A Phase 1, Blinded, Placebo-Controlled Study of the Safety, Tolerability, Pharmacokinetics of Single and Multiple Ascending Doses of ABI-4334 in Healthy Subjects
Phase: PHASE1
Conditions: Chronic Hepatitis B
Sponsor: Assembly Biosciences

Study Title: A Phase 1, Blinded, Placebo-controlled Study of the Safety, Tolerability, 
Pharmacokinetics of Single- and Multiple-Ascending Doses of ABI-4334 in Healthy Subjects 
NCT Number: NCT05569941 
Date of Document: 16 June 2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ABI-4334  
Study ABI-4334-101 Original Protocol 16 June 2022  
 
Assembly Biosciences  
Confidential 
Page 1 of 95 
 
 
 
 
CLINICAL STUDY PROTOCOL 
PROTOCOL TITLE  
A Phase 1, Blinded, Placebo-controlled Study of the 
Safety, Tolerability, Pharmacokinetics of Single- and 
Multiple-Ascending Doses of ABI-4334 in Healthy 
Subjects 
PROTOCOL NUMBER  
ABI-4334-101 
DRUG NAME  
ABI-4334 
REGULATORY AGENCY 
IDENTIFIER NUMBER(S) 
Not Available  
SPONSOR 
Assembly Biosciences, Inc.  
331 Oyster Point Boulevard, 4th Floor 
South San Francisco, California 94080, USA 
(833) 509-4583 
PROTOCOL – DATE 
Original – 16 June 2022   
PROTOCOL HISTORY  
Not Applicable   
 
CONFIDENTIALITY STATEMENT  
The information contained in this document and all other information relevant to Assembly 
Biosciences are the confidential and proprietary information of Assembly Biosciences 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 Assembly Biosciences.  

ABI-4334  
Study ABI-4334-101 Original Protocol 16 June 2022  
 
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CLINICAL STUDY PROTOCOL SPONSOR APPROVAL FORM  
Protocol Title  
A Phase 1, Blinded, Placebo-controlled Study of the Safety, 
Tolerability, Pharmacokinetics of Single- and Multiple-Ascending 
Doses of ABI-4334 in Healthy Subjects 
Protocol Number  
ABI-4334-101 
Protocol Version – 
Date  
Original – 16 June 2022   
 
This clinical study protocol was subject to critical review and has been approved by the appropriate 
protocol review personnel of the Sponsor. The information contained in this protocol is consistent 
with: 
 The current risk-benefit evaluation of the investigational product. 
 The ethical and scientific standards governing clinical research that are set out in the 
current International Council for Harmonisation (ICH) guideline (E6) on Good 
Clinical Practice (GCP), US Title 21 of the Code of Federal Regulations (CFR) Parts 
50, 54, 56, and 312, and other applicable local requirements. 
The Principal Investigator will be supplied with details of any significant or new findings, 
including adverse events, relating to treatment with the investigational product. 
Sponsor Signatory: 
 
 
Assembly Biosciences  
Approval Signature and Date 
 
 
 
 
 
 
 

ABI-4334  
Study ABI-4334-101 Original Protocol 16 June 2022  
 
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INVESTIGATOR STATEMENT 
Protocol Title  
A Phase 1, Blinded, Placebo-controlled Study of the Safety, 
Tolerability, Pharmacokinetics of Single- and Multiple-Ascending 
Doses of ABI-4334 in Healthy Subjects 
Protocol Number  
ABI-4334-101 
Protocol Version – 
Date  
Original – 16 June 2022   
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 
described herein, in accordance with Good Clinical Practice (GCP) as set out in the current 
International Council for Harmonisation (ICH) guidelines (E6) and other applicable national or 
local requirements, 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 Assembly Biosciences or specified 
designees. I will discuss the material with them to ensure that they are fully informed about 
Assembly Biosciences and the study. 
 
Principal Investigator Signature:  
Print Name:  
Date:  
Please keep the original, signed copy of this Investigator signature page in your records and email 
a copy to your site monitor for archival in the Trial Master File (TMF). 
 
 

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TABLE OF CONTENTS 
TABLE OF CONTENTS ............................................................................................................. 4 
ABBREVIATIONS AND TERMS .............................................................................................. 9 
PROTOCOL CHANGE HISTORY .......................................................................................... 13 
1 
SYNOPSIS ............................................................................................................................ 14 
2 
INTRODUCTION ............................................................................................................... 23 
2.1 
Chronic Hepatitis B Virus Infection ........................................................................... 23 
2.2 
ABI-4334 ....................................................................................................................... 24 
2.2.1 
Description ............................................................................................................. 24 
2.2.2 
Nonclinical Studies ................................................................................................ 24 
2.2.3 
Clinical Studies ...................................................................................................... 25 
2.3 
Study Rationale ............................................................................................................ 25 
2.3.1 
Rationale for Dose Selection ................................................................................ 25 
2.4 
Risk-Benefit Profile ...................................................................................................... 26 
3 
Study Objectives and Endpoints ........................................................................................ 28 
3.1 
Study Objectives ........................................................................................................... 28 
3.1.1 
Primary Objective ................................................................................................. 28 
3.1.2 
Secondary Objectives............................................................................................ 28 
3.1.3 
Exploratory Objective .......................................................................................... 28 
3.2 
Study Endpoints ........................................................................................................... 28 
3.2.1 
Primary Endpoint ................................................................................................. 28 
3.2.2 
Secondary Endpoints ............................................................................................ 28 
3.2.3 
Exploratory Endpoint ........................................................................................... 29 
4 
Study Design ......................................................................................................................... 30 
4.1 
Overview ....................................................................................................................... 30 
4.1.1 
Part A (SAD in Healthy Subjects) ....................................................................... 30 
4.1.2 
Part B (MAD in Healthy Subjects) ...................................................................... 32 
4.2 
Study Treatments ......................................................................................................... 33 
4.2.1 
Part A (SAD in Healthy Subjects) ....................................................................... 33 
4.2.2 
Part B (MAD in Healthy Subjects: 8-Day Dosing Duration) ............................ 33 
4.3 
Duration of Treatment ................................................................................................. 34 
4.4 
Duration of Study ......................................................................................................... 34 

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4.5 
End of Study Definition ............................................................................................... 34 
5 
Study Population ................................................................................................................. 35 
5.1 
Number of Subjects ...................................................................................................... 35 
5.2 
Inclusion Criteria ......................................................................................................... 35 
5.3 
Exclusion Criteria ........................................................................................................ 35 
5.4 
Screen Failures ............................................................................................................. 36 
5.5 
Dietary and Lifestyle Restrictions .............................................................................. 37 
5.6 
Meals .............................................................................................................................. 38 
5.6.1 
Test Meal for Subjects in the Food Effect Cohorts ............................................ 38 
6 
Study Drugs .......................................................................................................................... 39 
6.1 
Investigational Medicinal Product(s) (IMPs) ............................................................ 39 
6.1.1 
ABI-4334 ................................................................................................................ 39 
6.1.2 
Accountability of IMP .......................................................................................... 41 
6.2 
Non-Investigational Medicinal Products(s) ............................................................... 41 
6.3 
Concomitant Medications and Procedures ................................................................ 41 
6.3.1 
Prohibited Concomitant Therapy ....................................................................... 42 
6.4 
Randomization, Blinding, and Treatment Codes ...................................................... 42 
6.4.1 
Randomization ...................................................................................................... 42 
6.4.2 
Blinding .................................................................................................................. 42 
7 
DISCONTINUATION OF STUDY TREATMENT OR STUDY ................................... 43 
7.1 
Discontinuation of Study Treatment for A Subject .................................................. 43 
7.1.1 
Criteria for Discontinuation of Study Treatment for a Subject ....................... 43 
7.1.2 
Subject Discontinuation or Withdrawal from the Study .................................. 43 
7.1.3 
Subject Lost to Follow-Up .................................................................................... 44 
7.2 
Criteria for Discontinuation of Study Treatment for a Cohort ............................... 44 
7.3 
Discontinuation of the Study ....................................................................................... 45 
8 
Study Procedures and Assessments ................................................................................... 46 
8.1 
Schedule of Assessments .............................................................................................. 46 
8.2 
Study Visit Procedures ................................................................................................. 46 
8.2.1 
Screening Assessments.......................................................................................... 46 
8.2.2 
Subject Enrollment and Treatment Assignment ............................................... 46 
8.3 
Assessment of Safety .................................................................................................... 46 

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8.3.1 
Physical Examination ........................................................................................... 46 
8.3.2 
Vital Signs .............................................................................................................. 47 
8.3.3 
Electrocardiograms............................................................................................... 47 
8.3.4 
Holter Data Collection .......................................................................................... 48 
8.3.5 
Clinical Laboratory Assessments ........................................................................ 48 
8.4 
Assessment of Pharmacokinetics ................................................................................ 49 
8.5 
Unscheduled Visit Procedures..................................................................................... 49 
8.6 
Premature Study Termination Visit Procedures ....................................................... 49 
9 
Adverse Events and Toxicity Management ....................................................................... 50 
9.1 
Definition of Adverse Event ........................................................................................ 50 
9.2 
Documenting Adverse Events ..................................................................................... 50 
9.3 
Assessment of Intensity ................................................................................................ 51 
9.4 
Assessment of Causality ............................................................................................... 51 
9.5 
Adverse Event Follow-up ............................................................................................. 51 
9.6 
Serious Adverse Events ................................................................................................ 52 
9.6.1 
Definition of Serious Adverse Event ................................................................... 52 
9.6.2 
Definition of Terms ............................................................................................... 52 
9.6.3 
Reporting Serious Adverse Events ...................................................................... 53 
9.7 
Laboratory Abnormalities and Other Abnormal Assessments as AEs or SAEs .... 53 
9.8 
Overdose ........................................................................................................................ 53 
9.9 
Pregnancy ...................................................................................................................... 54 
9.9.1 
Female Subjects Who Become Pregnant ............................................................ 54 
9.9.2 
Male Subjects With Partners Who Become Pregnant ....................................... 54 
9.10 Toxicity Management .................................................................................................. 54 
9.10.1 
Grades 1 and 2 Adverse Event ............................................................................. 55 
9.10.2 
Grade 3 or Grade 4 Adverse Event ..................................................................... 55 
10 Statistical Considerations.................................................................................................... 56 
10.1 General Considerations ............................................................................................... 56 
10.2 Determination of Sample Size ..................................................................................... 56 
10.3 Analysis Populations .................................................................................................... 56 
10.4 Planned Analyses .......................................................................................................... 56 
10.4.1 
Disposition of the Study Subjects ........................................................................ 57 

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10.4.2 
Demographics ........................................................................................................ 57 
10.4.3 
Extent of Exposure ................................................................................................ 57 
10.4.4 
Analysis of Safety Endpoints................................................................................ 57 
10.4.5 
Analysis of Pharmacokinetic Endpoints ............................................................. 57 
10.5 Interim Analysis ........................................................................................................... 60 
10.6 Data Review Committee .............................................................................................. 60 
10.6.1 
Overview of Data Review Committee ................................................................. 60 
10.6.2 
Data Review Committee Procedures ................................................................... 61 
11 Responsibilities..................................................................................................................... 62 
11.1 Investigator Responsibilities ........................................................................................ 62 
11.1.1 
Good Clinical Practice .......................................................................................... 62 
11.1.2 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ....... 62 
11.1.3 
Informed Consent ................................................................................................. 62 
11.1.4 
Confidentiality ....................................................................................................... 63 
11.1.5 
Study Files and Retention of Records ................................................................. 63 
11.1.6 
Audits and Inspections ......................................................................................... 63 
11.1.7 
Protocol Compliance ............................................................................................. 64 
11.2 Sponsor Responsibilities .............................................................................................. 64 
11.2.1 
Protocol Amendments and Modifications .......................................................... 64 
11.2.2 
Data Management ................................................................................................. 64 
11.2.3 
Study Report and Publications ............................................................................ 64 
REFERENCES ............................................................................................................................ 66 
APPENDICES ............................................................................................................................. 68 
APPENDIX 1a.  SCHEDULE OF ASSESSMENTS FOR SCHEDULED VISITS: PART 
A – SAD (COHORTS A1-A5, COHORT A7 Period 1) IN HEALTHY SUBJECTS ........... 69 
APPENDIX 1b.  SCHEDULE OF ASSESSMENTS FOR SCHEDULED VISITS: PART 
A – SAD (COHORT A6, COHORT A7 Period 2) ................................................................... 71 
APPENDIX 2. 
SCHEDULE OF ASSESSMENTS FOR SCHEDULED VISITS: PART B 
– MAD IN HEALTHY SUBJECTS .......................................................................................... 73 
APPENDIX 3.  SCHEDULE OF ASSESSMENTS FOR OTHER VISITS ........................ 76 
APPENDIX 4. TOXICITY GRADING SCALE FOR ADVERSE EVENTS AND 
LABORATORY ABNORMALITIES ...................................................................................... 77 

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APPENDIX 5. PREGNANCY PRECAUTIONS AND THE DEFINITION OF 
CHILDBEARING POTENTIAL AND CONTRACEPTIVE REQUIREMENTS............... 93 
APPENDIX 6. PROTOCOL AMENDMENT SUMMARY OF CHANGES ........................ 95 
 
LIST OF TABLES  
Table 1. 
Assumed NO(A)EL Doses in Nonclinical Species and Proposed Clinical Dose
............................................................................................................................... 26 
Table 2. 
Clinical Laboratory Tests................................................................................... 48 
Table 3. 
Plasma Pharmacokinetic Parameters: Parts A and B; Day 1......................... 58 
Table 4. 
Plasma Pharmacokinetic Parameters: Part B (MAD) Day 8.......................... 58 
Table 5. 
Urine Pharmacokinetic Parameters: Part B (MAD) Day 8 ............................ 59 
 
LIST OF FIGURES  
Figure 1. 
Overview of Study Design – Parts A & B (SAD and MAD)............................ 30 
Figure 2. 
Study Design Schematic – Part A (SAD in Healthy Subjects) ........................ 31 
Figure 3. 
Study Design Schematic – Part B (MAD in Healthy Subjects) ....................... 33 

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ABBREVIATIONS AND TERMS  
Abbreviation 
Definition 
Ab(s) 
Antibody(ies) 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
aPTT 
Activated partial thromboplastin time  
AST 
Aspartate aminotransferase 
AUC 
Area under the concentration-time curve  
BID  
Twice daily  
BMI 
Body mass index  
cccDNA 
Covalently closed circular DNA 
CFR 
Code of Federal Regulations 
cHBV 
Chronic hepatitis B virus infection 
Cmax 
Maximum observed plasma concentration  
CRO 
Clinical Research Organization 
CSR 
Clinical Study Report 
CV 
Coefficient of variation  
DAIDS 
Division of AIDS 
DNA 
Deoxyribonucleic acid 
DRC 
Data Review Committee 
ECG 
Electrocardiogram  
eCRF 
Electronic Case Report Form 
EMA 
European Medicines Agency  
EOS 
End of study  
ETV 
Entecavir  
EU 
European Union  
FDA 
Food and Drug Administration 

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Abbreviation 
Definition 
FIH 
First-in-human 
GCP 
Good Clinical Practices 
GGT 
Gamma-glutamyl transferase 
GLP 
Good Laboratory Practices  
GMP 
Good Manufacturing Practices  
HBcAb 
Antibody to the HBV core protein 
HBcrAg 
Hepatitis B core-related antigen 
HBeAb 
Antibody to hepatitis B e antigen  
HBeAg 
Hepatitis B e antigen 
HBsAb 
Antibody to hepatitis B surface antigen  
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B virus  
HCC 
Hepatocellular carcinoma 
HCV 
Hepatitis C virus  
HDV  
Hepatitis D virus  
HDPE 
High-density polyethylene 
HED 
Human equivalent dose  
HIV 
Human immunodeficiency virus 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
IEC 
Independent Ethics Committee 
IFNα 
Interferon alpha 
IgM 
Immunoglobulin M 
IMPs 
Investigational medicinal product(s) 

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Abbreviation 
Definition 
IRB 
Institutional Review Board 
ISMPP 
International Society for Medical Publication Professionals 
IUD 
Intrauterine device 
LDD 
Last day of dosing  
LDH 
Lactate dehydrogenase  
LLN 
Lower limit of normal 
LLOQ 
Lower limit of quantification 
MCV 
Mean corpuscular volume 
MRSD 
Maximum recommended starting dose  
NA 
Not applicable  
NOAEL 
No observed adverse effect level 
NOEL 
No observed effect level  
NrtI  
Nucleos(t)ide/reverse transcriptase inhibitor 
OTC 
Over-the-Counter 
PBO 
Placebo 
pgRNA 
Pregenomic ribonucleic acid 
PK 
Pharmacokinetic(s) 
PKAP 
Pharmacokinetics Analysis Plan  
PO 
Orally by mouth 
PRN 
As needed 
QD 
Once daily  
RBC 
Red blood cell 
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Standard deviation 

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Abbreviation 
Definition 
SDD 
Spray Dried Dispersion 
SVR 
Sustained virologic response 
TBD  
To be determined  
TEAE 
Treatment-emergent adverse event 
TFV 
Tenofovir 
TMF 
Trial Master File 
ULN 
Upper limit of normal  
US 
United States 
WHO 
World Health Organization 
 
 
 

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PROTOCOL CHANGE HISTORY  
Not Applicable (Appendix 6). 

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1 SYNOPSIS  
Protocol Title  
A Phase 1, Blinded, Placebo-controlled Study of the Safety, Tolerability, 
Pharmacokinetics of Single- and Multiple-Ascending Doses of ABI-4334 in 
Healthy Subjects  
Protocol 
Number  
ABI-4334-101 
Test Product, 
Dose, and 
Mode of 
Administration  
ABI-4334 will be provided as 10 mg and 50 mg tablets for oral, by mouth (PO) 
administration.  
Part A (Single-ascending dose [SAD] in Healthy Subjects) 
• 
Cohort A1: 30 mg ABI-4334 or matching placebo (PBO), PO, single dose, 
fasted 
• 
Cohort A2: to be determined (TBD) mg ABI-4334 or PBO, PO, single 
dose, fasted 
• 
Cohort A3: TBD mg ABI-4334 or PBO, PO, single dose, fasted 
• 
Cohort A4: TBD mg ABI-4334 or PBO, PO, single dose, fasted 
• 
Cohort A5: TBD mg ABI-4334 or PBO, PO, single dose, fasted 
• 
Cohort A6: Food effect cohort with subjects from a previous fasted cohort, 
TBD mg ABI-4334 or PBO, PO, single dose, fed 
• 
Cohort A7: Additional food effect cohort (if needed), TBD mg ABI-4334, 
PO, single dose, 2-period crossover (fasted & fed) 
Part B (Multiple-ascending dose [MAD] in Healthy Subjects: 8-Day Dosing 
Duration) 
• 
Cohort B1: TBD mg ABI-4334 or PBO, PO, multiple doses 
• 
Cohort B2: TBD mg ABI-4334 or PBO, PO, multiple doses 
The dose level for Part A (SAD) Cohort A1 is defined. The dose levels for 
subsequent cohorts and once daily (QD) or twice daily (BID) dosing schedule for 
Part B (MAD) will be selected based on evaluation of safety, tolerability, and 
available pharmacokinetics (PK) from the previous cohorts. In no case would each 
individual dose escalation be greater than 3.3-fold compared with the previous dose. 
Some prespecified cohorts may not be enrolled. 
Reference 
Therapy, Dose, 
and Mode of 
Administration  
Matching placebo tablets for oral administration will be supplied for each ABI-4334 
dosage strength. The dosing schedule will follow that of ABI-4334 for the 
respective cohort.  
Target 
Population  
Healthy male or female subjects 
 
Phase  
1 
Number of 
Subjects 
Planned  
Part A (SAD): Up to 46 (approximately 8 subjects/Cohorts A1-A6; 6 
subjects/Cohort A7 [Note: Cohort A6 will enroll returning subjects from a previous 
SAD cohort]) 

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Part B (MAD): Up to 16 (approximately 8 subjects/cohort) 
Study Sites and 
Location 
A single site in New Zealand  
Treatment 
Duration  
Part A (SAD): 1 day 
Part B (MAD): 8 days 
Study Duration  Part A (SAD): Up to 36 days per cohort, including 28 days of screening, 1 day of 
treatment, 7 days of follow up. The duration of the study will be longer for subjects 
in the food effect cohort(s) (see Study Design).  
Part B (MAD): Up to 43 days, including 28 days of screening, 8 days of treatment, 
and 7 days of follow up. 
Note: For each subject, end of study (EOS) is defined as completion of the last visit 
in the follow-up period or premature study termination, or subject is lost-to-follow-
up. The study will end when the last subject completes the last visit of the follow-up 
period or is considered “lost to follow-up,” whichever is later.  
Rationale  
Chronic hepatitis B virus infection is a major cause of liver-related morbidity and 
mortality affecting approximately 296 million people worldwide. While therapy 
with nucleos(t)ide reverse transcriptase inhibitors (NrtI) is able to achieve adequate 
viral suppression in most HBeAg negative patients and three quarters of HBeAg 
positive patients after 1-year, sustained virologic response (SVR) and loss of 
hepatitis B surface antigen (HBsAg) are rare (< 5%). Novel agents, administered 
alone or in combination with other therapies, are likely required to provide durable 
off-treatment virologic responses. 
ABI-4334 is one such agent, which following oral administration, provides potent 
and selective inhibition of the HBV core protein. Through interference with the 
essential functions of the HBV core protein, ABI-4334 inhibits HBV replication by 
orthogonal mechanisms distinct from NrtIs or IFNα. Thus, when used in 
combination with currently approved or other investigational HBV antivirals or 
immune modulators, ABI-4334 offers the potential to improve therapy for cHBV 
and provide patients with enhanced rates of durable off-treatment virologic 
responses following a finite treatment period. 
Study of ABI-4334-101 is a first-in-human (FIH) study assessing the safety, 
tolerability, and pharmacokinetics (PK) of single- (Part A, SAD) and multiple-
ascending doses (Part B, MAD) of ABI-4334 in healthy subjects. 
Objectives  
Primary Objectives 
The primary objective of this study is:  
• 
To assess the safety and tolerability of orally administered ABI-4334 in 
healthy subjects following single (Part A, SAD) and 8-day multiple (Part B, 
MAD) oral doses 
Secondary Objectives  
The secondary objectives of this study are: 

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• 
To characterize the PK of ABI-4334 in plasma following single doses and 
8-day multiple doses in healthy subjects  
• 
To evaluate the effect of food on the PK of ABI-4334 following a single 
dose in healthy subjects (Part A food-effect cohort(s) only) 
Exploratory Objective 
The exploratory objective of this study is:  
• 
To evaluate the PK of ABI-4334 in urine following 8-day multiple doses in 
healthy subjects (Part B, MAD)  
Endpoints  
Primary Endpoints 
The primary endpoint is: 
• 
Proportion of subjects with adverse events (AEs), premature treatment and 
study discontinuation due to AEs, and abnormal laboratory results (for each 
part) 
Secondary Endpoints 
The secondary endpoints are: 
• 
Noncompartmental plasma PK parameters such as AUClast, AUC0-inf, 
AUCtau, Cmax, Tmax, Ctrough, kel, t½, CL/F, Vz/F, dose normalized AUCs and 
Cmax, accumulation ratios and linearity factor (as applicable for each part) 
• 
Comparison of AUC and Cmax between fasted and fed treatments (Part A, 
SAD, food effect cohort(s) only)  
Exploratory Endpoints 
The exploratory endpoint is: 
• 
Noncompartmental urine PK parameters such as Ae, Ae0-24, CLr, %Fe (Part 
B, MAD)  
Study Design 
This is a Phase 1, FIH, randomized, blinded, PBO-controlled, single- and multiple-
dose dose escalation study of ABI-4334 in healthy subjects. Part A is designed to 
assess the safety, tolerability, and PK profile of ABI-4334 following SAD in 
healthy subjects, as well as the effect of food on ABI-4334. Part B is designed to 
assess the safety, tolerability, and PK profile of ABI-4334 following MAD in 
healthy subjects. The following figure provides an overview of the 2-Part study 
design.  

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Overview of Study Design - Parts A & B (SAD and MAD) 
Part A (SAD)
Single oral PO dose 
Healthy subjects
Per Cohort: 6 active, 2 PBO*  
Part B (MAD)
8-day multiple oral PO doses 
(QD or BID; fasted or fed)
Healthy subjects
Per Cohort: 6 active, 2 PBO  
• Cohort A1: 30 mg ABI-4334 or PBO, 
orally  fasted
• Cohort A2: TBD mg fasted
• Cohort A3: TBD mg fasted
• Cohort A4: TBD mg fasted
• Cohort A5: TBD mg fasted
• Cohort A6: Food effect cohort, TBD 
mg, fed
• Cohort A7: Food effect cohort, TBD 
mg (2-period crossover: fasted & fed)
• Cohort B1: TBD mg 
• Cohort B2: TBD mg
DRC Review** 
 
Abbreviations: BID=twice daily; MAD=multiple ascending dose; PBO=placebo; PO=orally by mouth; QD=once daily; 
SAD=single ascending dose; TBD=to be determined 
*Applies to SAD cohorts, except Cohort A7, which will only have 6 active subjects (ie, randomized to ABI-4334), no PBO 
subjects.  
**Part B dosing may commence prior to Part A being completed 
 
Part A (SAD in Healthy Subjects) 
Part A of the study will enroll up to 5 fasted cohorts, ie, Cohorts A1-A5, and up to 2 
fed cohorts to evaluate food effect, ie, Cohort A6 (with subjects from a previous 
fasted cohort), and an additional cohort, ie, Cohort A7, if needed (with new 
subjects).  
The first cohort of Part A, ie, Cohort A1, will evaluate a single dose of 30 mg ABI-
4334 (see Study Design Schematic for Part A). Dose levels for subsequent cohorts 
will be determined based on interim cohort review performed by an unblinded Data 
Review Committee (DRC) between SAD cohorts for purposes of dose escalation. 
Study data will include safety data from Day 1 through Day 4 for the present cohort 
and all available safety data for preceding cohorts. In addition, PK data through 
24 hours after dosing for the present cohort and available PK data for preceding 
cohorts will be reviewed. In no case would a dose escalation be greater than 3.3-
fold compared with the previous dose. The maximum dose of ABI-4334 to be 
evaluated in Part A (SAD) will not exceed the exposures observed in dogs at the no 
observed effect level (NOEL) dose of 30 mg/kg/day, or 1000 mg/day, whichever is 
lower. 

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Study Design Schematic – Part A (SAD in Healthy Subjects)
Screening 
(28-Day) 
Randomization
6 active; 2 PBO 
(Day 1)
Sentinel Dosing 
(N=2)
Observe for 3 days 
Dosing of Remaining Subjects 
(N=6) 
7-day follow-up visits 
(ie, Day 5-Day 7)
DRC Review 
COHORTS A1-A5
FOOD EFFECT COHORTS A6-A7
DRC Review for selection 
of a subsequent SAD dose 
or food effect cohort 
Cohort A6 
(N=8)
DRC 
Review
Cohort A7 
(N=6) 
DRC Review 
7-day washout
Discharge on 
Day 4
or
Screening 
(28-Day) 
Randomization
6 active
 (Day 1)
 
Abbreviations: DRC=Data Review Committee; PBO=placebo; SAD=single ascending dose 
 
Each of the Cohorts A1-A5 will enroll 8 healthy subjects who will be randomized 
in a 6:2 ratio to receive a single oral dose of the study drug, ie, ABI-4334 (6 
subjects) or PBO (2 subjects) in a fasted state, followed by a 7-day follow-up 
period. Subjects will remain confined to the study clinic from Days -1 to 4, with 
outpatient follow-up visits, as specified in Appendix 1. Dosing of a subsequent 
SAD cohort can begin at least 8 days after dosing of the sentinel subjects from the 
previous cohort (see below).  
Because this is a FIH study, a sentinel dosing approach will be utilized for each 
Cohort A1-A5, where initially only 2 subjects per cohort will be dosed (one 
receiving ABI-4334 and one receiving PBO). These sentinel subjects will be 
observed for a minimum of 3 days postdose to ensure acceptable tolerability of the 
study drug, as determined by the DRC, before dosing of the remaining subjects 
within the cohort can proceed.  
The DRC will select a single dose level from Cohorts A1-A5 for evaluation of food 
effect. The selection of this dose level can be made prior to completion of all fasted 
SAD cohorts and will be based on a preliminary evaluation by the DRC of the 
available safety, tolerability, and PK data from Cohorts A1-A5. Subjects who 
complete participation in this selected cohort will be asked to return to the study site 
to be enrolled into the food effect cohort (ie, Cohort A6), following a minimum of 
7-day washout period since their last study drug dose. While Baseline evaluations 
will be conducted prior to dosing in Cohort A6, repeat assessment of all study 
eligibility criteria will not be performed. Returning subjects will retain their original 
subject number and randomized treatment assignment. After the Day 7 visit in the 
original cohort (from Cohort A1-A5), the study drug will be administered 
30 minutes after the complete consumption of a high fat meal (approximately 50% 
calories from fat). 
If there is an insufficient number of subjects from previous fasted SAD cohorts (ie, 
A1-A5), who are willing to participate in Cohort A6, then a separate Cohort A7 

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may be enrolled, comprising 6 new subjects meeting the study eligibility criteria, 
who will all receive ABI-4334. Cohort A7 will involve a two-period crossover 
assessment of food effect (ie, Period 1: dosing under fasted or high fat-fed 
conditions; Period 2: dosing under condition opposite of Period 1), with a minimum 
7-day washout period between dosing in Period 1 and Period 2, and a 7-day 
postdose follow-up in Period 2.  
Part B (MAD in Healthy Subjects) 
Part B dosing may commence prior to Part A being completed. The dose level and 
dosing schedule for the first cohort of Part B, ie, Cohort B1, will be determined 
based on emergent safety, tolerability, and PK data from completed Part A cohorts, 
with the daily dose at least 2-fold lower than a Part A dose level deemed safe and 
tolerable.  
Both cohorts planned for Part B, ie, Cohort B1 and Cohort B2, will enroll 8 healthy 
subjects who will be randomized in a 6:2 ratio to receive oral daily doses of the 
study drug, ie, ABI-4334 (6 subjects) or PBO (2 subjects), for 8 consecutive days, 
followed by a 7-day follow-up period (see Study Design Schematic for Part B). 
Dosing may occur under fasted or fed conditions, depending on the results from the 
food effect cohorts in Part A. Subjects will remain confined to the study site from 
Day -1 to Day 11 (ie, 3 days post last day of dosing), with outpatient follow-up 
visits, as specified in Appendix 2.  
The dose level and dosing schedule for Cohort B2 will be based on an evaluation by 
the DRC of safety data from Day 1 through Day 8 for Cohort B1 and all available 
safety data for preceding cohorts. In addition, PK data through 24 hours after dosing 
on Day 8 for Cohort B1 and available PK data for preceding cohorts will be 
reviewed. In no case would the dose escalation be greater than 3.3-fold compared 
with the previous dose. Dosing of Cohort B2 can begin at least 11 days after the 
first day dosing of subjects in Cohort B1. The maximum dose of ABI-4334 to be 
evaluated in Part B (MAD) will not exceed the exposures observed in dogs at the 
NOEL dose of 30 mg/kg/day, or 1000 mg/day, whichever is lower. 

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Study Design Schematic – Part B (MAD in Healthy Subjects) 
Screening (28-Day) 
Dosing (Days 1 through 8)
7-Day Follow-up visit (ie, Day 15)
DRC 
Review   
Randomization (Day 1)
6 active, 2 PBO
Discharge on Day 11
COHORTS B1-B2
 
Abbreviations: DRC=Data Review Committee; PBO=placebo 
Study 
Population  
Inclusion Criteria  
Subjects must meet all the following inclusion criteria in order to be eligible for the 
study: 
1. Is willing and able to provide informed consent prior to Screening. 
2. Male or female ≥ 18 and ≤ 65 years of age at Screening.  
3. Subject has a body mass index (BMI) between 18.0 and 30.0 kg/m2 
(inclusive) at Screening. 
4. Subject is in good health (as determined by the Investigator) based on 
medical history, physical examination, 12-lead electrocardiogram (ECG), 
and clinical laboratory results. Medical history and physical examination 
must be without major or clinically significant findings. 
5. Subject has serum chemistry (fasting), hematology, coagulation, and 
urinalysis values within reference range or has values outside the reference 
range, which are deemed not clinically significant deviations from the 
reference range, during the screening period (as determined by the 
Investigator). 
6. Female subjects of childbearing potential (defined in Appendix 5) must be 
nonpregnant and have a negative serum pregnancy test at Screening and 
Day -1 and a negative urine pregnancy test on Day 1, obtained prior to 
dosing.  
7. Agreement to comply with protocol-specified contraceptive requirements 
(Appendix 5). 

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8. Male subjects must agree not to donate sperm from Screening through at 
least 90 days after administration of the last dose of study drug (Appendix 
5). 
Exclusion Criteria  
Subjects who meet any of the following exclusion criteria will not be eligible for 
the study: 
1. Subject has positive results for any of the following serology tests: HBsAg, 
hepatitis B core antibody (HBcAb IgM), hepatitis C virus antibody (HCV Ab), 
or HIV-1 or -2 antibody. 
2. Females who are pregnant, lactating, or wish to become pregnant during the 
course of the study. 
3. Subject has a history of any illness that, in the opinion of the Investigator, might 
confound the results of the study, pose an additional risk in administering study 
drug to the subject, or a condition known to interfere with the absorption/ 
distribution/elimination of drugs. This may include, but is not limited to, a 
history of relevant food allergies, history of cardiovascular or central nervous 
system disease, history or presence of clinically significant pathology, or 
history of mental disease. 
4. Subject has a history of malignancy in the last 5 years, with the exception of 
nonmetastatic basal cell or squamous cell carcinoma of the skin or localized 
carcinoma of the cervix. 
5. Subject has had an illness within 5 days before receiving the first dose of study 
drug (“illness” is defined as a recent nonserious, nonacute condition such as the 
flu or the common cold). 
6. Subject has hypersensitivity or history of idiosyncratic reaction to any 
components or excipients of the study drug (ABI-4334 or PBO). 
7. Subject has a history of any significant (as determined by the Investigator) 
drug-related allergic reactions such as anaphylaxis, Stevens-Johnson syndrome, 
urticaria, or multiple drug allergies. 
8. Subject has a history of persistent alcohol abuse (alcohol consumption 
exceeding 2 standard drinks per day on average [1 standard drink=14 grams of 
alcohol]) or illicit substance/drug use within 3 years prior to Screening. 
9. Unwillingness to abstain from the use of marijuana from Screening through end 
of study.  
10. Unwillingness to abstain from alcoholic beverage consumption 48 hours prior 
to Day 1 dosing through end of study. 
11. Unwillingness to abstain from consumption of grapefruit, pomelo, or Seville 
oranges whole fruits or juices for 7 days prior to Day 1 dosing through end of 
study. 
12. Subject has a smoking habit, uses, or has used tobacco or nicotine-containing 
products (eg, including but not limited to cigarettes, e-cigarettes, pipes, cigars, 
chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 3 

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months before Day 1 dosing AND is unwilling to abstain from tobacco or 
nicotine-containing products through end of study. 
13. Unwillingness to abstain from caffeine in any form, including tea, cola, and 
caffeinated beverages consumption 48 hours prior to Day 1 dosing through end 
of study. 
14. Subject must be willing to stop herbal/dietary supplements (eg, vitamins, St. 
John’s Wort, ginkgo biloba, garlic supplements), over-the-counter (OTC) 
medications (except for paracetamol), or any prescription medication beginning 
14 days prior to the Day 1 dosing or 5 half-lives, whichever is longer, and through 
end of study. 
15. Subject has participated in a clinical study involving administration of either an 
investigational or a marketed drug within 2 months or 5 half-lives (whichever is 
longer) before Screening. 
16. Subject has donated or lost more than 1 unit of blood (500 mL) within 60 days 
prior to Screening, or plasma donation within 7 days prior to Screening, or 
plans to donate blood or plasma during the study. 
Statistical 
Considerations  
This is a FIH study. The sample size is similar to that previously utilized for this 
type of study and is not based upon statistical considerations. 
All safety and PK endpoints will be summarized using descriptive statistics by 
treatment. Continuous endpoints will be summarized using the mean, standard 
deviation, median, minimum, and maximum. Categorical endpoints will be 
described using the number and percent of subjects who meet the endpoint criterion.  
Due to sample size limitations, no formal statistical inference is planned.  
 
 

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2 INTRODUCTION 
2.1 
Chronic Hepatitis B Virus Infection 
Worldwide approximately 296 million people are chronically infected with the hepatitis B virus 
(HBV), and chronic hepatitis B virus infection (cHBV) is a major cause of severe liver morbidity 
and liver-related mortality (WHO 2021). An estimated 600,000 to 1 million people die each year 
due to cirrhosis and hepatocellular carcinoma (HCC), the end-stage complications of cHBV 
(Colvin 2010, El-Serag 2012, Lampertico 2017, Terrault 2018, WHO 2019). The global prevalence 
of cHBV shows wide geographic variation, with a prevalence of more than 8% of people in highly 
endemic regions (eg, East Asia and equatorial Africa), 2% to 7% of people in moderately endemic 
regions (eg, the Middle East and the Indian subcontinent), and less than 2% in locales of low 
endemicity (eg, North America and Europe) (Schweitzer 2015). Despite broad implementation of 
HBV vaccination programs, new cases of HBV infection are still common. The World Health 
Organization (WHO) estimates that there are greater than 4 million acute HBV infections 
worldwide each year (WHO 2021).  
The clinical stages of cHBV represent different risks for ongoing liver injury depending on the 
degree of HBV replication and individuals’ concurrent immune responses (Yim 2006, Hoofnagle 
2007, Lok 2009, Sorrell 2009, Pungpapong 2013, Gish 2015, Lampertico 2017). The standard 
virologic and serologic markers for HBV infection include HBV deoxyribonucleic acid (DNA), 
hepatitis B surface antigen (HBsAg), antibody to the hepatitis B surface antigen (HBsAb), hepatitis 
B e antigen (HBeAg), antibody to the hepatitis B e antigen (HBeAb), and in almost all patients, 
antibody to the HBV core protein (HBcAb). More recently, HBV pregenomic ribonucleic acid 
(pgRNA) and HBV core-related antigen (HBcrAg) have also been used as markers of infection. In 
particular, HBV pgRNA is recognized as a direct measure of HBV covalently closed circular DNA 
(cccDNA) transcriptional activity, and the number of infected cells (Fanning 2019). Historically, 
treatment goals include prevention of HBV-related liver injury through suppression of HBV DNA, 
achievement of HBeAg loss and seroconversion, and loss of HBsAg and seroconversion. A 
transition to an HBsAg negative, minimally replicative state is rare (occurring spontaneously in 
only 1-3% of patients per year, and < 5% per year in NrtI-treated patients) but usually durable and, 
if it precedes the development of cirrhosis and HCC, is associated with improved long-term clinical 
outcomes (Lampertico 2017). As such, HBsAg seroconversion is considered a “functional cure” 
and a potential endpoint for cHBV therapy. However, as HBsAg is derived from both HBV 
cccDNA as well as integrated HBV DNA, sustained undetectable HBV DNA with or without 
HBsAg loss after stopping treatment (“off-therapy sustained virologic response [SVR]”) is 
considered an intermediate goal (Lampertico 2017, Cornberg 2019). 
Currently, there are 2 clinically accepted, first-line treatment options for cHBV: nucleos(t)ide 
reverse transcriptase inhibitors (NrtIs) of the HBV polymerase and interferon alpha (IFNα). The 
NrtIs are orally administered, potent, direct-acting antivirals targeting the reverse transcription of 
HBV pgRNA to HBV DNA. They are broadly used, generally safe and well-tolerated and have 
demonstrated success in achieving and maintaining viral suppression in most patients (Lampertico 
2012). However, despite suppression of HBV DNA for extended periods of time with NrtIs, 

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HBeAg and HBsAg loss is uncommon and the template for ongoing viral replication, HBV 
cccDNA, is not eliminated in most patients. As a result, off therapy SVR with NrtIs are rare, 
necessitating long-term chronic suppressive treatment. In contrast, IFNα is an approved, 
subcutaneously administered protein with a finite treatment duration of 48 weeks. While the 
specific mechanism of action is not fully understood, it is thought that IFNα directly and indirectly 
targets HBV by inhibiting multiple steps in the viral lifecycle resulting in modest antiviral activity 
(Konerman 2016). In addition, IFNα augments innate immunity and triggers HBV-specific T cell 
responses. Pegylated (Peg)-IFNα is the preferred formulation due to increased pharmacokinetic 
(PK) and pharmacodynamic half-life supporting weekly dosing. Compared with NrtIs, IFNα is 
poorly tolerated due to common side effects, including flu-like symptoms, mood disturbances, and 
cytopenias. After 48 weeks of treatment, although IFNα may provide higher rates of durable HBV 
DNA suppression compared to NrtIs, rates of HBeAg and HBsAg loss remain low (Marcellin 
2016). Consequently, despite the incremental improvements in virologic response of Peg-IFNα 
monotherapy, this regimen remains suboptimal and is offset by its safety and tolerability profile. 
There is a need for improved, novel HBV therapies that further reduce HBV replication and result 
in a higher proportion of patients achieving SVR (HBV DNA < LLOQ with or without HBsAg 
loss) with a subsequent improvement in long-term patient outcomes, ie, reduction of HBV 
associated hepatic inflammation leading to reduced morbidity and mortality from end-stage liver 
disease and HCC. Additionally, such deeper virologic responses may enable patients to achieve 
durable virologic and clinical outcomes following finite treatment duration. 
2.2 
ABI-4334 
2.2.1 Description  
ABI-4334 is an orally administered, potent and selective, next-generation, small molecule inhibitor 
of HBV core protein. ABI-4334 interferes with essential functions of the HBV core protein, and 
therefore inhibits HBV replication by different mechanisms than NrtIs or IFNα. ABI-4334 binds 
to the HBV core protein, and induces altered, non-functional core protein assembly in preclinical 
models. Thus, inhibition of HBV core protein functions by ABI-4334, when used in combination 
with currently approved HBV antivirals, offers the potential to improve therapy for cHBV and 
provide patients with enhanced rates of durable off-treatment virologic responses following a finite 
treatment period. 
Refer to the Investigator’s Brochure (IB) for detailed information on ABI-4334.  
2.2.2 Nonclinical Studies  
2.2.2.1 In-vitro Activity  
In primary human hepatocytes, ABI-4334 exhibited potent antiviral activity against HBV 
replication (0.5 nM). Furthermore, ABI-4334 potently inhibited the formation of HBV cccDNA 
(2.4 nM), which is distinct from the mechanisms of action of NrtIs. ABI-4334 is pan-genotypic, 
with activity across HBV genotypes A-J. No cytotoxicity was observed with ABI-4334 across 

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multiple cell types and cell lines and the activity is specific to HBV. ABI-4334 remains fully active 
against a panel of NrtI-resistant viruses. A panel of 16 core inhibitor binding pocket variants were 
evaluated for sensitivity to ABI-4334; 1 of 16 variants exhibited > 10-fold reduced susceptibility 
to ABI-4334. Combination studies with ABI-4334 and NrtI (ie, tenofovir [TFV] or entecavir 
[ETV]) demonstrated additive effects.  
Refer to the IB for results from other nonclinical studies, including pharmacology, 
pharmacokinetics, and toxicology.  
2.2.3 Clinical Studies  
No clinical studies have been conducted with ABI-4334.  
2.3 
Study Rationale  
Chronic hepatitis B virus infection is a major cause of liver-related morbidity and mortality 
affecting approximately 296 million people worldwide. While therapy with NrtI is able to achieve 
adequate viral suppression in most HBeAg negative patients and three quarters of HBeAg positive 
patients after 1 year, SVR and loss of HBsAg are rare (< 5%). Novel agents, administered alone 
or in combination with other therapies, are likely required to provide durable off-treatment 
virologic responses.  
ABI-4334 is one such agent, which following oral administration, provides potent and selective 
inhibition of the HBV core protein. Through interference with the essential functions of the HBV 
core protein, ABI-4334 inhibits HBV replication by orthogonal mechanisms distinct from NrtIs or 
IFNα. Thus, when used in combination with currently approved or other investigational HBV 
antivirals or immune modulators, ABI-4334 offers the potential to improve therapy for cHBV and 
provide patients with enhanced rates of durable off-treatment virologic responses following a finite 
treatment period. 
Study of ABI-4334-101 is a first-in-human (FIH) study assessing the safety, tolerability, and 
pharmacokinetics (PK) of single- (Part A; SAD) and multiple-ascending doses (Part B; MAD) of 
ABI-4334 in healthy subjects. 
2.3.1 Rationale for Dose Selection  
The starting dose for the proposed Phase 1 FIH clinical study has been determined based on the 
United States (US) Food and Drug Administration (FDA) guideline on estimating the maximum 
safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers (FDA 2005) 
and the European Medicines Agency’s (EMA) guideline on strategies to identify and mitigate risks 
for first-in-human clinical trials with investigational medicinal products (EMA 2018). 
The conclusions from the 28-day repeat-dose Good Laboratory Practices (GLP) toxicology studies 
were that the no observed adverse effect level (NOAEL) in rats was 300 mg/kg/day, and the no 
observed effect level (NOEL) in dogs was 30 mg/kg/day (the highest doses tested). Defining the 
“most appropriate species” as the one that produces the lowest HED, the dog NOEL of 

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30 mg/kg/day and corresponding HED of 16.7 mg/kg, or approximately 1000 mg for a 60 kg 
human subject, have been used to calculate the starting dose for the proposed FIH clinical study. 
Using the standard safety factor of 10 discussed in the FDA guideline (FDA 2005) results in a 
maximum recommended starting dose of 100 mg. To provide an additional margin of safety, a 
starting dose of 30 mg is proposed for the initial cohort of healthy subjects in Part A of this study. 
Thus, the actual safety factor for the proposed starting dose in this study is approximately 33. The 
ratio of the HED to the proposed starting dose is shown in Table 1. 
Table 1. 
Assumed NO(A)EL Doses in Nonclinical Species and Proposed Clinical Dose 
Species NO(A)EL 
(mg/kg/day) 
ABI-4334 PK 
Parameter 
HEDb 
(mg/kg) 
HEDc 
(mg) 
MRSDd  
(mg)  
Proposed 
Starting Dose 
Safety Factor for 
Proposed Starting 
Human Dosef 
Cmaxa 
(ng/mL) 
AUC0-24a 
(ng*hour/mL) 
Rat 
300 
36,100 
424,000 
48.4 
2900 290 
NA 
NA 
Dog 
30 
15,900 
183,500 
16.7 
1000 100 
30e 
33 
Abbreviations: HED = human equivalent dose; MRSD = maximum recommended starting dose; NA = not applicable; NO(A)EL 
= no observed (adverse) effect level; PK = pharmacokinetics 
a 
Day 28 parameters, averaged for males and females  
b  
Determined according to the FDA guidance, Estimating the Safe Starting Dose in Clinical Trials for Therapeutics in Adult 
Healthy Subjects; conversion factor of 1.8 for dog and 6.2 for the rat. 
c 
Assumes 60 kg human.  
d 
Using the standard safety factor of 10. 
e 
The dog was considered the most appropriate species for calculating the starting dose in this FIH study.  
f 
Ratio of the HED to the proposed starting dose for this FIH study. 
 
The maximum dose in the study will not exceed the exposures in dogs at the NOEL dose of 
30 mg/kg/day (maximum observed plasma concentration [Cmax] of 15900 ng/mL or area under the 
concentration-time curve [AUC] of 183,500 ng*hour/mL). Although the maximum doses 
correspond to approximately 1800 mg/day based on Cmax and 2400 mg/day based on AUC using 
current human predictions, doses higher than 1000 mg/day will not be administered in this study. 
Therefore, the maximum dose of ABI-4334 to be evaluated in this study will not exceed the 
exposures observed in dogs at the NOEL dose of 30 mg/kg/day, or 1000 mg/day, whichever is 
lower. 
2.4 
Risk-Benefit Profile  
ABI-4334 is being developed for the treatment of cHBV. Since this is a FIH study of ABI-4334, 
the therapeutic potential of ABI-4334 is yet to be determined. Nonclinical data generated with 
ABI-4334 as well as clinical data from other core inhibitors in development suggest that, as 
compared to monotherapy with NrtIs, there may be several potential benefits of ABI-4334 either 
alone or in combination with NrtIs for the treatment of cHBV. These include: 
• Greater on-treatment antiviral activity in combination (more rapid suppression of HBV 
replication) compared to current NrtI alone 
• Greater inhibition of HBV cccDNA establishment and thus greater loss of HBV cccDNA 
over time as compared to current NrtI alone 
• Potential for finite therapy as compared to NrtIs which are often lifelong therapies 

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In the 28-day GLP-compliant oral repeat-dose toxicity studies, ABI-4334 was well-tolerated at 
doses up to 300 mg/kg/day in rats, and in dogs up to 30 mg/kg/day, the highest doses tested. In 
rats, there were no drug-related clinical signs or changes in body weights, food consumption, nor 
changes in clinical pathology data. Non-adverse ABI-4334-related findings were limited to the 
adrenal gland. In dogs, there were no ABI-4334-related findings at any dose tested. There were no 
drug-related clinical signs or changes in body weights, food consumption, nor changes in clinical, 
gross, or histopathology data. Therefore, following daily oral doses for 28 days, the NO(A)ELs for 
the rat and the dog are 300 mg/kg/day (AUC ≤ 455,000 ng*hour/mL) and 30 mg/kg/day (AUC 
≤ 185,000 ng*hour/mL), respectively (the highest doses tested).   
During the conduct of this study to help ensure subject safety, a data review committee (DRC) and 
the enrolling study Investigator will perform ongoing safety data reviews of the frequent clinical 
and laboratory assessments, as defined in the DRC charter.  
No therapeutic benefit is anticipated for the healthy subjects participating in this study. Any 
potential benefit is anticipated to be limited to the no-cost clinical and laboratory evaluations 
associated with the study, and the possibility that ABI-4334 could potentially benefit patients with 
cHBV in the future if additional studies establish ABI-4334 as a therapeutic advance for patients 
with cHBV. 
Overall, the risk-benefit profile of ABI-4334 is favorable.  

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3 STUDY OBJECTIVES AND ENDPOINTS  
3.1 
Study Objectives  
3.1.1 Primary Objective 
The primary objective of this study is: 
• To assess the safety and tolerability of orally administered ABI-4334 in healthy subjects 
following single (Part A, SAD) and 8-day multiple (Part B, MAD) oral doses 
3.1.2 Secondary Objectives  
The secondary objectives of this study are:  
• To characterize the PK of ABI-4334 in plasma following single doses and 8-day multiple 
doses in healthy subjects  
• To evaluate the effect of food on the PK of ABI-4334 following a single dose in healthy 
subjects (Part A food-effect cohort(s) only) 
3.1.3 Exploratory Objective 
The exploratory objective of this study is:  
• To evaluate the PK of ABI-4334 in urine following 8-day multiple doses in healthy 
subjects (Part B, MAD) 
3.2 
Study Endpoints  
3.2.1 Primary Endpoint 
The primary endpoint is: 
• Proportion of subjects with adverse events (AEs), premature treatment and study 
discontinuation due to AEs, and abnormal laboratory results (for each part) 
3.2.2 Secondary Endpoints 
The secondary endpoints are:  
• Noncompartmental plasma PK parameters such as AUClast, AUC0-inf, AUCtau, Cmax, Tmax, 
Ctrough, kel, t½, CL/F, Vz/F, dose normalized AUCs and Cmax, accumulation ratios and 
linearity factor (as applicable for each part) 
• Comparison of AUC and Cmax between fasted and fed treatments (Part A, SAD, food 
effect cohorts only)  

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3.2.3 Exploratory Endpoint 
The exploratory endpoint is:  
• Noncompartmental urine PK parameters such as Ae, Ae0-24, CLr, %Fe (Part B, MAD) 

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4 STUDY DESIGN  
4.1 
Overview  
This is a Phase 1, FIH, randomized, blinded, placebo (PBO)-controlled, single- and multiple-dose, 
dose escalation study of ABI-4334 in healthy subjects. Part A is designed to assess the safety, 
tolerability, and PK profile of ABI-4334 following SAD in healthy subjects, as well as the effect 
of food on ABI-4334. Part B is designed to assess the safety, tolerability, and PK profile of ABI-
4334 following MAD in healthy subjects. Figure 1 provides an overview of the 2-Part study design.  
Figure 1. 
Overview of Study Design – Parts A & B (SAD and MAD) 
Part A (SAD)
Single oral PO dose 
Healthy subjects
Per Cohort: 6 active, 2 PBO*  
Part B (MAD)
8-day multiple oral PO doses 
(QD or BID; fasted or fed)
Healthy subjects
Per Cohort: 6 active, 2 PBO  
• Cohort A1: 30 mg ABI-4334 or PBO, 
orally  fasted
• Cohort A2: TBD mg fasted
• Cohort A3: TBD mg fasted
• Cohort A4: TBD mg fasted
• Cohort A5: TBD mg fasted
• Cohort A6: Food effect cohort, TBD 
mg, fed
• Cohort A7: Food effect cohort, TBD 
mg (2-period crossover: fasted & fed) 
• Cohort B1: TBD mg 
• Cohort B2: TBD mg
DRC Review** 
 
Abbreviations: BID=twice daily; MAD=multiple ascending dose; PBO=placebo; PO=orally by mouth; QD=once daily; 
SAD=single ascending dose; TBD=to be determined 
*Applies to all SAD cohorts, except Cohort A7, which will only have 6 active subjects (ie, randomized to ABI-4334), no PBO 
subjects. 
**Part B dosing may commence prior to Part A being completed. 
4.1.1 Part A (SAD in Healthy Subjects) 
Part A of the study will enroll up to 5 fasted cohorts, ie, Cohorts A1-A5, and up to 2 fed cohorts 
to evaluate food effect, ie, Cohort A6 (with subjects from a previous fasted cohort), and an 
additional cohort, ie, Cohort A7, if needed (with new subjects).  
The first cohort of Part A, ie, Cohort A1, will evaluate a single dose of 30 mg ABI-4334 (Figure 
2). Dose levels for subsequent cohorts will be determined based on interim cohort review 
performed by an unblinded DRC (see Section 10.6 for details on DRC procedures) between SAD 
cohorts for purposes of dose escalation. Study data will include safety data from Day 1 through 
Day 4 for the present cohort and all available safety data for preceding cohorts. In addition, PK 

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data through 24 hours after dosing for the present cohort and available PK data for preceding 
cohorts will be reviewed. In no case would a dose escalation be greater than 3.3-fold compared 
with the previous dose. The maximum dose of ABI-4334 to be evaluated in Part A (SAD) will not 
exceed the exposures observed in dogs at the NOEL dose of 30 mg/kg/day, or 1000 mg/day, 
whichever is lower.  
Figure 2. 
Study Design Schematic – Part A (SAD in Healthy Subjects) 
Screening 
(28-Day) 
Randomization
6 active; 2 PBO
 (Day 1)
Sentinel Dosing 
(N=2)
Observe for 3 days 
Dosing of Remaining Subjects 
(N=6) 
7-day follow-up visits 
(ie, Day 5-Day 7)
DRC Review 
COHORTS A1-A5
FOOD EFFECT COHORTS A6-A7
DRC Review for selection 
of a subsequent SAD dose 
or food effect cohort 
Cohort A6 
(N=8)
DRC 
Review
Cohort A7 
(N=6) 
DRC Review 
7-day washout
Discharge on 
Day 4
or
Screening 
(28-Day) 
Randomization
6 active 
 (Day 1)
 
Abbreviations: DRC=Data Review Committee; PBO=placebo; SAD=single ascending dose 
Each of the Cohorts A1-A5 will enroll 8 healthy subjects who will be randomized in a 6:2 ratio to 
receive a single oral dose of the study drug, ie, ABI-4334 (6 subjects) or PBO (2 subjects) in a 
fasted state, followed by a 7-day follow-up period. Subjects will remain confined to the study clinic 
from Days -1 to 4, with outpatient follow-up visits, as specified in Appendix 1. Dosing of a 
subsequent SAD cohort can begin at least 8 days after dosing of the sentinel subjects from the 
previous cohort (see below).  
Because this is a FIH study, a sentinel dosing approach will be utilized for each Cohort A1-A5, 
where initially only 2 subjects per cohort will be dosed (one receiving ABI-4334 and one receiving 
PBO). These sentinel subjects will be observed for a minimum of 3 days postdose to ensure 
acceptable tolerability of the study drug, as determined by the DRC, before dosing of the remaining 
subjects within the cohort can proceed.  
The DRC will select a single dose level from Cohorts A1-A5 for evaluation of food effect. The 
selection of this dose level can be made prior to completion of all fasted SAD cohorts and will be 
based on a preliminary evaluation by the DRC of the available safety, tolerability, and PK data 
from selected Cohorts A1-A5. Subjects who complete participation in this selected cohort will be 
asked to return to the study site to be enrolled into the food-effect cohort (ie, Cohort A6), following 
a minimum of 7-day washout period since their last study drug dose. While Baseline evaluations 
will be conducted prior to dosing in Cohort A6, repeat assessment of all study eligibility criteria 
will not be performed. Returning subjects will retain their original subject number and randomized 
treatment assignment. After the Day 7 visit in the original cohort (from Cohort A1-A5), the study 

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drug will be administered 30 minutes after the complete consumption of a high fat meal 
(approximately 50% calories from fat). 
If there is an insufficient number of subjects from previous fasted SAD cohorts (ie, A1-A5), who 
are willing to participate in Cohort A6, then a separate Cohort A7 may be enrolled, comprising 6 
new subjects meeting the study eligibility criteria, who will all receive ABI-4334. Cohort A7 will 
involve a two-period crossover assessment of food effect (ie, Period 1: dosing under fasted or high 
fat-fed conditions; Period 2: dosing under condition opposite of Period 1), with a minimum 7-day 
washout period between dosing in Period 1 and Period 2, and a 7-day postdose follow-up in Period 
2.  
Details on PK sampling for Part A (SAD) are provided in Section 8.4 and Appendix 1. 
4.1.2 Part B (MAD in Healthy Subjects) 
Part B dosing may commence prior to Part A being completed. The dose level and dosing schedule 
for the first cohort of Part B, ie, Cohort B1, will be determined based on emergent safety, 
tolerability, and PK data from completed Part A cohorts, with the daily dose at least 2-fold lower 
than a Part A dose level deemed safe and tolerable.  
Both cohorts planned for Part B, ie, Cohort B1 and Cohort B2, will enroll 8 healthy subjects who 
will be randomized in a 6:2 ratio to receive oral daily doses of the study drug, ie, ABI-4334 (6 
subjects) or PBO (2 subjects), for 8 consecutive days, followed by a 7-day follow-up period (Figure 
3). Dosing may occur under fasted or fed conditions, depending on the results from the food-effect 
cohorts in Part A. Subjects will remain confined to the study site from Days -1 to Day 11 (ie, 3 
days post last day of dosing), with outpatient follow-up visits, as specified in Appendix 2.  
The dose level and dosing schedule for Cohort B2 will be based on an evaluation by the DRC of 
safety data from Day 1 through Day 8 for Cohort B1 and all available safety data for preceding 
cohorts. In addition, PK data through 24 hours after dosing on Day 8 for Cohort B1 and available 
PK data for preceding cohorts will be reviewed. In no case would the dose escalation be greater 
than 3.3-fold compared with the previous dose. Dosing of Cohort B2 can begin at least 11 days 
after the first day dosing of subjects in Cohort B1. The maximum dose of ABI-4334 to be evaluated 
in Part B (MAD) will not exceed the exposures observed in dogs at the NOEL dose of 
30 mg/kg/day, or 1000 mg/day, whichever is lower. 
Details on PK sampling for Part B (MAD) are provided in Section 8.4 and Appendix 2. 

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Figure 3. 
Study Design Schematic – Part B (MAD in Healthy Subjects) 
Screening (28-Day) 
Dosing (Days 1 through 8)
7-Day Follow-up visit (ie, Day 15)
DRC 
Review   
Randomization (Day 1)
6 active, 2 PBO
Discharge on Day 11
COHORTS B1-B2
 
Abbreviations: DRC=Data Review Committee; PBO=placebo  
4.2 
Study Treatments 
As previously described, the starting dose of 30 mg for SAD Cohort A1 is based on nonclinical 
safety findings and regulatory guidelines for selection of starting doses for FIH studies (see Section 
2.3.1). For all subsequent parts of the study described below, the decision to enroll a cohort and its 
dose level and once daily (QD) or twice daily (BID) dosing schedule will be based on the 
assessment of available data, and some prespecified cohorts may not be enrolled.  
4.2.1 Part A (SAD in Healthy Subjects) 
• Cohort A1: 30 mg ABI-4334 or PBO, orally (PO), single dose, fasted 
• Cohort A2: to be determined (TBD) mg ABI-4334 or PBO, PO, single dose, fasted  
• Cohort A3: TBD mg ABI-4334 or PBO, PO, single dose, fasted 
• Cohort A4: TBD mg ABI-4334 or PBO, PO, single dose, fasted 
• Cohort A5: TBD mg ABI-4334 or PBO, PO, single dose, fasted 
• Cohort A6: Food effect cohort with subjects from a previous fasted cohort, TBD mg 
ABI-4334 or PBO, PO, single dose, fed 
• Cohort A7: Additional food effect cohort (if needed), TBD mg ABI-4334, PO, single 
dose, 2-period crossover (fasted & fed) 
4.2.2 Part B (MAD in Healthy Subjects: 8-Day Dosing Duration) 
• Cohort B1: TBD mg ABI-4334 or PBO, PO, multiple doses 

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• Cohort B2: TBD mg ABI-4334 or PBO, PO, multiple doses  
For detailed information regarding dosing and administration, refer to Section 6.1.1.4. 
4.3 
Duration of Treatment  
The duration of treatment for each part of the study is provided below:  
• Part A (SAD): 1 day 
• Part B (MAD): 8 days  
4.4 
Duration of Study  
• Part A (SAD): Up to 36 days per cohort, including 28 days of screening, 1 day of 
treatment, 7 days of follow up. The duration of the study will be longer for subjects in the 
food effect cohort(s).  
• Part B (MAD): Up to 43 days, including 28 days of screening, 8 days of treatment, and 7 
days of follow up. 
4.5 
End of Study Definition  
For each subject, EOS is defined as completion of the last visit in the follow-up period or premature 
study termination, or subject is lost-to-follow-up.  
The study will end when the last subject completes the last visit of the follow-up period or is 
considered “lost to follow-up,” whichever is later.  

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5 STUDY POPULATION  
5.1 
Number of Subjects  
• Part A: Up to 46 (approximately 8 subjects/Cohorts A1-A6; 6 subjects/Cohort A7 [Note: 
Cohort A6 will enroll returning subjects from a previous SAD cohort]) 
• Part B: Up to 16 (approximately 8 subjects/cohort) 
5.2 
Inclusion Criteria  
Subjects must meet all of the following inclusion criteria in order to be eligible for the study:  
1. Is willing and able to provide informed consent prior to Screening. 
2. Male or female ≥ 18 and ≤ 65 years of age at Screening.  
3. Subject has a body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive) at Screening. 
4. Subject is in good health (as determined by the Investigator) based on medical history, 
physical examination, 12-lead electrocardiogram (ECG), and clinical laboratory results. 
Medical history and physical examination must be without major or clinically significant 
findings. 
5. Subject has serum chemistry (fasting), hematology, coagulation, and urinalysis values within 
reference range or has values outside the reference range, which are deemed not clinically 
significant deviations from the reference range, during the screening period (as determined 
by the Investigator). 
6. Female subjects of childbearing potential (defined in Appendix 5) must be nonpregnant and 
have a negative serum pregnancy test at Screening and Day-1 and a negative urine pregnancy 
test on Day 1, obtained prior to dosing.  
7. Agreement to comply with protocol-specified contraceptive requirements (Appendix 5). 
8. Male subjects must agree not to donate sperm from Screening through at least 90 days after 
administration of the last dose of study drug (Appendix 5). 
5.3 
Exclusion Criteria  
Subjects who meet any of the following exclusion criteria will not be eligible for the study:  
1. Subject has positive results for any of the following serology tests: HBsAg, hepatitis B core 
antibody (HBcAb IgM), hepatitis C virus antibody (HCV Ab), or HIV-1 or -2 antibody. 
2. Females who are pregnant, lactating, or wish to become pregnant during the course of the 
study. 
3. Subject has a history of any illness that, in the opinion of the Investigator, might confound 
the results of the study, pose an additional risk in administering study drug to the subject, or a 
condition known to interfere with the absorption/distribution/elimination of drugs. This may 
include, but is not limited to, a history of relevant food allergies, history of cardiovascular or 

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central nervous system disease, history or presence of clinically significant pathology, or 
history of mental disease. 
4. Subject has a history of malignancy in the last 5 years, with the exception of nonmetastatic 
basal cell or squamous cell carcinoma of the skin or localized carcinoma of the cervix. 
5. Subject has had an illness within 5 days before receiving the first dose of study drug 
(“illness” is defined as a recent nonserious, nonacute condition such as the flu or the common 
cold). 
6. Subject has hypersensitivity or history of idiosyncratic reaction to any components or 
excipients of the study drug (ABI-4334 or PBO). 
7. Subject has a history of any significant (as determined by the Investigator) drug-related 
allergic reactions such as anaphylaxis, Stevens-Johnson syndrome, urticaria, or multiple drug 
allergies. 
8. Subject has a history of persistent alcohol abuse (alcohol consumption exceeding 2 standard 
drinks per day on average [1 standard drink=14 grams of alcohol]) or illicit substance/drug 
use within 3 years prior to Screening. 
9. Unwillingness to abstain from the use of marijuana from Screening through end of study.  
10. Unwillingness to abstain from alcoholic beverage consumption 48 hours prior to Day 1 
dosing through end of study. 
11. Unwillingness to abstain from consumption of grapefruit, pomelo, or Seville oranges whole 
fruits or juices for 7 days prior to Day 1 dosing through end of study. 
12. Subject has a smoking habit, uses, or has used tobacco or nicotine-containing products (eg, 
including but not limited to cigarettes, e-cigarettes, pipes, cigars, chewing tobacco, nicotine 
patches, nicotine lozenges, or nicotine gum) within 3 months before Day 1 dosing AND is 
unwilling to abstain from tobacco or nicotine-containing products through end of study. 
13. Unwillingness to abstain from caffeine in any form, including tea, cola, and caffeinated 
beverages consumption 48 hours prior to Day 1 dosing through end of study. 
14. Subject must be willing to stop herbal/dietary supplements (eg, vitamins, St. John’s Wort, 
ginkgo biloba, garlic supplements), over-the-counter (OTC) medications (except for 
paracetamol), or any prescription medication beginning 14 days prior to the Day 1 dosing or 5 
half-lives, whichever is longer, and through end of study. 
15. Subject has participated in a clinical study involving administration of either an 
investigational or a marketed drug within 2 months or 5 half-lives (whichever is longer) 
before Screening. 
16. Subject has donated or lost more than 1 unit of blood (500 mL) within 60 days prior to 
Screening, or plasma donation within 7 days prior to Screening, or plans to donate blood or 
plasma during the study. 
5.4 
Screen Failures  
Screen failures are defined as subjects who sign the Informed Consent Form (ICF), are assigned a 
subject number, complete screening procedures but are not subsequently randomized to study 

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treatment. Minimal information to be retained on all screen failures includes demography, screen 
failure details, eligibility criteria, and any SAE information. 
Individuals who do not meet the protocol eligibility criteria for participation in this study (screen 
failure) may be allowed to rescreen (once). Rescreening may occur following resolution of acute 
exclusionary conditions or stabilization of conditions that were exclusionary and reversible (eg, 
unstable hypothyroidism, electrolyte abnormalities) and with the approval of the study Medical 
Monitor. 
A single retest for a laboratory parameter(s) is permitted if there is a specific issue related to the 
collection, shipping, processing or analysis of a sample (eg, receipt of a hemolyzed sample at the 
testing laboratory, or samples received by the testing laboratory outside of the acceptable time 
window or temperature range) or related to a resolved condition.  
If more than 28 days are required to obtain a result of a screening procedure and/or test conducted 
within the permitted window, the screening period may be extended until results are obtained. 
However, the clinical safety laboratory tests may need to be repeated under the instruction of the 
study Medical Monitor if the screening period is beyond 28 days.  
5.5 
Dietary and Lifestyle Restrictions  
Subjects will be required to comply with the following restrictions during study participation: 
• Subjects will not engage in strenuous exercise beyond their accustomed daily level of 
activity from Day 1 dosing through end of study. 
• Subjects are prohibited from illicit substance/drug use and the use of marijuana before 
dosing on Day 1 through end of study.  
• Subjects are prohibited from consuming any amount of alcohol 48 hours before dosing on 
Day 1 through end of study. 
• Subjects are prohibited from nicotine consumption from Screening through end of study. 
• Subjects are prohibited from consuming caffeine in any form, including tea, cola, and 
caffeinated beverages 48 hours before dosing on Day 1 through end of study. 
• Subjects are prohibited from consuming grapefruit, pomelo, or Seville orange whole fruits 
or juice for 7 days before dosing on Day 1 through end of study. 
• Subjects will be advised to take measures to minimize exposure to ultraviolet light from 
Day 1 through 7 days after the last dose of study drug, as an initial assessment for the 
potential for phototoxicity has not yet been conducted. 

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• Subjects who are women of childbearing potential should not plan to become pregnant 
during the study and all subjects should adhere to the contraception guidelines specified in 
Appendix 5.  
• Subjects must be fasting for at least 8 hours before chemistry assessments (Note fasting 
requirements for assessment of PK are provided in Sections 6.1.1.4.1 and 6.1.1.4.2). 
5.6 
Meals  
To reduce the potential impact of meal composition on safety and PK parameters, it is 
recommended standardized meals be provided while subjects are confined to the clinical study 
site: Part A (SAD) Day -1 to Day 4; Part B (MAD) Day -1 to Day 11 (ie, 3 days post last day of 
dosing). The meals will be consistent in calorie count and nutritional content (eg, similar amounts 
of protein, carbohydrate, and fat) and will be scheduled around required fasting/fed periods for 
study dosing and procedures. The meal timing and consumption will be documented in the source 
document. Other than the 240 mL of water administered with dosing, water and other fluids will 
be restricted from 1 hour before dosing to 1 hour after dosing. All food and beverages will be 
provided by the study site and no additional food, snacks, sweets, drinks, or any similar items will 
be allowed during the clinic visits. 
5.6.1 Test Meal for Subjects in the Food Effect Cohorts  
Subjects in the food effect Cohort A6 (and additional Cohort A7 if needed) in Part A (SAD) will 
consume a high-fat, high-calorie test meal, containing approximately 800 to 1000 calories, 30 
minutes prior to dosing on Day 1. Subjects will be instructed to consume the entire test meal within 
30 minutes. This test meal will derive approximately 150, 250, and 500 to 600 calories from 
protein, carbohydrate, and fat, respectively. Approximately 50 percent of total caloric content will 
be fat. An example high-fat, high-calorie test meal would be two eggs fried in butter, two strips of 
bacon, two slices of toast with butter, four ounces of hash brown potatoes, and eight ounces of 
whole milk (FDA 2019). Substitutions to this test meal can be made if the substituted test meal 
provides a similar number of calories from protein, carbohydrate, and fat and has comparable 
volume and viscosity.  

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6 STUDY DRUGS  
6.1 
Investigational Medicinal Product(s) (IMPs) 
The investigational medicinal products (IMPs) to be used in this study are ABI-4334 and PBO. 
6.1.1 ABI-4334 
6.1.1.1 Formulation  
The drug product is a tablet containing approximately 10 mg or 50 mg of ABI-4334 and standard 
pharmaceutical excipients, such as microcrystalline cellulose, lactose, croscarmellose sodium, 
sodium lauryl sulfate, hypromellose, and magnesium stearate that are compressed into a tablet 
according to Good Manufacturing Practices (GMP). 
Matching placebo tablets contain standard compendial excipients and are manufactured in 
conformance with GMP. Matching placebo tablets have the same appearance as the ABI-4334 
active tablets. 
6.1.1.2 Packaging and Labeling  
The study drugs are packaged in high-density polyethylene (HDPE) bottles, induction sealed with 
child-resistant screw caps. Study drug will be labelled in accordance with the US FDA 
requirements and the European Union (EU) GMP Annex 13, Investigational Medicinal Products. 
Additional local labelling requirements in countries of study conduct will be incorporated in the 
study drug label(s).  
6.1.1.3 Storage and Handling  
Bottled study drug tablets at the study site should be stored at controlled room temperature (15 °C 
to 30 °C [59 °F to 86 °F]) in a secure, locked location at the sites, accessible only to authorized 
study personnel. 
6.1.1.4 Dosage and Administration  
Study drug doses will be administered with 240 mL of water in the clinic under supervision. 
Subjects will remain in an upright or sitting position for at least 30 minutes after ingestion unless 
a semi-recumbent or recumbent position is required for ECGs or vital signs. Water, other than for 
drug administration, will be restricted for 1 hour before and 1 hour after each oral dose. After study 
drug administration, site personnel will perform a hand and mouth check to verify that the 
administered dose was swallowed.  
If the PK results for Part A Cohorts A1-A5 indicate that BID dosing should be assessed, then 
subjects in one or both of the Part B Cohorts ie, B1-B2, may receive their study drug as two divided 
doses, separated by approximately 12 hours on the dosing days.  
Fasting requirements for dosing are described below. 

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6.1.1.4.1 Fasting Requirements  
The fasting requirements for all subjects in Part A (SAD) Cohorts A1-A5, for subjects in Cohort 
A7 during the fasting period, and for subjects in Part B (MAD) Cohorts B1 and B2 are described 
in this section.  
On Day 1 for Part A and Days 1 and 8 for Part B, study drug doses will be administered in the 
morning after an overnight fast of at least 10 hours. Subjects will continue fasting for 4 hours after 
dosing, and will receive standardized lunch, dinner, and an evening snack at approximately 4 
hours, 10 hours, and 12 hours after dosing, respectively. On Days 2 to 7 for Part B, study drug will 
be administered in the morning after an overnight fast of at least 10 hours. Subjects will continue 
fasting for 1 hour after dosing, and will receive standardized snack, lunch, dinner, and an evening 
snack at approximately 1 hour, 4 hours, 10 hours, and 12 hours after dosing, respectively. Subjects 
will have approximately 30 minutes to consume the meals.  
On all other days (Days 2 to 4 for Part A and Days 9 (ie, 1 day post last day of dosing) to Day 11 
(ie, 3 days post last day of dosing) for Part B, subjects will receive a standardized breakfast at 
approximately the same time as dosing time on dosing days, and lunch, dinner, and an evening 
snack approximately 4 hours, 10 hours, and 12 hours later. Subjects will have approximately 30 
minutes to consume the meals. Meals on Day 4 Part A and Day 11 (ie, 3 days post last day of 
dosing) Part B are optional due to discharge from the clinic.  
If a BID dosing schedule is indicated, the requirements will be the same for the morning doses. 
Evening doses should be taken on an empty stomach, at least 2 hours after a meal and 1 hour before 
the next meal. 
If it is determined subjects in Part B should take their study drug doses in a fed status, all morning 
doses will be administered 30 minutes after start of a standardized breakfast. Subjects will receive 
standardized lunch, dinner, and an evening snack at approximately 4 hours, 10 hours, and 12 hours 
after dosing, respectively. Subjects will have approximately 30 minutes to consume the meals. If 
a BID dosing schedule is indicated, the requirements will be the same for the morning doses. 
Evening doses should be taken 30 minutes after start of a meal. 
6.1.1.4.2 Fasting Requirements for Part A (SAD) Food Effect Cohorts  
The fasting requirements for subjects in Part A (SAD) Cohort A6 and the fed period of Cohort A7 
are provided in this section.  
On Day 1, subjects in the food effect Cohort A6 (and the fed period for the Cohort A7), will fast 
for at least 10 hours until 30 minutes before dosing when they will receive a high-fat, high-calorie 
test meal and will continue fasting for 4 hours after dosing. Subjects will receive standardized 
lunch, dinner, and an evening snack at approximately 4 hours, 10 hours, and 12 hours after dosing, 
respectively. Subjects will have approximately 30 minutes to consume the meals. 
 
On all other days (Days 2 to 4), subjects will receive a standardized breakfast at approximately the 
same time as dosing time on dosing days, and lunch, dinner, and an evening snack approximately 

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4 hours, 10 hours, and 12 hours later. Subjects will have approximately 30 minutes to consume the 
meals. Meals on Day 4 are optional due to discharge from the clinic. 
6.1.2 Accountability of IMP  
Regulatory requirements stipulate accounting of all IMPs received by the study site. Records of 
drug disposition must include the date received by the site, date administered, quantity 
administered, and the subject to whom IMP was administered. The Investigator is responsible for 
the accountability of all IMPs at their site. The study site is to use an IMP accountability record to 
document study drug disposition. All items on this form are to be fully completed. The Sponsor or 
the clinical research organization (CRO) will confirm if the method of recording study drug 
accountability by the site and the location of IMP records at the site is appropriate. 
Each time designated site personnel dispense IMP for a subject, he or she is to record the date 
dispensed, the quantity of study drug dispensed, and his or her initials. Study site personnel are to 
monitor the inventory of study drug and maintain a count of all used and unused study drug. The 
site monitor will review the study drug accountability records during monitoring visits. The site 
pharmacist or designated staff member will keep accurate records of drug dispensation routinely 
during the study.  
6.1.2.1 Return or Disposal of IMP  
Procedures for the return of IMP or provisions for onsite destruction (where approved 
prospectively by Assembly or designee) are described separately in the Pharmacy Manual. 
6.2 
Non-Investigational Medicinal Products(s)  
Not applicable.  
6.3 
Concomitant Medications and Procedures   
A concomitant medication is defined as any prescription or OTC preparation, including vitamins, 
medications, vaccinations, herbal preparations, and supplements (including traditional Chinese 
medicine) that is taken by a subject during the conduct of the clinical trial.  
All concomitant medications taken during the study from the date the ICF is signed through the 
end of study participation (Section 4.4) (ie, completion of the follow-up period or the subject is 
“lost to follow-up”) must be recorded in the subject’s source documentation. This information 
should include the name of the medication, the start and stop dates, the dosage, route of 
administration, and the indication for which the concomitant medication was administered. 
Medications taken for a procedure will also be included. Concomitant medications will be coded 
using the World Health Organization Drug Reference List.  
Elective procedures should not be performed during the study.  

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6.3.1 Prohibited Concomitant Therapy  
As the potential for drug-drug interactions between ABI-4334 and other compounds has not yet 
been fully evaluated, all concomitant medications (defined in Section 6.3) being taken at the time 
of Screening, except for paracetamol (also known as acetaminophen), should be washed out 
beginning 14 days or 5 half-lives whichever is longer prior to Day 1 dosing. Paracetamol (up to 4 
g/day) and topical agents are allowed, as needed (PRN) during the course of the study at the 
Investigator’s discretion. All other concomitant medications are prohibited through end of study.  
6.4 
Randomization, Blinding, and Treatment Codes  
6.4.1 Randomization  
All subjects will be assigned a unique subject number at Screening and will be randomized upon 
meeting all protocol eligibility requirements. Randomization will be performed by an unblinded 
pharmacist. 
6.4.2 Blinding  
All study team members (including Sponsor team members, Investigator, site personnel 
administering the study drug, performing the clinical assessments, and handling data on the study 
subjects), except the members of the DRC (specified in the DRC charter), will be blinded to 
individual subject treatment assignments throughout the duration of the study. The study subjects 
will also be blinded to their treatment assignment throughout the duration of the study.  
The DRC will be unblinded to individual subjects’ treatment assignments throughout the study to 
ensure timely analysis of any emergent safety and tolerability issues, and completion of the 
prespecified safety and PK data reviews. The unblinded individuals will be identified in the DRC 
charter along with their specific roles and responsibilities. All other Sponsor personnel will remain 
blinded until completion of the study. The CRO’s Medical Monitor may be unblinded to individual 
subjects’ treatment assignments where required for assessment of emergent safety/tolerability 
issues. 
6.4.2.1 Unblinding in Emergency Situations  
During the study, the randomization code must not be broken except in emergency situations where 
the identification of a subject’s study treatment is required by the Investigator for further treatment 
to the subject. Randomization information will be held by designated individual(s). When possible, 
the Investigator should discuss the emergency with the Sponsor prior to unblinding. The date and 
reason for breaking the blind must be recorded. 
The unblinded pharmacist will be used to unblind a subject’s assigned treatment. In the event that 
an individual subject’s treatment assignment is unblinded, the date and reason that the blind was 
broken must be recorded in the source documentation, as applicable. Any treatment assignments 
that are unblinded must be immediately reported to the Sponsor and Medical Monitor. 

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7 DISCONTINUATION OF STUDY TREATMENT OR STUDY  
7.1 
Discontinuation of Study Treatment for A Subject  
The Investigator (upon consultation with the Sponsor, if possible) may discontinue subject 
treatment with study drug if any of the treatment discontinuation criteria listed in Section 7.1.1 are 
met. Discontinuation from treatment does not mean discontinuation from the study.  
Any subject in Part B who prematurely discontinues their assigned treatment regimen, will enter a 
7-day follow-up period, during which the subject will undergo the assessments listed under the 
follow-up visits specified in Appendix 2.   
7.1.1 Criteria for Discontinuation of Study Treatment for a Subject  
Study drug treatment may be discontinued in the following instances:  
• Unacceptable tolerance of study drug treatment due to AE, in the judgement of the 
Investigator 
• Intercurrent illness that would, in the judgement of the Investigator, affect assessments of 
clinical status to a significant degree 
• Unacceptable toxicity as defined in Section 9.10 (Toxicity Management), or toxicity that, 
in the judgment of the Investigator, compromises the ability to continue study-specific 
procedures or is considered to not be in the subject’s best interest 
• Subject noncompliance 
• Pregnancy during the study  
• Discontinuation of the study at the request of the Sponsor, a regulatory agency or an 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) 
7.1.2 Subject Discontinuation or Withdrawal from the Study  
A subject may withdraw from the study at any time at his/her own request. The subject may also 
be withdrawn from the study at any time at the discretion of the Investigator or Sponsor for safety, 
behavioral, compliance, or administrative reasons. At the time of discontinuing from the study, if 
possible, a Premature Study Termination visit should be conducted, as soon as feasibly possible 
(Section 8.6; Appendix 3). If the subject withdraws consent for disclosure of future information, 
the Sponsor may retain and continue to use any data collected before withdrawal of consent. If a 
subject withdraws from the study, they may request destruction of any samples in storage, and the 
Investigator must document this in the site study record and inform the Sponsor.  

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Subjects withdrawn due to a study drug-related AE will not be replaced. Subjects who are 
withdrawn for other reasons may be replaced as required by agreement between the Investigator 
and Sponsor to ensure a sufficient number of subjects for each cohort. 
7.1.3 Subject Lost to Follow-Up   
The following actions must be taken if a subject fails to return to the clinic for a required study 
visit: 
• The site must attempt to contact the subject, reschedule the missed visit as soon as possible, 
and counsel the subject on the importance of maintaining the assigned visit schedule and 
ascertain whether or not the subject wishes to and/or should continue in the study 
• Before a subject is deemed lost to follow-up, the Investigator or designee must make every 
effort to regain contact with the subject (where possible, 3 telephone calls and, if necessary, 
a certified letter to the subject’s last known mailing address or local equivalent methods). 
These contact attempts should be documented in the subject’s medical record 
Should the subject continue to be unreachable, they will be considered lost to follow-up. 
7.2 
Criteria for Discontinuation of Study Treatment for a Cohort  
Study enrollment and drug administration in the current cohort will be stopped pending a full safety 
review for any the following: 
• Any SAE considered as at least possibly related to study drug by the Investigator and/or 
the Sponsor’s Medical Monitor 
• Any Grade 4 AE considered as at least possibly related to the study drug by the Investigator 
and/or the Sponsor’s Medical Monitor 
• Two Grade 3 AEs that are similar in nature and considered as at least possibly related to 
the study drug by the Investigator and/or the Sponsor’s Medical Monitor 
• A pattern of significant symptoms, physical findings, or confirmed laboratory 
abnormalities (AEs) that, although individually minor, collectively represent a safety 
concern in the opinion of the Investigator and/or the Sponsor’s Medical Monitor and are 
judged to be at least possibly related to study drug 
If any of the above predefined criteria are met, the Sponsor will rapidly inform the study sites that 
the study drug should not be administered to additional subjects at the same or higher doses until 
the safety concern is reviewed and considered resolved by the DRC and the Investigator. A cohort 
with lower dose might be considered subsequently to continue to explore the study objectives. 
If the study is stopped or suspended for reasons of safety, the Sponsor will notify the relevant 
regulatory agencies.  

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7.3 
Discontinuation of the Study   
The Sponsor or designee reserves the right to terminate the study at any time for any reason at the 
sole discretion of the Sponsor. If the study is prematurely terminated or suspended, the Sponsor 
shall promptly inform the Investigator, the IECs/IRBs, the regulatory authorities, and any CROs 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The Investigator shall promptly inform the study subjects and should 
ensure appropriate follow-up. 

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8 STUDY PROCEDURES AND ASSESSMENTS  
8.1 
Schedule of Assessments  
All procedures and assessments of this study and associated timepoints are outlined in the Schedule 
of Assessments for scheduled visits in Appendix 1 for Part A, Appendix 2 for Part B, and for all 
other visits in Appendix 3.  
8.2 
Study Visit Procedures  
8.2.1 Screening Assessments  
Subjects who agree to participate will sign the ICF prior to undergoing any other Screening 
procedure. The Screening period begins once the ICF has been signed. The ICFs for enrolled 
subjects and for subjects who are screened but not enrolled will be maintained at the study site.  
Screening evaluations must be completed and reviewed to confirm that a subject meets all 
eligibility criteria before randomization. Refer to Section 5.4 for instructions regarding screen 
failure.  
The Investigator will maintain a Screening log to record details of all subjects screened and to 
confirm eligibility or record reasons for screen failure, as applicable. 
8.2.2 Subject Enrollment and Treatment Assignment  
The Investigator will assess and confirm the eligibility of each subject. All Screening procedure 
results, and relevant medical history must be available before eligibility can be determined. All 
inclusion criteria must be met and none of the exclusion criteria may apply. No eligibility waivers 
will be granted. 
Following provision of informed consent and completion of all Screening and Day 1 predose 
assessments, if a subject meets all protocol eligibility requirements the Investigator or designee 
will randomize the subject as described in Section 6.4.1. 
8.3 
Assessment of Safety  
8.3.1 Physical Examination  
A complete or symptom-directed physical examination will be performed at timepoints indicated 
in Appendix 1, Appendix 2, and Appendix 3. Height and weight will also be recorded.  
The complete physical examination will consist of the following body systems: head, eyes, ears, 
nose, and throat; cardiovascular; respiratory; gastrointestinal; dermatologic; musculoskeletal; 
nervous; extremities; and lymph nodes. Additional body systems may be evaluated at the 
Investigator’s discretion. Examination of the breast and genitalia are not required unless clinically 
indicated. 

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Additional symptom-directed or complete physical examinations may be performed at the 
Investigator’s discretion throughout the course of the study. If the subject reports feeling unwell 
or has ongoing AEs, the Investigator or qualified subinvestigator will examine the appropriate 
body system(s). 
8.3.2 Vital Signs  
Vital sign assessments will include temperature, heart rate, respiration rate, and blood pressure at 
timepoints specified in Appendix 1, Appendix 2, and Appendix 3.  
8.3.3 Electrocardiograms  
A standard 12-lead ECG will be obtained as indicated in Appendix 1, Appendix 2, and Appendix 
3. The ECGs will be measured in triplicates at 3 minutes apart only at Screening. Single ECGs 
will be collected thereafter, unless required by the Investigator.  
Prior to the conduct of 12-lead ECGs, subjects should rest in a supine position for 10 minutes. 
Electrocardiograms should be conducted in accordance with local practice and equipment. The 
ECG assessment will include interpretation of the tracings (eg, rhythm, presence of arrhythmia or 
conduction defects, morphology, any evidence of myocardial infarction, or ST segment, T-wave, 
and Uwave abnormalities). The Investigator or a physician subinvestigator is responsible for 
reviewing and overreading the ECG interpretation, for assessing whether the ECG machine 
interpretation findings are accurate, appropriate, normal or abnormal, and for providing corrected 
interpretations as appropriate. In addition, any abnormal ECGs will be assessed for clinical 
significance. 
Additional ECGs may be obtained if clinically indicated and will be obtained if abnormal and 
clinically significant or thought to be an error (eg, lead placement error, movement artifact, etc). 
Any additional relevant data obtained by the Investigator during the course of this study will be 
recorded in the subject’s source documentation. The Investigator or a physician subinvestigator 
will review all ECGs, evaluate the results, and sign/date the tracing or report. For any ECG 
abnormality that the Investigator considers clinically significant, the Investigator will:  
• Repeat the ECG 
• Obtain follow-up ECG(s) if any significant abnormalities are detected after study drug 
administration to document resolution and as clinically indicated 
• Record as an AE any ECG abnormality that: (1) is confirmed and the Investigator considers 
clinically significant; or (2) requires a subject to be discontinued from the study; or (3) the 
abnormality requires a subject to receive treatment 

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8.3.4 Holter Data Collection  
Holter data collection will be performed at the timepoints indicated in Appendix 1 and Appendix 
2 and will be performed on Day 1 for Part A (except for the food effect Cohorts A6 and A7) and 
on Days 1 and 8 for Part B. The ECG extraction will be performed by the central ECG laboratory 
with replicate (minimum of 3) recordings extracted according to the central laboratory’s standard 
practice. At the timepoints for ECG extraction, subjects will be in the supine or semirecumbent 
position for at least 10 minutes prior to and 5 minutes after. Note: Subjects must be in the upright 
position for dosing and then return to the supine or semirecumbent position for ECG monitoring. 
Holter data will be collected and downloaded by the clinical site and subsequently transferred to 
the Sponsor and stored for possible future analysis. 
8.3.5 Clinical Laboratory Assessments  
Clinical laboratory tests will be performed at the designated central laboratories at the timepoints 
indicated in Appendix 1, Appendix 2, and Appendix 3. Should any laboratory parameter require 
urgent testing to support eligibility determination or immediate medical care of a subject, samples 
can be collected for local laboratory testing. However, only the results from the central laboratories 
will be reported in the study database for analysis purposes. 
The specific components of the clinical laboratory tests are listed below in Table 2. 
Table 2. 
Clinical Laboratory Tests  
Panel  
Tests  
Chemistry  
Glucose, sodium, potassium, chloride, bicarbonate, calcium, blood urea nitrogen, 
creatinine, creatine kinase, uric acid, total and direct bilirubin, ALT, aspartate 
aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase, 
lactate dehydrogenase (LDH), triglycerides, total cholesterol, phosphorous (inorganic), 
total protein, albumin, amylase, lipase 
Hematology 
Hemoglobin, hematocrit, red blood cell count, RBC indices (MCV), reticulocyte count, 
white blood cell count including, lymphocytes, monocytes, neutrophils, eosinophils, 
basophils, platelet counts 
Coagulation  
Prothrombin time/INR, aPTT 
Urinalysis  
pH, specific gravity, protein, glucose, ketones, occult blood 
Pregnancy tests for 
female subjects of 
childbearing potential  
Serum pregnancy test and/or urine dipstick pregnancy test  
Drug Screen  
Dipstick  
Serology  
HIV-1 Ab, HIV-2 Ab, HCV Ab, HBcAb IgM, HBsAg  
Note: For antibody tests, if antibody is positive, reflex to DNA or RNA, as applicable 
Alcohol 
Urine dipstick or breathalyzer 

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Panel  
Tests  
Other  
FSH for female subjects < 54 years of age with no spontaneous menses > 12 months 
Abbreviations: Ab=antibody; ALT=alanine aminotransferase; aPTT=activated partial thromboplastin time; AST=aspartate 
aminotransferase; DNA=deoxynucleic acid; FSH=follicle stimulating hormone; GGT=gamma-glutamyl transferase; 
HBcAb=antibody to the HBV core protein; HBsAg= hepatitis B surface antigen; HCV=hepatitis C virus; HIV=human 
immunodeficiency virus; IgM=immunoglobulin M; INR=international normalized ratio; LDH=lactate dehydrogenase; 
MCV=mean corpuscular volume; RBC=red blood cell; RNA=ribonucleic acid 
8.4 
Assessment of Pharmacokinetics  
Plasma PK samples will be collected at time points specified in the PK sampling schedules 
provided in Appendix 1 (Part A [SAD]) and  Appendix 2 (Part B [MAD]). In Part B (MAD), urine 
will also be collected as specified in Appendix 2. Blood and urine sample collection, processing, 
and shipping details will be outlined in a separate lab manual or instructions. 
Plasma and urine concentrations of ABI-4334 will be determined using a validated assay at a 
contracted bioanalytical laboratory. Plasma and urine concentrations of any potential ABI-4334 
metabolites may also be determined. Furthermore, blood and urine samples will be stored for 
potential future bioanalytical testing of the parent drug or any metabolites and to support the 
validity of the study.  
8.5 
Unscheduled Visit Procedures  
An Unscheduled Visit may be performed at any time at the discretion of the Investigator in order 
to further evaluate a subject. The specific assessments to be performed at these visits would be 
determined by the Investigator according to the nature of the subject-specific follow-up required. 
Suggested assessments, as applicable, are indicated in Appendix 3. 
Assessments performed should be documented in the subject’s source documentation. Refer to 
Section 8.3.5 for clinical laboratory assessments. 
8.6 
Premature Study Termination Visit Procedures  
Should a subject prematurely discontinue from the study (Section 7.1.2), a Premature Study 
Termination Visit should be scheduled, as feasible. While the Investigator may include additional 
assessments and evaluations determined by the status of the individual subject, at a minimum, the 
assessments indicated in Appendix 3 should be performed as soon as feasibly possible. 

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9 ADVERSE EVENTS AND TOXICITY MANAGEMENT  
9.1 
Definition of Adverse Event  
An AE is any untoward medical occurrence in a study subject administered a study drug regardless 
of the causal relationship with treatment. 
An AE, therefore, can be any unfavorable and unintended sign, symptom, or disease temporally 
associated with participation in an investigational study, whether or not considered study drug 
related. In addition to new events, any increase in the severity or frequency of a pre-existing 
condition that occurs after the subject signs the ICF for participation is considered an adverse 
event. This includes any side effect, injury, toxicity, or sensitivity reaction. AEs may also include 
complications associated with protocol mandated procedures.  
An AE does not include the following: 
• Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and 
transfusion. The condition that led to the procedure may be an AE and must be reported 
• Pre-existing diseases, conditions, or clinically significant laboratory abnormalities present 
or detected before the screening visit that do not worsen during the study 
• Situations where an untoward medical occurrence has not occurred (eg, hospitalization for 
elective surgery, social and/or convenience admissions) 
• Overdose without clinical sequelae  
• Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not 
an AE. It is considered to be pre-existing and should be documented on the medical history 
CRF 
9.2 
Documenting Adverse Events  
Adverse events will be monitored and recorded from the written informed consent obtained 
through end of study (completion of follow-up period or “lost to follow-up”). The Investigator will 
ask the subject at each visit if they have experienced any untoward effects since the last study visit. 
All AEs will be entered in the electronic case report forms (eCRFs); refer to the eCRF Completion 
Guidelines for additional information. 
For the follow-up period for AEs, see Section 9.5. For the definition of TEAEs, see Section 10.4.4. 

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9.3 
Assessment of Intensity 
The severity of each AE is to be assessed by the Investigator according to the modified Division 
of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric AEs (Appendix 4), which 
grades the severity of clinical AEs and laboratory abnormalities in a 4-category system. 
For AEs not included in Appendix 4, the following guidelines will be used to describe severity: 
• Grade 1 (Mild): Mild symptoms causing no or minimal interference with usual social and 
functional activities with intervention not indicated 
• Grade 2 (Moderate): Moderate symptoms causing greater than minimal interference with 
usual social & functional activities with intervention indicated 
• Grade 3 (Severe): Severe symptoms causing inability to perform usual social and 
functional activities with intervention or hospitalization indicated (Of note, the term 
“severe” does not necessarily equate to “serious”) 
• Grade 4 (Life-Threatening): Potentially life-threatening symptoms causing inability to 
perform basic self-care functions with intervention indicated to prevent permanent 
impairment, persistent disability, or death 
9.4 
Assessment of Causality 
All AEs must have their relationship to study intervention assessed by the clinician who examines 
and evaluates the subject based on temporal relationship and his/her clinical judgment. Each AE 
must be recorded in the source documentation, whether serious or not serious. For the purposes of 
this study, each event is to be assessed with regard to the following causality categorizations, in 
the Investigator’s considered judgment: 
• Not related: An AE with sufficient evidence to accept that there was no causal relationship 
to administration of study drug (eg, no temporal relationship because the study drug was 
administered after the onset of the event, an investigation showed that study drug was not 
administered, another cause was proven) 
• Related: An AE occurred in a plausible time relationship to administration of study drug 
and that could not be explained by a concurrent disease or other drugs or events. The 
response to withdrawal of the drug (dechallenge) was clinically reasonable 
9.5 
Adverse Event Follow-up 
The Investigator is responsible to follow all AEs should through resolution, unless the event is 
considered by the Investigator to be unlikely to resolve due to the subject’s underlying disease, or 
the subject is lost to follow-up. 

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9.6 
Serious Adverse Events 
9.6.1 Definition of Serious Adverse Event 
An SAE is any event that meets any of the following criteria: 
• Death 
• Life-threatening 
• Inpatient hospitalization or prolongation of existing hospitalization 
• Persistent or significant disability/incapacity 
• Congenital anomaly/birth defect in the offspring of a subject  
• Other: Important medical events that may not result in death, be life-threatening, or require 
hospitalization, may be considered an SAE when, based upon appropriate medical 
judgment, they may jeopardize the subject and may require medical or surgical intervention 
to prevent 1 of the outcomes listed in this definition. Examples of such events are: 
o Intensive treatment in an emergency room or at home for allergic bronchospasm 
o Blood dyscrasias or convulsions that do not result in inpatient hospitalization 
o Development of drug dependency or drug abuse 
9.6.2 Definition of Terms 
• Life threatening: An AE is life-threatening if the subject was at immediate risk of death 
from the event as it occurred; ie, it does not include a reaction that if it had occurred in a 
more serious form might have caused death. For example, drug-induced hepatitis that 
resolved without evidence of hepatic failure would not be considered life threatening even 
though drug induced hepatitis can be fatal 
• Hospitalization: AEs requiring hospitalization should be considered SAEs. Hospitalization 
for elective surgery or routine clinical procedures that are not the result of AEs (eg, elective 
surgery for a pre-existing condition that has not worsened) need not be considered AEs or 
SAEs. If anything untoward is reported during the procedure, that occurrence must be 
reported as an AE, either “serious” or “non-serious” according to the usual criteria 
• In general, hospitalization signifies that the subject has been detained (usually involving at 
least an overnight stay) at the hospital for observation and/or treatment that would not have 
been appropriate in the physician's office or outpatient setting. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered serious 

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• Disability/incapacitating: An AE is incapacitating or disabling if the experience results in 
a substantial and/or permanent disruption of the subject's ability to carry out normal life 
functions 
9.6.3 Reporting Serious Adverse Events 
All SAEs must be reported by the investigational staff within 24 hours of learning about the event 
using the SAE Report form to the Sponsor or its designee (eg, CRO Pharmacovigilance group). 
The initial report should be promptly followed by detailed, written reports, which will include 
copies of relevant hospital case reports, autopsy reports, and other documents when requested and 
applicable. 
For a follow-up report to the authorities, the monitor may be required to collect further information 
for a final evaluation of the case. Reporting to the respective country Health Authorities will be 
the responsibility of the Sponsor and the CRO. 
The CRO will be responsible for informing all central Institutional Review Boards 
(IRBs)/Independent Ethics Committees (IECs) of SAEs as required. It will be the responsibility of 
the individual Investigators to inform any local IRBs/IECs of SAEs as required. Correspondence 
with the IRB(s)/IEC(s) relating to the reporting of SAEs will be retained in the study file. 
9.7 
Laboratory Abnormalities and Other Abnormal Assessments as AEs or SAEs 
Laboratory abnormalities (defined as outside of reference range) are usually not recorded as AEs 
or SAEs, unless they are clinically significant (see definition of AEs in Section 9.1), as determined 
by the Investigator. Clinical laboratory abnormalities that require medical or surgical intervention 
or lead to study drug interruption or discontinuation must be recorded as an AE or SAE, if 
applicable. The modified DAIDS Table for Grading the Severity of Adult and Pediatric AEs 
(Appendix 4) will be used to assess the severity of laboratory abnormalities. In addition, laboratory 
or other abnormal assessments (eg, ECG and vital signs) that are associated with signs and/or 
symptoms must be recorded as an AE or SAE if they meet the definition of an AE or SAE described 
in Sections 9.1 and 9.6. If the laboratory abnormality or abnormal assessment is part of a syndrome 
or diagnosis, record the syndrome or diagnosis (eg, anemia), not the laboratory result (ie, decreased 
hemoglobin).  
9.8 
Overdose 
An overdose is defined as the accidental or intentional administration of any dose of a product 
which is above the maximum recommended dose as per protocol or in the product labelling (as it 
applies to the daily dose of the subject in question). The Medical Monitor may be contacted for 
questions concerning potential cases of overdose. An overdose is not in and of itself considered to 
be an AE unless it results in untoward medical effects. Any AE associated with an overdose or 
incorrect administration of study drug should be entered in the subject’s source documentation and 

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Adverse Event eCRF. If the associated AE fulfills the criteria of an SAE, then the event should be 
reported to the Sponsor or CRO within 24 hours after the site learns of the event. 
9.9 
Pregnancy 
9.9.1 Female Subjects Who Become Pregnant 
The Investigator will collect pregnancy information on any female subject who becomes pregnant 
while participating in this study (see Appendix 5 for contraceptive requirements). The initial 
information will be recorded on the Pregnancy Reporting form and submitted to the Sponsor or its 
designee within 24 hours of learning of a subject’s pregnancy.  
The subject will be followed to determine the outcome of the pregnancy. The Investigator will 
collect follow-up information on the subject and the neonate and the information will be forwarded 
to the Sponsor or its designee. Generally, follow-up will not be required for longer than 6 to 8 
weeks beyond the estimated delivery date. Any termination of pregnancy will be reported, 
regardless of fetal status (presence or absence of anomalies) or indication for the procedure. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. A 
spontaneous abortion (occurring at < 22 weeks gestational age) or still birth (occurring at > 22 
weeks gestational age) is always considered to be an SAE and will be reported as such. 
Any female subject who becomes pregnant while participating in the study will discontinue the 
study drug(s) immediately. 
9.9.2 Male Subjects With Partners Who Become Pregnant 
The Investigator will attempt to collect pregnancy information on any male subject’s female 
partner who becomes pregnant while the male subject is participating in this study (see Appendix 
5 for contraceptive requirements).  
After obtaining the necessary signed informed consent from the pregnant female partner directly, 
the Investigator will record pregnancy information on the Pregnancy Reporting form and submit 
it to the Sponsor or its designee within 24 hours of learning of the partner’s pregnancy. The female 
partner will also be followed to determine the outcome of the pregnancy. Information on the status 
of the mother and child will be forwarded to the Sponsor. Generally, the follow-up will be no 
longer than 6 to 8 weeks following the estimated delivery date. Any termination of the pregnancy 
will be reported regardless of fetal status (presence or absence of anomalies) or indication for the 
procedure. 
9.10 Toxicity Management  
Administration of study drug may be discontinued due to an adverse event. The Medical Monitor 
should be consulted prior to dose interruption or discontinuation of study drug, if possible, unless 

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the Investigator believes that immediate action is warranted to ensure the continued safety of 
subject, in which case the Medical Monitor should be notified immediately after. 
Grade 3 and 4 clinically significant laboratory abnormalities (reported as AEs) should be 
confirmed by repeat testing within 3 days of receipt of results and before study drug 
discontinuation, unless such a delay is not consistent with good medical practice. 
Any questions regarding toxicity management should be directed to the Medical Monitor. 
9.10.1 Grades 1 and 2 Adverse Event  
• Continue study drug at the discretion of the Investigator 
9.10.2 Grade 3 or Grade 4 Adverse Event  
• For Grade 3 or Grade 4 AE, the study drug may be continued if considered to be unrelated 
to the study drug 
• For a Grade 3 or Grade 4 AE that is considered to be related to the study drug, the study 
drug should be discontinued 
• For a Grade 4 laboratory abnormality (reported as an AE) confirmed by repeat testing that 
is considered related to the study drug, the subject should be followed as clinically 
indicated until the laboratory abnormality returns to Baseline (as defined in Section 10.1) 
or is otherwise explained, whichever occurs first  
 

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10 STATISTICAL CONSIDERATIONS  
10.1 General Considerations 
This section provides the key details of the statistical analyses to be performed using data captured 
according to this protocol. A complete Statistical Analysis Plan (SAP) describing all planned 
analyses will be finalized prior to database lock. For all analyses, Baseline will be defined as 
predose, Day 1 or Screening closest to Day 1 (predose) if Day 1 testing is not available.  
10.2 Determination of Sample Size 
This is a first in human study. The sample size is similar to that previously utilized for this type of 
study and is not based upon statistical considerations. 
10.3 Analysis Populations 
The following populations will be considered for analysis of various endpoints: 
• Randomized Set: It includes all randomized subjects, classified according to the treatment 
to which they were randomized, regardless of the actual treatment received. 
• Full Analysis Set: It includes all randomized subjects, classified according to the treatment 
to which they were randomized, regardless of the actual treatment received, who took at 
least 1 dose of study drug.  
• Safety Analysis Set: It includes all subjects, classified according to the actual treatment 
received regardless of random assignment, who took at least one dose of study drug. This 
is the main analysis population for all safety analyses. 
• Pharmacokinetic-Evaluable Set: It consists of all subjects, classified according to the actual 
treatment received regardless of random assignment, who receive at least 1 dose of study 
drug. At least 1 evaluable pharmacokinetic blood sample following a dose of study 
treatment is required for inclusion in this analysis. This is the main analysis population for 
all pharmacokinetic analyses. 
Based on the actual deviations, the criteria for exclusion of subjects from the different data sets 
will be specified and updated, if necessary, prior to database lock. 
10.4 Planned Analyses  
All safety and PK endpoints will be summarized using descriptive statistics by treatment. 
Continuous endpoints will be described using the mean, standard deviation, median, minimum, 
and maximum. Categorical endpoints will be described using the number and percent of subjects 
who meet the endpoint criterion. The safety and PK analyses will be presented according to the 
treatment received. Due to sample size limitations, no formal statistical inference is planned. 

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10.4.1 Disposition of the Study Subjects 
The disposition of subjects will be described with summaries by treatment of the number of 
subjects in each analysis set described above, the number of subjects who completed the study, 
and the number of subjects for whom study drug was permanently discontinued (including the 
reasons for discontinuation). Randomized Analysis Set will be used to produce this analysis. 
10.4.2 Demographics  
The demographics will be summarized using standard descriptive methods by treatment and 
overall. Demographic summaries will include age, sex, race, ethnicity, body weight, and body 
mass index. 
10.4.3 Extent of Exposure  
Extent of exposure to study drug will be examined by assessing the total duration of study drug 
exposure and the level of adherence to the study drug by treatment for the Safety Analysis Set. 
10.4.4 Analysis of Safety Endpoints  
The safety parameters to be assessed are described in Section 8.3. Displays for safety results will 
utilize descriptive statistics. No formal hypothesis testing of safety data is planned. 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). 
A treatment-emergent adverse event (TEAE) will be defined as any AE that has an onset date or 
worsening in severity from Baseline on or after the first dose of study drug through end of study 
(defined in Section 4.5). Incidence of each body system and preferred term will be tabulated for 
each treatment. Summaries will include all TEAEs, TEAEs considered related to study treatment 
by the Investigator, graded TEAEs, serious TEAEs, TEAEs leading to premature discontinuation 
from the study intervention. All AEs, emergent or nonemergent, will be listed by subject.  
Clinical laboratory results will be summarized descriptively by treatment including values, 
changes from Baseline, and incidence of laboratory abnormalities. Laboratory results will be listed 
for each subject. 
Vital signs data and ECG findings reported at each visit will be displayed by treatment, using 
descriptive statistics for observed and change from Baseline values. 
10.4.5 Analysis of Pharmacokinetic Endpoints  
The PK parameters as shown in Table 3 and Table 4 will be estimated from the plasma 
concentrations of ABI-4334 (and potential metabolites) using noncompartmental methods in 
Phoenix® WinNonlin® as applicable. Additional parameters may be estimated, as appropriate. 

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Table 3. 
Plasma Pharmacokinetic Parameters: Parts A and B; Day 1  
Parameter 
Definition 
AUC0-last 
AUC from time 0 to the time of the last quantifiable concentration (time t) 
AUC0-24 
AUC from time 0 to 24 hours postdose  
AUC0-inf* 
AUC from time 0 extrapolated to infinity  
%AUCext* 
Percent of AUC0-inf that is extrapolated to infinity  
Cmax 
Maximum observed plasma concentration  
Tmax 
Time to Cmax 
kel* 
Apparent first-order terminal elimination rate constant 
t1/2* 
Apparent terminal elimination half-life 
Vz/F* 
Apparent volume of distribution  
CL/F* 
Apparent systemic clearance  
Cmax_DN 
Dose normalized Cmax 
AUC0-24_DN 
Dose-normalized AUC0-24  
AUC0-last_DN 
Dose-normalized AUC0-last 
AUC0-inf_DN* 
Dose-normalized AUC0-inf 
* Parameters will be reported only if the apparent terminal phase can be adequately characterized. 
Table 4. 
Plasma Pharmacokinetic Parameters: Part B (MAD) Day 8  
Parameter 
Definition 
AUCtau 
AUC from time 0 to the end of the dosing interval 
Cmax,ss 
Maximum observed plasma concentration during the dosing interval 
Cav 
Average plasma concentration over the dosing interval 
Tmax,ss 
Time to Cmax,ss 
kel* 
Apparent first order terminal elimination rate constant  
t1/2* 
Apparent terminal elimination half-life 
C24hr 
Observed plasma concentration at 24 hours postdose 
Vz/F 
Apparent volume of distribution 
CLss/F 
Apparent systemic clearance 
Cmax,ss_DN 
Dose-normalized Cmax,ss 
AUCtau_DN 
Dose-normalized AUCtau 
RA_Cmax,ss 
Accumulation ratio based on Cmax,ss  
RA_AUCtau 
Accumulation ratio based on AUC  
Linearity factor** 
Ratio of AUCtau (Day 8) to AUC0-inf (Day 1)  
* Parameters will be reported only if the apparent terminal phase can be adequately characterized. 

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** Parameter will be reported only if AUC0-inf on Day 1 is reported. 
The PK parameters as shown in Table 5 will be estimated from the urine concentrations of ABI-
4334 (and potential metabolites) using noncompartmental methods in Phoenix® WinNonlin®, as 
applicable. Additional parameters may be estimated, as appropriate. 
Table 5. 
Urine Pharmacokinetic Parameters: Part B (MAD) Day 8 
Parameter 
Definition 
Ae 
Amount of drug excreted in urine over a collection interval 
Aetau 
Amount of drug excreted in urine over the last dosing interval 
%Fe 
Fraction of the dose excreted in urine as unchanged ABI-4334 over the last dosing interval 
CLr 
Renal Clearance 
Concentrations will be used for the PK analysis as reported by the bioanalytical laboratory. Urine 
volumes will be presented and used as supplied from the clinical data base. The handling of values 
that are below the limit of quantitation will be addressed in the SAP (or the Pharmacokinetics 
Analysis Plan [PKAP], if needed). 
Plasma pharmacokinetic analysis will be carried out using actual postdose blood draw times 
relative to dosing times recorded in the raw data. If an actual blood draw time or a dosing time is 
missing, nominal time may be used. Interim analysis may be performed using nominal blood draw 
times.  
10.4.5.1 Statistical Analysis of PK Parameters  
Summary statistics (number, arithmetic mean, standard deviation [SD], percent coefficient of 
variation [%CV], minimum, median, maximum, geometric mean, and %CV for the geometric 
mean) will be presented for plasma concentrations by nominal PK sampling time and for the 
plasma PK parameters by cohort and day. Individual subject and mean plasma ABI-4334 
concentrations versus time will be plotted on linear and semi-logarithmic axes. Mean (SD) trough 
concentrations will be plotted on a linear axis for visual assessment of steady-state conditions. 
Dose proportionality of PK exposure parameters (Cmax and AUC parameters) across dose levels 
may be explored using dose-normalized Cmax and AUC, calculated for each subject by dividing 
AUC and Cmax by dose. Scatter plots of natural log (ln)-transformed PK parameters versus ln-
transformed ABI-4334 dose will be presented. A power model may also be used to further evaluate 
dose proportionality. This assessment will be performed on the Day 1 PK for the Part A (SAD), 
on the Day 8 PK for the Part B (MAD). 
The effect of food on the steady state pharmacokinetics of ABI-4334 will be explored in the food 
effect cohorts of Part A (SAD), ie, Cohorts A6 and A7, as appropriate. The PK parameters after 
administration under fed (test) compared with fasted (reference) conditions will be presented, and 
the ratios (fed to fasted) of the geometric least squares means for AUC and Cmax will be presented 
for the PK evaluable population. 

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An assessment of time to achieve steady state will be performed on the ln-transformed predose 
concentrations of ABI-4334 obtained in Part B of the study on Days 3 through 8, for each cohort.  
Details of the PK and associated statistical analyses will be included in the SAP (or PKAP, if 
needed). 
10.5 Interim Analysis  
The DRC will review the cumulative safety and PK data from each previous cohorts to determine 
dose level and dosing schedule for the subsequent cohorts (see Section 10.6). 
10.6 Data Review Committee  
10.6.1 Overview of Data Review Committee  
The DRC will review data as described in Section 10.6.2. Other designated unblinded team 
members may participate in the DRC review meetings, as required.  
For each interim cohort review, study data will include safety data from Day 1 through Day 4 (Part 
A, SAD cohorts) or Day 1 through Day 8 (Part B, MAD cohorts) for the present cohort and all 
available safety data for preceding cohorts. In addition, PK data through 24 hours after dosing 
(SAD cohorts) or from the first 24 hours after dosing on Day 8 (MAD cohorts) for the present 
cohort and available PK data for preceding cohorts will be reviewed.  
The DRC will make recommendations for dose level and dosing schedule, as per below:  
• Continue with the next cohort at a higher or lower dose, OR 
• Repeat a dose, OR 
• Modify the next cohort(s), including addition of assessments or procedures, OR 
• Discontinue a cohort, OR 
• Discontinue the study 
A decision to reduce the dose in the next cohort may be made for either safety findings (if there is 
a concern for a dose related toxicity), or to fully evaluate the PK.  
A decision to increase the dose in the next cohort may be made if the dose under evaluation is 
found to be sufficiently safe and well tolerated, and a higher dose is required to fully evaluate the 
PK. 

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10.6.2 Data Review Committee Procedures  
For the purposes of the DRC safety reviews, any of the following observations in an ongoing or 
recently completed study cohort will be defined as a “potential safety concern” requiring a specific 
assessment by the DRC: 
• A single SAE or Grade 4 AE regardless of relatedness to study treatment 
• Two or more Grade 3 AEs that are similar in nature, affecting 2 or more subjects in the 
given cohort 
Using the criteria described above, if no potential safety concerns are apparent in the safety 
observations for a given dosing cohort, then the tabulated treatment blinded safety data summary 
for the cohort combined with a Sponsor recommendation for treatment in the next cohort will be 
circulated to the Investigator by email for their review and approval of dose level and dosing 
schedule modification. This recommendation email should be forwarded to the clinical site IEC 
by the Investigator. 
Additionally, if deemed appropriate, the DRC may also elect to terminate a cohort early based on 
ongoing analysis of safety or PK data. 
Any such recommendations by the DRC will be documented in writing via email and circulated to 
the Investigator. Any DRC recommendations or safety issues engendering changes in the study 
conduct will be communicated to the Investigator’s IEC. Also, any safety-related change in study 
dosing levels, changes in safety-related clinical or laboratory assessments, or changes in study 
design, will be submitted as protocol amendments to the IEC and as required, to the national 
regulatory authorities for approval prior to implementation. 
 

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11 RESPONSIBILITIES  
11.1 Investigator Responsibilities 
11.1.1 Good Clinical Practice 
This study will be conducted in compliance with IRB/IEC and International Council for 
Harmonisation (ICH) Good Clinical Practices (GCP) Guidelines; Title 21 Part 56 of the US Code 
of Federal Regulations (CFR) relating to IRBs/IECs and GCP as described in the US FDA CFR 
(21 CFR § 50, 56, 312; China GCP; applicable ICH guidelines regarding clinical safety data 
management (E2A, E2B(R3)); European Community directives 2001/20, 2001/83, 2003/94 and 
2005/28 as enacted into local law, and with ICH guidelines regarding scientific integrity (E4, E8, 
E9, and E10). In addition, this study will adhere to all local regulatory requirements, and 
requirements for data protection. 
11.1.2 Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Before initiating a trial/study, the Investigator/institution must have written and dated 
approval/favorable opinion from the IRB/IEC for the study protocol/amendment(s), written ICF, 
any consent form updates, subject recruitment procedures (eg, advertisements), and any written 
information to be provided to subjects and a statement from the IRB/IEC that they comply with 
GCP requirements. The IRB/IEC approval must identify the protocol version as well as the 
documents reviewed. 
11.1.3 Informed Consent 
The Investigator will explain the benefits and risks of participation in the study to each subject or 
the subject’s legally acceptable representative and obtain written informed consent. Written 
informed consent must be obtained prior to the subject entering the study and before initiation of 
any study-related procedure (including administration of investigational product). 
The Sponsor or its designee will provide a sample ICF. The final, version dated, ICF must be 
agreed to by the Sponsor or its designees and the IRB/IEC and will contain all elements in the 
sample form, in language readily understood by the subject. Each subject’s original consent form 
must be personally signed and dated by the subject or by the subject’s legally acceptable 
representative, and by the person who conducted the informed consent discussion. The original, 
signed ICF will be retained by the Investigator. The Investigator will supply all enrolled subjects 
with a copy of their signed ICF. 
The ICF may need to be revised during the study should important new information become 
available that may be relevant to the safety of the subject. In this instance approval should always 
be given by the IRB/IEC and existing subjects informed of the changes and reconsented. This is 
documented in the same way as previously described. 
The Investigator should encourage subjects to inform their primary physician about their 
participation in the clinical study. 

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11.1.4 Confidentiality 
All information generated in this study is considered confidential and must not be disclosed to any 
person or entity not directly involved with the study unless prior written consent is gained from 
the Sponsor. However, authorized regulatory officials, IRB/IEC personnel, and the Sponsor and 
the Sponsor’s authorized representatives are allowed full access to the records. 
Identification of subjects and eCRFs shall be by Subject Number only. If required, the subject's 
full name may be made known to an authorized regulatory agency or other authorized official. 
11.1.5 Study Files and Retention of Records 
Records must be retained in accordance with the current ICH guidelines on GCP. All essential 
study documents including records of subjects, source documents, eCRFs, and investigational 
product inventory must be kept on file. 
Essential documents should be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing applications 
in an ICH region, or until at least 2 years have elapsed since the formal discontinuation of clinical 
development of the investigational products. However, essential documents may be retained for a 
longer period if required by the applicable regulatory requirements or by agreement with the 
Sponsor. The Sponsor is responsible for informing the Investigator when these documents need no 
longer be retained. 
The Investigator will not dispose of any records relevant to this study without written permission 
from the Sponsor and will give the Sponsor the opportunity to collect such records. The 
Investigator shall take responsibility for maintaining adequate and accurate hard copy source 
documents of all observations and data generated during this study. Such documentation is subject 
to inspection by the Sponsor, its representatives, and regulatory authorities. 
If an Investigator moves, withdraws from an investigation, or retires, responsibility for maintaining 
the records may be transferred to another person who will accept responsibility. Notice of transfer 
must be made to and agreed by the Sponsor. 
11.1.6 Audits and Inspections 
The Sponsor or their designee, the CRO, may conduct audits at the investigative sites including, 
but not limited to, drug supply, presence of required documents, the informed consent process, and 
comparison of eCRFs with source documents. All medical records (progress notes) must be 
available for audit. The Investigator agrees to participate with audits conducted at a convenient 
time in a reasonable manner. 
Government regulatory authorities may also inspect the site during or after the study. The 
Investigator or designee should contact the Sponsor and/or the CRO, immediately if this occurs. 
The site must cooperate fully with regulatory authorities or other audits conducted at a convenient 
time in a reasonable manner. 

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The purpose of an audit is to assess whether ethical, regulatory, and quality requirements are 
fulfilled. 
11.1.7 Protocol Compliance 
It is the responsibility of the Investigator to ensure that the study is conducted at their respective 
site in accordance with this protocol. Protocol compliance assessments will be conducted during 
routine site monitoring visits. 
11.2 Sponsor Responsibilities 
11.2.1 Protocol Amendments and Modifications 
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by the Sponsor. A protocol change intended to eliminate an apparent immediate hazard 
to subjects may be implemented immediately, provided the IRB/IEC is notified within 5 days. 
Any permanent, significant change to the protocol must be handled as a protocol amendment. The 
written amendment must be submitted to the IRB/IEC and the Investigator must await approval 
before implementing the changes. The Sponsor will submit protocol amendments to the 
appropriate regulatory authorities for approval. 
If, in the judgment of the IRB/IEC, the Investigator, and/or the Sponsor, the amendment to the 
protocol substantially changes the study design and/or increases the potential risk to the subject 
and/or has an impact on the subject's involvement as a study subject, the currently approved written 
ICF will require similar modification. In such cases, subjects will be required for to sign the 
amended informed consent prior to continued participation in the study. 
11.2.2 Data Management 
A set of data management documents will be created under the responsibility of the Sponsor, or 
designated CRO, to describe the processes being used to ensure data quality. 
The data management plan, and other associated documentations, will specify data capture 
methods, who is authorized to enter data, decisions about ownership of data, source data storage, 
which data will be transferred (including timing of transfers), and the origin/destination of data. 
11.2.3 Study Report and Publications 
The Sponsor or its designee is responsible for preparing and providing the appropriate regulatory 
authorities with the Clinical Study Report (CSR) according to the applicable regulatory 
requirements. CSR will be developed in accordance with the ICH E3 Guideline on the ‘Structure 
and Content of Clinical Study Reports’. Local country requirements will be considered during 
CSR preparation. 

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The Sponsor or its designee is responsible for posting clinical trial information for public access 
according to country-specific requirements. At a minimum, clinical trial information will be posted 
according to US NIH CT.gov regulations.  
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the Investigator agrees to submit all proposed manuscripts or abstracts to the Sponsor before 
submission. This allows the Sponsor to protect proprietary information and to provide comments. 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a coordinating 
Investigator will be designated by mutual agreement.  
Assembly Biosciences follows the guidelines and recommendations of the International 
Committee of Medical Journal Editors (ICMJE) and the International Society for Medical 
Publication Professionals (ISMPP) when preparing publications associated with clinical studies 
(Battisti 2015, ICMJE 2019). 
 
 

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REFERENCES  
Battisti WP, Wager E, Baltzer L, et al (2015) Good Publication Practice for Communicating 
Company-Sponsored Medical Research: GPP3. Ann Intern Med 163(6):461-464. 
Colvin H, Mitchell AE (2010). Hepatitis and Liver Cancer: A National Strategy for Prevention 
and Control of Hepatitis B and C. Washington, D.C., The National Academies Press. 
Cornberg M, Lok AS, Terrault NA, et al (2019) Guidance for design and endpoints of clinical 
trials in chronic hepatitis B - Report from the 2019 EASL-AASLD HBV Treatment Endpoints 
Conference. Hepatology. 
El-Serag HB (2012) Epidemiology of viral hepatitis and hepatocellular carcinoma. 
Gastroenterology 142(6):1264-1273 e1261. 
EMA (2018) Guideline:  Strategies to identify and mitigate risks for first-in-human clinical trials 
with investigational medicinal products. 
Fanning GC, Zoulim F, Hou J, et al (2019) Therapeutic strategies for hepatitis B virus infection: 
towards a cure. Nat Rev Drug Discov 18(11):827-844. 
FDA (2019)  Guidance for Industry Food-Effect Bioavailability and Fed Bioequivalence Studies 
Center for Drug Evaluation and Research, Rockville, Maryland Retrieved 14 June 2022  from 
https://www.fda.gov/files/drugs/published/Food-Effect-Bioavailability-and-Fed-Bioequivalence-
Studies.pdf. 
FDA US (2005) Guidance for Industry: Estimating the maximum safe starting dose in initial 
clinical trials for therapeutics in adult healthy volunteers. 
Gish RG, Given BD, Lai CL, et al (2015) Chronic hepatitis B: Virology, natural history, current 
management and a glimpse at future opportunities. Antiviral Res 121:47-58. 
Hoofnagle JH, Doo E, Liang TJ, et al (2007) Management of hepatitis B: summary of a clinical 
research workshop. Hepatology 45(4):1056-1075. 
ICMJE (2019) Recommendations for the Conduct, Reporting, Editing, and Publication of 
Scholarly Work in Medical Journals.  International committee of medical journal editors.   
Konerman MA and Lok AS (2016) Interferon Treatment for Hepatitis B. Clin Liver Dis 20(4):645-
665. 
Lampertico P, Agarwal K, Berg T, et al (2017) Clinical Practice Guidelines on the management of 
hepatitis B virus infection. Journal of Hepatology 67(2):370-398. 

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Lampertico P and Liaw YF (2012) New perspectives in the therapy of chronic hepatitis B. Gut 61 
Suppl 1:i18-24. 
Lok AS and McMahon BJ (2009) Chronic hepatitis B: update 2009. Hepatology 50(3):661-662. 
Marcellin P, Ahn SH, Ma X, et al (2016) Combination of Tenofovir Disoproxil Fumarate and 
Peginterferon alpha-2a Increases Loss of Hepatitis B Surface Antigen in Patients With Chronic 
Hepatitis B. Gastroenterology 150(1):134-144 e110. 
Pungpapong S and Kim WR (2013) In the eye of the B-holder: natural history of chronic hepatitis 
B. Hepatology 58(1):6-8. 
Schweitzer A, Horn J, Mikolajczyk RT, et al (2015) Estimations of worldwide prevalence of 
chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. 
Lancet 386(10003):1546-1555. 
Sorrell MF, Belongia EA, Costa J, et al (2009) National Institutes of Health Consensus 
Development Conference Statement: management of hepatitis B. Ann Intern Med 150(2):104-110. 
Terrault (2018) Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 
2018 hepatitis B guidance. Hepatology 67(4):1560-1599. 
WHO (2021) Hepatitis B Retrieved 05 April 2022  from https://www.who.int/en/news-room/fact-
sheets/detail/hepatitis-b. 
Yim HJ and Lok AS (2006) Natural history of chronic hepatitis B virus infection: what we knew 
in 1981 and what we know in 2005. Hepatology 43(2 Suppl 1):S173-181. 

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APPENDICES 

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APPENDIX 1a. 
 SCHEDULE OF ASSESSMENTS FOR SCHEDULED VISITS: PART A – SAD (COHORTS A1-A5, 
COHORT A7 Period 1) IN HEALTHY SUBJECTS  
Period of Visit 
Screening  
 
Treatment  
Follow-Up 
Study Day  Day -28 to Day 
-2  
Day -1  
Day 1  
(LDD) 
Day 2  
Day 3  
Day 4  
Day 5  
Day 6  
Day 7  
(EOS) 
Visit Windows (days) 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
In-Clinic Assessments 
Informed Consent(s) 
X 
 
 
 
 
 
 
 
 
Confined to Study 
Clinic  
 
X 
X 
X 
X 
 
 
 
 
Discharge  
 
 
 
 
 
X 
 
 
 
Demographics  
X 
 
 
 
 
 
 
 
 
Medical History 
X 
X 
 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
 
 
 
 
X 
Complete Physical 
Exam 
X 
X 
 
 
 
X h  
 
 
 
Symptom-Directed 
Physical Exam 
 
 
X 
X 
X 
 
X 
X 
X 
Vital Signs a 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECG a 
X 
X 
X 
X 
 
X 
 
 
X 
Holter Data Collection 
b 
 
 
X 
X 
 
 
 
 
 
Concomitant 
Medications & 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Alcohol Testing  
X 
X 
 
 
 
 
 
 
 
Urine Drug Test  
X 
X 
 
 
 
 
 
 
 
FSH Testing c 
X 
 
 
 
 
 
 
 
 
Urine Pregnancy Test 
(females of 
childbearing potential) 
d 
 
 
X 
 
 
X 
 
 
 
Confirm Subject 
Eligibility 
 
X 
X 
 
 
 
 
 
 
Randomization 
(predose) 
 
 
X 
 
 
 
 
 
 

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Period of Visit 
Screening  
 
Treatment  
Follow-Up 
Study Day  Day -28 to Day 
-2  
Day -1  
Day 1  
(LDD) 
Day 2  
Day 3  
Day 4  
Day 5  
Day 6  
Day 7  
(EOS) 
Visit Windows (days) 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
In Clinic Study Drug 
Dosing  
 
 
X 
 
 
 
 
 
 
Laboratory Assessments 
HIV-1 Ab, HIV-2 Ab, 
HCV Ab, HBcAb IgM, 
HBsAg e 
X 
 
 
 
 
 
 
 
 
Chemistry  
X 
X 
X f 
X 
X 
 
X 
 
X 
Hematology  
X 
X 
X f 
X 
X 
 
X 
 
X 
Coagulation  
X 
X 
X f 
X 
X 
 
 
 
X 
Urinalysis 
X 
X 
X f 
X 
X 
 
 
 
X 
Serum Pregnancy Test 
(females of 
childbearing potential) 
d 
X 
X 
 
 
 
 
 
 
 
Pharmacokinetics Assessments 
PK Sampling g 
 
 
X 
X 
X 
X 
X 
X 
X 
Abbreviations Ab=antibody; ECG=electrocardiogram; EOS=end of study; FSH=follicle-stimulating hormone; HBcAb=antibody to the HBV core protein; HBsAg=hepatitis B 
surface antigen; HCV=hepatitis C virus; HIV=human immunodeficiency virus; IgM=immunoglobulin M; LDD=last day of dosing; NA=not applicable; PK=pharmacokinetic 
Note: When multiple procedures are scheduled at the same time, the order of events will be: Holter extraction, followed by 12-lead ECGs, vital signs, PK blood sample collection 
(to be collected on the scheduled time point), and meals. The only exception will be at 2 and 4 hours postdose, when the 12-lead ECG will be performed before the Holter 
extraction 
a  
Collection of vital signs and ECG will be repeated throughout the day. Specifically, vital signs will be collected predose (within 2 hours before dosing) on Day 1, and at 2, 4, 
8, 12, 24, 48, 72, 96, 120, and 144 hours after dosing on Day 1. Collection of ECG will be performed predose on Day 1, and at 2, 4, 12, and 24 hours (ie, Day 2) after dosing 
on Day 1; and anytime on Days 4 and 7. The window for collection of vital signs and ECGs will be ±15 minutes.   
b  
Holter data collection timepoints on Day 1 are -60, -45, and -30 minutes predose and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 18, and 24 hours (ie, Day 2) postdose (time matched to PK 
assessments). Holter monitoring will not be performed for Cohort A7.  
c  
Only for female subjects < 54 years of age with no spontaneous menses for > 12 months. 
d 
A serum pregnancy test is required at Screening and Day -1 for female subjects of childbearing potential. On Day 1, a urine pregnancy test will be performed for females of 
childbearing potential, prior to dosing. All post Day 1 pregnancy tests may be conducted by urine dipstick. If positive on dipstick, reflex to serum. 
e 
For antibody tests, if antibody is positive, reflex to DNA or RNA (as applicable). 
f 
On Day 1, samples for clinical laboratory tests will be taken predose.  
g 
Blood samples for PK analysis of ABI-4334 in plasma will be collected at the following time points: predose (within 0.5 hours before dosing) and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 
18, 24, 36, 48, 72, 96, 120, and 144 hours after dosing on Day 1; Time point windows are ±2 minutes for 0.5- and 1-hour postdose samples and ±5 minutes for samples from 
2 through 18 hours postdose and ±30 minutes for samples 24 hours postdose and after. 
h 
A complete physical exam will be done before the subject is discharged from the study site.  

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APPENDIX 1b. 
 SCHEDULE OF ASSESSMENTS FOR SCHEDULED VISITS: PART A – SAD (COHORT A6, 
COHORT A7 Period 2) 
Period of Visit 
 
Treatment  
Follow-Up 
Study Day  Day -1  
Day 1 (LDD) 
Day 2  
Day 3  
Day 4  
Day 5  
Day 6  
Day 7  
(EOS) 
Visit Windows (days) 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
In-Clinic Assessments 
Confined to Study Clinic  
X 
X 
X 
X 
 
 
 
 
Discharge  
 
 
 
 
X 
 
 
 
Complete Physical Exam 
X 
 
 
 
X e 
 
 
 
Symptom-Directed Physical Exam 
 
X 
X 
X 
 
X 
X 
X 
Vital Signs a 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECG a 
 
X 
X 
 
X 
 
 
X 
Weight 
X 
 
 
 
 
 
 
X 
Concomitant Medications & 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
Alcohol Testing  
X 
 
 
 
 
 
 
 
Urine Drug Test  
X 
 
 
 
 
 
 
 
Urine pregnancy test (females of 
childbearing potential) b 
 
X 
 
 
X 
 
 
 
Confirm Subject Eligibility 
X 
X 
 
 
 
 
 
 
In Clinic Study Drug Dosing  
 
X 
 
 
 
 
 
 
Laboratory Assessments 
Chemistry  
 
X c 
X 
X 
 
X 
 
X 
Hematology  
 
X c 
X 
X 
 
X 
 
X 
Coagulation  
 
X c 
X 
X 
 
 
 
X 
Urinalysis 
 
X c 
X 
X 
 
 
 
X 
Serum Pregnancy Test (females of 
childbearing potential) b 
X 
 
 
 
 
 
 
 
Pharmacokinetics Assessments 
PK Sampling d 
 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: ECG=electrocardiogram; EOS=end of study LDD=last day of dosing; NA=not applicable; PK=pharmacokinetic 
Note: When multiple procedures are scheduled at the same time, the order of events will be: 12-lead ECGs, vital signs, PK blood sample collection (to be collected on the 
scheduled time point), and meals.  

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a  
Collection of vital signs and ECG will be repeated throughout the day. Specifically, vital signs will be collected predose (within 2 hours before dosing) on Day 1, and at 2, 4, 
8, 12, 24, 48, 72, 96, 120, and 144 hours after dosing on Day 1. Collection of ECG will be performed predose on Day 1, and at 2, 4, 12, and 24 hours (ie, Day 2) after dosing 
on Day 1; and anytime on Days 4 and 7. The window for collection of vital signs and ECGs will be ±15 minutes.   
b 
A serum pregnancy test is required at Day -1 for female subjects of childbearing potential. On Day 1, a urine pregnancy test will be performed for females of childbearing 
potential, prior to dosing. All post Day 1 pregnancy tests may be conducted by urine dipstick. If positive on dipstick, reflex to serum. 
c 
On Day 1, samples for clinical laboratory tests will be taken predose.  
d 
Blood samples for PK analysis of ABI-4334 in plasma will be collected at the following time points: predose (within 0.5 hours before dosing) and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 
18, 24, 36, 48, 72, 96, 120, and 144 hours after dosing on Day 1; Time point windows are ±2 minutes for 0.5- and 1-hour postdose samples and ±5 minutes for samples from 
2 through 18 hours postdose and ±30 minutes for samples 24 hours postdose and after. 
e 
A complete physical exam will be done before the subject is discharged from the study site.  
 
 
 
 
 
 

ABI-4334  
Study ABI-4334-101 Original Protocol 16 June 2022  
 
Assembly Biosciences  
Confidential 
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APPENDIX 2. 
SCHEDULE OF ASSESSMENTS FOR SCHEDULED VISITS: PART B – MAD IN HEALTHY 
SUBJECTS  
Period of Visit Screening   
Treatment 
Follow-Up 
Study Day Day -28 to 
Day -2  
Day -1 Day 
1  
Day  
2  
Day  
3  
Day  
4  
Day  
5  
Day  
6  
Day  
7  
Day 8 
(LDD) 
1 Day 
Post LDD 
 
2 Days 
Post 
LDD  
3 Days 
Post 
LDD 
4 Days 
Post 
LDD 
5 Days 
Post 
LDD 
7 Days 
Post LDD 
(EOS) 
Visit Windows (days) NA 
NA 
NA 
NA 
NA 
NA 
NA NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
In-Clinic Assessments 
Informed Consent(s) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confined to Study Clinic  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Discharge  
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Demographics  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Complete Physical Exam 
X 
X 
 
 
 
 
 
 
 
 
 
 
X i 
 
 
 
Symptom-Directed 
Physical Exam 
 
 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
X 
X 
X 
Vital Signs a 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECG a 
X 
X 
X 
 
X 
 
X 
 
 
X 
 
 
X 
 
 
X 
Holter Data Collection b 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Concomitant 
Medications & Adverse 
Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Alcohol Testing  
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Drug Test  
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Pregnancy Test 
(females of childbearing 
potential) c 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
FSH Testing d 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirm Subject 
Eligibility 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization (predose) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
In Clinic Study Drug 
Dosing e 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
Laboratory Assessments 

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Study ABI-4334-101 Original Protocol 16 June 2022  
 
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Period of Visit Screening   
Treatment 
Follow-Up 
Study Day Day -28 to 
Day -2  
Day -1 Day 
1  
Day  
2  
Day  
3  
Day  
4  
Day  
5  
Day  
6  
Day  
7  
Day 8 
(LDD) 
1 Day 
Post LDD 
 
2 Days 
Post 
LDD  
3 Days 
Post 
LDD 
4 Days 
Post 
LDD 
5 Days 
Post 
LDD 
7 Days 
Post LDD 
(EOS) 
Visit Windows (days) NA 
NA 
NA 
NA 
NA 
NA 
NA NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
HIV-1 Ab, HIV-2 Ab, 
HCV Ab, HBcAb IgM, 
HBsAg f 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chemistry  
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
X 
 
 
X 
Hematology  
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
X 
 
 
X 
Coagulation  
X 
X 
X 
X 
 
X 
 
 
 
X 
 
 
X 
 
 
X 
Urinalysis 
X 
X 
X 
X 
 
X 
 
 
 
X 
 
 
 
 
 
X 
Serum Pregnancy Test 
(females of childbearing 
potential) c 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pharmacokinetics Assessments 
PK Sampling (Blood) g 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
PK Sampling (Urine) h 
 
 
 
 
 
 
 
 
 
X 
X 
 
 
 
 
 
Abbreviations Ab=antibody; ECG=electrocardiogram; EOS=end of study; FSH=follicle-stimulating hormone; HBcAb=antibody to the HBV core protein; HBsAg=hepatitis B 
surface antigen; HCV=hepatitis C virus; HIV=human immunodeficiency virus; IgM=immunoglobulin M; LDD=last day of dosing; NA=not applicable; PK=pharmacokinetic 
Note: When multiple procedures are scheduled at the same time, the order of events will be: Holter extraction, followed by 12-lead ECGs, vital signs, PK blood sample collection 
(to be collected on the scheduled time point), and meals. The only exception will be at 2 and 4 hours postdose, when the 12-lead ECG will be performed before the Holter 
extraction. 
a  
From Day 1 through Day 8, vital signs will be collected predose (within 2 hours before dosing) and at 2, 4, 8, and 12 hours postdose. After Day 8, vital signs will be 
collected every 24 hours through 5 days post last day of dosing, and anytime on EOS. Collection of ECGs will be performed predose on Day 1, and on Days 1, 3, 5, and 8 at 
2, 4, and 12 hours postdose; anytime on 3 days and 7 days post last day of dosing. The window for collection of vital signs and ECGs will be ±15 minutes. 
b  
Holter data collection timepoints on Days 1 and 8 are -60, -45, and -30 minutes predose and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 18, and 24 hours postdose (time matched to PK 
assessments).  
If a BID dosing schedule is indicated for Part B, Holter data will be collected on Day 1: -60, -45, and -30 minutes predose and then post morning dose at 0.5, 1, 2, 3, 4, 5, 6, 
9, and 12 hours. On Day 8: -60, -45, and -30 minutes predose and then postdose at 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 18, and 24 hours. 
c  
A serum pregnancy test is required at Screening and Day -1 for female subjects of childbearing potential. On Day 1, a urine pregnancy test will be performed for females of 
childbearing potential, prior to dosing. All post Day 1 pregnancy tests may be conducted by urine dipstick. If positive on dipstick, reflex to serum. 
d 
Only for female subjects < 54 years of age with no spontaneous menses for > 12 months. 
e  
Study drug dosing (Days 1-8) will be administered with 240 mL of water in the clinic under supervision.  
If a BID dosing schedule is indicated for Part B, study drug will be administered twice a day, 12 hours apart, from Day 1 to Day 7. On Day 8, subjects will receive their last 
dose in the morning. 
f 
For antibody tests, if antibody is positive, reflex to DNA or RNA (as applicable). 
 
 

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g 
Blood samples for PK analysis of ABI-4334 in plasma will be collected at the following time points:  
• 
Day 1: predose (within 0.5 hours before dosing) and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 18, and 24 hours after dosing on Day 1. Note: The 24-hour sample after the Day 1 
dose is the predose sample on Day 2. 
• 
Day 8: predose (within 0.5 hours before dosing) and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48, 72, 96, and 120 hours after dosing on Day 8. 
• 
Days 2, 3, 4, 5, 6, and 7: predose (within 0.5 hours before dosing). 
If a BID dosing schedule is indicated for Part B, blood samples for PK analysis of ABI-4334 in plasma will be collected at the following time points: 
• 
Day 1: predose (within 0.5 hours before morning dosing) and 0.5, 1, 2, 3, 4, 5, 6, 9, and 12 hours after morning dosing on Day 1. Note: The 12-hours sample 
should be taken prior to the evening dose on Day 1.  
• 
Day 8: predose (within 0.5 hours before dosing) and 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48, 72, 96, and 120 hours after dosing on Day 8. 
• 
Days 3, 4, 5, 6, and 7: predose (within 0.5 hours before morning dosing) 
Time point windows are ±2 minutes for 0.5- and 1-hour postdose samples and ±5 minutes for samples from 2 through 18 hours postdose and ±30 minutes for samples 24 
hours postdose and after. 
h 
Urine for PK assessment will be collected over 24-hours and will include predose on Day 8 (void and discard), and at times 0-4, 4-8, 8-12, and 12-24 hours postdose. All 
excreted urine will be collected during each time interval.  
If a BID dosing schedule is indicated for Part B, the same schedule of urine sample collection should be followed. All excreted urine will be collected during each time 
interval. 
i 
A complete physical exam will be done before the subject is discharged from the study site.  

ABI-4334  
Study ABI-4334-101 Original Protocol 16 June 2022  
 
Assembly Biosciences  
Confidential 
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APPENDIX 3.  
SCHEDULE OF ASSESSMENTS FOR OTHER VISITS  
Study Visit 
Premature Study 
Termination 
Unscheduled  
Visit Timing or Frequency a 
As soon as feasibly possible 
As Applicable 
Weight 
X 
 
Vital Signs 
X 
X 
Complete Physical Exam 
X 
 
Symptom-Directed Physical Exam 
 
X 
12-Lead ECG 
X 
 
Concomitant Medications & Adverse Events 
X 
X 
Urinalysis 
X 
X 
Urine Pregnancy Test (females of childbearing 
potential) b 
X 
X 
Chemistry, Hematology, Coagulation, Alcohol 
testing 
X 
X 
Any time PK Sample 
X 
X 
Abbreviations: ECG=electrocardiogram PK=pharmacokinetic 
a  
Tests to be conducted as applicable, based on Investigator discretion, and may include tests not specified in the Schedule of 
Assessments. 
b 
Pregnancy tests for females of childbearing potential to be conducted by urine dipstick. If positive on dipstick, reflex to 
serum. 

ABI-4334  
Study ABI-4334-101 Original Protocol 16 June 2022  
 
Assembly Biosciences  
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APPENDIX 4. TOXICITY GRADING SCALE FOR ADVERSE EVENTS AND 
LABORATORY ABNORMALITIES 
Adapted from the U.S. National Institutes of Health (Division of AIDS) Table for Grading 
Severity of Adult Adverse Experiences (Corrected Version 2.1, July 2017) 
[https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf]  
MAJOR CLINICAL CONDITIONS 
Parameter 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Potentially 
life -threatening 
CARDIOVASCULAR 
Arrhythmia  
(by ECG or physical 
examination) 
Specify type, if 
applicable 
No symptoms AND 
No intervention 
indicated 
No symptoms AND 
Non-urgent 
intervention 
indicated 
Non-life-threatening 
symptoms AND 
Non-urgent 
intervention 
indicated 
Life-threatening 
arrhythmia OR 
Urgent intervention 
indicated 
Blood Pressure 
Abnormalities 
Hypertension (with 
the lowest reading 
taken after repeat 
testing during a 
visit) 
≥ 18 years of age 
140 to < 160 mmHg 
systolic  
OR 90 to 
< 100 mmHg 
diastolic 
≥ 160 to 
< 180 mmHg 
systolic  
OR ≥ 100 to 
< 110 mmHg 
diastolic 
≥ 
180 
mmHg 
systolic  
OR  
≥ 
110 
mmHg 
diastolic 
Life-threatening 
consequences in a 
participant not 
previously 
diagnosed with 
hypertension (e.g., 
malignant 
hypertension) OR 
Hospitalization 
indicated 
Hypotension 
No symptoms 
Symptoms corrected 
with oral fluid 
replacement 
Symptoms AND IV 
fluids indicated 
Shock requiring use 
of vasopressors or 
mechanical 
assistance to 
maintain blood 
pressure 
Cardiac Ischemia or 
Infarction 
Report only one 
NA 
NA 
New symptoms 
with ischemia 
(stable angina) OR 
New testing 
consistent with 
ischemia 
Unstable angina OR 
Acute myocardial 
infarction 
Heart Failure 
No symptoms AND 
Laboratory or 
cardiac imaging 
abnormalities 
Symptoms with 
mild to moderate 
activity or exertion 
Symptoms at rest or 
with minimal 
activity or exertion 
(e.g., hypoxemia) 
OR Intervention 
indicated (e.g., 
oxygen) 
Life-threatening 
consequences OR 
Urgent intervention 
indicated (e.g., 
vasoactive 
medications, 
ventricular assist 
device, heart 
transplant) 

ABI-4334  
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Parameter 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Potentially 
life -threatening 
Hemorrhage  
(with significant 
acute blood loss) 
NA 
Symptoms AND No 
transfusion 
indicated 
Symptoms AND 
Transfusion of 
≤ 2 units packed 
RBCs indicated 
Life-threatening 
hypotension OR 
Transfusion of 
> 2 units 
packed RBCs (for 
children, packed 
RBCs > 10 cc/kg) 
indicated 
Prolonged PR 
Interval or AV 
Block 
Report only one 
> 16 years of age 
PR interval 0.21 to 
< 0.25 seconds 
PR interval 
≥ 0.25 seconds OR 
Type I 2nd degree 
AV block 
Type II 2nd degree 
AV block OR 
Ventricular pause 
≥ 3.0 seconds 
Complete AV block 
Prolonged QTc 
Interval 2 
0.45 to 0.47 seconds 
> 0.47 to 
0.50 seconds 
> 0.50 seconds OR ≥ 
0.06 seconds above 
baseline 
Life-threatening 
consequences (e.g., 
Torsade de pointes, 
other associated 
serious ventricular 
dysrhythmia) 
Thrombosis or 
Embolism 
Report only one 
 
NA 
Symptoms AND No 
intervention 
indicated 
Symptoms AND 
Intervention 
indicated 
Life-threatening 
embolic event (e.g., 
pulmonary 
embolism, 
thrombus) 
DERMATOLOGIC  
Alopecia  
(scalp only) 
Detectable by study 
participant, 
caregiver, or 
physician AND 
Causing no or 
minimal 
interference with 
usual social & 
functional activities 
Obvious on visual 
inspection AND 
Causing greater 
than minimal 
interference with 
usual social & 
functional activities 
NA 
NA 
Bruising  
Localized to one 
area 
Localized to more 
than one area 
Generalized  
NA 
Cellulitis  
NA 
Non-parenteral 
treatment indicated 
(e.g., oral 
antibiotics, 
antifungals, 
antivirals) 
IV treatment 
indicated (e.g., IV 
antibiotics, 
antifungals, 
antivirals) 
Life-threatening 
consequences (e.g., 
sepsis, tissue 
necrosis) 
Hyperpigmentation 
Slight or localized 
causing no or 
minimal 
interference with 
Marked or 
generalized causing 
greater than 
minimal 
interference with 
NA 
NA 

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Study ABI-4334-101 Original Protocol 16 June 2022  
 
Assembly Biosciences  
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Parameter 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Potentially 
life -threatening 
usual social & 
functional activities 
usual social & 
functional activities 
Hypopigmentation 
Slight or localized 
causing no or 
minimal 
interference with 
usual social & 
functional activities 
Marked or 
generalized causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
NA 
NA 
Petechiae 
Localized to one 
area 
Localized to more 
than one area 
Generalized 
NA 
Pruritus 3 
(without skin 
lesions) 
Itching causing no 
or minimal 
interference with 
usual social & 
functional activities 
Itching causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Itching causing 
inability to perform 
usual social & 
functional activities 
NA 
Rash 
Specify type, if 
applicable 
Localized rash  
Diffuse rash OR 
Target lesions 
Diffuse rash AND 
Vesicles or limited 
number of bullae or 
superficial 
ulcerations of 
mucous membrane 
limited to one site 
Extensive or 
generalized bullous 
lesions OR 
Ulceration of 
mucous membrane 
involving two or 
more distinct 
mucosal sites OR 
Stevens-Johnson 
syndrome OR Toxic 
epidermal 
necrolysis 
ENDOCRINE AND METABOLIC 
Diabetes Mellitus 
Controlled without 
medication 
Controlled with 
medication OR 
Modification of 
current medication 
regimen 
Uncontrolled 
despite treatment 
modification OR 
Hospitalization for 
immediate glucose 
control indicated 
Life-threatening 
consequences (e.g., 
ketoacidosis, 
hyperosmolar 
nonketotic coma, 
end organ failure) 
Gynecomastia 
Detectable by study 
participant, 
caregiver, or 
physician AND 
Causing no or 
minimal 
interference with 
usual social & 
functional activities 
Obvious on visual 
inspection AND 
Causing pain with 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Disfiguring changes 
AND Symptoms 
requiring 
intervention or 
causing inability to 
perform usual social 
& functional 
activities 
NA 

ABI-4334  
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Assembly Biosciences  
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Parameter 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Potentially 
life -threatening 
Hyperthyroidism 
No symptoms AND 
Abnormal 
laboratory value 
Symptoms causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
OR Thyroid 
suppression therapy 
indicated 
Symptoms causing 
inability to perform 
usual social & 
functional activities 
OR Uncontrolled 
despite treatment 
modification 
Life-threatening 
consequences (e.g., 
thyroid storm) 
Hypothyroidism 
No symptoms AND 
Abnormal 
laboratory value 
Symptoms causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
OR Thyroid 
replacement therapy 
indicated 
Symptoms causing 
inability to perform 
usual social & 
functional activities 
OR Uncontrolled 
despite treatment 
modification 
Life-threatening 
consequences (e.g., 
myxedema coma) 
Lipoatrophy4 
Detectable by study 
participant, 
caregiver, or 
physician AND 
Causing no or 
Minimal 
interference with 
usual social & 
functional activities 
Obvious on visual 
inspection AND 
Causing greater 
than minimal 
interference with 
usual social & 
functional activities 
Disfiguring changes 
NA 
Lipohypertrophy5 
Detectable by study 
participant, 
caregiver, or 
physician AND 
Causing no or 
minimal 
interference with 
usual social & 
functional activities 
Obvious on visual 
inspection AND 
Causing greater 
than minimal 
interference with 
usual social & 
functional activities 
Disfiguring changes  NA 
GASTROINTESTINAL  
Anorexia  
Loss of appetite 
without decreased 
oral intake 
Loss of appetite 
associated with 
decreased oral 
intake without 
significant weight 
loss 
Loss of appetite 
associated with 
significant weight 
loss 
Life-threatening 
consequences OR 
Aggressive 
intervention 
indicated (e.g., tube 
feeding, total 
parenteral nutrition) 
Ascites 
No symptoms 
Symptoms AND 
Intervention 
indicated (e.g., 
Symptoms recur or 
persist despite 
intervention 
Life-threatening 
consequences 

ABI-4334  
Study ABI-4334-101 Original Protocol 16 June 2022  
 
Assembly Biosciences  
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Parameter 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Potentially 
life -threatening 
diuretics, 
therapeutic 
paracentesis) 
Bloating or 
Distension 
Report only one 
Symptoms causing 
no or minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
inability to perform 
usual social & 
functional activities 
NA 
Cholecystitis 
NA 
Symptoms AND 
Medical 
intervention 
indicated 
Radiologic, 
endoscopic, or 
operative 
intervention 
indicated 
Life-threatening 
consequences (e.g., 
sepsis, perforation) 
Constipation  
NA  
Persistent 
Constipation 
requiring regular 
use of dietary 
modifications, 
laxatives, or enemas 
Obstipation with 
manual evacuation 
indicated 
Life-threatening 
consequences (e.g., 
obstruction) 
Diarrhea 
≥ 1 year of age 
Transient or 
Intermittent 
episodes of 
unformed stools OR 
Increase of ≤ 3 
stools over baseline 
per 24-hour period 
Persistent episodes 
of unformed to 
watery stools OR 
Increase of 4 to 6 
stools over baseline 
per 24-hour period 
Increase of ≥ 7 stools 
per 24-hour period 
OR 
IV 
fluid 
replacement 
indicated 
Life-threatening 
consequences (e.g., 
hypotensive shock) 
Dysphagia or 
Odynophagia 
Report only one and 
specify location 
Symptoms but able 
to eat usual diet 
Symptoms causing 
altered dietary 
intake with no 
intervention 
indicated 
Symptoms causing 
severely altered 
dietary intake with 
intervention 
indicated 
Life-threatening 
reduction in oral 
intake 
Gastrointestinal 
Bleeding 
Not requiring 
intervention other 
than iron 
supplement 
Endoscopic 
intervention 
indicated 
Transfusion 
indicated 
Life-threatening 
consequences (e.g., 
hypotensive shock) 
Mucositis or 
Stomatitis 
Report only one and 
specify location 
Mucosal erythema 
Patchy 
pseudomembranes 
or ulcerations 
Confluent 
pseudomembranes 
or ulcerations OR 
Mucosal bleeding 
with minor trauma 
Life-threatening 
consequences (e.g., 
aspiration, choking) 
OR Tissue necrosis 
OR Diffuse 
spontaneous 
mucosal bleeding 
Nausea 
Transient 
(< 24 hours) or 
intermittent AND 
No or minimal 
Persistent nausea 
resulting in 
decreased oral 
intake for 24 to 
48 hours 
Persistent nausea 
resulting in minimal 
oral intake for 
> 48 hours OR 
Rehydration 
Life-threatening 
consequences (e.g., 
hypotensive shock) 

ABI-4334  
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Parameter 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Potentially 
life -threatening 
interference with 
oral intake 
indicated (e.g., IV 
fluids) 
Pancreatitis 
NA 
Symptoms with 
hospitalization not 
indicated 
Symptoms with 
hospitalization 
indicated 
Life-threatening 
consequences (e.g., 
circulatory failure, 
hemorrhage, sepsis) 
Perforation 
(colon or rectum) 
NA 
NA 
Intervention 
indicated 
Life-threatening 
consequences 
Proctitis 
Rectal discomfort 
with no intervention 
indicated 
Symptoms causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
OR Medical 
intervention 
indicated 
Symptoms causing 
inability to perform 
usual social & 
functional activities 
OR Operative 
intervention 
indicated 
Life-threatening 
consequences (e.g., 
perforation) 
Rectal Discharge 
Visible discharge 
Discharge requiring 
the use of pads 
NA 
NA 
Vomiting  
Transient or 
intermittent AND 
No or minimal 
interference with 
oral intake 
Frequent episodes 
with no or mild 
dehydration 
Persistent vomiting 
resulting in 
orthostatic 
hypotension OR 
Aggressive 
rehydration 
indicated (e.g., IV 
fluids) 
Life-threatening 
consequences (e.g., 
hypotensive shock) 
MUSCULOSKELETAL 
Arthralgia 
Joint pain causing 
no or minimal 
interference with 
usual social & 
functional activities 
Joint pain causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Joint pain causing 
inability to perform 
usual social & 
functional activities 
Disabling joint pain 
causing inability to 
perform basic 
self-care functions 
Arthritis 
Stiffness or joint 
swelling causing no 
or minimal 
interference with 
usual social & 
functional activities 
Stiffness or joint 
swelling causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Stiffness or joint 
swelling causing 
inability to perform 
usual social & 
functional activities 
Disabling joint 
stiffness or swelling 
causing inability to 
perform basic self-
care functions 
Myalgia 
(generalized) 
Muscle pain causing 
no or Minimal 
interference with 
usual social & 
functional activities 
Muscle pain causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Muscle pain causing 
inability to perform 
usual social & 
functional activities 
Disabling muscle 
pain causing 
inability to perform 
basic self-care 
functions 

ABI-4334  
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Parameter 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Potentially 
life -threatening 
Osteonecrosis 
NA 
No symptoms but 
with radiographic 
findings AND No 
operative 
intervention 
indicated 
Bone pain with 
radiographic 
findings OR 
Operative 
intervention 
indicated 
Disabling bone pain 
with radiographic 
findings causing 
inability to perform 
basic self-care 
functions 
Osteopenia6 
≥ 30 years of age 
BMD t-score 
-2.5 to -1 
NA 
NA 
NA 
< 30 years of age 
BMD z-score  
-2 to -1 
NA 
NA 
NA 
Osteoporosis6 
≥ 30 years of age 
NA 
BMD t-score < -2.5 
Pathologic fracture 
(e.g., compression 
fracture causing loss 
of vertebral height) 
Pathologic fracture 
causing 
life-threatening 
consequences 
< 30 years of age 
NA 
BMD z-score < -2 
Pathologic fracture 
(e.g., compression 
fracture causing loss 
of vertebral height) 
Pathologic fracture 
causing 
life-threatening 
consequences 
NEUROLOGIC 
Acute CNS 
Ischemia 
NA 
NA 
Transient ischemic 
attack 
Cerebral vascular 
accident (e.g., 
stroke with 
neurological deficit) 
Altered Mental 
Status 
(for Dementia, see 
Cognitive, 
Behavioral, or 
Attentional 
Disturbance below) 
Changes causing no 
or minimal 
interference with 
usual social & 
functional activities 
Mild lethargy or 
somnolence causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Confusion, memory 
impairment, 
lethargy, or 
somnolence causing 
inability to perform 
usual social & 
functional activities 
Delirium OR 
Obtundation OR 
Coma 
Ataxia 
Symptoms causing 
no or minimal 
interference with 
usual social & 
functional activities 
OR No symptoms 
with ataxia detected 
on examination 
Symptoms causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
inability to perform 
usual social & 
functional activities 
Disabling symptoms 
causing inability to 
perform basic 
self-care functions 
Cognitive, 
Behavioral, or 
Attentional 
Disturbance 
(includes dementia 
and attention deficit 
disorder) Specify 
type, if applicable 
Disability causing 
no or minimal 
interference with 
usual social & 
functional activities 
OR Specialized 
resources not 
indicated 
Disability causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
OR Specialized 
resources on 
Disability causing 
inability to perform 
usual social & 
functional activities 
OR Specialized 
resources on a 
fulltime basis 
indicated 
Disability causing 
inability to perform 
basic self-care 
functions OR 
Institutionalization 
indicated 

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Study ABI-4334-101 Original Protocol 16 June 2022  
 
Assembly Biosciences  
Confidential 
Page 84 of 95 
 
Parameter 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Potentially 
life -threatening 
parttime basis 
indicated 
Headache 
Symptoms causing 
no or minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
inability to perform 
usual social & 
functional activities 
Symptoms causing 
inability to perform 
basic self-care 
functions OR 
Hospitalization 
indicated OR 
Headache with 
significant 
impairment of 
alertness or other 
neurologic function 
Neuromuscular 
Weakness (includes 
myopathy and 
neuropathy)  
Specify type, if 
applicable 
Minimal muscle 
weakness causing 
no or minimal 
interference with 
usual social & 
functional activities 
OR No symptoms 
with decreased 
strength on 
examination 
Muscle weakness 
causing greater than 
minimal 
interference with 
usual social & 
functional activities 
Muscle weakness 
causing inability to 
perform usual social 
& functional 
activities 
Disabling muscle 
weakness causing 
inability to perform 
basic self-care 
functions OR 
Respiratory muscle 
weakness impairing 
ventilation 
Neurosensory 
Alteration (includes 
paresthesia and 
painful neuropathy) 
Specify type, if 
applicable 
Minimal paresthesia 
causing no or 
minimal 
interference with 
usual social & 
functional activities 
OR No symptoms 
with sensory 
alteration on 
examination 
Sensory alteration 
or paresthesia 
causing greater than 
minimal 
interference with 
usual social & 
functional activities 
Sensory alteration 
or paresthesia 
causing inability to 
perform usual social 
& functional 
activities 
Disabling sensory 
alteration or 
paresthesia causing 
inability to perform 
basic self-care 
functions 
Seizures New Onset 
Seizure ≥ 18 years of 
age 
NA 
NA 
1 to 3 seizures 
Prolonged and 
repetitive seizures 
(e.g., status 
epilepticus) OR 
Difficult to control 
(e.g., refractory 
epilepsy) 
Pre-existing Seizure 
NA 
Increased frequency 
from previous level 
of control without 
change in seizure 
character 
Change in seizure 
character either in 
duration or quality 
(e.g., severity or 
focality) 
Prolonged and 
repetitive seizures 
(e.g., status 
epilepticus) OR 
Difficult to control 
(e.g., refractory 
epilepsy) 

ABI-4334  
Study ABI-4334-101 Original Protocol 16 June 2022  
 
Assembly Biosciences  
Confidential 
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Parameter 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Potentially 
life -threatening 
Syncope 
Near syncope 
without loss of 
consciousness (e.g., 
pre-syncope) 
Loss of 
consciousness with 
no intervention 
indicated 
Loss of 
consciousness AND 
Hospitalization or 
intervention 
required 
NA 
PREGNANCY, PUERPERIUM, AND PERINATAL 
Stillbirth (report 
using mother’s 
participant ID) 
Report only one 
NA 
NA 
Fetal death 
occurring at 
≥ 20 weeks 
gestation 
NA 
Preterm Birth 
(report using 
mother’s participant 
ID) 
Live birth at 34 to 
< 37 weeks 
gestational age 
Live birth at 28 to 
< 34 weeks 
gestational age 
Live birth at 24 to 
< 28 weeks 
gestational age 
Live birth at 
< 24 weeks 
gestational age 
Spontaneous 
Abortion or 
Miscarriage7 (report 
using mother’s 
participant ID) 
Report only one 
Chemical pregnancy 
Uncomplicated 
spontaneous 
abortion or 
miscarriage 
Complicated 
spontaneous 
abortion or 
miscarriage 
NA 
PSYCHIATRIC 
Insomnia  
Mild difficulty 
falling asleep, 
staying asleep, or 
waking up early 
causing no or 
minimal 
interference with 
usual social & 
functional activities 
Moderate difficulty 
falling asleep, 
staying asleep, or 
waking up early 
causing more than 
minimal 
interference with 
usual social & 
functional activities 
Severe difficulty 
falling asleep, 
staying asleep, or 
waking up early 
causing inability to 
perform usual social 
& functional 
activities requiring 
intervention or 
hospitalization 
NA 
Psychiatric 
Disorders 
(includes anxiety, 
depression, mania, 
and psychosis) 
Specify disorder 
Symptoms with 
intervention not 
indicated OR 
Behavior causing no 
or minimal 
interference with 
usual social & 
functional activities 
Symptoms with 
Intervention 
indicated OR 
Behavior causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Symptoms with 
Hospitalization 
indicated OR 
Behavior causing 
inability to perform 
usual social & 
functional activities 
Threatens harm to 
self or others OR 
Acute psychosis OR 
Behavior causing 
inability to perform 
basic self-care 
functions 
Suicidal Ideation or 
Attempt 
Report only one 
Preoccupied with 
thoughts of death 
AND No wish to 
kill oneself 
Preoccupied with 
thoughts of death 
AND Wish to kill 
oneself with no 
specific plan or 
intent 
Thoughts of killing 
oneself with partial 
or complete plans 
but no attempt to do 
so OR 
Hospitalization 
indicated 
Suicide attempted 

ABI-4334  
Study ABI-4334-101 Original Protocol 16 June 2022  
 
Assembly Biosciences  
Confidential 
Page 86 of 95 
 
Parameter 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Potentially 
life -threatening 
RESPIRATORY  
Acute 
Bronchospasm 
Forced expiratory 
volume in 1 second 
or peak flow 
reduced to ≥ 70 to 
< 80% OR Mild 
symptoms with 
intervention not 
indicated 
Forced expiratory 
volume in 1 second 
or peak flow 50 to 
< 70% OR 
Symptoms with 
intervention 
indicated OR 
Symptoms causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Forced expiratory 
volume in 1 second 
or peak flow 25 to 
< 50% OR 
Symptoms causing 
inability to perform 
usual social & 
functional activities 
Forced expiratory 
volume in 1 second 
or peak flow < 25% 
OR Life-threatening 
respiratory or 
hemodynamic 
compromise OR 
Intubation 
Dyspnea or 
Respiratory Distress 
Report only one 
Dyspnea on 
exertion with no or 
minimal 
interference with 
usual social & 
functional activities 
OR Wheezing OR 
Minimal increase in 
respiratory rate for 
age 
Dyspnea on 
exertion causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
OR Nasal flaring 
OR Intercostal 
retractions OR 
Pulse oximetry 90 
to < 95% 
Dyspnea at rest 
causing inability to 
perform usual social 
& functional 
activities OR Pulse 
oximetry < 90% 
Respiratory failure 
with ventilator 
support indicated 
(e.g., CPAP, 
BPAP, intubation) 
SENSORY 
Hearing Loss 
≥ 12 years of age 
NA 
Hearing aid or 
intervention not 
indicated 
Hearing aid or 
intervention 
indicated 
Profound bilateral 
hearing loss 
(>80 dB at 2 kHz 
and above) OR 
Non-serviceable 
hearing (i.e., 
>50 dB audiogram 
and <50% speech 
discrimination) 
Tinnitus 
Symptoms causing 
no or minimal 
interference with 
usual social & 
functional activities 
with intervention 
not indicated 
Symptoms causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
with intervention 
indicated 
Symptoms causing 
inability to perform 
usual social & 
functional activities 
NA 
Uveitis 
No symptoms AND 
Detectable on 
examination 
Anterior uveitis 
with symptoms OR 
Medical 
Posterior or 
panuveitis OR 
Operative 
Disabling visual 
loss in affected 
eye(s) 

ABI-4334  
Study ABI-4334-101 Original Protocol 16 June 2022  
 
Assembly Biosciences  
Confidential 
Page 87 of 95 
 
Parameter 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Potentially 
life -threatening 
intervention 
indicated 
Intervention 
indicated 
Vertigo 
Vertigo causing no 
or minimal 
interference with 
usual social & 
functional activities 
Vertigo causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Vertigo causing 
inability to perform 
usual social & 
functional activities 
Disabling vertigo 
causing inability to 
perform basic 
self-care functions 
Visual Changes 
(assessed from 
baseline) 
Visual changes 
causing no or 
minimal 
interference with 
usual social & 
functional activities 
Visual changes 
causing greater than 
minimal 
interference with 
usual social & 
functional activities 
Visual changes 
causing inability to 
perform usual social 
& functional 
activities 
Disabling visual 
loss in affected 
eye(s) 
SYSTEMIC 
Acute Allergic 
Reaction 
Localized urticaria 
(wheals) with no 
medical intervention 
indicated 
Localized urticaria 
with intervention 
indicated OR Mild 
angioedema with no 
intervention 
indicated 
 
Generalized 
urticaria OR 
Angioedema with 
intervention 
indicated OR 
Symptoms of mild 
bronchospasm 
Acute anaphylaxis 
OR Life-threatening 
bronchospasm OR 
Laryngeal edema 
Chills  
Symptoms causing 
no or minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
inability to perform 
usual social & 
functional activities 
NA 
Cytokine Release 
Syndrome8 
Mild signs and 
symptoms AND 
Therapy (i.e., 
antibody infusion) 
interruption not 
indicated 
Therapy (i.e., 
antibody infusion) 
interruption 
indicated AND 
Responds promptly 
to symptomatic 
treatment OR 
Prophylactic 
medications 
indicated for ≤ 24 
hours 
 
Prolonged severe 
signs and symptoms 
OR Recurrence of 
symptoms following 
initial improvement 
 
Life-threatening 
consequences (e.g., 
requiring pressor or 
ventilator support) 
Fatigue or Malaise 
Report only one 
Symptoms causing 
no or minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
inability to perform 
usual social & 
functional activities 
 
Incapacitating 
symptoms of fatigue 
or malaise causing 
inability to perform 

ABI-4334  
Study ABI-4334-101 Original Protocol 16 June 2022  
 
Assembly Biosciences  
Confidential 
Page 88 of 95 
 
Parameter 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Potentially 
life -threatening 
basic self-care 
functions 
Fever (non-axillary 
temperatures only) 
38.0 to < 38.6°C or 
100.4 to < 101.5°F 
≥ 38.6 to < 39.3°C 
or ≥ 101.5 to < 
102.7°F 
≥ 39.3 to < 40.0°C 
or ≥ 102.7 to < 
104.0°F 
≥ 
40.0°C 
or 
≥ 
104.0°F 
Pain9 (not 
associated with 
study agent 
injections and not 
specified elsewhere) 
Specify location 
Pain causing no or 
minimal 
interference with 
usual social & 
functional activities 
Pain causing greater 
than minimal 
interference with 
usual social & 
functional activities 
Pain causing 
inability to perform 
usual social & 
functional activities 
Disabling pain 
causing inability to 
perform basic 
self-care functions 
OR Hospitalization 
indicated 
Serum Sickness10 
Mild signs and 
symptoms 
Moderate signs and 
symptoms AND 
Intervention 
indicated (e.g., 
antihistamines) 
Severe signs and 
symptoms AND 
Higher level 
intervention 
indicated (e.g., 
steroids or IV 
fluids) 
Life-threatening 
consequences (e.g., 
requiring pressor or 
ventilator support) 
Underweight  
> 5 to 19 years of 
age 
WHO BMI z-score 
< -1 to -2 
WHO BMI z-score 
< -2 to -3 
WHO BMI z-score 
< -3 
WHO BMI z-score 
< -3 with 
life-threatening 
consequences 
Unintentional 
Weight Loss 
(excludes 
postpartum weight 
loss) 
NA 
5 to < 9% loss in 
body weight from 
baseline 
≥ 9 to < 20% loss in 
body weight from 
baseline 
≥ 20% loss in body 
weight from 
baseline OR 
Aggressive 
intervention 
indicated (e.g., tube 
feeding, total 
parenteral nutrition) 
URINARY 
Urinary Tract 
Obstruction 
NA 
Signs or symptoms 
of urinary tract 
obstruction without 
hydronephrosis or 
renal dysfunction 
Signs or symptoms 
of urinary tract 
obstruction with 
hydronephrosis or 
renal dysfunction 
Obstruction causing 
life-threatening 
consequences 
2 
As per Bazett’s formula. 
3 
For pruritus associated with injections or infusions, see the Site Reactions to Injections and Infusions section. 
4 
Definition: A disorder characterized by fat loss in the face, extremities, and buttocks. 
5 
Definition: A disorder characterized by abnormal fat accumulation on the back of the neck, breasts, and abdomen. 
6 
BMD t and z scores can be found in: Kanis JA on behalf of the World Health Organization Scientific Group (2007). 
Assessment of osteoporosis at the primary health-care level. Technical Report. World Health Organization 
Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, UK. 2007: Printed by the University of 
Sheffield. 
7 
Definition: A pregnancy loss occurring at < 20 weeks gestational age. 
8 
Definition: A disorder characterized by nausea, headache, tachycardia, hypotension, rash, and/or shortness of breath.  

ABI-4334  
Study ABI-4334-101 Original Protocol 16 June 2022  
 
Assembly Biosciences  
Confidential 
Page 89 of 95 
 
9 
For pain associated with injections or infusions, see the Site Reactions to Injections and Infusions section. 
10 
Definition: A disorder characterized by fever, arthralgia, myalgia, skin eruptions, lymphadenopathy, marked 
discomfort, and/or dyspnea.  
 
 
LABORATORY VALUES* CHEMISTRIES  
 
Parameter 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Potentially 
life-threatening 
Acidosis 
NA 
pH ≥ 7.3 to < LLN 
pH < 7.3 without 
life-threatening 
consequences 
pH < 7.3 with 
life-threatening 
consequences 
Albumin, Low 
(g/dL; g/L) 
3.0 to < LLN  
30 to < LLN 
≥ 2.0 to < 3.0  
≥ 20 to < 30 
< 2.0 
 < 20 
NA 
Alkaline 
Phosphatase, High 
1.25 to < 2.5 x ULN 
2.5 to < 5.0 x ULN 
5.0 to < 10.0 x ULN 
≥ 10.0 x ULN 
Alkalosis 
NA 
pH > ULN to ≤ 7.5 
pH > 7.5 without 
life-threatening 
consequences 
pH > 7.5 with 
life-threatening 
consequences 
ALT or SGPT, High 
Report only one 
1.25 to < 2.5 x ULN 
2.5 to < 5.0 x ULN 
5.0 to < 10.0 x ULN 
≥ 10.0 x ULN 
Amylase 
(Pancreatic) or 
Amylase (Total), 
High  
Report only one 
1.1 to < 1.5 x ULN 
1.5 to < 3.0 x ULN 
3.0 to < 5.0 x ULN 
≥ 5.0 x ULN 
AST or SGOT, 
High Report only 
one 
1.25 to < 2.5 x ULN 
2.5 to < 5.0 x ULN 
5.0 to < 10.0 x ULN 
≥ 10.0 x ULN 
Bicarbonate, Low 
(mEq/L; mmol/L) 
16.0 to < LLN  
16.0 to < LLN 
11.0 to < 16.0  
11.0 to < 16.0 
8.0 to < 11.0  
8.0 to < 11.0 
< 8.0  
< 8.0 
Bilirubin  
Direct Bilirubin13, 
High  
> 28 days of age 
NA 
NA 
> ULN with other 
signs and symptoms 
of hepatotoxicity 
> ULN with 
life-threatening 
consequences (e.g., 
signs and symptoms 
of liver failure) 
Total Bilirubin, 
High  
> 28 days of age 
1.1 to < 1.6 x ULN 
1.6 to < 2.6 x ULN 
2.6 to < 5.0 x ULN 
≥ 5.0 x ULN 
Calcium, High 
(mg/dL; mmol/L) 
≥ 7 days of age 
10.6 to < 11.5  
2.65 to < 2.88 
11.5 to < 12.5  
2.88 to < 3.13 
12.5 to < 13.5  
3.13 to < 3.38 
≥ 13.5 
 ≥ 3.38 
Calcium (Ionized), 
High (mg/dL; 
mmol/L) 
> ULN to < 6.0  
> ULN to < 1.5 
6.0 to < 6.4  
1.5 to < 1.6 
6.4 to < 7.2  
1.6 to < 1.8 
≥ 7.2 
 ≥ 1.8 

ABI-4334  
Study ABI-4334-101 Original Protocol 16 June 2022  
 
Assembly Biosciences  
Confidential 
Page 90 of 95 
 
Parameter 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Potentially 
life-threatening 
Calcium, Low 
(mg/dL; mmol/L) 
≥ 7 days of age 
7.8 to < 8.4  
1.95 to < 2.10 
7.0 to < 7.8  
1.75 to < 1.95 
6.1 to < 7.0  
1.53 to < 1.75 
< 6.1  
< 1.53 
Calcium (Ionized), 
Low (mg/dL; 
mmol/L) 
< LLN to 4.0  
< LLN to 1.0 
3.6 to < 4.0  
0.9 to < 1.0 
3.2 to < 3.6  
0.8 to < 0.9 
< 3.2  
< 0.8 
Cardiac Troponin I, 
High 
NA 
NA 
NA 
Levels consistent 
with myocardial 
infarction or 
unstable angina as 
defined by the local 
laboratory 
Creatine Kinase, 
High 
3 to < 6 x ULN 
6 to < 10x ULN 
10 to < 20 x ULN 
≥ 20 x ULN 
Creatinine, High 
**Report only one 
1.1 to 1.3 x ULN 
> 1.3 to 1.8 x ULN 
OR Increase to 1.3 
to < 1.5 x 
participant’s 
baseline 
> 1.8 to < 3.5 x 
ULN OR Increase 
to 1.5 to < 2.0 x 
participant’s 
baseline 
≥ 3.5 x ULN OR 
Increase of ≥ 2.0 x 
participant’s 
baseline 
Creatinine 
Clearance 14 or 
eGFR, Low 
14**Report only one 
NA 
< 90 to 60 ml/min 
or ml/min/1.73 m2 
OR 10 to < 30% 
decrease from 
participant’s 
baseline 
< 60 to 30 ml/min 
or ml/min/1.73 m2 
OR 30 to < 50% 
decrease from 
participant’s 
baseline 
< 30 ml/min or 
ml/min/1.73 m2 OR 
≥ 50% decrease 
from participant’s 
baseline or dialysis 
needed 
Glucose (mg/dL; 
mmol/L) Fasting, 
High 
110 to 125  
6.11 to < 6.95 
> 125 to 250  
6.95 to < 13.89 
> 250 to 500  
13.89 to < 27.75 
≥ 500  
≥ 27.75 
Nonfasting, High 
116 to 160  
6.44 to < 8.89 
> 160 to 250  
8.89 to < 13.89 
> 250 to 500  
13.89 to < 27.75 
≥ 500 
 ≥ 27.75 
Glucose, Low 
(mg/dL; mmol/L) 
≥ 1 month of age 
55 to 64  
3.05 to <3.55 
40 to < 55  
2.22 to < 3.05 
30 to < 40  
1.67 to < 2.22 
< 30  
< 1.67 
Lactate, High 
ULN to < 2.0 x 
ULN without 
acidosis 
≥ 2.0 x ULN 
without acidosis 
Increased lactate 
with pH < 7.3 
without 
life-threatening 
consequences 
Increased lactate 
with pH < 7.3 with 
life-threatening 
consequences 
Lipase, High 
1.1 to < 1.5 x ULN 
1.5 to < 3.0 x ULN 
3.0 to < 5.0 x ULN 
≥ 5.0 x ULN 
Lipid 
Disorders 
(mg/dL; 
mmol/L) 
Cholesterol, Fasting, 
High  
≥ 18 years of age 
200 to < 240  
5.18 to < 6.19 
240 to < 300  
6.19 to < 7.77 
≥ 300  
≥ 7.77 
NA 

ABI-4334  
Study ABI-4334-101 Original Protocol 16 June 2022  
 
Assembly Biosciences  
Confidential 
Page 91 of 95 
 
Parameter 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Potentially 
life-threatening 
LDL, Fasting, High 
≥ 18 years of age 
130 to < 160  
3.37 to < 4.12 
160 to < 190 
4.12 to < 4.90 
≥ 190  
≥ 4.90 
NA 
Triglycerides, 
Fasting, High 
150 to 300  
1.71 to 3.42 
>300 to 500  
>3.42 to 5.7 
>500 to < 1,000 
>5.7 to 11.4 
> 1,000 
 > 11.4 
Magnesium15, Low 
(mEq/L; mmol/L) 
1.2 to < 1.4  
0.60 to < 0.70 
0.9 to < 1.2  
0.45 to < 0.60 
0.6 to < 0.9  
0.30 to < 0.45 
< 0.6  
< 0.30 
Phosphate, Low 
(mg/dL; mmol/L) 
> 14 years of age 
2.0 to < LLN  
0.65 to < LLN 
1.4 to < 2.0  
0.45 to < 0.65 
1.0 to < 1.4  
0.32 to < 0.45 
< 1.0  
< 0.32 
Potassium, High 
(mEq/L; mmol/L) 
5.6 to < 6.0  
5.6 to < 6.0 
6.0 to < 6.5  
6.0 to < 6.5 
6.5 to < 7.0  
6.5 to < 7.0 
≥ 7.0 
 ≥ 7.0 
Potassium, Low 
(mEq/L; mmol/L) 
3.0 to < 3.4  
3.0 to < 3.4 
2.5 to < 3.0  
2.5 to < 3.0 
2.0 to < 2.5  
2.0 to < 2.5 
< 2.0  
< 2.0 
Sodium, High 
(mEq/L; mmol/L) 
146 to < 150  
146 to < 150 
150 to < 154  
150 to < 154 
154 to < 160  
154 to < 160 
≥ 160  
≥ 160 
Sodium, Low 
(mEq/L; mmol/L) 
130 to < 135  
130 to < 135 
125 to < 130  
125 to < 130 
121 to < 125  
121 to < 125 
≤ 120  
≤ 120 
Uric Acid, High 
(mg/dL; mmol/L) 
7.5 to < 10.0  
0.45 to < 0.59 
10.0 to < 12.0  
0.59 to < 0.71 
12.0 to < 15.0  
0.71 to < 0.89 
≥ 15.0  
≥ 0.89 
HEMATOLOGY 
Absolute CD4+ 
Count, Low 
(cell/mm3; cells/L) 
> 5 years of age (not 
HIV infected) 
300 to < 400  
300 to < 400 
200 to < 300  
200 to < 300 
100 to < 200  
100 to < 200 
< 100  
< 100 
Absolute 
Lymphocyte Count, 
Low (cell/mm3; 
cells/L) > 5 years of 
age (not HIV 
infected) 
600 to < 650 
0.600 x 109 to  
< 0.650 x 109 
500 to < 600  
0.500 x 109 to  
< 0.600 x 109 
350 to < 500 
0.350 x 109 to  
< 0.500 x 109 
< 350  
< 0.350 x 109 
Absolute Neutrophil 
Count (ANC), Low 
(cells/mm3; cells/L) 
> 7 days of age 
800 to 1,000  
0.800 x 109 to 1.000 
x 109 
600 to 799  
0.600 x 109 to 0.799 
x 109 
400 to 599  
0.400 x 109 to 0.599 
x 109 
< 400  
< 0.400 x 109 
Fibrinogen, 
Decreased  
(mg/dL; g/L) 
100 to < 200  
1.00 to < 2.00 OR 
0.75 to < 1.00 x 
LLN 
75 to < 100  
0.75 to < 1.00 OR ≥ 
0.50 to < 0.75 x 
LLN 
50 to < 75  
0.50 to < 0.75 OR 
0.25 to < 0.50 x 
LLN 
< 50  
< 0.50 OR  
< 0.25 x LLN OR 
Associated with 
gross bleeding 
Hemoglobin16, Low 
(g/dL; mmol/L)17 
≥ 13 years of age 
(male only) 
10.0 to 10.9  
6.19 to 6.76 
9.0 to < 10.0  
5.57 to < 6.19 
7.0 to < 9.0  
4.34 to < 5.57 
< 7.0  
< 4.34 
≥ 13 years of age 
(female only) 
9.5 to 10.4  
5.88 to 6.48 
8.5 to < 9.5  
5.25 to < 5.88 
6.5 to < 8.5  
4.03 to < 5.25 
< 6.5  
< 4.03 

ABI-4334  
Study ABI-4334-101 Original Protocol 16 June 2022  
 
Assembly Biosciences  
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Parameter 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Potentially 
life-threatening 
INR, High (not on 
anticoagulation 
therapy) 
1.1 to < 1.5 x ULN 
1.5 to < 2.0 x ULN 
2.0 to < 3.0 x ULN 
≥ 3.0 x ULN 
Methemoglobin (% 
hemoglobin) 
5.0 to < 10.0% 
10.0 to < 15.0% 
15.0 to < 20.0% 
≥ 20.0% 
PTT, High (not on 
anticoagulation 
therapy) 
1.1 to < 1.66 x ULN 
1.66 to < 2.33 x 
ULN 
2.33 to < 3.00 x 
ULN 
≥ 3.00 x ULN 
Platelets, Decreased 
(cells/mm3; cells/L) 
100,000 to < 
125,000  
100.000 x 109 to < 
125.000 x 109 
50,000 to < 100,000 
50.000 x 109 to < 
100.000 x 109 
25,000 to < 50,000 
25.000 x 109 to < 
50.000 x 109 
< 25,000  
< 25.000 x 109 
PT, High (not on 
anticoagulation 
therapy 
1.1 to < 1.25 x ULN 
1.25 to < 1.50 x 
ULN 
1.50 to < 3.00 x 
ULN 
≥ 3.00 x ULN 
WBC, Decreased 
(cells/mm3; cells/L) 
> 7 days of age 
2,000 to 2,499 
2.000 x 109 to 2.499 
x 109 
1,500 to 1,999 
1.500 x 109 to 1.999 
x 109 
1,000 to 1,499 
1.000 x 109 to 1.499 
x 109 
< 1,000  
< 1.000 x 109 
URINALYSIS 
Glycosuria (random 
collection tested by 
dipstick) 
Trace to 1+ or ≤ 250 
mg 
2+ or ˃ 250 to  
≤ 500 mg 
> 2+ or > 500 mg  
NA 
Hematuria (not to 
be reported based 
on dipstick findings 
or on blood believed 
to be of menstrual 
origin) 
6 to < 10 RBCs per 
high power field 
≥ 10 RBCs per high 
power field 
Gross, with or 
without clots OR 
With RBC casts OR 
Intervention 
indicated 
Life-threatening 
consequences 
Proteinuria (random 
collection tested by 
dipstick) 
1+ 
2+ 
3+ or higher 
NA 
* 
Reminder: An asymptomatic abnormal laboratory finding without an accompanying AE should not be reported to 
DAIDS in an expedited time frame unless it meets protocol-specific reporting requirements. 
13 
Direct bilirubin >1.5 mg/dL in a participant < 28 days of age should be graded as grade 2, if < 10% of the total 
bilirubin. 
** 
Reminder: Choose the method that selects for the higher grade. 
14 
Use the applicable formula (ie, Cockcroft-Gault in mL/min or Schwartz, MDRD, CKD-Epi in mL/min/1.73m2). Sites 
should choose the method defined in their study and when not specified, use the method most relevant to the study 
population.  
15 
To convert a magnesium value from mg/dL to mmol/L, laboratories should multiply by 0.4114. 
16 
Male and female sex are defined as sex at birth. For transgender participants ≥13 years of age who have been on 
hormone therapy for more than 6 consecutive months, grade hemoglobin based on the gender with which they identify 
(ie, a transgender female should be graded using the female sex at birth hemoglobin laboratory values). 
17 
The most commonly used conversion factor to convert g/dL to mmol/L is 0.6206. For grading hemoglobin results 
obtained by an analytic method with a conversion factor other than 0.6206, the result must be converted to g/dL using 
appropriate conversion factor for the particular laboratory. 
 
 

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APPENDIX 
5. 
PREGNANCY 
PRECAUTIONS 
AND 
THE 
DEFINITION 
OF 
CHILDBEARING POTENTIAL AND CONTRACEPTIVE REQUIREMENTS 
Pregnancy Precautions 
The effect of ABI-4334 on pregnancy, including preclinical development and reproductive 
toxicology, has not been assessed. As such, pregnancy precautions are required and contraceptive 
requirements for female subjects of childbearing potential are described below. 
Definition of Female Subjects of Childbearing Potential  
As defined in this protocol, “women of childbearing potential” are female subjects who are 
physiologically capable of becoming pregnant. Conversely, “women of no childbearing potential” 
are defined as female subjects meeting any of the following criteria:  
• Surgically sterile (ie, through bilateral salpingectomy, bilateral oophorectomy, or 
hysterectomy) or with medically documented ovarian failure  
• Postmenopausal, defined as ≥ 54 years of age with no spontaneous menses for 
≥ 12 months without alternative medical condition   
If female subject is < 54 years of age with no spontaneous menses for ≥ 12 months without 
alternative medical condition, then follicle-stimulating hormone (FSH) levels should be consistent 
with menopause at Screening.  
Documentation to determine childbearing potential can come from the site personnel’s review of 
the subject’s medical records, medical examination, or medical history interview.   
Contraceptive Requirements 
Note that the drug-drug interaction of ABI-4334 and systemic (oral/injectable/implantable) 
hormonal contraceptives has not been assessed and so systemic hormonal contraceptives are not 
considered an effective contraceptive method for female subjects of childbearing potential for the 
purposes of this study.   
Female subjects of childbearing potential must have a negative serum pregnancy test at Screening 
and Day -1 and a negative urine pregnancy test prior to receiving the first dose of study drug on 
Day 1. Subjects will be instructed to notify the Investigator if they become pregnant at any time 
during the study, or if they become pregnant within 28 days of the last dose of study drug. 
Instructions for reporting pregnancy and pregnancy outcomes are outlined in Section 9.9 of the 
protocol.  
1) Female subjects of childbearing potential (defined above) must agree to use two effective 
contraceptive methods, or complete abstinence for the duration of the study and follow-
up.  
• Effective contraceptive methods (two are required): 

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o Male OR female condom, but not together due to increased risk of breakage 
o Intra-uterine device (hormonal or copper IUD) 
o Diaphragm or cervical cap with spermicide (where locally available).  
o Vasectomy of male partner at least 6 months prior to the first study drug 
administration 
o Bilateral tubal ligation 
•  Complete abstinence from heterosexual intercourse of reproductive potential.  
o Note: Abstinence does not require a second contraceptive method and is an 
acceptable method of contraception only if it is in line with the subject’s preferred 
and usual lifestyle. Periodic abstinence (eg, calendar, ovulation, symptothermal, 
post-ovulation methods) and withdrawal are not acceptable methods of 
contraception.  
2) Female subjects must avoid egg donation from Screening through at least 28 days after 
administration of the last dose of study drug.  All male subjects that are able to procreate 
(if their female partner is of childbearing potential) must agree to use two effective 
contraceptive methods with their female partners, or complete abstinence for the duration 
of the study and follow-up.  
• Please refer to the contraceptive requirements listed above. Note: In the case of 
female partners of male subjects, systemic hormonal birth control may be utilized. 
Male subjects must avoid sperm donation from Screening through at least 90 days after 
administration of the last dose of study drug.   
   
  
 
 

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APPENDIX 6. PROTOCOL AMENDMENT SUMMARY OF CHANGES  
Not Applicable.  

Study Title: A Phase 1, Blinded, Placebo-controlled Study of the Safety, Tolerability, 
Pharmacokinetics of Single- and Multiple-Ascending Doses of ABI-4334 in Healthy Subjects 
 
NCT Number: NCT05569941 
Date of Document: 11 May 2023 

ABI-4334-101 
Statistical Analysis Plan 
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STATISTICAL ANALYSIS PLAN 
 
Sponsor:  
Assembly Biosciences, Inc  
331 Oyster Point Blvd 
South San Francisco, CA 94030  
 
 
Protocol Number: 
ABI-4334-101  
 
 
Protocol Title: 
A Phase 1, Blinded, Placebo-controlled Study of the 
Safety, Tolerability, Pharmacokinetics of Single- and 
Multiple-Ascending Doses of ABI-4334 in Healthy 
Subjects  
 
 
Product: 
ABI-4334 
 
 
Protocol Version (Date): 
Original (16 June 2022) 
 
Indication: 
Chronic Hepatitis B Virus Infection 
 
Analysis Type: 
Final Analysis  
 
 
 
Analysis Plan Version (Date): 
Version 2.0 (11 May 2023) 
 
 
 
 
 
Analysis Plan Author: 
 
 
 
CONFIDENTIAL AND PROPRIETARY INFORMATION

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STATISTICAL ANALYSIS PLAN APPROVAL FORM 
 
Protocol Title: 
A Phase 1, Blinded, Placebo-controlled Study of the Safety, 
Tolerability, Pharmacokinetics of Single- and Multiple-
Ascending Doses of ABI-4334 in Healthy Subjects  
Protocol Number: 
ABI-4334-101 
SAP Version (Date): 
Version 2.0 (11 May 2023) 
The SAP was subject to critical review and has been approved. 
Name and Title 
Approval Signature/Date 
 
 
Assembly Biosciences 
 
 
See e-signature 
 
 
Assembly Biosciences 
 
 
See e-signature 
 
 
Assembly Biosciences 
 
 
See e-signature 
 
 
 
 

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DOCUMENT HISTORY 
Version 
Date 
(DD MMM YYYY) 
Summary of Changes 
1.0 
30 NOV 2022 
Original 
2.0 
11 MAY 2023 
Adjusted for study completion and CSR 
 
 
 

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TABLE OF CONTENTS 
DOCUMENT HISTORY .............................................................................................................................................. 3 
TABLE OF CONTENTS .............................................................................................................................................. 4 
LIST OF ABBREVIATIONS ........................................................................................................................................ 6 
1 
INTRODUCTION ................................................................................................................................................ 8 
1.1.1 
Study Objectives .................................................................................................................... 8 
1.2 
Study Design ............................................................................................................................................ 8 
1.2.1 
Part A (SAD in Healthy Subjects) .......................................................................................... 9 
1.2.2 
Part B (MAD in Healthy Subjects) ....................................................................................... 11 
1.3 
Sample Size and Power .......................................................................................................................... 12 
1.4 
Methods of Assigning Subjects to Treatment ........................................................................................ 12 
1.4.1 
Randomization ..................................................................................................................... 12 
1.4.2 
Blinding ................................................................................................................................ 12 
2 
TYPE OF PLANNED ANALYSIS .................................................................................................................... 14 
2.1 
DRC Interim Analyses ........................................................................................................................... 14 
2.2 
Final Analysis ........................................................................................................................................ 14 
3 
GENERAL CONSIDERATIONS FOR DATA ANALYSES ............................................................................ 15 
3.1 
Analysis Populations .............................................................................................................................. 15 
3.1.1 
Randomized Set.................................................................................................................... 15 
3.1.2 
Full Analysis Set .................................................................................................................. 15 
3.1.3 
Safety Analysis Set ............................................................................................................... 15 
3.1.4 
PK-Related Sets.................................................................................................................... 15 
3.2 
Subject Grouping ................................................................................................................................... 15 
3.3 
Data Handling Conventions and Transformations ................................................................................. 16 
3.4 
Missing Data and Outliers ...................................................................................................................... 16 
3.4.1 
Missing Data ........................................................................................................................ 16 
3.4.2 
Outliers ................................................................................................................................. 16 
3.5 
Analytic Definitions ............................................................................................................................... 16 
3.5.1 
Definition of Study Drug ...................................................................................................... 16 
3.5.2 
Definition of Study Period ................................................................................................... 16 
3.5.2.1 
All Cohorts Except Cohort A7 ........................................................................ 16 
3.5.2.2 
Cohort A7 ....................................................................................................... 16 
3.5.3 
Definition of Study Day ....................................................................................................... 17 
3.5.3.1 
All Cohorts Except Cohort A7 ........................................................................ 17 
3.5.3.2 
Cohort A7 ....................................................................................................... 17 
3.5.4 
Definition of Baseline .......................................................................................................... 18 
3.5.5 
Analysis Visit Windows ....................................................................................................... 18 
3.5.6 
Selection of Data in the Event of Multiple Records on Same Analysis 
Visit Day .............................................................................................................................. 18 
4 
SUBJECT DISPOSITION .................................................................................................................................. 19 
4.1 
Subject Enrollment and Disposition ....................................................................................................... 19 
4.2 
Protocol Deviations ................................................................................................................................ 19 
4.3 
Extent of Study Drug Exposure and Compliance ................................................................................... 20 
4.3.1 
Duration of Exposure to Study Drug .................................................................................... 20 
4.3.2 
Study Drug On-Treatment Compliance ................................................................................ 20 
4.4 
Meal Times and PK Sample Collection ................................................................................................. 21 
4.5 
Medical History ...................................................................................................................................... 21 

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4.6 
Demographics and Baseline Characteristics .......................................................................................... 21 
5 
SAFETY ANALYSES ........................................................................................................................................ 22 
5.1 
Adverse Events and Deaths .................................................................................................................... 22 
5.1.1 
Adverse Event Dictionary .................................................................................................... 22 
5.1.2 
Adverse Event Severity ........................................................................................................ 22 
5.1.3 
Relationship of Adverse Events to Study Drug .................................................................... 22 
5.1.4 
Serious Adverse Events ........................................................................................................ 22 
5.1.5 
Treatment-Emergent Adverse Events ................................................................................... 22 
5.1.5.1 
Definition of Treatment-Emergent Adverse Events ....................................... 22 
5.1.5.2 
Incomplete Dates ............................................................................................ 22 
5.1.6 
Summaries of Adverse Events and Deaths ........................................................................... 23 
5.2 
Laboratory Evaluations .......................................................................................................................... 24 
5.2.1 
Graded Laboratory Values ................................................................................................... 24 
5.2.1.1 
Treatment-Emergent Laboratory Abnormalities ............................................. 25 
5.2.1.2 
Summaries of Laboratory Abnormalities ........................................................ 25 
5.2.2 
Ungraded Laboratory Values ............................................................................................... 25 
5.2.3 
Summaries of Numeric Laboratory Results ......................................................................... 25 
5.2.4 
Summaries of Categorical Laboratory Results ..................................................................... 26 
5.3 
Body Weight and Vital Signs ................................................................................................................. 26 
5.4 
Prior and Concomitant Medications ....................................................................................................... 26 
5.4.1 
Prior Medications ................................................................................................................. 26 
5.4.2 
Concomitant Medications ..................................................................................................... 27 
5.5 
Electrocardiogram Results ..................................................................................................................... 28 
5.6 
Other Safety Measures ........................................................................................................................... 28 
6 
PK ANALYSES .................................................................................................................................................. 29 
7 
REFERENCES ................................................................................................................................................... 30 
8 
SOFTWARE ....................................................................................................................................................... 31 
9 
APPENDICES .................................................................................................................................................... 32 
LIST OF IN-TEXT FIGURES 
 
Figure 1. 
Overview of Study Design – Parts A & B (SAD and MAD) ................................................ 9 
Figure 2. 
Study Design Schematic – Part A (SAD in Healthy Subjects) .......................................... 10 
Figure 3. 
Study Design Schematic – Part B (MAD in Healthy Subjects) ......................................... 12 
 
 
 

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LIST OF ABBREVIATIONS 
 
AE 
adverse event 
ALT 
alanine aminotransferase 
ATC 
anatomical therapeutic chemical 
BMI 
body mass index 
CRO 
clinical research organization  
CSR 
clinical study report 
DAIDS  
Division of AIDS  
DRC 
data review committee 
ECG 
Electrocardiogram 
eCRF 
case report form 
FAS 
full analysis set 
FIH 
first-in-human 
HLGT 
high-level group term 
HLT 
high-level term 
IPD 
important protocol deviation(s) 
LLOQ 
lower limit of quantitation  
LLT 
lower-level term 
LOD 
limit of detection 
LOQ 
limit of quantitation 
MAD 
multiple ascending dose 
MedDRA 
medical dictionary for regulatory activities 
NOEL 
No observed effect level  
PBO 
Placebo 
PD 
protocol deviation(s) 
PK 
pharmacokinetics 
PKAP 
PK analysis plan  
PT 
preferred term 
Q1, Q3 
first quartile, third quartile 
QD 
once daily  
SAD 
single ascending dose 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SE 
standard error 
SOC 
system organ class 
TE 
treatment-emergent 
TEAE 
treatment-emergent adverse event 

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TFLs 
tables, figures, and listings 
WHO 
world health organization 
 
 

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1 INTRODUCTION 
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) in the clinical study report (CSR) 
for Study ABI-4334-101. This SAP is based on the original study protocol version 1.0, dated 16 
June 2022 and the electronic case report form (eCRF) version 1.0, dated 18 October 2022. The 
SAP will be finalized before database lock. Any changes made after the finalization of the SAP 
will be documented in the CSR.  
1.1.1 Study Objectives 
The primary objective is:  
 To assess the safety and tolerability of orally administered ABI-4334 in healthy subjects 
following single (Part A, single ascending dose [SAD]) and 8-day multiple (Part B, 
multiple ascending dose [MAD]) oral doses. 
The secondary objectives are: 
 To characterize the pharmacokinetics (PK) of ABI-4334 in plasma following single doses 
and 8-day multiple doses in healthy subjects.  
 To evaluate the effect of food on the PK of ABI-4334 following a single dose in healthy 
subjects (Part A food-effect cohort(s) only). 
The exploratory objectives are: 
 To evaluate the PK of ABI-4334 in urine following 8-day multiple doses in healthy 
subjects (Part B, MAD). 
 
1.2 
Study Design 
This is a Phase 1, first-in-human (FIH), randomized, blinded, placebo (PBO)-controlled, single- 
and multiple-dose, dose escalation study of ABI-4334 in healthy subjects. Part A is designed to 
assess the safety, tolerability, and PK profile of ABI-4334 following SAD in healthy subjects, as 
well as the effect of food on ABI-4334. Part B is designed to assess the safety, tolerability, and 
PK profile of ABI-4334 following MAD in healthy subjects. Figure 1Figure 1 provides an 
overview of the 2-Part study design.  

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Figure 1. 
Overview of Study Design – Parts A & B (SAD and MAD) 
Part A (SAD)
Single oral PO dose 
Healthy subjects
Per Cohort: 6 active, 2 PBO*  
Part B (MAD)
8-day multiple oral PO doses 
(QD or BID; fasted or fed)
Healthy subjects
Per Cohort: 6 active, 2 PBO  
 Cohort A1: 30 mg ABI-4334 or PBO, 
orally  fasted
 Cohort A2: TBD mg fasted
 Cohort A3: TBD mg fasted
 Cohort A4: TBD mg fasted
 Cohort A5: TBD mg fasted
 Cohort A6: Food effect cohort, TBD 
mg, fed
 Cohort A7: Food effect cohort, TBD 
mg (2-period crossover: fasted & fed) 
 Cohort B1: TBD mg 
 Cohort B2: TBD mg
DRC Review** 
 
Abbreviations: BID=twice daily; MAD=multiple ascending dose; PBO=placebo; QD=once daily; SAD=single ascending dose; 
TBD=to be determined 
*Applies to all SAD cohorts, except Cohort A7, which will only have 6 active subjects (ie, randomized to ABI-4334), no PBO 
subjects. 
**Part B dosing may commence prior to Part A being completed. 
1.2.1 Part A (SAD in Healthy Subjects) 
Part A of the study will enroll up to 5 fasted cohorts, ie, Cohorts A1-A5, and up to 2 fed cohorts 
to evaluate food effect, ie, Cohort A6 (with subjects from a previous fasted cohort), and an 
additional cohort, ie, Cohort A7, if needed (with new subjects).  
The first cohort of Part A, ie, Cohort A1, will evaluate a single dose of 30 mg ABI-4334. Dose 
levels for subsequent cohorts will be determined based on interim cohort review performed by an 
unblinded Data Review Committee (DRC) between SAD cohorts for purposes of dose 
escalation. In no case would a dose escalation be greater than 3.3-fold compared with the 
previous dose. The maximum dose of ABI-4334 to be evaluated in Part A (SAD) will not exceed 
the exposures observed in dogs at the no observed effect level (NOEL) dose of 30 mg/kg/day, or 
1000 mg/day, whichever is lower. Figure 2 provides an overview of Part A study design. 

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Figure 2. 
Study Design Schematic – Part A (SAD in Healthy Subjects) 
Screening 
(28-Day) 
Randomization
6 active; 2 PBO
 (Day 1)
Sentinel Dosing 
(N=2)
Observe for 3 days 
Dosing of Remaining Subjects 
(N=6) 
7-day follow-up visits 
(ie, Day 5-Day 7)
DRC Review 
COHORTS A1-A5
FOOD EFFECT COHORTS A6-A7
DRC Review for selection 
of a subsequent SAD dose 
or food effect cohort 
Cohort A6 
(N=8)
DRC 
Review
Cohort A7 
(N=6) 
DRC Review 
7-day washout
Discharge on 
Day 4
or
Screening 
(28-Day) 
Randomization
6 active 
 (Day 1)
 
Abbreviations: DRC=Data Review Committee; PBO=placebo; SAD=single ascending dose 
Each of the Cohorts A1-A5 will enroll 8 healthy subjects who will be randomized in a 6:2 ratio 
to receive a single oral dose of the study drug, ie, ABI-4334 (6 subjects) or PBO (2 subjects) in a 
fasted state, followed by a 7-day follow-up period. Subjects will remain confined to the study 
clinic from Days -1 to 4, with outpatient follow-up visits. Dosing of a subsequent SAD cohort 
can begin at least 8 days after dosing of the sentinel subjects from the previous cohort (see 
below).  
Because this is a FIH study, a sentinel dosing approach will be utilized for each Cohort A1-A5, 
where initially only 2 subjects per cohort will be dosed (one receiving ABI-4334 and one 
receiving PBO). These sentinel subjects will be observed for a minimum of 3 days postdose to 
ensure acceptable tolerability of the study drug, as determined by the DRC, before dosing of the 
remaining subjects within the cohort can proceed.  
The DRC will select a single dose level from Cohorts A1-A5 for evaluation of food effect. The 
selection of this dose level can be made prior to completion of all fasted SAD cohorts and will be 
based on a preliminary evaluation by the DRC of the available safety, tolerability, and PK data 
from selected Cohorts A1-A5. Subjects who complete participation in this selected cohort will be 
asked to return to the study site to be enrolled into the food-effect cohort (ie, Cohort A6), 
following a minimum of 7-day washout period since their last study drug dose. While Baseline 
evaluations will be conducted prior to dosing in Cohort A6, repeat assessment of all study 
eligibility criteria will not be performed. Returning subjects will retain their original subject 
number and randomized treatment assignment. After the Day 7 visit in the original cohort (from 
Cohort A1-A5), the study drug will be administered 30 minutes after the complete consumption 
of a high fat meal (approximately 50% calories from fat). 
If there is an insufficient number of subjects from previous fasted SAD cohorts (ie, A1-A5), who 
are willing to participate in Cohort A6, then a separate Cohort A7 may be enrolled, comprising 6 
new subjects meeting the study eligibility criteria, who will all receive ABI-4334. Cohort A7 will 

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involve a two-period crossover assessment of food effect (ie, Period 1: dosing under fasted or 
high fat-fed conditions; Period 2: dosing under condition opposite of Period 1), with a minimum 
7-day washout period between dosing in Period 1 and Period 2, and a 7-day postdose follow-up 
in Period 2.  
1.2.2 Part B (MAD in Healthy Subjects) 
Part B dosing may commence prior to Part A being completed. The dose level and dosing 
schedule for the first cohort of Part B, ie, Cohort B1, will be determined based on emergent 
safety, tolerability, and PK data from completed Part A cohorts, with the daily dose at least 2-
fold lower than a Part A dose level deemed safe and tolerable.  
Both cohorts planned for Part B, ie, Cohort B1 and Cohort B2, will enroll 8 healthy subjects who 
will be randomized in a 6:2 ratio to receive oral daily doses of the study drug, ie, ABI-4334 (6 
subjects) or PBO (2 subjects), for 8 consecutive days, followed by a 7-day follow-up period. 
Dosing may occur under fasted or fed conditions, depending on the results from the food-effect 
cohort(s) in Part A. Subjects will remain confined to the study site from Days -1 to Day 11 (ie, 3 
days post last day of dosing), with outpatient follow-up visits.  
The dose level and dosing schedule for Cohort B2 will be based on an evaluation by the DRC of 
safety data from Day 1 through Day 8 for Cohort B1 and all available safety data for preceding 
cohorts. In addition, PK data through 24 hours after dosing on Day 8 for Cohort B1 and available 
PK data for preceding cohorts will be reviewed. In no case would the dose escalation be greater 
than 3.3-fold compared with the previous dose. Dosing of Cohort B2 can begin at least 11 days 
after the first day dosing of subjects in Cohort B1. The maximum dose of ABI-4334 to be 
evaluated in Part B (MAD) will not exceed the exposures observed in dogs at the NOEL dose of 
30 mg/kg/day, or 1000 mg/day, whichever is lower. Figure 3 provides an overview of Part B 
study design. 

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Figure 3. 
Study Design Schematic – Part B (MAD in Healthy Subjects) 
Screening (28-Day) 
Dosing (Days 1 through 8)
7-Day Follow-up visit (ie, Day 15)
DRC 
Review   
Randomization (Day 1)
6 active, 2 PBO
Discharge on Day 11
COHORTS B1-B2
 
Abbreviations: DRC=Data Review Committee; PBO=placebo  
1.3 
Sample Size and Power 
Approximately 8 healthy subjects will be enrolled in each cohort. Approximately 6 subjects will 
be enrolled in Cohort 7 of Part A if necessary. For this FIH study, the sample sizes are similar to 
those previously utilized for this type of study and are not based on statistical considerations. 
1.4 
Methods of Assigning Subjects to Treatment 
1.4.1 Randomization 
For cohorts A1-A4 and B1-B2, all subjects will be assigned a unique subject number at 
Screening and will be randomized to treatment with either ABI-4334 or placebo, upon meeting 
all protocol eligibility requirements. Randomization will be performed by an unblinded 
pharmacist. Subjects returning as part of cohort A6 will retain their original subject number and 
randomized treatment assignment.  
Subjects in cohort A7 will take only ABI-4334. Subjects will be randomized, with 3 subjects 
being fed then fasted, and 3 subjects fasted then fed, in each of the two periods.  
1.4.2 Blinding 
Except for DRC members, unblinded site pharmacists, and other personnel administering 
treatment randomization, all study team members will be blinded to individual subject treatment 
assignments for cohorts A1-A4 and cohorts B1-B2 throughout the duration of the study. The 

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study subjects will also be blinded to their treatment assignment throughout the duration of the 
study.  
The DRC will be unblinded to individual subjects’ treatment assignments throughout the study to 
ensure timely analysis of any emergent safety and tolerability issues, and completion of the 
prespecified safety and PK data reviews. The unblinded individuals will be identified in the DRC 
charter along with their specific roles and responsibilities. The clinical research organization’s 
(CRO) Medical Monitor may be unblinded to individual subjects’ treatment assignments where 
required for assessment of emergent safety/tolerability issues. 
 

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2 TYPE OF PLANNED ANALYSIS 
2.1 
DRC Interim Analyses 
The DRC will review the cumulative safety and PK data from each previous cohort to determine 
dose level and dosing schedule for the subsequent cohort(s). Details concerning the DRC will be 
documented in the DRC charter. 
 
2.2 
Final Analysis 
The final analysis will be performed after all subjects have completed the study, outstanding data 
queries have been resolved or adjudicated as unresolvable, and the data have been cleaned and 
finalized.   

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3 GENERAL CONSIDERATIONS FOR DATA ANALYSES 
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of subjects in each category will be presented; for continuous variables, 
the number of subjects (n), mean, standard deviation (SD) or standard error (SE), median, first 
quartile (Q1), third quartile (Q3), minimum, and maximum will be presented. 
Summary tables will be presented by cohort and treatment. For cohort A7, summary tables will 
be presented fasting order (i.e. “fed,fasted” or “fasted,fed”).  
No formal inference is planned in this study. Hence, no multiplicity adjustment is required. 
3.1 
Analysis Populations 
Analysis populations or sets define the subjects to be included in an analysis. Analysis sets and 
their definitions are provided in this section. The analysis set will be identified and included as a 
subtitle of each table, figure, and listing. For each analysis set, the number and percentage of 
subjects eligible for inclusion will be summarized by treatment and cohort. A listing of reasons 
for exclusion from analysis sets will be provided by cohort and subject. 
3.1.1 Randomized Set 
Randomized Set includes all randomized subjects, classified according to the treatment to which 
they were randomized, regardless of the actual treatment received.  
3.1.2 Full Analysis Set 
The Full Analysis Set (FAS) includes all randomized subjects, classified according to the 
treatment to which they were randomized, regardless of the actual treatment received, who took 
at least 1 dose of study drug.  
3.1.3 Safety Analysis Set 
The Safety Analysis Set includes all randomized subjects, classified according to the actual 
treatment received regardless of randomized assignment, who took at least 1 dose of study drug. 
This is the main analysis set for all safety analyses. 
3.1.4 PK-Related Sets 
PK-related sets will be described in a separate PK analysis plan (PKAP). 
3.2 
Subject Grouping 
For analyses based on the Randomized Set and FAS, subjects will be grouped according to the 
treatment to which they were randomized, regardless of actual treatment received. For analyses 
based on the Safety Analysis Set, subjects will be grouped according to the actual treatment 

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received, regardless of random assignment. The actual treatment received will differ from the 
randomized treatment only when the actual treatment differs from randomized treatment for the 
entire treatment duration. 
3.3 
Data Handling Conventions and Transformations 
Subject age, collected at the Screening visit, will be used for analyses and will be presented in 
listings. 
Total bilirubin values entered as < 0.2 mg/dL will be analyzed as 0.1 mg/dL; direct bilirubin 
values entered as < 0.1 mg/dL will be analyzed as 0.05 mg/dL (according to the methods of 
Nehls and Akland, 1973).  
3.4 
Missing Data and Outliers 
3.4.1 Missing Data 
In general, missing data will not be imputed unless methods for handling missing data are 
specified. Exceptions are presented in this document. 
For missing last dose date of study drug, imputation rules are described in Section 4.3.1. The 
handling of missing or incomplete dates for adverse event (AE) onset is described in Section 
5.1.5.2, and for prior and concomitant medications in Section 5.3. 
3.4.2 Outliers 
Outliers will be identified during the data management review process. No sensitivity analyses 
will be conducted. All data will be included in the data analysis. 
3.5 
Analytic Definitions 
3.5.1 Definition of Study Drug 
The study drugs in this study are ABI-4334 and PBO. 
3.5.2 Definition of Study Phase  
3.5.2.1 All Cohorts Except Cohort A7  
The following periods will be defined for all cohorts except cohort A7:  
 On-Treatment Period: From first dose date/time through last dose date/time. 
 Follow-Up Period: From last dose date/time +1 through end of study. 
3.5.2.2 Cohort A7  
The following periods will be defined for cohort A7:  

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 On-Treatment Period 1: Period 1 dose date 
 Follow-Up Period 1: From Period 1 dose date +1 until Period 2 dose date. 
 On-Treatment Period 2: Period 2 dose date. 
 Follow-Up Period 2: From period 2 dose date +1 through end of study. 
For each subject, end of study will be defined as completion of the last follow-up visit or premature 
study termination, or subject is lost-to-follow-up.  
 
The study will end when the last subject completes the last visit of the follow-up period or is 
considered “lost to follow-up,” whichever is later.  
 
3.5.3 Definition of Study Day 
The first dose date of study drug will be calculated where applicable. The last dose date of study 
drug will be calculated where applicable. The last dose date of study drug will be the end date on 
study drug administration eCRF. 
3.5.3.1 All Cohorts Except Cohort A7  
Study Day 1 is defined as the first dose date of study drug. If the first dose date is missing, the 
date of randomization will be used. 
For the On-Treatment Period, study days will be calculated from Study Day 1 and derived as 
follows: 
 For days prior to the first dose: Assessment Date – Study Day 1. 
 For postdose study days: Assessment Date – Study Day 1 + 1. 
For the Follow-Up Period, the Follow-Up Study Day 1 will be defined as the day after the last 
dose date of study drug and the follow-up study day will be calculated from the last dose date 
and derived as Assessment Date − Last Dose Date of study drug. 
3.5.3.2 Cohort A7  
Period 1 Study Day 1 is defined as the period 1 dose date of study drug. Period 2 Study Day 1 is 
defined as the period 2 dose date of study drug. 
Study days will be calculated for each study period.  
In On-Treatment Period 1, for days prior to the first dose, Period 1 study days will be derived as 
Assessment Date – Period 1 Study Day 1. 

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For the Follow-Up Period 1, the Follow-Up Period 1 Study Day 1 will be defined as the day after 
the Period 1 study drug dose date and Follow-Up Period 1 study days will be calculated from 
Follow-Up Period 1 Study Day 1 and derived as Assessment Date − Follow-Up Period 1 Study 
Day 1 + 1. Follow-Up Period 2 will be treated similarly. 
3.5.4 Definition of Baseline  
For all analyses, Baseline will be defined as the last non-missing evaluation prior to the first dose 
date/time. For cohort A7, Period 2 Baseline will be defined as last non-missing evaluation prior to 
the dosing on Period 2 Study Day 1.  
 
For all cohorts, except cohort A7 Period 2, Change from Baseline will be defined as the result at 
desired timepoint minus the result at Baseline. For cohort A7 Period 2, Change from Baseline will 
be defined as the result at desired timepoint minus the result at Period 2 Baseline. 
 
3.5.5 Analysis Visit Windows  
Analysis visit windowing will not be used for this study. Nominal scheduled study visits will be 
used as analysis visits. Unscheduled visits and premature termination visits that occur on or in 
place of a scheduled study visit will be mapped to the same analysis visit as the scheduled study 
visit. 
3.5.6 Selection of Data in the Event of Multiple Records on Same Analysis Visit Day 
Depending on the statistical analysis method, single values may be required for each analysis 
visit day. If a single value is needed, but multiple valid, nonmissing measurements exist in an 
analysis visit day, records will be chosen based on the following: 
 For Baseline, the last nonmissing value on or prior to the first dose date of study drug will be 
selected, unless specified differently. If there are multiple records with the same time or no 
time recorded on the same day, the record with the lowest accession number will be used. 
 For post-Baseline values, the latest record will be selected. If there is more than 1 record with 
sample collected on the same day with the same time, the retest record will be selected. If 
there is no clear indication for which record is the retest record, then the record with the 
lowest accession number will be used. 

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4 SUBJECT DISPOSITION 
4.1 
Subject Enrollment and Disposition 
A summary of subject enrollment will be provided by treatment and cohort. The summary will 
present the number and percentage of subjects enrolled. For each column, the denominator for 
the percentage calculation will be the total number of subjects analyzed for that column. 
The randomization schedule used for the study will be provided as an appendix to the CSR.  
A summary of subject disposition will be provided by treatment and cohort. This summary will 
present the number of subjects in each of the categories listed below: 
 Randomized Set 
 Full Analysis Set   
 Safety Analysis Set   
The number and percentage of the subjects in the following categories will be summarized using 
the Safety Analysis Set: 
 Completed study drug  
 Did not complete study drug and reasons for study drug discontinuation  
 Completed study  
 Did not complete the study and reasons for study discontinuation  
For the status of study drug and study completion and reasons for discontinuation, the number 
and percentage of subjects in each category will be provided. The denominator for the 
percentage calculation will be the total number of subjects in the Safety Analysis Set 
corresponding to that column.   
The following by-subject listings will be provided by cohort and subject number in ascending 
order: 
 Reasons for premature study drug or study discontinuation. 
4.2 
Protocol Deviations  
Subjects who did not meet the eligibility criteria for study entry but enrolled in the study will be 
summarized. The number and percentage of subjects who did not meet at least 1 eligibility 
criterion will be provided by treatment and cohort for each specific criteria based on the 
Randomized Set. A by-subject listing will be provided for those subjects who did not meet at least 

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1 eligibility (inclusion or exclusion) criterion. The listing will present the eligibility criterion (or 
criteria if more than 1 deviation) that subjects did not meet and related comments, if collected. 
Protocol deviations (PDs) occurring after subjects entered the study are documented during 
routine monitoring. The number and percentage of subjects with important PDs (IPDs) by 
deviation category will be summarized by treatment and cohort for the Randomized Set. A by-
subject listing will be provided for those subjects with any PDs. 
A table will be provided to summarize any COVID-19 related PDs with the deviation reason by 
treatment and cohort. A listing of subjects who had study disruption due to COVID-19 will be 
provided with a description.  
4.3 
Extent of Study Drug Exposure and Compliance 
Extent of exposure to study drug will be examined by assessing the total duration of exposure to 
study drug and the level of compliance relative to the study drug regimen specified in the 
protocol. Summary tables will be provided. 
4.3.1 Duration of Exposure to Study Drug 
Total duration of exposure to study drug will be summarized. Total duration of exposure will be 
defined as the last dose date of study drug minus the first dose date plus 1. If the last study drug 
dose date is missing, the latest date among the study drug end date, clinical visit date, laboratory 
sample collection date, and vital signs assessment date that occurred during the On-Treatment 
Period will be used for subjects included in the final analyses or the last available date in the 
database snapshot for subjects who were still on treatment at the time of an interim analysis.  
The total duration of exposure to study drug will be summarized using descriptive statistics. 
Summaries will be provided by treatment and cohort for the Safety Analysis Set. The expected 
total duration of exposure is 1 day for subjects in Part A and 8 days for subjects in Part B.  
4.3.2 Study Drug On-Treatment Compliance  
The level of on-treatment compliance to the study drug will be determined by the total amount of 
study drug administered relative to the total amount of study drug expected to be administered 
during a subject’s actual on-treatment period. 
The level of on-treatment compliance for each study drug will be expressed as a percentage 
using the following formula: 
On-Treatment Compliance (%) = (
Total Amount of Study Drug Administered
Total Amount of Study Drug Expected to be Administered on Treatment)  x 100 
For subjects that prematurely discontinue, the denominator will be the total amount of study drug 
expected to be administered on treatment by the date of premature discontinuation.  

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Descriptive statistics for the level of on-treatment compliance with the number and percentage of 
subjects belonging to compliance categories (e.g. ≤ 80%, > 80- 90%, and ≥ 90%) will be 
provided by treatment and cohort for the Safety Analysis Set.  
A by-subject listing of study drug administration will be provided by cohort and subject number 
in ascending order and visit in chronological order. 
4.4 
Meal Times and PK Sample Collection  
Meal time information is collected in eCRF and will be listed for each subject. Listing will include 
date, start time, stop time, and percent of meal consumed. 
PK plasma sample collection data is collected in eCRF and will be listed for each subject. Listing 
will include collection date/time, time of collection relative to dosing, and deviation from nominal 
sample time. 
PK urine sample collection data is collected in eCRF and will be listed for each subject. Listing 
will include collection date/time, interval of collection relative to dosing, and total volume 
collected. 
4.5 
Medical History 
Medical history collected at screening will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) Version (v) 25.1. 
Medical history will be summarized by preferred term (PT), treatment, and cohort. Subjects who 
report 2 or more medical history items that are coded to the same PT will be counted only once 
by the unique coded term in the summary. The summary will be provided for the Safety Analysis 
Set.  
A by-subject listing of medical history will be provided by cohort and subject number in 
ascending order. 
4.6 
Demographics and Baseline Characteristics 
Subject demographic variables (ie, age, sex, race, and ethnicity), Baseline characteristics (body 
weight [in kg], height [in m], and body mass index [BMI; in kg/m2]) will be summarized by 
treatment and cohort using descriptive statistics for continuous variables and using number and 
percentage of subjects for categorical variables. The summary of demographic data will be 
provided for the Safety Analysis Set. 
A by-subject demographic listing, including the informed consent date, will be provided by 
cohort and subject number in ascending order. 

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5 SAFETY ANALYSES 
5.1 
Adverse Events and Deaths 
5.1.1 Adverse Event Dictionary 
Clinical and laboratory adverse events (AEs) will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA) Version (v) 25.1. System organ class (SOC), high-level group 
term (HLGT), high-level term (HLT), preferred term (PT), and lower-level term (LLT) will be 
provided in the AE dataset. 
 
5.1.2 Adverse Event Severity 
Adverse events are graded by the Investigator as Grade 1, 2, 3, or 4 according to the toxicity 
criteria specified in the protocol. The severity grade of events for which the investigator did not 
record severity will be categorized as “missing” for tabular summaries and data listings. The 
missing category will be listed last in summary presentation. 
5.1.3 Relationship of Adverse Events to Study Drug 
Related AEs are those for which the investigator selected “Related” on the AE CRF to the 
question of “Relationship to Study Treatment” based on the his/her clinical assessment. Events 
for which the investigator did not record relationship to an applicable study drug will be 
considered related to study drug for summary purposes. However, by-subject data listings will 
show the relationship as missing. 
5.1.4 Serious Adverse Events 
Serious adverse events (SAEs) will be identified and captured as SAEs if the AEs met protocol-
specified definitions of a SAE.  
5.1.5 Treatment-Emergent Adverse Events  
5.1.5.1 Definition of Treatment-Emergent Adverse Events 
A treatment-emergent adverse event (TEAE) will be defined as any AE that has an onset 
date/time or worsening in severity from Baseline on or after the first dose date/time of study drug 
through end of study. 
 
5.1.5.2 Incomplete Dates 
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dose date of 
any study drug, then the month and year (or year alone if month is not recorded) of onset 
determine whether an AE is treatment emergent. The event is considered treatment emergent if 
both of the following 2 criteria are met: 

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 The AE onset is the same as or after the month and year (or year) of the first dose date of 
study drug, and 
 The AE onset date is the same as or before the month and year (or year) of the end of study.  
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date later than the first dose date of study drug, will be considered to be treatment emergent. In 
addition, an AE with the onset date missing and incomplete stop date with the same or later 
month and year (or year alone if month is not recorded) as the first dose date of any study drug 
will be considered treatment emergent. 
5.1.6 Summaries of Adverse Events and Deaths 
Treatment-emergent AEs will be summarized based on the Safety Analysis Set. 
A brief, high-level summary of the number and percentage of subjects who experienced at least 1 
TEAE in the categories described below will be provided by treatment and cohort. All deaths 
observed in the study will also be included in this summary. The number and percentage of 
subjects will be provided by SOC, PT, treatment, and cohort for each AE category and also by 
PT only in descending order of total frequency: 
 TEAEs  
 TEAEs by severity grade  
 TEAEs related to study drug  
 TE SAEs 
 TE SAEs related to study drug 
 TEAEs leading to study drug discontinuation 
 TEAEs leading to study discontinuation 
 TEAEs leading to death (ie, outcome of death) 
 COVID-19 specific TEAEs 
 COVID-19 specific TE SAEs 
Multiple events will be counted only once per subject in each summary. Adverse events will be 
summarized and listed first in alphabetic order of SOC, and then by PT in descending order of 
total frequency within each SOC. For summary by severity grade, the most severe non-missing 
grade will be used for those AEs that occurred more than once in an individual subject during the 
study.  

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Data listings will be provided for the following: 
 All AEs 
 All treatment-related AEs 
 All SAEs 
 All treatment-related SAEs 
 All AEs with severity of Grade 3 or higher 
 All AEs leading to discontinuation of study drug  
 All AEs leading to discontinuation of study  
 All AEs leading to death (ie, outcome of death) 
 All Deaths 
5.2 
Laboratory Evaluations 
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods based on the Safety Analysis Set. The lab values that are 
below LLOQ or above the upper LOQ will be listed as such, and the closest imputed value will 
be used for the purpose of calculating summary statistics as specified in Section 3.3.  
A by-subject listing for laboratory test results will be provided by cohort, subject number, and 
visit in chronological order for hematology, serum chemistry, coagulation and urinalysis 
separately. Values falling outside of the relevant reference range and/or having a United States 
National Institutes of Health Division of AIDS (DAIDS) severity grade of 1 or higher will be 
flagged in the data listings, as appropriate. 
 
5.2.1 Graded Laboratory Values 
The criteria specified in the study protocol will be used to grade laboratory results as normal (no 
grade), mild (Grade 1), moderate (Grade 2), severe (Grade 3) or potentially life threatening 
(Grade 4). See Appendix 4 of the protocol for detailed DAIDS grading criteria on the relevant 
laboratory tests. For laboratory tests with criteria for both increased and decreased levels, 
analyses for each direction (ie, increased, decreased) will be presented separately. 
Some lab tests require fasting to be graded (i.e. triglycerides and cholesterol). For those lab tests, 
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5.2.1.1 Treatment-Emergent Laboratory Abnormalities 
Treatment-emergent laboratory abnormalities will be defined as values that increase at least 
1 toxicity grade from Baseline at any post-Baseline time point. If the relevant Baseline 
laboratory value is missing, any abnormality of at least Grade 1 observed within the time frame 
specified above will be considered treatment emergent. 
5.2.1.2 Summaries of Laboratory Abnormalities 
Treatment-emergent graded laboratory abnormalities will be summarized (number and 
percentage of subjects) by cohort, lab test, and treatment group; subjects will be categorized 
according to the most severe post-baseline abnormality grade for a given lab test. 
For all summaries of laboratory abnormalities, the denominator is the number of subjects with 
nonmissing post-Baseline values.  
The maximum post-Baseline grade observed will be tabulated for each laboratory test, and 
percentages will be based on the number of subjects with a post-Baseline evaluation of the 
specific laboratory test. A by-subject listing of graded laboratory abnormalities will be provided 
by cohort, subject number, and visit in chronological order. This listing will include all test 
results that were collected throughout the study for the lab test of interest, with all applicable 
severity grades displayed. 
5.2.2 Ungraded Laboratory Values 
Treatment-emergent abnormal direct bilirubin will be summarized by cohort and treatment 
group. A treatment-emergent abnormal direct bilirubin record is defined as a record with value > 
baseline and >=ULN. The highest direct bilirubin measurement will be counted for each subject. 
A by-subject listing of visits with abnormal direct bilirubin will be provided. 
5.2.3 Summaries of Numeric Laboratory Results 
Descriptive statistics will be provided by treatment and cohort for each laboratory test specified 
in the study protocol as follows: 
 Baseline values 
 Values at each post-Baseline visit 
 Change from Baseline at each post-Baseline visit 
A Baseline laboratory value will be defined as the last measurement obtained on or prior to the 
date/time of first dose of study drug. Change from Baseline to a post-Baseline visit will be 
calculated for any post-Baseline visit including follow-up visits. For Cohort A7 Period 2, Period 
2 Baseline and Change from Period 2 Baseline will be used instead.  

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In the case of multiple values in a visit day, data will be selected for analysis as described in 
Section 3.5.6. 
5.2.4 Summaries of Categorical Laboratory Results 
For categorical urinalysis parameters, the number and percentage of subjects in each category 
will be presented by treatment and cohort at each visit. 
5.3 
Body Weight and Vital Signs 
Descriptive statistics will be provided by treatment and cohort for body weight, BMI, and vital 
signs (systolic and diastolic blood pressure [mmHg], pulse [beats/min], respiration [breaths/min], 
and body temperature [oC]) as follows: 
 Baseline value 
 Values at each post-Baseline visit 
 Change from baseline at each post-Baseline visit 
A Baseline value will be defined as the last available value collected on or prior to the date/time 
of first dose of study drug. Change from Baseline to a post-Baseline visit will be calculated for 
any post-Baseline visit including follow-up visits. 
For Cohort A7 Period 2, Period 2 Baseline and Change from Period 2 Baseline will be used 
instead.  
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.5.6.   
A by-subject listing of vital signs will be provided by cohort, subject number, and visit in 
chronological order. In the same manner, a by-subject listing of body weight, height, and BMI 
will be provided separately. 
5.4 
Prior and Concomitant Medications 
Medications collected at Screening and during the study will be coded using the current version 
of the World Health Organization (WHO) Drug dictionary (WHO Drug Global 1SEP2022). 
5.4.1 Prior Medications 
Prior medications will be defined as any medications taken before a subject took the first study 
drug. Prior medications will be summarized by Anatomical Therapeutic Chemical (ATC) drug 
class Level 2 and preferred name using the number and percentage of subjects for each treatment 
and cohort. A subject reporting the same medication more than once will be counted only once 
within each ATC drug class. The summary will be ordered alphabetically by ATC medical class 

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and then by preferred term in order of descending overall frequency within each ATC medical 
class. For drugs with the same frequency, sorting will be done alphabetically. 
A medication will be considered as a prior medication if it meets one of the following criteria: 
 A medication with a start date prior to the first dose date of study drug will be included in 
the prior medication summary regardless of when the stop date is.  
 If a partial start date is entered, the medication will be considered prior unless the month 
and year (if day is missing) or year (if day and month are missing) of the start date are 
after the first dose date.  
 A medication with a completely missing start date will be included in the prior 
medication summary, unless otherwise specified. 
Summaries will be based on the Safety Analysis Set.  
5.4.2 Concomitant Medications 
Concomitant medications will be defined as any prescription or over-the-counter preparation, 
including vitamins, medications, vaccinations, herbal preparations, and supplements (including 
traditional Chinese medicine) taken by a subject during the study. Use of concomitant 
medications will be summarized by ATC drug class Level 2 and preferred name using the 
number and percentage of subjects for each treatment and cohort. A subject reporting the same 
medication more than once within each ATC drug class will be counted only once when 
calculating the number and percentage of subjects who received that medication. Medications 
may appear under multiple ATC drug classes. The summary will be ordered alphabetically by 
ATC medical class and then by preferred term in descending overall frequency within each ATC 
medical class. For drugs with the same frequency, sorting will be done alphabetically. 
A medication will be considered as a concomitant medication if it meets one of the following 
criteria: 
 A medication with a start date prior to or on the first dose date of study drug, and 
continued to be taken after the first dose date.  
 A medication started after the first dose date but prior to or on the last dose date of study 
drug.  
 If a partial start date is entered, any medication with the month and year (if day is 
missing) or year (if day and month are missing) before the study drug stop date, and with 
the stop date after the first dose date of study drug. If a partial stop date is entered, any 
medication with the month and year (if day is missing) or year (if day and month are 
missing) after the first dose date of study drug. 

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 A medication started and stopped on the same day as the first dose date or the last dose 
date of study drug. 
 Medications with completely missing start and stop dates, unless otherwise specified. 
A medication with a stop date prior to the date of first dose date of study drug or a start date after 
the last dose date of study drug will be excluded from the summary.  
Summaries of prior and concomitant medications will be based on the Safety Analysis Set.   
All the prior and concomitant medications will be provided in a by-subject listing sorted by 
cohort, subject number, and administration date in chronological order. 
5.5 
Electrocardiogram Results 
A shift table of the Investigators’ assessment of electrocardiogram (ECG) results at each visit 
compared with Baseline values will be presented by treatment and cohort using the following 
categories:  
 normal 
 abnormal (not clinically significant)  
 abnormal (clinically significant)  
 missing/not done 
The number and percentage of subjects in each cross-classification group of the shift table will 
be presented. Subjects with a missing value at Baseline or post-Baseline will not be included in 
the denominator for percentage calculation.  
A by-subject listing for ECG assessment results will be provided by cohort, subject number, and 
visit in chronological order. 
5.6 
Other Safety Measures 
Pregnancy test results, alcohol test results, and urine drug test results will be listed by cohort and 
subject number. 

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6 PK ANALYSES 
Analysis of PK data will be performed for the interim DRC reviews and at the end of the study 
and will be outlined in a separate PKAP. 
 

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7 REFERENCES 
Nehls G, Akland G. Procedures for Handling Aerometric Data. Journal of the Air Pollution 
Control Association 1973;23 (3):180-4. 
 

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8 SOFTWARE 
SAS® Software Version 9.4. SAS Institute Inc., Cary, NC, USA. 

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9 APPENDICES 
None. 
 

Signature Page for VV-TMF-57312 v2.0
Signature Page for VV-TMF-57312 v2.0
Reason for signing: Approved
Date of signature: 11-May-2023 20:25:14 GMT+0000
Reason for signing: Approved
Date of signature: 11-May-2023 23:56:43 GMT+0000
Reason for signing: Approved
Date of signature: 12-May-2023 16:30:09 GMT+0000