetase syndrome 
x Dermatomyositis 
x Juvenile chronic arthritis (including Still’s disease) 
x Mixed connective tissue disorder 
x Polymyalgia rheumatic 
x Polymyositis 
x Psoriatic arthropathy 
x Relapsing polychondritis 
x Rheumatoid arthritis 
x Scleroderma, including diffuse systemic form and CREST syndrome 
x Spondyloarthritis, including ankylosing spondylitis, reactive arthritis (Reiter's 
Syndrome) and undifferentiated spondyloarthritis 

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x Systemic lupus erythematosus 
x Systemic sclerosis 
Neuroinflammatory disorders 
x Acute disseminated encephalomyelitis, including site specific variants (eg, 
noninfectious encephalitis, encephalomyelitis, myelitis, radiculomyelitis) 
x Cranial nerve disorders, including paralyses/paresis (eg, Bell’s palsy) 
x Guillain-Barré syndrome, including Miller Fisher syndrome and other variants 
x Immune-mediated peripheral neuropathies and plexopathies, including 
chronic inflammatory demyelinating polyneuropathy, multifocal motor 
neuropathy and polyneuropathies associated with monoclonal gammopathy 
x Multiple sclerosis 
x Narcolepsy 
x Optic neuritis 
x Transverse myelitis 
x Myasthenia gravis, including Eaton-Lambert syndrome 
Skin disorders 
x Alopecia areata  
x Autoimmune bullous skin diseases, including pemphigus, pemphigoid and 
dermatitis herpetiformis 
x Cutaneous lupus erythematosus 
x Erythema nodosum 
x Morphoea 
x Lichen planus 
x Psoriasis 
x Rosacea 
x Sweet’s syndrome 
x Vitiligo 
Vasculitides 
x Large vessels vasculitis including: giant cell arteritis such as Takayasu's 
arteritis and temporal arteritis 
x Medium sized and/or small vessels vasculitis including: polyarteritis nodosa, 
Kawasaki's disease, microscopic polyangiitis, Wegener's granulomatosis, 

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Churg–Strauss syndrome (allergic granulomatous angiitis), Buerger’s disease 
thromboangiitis obliterans, necrotizing vasculitis and anti-neutrophil 
cytoplasmic antibody (ANCA) positive vasculitis (type unspecified), Henoch- 
Schonlein purpura, Behcet's syndrome, leukocytoclastic vasculitis 
Others 
x Antiphospholipid syndrome 
x Autoimmune hemolytic anemia 
x Autoimmune glomerulonephritis (including IgA nephropathy, 
glomerulonephritis rapidly progressive, membranous glomerulonephritis, 
membranoproliferative glomerulonephritis, and mesangioproliferative 
glomerulonephritis) 
x Autoimmune myocarditis/cardiomyopathy 
x Autoimmune thrombocytopenia 
x Goodpasture syndrome 
x Idiopathic pulmonary fibrosis 
x Pernicious anemia 
x Raynaud’s phenomenon 
x Sarcoidosis 
x Sjögren’s syndrome 
x Stevens-Johnson syndrome 
x Uveitis