Clinical trial NCT04465916
Conditions: Hepatitis B, Chronic
Sponsor: Enyo Pharma
Start date: 2020-05-12; Completion date: 2021-11-25
Enrollment: 26 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a prospective, multi-centre, randomized, double-blind, placebo-controlled, Phase 2a experimental study of oral FXR modulator EYP001a/placebo combined with NAs in virologically suppressed CHB patients to improve functional cure rates.

Detailed description:
A total of 49 eligible patients will be enrolled and randomized at approximately 14 study sites. Patients will be randomized prior to study drug (EYP001a or placebo and NA) administration on Day 1 in the ratio of 3:1 into 2 arms:

* Experimental Arm: EYP001a Dose A QD + NA daily (37 patients)
* Control Arm: Placebo + NA daily (12 patients)

The maximum total engagement duration for eligible patients in this study is up to 370 days: 90 days screening, 112 days (16 weeks) treatment period and 168 days (24 weeks) follow-up.

Patients enrolled in the study will be assessed as outpatients. Patient screening will occur no more than 90 days prior to the Day 1 visit. Eligible patients will undergo further assessments on Day 1 to qualify for study drug administration on Day 1.

The visits during the study are planned as below:

* Screening visit: 12 weeks (90 days)
* 16 weeks treatment period:
* Treatment Visit 1 (Week 1 \[Day 1\])
* Treatment Visit 2 (Week 2 \[Day 14 ±3 days\])
* Treatment Visit 3 (Week 4 \[Day 28 ±3 days\])
* Treatment Visit 4 (Week 6 \[Day 42 ±3 days\])
* Treatment Visit 5 (Week 8 \[Day 56 ±3 days\])
* Treatment Visit 6 (Week 10 \[Day 70 ± 3 days\])
* Treatment Visit 7 (Week 12 \[Day 84 ± 3 days\])
* Treatment Visit 8 (Week 14 \[Day 98 ± 3 days\])
* Treatment Visit 9 (Week 16 \[Day 112±3 days\])
* 24 weeks safety follow-up period:
* Follow-up Visit 1 (Week 20 \[Day 140 ±7 days\])
* Follow-up Visit 2 (Week 28 \[Day 196 ±7 days\])
* Follow-up Visit 3 (Week 40 \[Day 280 ±7 days\]) Note: during follow-up patients are kept on NA until the end of the trial: Week 40 (consolidation Phase).

Arms: arm 1: Experimental Arm: EYP001a Dose A QD + NA daily (37 patients) arm 2: Control Arm: Placebo + NA daily (12 patients)
Interventions: intervention 1: EYP001a intervention 2: Placebo intervention 3: Nucleotide analogue (Entecavir or Tenofovir Disoproxil)
Intervention descriptions: intervention 1: Oral tablets intervention 2: Oral tablets intervention 3: Oral tablets

Protocol documents:
Prot_000.pdf: 
 
ENYO Pharma SA 
 
 
Lyon, France 
 
 
Protocol Number: EYP001-201 
 
 
IND Number: 142570 
 
EudraCT number: 2019-001629-28 
 
A PHASE 2a, RANDOMIZED DOUBLE-BLIND 
PLACEBO-CONTROLLED STUDY OF ORAL 
FXR MODULATOR EYP001a COMBINED 
WITH NUCLEOS(T)IDE ANALOGUES (NA) IN 
VIROLOGICALLY SUPPRESSED CHRONIC 
HEPATITIS B PATIENTS TO IMPROVE 
FUNCTIONAL CURE RATES 
 
Investigational Product: 
EYP001a 
Study Phase: 
Phase 2a 
Study Director:  
ENYO Pharma SA 
60 avenue Rockefeller,  
Bâtiment Bioserra B. 69008 LYON 
FRANCE 
 
Version / Date: 
3.0 (Amendment 4) / 22 January 2020 
 
  
The name, title, address and telephone number(s) of the sponsor’s medical monitor is documented 
in the study contact list located in the site’s study folder. 
 
 
 
 
CONFIDENTIALITY STATEMENT:  
The information contained in this document is confidential and is the property of ENYO Pharma SA. 
This information should not be reproduced, revealed, or sent to third parties other than the 
Independent Ethics Committee/Institutional Review Board, Regulatory Authorities, and the 
Investigator’s research support staff for the conduct of the study, without the proper written 
authorisation of ENYO Pharma SA. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 2 of 123 
 
 
 
SPONSOR PROTOCOL SIGNATURE PAGE 
 
 
 
Protocol Number: EYP001-201 
 
Protocol Title: A Phase 2a, randomized, double-blind, placebo-controlled study of 
oral FXR modulator EYP001a combined with Nucleos(t)ide analogues (NA) in 
virologically suppressed chronic hepatitis B patients to improve functional cure rates 
 
This study has been prepared and reviewed by the Sponsor for distribution to designated 
clinical sites, associated ethics committees/institutional review boards, designated 
contractors, regulatory agencies, and with permission by the Sponsor.  
 
 
The information it contains is consistent with current knowledge of the risks and benefits 
of the investigational product, as well as with the moral, ethical, and scientific principles 
governing clinical research as set out in the current Declaration of Helsinki and the 
guidelines on Good Clinical Practice. 
 
 
Approved by the following: 
 
Pietro Scalfaro 
 
 
 
Chief Medical Officer 
Signature 
 
Date 
ENYO PHARMA 
 
 
 
 
 
 
 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 3 of 123 
 
 
 
INVESTIGATOR ACKNOWLEDGEMENT 
 
Protocol Number: EYP001-201 
 
Protocol Title: A Phase 2a, randomized, double-blind, placebo-controlled study of 
oral FXR modulator EYP001a combined with nucleos(t)ide analogues (NA) in 
virologically suppressed chronic hepatitis B patients to improve functional cure rates 
 
 
 
 
I have read this protocol and agree to conduct this trial in accordance with all stipulations 
of the protocol and in accordance with International Council for Harmonisation Good 
Clinical Practice (ICH-GCP) guidelines, the Declaration of Helsinki and local regulations 
(as applicable). 
 
I agree to maintain the confidentiality of all information received or developed in 
connection with this protocol.  
I will provide all study personnel under my supervision with copies of this protocol and its 
related investigational product Investigator’s Brochure, and access to all study-related 
information provided by the Sponsor and designated study monitor. I will discuss this 
study-related information with my staff to ensure that they are fully informed about the 
investigational product and the protocol.  
I agree to provide all participants with a signed and dated copy of the informed consent 
document, as required by local regulations and ICH-GCP. I further agree to report to the 
Sponsor on any adverse events in accordance with the terms of this protocol, as per the 
applicable regulations where applicable. 
 
 
 
 
Principal Investigator 
 
 
 
 
Signature 
 
Date 
 
 


ENYO Pharma SA 
 
 
 
 
 
Protocol No: EYP001-201 
 
 
 
 
Version/date: 3.0 / 22 January 2020 
 
                                                                             Confidential 
 
 
 
 
                  Page 4 of 123 
 
 
 
PROTOCOL AMENDMENT SUMMARY 
Document History 
Document 
Date of Issue 
Protocol version 3.0 (Amendment 4) 
 
22 January 2020 
Protocol version 2.2 (Amendment 3) 
09 August 2019 
Protocol version 2.1 (Amendment 2) 
17 July 2019 
Protocol version 2.0 (Amendment 1) 
03 July 2019 
Original Protocol version 1.0 
16 April 2019 
 
Summary of Changes 
 
 
LIST OF PROTOCOL CHANGES FROM PROTOCOL VERSION 2.2 (AMENDMENT 3) DATED 09 August 2019 TO 
PROTOCOL VERSION 3.0 (AMENDMENT 4) DATED 22 January 2020 
 
 
Change ID# Section Number 
Protocol Version 2.2 (Amendment 3) dated 09 
August 2019 
Protocol Version 3.0 (Amendment 4) dated 22 
January 2020 
1 
Title Page and 
Header 
throughout 
the 
document 
Change/rationale: Updated Title Page, and Header throughout the document to reflect the updated version no. 
and date. 
Typo corrected in Enyo Pharma address in title page and address corrected in INVESTIGATORS AND 
STUDY ADMINISTRATIVE STRUCTURE p55: 
 
Previously read: 
ENYO Pharma SA 
60 avenue Rockfeller,  
Bâtiment Biosera B. 69008 LYON 
FRANCE 
Now reads: 
ENYO Pharma SA 
60 avenue Rockefeller,  
Bâtiment Bioserra B. 69008 LYON 
FRANCE 


ENYO Pharma SA 
 
 
 
 
 
Protocol No: EYP001-201 
 
 
 
 
Version/date: 3.0 / 22 January 2020 
 
                                                                             Confidential 
 
 
 
 
                  Page 5 of 123 
 
 
 
Previously read: 
Version 2.2 (Amendment 3) / 09 August 2019 
Now reads: 
Version 2.23.0 (Amendment 34) / 09 August 201922 
January 2020 
2 
Throughout 
the 
document. 
Sections 
1.4.3.3, 
1.5.1 and 5.4 
Change/rationale: The daily oral EYP001a dose to be administered during 16 weeks is reduced from 400 mg 
QD (two 200 mg tablets) to 200 mg QD (one 200 mg tablet). The rationale for dose selection has also been 
updated. The rationale for the change is as following: 
In an ongoing phase 2a trial (EYP001-202, 24 NASH subjects enrolled as of 18 December 2019) and in an 
ongoing phase 1 trial (EYP001-107, 9 NASH and 4 healthy subjects enrolled as of 18 December 2019), 100mg 
and 200mg EYP001a oral tablets were tested at the dose levels 100mg BID, 200mg QD and 400mg QD. These 
are the preliminary findings: 
PK profile of EYP001 tablet:  
● The oral EYP001a tablet formulation appears to have higher bioavailability compared to the oral capsule 
formulation previously used in EYP001 phase 1 studies in healthy and subjects with CHB.  
● The similar exposure seen in NASH subjects with the 200mg QD (1x200mg tablet) and the 400mg QD 
(2x200mg tablets) suggests a saturation phenomenon with exposure reaching a plateau over the 200mg 
dose level  
● A similar EYP001 plasma concentrations were obtained in simulations performed for CHB subjects for 
the 200mg QD (1x200mg tablet) compared to concentrations after administration of the 400mg QD 
(2x200mg capsules). The later was previously tested and well tolerated in study EYP001-103 in CHB 
subjects. 
● Finally the differences of the PK parameters after administration of 200mg, 400mg QD repeated oral 
EYP001a doses either as capsules or tablet show that the daily dose of 200mg given as tablet leads to 
an exposure similar to a daily dose of 400mg given as capsules (details in to IB memorandum dated 16 
January 2020 [IB Memo, 2020]).  
 
Safety & Tolerance:  
● Pruritus: In ongoing study EYP001-202, NASH subjects treated during 12 weeks with EYP001a 
100mg BID or 200mg QD or 400mg QD or Placebo tablets, had an overall pruritus frequency of 15/24 
(64%) subjects, all mild or moderate episodes, except for three Grade 3. Five pruritus episodes led to 


ENYO Pharma SA 
 
 
 
 
 
Protocol No: EYP001-201 
 
 
 
 
Version/date: 3.0 / 22 January 2020 
 
                                                                             Confidential 
 
 
 
 
                  Page 6 of 123 
 
 
 
early treatment termination. This is in contrast with previous experience in study EYP001-103, in which 
CHB subjects were treated during 4 weeks with EYP001a capsules, and had mostly mild or moderate 
pruritus episodes: 1 subject of 7 to 9 (11% to 14%) in each of the EYP001 arms (100 mg, 200 mg and 
400 mg QD) but increased to 6 of 9 (67%) subjects treated with 200 mg BID. One subject terminated 
early because of pruritus. 
 
● ALT/AST: In study EYP001-202, two grade 3 cases of isolated transient ALT/AST increases, with no 
signs of liver impairment, occurred around Day 56 of treatment. No Hy’s law cases occurred (no 
confirmed DILI). The designation by the Primary Investigators (PIs) of the liver enzyme elevations did 
not consider these as clinically significant, with a variance over time with few outliers, overall not 
unexpected in the NASH patient population.. This compares and is in line with previous phase 1 trials 
results, where ALT and AST values were within the normal range following EYP001a administration 
in healthy subjects and in study EYP001-103 after 4 weeks of administration of EYP001a to CHB 
subjects, 5 subjects had Grade 3 (n=4) or 4 (n=1) ALT/AST increases without signs of liver impairment. 
The changes were interpreted as hepatic flares or typical of those seen in subjects with underlying 
chronic viral HBV liver disease. 
Taken together, these PK and safety/tolerance preliminary findings in the ongoing NASH and phase 1 trial 
obtained with the EYP001a tablet formulation do not support the use of the 400mg daily EYP001 dose as a 
tablet. The reduction to 200mg QD (1x200mg tablet) will generate an exposure similar to previously tested and 
well tolerated 400mg QD (2x200mg capsules). EYP001a 200mg tablet QD dose can be assessed safely in CHB 
subjects over the planned 16 week treatment period. For more details, please refer to IB memorandum dated 16 
January 2020 (IB Memo, 2020) 
Previously read: 
- 
EYP001a 400 mg once daily 
- 
2 x tablets of 200 mg 
- 
400 mg QD was selected because it is the 
highest tested and well tolerated dose 
administered during 4 weeks to CHB patients 
with an effect on HBsAg reduction 
 
 
1.4.3.3. Clinical Safety 
Now reads: 
- 
EYP001a 200 400 mg once daily 
- 
2 x 1 tablets of 200 mg 
- 
An initial dose of 400 mg QD capsules was 
selected because it is was the highest tested 
and well tolerated dose administered during 4 
weeks to CHB patients with an effect on 
HBsAg reduction 
 
1.4.3.3. Clinical Safety 


ENYO Pharma SA 
 
 
 
 
 
Protocol No: EYP001-201 
 
 
 
 
Version/date: 3.0 / 22 January 2020 
 
                                                                             Confidential 
 
 
 
 
                  Page 7 of 123 
 
 
 
Overall EYP001a is considered safe over the dose 
range of 100 mg to 400 mg QD and 200 mg BID. 
Aforementioned data support the selection of the 400 
mg dose for study EYP001 201. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1.5.1. Rationale for Study Conduct 
Overall given the high need to improve functional 
HBV cure rates with a finite treatment and the 
observations of oral QD doses of EYP001a to be well 
tolerated, with a dose dependent signal on HBsAg 
reduction after only 4 weeks therapy, the exploration 
of an EYP001a prolonged treatment on top of NA 
seems justified. This study was designed to test the 
safety and the antiviral effect of 400 mg QD 
EYP001a when administered in combination with 
stable NA therapy over 16 weeks on HBsAg in CHB 
patients who are virologically suppressed on a stable 
NA therapy1. 
 
 
 
Overall EYP001a is considered safe over the dose 
range of 100 mg to 400 mg QD and 200 mg BID 
given as capsules. Aforementioned data initially 
supported the selection of the 400 mg tablet dose for 
study EYP001 201. Nevertheless, PK and 
safety/tolerance preliminary findings in ongoing 
EYP001-202 NASH phase 2a and in the 
EYP001-107 phase 1 NASH trials with the 
EYP001a tablet formulation, do not support the 
use of the 400mg daily single oral EYP001 dose 
with the tablet formulation. The reduction to 
200mg QD (1x200mg tablet) will generate an 
exposure similar to 400mg QD (2x200mg capsules) 
dose that was previously tested and well tolerated. 
EYP001a 200mg tablet QD dose can be assessed 
safely in CHB subjects over the planned 16 week 
treatment period. 
 
1.5.1. Rationale for Study Conduct 
Overall given the high need to improve functional 
HBV cure rates with a finite treatment and the 
observations of oral QD doses of EYP001a to be well 
tolerated, with a dose dependent signal on HBsAg 
reduction after only 4 weeks therapy, the exploration 
of an EYP001a prolonged treatment on top of NA 
seems justified. This The study EYP001-201was 
initially designed to test the safety and the antiviral 
effect of 400 mg QD EYP001a when administered in 
combination with stable NA therapy over 16 weeks 
on HBsAg in CHB patients who are virologically 
suppressed on a stable NA therapy1. 
Nevertheless, in light of preliminary findings in 
ongoing EYP001-202 NASH phase 2a and in the 
EYP001-107 phase 1 NASH trials (Section 1.4.3.3) 


ENYO Pharma SA 
 
 
 
 
 
Protocol No: EYP001-201 
 
 
 
 
Version/date: 3.0 / 22 January 2020 
 
                                                                             Confidential 
 
 
 
 
                  Page 8 of 123 
 
 
 
 
 
 
 
 
5.4. 
Dose Rationale and Selection of Doses in 
the Study 
A dose of 400 mg QD EYP001a was selected because 
it is the so far highest tested over 4 weeks and was 
well tolerated by chronically infected-HBV patients. 
It also showed an apparent dose dependent signal on 
HBsAg reduction.  
Overall, EYP001a was safe and well tolerated over 
the dose range of 100 mg to 500 mg QD and 200 mg 
BID but was better tolerated with the QD regimen 
than with BID dosing. 
This is an early stage Phase 2a exploratory study to 
determine if adding EYP001a 16 week treatment on 
top of NA can induce a clinically meaningful and 
statistically significant reduction of HBsAg plasma 
levels after 16 weeks of combined treatment. A dose 
strength of 400 mg QD EYP001a was selected 
because it is the so far highest tested dose over 4 
weeks and was well tolerated by CHB patients. It also 
showed an apparent dose dependent signal on HBsAg 
reduction. For practical reasons, no lower EYP001a 
doses are included in this study and an appropriate 
dose ranging study will be performed later, should 
results meet the study endpoints. 
the dosage has been modified to 200mg QD 
(1x200mg tablet) which generates a similar plasma 
exposure as 400mg QD (2x200mg ) capsules, 
previously tested and well tolerated dose. 
 
5.4. 
Dose Rationale and Selection of Doses in 
the Study 
A dose of 400 mg QD EYP001a was selected because 
it is the so far highest tested over 4 weeks and was 
well tolerated by chronically infected-HBV patients. 
It also showed an apparent dose dependent signal on 
HBsAg reduction.  
Overall, EYP001a was safe and well tolerated over 
the dose range of 100 mg to 500 mg QD and 200 mg 
BID but was better tolerated with the QD regimen 
than with BID dosing. 
This is an early stage Phase 2a exploratory study to 
determine if adding EYP001a 16 week treatment on 
top of NA can induce a clinically meaningful and 
statistically significant reduction of HBsAg plasma 
levels after 16 weeks of combined treatment. An 
initial dose strength of 400 mg QD EYP001a 
capsules was selected because it is the so far highest 
tested dose over 4 weeks and was well tolerated by 
CHB patients. It also showed an apparent dose 
dependent signal on HBsAg reduction. For practical 
reasons, no lower EYP001a doses are included in this 
study and an appropriate dose ranging study will be 
performed later, should results meet the study 
endpoints. 
However in an ongoing phase 2a trial (EYP001-
202, 24 NASH subjects enrolled as of 18 December 
2019) and in an ongoing phase 1 trial (EYP001-
107, 9NASH and 4 healthy subjects enrolled as of 


ENYO Pharma SA 
 
 
 
 
 
Protocol No: EYP001-201 
 
 
 
 
Version/date: 3.0 / 22 January 2020 
 
                                                                             Confidential 
 
 
 
 
                  Page 9 of 123 
 
 
 
18 December 2019), 100mg and 200mg EYP001a 
oral tablets were tested at the dose levels 100mg 
BID, 200mg QD and 400mg QD. These are the 
preliminary findings: 
PK profile of EYP001 tablet:  
● The oral EYP001a tablet formulation 
appears to have higher bioavailability 
compared to the oral capsule formulation 
previously used in EYP001 phase 1 studies 
in healthy and subjects with NASH.  
● The similar exposure seen in NASH 
subjects with the 200mg QD (1x200mg 
tablet) and the 400mg QD (2x200mg 
tablets) suggests a saturation phenomenon 
with exposure reaching a plateau over the 
200mg dose level  
● A similar EYP001 plasma concentrations 
were obtained in simulations performed 
for CHB subjects for the 200mg QD 
(1x200mg tablet) compared to 
concentrations after administration of the 
400mg QD (2x200mg capsules). The later 
was previously tested and well tolerated in 
study EYP001-103 in CHB subjects. 
● Finally the differences of the PK 
parameters after administration of 200mg, 
400mg QD repeated oral EYP001a doses 
either as capsules or tablet  
 
Safety & Tolerance:  
● Pruritus: In an ongoing study EYP001-202 
, NASH subjects treated during 12 weeks 
(with EYP001a 100mg BID or 200mg QD 
or 400mg QD or Placebo tablets) had an 


ENYO Pharma SA 
 
 
 
 
 
Protocol No: EYP001-201 
 
 
 
 
Version/date: 3.0 / 22 January 2020 
 
                                                                             Confidential 
 
 
 
 
                  Page 10 of 123 
 
 
 
overall pruritus frequency of 15/24 (64%) 
subjects, all mild or moderate episodes, 
except for three Grade 3. Five pruritus 
episodes led to early treatment 
termination. This is in contrast with 
previous experience in study EYP001-103, 
in which CHB subjects were treated during 
4 weeks with EYP001a capsules, and had 
mostly mild or moderate pruritus episodes: 
1 subject of 7 to 9 (11% to 14%) in each of 
the EYP001 arms (100 mg, 200 mg and 400 
mg QD) but increased to 6 of 9 (67%) 
subjects treated with 200 mg BID. One 
subject terminated early because of 
pruritus. 
● ALT/AST: In study EYP001-202, two 
grade 3 cases of isolated transient 
ALT/AST increases, with no signs of liver 
impairment, occurred around Day 56 of 
treatment. No Hy’s law cases occurred (no 
confirmed DILI). The designation by the 
Primary Investigators (PIs) of the liver 
enzyme elevations did not consider these as 
clinically significant, with a variance over 
time with few outliers, overall not 
unexpected in the NASH patient 
population. This compares and is in line 
with previous phase 1 trials results, where 
ALT and AST values were within the 
normal range following EYP001a 
administration in healthy subjects and in 
study EYP001-103 after 4 weeks of 
administration of EYP001a to CHBV 
subjects, 5 subjects had Grade 3 (n=4) or 4 


ENYO Pharma SA 
 
 
 
 
 
Protocol No: EYP001-201 
 
 
 
 
Version/date: 3.0 / 22 January 2020 
 
                                                                             Confidential 
 
 
 
 
                  Page 11 of 123 
 
 
 
(n=1) ALT/AST increases without signs of 
liver impairment. The changes were 
interpreted as hepatic flares or typical of 
those seen in subjects with underlying 
chronic viral HBV liver disease. 
Taken together, these PK and safety/tolerance 
preliminary findings in the ongoing NASH and 
phase 1 trial obtained with the EYP001a tablet 
formulation do not support the use of the 400mg 
daily EYP001 dose as atablet. The reduction to 
200mg QD (1x200mg tablet) will generate an 
exposure similar to previously tested and well 
tolerated 400mg QD (2x200mg capsules). EYP001a 
200mg tablet QD dose can be assessed safely in 
CHB subjects over the planned 16 week treatment 
period.  
For more details, please refer to IB memorandum 
dated 16 January 2020 (IB Memo, 2020). 
3 
Throughout the 
document 
Change/rationale: Visit Day 0 has been updated to Day 1 to be consistent with EYP001 other clinical studies. 
Previously read: 
 
Day 0 
Now reads: 
 
Day 0 Day 1 
4 
Follow-up 
visits 
time 
window 
throughout 
the 
document 
Change/rationale: Extended time window for follow-up visit during maintenance period: helpful for the visit 
date arrangement for site 
Previously read: 
FU visit 1 (Week 20 [Day 140 ± 3 days]) 
FU visit 2 (Week 28 [Day 196 ± 3 days])  
FU visit 3 (Week 40 [Day 280 ± 3 days]) 
Now reads: 
FU visit 1 (Week 20 [Day 140 ± 3 7 days]) 
FU visit 2 (Week 28 [Day 196 ± 3 7 days])  
FU visit 3 (Week 40 [Day 280 ± 3 7 days]) 
5 
Section 6.2.2.9 
Change/rationale: error  


ENYO Pharma SA 
 
 
 
 
 
Protocol No: EYP001-201 
 
 
 
 
Version/date: 3.0 / 22 January 2020 
 
                                                                             Confidential 
 
 
 
 
                  Page 12 of 123 
 
 
 
Previously read: 
 
6.2.2.9. Treatment Visit 9 (Week 16 [Day 112± 3 
days])  
 
• 
Dispense EYP001a or placebo and NA 
Now reads: 
 
6.2.2.9. Treatment Visit 9 (Week 16 [Day 112± 3 
days])  
 
• 
Dispense EYP001a or placebo and NA 
6 
Section 6.2.3.2 
and 6.2.3.3 
Change/rationale: discrepancy between section 6.2.3.2 and 6.2.3.3 and section 19.1 Appendix A - Schedule of 
Assessment* 
Previously read: 
 
6.2.3.2. Follow-up Visit 2 (Week 28 [Day 196± 3 
days]) (Page 97 of 139 in the Protocol) • Perform 
liver imaging to screen patient for HCC. For patients 
with risk factors for HCC, i.e. any of these: family 
history with HCC, >40 years of age, male sex, born in 
Sub-Saharan Africa, Metabolic syndrome (obesity, 
diabetes), smoking, ALT>ULN, HBV DNA (>2,000 
IU/mL), HBeAg-negative, Genotype C) during 
follow-up phase liver imaging is also performed at 
week 28. 
 
6.2.3.3. Follow-up Visit 3/EoS Visit (Week 40 [Day 
280± 3 days]) (Page 97 of 139 in the Protocol) 
none 
Now reads: 
 
6.2.3.2. Follow-up Visit 2 (Week 28 [Day 196± 37 
days]) (Page 97 of 139 in the Protocol) • Perform 
liver imaging to screen patient for HCC. For patients 
with risk factors for HCC, i.e. any of these: family 
history with HCC, >40 years of age, male sex, born in 
Sub-Saharan Africa, Metabolic syndrome (obesity, 
diabetes), smoking, ALT>ULN, HBV DNA (>2,000 
IU/mL), HBeAg-negative, Genotype C) during 
follow-up phase liver imaging is also performed at 
week 28. 
 
6.2.3.3. Follow-up Visit 3/EoS Visit (Week 40 [Day 
280± 37 days]) (Page 97 of 139 in the Protocol) • 
Perform liver imaging to screen patient for HCC. 
For patients with risk factors for HCC, i.e. any of 
these: family history with HCC, >40 years of age, 
male sex, born in Sub-Saharan Africa, Metabolic 
syndrome (obesity, diabetes), smoking, ALT>ULN, 
HBV DNA (>2,000 IU/mL), HBeAg-negative, 
Genotype C) during follow-up phase liver imaging 
is also performed at week 40.  
7 
Section 19.2 
Change/rationale: Visual Analogue Scale (VAS) had been omitted and therefore was added in Appendix B 
along with 5-D pruritus scale previously appended to the study protocol. 


ENYO Pharma SA 
 
 
 
 
 
Protocol No: EYP001-201 
 
 
 
 
Version/date: 3.0 / 22 January 2020 
 
                                                                             Confidential 
 
 
 
 
                  Page 13 of 123 
 
 
 
Previously read : 
 
19.2. 
Appendix B: 5-D Pruritus Scale 
No VAS 
Now reads: 
 
19.2. 
Appendix B: 5-D Pruritus Scale 
 
8 
Section 5.8 
Change/rationale: 
The occurrence of pruritus is a known class effect of FXR agonist. It has been reported at varying 
frequency after the administration of EYP001a (12 to 66% depending on dose level and dosing 
regimen). Intensity is usually mild or moderate but can be severe interfering with subject daily 
activities. Recommendation of symptomatic treatment options are introduced in the protocol as well as 
criteria for a short drug holiday.  
Previously read: 
void 
Now reads: 
 
5.8.1. 
Pruritus 
management: 
guidance 
to 
investigators  
 
Self-limited, mostly mild to moderate pruritus has been 
observed in clinical trials with EYP001 and in a higher 
proportion of patients who received twice daily dosing 
regimens. Pruritus has also been reported with other 
FXR agonists and in patients with NASH as part of the 
disease natural symptomatology and independent of 
any pharmacological treatment. Tolerance to pruritus 
may develop over continuous uninterrupted dosing of 
EYP001. 
 


ENYO Pharma SA 
 
 
 
 
 
Protocol No: EYP001-201 
 
 
 
 
Version/date: 3.0 / 22 January 2020 
 
                                                                             Confidential 
 
 
 
 
                  Page 14 of 123 
 
 
 
The following three level therapeutic approach to 
pruritus can be applied: 
 
1. Topical non-pharmacological or over the 
counter interventions to improve pruritus may 
be tried and can be advised to patients. These 
include application of moisturizers, cooling 
agents, 
antihistamines, 
taking 
cool 
showers/showering in the morning, using 
clear/gentle soaps and laundry detergents, 
application of cold packs or fabric strips 
soaked in cold water, avoidance of wool or 
other irritating fabrics, wearing loose-fitting 
clothing.  
2. With likely no improvement of severe pruritus, 
a drug holiday of 2 to maximum 5 days may 
be considered and in such cases, we would 
encourage to contact the Medical Monitor 
3. In situation where pruritus prevails and 
requires 
systemic 
oral 
pharmacological 
treatment, the following drugs may be 
considered at the investigator’s judgment and 
taking 
into 
account 
individual 
clinical 
situation, pruritus severity and concomitant 
medications 
and 
comorbidities: 
antihistamines, 
hydroxyzine, 
opioid 
antagonists, 
gabapentin 
(note 
that 
the 
concomitant use of opioid agonists and 
gabapentin is not recommended). 
 
9 
Synopsis and 
Section 3.1 
Change/rationale: 
Number of study sites has been updated from 10 sites to 14 sites 
Previously read: 
Now reads: 


ENYO Pharma SA 
 
 
 
 
 
Protocol No: EYP001-201 
 
 
 
 
Version/date: 3.0 / 22 January 2020 
 
                                                                             Confidential 
 
 
 
 
                  Page 15 of 123 
 
 
 
 
Synopsis 
Number of Planned Participants:  
49 patients are planned to be enrolled from 
approximately 10 sites. 
 
Study Design:  
A total of 49 eligible patients will be enrolled 
and randomized at approximately 10 study sites. 
 
3.1. 
Description of Overall Study Design 
and Plan 
In total 49 eligible patients will be enrolled and 
randomized at approximately 10 study sites. 
 
Synopsis 
Number of Planned Participants:  
49 patients are planned to be enrolled from 
approximately 10 14 sites. 
 
Study Design:  
A total of 49 eligible patients will be enrolled and 
randomized at approximately 10 14 study sites. 
 
3.1. 
Description of Overall Study Design 
and Plan 
In total 49 eligible patients will be enrolled and 
randomized at approximately 10 14 study sites. 
10 
Synopsis and 
Section 2.1.2 
Change/rationale: Secondary objective for HBV viral markers has been updated to include additional 
parameters for consistency with the assessments. 
Previously read: 
• 
To determine HBV viral response, HBV 
pgRNA, HbcrAg and HbeAg at the end of the 
16-week EYP001a treatment and Week 40 of 
follow-up. 
 
Now reads: 
• 
To determine HBV viral response, HBV 
pgRNA, HbBcrAg and HbBeAg, anti-HBe 
and anti-HBs at the end of the 16-week 
EYP001a treatment and at Week 40 of 
follow-up. 
 
11 
Synopsis, 
Sections 2.2.2, 7.1 
and 11.3.3.2 
Change/rationale: Timepoint Week 40 of maintenance period has been added to secondary endpoints 
HBV-pgRNA decline (Δ log10) and HBcrAg decline (Δ log10). 
Previously read: 
• 
HBV pgRNA decline (Δ log10) from Day 0 to 
Weeks 4, 8, 12 and 16 of treatment period 
• 
HBcrAg decline (Δ log10) from Day 0 to 
Weeks 4, 8, 12 and 16 of treatment period 
 
Now reads: 
• 
HBV-pgRNA decline (Δ log10) from Day 1 to 
Weeks 4, 8, 12, 16 of treatment period and 
Week 40 of maintenance period 
• 
HBcrAg decline (Δ log10) from Day 1 to 
Weeks 4, 8, 12, 16 of treatment period and 
Week 40 of maintenance period 


ENYO Pharma SA 
 
 
 
 
 
Protocol No: EYP001-201 
 
 
 
 
Version/date: 3.0 / 22 January 2020 
 
                                                                             Confidential 
 
 
 
 
                  Page 16 of 123 
 
 
 
 
12 
Section 8 
Change/rationale: Condition and procedure for additional chemistry has been included for clarity. 
Previously read: 
 
8. 
Safety Assessments 
Clinical laboratory assessments will include: 
• 
Additional chemistry: Alpha 2 
macroglobulin, autotaxin, cardiac troponin I, 
ferritin, phosphate and TSH 
Previously read: 
 
8. 
Safety Assessments 
Clinical laboratory assessments will include: 
Additional chemistry: Alpha 2 macroglobulin, 
autotaxin, cardiac troponin I, ferritin, phosphate and 
TSH. These markers will be assessed at the end of 
study on existing chemistry plasma aliquots 
collected on Day 1, Day 112 and Day 280, only if 
relevant improvements in liver inflammation or 
fibrosis are apparent. 
Additional minor changes have been made to improve clarity and consistency. 
 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 17 of 123 
 
 
 
CLINICAL PROTOCOL SYNOPSIS  
Title of Study: 
A Phase 2a, randomized, double-blind, placebo-controlled study 
of oral FXR modulator EYP001a combined with nucleos(t)ide 
analogues (NA) in virologically suppressed chronic hepatitis B 
patients to improve functional cure rates 
Protocol Number: 
EYP001-201 
EudraCT number 
2019-001629-28 
Investigational Product: 
Name: EYP001a tablets  
Dose: 200 mg (1x tablet of 200 mg)  
Route of Administration: Oral 
Reference/Comparator 
Product: 
Name: Matching Placebo tablets 
Dose: 1 matching tablet 
Route of Administration: Oral 
Combination Treatment: NA: Entecavir (ETV) 0.5 mg daily (or per country specific 
label) or Tenofovir Disoproxil Fumarate (TDF) 300 mg daily 
which is equivalent to 245 mg of tenofovir disoproxil per 
country specific label, will be provided as the standard of care 
(SOC) 
Indication: 
Chronic hepatitis B (CHB) 
Phase of Development: 
Phase 2a 
Study Centres: 
Multi-centre study 
Number of Planned 
Participants: 
49 patients are planned to be enrolled from approximately 14 sites 
Study Objectives: 
Primary Objective: 
• 
To determine the effect of EYP001a on top of NA SOC 
therapy) on Hepatitis B surface antigen (HBsAg) plasma 
levels 
Secondary Objectives: 
• 
To establish the effect of EYP001a on top of NA on 
HBsAg responder rate at the end of the 16-week 
EYP001a treatment and at 24-week of follow-up (Week 
40).  
• 
To establish the effect of EYP001a on top of NA on 
HBsAg loss rate at the end of the 16-week EYP001a 
treatment and at 24-week of follow-up (Week 40).  
• 
To establish the HBV virologic failure rate 
(breakthrough)1 during the 24 weeks follow-up period 
after stopping EYP001a with ongoing NA (SOC 
therapy).  
 
 
1 Breakthrough is defined by quantifiable HBV DNA increase of ≥ 1 log10 HBV DNA copies/mL 
above LLOQ. Breakthrough samples will be further assessed for resistance assessments, 
including both for the nucleos(t)ide analogue as well as for EYP001a (e.g., sequence analysis of 
FXR response elements in HBV genome). Details will be described in the Laboratory manual. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 18 of 123 
 
 
 
• 
To determine HBV viral response, HBV pgRNA, 
HBcrAg, HBeAg, anti-HBe and anti-HBs at the end of 
the 16-week EYP001a treatment and at Week 40 of 
follow-up. 
• 
To explore the safety profile of EYP001a treatment in 
combination with NA. 
• 
To determine the plasma concentration of EYP001a and 
PD markers (plasma C4 
[7α-hydroxy-4-cholesten-3-one]), FGF19 (Fibroblast 
Growth Factor 19) and bile acid (BA). 
Study Endpoints 
Primary Endpoint 
• 
Efficacy assessed as HBsAg decline (Δ log10) from Day 
1 to Week 16 of treatment 
Secondary Endpoints 
• 
Efficacy assessed as: 
o HBsAg responder rate (decrease from baseline ≥ 1.0 
on the log10 scale) at Week 16 of treatment and 
Weeks 20, 28 and 40 of follow-up. 
o HBsAg responder rate (decrease from baseline ≥ 0.5 
on the log10 scale) at Weeks 12 and 16 of treatment 
and Weeks 20, 28 and 40 of follow up. 
o HBsAg loss rate (% patients with HBsAg < lower 
limit of quantification [LLOQ]) at Week 16 of 
treatment and Weeks 20, 28 and 40 of follow-up 
o HBsAg loss rate (Proportion of results that are 
Target Not Detected versus Target Detected) at 
Week 16 of treatment and Weeks 20, 28 and 40 of 
follow-up 
o Relapse rate HBsAg (% patients who became 
negative [HBsAg < LLOQ], then increased with 
HBsAg > LLOQ) at Week 16 of treatment period 
and Weeks 20, 28 and 40 during follow-up period 
o Virologic failure rate (breakthrough)2of HBV-DNA 
(% patients with a confirmed quantifiable HBV 
DNA increase of ≥ 1log10 HBV DNA copies/mL 
above LLOQ3) assessed at Week 16 of treatment 
period and Weeks 20, 28 and 40 during follow-up 
period 
 
 
2 Breakthrough samples will be further assessed for resistance assessments, including both for 
the nucleos(t)ide analogue as well as for EYP001a (e.g., sequence analysis of FXR response 
elements in HBV genome). Details will be described in the Laboratory manual. Also refer footnote 
no. 8 below. 
3 HBV DNA results <LLOQ will be reported as either <LLOQ/Detected (i.e. LLOQ/TD) or 
<LLOQ/Target Not Detected (i.e. LLOQ/TND), both are considered LLOQ. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 19 of 123 
 
 
 
o HBV-pgRNA decline (Δ log10) from Day 1 to 
Weeks 4, 8, 12, 16 of treatment period and Week 40 
of maintenance period 
o HBcrAg decline (Δ log10) from Day 1 to Weeks 4, 
8, 12, 16 of treatment period and Week 40 of 
maintenance period 
o HBeAg quantification for HBeAg pos patients and 
changes at Week 16 of treatment and Week 40 of 
follow-up 
o Fibroscan VCTE change from screening value to 
Weeks 16 and 40 or ET value 
 
• 
Safety and Tolerability assessed as: 
o Treatment-emergent adverse events (TEAEs) 
(including serious adverse events [SAEs]) 
o All-cause mortality  
o Clinical laboratory tests 
o Pruritus assessment 
o Vital signs (blood pressure, heart rate, respiratory 
rate, and temperature) 
o Concomitant medications 
o Physical examinations 
o 12-lead ECG 
 
• 
PK assessed as: 
o Plasma concentration of EYP001a or any relevant 
active metabolites (as identified in an ongoing phase 
1 study). 
 
• 
PD markers: 
o Plasma C4 (7α-hydroxy-4-cholesten-3-one) 
o FGF19 
o Plasma primary and secondary Bas 
Study Design: 
This is a prospective, multi-centre, randomized, double-blind, 
placebo-controlled, Phase 2a experimental study of oral FXR 
modulator EYP001a/placebo combined with NAs in virologically 
suppressed CHB patients to improve functional cure rates. 
A total of 49 eligible patients will be enrolled and randomized at 
approximately 14 study sites. Patients will be randomized prior to 
study drug (EYP001a or placebo and NA) administration on Day 
1 in the ratio of 3:1 into 2 arms: 
• 
Experimental Arm: EYP001a 200 mg QD + NA 
daily (37 patients) 
• 
Control Arm: Placebo + NA daily (12 patients) 
Patients will also be stratified per HBeAg status, based on 
medical history or established during screening, to obtain a 
balanced randomization to both study arms. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 20 of 123 
 
 
 
The maximum total engagement duration for eligible patients in 
this study is up to 370 days: 90 days screening, 112 days (16 
weeks) treatment period and 168 days (24 weeks) follow-up. 
Patients enrolled in the study will be assessed as outpatients. 
Patient screening will occur no more than 90 days prior to the Day 
1 visit. Eligible patients will undergo further assessments on Day 
1 to qualify for study drug administration on Day 1. 
The visits during the study are planned as below: 
• 
Screening visit: 12 weeks (90 days) 
• 
16 weeks treatment period: 
• 
Treatment Visit 1 (Week 1 [Day 1]) 
• 
Treatment Visit 2 (Week 2 [Day 14 ±3 days]) 
• 
Treatment Visit 3 (Week 4 [Day 28 ±3 days]) 
• 
Treatment Visit 4 (Week 6 [Day 42 ±3 days]) 
• 
Treatment Visit 5 (Week 8 [Day 56 ±3 days]) 
• 
Treatment Visit 6 (Week 10 [Day 70 ± 3 
days]) 
• 
Treatment Visit 7 (Week 12 [Day 84 ± 3 
days]) 
• 
Treatment Visit 8 (Week 14 [Day 98 ± 3 
days]) 
• 
Treatment Visit 9 (Week 16 [Day 112±3 
days]) 
• 
24 weeks safety follow-up period: 
• 
Follow-up Visit 1 (Week 20 [Day 140 ±7 
days]) 
• 
Follow-up Visit 2 (Week 28 [Day 196 ±7 
days]) 
• 
Follow-up Visit 3 (Week 40 [Day 280 ±7 
days]) 
Note: during follow-up patients are kept on NA until the end of 
the trial: Week 40 (consolidation Phase). 
Post study consolidation period: after Week 40, investigators can 
continue or stop NA therapy provided the following 
recommended plan is respected at the end of the study: after 
cessation of antiviral therapy, there is a transition of HBV care to 
a local provider for continued monitoring every 3 months for at 
least one year to monitor eventual HBV flares. 
Safety, tolerance, PK /PD and efficacy of EYP001a will be 
established in an outpatient setting. 
Data Safety Monitoring 
Committee  
An external, independent Data Safety Monitoring Committee 
(DSMC) will review all available unblinded preliminary safety 
study data when any stopping rules are met in two or more 
subjects. (Stopping rules details are described in the protocol 
Section 4.6.). DSMC will also review on two scheduled occasions 
for an interim analysis:  


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 21 of 123 
 
 
 
1. First interim analysis on all available unblinded 
preliminary safety study data:  
Safety assessment when 50% (n=25) patients reach 
week 8 resulting in a decision on continuation of the 
study based on safety (Go/No go decision); 
enrolment would remain ongoing during this review 
2. Second interim analysis on all available unblinded 
preliminary virology, safety, PK and PD study data:  
Safety and futility when 50% patients (n=25) 
reached week 12, resulting in a decision on 
continuation of the study (Go/No go decision) based 
on safety and evidence of a benefit of EYP001 
(HBsAg, other secondary viral markers); enrolment 
is ongoing during this review 
The interim analyses will be performed on all available primary 
and secondary endpoints according to the SAP and DSMC 
charter, which describes the overall guidelines, composition, 
roles, and responsibilities of the independent DSMC for the 
EYP001-201 study, including the selection of DSMC members, 
timing of meetings, methods of providing information to and from 
the DSMC, frequency and format of meetings, data analysis 
recommendations, and DSMC relationships with other parties 
participating in the conduct of this study.  
 
Futility assessment will be performed by the DSMC according to 
defined rules (Section 11.5) to determine if EYP001 has no 
benefit at a point when 50% of subjects have reached 12 weeks 
of dosing. The study will not stop for efficacy at Week 12 interim 
analyses, even if efficacy boundary is crossed. The stopping of 
the study for futility will be considered by the DSMC by applying 
these rules. The criteria are not binding and DSMC can overrule 
if other interim results show beneficial results.  
 
 
Study Stopping Rules 
Stopping rules details will be further described in the Section 4.6.  
Dosing for a patient will be discontinued for any of the following 
events: 
1. One occurrence of an SAE assessed to be definitely, 
probably or possibly related to dosing with the study 
drug. 
2. One occurrence of a Grade 4 AE (i.e. life-threatening) 
assessed to be considered “possibly related” or “probably 
related” to the study drug 
3. One occurrence a Grade 3 rash or higher or acute 
systemic allergic reaction. 
4. Confirmation of any of the study drug discontinuation 
criteria as described in Section 8.3. 
5. Occurrence of any condition that, in the opinion of the 
Investigator, significantly jeopardizes the wellbeing and 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 22 of 123 
 
 
 
safety of the patient and is assessed to be probably related 
to dosing with the study drug. 
6. Clinically significant changes in vital signs or ECGs 
(such as arrhythmias) assessed to be considered “possibly 
related” or “probably related” to the study drug (i.e., no 
alternative explanation likely).  
7. Clinically significant changes in the safety laboratory 
tests assessed to be considered “probably related” to the 
study drug (i.e., no alternative explanation likely).  
8. A subject experiences a breakthrough (defined by 
quantifiable HBV DNA increase of ≥ 1 log10 HBV DNA 
copies/mL above LLOQ) the subject should return to the 
study site for a confirmatory measurement within two 
weeks, and if virologic breakthrough is confirmed, 
EYP001a or placebo dosing should be stopped and NA 
treatment should be continued or modified at the 
investigator’s discretion. 
If two or more patients meet study drug stopping criteria #1, or 
#3 to #8, recruitment and dosing should be suspended or 
terminated for the remaining patients, pending the outcome of a 
DSMC review. The DSMC must review all safety data and 
provide clearance prior to dosing any additional patients. 
If one patient meets study drug stopping criteria #2, recruitment 
and dosing should be suspended or terminated for the remaining 
patients, pending the outcome of a DSMC review. 
If one patient experiences a Grade 5 common terminology criteria 
for adverse event (CTCAE) toxicity (based on CTCAE, version 
5.0), or if more than 2 patients develop a Grade 3 CTCAE toxicity 
in the same category, the study will be paused, and safety reports 
will be submitted to the DSMC for review and clearance prior to 
dosing any additional patients. 
In other situations, re-initiation of study drug may be considered 
after consultation with the Medical Monitor. 
Diagnosis and main 
criteria for Inclusion and 
Exclusion: 
 
The study is open to chronic HBV carriers with no recent (3 
months) history of any clinically significant conditions, which, in 
the opinion of the investigator, would jeopardize the safety of the 
patient or impact the validity of the study results. 
Diagnosed CHB is defined by the following values established 
during screening period: 
• 
HBV virally suppressed with HBV DNA < LLOQ4 and 
on stable single NA treatment of at least 12 months 
 
 
4 The performance characteristics of the quantitative HBV DNA assay will be reported in the 
laboratory manual. The same assay will be used for all study visits. An FDA approved test will be 
used such as Abbott Realtime HBV Assay or COBAS HBV Test.  


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 23 of 123 
 
 
 
duration (ETV or TDF)5 
• 
All genotypes, stratified A vs. non-A6 
• 
HBeAg negative or positive (expected ratio 7/3): 
stratification across study arms 
• 
HBsAg plasma levels >100 IU/mL7. 
 
Inclusion Criteria: 
Patients must satisfy all of the following criteria during screening 
to be enrolled in the study: 
1. Has given voluntary written informed consent before 
performance of any study related procedure. 
2. Must be 18 to 65 years of age, inclusive 
3. Are on stable NA therapy for at least 12 months from the 
screening date (ETV or TDF)8 
4. Has virally suppressed CHB: 
a. HBV DNA < LLOQ and serum HBsAg >100 
IU/mL 
5. Has liver imaging to screen for hepatocellular carcinoma 
or concomitant pancreaticobiliary disease either in the 
prior 6 months or at screening. 
6. Has liver tests during the Screening Period defined as 
follows: 
a. The baseline values (i.e. two measurements at 
least 3 days apart: one can be from medical 
history if not older than 12 months and one 
during 
screening 
period) 
with 
both 
measurements of ALT or AST are ≤ 2 × ULN 
b. Normal or clinically not relevant levels of ALP 
(≤ 1.5 ULN) 
c. Has total bilirubin (TBL) ≤ 22.2 μmol/L, which 
corresponds to ≤ 1.3 mg/dL.  
d. Has conjugated (direct) bilirubin of ≤ 0.3 mg/dL 
(i.e. 5.1 μmol/L) 
 
 
5 Or equivalent effective NA: Lamivudine, adefovir dipivoxil, ETV, telbivudine and TDF have been 
approved in most Asia Pacific countries. Patients will be switched to ETV 0.5 mg or Tenofovir 
Disopropil 245 mg or Tenofovir Disoproxil Fumarate (TDF) 300 mg during screening period if they 
are not already taking this drug with the same dosage or equivalent. 
6 Genotype information will be collected from medical history, if not available best effort to assess 
in virologically appropriate plasma sample will be used. 
7 The performance characteristics of the HBsAg quantitative assay will be reported in the laboratory 
manual. The same assay will be used for all study visits. A validated test will be used (such as 
Quest Diagnostics quantitative HBsAg or DIASORIN LIAISON® XL HBsAg Quant ([REF] 310250).  
Rational: HBsAg level <100 IU/mL predictive for sustained response 2 years after EOT. The role 
of HBsAg levels in the current management of chronic HBV infection [Höner et al, 2014]. 
8 Cross resistance has been described between lamivudine and ETV, as well as telbivudine. In 
case of previous therapy with lamivudine or telbivudine and current treatment with ETV, a 
possible cross resistance must be documented as to be unlikely by appropriate in vitro testing 
(mutational analysis M204V/I, rtT184, rtS202, or rtM250), else history of previous Lamivudine 
therapy leads to exclusion. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 24 of 123 
 
 
 
e. Has normal or clinically not relevant levels of 
GGT (≤ 2.0 ULN) 
f. International normalized ratio ≤ 1.2 x ULN, 
unless on anticoagulant therapy 
g. Platelet count ≥ 100 G/L 
h. Has albumin ≥3.5 g/dL. 
7. Is not of childbearing potential or, if of childbearing 
potential, is not pregnant as confirmed by a negative 
serum human chorionic gonadotropin test at screening 
and is not planning a pregnancy during the course of the 
study. 
8. Women of childbearing potential (WOCBP) and male 
patients with WOCBP partners must agree to use a dual 
method of contraception as defined in the study protocol 
or practice complete abstinence from sexual intercourse 
if this is the patient’s usual and preferred lifestyle 
throughout the duration of the study and for 90 days after 
stopping study drug. Patients who are using hormonal 
contraceptives should be instructed to use an additional 
contraceptive measure during the study. Note: A woman 
is considered of childbearing potential following 
menarche and until becoming postmenopausal unless 
permanently sterile. A postmenopausal state is defined as 
no menses for >12 consecutive months without an 
alternative 
medical 
cause. 
A 
follicle-stimulating 
hormone 
level 
in 
the 
postmenopausal range will be used to confirm a 
postmenopausal state in women <55 years of age. 
Permanent sterilization methods include hysterectomy, 
bilateral salpingectomy, and bilateral oophorectomy. 
Exclusion Criteria: 
A patient who meets any of the following exclusion criteria will 
be excluded from participation in the study: 
1. Is an employee of a contract research organization 
(CRO), vendor, or Sponsor involved with this study. 
2. Has 
known 
hepatocellular 
carcinoma 
or 
pancreaticobiliary disease.  
3. Neutropenia (defined by two confirmed values within 
screening period of <1500/μL). 
4. Has Gilbert syndrome. 
5. Shows evidence of worsening liver function, defined as 
either a confirmed (two assessments at least 3 days apart) 
increase >2 ULN ALT or AST or an increase of >1.5 × 
first assessed value of TBL or associated with clinical 
signs or symptoms of liver impairment. 
6. Has known or suspected non-CHB liver disease, 
including, but not limited to, Hepatitis D virus co-
infection, 
alcoholic 
liver 
disease, 
non-alcoholic 
steatohepatitis diagnosed with liver biopsy, autoimmune 
disease, human immunodeficiency virus, active hepatitis 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 25 of 123 
 
 
 
C virus (HCV 9 ), Wilson disease, hemochromatosis, 
hepatocellular carcinoma (normal AFP at screening 
required) or suspected or known other liver cancer, 
primary 
biliary 
cholangitis, 
primary 
sclerosing 
cholangitis, drug-induced liver injury (DILI), bile duct 
obstruction. 
7. History of cirrhosis or liver decompensation, including 
ascites, hepatic encephalopathy, or presence of 
oesophageal varices. 
8. Probable or possible F3 stage with a vibration controlled 
transient elastography (VCTE). Patients with normal 
baseline ALT and VCTE >8.8 kPa are excluded. Patients 
with baseline ALT >ULN (but <2ULN per EC5) and who 
have VCTE >10.5 kPa at baseline are excluded10. 
9. Has known history of alcohol abuse or daily heavy 
alcohol consumption (females: >14 units of alcohol per 
week; males: >21 units of alcohol per week [1 unit of 
alcohol is equivalent to a half pint of beer {285 mL}, 1 
measure of spirits {25 mL}, or 1 glass of wine {125 
mL}]). Has an Alcohol Use Disorders Identification 
Test-Concise (AUDIT-C) score of >3 points for men and 
women AND a full AUDIT score of >8 points at 
screening. Note: Only patients with AUDIT-C scores >3 
points at screening will receive the full AUDIT and will 
be excluded if they score >8 points on the full AUDIT. 
Patients with AUDIT-C scores <3 points will not receive 
the full AUDIT. 
10. Is pregnant or breastfeeding. 
11. Has clinically relevant immunosuppression, including, 
but not limited to, immunodeficiency conditions such as 
common variable hypogammaglobulinemia. 
12. Has a known pre-existing medical or psychiatric 
condition that could interfere with the patient’s ability to 
provide informed consent or participate in study conduct, 
or that may confound study findings. 
13. Has known dyslipidaemia with higher cardio-vascular 
risk from worsening lipid parameters (history of 
clinically significant cardiovascular or cerebrovascular 
disease during 12 months prior to study entry). 
14. Has, in the opinion of the Investigator, clinically 
significant cardiovascular or cerebrovascular disease 
 
 
9 Note: HCV antibody (HCV Ab) positive individuals are not eligible, with the following 2 
exceptions: (a) Patients previously treated with a registered drug for viral hepatitis C with at least 
a 1-year period since documented sustained virologic response may be eligible if HCV ribonucleic 
acid (RNA) is below the lower limit of quantification (LLOQ) and if all other eligibility criteria are 
met, and (b) patients with presence of HCV Ab if HCV RNA is below the LLOQ at screening 
without treatment (i.e., spontaneous clearance) may be eligible if all other eligibility criteria are 
met. 
10Tapper et al., 2015, Liang, 2017, Marcellin et al., 2009, Chon et al., 2012 and Chan et al., 2009. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 26 of 123 
 
 
 
within 12 months prior to the first study drug 
administration, including, but not limited to, myocardial 
infarction, acute coronary syndrome, revascularization 
(percutaneous coronary intervention or coronary artery 
bypass grafting) or ischemic stroke, or implanted 
defibrillator or pacemaker. 
15. Has participated in any study with administration of an 
investigational drug in the past 30 days, or 5 half-lives, 
whichever is longer, prior to the first study drug 
administration in the current study. 
16. Has had major visceral or orthopaedic surgery within 30 
days prior to the first study drug administration in the 
current study. 
17. Has a hypersensitivity to the study drug or to any of the 
excipients or placebo. 
18. Has a history of relevant drug and/or food allergies. The 
term “relevant” applies if any of the following allergy 
conditions are met: 
a. Has had several episodes of drug-induced 
urticaria. 
b. Immediate 
allergic 
signs 
(e.g. 
rhinoconjunctivitis, respiratory) with 2 or more 
episodes (at whatever time in medical history) 
due to an identified drugs or food (seasonal 
rhinoconjunctivitis is not an exclusion). 
c. Has ongoing urticaria episodes (attributed to 
whatever allergen) or has other active (current) 
immediate type reaction allergies (e.g. allergic 
rhinoconjunctivitis, allergic asthma, or latex 
allergy). 
d. Has had a moderate or severe allergic reaction 
(Grade 2 per the World Allergy Organization 
reference table, i.e., isolated non-drug induced 
urticaria of Grade 1 is not relevant). 
e. Has any allergic condition that might require an 
emergency epinephrine injection (similar to the 
EpiPen® Auto-Injector). 
19. Has used anti-HBV medications other than NAs within 
90 days prior to screening. 
20. Is using any of the following disallowed medications 
within 30 days or 5 half-lives prior to screening 
whichever is longer, or planned use later during study 
participation: vitamin K antagonists such as warfarin, 
anticancer (except anti-hormonal which are allowed) 
drug(s), immunomodulator(s), or immunosuppressant(s) 
or any drug with known liver toxicity for >2 weeks in the 
year prior to screening (e.g. amiodarone, methotrexate, 
systemic glucocorticoids, tetracyclines, estrogens at 
doses greater than those used for hormone replacement, 
anabolic steroids, or valproic acid or other known 
hepatotoxins at the Investigator or Medical Monitor’s 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 27 of 123 
 
 
 
discretion), ursodeoxycholic acid, or obeticholic acid 
within 90 days prior to screening. Agents (including 
over-the-counter 
weight 
loss 
preparations) 
or 
medications known to significantly impact body weight 
within 30 days prior to screening (e.g. sibutramine, 
phenetamine, and orlistat). 
21. Is using lipid lowering drugs such as statins (other than 
rosuvastatin, 
atorvastatin, 
simvastatin, 
pravastatin, 
fluvastatin or lovastatin). 
22. Has planned major visceral, orthopaedic or neuro surgery 
during the study period. 
23. Has uncontrolled type 1 diabetes mellitus or type 2 
diabetes mellitus (T2DM) (haemoglobin A1c >9.5%). 
24. Has any of the following exclusionary laboratory results 
at screening: 
a. Estimated 
glomerular 
filtration 
rate 
<60 
mL/min/1.73 m2 (the Modification of Diet in 
Renal Disease formula). 
b. Thyroid-stimulating hormone >1.5× ULN or 
abnormal free triiodothyronine or free thyroxine. 
Note: Unless otherwise specified, repeat testing may be 
performed in consultation with the Medical Monitor if 
any of the above laboratory abnormalities are found. 
25. Has a history of clinically significant gastrointestinal 
disease, especially peptic ulcerations, gastrointestinal 
bleeding, inflammatory bowel disease, bariatric surgery, 
renal, neurologic, hematologic, endocrine, oncologic, 
pulmonary, immunologic, or cardiovascular disease or 
any other condition, which, in the opinion of the 
Investigator, would jeopardize the safety of the patient or 
impact the validity of the study results. 
Duration of Treatment: 
The maximum total engagement duration for eligible patients in 
this study is up to 370 days: 90 days screening, 112 days (16 
weeks) treatment period and 168 days (24 weeks) follow-up 
Criteria for Evaluation: 
Efficacy Variables 
● Primary 
o HBsAg decline (Δ log10) from Day 1 to Week 16 of 
treatment 
● Secondary 
o HBsAg responder rate (decrease from baseline ≥ 1.0 on 
the log10 scale) at Week 16 of treatment and Weeks 20, 
28 and 40 of follow-up 
o HBsAg responder rate (decrease from baseline ≥ 0.5 on 
the log10 scale) at Weeks 12 and 16 of treatment and 
Weeks 20, 28 and 40 of follow up. 
o HBsAg loss rate (% patients with HBsAg < LLOQ) at 
Week 16 of treatment and Weeks 20, 28 and 40 of 
follow-up 
o HBsA loss rate (Proportion of results that are Target Not 
Detected versus Target Detected) at Week 16 of 
treatment and Weeks 20, 28 and 40 of follow-up 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 28 of 123 
 
 
 
o Relapse rate HBsAg (% patients who became negative 
[HBsAg < LLOQ], then increased with HBsAg > 
LLOQ) at Week 16 of treatment period and Weeks 20, 
28 and 40 during follow-up period 
o Virologic failure rate (breakthrough)11 of HBV-DNA (% 
patients with a confirmed quantifiable HBV DNA 
increase of ≥ 1log10 HBV DNA copies/mL above 
LLOQ12) assessed at Week 16 of treatment period and 
Weeks 20, 28 and 40 during follow-up period  
o HBV-pgRNA decline (Δ log10) from Day 1 to Weeks 4, 
8, 12 and 16 of treatment period and Week 40 of 
maintenance period. 
o HBcrAg decline (Δ log10) from Day 1 to Weeks 4, 8, 12 
and 16 of treatment period and Week 40 of maintenance 
period 
o HBeAg quantification for HBeAg pos patients and 
changes at Week 16 of treatment and Week 40 of 
follow-up 
o Fibroscan VCTE change from screening value to Weeks 
16 and 40 or ET value 
 
Pharmacokinetic Variables 
Plasma concentration of EYP001a or any relevant active 
metabolites (as identified in an ongoing phase 1 study) will be 
assessed. 
Fasting plasma samples will be collected at all study visits pre-
dose in the morning on Day 1 and at Weeks 2, 4, 6, 8, 10, 12, 14, 
and 16, and in the morning at the ET Visit. 
If by error patient has taken study medication on study visit days 
prior to coming to the clinic the accurate time of last dosing and 
blood draw will be recorded. 
Plasma will be stored at -80°C until analysis. Plasma samples 
will be analysed for EYP001a and any active metabolites using 
a validated liquid chromatography/mass spectrometry 
(LC-MS/MS) method. 
Pharmacodynamic markers 
EYP001a PD parameters to be determined include: 
o Plasma C4 (7α-hydroxy-4-cholesten-3-one) 
o FGF19 
o Plasma primary and secondary Bas  
 
 
11 Breakthrough samples will be further assessed for resistance assessments, including both for 
the nucleos(t)ide analogue as well as for EYP001a (e.g., sequence analysis of FXR response 
elements in HBV genome). Details will be described in the Laboratory manual. 
12 HBV DNA results <LLOQ will be reported as either <LLOQ/Detected (i.e. LLOQ/TD) or 
<LLOQ/Target Not Detected (i.e. LLOQ/TND), both are considered LLOQ. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 29 of 123 
 
 
 
Plasma C4, FGF19; Bas (total, primary, and secondary Bas [such 
as chenodeoxycholic acid {CDCA}, deoxycholic acid {DCA}, 
lithocholic acid {LCA}, and/or others as appropriate]) sampling 
will occur pre-dose paired with PK sampling at all visits during 
treatment period. A sample will also be collected at the Weeks 28 
and 40 (EoS) or ET Visits.  
Samples for Bas will be collected and stored centrally frozen for 
subsequent assessment after the end of study pending ongoing BA 
profiling related to EYP001a pharmacology. 
Safety and Tolerability 
The safety and tolerability of EYP001a will be assessed 
throughout the study. 
Safety and tolerability will be determined by evaluating medical 
history (including evaluation of AEs and concomitant 
medication use) and assessments will include the monitoring of 
adverse events (AEs) and SAEs, and findings from physical 
examinations, vital signs, 12-lead ECGs, and clinical laboratory 
parameters.  
Statistical Methods: 
Statistical Analysis Plan and General Statistical Methods 
All data will be handled and processed according to the 
sponsor’s representative (Novotech (Australia) Pty Ltd) SOPs, 
which are written based on the principles of GCP. 
A Statistical Analysis Plan (SAP) containing the detailed 
planned statistical methods will be finalized prior to locking of 
the study database for the interim and final analysis and will 
form the basis for the programming of the displays and analyses 
of the final study data. All statistical calculations will be 
performed using SAS® (SAS Institute Inc., Cary, NC, USA) or 
similar software. 
The statistical analyses will consist of both inferential and 
descriptive statistics. In general, the data will be presented by 
dose group. All collected and derived data will be included in 
the patient data listings. 
Analysis Population: 
The following analysis sets are defined for this study. 
Intention-To-Treat (ITT) Set defined as the set of all randomized 
patients, irrespective of whether a patient receives any study 
drug. This set will be based on randomized treatment and will be 
used for the baseline, demographic summaries and efficacy 
summaries. 
Modified Intention-To-Treat (mITT) Set, defined as the set of all 
randomized patients, who received any amount of study drug, 
have a measurable baseline HBsAg assessment and a 16-week 
post baseline efficacy assessment. This set will be based on 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 30 of 123 
 
 
 
randomized treatment and will be used for efficacy analyses. 
Per Protocol (PP) Set defined as the set of patients who meet 
the mITT set requirements and were not associated with a major 
protocol violation. This set will be identified before the start of 
the final analysis and will be used to support the analysis 
conducted for the primary efficacy endpoint. Patients will be 
analysed based on the actual treatment received. 
Safety Analysis Set (SAS) defined as all patients who receive at 
least one confirmed dose of the study drug and will be based on 
actual treatment received. The SAS will be used for all safety 
and tolerability analyses. 
Pharmacokinetic (PK) Set will consist of all patients who 
received any study drug administration and that have sufficient 
and interpretable EYP001a concentrations data. Patients with 
missing sample concentrations will be included in the PK set 
provided that the PK parameters can be adequately characterized 
based upon the remaining data. Protocol violations and 
individual patient profiles will be assessed on a case-by-case 
basis to determine if the patient, or specific concentration 
values, should be excluded from the PK set.  
Pharmacodynamic (PD) Set will consist of all patients included 
in the SAS with a measurable baseline PD assessment and at 
least one measurable post baseline PD assessment, will be 
included in the PD set. 
Statistical Methods 
Patient disposition will be summarized using counts and 
percentages. Demographic and baseline information including 
treatment history, HBV genotype, age, gender, body mass index, 
weight, and height will be summarised by treatment group using 
the ITT set.  
All Efficacy analyses will be based on the ITT set unless 
otherwise specified. All efficacy data will be summarised by 
study visit and treatment group. 
The PK analysis will be based on the PK set. 
Individual plasma concentrations and trough levels of EYP001a 
and any active metabolites will be listed for each patient and 
summarised by nominal sampling time point and treatment 
group with descriptive statistics. All concentrations below the 
limit of quantification will be labelled as such in the 
concentration data listings. Listings of individual patient plasma 
concentrations and actual blood sampling times and graphs of 
concentration versus time will be prepared. Plasma 
concentrations will be summarized using descriptive statistics. 
The actual PK sampling timepoints will be used for the PK 
analysis. Appropriate validated PK software (eg, Phoenix 
WinNonlin v6.3) will be used. A non-compartmental analysis 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 31 of 123 
 
 
 
will not be performed. 
The PD analysis will be based on the PD set. PD marker 
parameters will be summarized using descriptive statistics and 
will also be presented graphically per treatment group. 
Listings and summaries for all safety data will be presented 
using the Safety Set. Safety endpoints will be summarised by 
treatment group. No formal inferential statistics will be 
performed on safety assessments.  
All AEs will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA®). All AE summaries will be 
restricted to TEAEs only and will be summarised by treatment 
group. 
All AEs will be listed and will include verbatim term, preferred 
term (PT), system organ class, treatment, severity, causality, 
seriousness, and action taken with regards to the study drug. 
Separate listings will be created for SAEs and events leading to 
treatment discontinuation. 
Clinical laboratory results will be summarised by treatment 
group and will include changes from baseline and counts of 
number of values out of normal range at each scheduled time 
point. Shift tables (categorical parameters) may also be used, as 
appropriate. Individual vital signs assessments will be listed for 
each patient. Summaries of vital signs by treatment group will 
include changes from baseline for each parameter at each 
scheduled time point. 
Individual ECG results will be listed for each patient. 
Summaries of ECGs by treatment group will include changes 
from baseline for each parameter at each scheduled time point. 
Physical examination findings will be listed for each patient and 
any changes described in the text of the final report. 
Exposure to study drug and concomitant medications will be 
listed by patient and coded using the most current WHO drug 
dictionary available at the Sponsor. The number and percentage 
of patients who used prior and/or concomitant medications will 
be summarised by Anatomic Therapeutic Chemical (ATC) 
classification levels and treatment group. 
Determination of Sample Size: 
Formal sample size calculations were performed. Using primary 
endpoint assessment assumptions, based on a t-test, 49 patients 
need to be enrolled.  
An unscheduled interim analysis of all available unblinded 
preliminary safety study data will be conducted when any 
stopping rules are met in two or more subjects.  
Two interim analysis are scheduled.  
 
1. First interim analysis on all available unblinded preliminary 
safety study data:  


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 32 of 123 
 
 
 
Safety assessment when 50% (n=25) patients reach week 8 
resulting in a decision on continuation of the study based on 
safety (Go/No go decision); enrolment would remain 
ongoing during this review 
2. Second interim analysis on all available unblinded 
preliminary virology, safety, PK and PD study data:  
Safety and futility when 50% patients (n=25) reached week 
12, resulting in a decision on continuation of the study 
(Go/No go decision) based on safety and evidence of a 
benefit of EYP001 (HBsAg, other secondary viral markers); 
enrolment is ongoing during this review 
 
The interim analyses will be performed on all available primary 
and secondary endpoints according to the SAP and DSMC 
charter, which describes the overall guidelines, composition, 
roles, and responsibilities of the independent DSMC for the 
EYP001-201 study, including the selection of DSMC members, 
timing of meetings, methods of providing information to and 
from the DSMC, frequency and format of meetings, data 
analysis recommendations, and DSMC relationships with other 
parties participating in the conduct of this study.  
 
The futility assessment will be performed to determine if EYP001 
has no benefit at a point when 50% of subjects have reached 12 
weeks of dosing. The futility assessment will be performed by the 
DSMC according to the following rules: 
• 
A treatment effect of -1.0 on a log10 scale of HBsAg for 
the primary endpoint at 16 weeks, and a common 
standard deviation of 1.08 was assumed and the treatment 
effect would be -0.5 after 12 weeks of treatment, with 
common standard deviation of 0.7. Using a one-sided 
alpha of 0.05 and 80% power, a group sequential design, 
incorporating a futility and efficacy O’Brien-Fleming 
analysis when 50% of patients have reached 12 weeks of 
treatment, needs inclusion of 49 patients.  
• 
Table 6 gives the probability of stopping early under the 
null and alternative hypothesis, at the time of the interim 
analysis. The probability of stopping correctly for 
futility is 40%. The probability of stopping wrongly for 
futility is only 3.5%.  
• 
The efficacy boundary is crossed when the 12-week p-
value is less than 0.001, or the difference is less than -
0.971 on a log scale. The futility boundary is crossed 
when the 12-week p-value is higher than 0.603, or the 
difference is more than 0.085 on a log scale.  
 
The stopping of the study for futility will be considered by the 
DSMC by applying these rules. The study will not stop for 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 33 of 123 
 
 
 
efficacy at Week 12 interim analyses, even if efficacy boundary 
is crossed. The criteria are not binding and DSMC can overrule if 
other interim results show beneficial results.  
 
Data will be summarized and presented by treatment group and 
time point in summary tables. Descriptive statistics including 
number of patients (N), means, standard deviations, medians, 
and minimum and maximum values will be presented for 
continuous variables. Counts and percentages will be presented 
for categorical variables. In addition, by-patient listing for all 
safety and efficacy data will be presented. 
Note that all interim analyses will be descriptive. The study 
design does not include any formal statistical guidelines for use 
at interim analysis.  
 
ENYO is developing a mathematical computational HBV 
disease model. The results from EYP001-201 will serve as 
clinical data for the calibration of in silico HBV patients 
simulating the effect of combinational treatments that will 
eventually support designing later trials. With its different sub-
models (HBV replication and excretion, Bas metabolism, 
cholesterol metabolism, immune system, fibrosis, blood virus 
related changes, and EYP001a, ETV and PEG-IFNα2a drug 
models) the disease model of chronic HBV infection will be 
used to predict quantitative efficacy on relevant endpoints (DNA 
HBV in blood, HBsAg) in a representative virtual population. 
The computational model is a system of ordinary differential 
equations (ODEs) which integrates more than 300 biological 
variables and more than 1000 parameters. It will be used to 
explore the effect of combinations of different treatments 
regimens including EYP001a, ETV and PEG-IFNα2a. Iterations 
of the validated model will serve for the exploration of 
alternative arms in the EYP001-203 study (conducted in parallel 
EYP001-201, with treatment naive or virologically non-
suppressed patients treated with EYP001a combined with NA 
and peg-IFN), by simulating different doses and treatment 
regimens. Disease model simulations will support future 
explorations of development strategies, with the upcoming 
EYP001a pivotal study designs. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 34 of 123 
 
 
 
LIST OF ABBREVIATIONS 
AE(s) 
Adverse Event(S) 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
Anti-HBe 
Antibody to Hepatitis B e antigen 
Anti-HBs 
Antibody to Hepatitis B surface antigen 
AST 
Aspartate Aminotransferase 
AUC 
Area Under the Curve 
AUClast 
Area Under the Curve From 0 To The Last Measurable Point 
AUDIT-C 
Alcohol Use Disorders Identification Test-Concise 
BA 
Bile Acid 
BID 
Twice Daily 
BMI 
Body Mass Index 
BP 
Blood Pressure 
BSEP 
Bile Salt Export Pump 
cccDNA 
Covalently Closed Circular Deoxyribonucleic Acid 
CDCA 
Chenodeoxycholic Acid 
CFR 
Code of Federal Regulations 
CHB 
Chronic Hepatitis B infection 
Cmax 
Maximum Plasma Concentration 
CRF(s) 
Case Report Form(S) 
CRO 
Contract Research Organization 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
Cytochrome 
DCA 
Deoxycholic Acid 
DILI 
Drug-Induced Liver Injury 
DNA 
Deoxyribonucleic Acid 
DSMC 
Data Safety Monitoring Committee 
EC50 
50% Of Maximal Effective Concentration 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EoS 
End of Study 
ETV 
Entecavir 
FDA 
Food and Drug Administration 
FGF19 
Fibroblast Growth Factor 19 
FXR 
Farnesoid X Receptor  
GGT 
Gamma-Glutamyl Transferase 
GI 
Gastrointestinal 
HBsAg 
Hepatitis B Surface Antigen 
HBcrAg 
Hepatitis B core-related Antigen 
HBeAg 
Hepatitis B e Antigen 
HBV 
Hepatitis B Virus 
HBV DNA 
Hepatitis B Virus Deoxyribonucleic Acid 
HBV pgRNA 
Hepatitis B Virus pregenomic RNA 
HBx 
Hepatitis B Virus X protein 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 35 of 123 
 
 
 
HCC 
Hepatocellular Carcinoma 
HCV 
Hepatitis C Virus 
HDL 
High Density Lipoprotein 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH-GCP 
International Council for Harmonisation – Good Clinical Practice 
IEC 
Institutional Ethics Committee 
IFN 
Interferon 
INR 
international normalized ratio 
IP 
Investigational Product 
IR 
Immediate Release 
IRB 
Institutional Review Board 
ITT 
Intent to Treat 
IWRS 
Interactive Web Response System 
LCA 
Lithocholic Acid 
LDH 
Lactic Acid Dehydrogenase 
LDL 
Low Density Lipoprotein 
LLOQ 
Lower Limit of Quantification 
MATE1 
Multidrug and Toxin Extrusion 1 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intent to Treat 
mRNA 
Messenger Ribonucleic Acid 
MRP2 
Multidrug Resistance-Associated Protein 2 
MS 
Metabolic Syndrome 
NA 
Nucleos(T)ide Analogue 
NTCP 
Sodium Dependent Taurocholic Co Transporting Polypeptide 
OATP 
Organic Anion Transporter Polypeptide 
ODE 
Ordinary Differential Equation 
PBC 
Primary Biliary Cholangitis 
PD 
Pharmacodynamic 
PE 
Polyethylene 
PK 
Pharmacokinetic 
PT 
Preferred term 
PVC 
Polyvinyl Chloride 
PVDC 
Polyvinylidene Chloride 
QD 
Once Daily 
RNA 
Ribonucleic Acid 
SAE(s) 
Serious Adverse Event(S) 
SAP 
Statistical Analysis Plan 
SOC 
Standard of Care 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TDF 
Tenofovir Disoproxil Fumarate 
TEAE(s) 
Treatment-Emergent Adverse Events 
TFV 
Tenofovir 
Tmax 
Time for Maximal Concentration 
TSH 
Thyroid Stimulating Hormone 
UDCA 
Ursodeoxycholic Acid 
ULN 
Upper Limit of Normal 
USA 
United States of America 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 36 of 123 
 
 
 
VCTE 
Vibration Controlled Transient Elastography 
VLDL 
Very Low-Density Lipoprotein 
WOCBP 
Women of Childbearing Potential 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 37 of 123 
 
 
 
INVESTIGATORS AND STUDY ADMINISTRATIVE 
STRUCTURE 
 
Investigators 
The investigators are identified in separate documents in the Trial Master File. 
 
Study Administrative Structure 
 
Chief Medical Officer 
Pietro Scalfaro MD, MBA, 
ENYO Pharma SA 
60 avenue Rockefeller, 
Bâtiment Bioserra B. 69008 LYON 
FRANCE 
Clinical Project Manager 
Noelie Barzic 
ENYO Pharma SA 
60 avenue Rockefeller, 
Bâtiment Bioserra B. 69008 LYON 
FRANCE 
Contract Research Organization 
Novotech Australia Pty. Ltd. 
Level 3, 235 Pyrmont St 
Pyrmont, NSW 2009 
Australia 
Phone: +61 2 8569 1400 
Fax: +61 2 8569 1498 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 38 of 123 
 
 
 
TABLE OF CONTENTS 
SPONSOR PROTOCOL SIGNATURE PAGE ........................................................ 2 
INVESTIGATOR ACKNOWLEDGEMENT........................................................... 3 
PROTOCOL AMENDMENT SUMMARY .............................................................. 4 
CLINICAL PROTOCOL SYNOPSIS ..................................................................... 17 
LIST OF ABBREVIATIONS ................................................................................... 34 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE ............. 37 
TABLE OF CONTENTS .......................................................................................... 38 
LIST OF TABLES AND FIGURES ......................................................................... 41 
1. 
Introduction .................................................................................................... 43 
1.1. 
Unmet Medical Need ................................................................................... 43 
1.2. 
Background .................................................................................................. 43 
1.3. 
Role of FXR in HBV Infection .................................................................... 43 
1.4. 
Overview of Investigational Product ........................................................... 45 
1.4.1. Mechanism of Action ............................................................................................. 45 
1.4.2. Summary of Nonclinical Experience ..................................................................... 48 
1.4.3. Summary of Clinical Experience ........................................................................... 49 
1.5. 
Research Hypothesis .................................................................................... 53 
1.5.1. Rationale for Study Conduct .................................................................................. 53 
1.5.2. Benefit-Risk Assessment ....................................................................................... 55 
2. 
Study Objectives and Endpoints................................................................... 56 
2.1. 
Study Objectives .......................................................................................... 56 
2.1.1. Primary Objective .................................................................................................. 56 
2.1.2. Secondary Objectives ............................................................................................. 56 
2.2. 
Study Endpoints ........................................................................................... 56 
2.2.1. Primary Endpoint ................................................................................................... 56 
2.2.2. Secondary Endpoints .............................................................................................. 56 
3. 
Study Plan ....................................................................................................... 57 
3.1. 
Description of Overall Study Design and Plan ............................................ 57 
3.2. 
Rationale for Study Design .......................................................................... 59 
3.3. 
Data Safety Monitoring Committee (DSMC) .............................................. 59 
3.4. 
End of Study Definition ............................................................................... 60 
4. 
Study Population ............................................................................................ 60 
4.1. 
Number of Participants ................................................................................ 60 
4.2. 
Inclusion Criteria ......................................................................................... 61 
4.3. 
Exclusion Criteria ........................................................................................ 62 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 39 of 123 
 
 
 
4.4. 
Prohibitions and Restrictions in the study ................................................... 65 
4.5. 
Screen Failures ............................................................................................. 65 
4.6. 
Stopping Rules ............................................................................................. 66 
4.7. 
Participant withdrawal criteria ..................................................................... 67 
4.8. 
Study Termination ....................................................................................... 67 
5. 
Treatments ...................................................................................................... 67 
5.1. 
Identity of Investigational Product ............................................................... 67 
5.1.1. Packaging and Labelling ........................................................................................ 68 
5.1.2. Storage ................................................................................................................... 68 
5.1.3. Description ............................................................................................................. 69 
5.2. 
Treatments Administered ............................................................................. 69 
5.3. 
Method of Assigning Participants to Treatment Groups ............................. 69 
5.4. 
Dose Rationale and Selection of Doses in the Study ................................... 70 
5.5. 
Selection and Timing of Dose for each Participant ..................................... 71 
5.6. 
Contraindications ......................................................................................... 71 
5.7. 
Potential Risks and Adverse Reactions........................................................ 72 
5.8. 
Dose Interruptions and Reductions .............................................................. 72 
5.8.1. Pruritus management: guidance to investigators .................................................... 72 
5.9. 
Blinding........................................................................................................ 73 
5.10. 
Prior and Concomitant Therapy ................................................................... 73 
5.11. 
Treatment Compliance ................................................................................. 74 
5.12. 
Drug Accountability..................................................................................... 74 
5.13. 
Investigational Product Handling and Disposal ........................................... 75 
6. 
Study Assessments and Procedures .............................................................. 75 
6.1. 
Informed Consent......................................................................................... 75 
6.2. 
Schedule of assessments .............................................................................. 75 
6.2.1. Screening Evaluations ............................................................................................ 76 
6.2.2. Treatment Period (Week 1 to Week 16) ................................................................ 77 
6.2.3. Follow-up Period (Week 17 to Week 40) .............................................................. 81 
6.2.4. Early Termination (ET) Visit ................................................................................. 83 
6.3. 
Appropriateness of Measurements ............................................................... 83 
7. 
Efficacy Variables .......................................................................................... 83 
7.1. 
Definitions.................................................................................................... 84 
7.2. 
Drug Concentration Measurements ............................................................. 85 
8. 
Safety Assessments ......................................................................................... 85 
8.1. 
Adverse Events and Adverse Event Reactions ............................................ 86 
8.1.1. Recording of Adverse Events................................................................................. 86 
8.1.2. Follow-up of Adverse Events................................................................................. 87 
8.1.3. Relationship to the Study Drug .............................................................................. 87 
8.1.4. Intensity Assessment .............................................................................................. 87 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 40 of 123 
 
 
 
8.1.5. Abnormal Laboratory Values ................................................................................. 88 
8.1.6. Pre-Existing Medical Conditions ........................................................................... 88 
8.2. 
Serious Adverse Events ............................................................................... 88 
8.2.1. Definition ............................................................................................................... 88 
8.2.2. Reporting of Serious Adverse Events .................................................................... 89 
8.2.3. Follow-up of Serious Adverse Events .................................................................... 90 
8.3. 
Drug-Induced Liver Injury ........................................................................... 91 
8.3.1. Normal values at baseline ...................................................................................... 91 
8.3.2. Elevated values at baseline..................................................................................... 93 
8.3.3. General Considerations .......................................................................................... 95 
8.4. 
Pruritus Assessment ..................................................................................... 96 
8.5. 
Pregnancy ..................................................................................................... 96 
9. 
PK and PD Methods ...................................................................................... 97 
9.1. 
Pharmacokinetics ......................................................................................... 97 
9.2. 
Pharmacodynamics ...................................................................................... 97 
10. 
Data Quality Assurance ................................................................................. 97 
11. 
Statistical Methods and Determination of Sample Size .............................. 98 
11.1. 
Statistical Analysis Plan and General Statistical Methods .......................... 98 
11.2. 
Definition of Analysis Sets .......................................................................... 99 
11.2.1. Intention-To-Treat (ITT) Set .................................................................................. 99 
11.2.2. Modified Intention-To-Treat (mITT) Set ............................................................... 99 
11.2.3. Per Protocol (PP) Set .............................................................................................. 99 
11.2.4. Safety Analysis Set (SAS) ..................................................................................... 99 
11.2.5. Pharmacokinetic Set ............................................................................................... 99 
11.2.6. Pharmacodynamic Set ............................................................................................ 99 
11.3. 
Statistical Methods ....................................................................................... 99 
11.3.1. Patient Disposition ................................................................................................. 99 
11.3.2. Demographic and Baseline Characteristics .......................................................... 100 
11.3.3. Efficacy Analyses ................................................................................................ 100 
11.3.4. PK Analyses ......................................................................................................... 101 
11.3.5. PD Analyses ......................................................................................................... 101 
11.3.6. Safety Analyses .................................................................................................... 102 
11.4. 
Determination of Sample Size ................................................................... 103 
11.4.1. Sample size calculations for the primary endpoint .............................................. 103 
11.4.2. Testing strategy and power for key secondary endpoints .................................... 103 
11.5. 
Interim Analyses ........................................................................................ 104 
11.6. 
Other Analysis ........................................................................................... 105 
12. 
Protocol Amendments, other Changes in Study Conduct ........................ 106 
12.1. 
Protocol Amendments ................................................................................ 106 
12.2. 
Other Changes in Study Conduct ............................................................... 106 
13. 
Ethical Considerations................................................................................. 106 
13.1. 
Independent Ethics Committee/Institutional Review Board ...................... 106 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 41 of 123 
 
 
 
13.2. 
Ethical Conduct of the Study ..................................................................... 106 
13.3. 
Participant Information and Consent ......................................................... 107 
13.4. 
Compensation Arrangements ..................................................................... 107 
13.5. 
Protected Health Information ..................................................................... 107 
14. 
Data Handling and Record Keeping .......................................................... 108 
15. 
Financing & Insurance ................................................................................ 108 
16. 
Financial Disclosure ..................................................................................... 109 
17. 
Reporting & Publication ............................................................................. 109 
17.1. 
Clinical Study Report ................................................................................. 109 
17.2. 
Confidentiality and Intellectual Property Rights of Study Data ................ 109 
17.3. 
Publication Policy ...................................................................................... 109 
18. 
References ..................................................................................................... 110 
19. 
Appendices .................................................................................................... 113 
19.1. 
Appendix A - Schedule of Assessment* .................................................... 113 
19.2. 
Appendix B: Pruritus Scale ........................................................................ 119 
19.3. 
Appendix C: Alcohol Use Disorders Identification Test-Concise ............. 121 
19.4. 
Appendix D: The Alcohol Use Disorders Identification Test: Interview Version
 
123 
 
LIST OF TABLES AND FIGURES 
List of Tables 
Table 1 
HBV replication marker changes from baseline to end of treatment (Day 29) 
and at follow up (Day 35) ................................................................................................. 50 
Table 2 
Comprehensive Details of EYP001a / placebo ............................................. 69 
Table 3 
Criteria for Determination of AE Relationship to Study Drug ..................... 87 
Table 4 
CTCAE Severity grade description .............................................................. 87 
Table 5 
Assumptions for primary endpoint ............................................................. 103 
Table 6 
Probability of different decisions at the interim analysis............................ 105 
List of Figures 
Figure 1 
FXR-induced BA Regulation ........................................................................ 44 
Figure 2 
HBV Entry and Replication Pathway ........................................................... 45 
Figure 3 
Representation of the HBV Life Cycle and Suggested Mechanism of Action 
of EYP001a and NAs on HBV Markers ........................................................................... 46 
Figure 4 
Current Model of FXR/HBV Interactions .................................................... 47 
Figure 5 
Individual changes HBsAg levels (log10 IU/mL) from Day 1 to Day 35, in 
cohort EYP001a 400mg QD group of study EYP001-103 ............................................... 51 
Figure 6 
Changes of HBsAg levels (log10 IU/mL) expressed as AUC from baseline 
Day 1 to Day 29 in study EYP001-103 ............................................................................ 52 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 42 of 123 
 
 
 
Figure 7 
Study Design ................................................................................................. 58 
Figure 8 
Normal liver transaminase and bilirubin at baseline ..................................... 92 
Figure 9 
Elevated liver transaminase and bilirubin at baseline ................................... 94 
 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 43 of 123 
 
 
 
1. 
Introduction 
1.1. 
Unmet Medical Need 
ENYO Pharma is developing EYP001a, a selective, synthetic, non-bile salt, carboxylic acid 
agonist, or modulator, of the farnesoid X receptor (FXR), for the treatment of chronic 
hepatitis B (CHB) virus infections. Chronic liver diseases are major public health problems 
[Sanyal, 2011]. Current worldwide estimations show that 844 million people have chronic 
liver diseases, with a mortality rate of 2 million deaths per year. Patients with chronic 
hepatitis B virus (HBV) infection have increased rates of liver-related mortality due to the 
development of complications, including fibrosis, cirrhosis, and hepatocellular carcinoma 
(HCC). Therefore, there is an urgent need for improved treatment options for chronic liver 
diseases. 
1.2. 
Background 
Hepatitis B is a viral infection that causes both acute and chronic disease, with widespread 
geographic distribution. The primary route for transmission reported in Asia is vertical 
transmission from mother to new-born child, while it is contracted early in childhood in 
sub-Saharan Africa. In contrast, individuals in North America and Europe most commonly 
contract hepatitis B by sexual transmission, intravenous injection drug use, or tattoos. 
Among the adult population exposed to hepatitis B, fewer than 5% will develop chronic 
infection [Hyams, 1995]. Approximately 360 million people worldwide have evidence of 
CHB infection [WHO, 2014]. 
Although HBV infection can be efficiently prevented by vaccination, and managed with 
available treatments, to date there is no reliable cure for the 257 million individuals that are 
chronically infected worldwide with only 9% being aware of their condition [WHO, 2018]. 
In 2017, HBV was still the main cause for liver cirrhosis and liver cancer. Current 
treatments can achieve viral suppression, but long-term to lifelong therapies are needed for 
the majority of infected patients [Misra et al., 2009]. 
Available standard of care (SOC) treatments based on interferon (IFN) and nucleos(t)ide 
analogues (NAs) often fail to induce functional cure, defined by the off-treatment 
suppression of viral replication and the plasma hepatitis B surface antigen (HBsAg) loss 
and undetectable HBV deoxyribonucleic acid (DNA) levels [EASL, 2017]. Small 
molecules interfering with the viral life cycle are strongly needed for more effective and 
better tolerated therapies. 
1.3. 
Role of FXR in HBV Infection 
The FXR belongs to a family of receptors known as the nuclear hormone receptors which 
is highly expressed in the liver, intestine, kidney, and adrenal glands. One of the primary 
functions of FXR activation is to maintain bile acid (BA) homeostasis and to regulate BA 
biosynthesis from cholesterol, as shown in Figure 1. 
Activation of FXR has favourable effect on liver growth and regeneration [Ali et al., 2015]. 
It has been shown to prevent and resolve liver fibrosis in rodents [Fiorucci et al., 2005] and 
to protect against HCC [Guo et al., 2015]. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 44 of 123 
 
 
 
In addition, FXR has been found to be an important regulator of triglyceride and glucose 
homeostasis and a modulator of the intestinal microbiome. FXR agonists are therefore 
gaining attention as potential therapeutic agents in metabolic and hepatobiliary diseases. 
 
Figure 1 
FXR-induced BA Regulation 
 
 
ASBT=apical 
sodium 
dependent 
bile 
acid 
transporter; 
BSEP=bile 
salt 
export 
pump; 
C4=7α-hydroxy-4-cholesten-3- 
one; 
CDCA=chenodeoxycholic 
acid; 
CYP7A1=cholesterol 
7α-hydroxylase; FGF19=fibroblast growth factor 19; FGFR4=fibroblast growth factor receptor 4; 
FXR=farnesoid X receptor; NTCP=sodium dependent taurocholic co-transporting polypeptide; 
OSTαβ=organic solute transporter α and β 
BAs are synthetized in the liver from cholesterol and secreted into the intestinal tract to facilitate 
digestion and absorption of nutrients. The BA precursor C4 has been shown to reflect BA biosynthesis. 
Most BAs are reabsorbed in the ileum, where they bind and activate FXR. This stimulates the synthesis 
of FGF19, which signals to the liver and downregulates BA biosynthesis (adapted from Schaap et al., 2013). 
 
HBV and bile salts metabolism appear tightly interdependent [Lamontagne et al., 2016]. 
Virions enter hepatocytes by binding to heparan sulphate proteoglycans and to the sodium 
dependent taurocholic co-transporting polypeptide (NTCP), a hepatocyte bile salt 
transporter, as shown in Figure 2. The HBV genome enhancer II/core promoter region has 
2 response elements for FXR. FXR agonists have a strong inhibitory effect on HBV 
pregenomic RNA (pgRNA), DNA, and protein synthesis and reverse partly virus induced 
modifications of FXR-dependent gene expressions [Yan et al., 2012]. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 45 of 123 
 
 
 
Figure 2 
HBV Entry and Replication Pathway 
 
 
In May 2016, the Food and Drug Administration (FDA) granted an accelerated approval to 
the synthetic bile salt and FXR agonist OCALIVA™ (obeticholic acid) for the treatment 
of primary biliary cholangitis (PBC) and liver cirrhosis in adults with an inadequate 
response to ursodeoxycholic acid (UDCA) [OCALIVA ® Summary Basis of Approval 
(SBA); OCALIVA US Package Insert (USPI), 2016]. No other FXR agonist has been 
approved so far. 
 
1.4. 
Overview of Investigational Product 
1.4.1. Mechanism of Action 
The FXR is a nuclear receptor that acts as a master regulator of BA metabolism and 
signalling, as well as glucose and lipid metabolism. Activation of FXR inhibits BA 
biosynthesis and increases BA conjugation, transport, and excretion, thereby protecting the 
liver from the harmful effects of bile accumulation. FXR led to considerable interest as a 
therapeutic target for the treatment of metabolic and hepatobiliary diseases.  
In EYP001a Phase 1 trials the physiological FXR engagement has been confirmed, both in 
healthy subjects and CHB patients via the analysis of 2 pharmacodynamic (PD) markers 
reflecting FXR activation: fibroblast growth factor 19 (FGF19) and the BA biosynthesis 
precursor C4 (7α- hydroxy-4-cholesten-3-one). In addition, FXR is a target for the 
inhibition of HBV replication as seen in non-clinical models (please refer to the IB, 2019).  
EYP001a is a synthetic, orally active, non-bile salt, non-steroidal, carboxylic acid FXR 
agonist. EYP001a is an agonist and modulator of the nuclear FXR, a key regulator of bile, 
lipid, and glucose metabolism.  


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 46 of 123 
 
 
 
FXR is an important part of the machinery required for the expression of an episomal HBV 
genome known as the covalently closed circular DNA (cccDNA), characterizing chronic 
infection in the nuclei of infected hepatocytes. cccDNA expression is necessary to produce 
all HBV encoded proteins and infectious viral particles. It encodes 2 FXR response 
elements to which the FXR receptor binds forming a large multimeric, transactivation 
protein complex on the cccDNA. Each of the proteins in the transactivation complex 
contributes to the efficiency of cccDNA expression. The hepatitis B virus X protein (HBx) 
participates in the transactivation complex, the activity of which is regulated by FXR 
modulators in such a manner that the allosteric effects of FXR/agonist binding cause the 
transactivation complex to fall apart, therefore impairing expression of the HBV cccDNA. 
Consequently, FXR agonists inhibit HBV cccDNA gene expression and the expression of 
the HBV encoded proteins and infectious viral particles. Overall FXR led to considerable 
interest as a therapeutic target for the treatment of metabolic and hepatobiliary diseases.  
The mechanism of action of EYP001a and the NAs tenofovir (TFV) and entecavir (ETV) 
is shown in Figure 3. 
Figure 3 
Representation of the HBV Life Cycle and Suggested Mechanism of 
Action of EYP001a and NAs on HBV Markers 
 
 
DNA: deoxyribonucleic acid; ETV: entecavir; HBeAg: hepatitis B e-antigen; HBsAg: hepatitis B surface 
antigen; mRNA: messenger ribonucleic acid; NA: nucleos(t)ide analogue; NTCP: sodium dependent 
taurocholic co-transporting polypeptide; pgRNA: pg/precure ribonucleic acid; TFV: tenofovir. 
 
1.4.1.1. 
Scientific Rationale 
The key HBV receptor at the hepatocyte plasma membrane is NTCP, which is the main 
bile salts receptor allowing internalization of the virus [Yan et al., 2012]. Competition of 
HBsAg and bile salts for NTCP modifies the flux of bile salts and their intracellular 
concentrations which in turn alter the function of the nuclear bile salt receptor FXR. HBV 
infection thus set up a low activation FXR equilibrium characterized by increased FXR 
expression and down or up-regulation of gene activated or repressed, respectively, by FXR 
[Oehler et al., 2014; Slijepcevic et al., 2015]. 
FXR is a proviral nuclear factor for both cccDNA maintenance and/or completion, and 
transcription rate of viral mRNAs in differentiated HepaRG cells [Radreau et al., 2016; 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 47 of 123 
 
 
 
Mouzannar et al., 2018]. FXR expression down-regulation reduces HBV replication. The 
2 proviral activities of FXR are repressed by treatment with FXR ligand GW4064. Down-
regulation of FXR expression and treatment with FXR ligand have additive effect on 
cccDNA while, on transcription, the effect of ligand seems to prevail on the effect of 
reduction of FXR expression. 
FXR is recruited at 2 FXR response elements, 2 short double-stranded DNA sequences, 
and the regulatory regions of the HBV genome [Ramière et al., 2008]. Binding of FXR is 
released by FXR ligand, an effect at odds of that is observed on the promoter of several 
genes dependent on FXR for their expression (manuscript in preparation). 
The effect of FXR ligand GW4064 on transcription is dependent on the presence of the 
viral protein HBx [Mouzannar et al., 2018]. Effect on cccDNA does not depend on HBx. 
FXR and HBx interact (FXRAF1/HBx 3d αhelix) [Niu et al., 2017] and FXR can recruit 
HBx on viral sequences. HBx is mandatory for efficient transcription and is actively 
recruited to the cccDNA [Belloni et al., 2009]. The mechanisms of the proviral activity of 
HBx are still under investigation in the HBV community. HBx might trigger cccDNA 
localization at perichromatin site forming transcriptionally active domains [Hensel et al., 
2018], but debated [Moreau et al., 2018], induce the degradation of the SMC5/6 complex 
[Decorsière et al., 2016], or regulate the balanced recruitment of Sirtuin 1 (SIRT1) and 
HBx on cccDNA [Belloni et al., 2009]. The current model of HBV/FXR interactions is 
depicted in Figure 4. 
Figure 4 
Current Model of FXR/HBV Interactions 
 
1. FXR is recruited to the viral genome at 2 FXRE. FXR recruitment to rcDNA may favour the 
recruitment of nuclear factors for cccDNA completion and maintenance 
2. FXR recruits HBx on the cccDNA, which is a critical viral pro-transcriptional factor 
3. HBx likely allows the tethering of cccDNA at fibre loops at perichromatin sites forming TAD; 
cccDNA is maintained in transcription active supranucleosomal structures 
4. FXR agonists may further regulate cccDNA transcriptional activity through regulation of the 
balance on cccDNA of FXR 2 interactants SIRT1 and HBx 
Bile salt/FXR pathway may define inner hepatocyte environments, defined by FXR expression and activation 
level and associated with various risks of chronic infection. Tuning of FXR pathway varies with age and may 
contribute to HBV infection evolution as suggested by the AAV-HBV model of infection in mice. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 48 of 123 
 
 
 
In the adeno-associated virus-HBV model of infection in mice, treatment with FXR ligand 
represses HBV replication (HBV DNA and HBsAg) in adult mice but not in young mice 
(<8 weeks). Bile salts pathway mature with intestine microbiome and age suggesting that 
indeed FXR-bile salts metabolism may contribute to age-dependent chronic versus acute 
HBV infections proportion [Mouzannar et al., 2018]. 
1.4.2. Summary of Nonclinical Experience 
In vitro, EYP001a activates FXR with a 50% of maximal effective concentration (EC50) of 
4 nM as measured by Fluorescence Resonance Energy Transfer and 3 µM as measured by 
FXR transactivation assay. 
A primary PD study in a model of diabetic mice (db/db mice) showed that treatment with 
EYP001a resulted in a dose-dependent reduction in total cholesterol and triglycerides. 
Safety pharmacology studies showed no effect of EYP001a up to 120 mg/kg on the central 
nervous system or cardiovascular system. No relevant findings were identified in the 
respiratory system. 
1.4.2.1. 
Pharmacokinetics 
Pharmacokinetic (PK) and toxicokinetic profiles of EYP001a were analysed in rats and 
dogs. In both species, reduced exposure was observed with repeat dosing, probably related 
to a decreased absorption resulting from a potential induced decrease of BA production. 
Exposure was consistently lower in males. 
EYP001a is mainly cleared via metabolism.  
In in vitro studies, EYP001a showed a slight induction of cytochrome P450 (CYP) 3A4 
mRNA expression in human hepatocytes and no induction of CYP1A2, CYP2B6, 
CYP2C8, CYP2C9, CYP2C19, or CYP2D6. EYP001a exhibited no inhibitory effect on 
human CYP1A2, CYP2C19, and CYP2D6, minor inhibition of CYP2B6, CYP3A4/5, and 
moderate to strong inhibition of CYP2C9 and CYP2C8. EYP001a showed in vitro 
inhibition of organic anion transporter polypeptide 1B1 and 1B3 (organic anion transporter 
polypeptide [OATP]1B1 and OATP1B3).  
EYP001a has a moderate inhibitory potency on bile salt export pump (BSEP) and a slight 
inhibitory potency on multidrug resistance-associated protein 2 (MRP2); EYP001a showed 
moderate inhibitory potency on multidrug and toxin extrusion 1 (MATE1) and multidrug 
and toxin extrusion 2K protein (MATE2K) uptake transporters. 
1.4.2.2. 
Pharmacodynamics 
Considering both urine and faeces in rats and dogs, the major metabolites were M24 
(resulting from cleavage of EYP001a) and M14 (a diol). Few metabolites were detected in 
plasma samples while most of them were excreted in faeces and, to a limited extent, in 
urine. 
1.4.2.3. 
Toxicology  
The potential toxicological effects of EYP001a have been evaluated in a standard battery 
of in vitro genotoxicity studies and in single- and repeat-dose studies in rats and dogs. 
These 2 species were selected based on metabolic studies which indicated that they 
represent best the metabolic fate of EYP001a. No lethal effect was noted up to 120 mg/kg, 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 49 of 123 
 
 
 
the highest dose tested, in any of the repeated dose toxicity studies performed in the 
2-animal species. 
EYP001a was not mutagenic in the bacterial reverse mutation test.  
Reproductive toxicity studies evaluating the fertility and early embryonic development 
were performed in rats and rabbits. There was no overt teratogenic potential of EYP001a.  
For more details on preclinical experience, please refer to Section 4 of the IB [IB, 2019]. 
1.4.3. Summary of Clinical Experience  
The PK, PD, and safety of EYP001a have been investigated in 180 subjects (96 healthy 
volunteers and 84 patients with CHB) across 4 EYP001a Phase 1 studies (for details, please 
refer to the IB [IB, 2019]). The subjects received treatment as follows: 137 have been 
treated with EYP001a (76 healthy volunteers and 61 chronic HBV patients). These 4 
studies include 3 completed clinical studies and in 1 study that is clinically complete but 
with the clinical study report (CSR) pending (data presented as of 27 August 2018). 
EYP001a was safe and well tolerated over the dose range of 60 mg to 500 mg once daily 
(QD) and 200 mg twice daily (BID). QD regimens were better tolerated compared to BID 
150 mg and 200 mg, with less treatment-related emergent AE i.e., pruritus. In a Phase 1b 
study (), 73 CHB patients were assessed during a 4-week EYP001a treatment: A total of 
48 subjects in Part A with EYP001a monotherapy and 25 subjects in Part B with EYP001a 
combined with pegylated interferon (peg-IFN,) comprised the study. Genotypes were: A: 
n=25, B: n=8, C: n=10, D: n=7 and E: n=4. 90% of patients were HBeAg negative and 
treatment naive. The most common treatment-emergent adverse events (TEAEs), typically 
transient and of mild to moderate intensity, were gastrointestinal (GI) disorders, headache, 
fatigue or flu-like (pyrexia, myalgia) symptoms mostly in Part B peg-IFN treated subjects. 
Pruritus was reported mainly by subjects receiving BID dosing regimen (200 mg BID 
[67%] and 150 mg BID [56%] vs. 11% to 14% in QD). No off-target findings, clinically 
significant changes in vital signs or electrocardiograms, serious adverse event (SAE) or 
suspected unexpected serious adverse reaction (SUSAR) were reported. After 4 weeks of 
EYP001a administration to chronically infected HBV subjects, alanine amino transferase 
(ALT) and aspartate amino transferase (AST) values were within the normal range. Three 
subjects had Grade 3 and 1 had a Grade 4 hepatic flare (ALT/AST increase without signs 
of liver dysfunction in other liver tests) which were normal (total bilirubin, gamma 
glutamyl transferase [GGT], alkaline phosphatase [ALP], international normalized ratio 
[INR] and albumin). These changes were interpreted as typical of those seen in subjects 
with underlying chronic liver disease with clinically not significant slight ALT changes. 
This Phase 1b study also explored the effect on HBV replication markers after 4-week 
treatment with EYP001a monotherapy or in combination with peg-IFN. A significant 
reduction of HBV DNA was seen with standard-of-care (SOC) drugs. More importantly, 
EYP001a reduced HBsAg (up to -0.3 log10 in some patients [AUC of HBsAg log10 
changes]), HBV pgRNA up to -1.7 log10 and a trend for HBcrAg up to -0.9 log10 when 
combined with peg-IFN were found (Table 1,Figure 5 and Figure 6).  
 
 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 50 of 123 
 
 
 
Table 1 
HBV replication marker changes from baseline to end of treatment 
(Day 29) and at follow up (Day 35)  
 
HBV DNA 
(Log10 IU/mL) 
HBV pgRNA 
(Log10 
Cps/mL) 
HBsAg 
(Log10 IU/mL) 
HBcrAg 
(Log10 
U/mL) 
Treatment 
Day 
n 
Mean 
SD 
Mean 
SD 
Mean 
SD 
Mean 
SD 
EYP001a 
(1x100 
mg/day) 
Day 
29 
7 
0.11 
0.5 
0.48 
1.2 
-0.02 
0.1 
-0.32 
1.1 
Day 
35 
7 
-0.40 
1.2 
-0.06 
1.2 
0.01 
0.1 
0.02 
0.5 
EYP001a 
(1x200 
mg/day) 
Day 
29 
8 
0.23 
0.4 
0.35 
1.7 
-0.03 
0.1 
0.24 
1.1 
Day 
35 
8 
0.16 
0.5 
0.90 
1.9 
-0.03 
0.1 
0.22 
0.6 
EYP001a 
(1x400 
mg/day) 
Day 
29 
8 
0.06 
0.3 
0.23 
1.4 
-0.09* 
0.1 
0.02 
0.1 
Day 
35 
8 
-0.04 
0.4 
0.51 
1.2 
-0.05 
0.1 
0.01 
0.2 
EYP001a 
(2x200 
mg/day) 
Day 
29 
7 
0.12 
0.3 
-0.08 
1.9 
-0.02 
0.1 
1.21 
2.2 
Day 
35 
8 
-0.10 
0.4 
-1.20 
1.6 
-0.03 
0.1 
0.78 
1.2 
EYP001a 
(1x300 
mg/day) 
+Peg-INF 
Day 
29 
8 
-2.23* 
1.4 
-1.65* 
1.9 
0 
0.1 
-0.92 
1.6 
Day 
35 
8 
-2.45* 
1.5 
-1.77* 
1.8 
0.04 
0.1 
-1.11 
1.4 
EYP001a 
(2x150 
mg/day) 
+Peg-INF 
Day 
29 
8 
-1.80* 
1.0 
-0.92 
1.8 
-0.05 
0.2 
-0.18 
0.2 
Day 
35 
9 
-1.78* 
1.3 
-1.08 
1.7 
-0.02 
0.1 
-0.29 
1.0 
ETV (open-
label 0.5 
mg/day) 
Day 
29 
7 
-3.61* 
0.7 
-0.34 
2.0 
-0.04 
0.1 
0.03 
0.6 
Day 
35 
7 
-3.79* 
0.6 
-1.14 
2.3 
-0.05 
0.1 
0.56 
1.4 
Placebo 
Day 
29 
8 
-0.14 
0.2 
-0.70 
1.0 
-0.04 
0.1 
0.18 
1.3 
Day 
35 
8 
-0.15 
0.2 
0.16 
2.4 
-0.01 
0.0 
0.31 
1.4 
Placebo 
+Peg-INF 
Day 
29 
8 
-2.35* 
0.9 
-0.24 
1.0 
0.12* 
0.1 
-0.36 
0.9 
Day 
35 
8 
-1.93* 
0.8 
-0.57 
0.6 
0.10* 
0.1 
0.18 
1.4 
Legend: bold are numerical trends (p<0.10) not statistically significant 
* statistically significant (p<0.05) 
 
 
 
 
 
 
 
 
 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 51 of 123 
 
 
 
Figure 5 
Individual changes HBsAg levels (log10 IU/mL) from Day 1 to Day 35, 
in cohort EYP001a 400mg QD group of study EYP001-103 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 52 of 123 
 
 
 
Figure 6 
Changes of HBsAg levels (log10 IU/mL) expressed as AUC from baseline 
Day 1 to Day 29 in study EYP001-103 
 
Legend: The coloured box represents the interquartile interval of the AUC; the thick black line corresponds 
to the median. The upper whisker extends from the hinge to the largest value no further than 1.5 * IQR from 
the hinge (where IQR is the inter-quartile range, or distance between the first and third quartiles). The lower 
whisker extends from the hinge to the smallest value at most 1.5 * IQR of the hinge. Black dots represent 
individual AUCs. 
Analysis of PD markers of FXR activation, confirmed physiological FXR engagement 
through EYP001a. 
For details pertaining to clinical experience, please refer to Section 1.5 of the IB [IB, 2019]. 
1.4.3.1. 
Clinical Pharmacokinetics 
The PK analysis from the phase I study revealed that EYP001a was rapidly absorbed in 
fasting conditions with a lag time of 15 to 30 minutes with plasma concentrations reaching 
Cmax between 2.3 and 4 hours.  
Results of food-effect phase I study EYP001-102 suggest that oral doses of EYP001a were 
well tolerated and did not produce any relevant drug-related TEAEs, other than mild GI 
symptoms, and one subject with mild self-limited pruritus. EYP001a reached similar Cmax 
with all 4 dosing conditions, whereas Tmax tended to increase with food. Overall, EYP001a 
PK in chronically infected HBV subjects seemed to be slightly influenced by food, with a 
delay of few hours in the absorption process, leading to a lower Cmax. EYP001a exposure 
(AUC) appeared to be slightly higher under food conditions and the variability on EYP001a 
PK and the small number of subjects (n=11) did not allow to demonstrate the 
bioequivalence on Cmax, AUClast and AUC. Despite rapid EYP001a elimination kinetics, 
FGF19 and C4 showed a prolonged FXR target engagement over at least 24 hours.  


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 53 of 123 
 
 
 
1.4.3.2. 
Clinical Pharmacodynamics 
Analysis of FGF19 and the BA biosynthesis precursor C4, which are two established PD 
markers of FXR activation, confirmed physiological FXR engagement through EYP001a. 
1.4.3.3. 
Clinical Safety 
Overall, EYP001a was safe and well tolerated over the dose range of 100 mg to 500 mg 
QD and 200 mg BID but was better tolerated with the QD regimen than with BID dosing. 
The most common treatment-emergent adverse events (TEAEs) were gastrointestinal (GI) 
disorders. These TEAEs were transient and were of mild to moderate intensity. Pruritus 
was reported, mainly in subjects in the 200 mg BID and 150 mg BID groups. No off-target 
effect was evidenced. There were no clinically significant changes in vital signs or 12-lead 
electrocardiograms (ECGs). No SAE or SUSAR was reported. 
In most cases, ALT and AST values were within the normal range following EYP001a 
administration in healthy subjects and after single administration in chronically infected 
HBV subjects. After 4 weeks of administration of EYP001a to chronically infected HBV 
subjects, 5 subjects had Grade 3 (n=4) or Grade 4 (n=1) ALT/AST increases without signs 
of liver dysfunction for all other liver tests (total bilirubin, gamma glutamyl transferase 
[GGT], ALP, international normalized ratio [INR], and albumin). These changes were 
interpreted as hepatic flares typical of those seen in patients with underlying chronic viral 
HBV liver disease with clinically not significant slight ALT changes. 
Overall EYP001a is considered safe over the dose range of 100 mg to 400 mg QD and 
200 mg BID given as capsules. Aforementioned data initially supported the selection of the 
400 mg tablet dose for study EYP001-201. Nevertheless, PK and safety/tolerance 
preliminary findings in ongoing EYP001-202 NASH phase 2a and in the EYP001-107 
phase 1 NASH trials with the EYP001a tablet formulation, do not support the use of the 
400mg daily single oral EYP001 dose with the tablet formulation. The reduction to 200mg 
QD (1x200mg tablet) will generate an exposure similar to 400mg QD (2x200mg capsules) 
dose that was previously tested and well tolerated. EYP001a 200mg tablet QD dose can be 
assessed safely in CHB subjects over the planned 16 week treatment period. 
For more details on effects in humans, please refer to Section 5 of the IB [IB, 2019]. 
1.5. 
Research Hypothesis  
1.5.1. Rationale for Study Conduct 
Based on the available nonclinical and clinical Phase 1 data, EYP001a shows engagement 
of FXR with pharmacological effects expected to be related to the hepatobiliary system and 
lipid metabolism. From the available data no off-target effect has been evidenced. In 
healthy human and chronically infected HBV patients, no clinically significant or relevant 
changes in safety laboratory tests were observed with the administration over 15 days of 
repeated oral doses of EYP001a from 60 to 500 mg QD.  
EYP001a showed no potential for QT prolongation in QT-EYP001a concentration 
analysis. Overall, clinical data showed that EYP001a was safe and well tolerated over the 
dose range of 60 mg to 500 mg QD and 200 mg BID. QD regimens were better tolerated 
compared to BID 150 mg and 200 mg, with less treatment-related emergent AE i.e., 
pruritus.  


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 54 of 123 
 
 
 
The phase I study explored the effect on HBV replication markers after 4-week treatment 
with EYP001a monotherapy or in combination with peg-IFN. A significant reduction of 
HBV DNA was seen with SOC drugs. EYP001a was also found to reduce HBsAg, HBV 
pgRNA and HBcrAg when combined with peg-IFN (Table 1, Figure 5 and Figure 6). 
Standard of care (SOC) HBV treatments based on interferon (IFN) and nucleos(t)ide 
analogues (NAs) often fail to induce a functional cure, which is defined by the off-treatment 
suppression of viral replication (i.e. undetectable HBV DNA levels) and the plasma HBsAg 
loss. NA are usually prescribed indefinitely to CHB patients and lead to HBV DNA 
particles suppression in the plasma. However, a functional cure, is not frequent, at best in 
the 1% to 3% range for NA and up to 10% with peg-IFN after 48 weeks of treatment. This 
is due to the persistence of HBV cccDNA in the hepatocytes. Current guidelines 
recommend indefinite NA because an expected high relapse rates after NA discontinuation. 
Pegylated interferon alfa (pegIFNa) treatment is therefore, often considered in mild to 
moderate CHB patients, however combination therapies with NA are not generally 
recommended, since no additional benefit is proven [Zhang et al., 2016]. In a recent 
randomised controlled trial, the 72-week HBsAg loss rates were superior in the pegIFNa 
and Tenofovir Disoproxil Fumarate (TDF) treated patients compared to those observed in 
patients receiving pegIFNa alone or TDF alone (9% vs. 3% vs. 0%) [Marcellin et al., 2016]. 
The clear dichotomy between the immune response present in acute, resolved versus 
chronic persistently HBV-infected patients leads to therapeutic strategies designed to boost 
HBV-specific immunity in CHB patients. Because antigen persistence in the liver seems 
to be a major factor driving the HBV-specific CD4 and CD8 T-cell defects, the suppression 
of HBV antigen production can lead to a functional reconstitution of antiviral T-cell 
responses [Tan et al., 2015]. From an epidemiology perspective it is important to note that 
the prevalence of HBeAg negative CHB has been increasing over the last few decades and 
has become the commonest type of HBV infection in many countries of the world 
[Alexopoulou and Karayiannis, 2014]. 
Finite Peg-IFN therapy for 48 weeks leads to more frequent HBsAg seroconversion, 
however it remains unclear if in combination with NA there is an additive effect. HBsAg 
loss is also more frequent with certain HBV genotypes (A>B>C>D), low HBV DNA loads, 
high ALT and low HBsAg levels. 
Finally although previous studies reported that after NA discontinuation a sustained viral 
response can be obtained in up to 50% of CHB patients virally suppressed with a stable 
yearlong NA therapy, recently two studies reported the unfavourable preliminary results 
for NA discontinuation: the Australian HBV-STOP interim showed in HBeAg negative 
patients that at week 48 after stopping NA 100% had reactivation of HBV DNA, 55% were 
in the immune control phase and 14% had restarted NA therapy. A HBsAg reduction >1 
log10 was observed in 57% at 48 weeks. Only 1/44 patients had an HBsAg loss and 32% 
had ALT flares (defined >5x ULN). The Toronto study in a similar HBV population of 
n=67, mostly Asian, HBeAg positive or negative, virologically suppressed patients and 
who were randomized to stop (67%) or maintain NA (33%), showed at 48 weeks of 
follow-up after stopping that 74% had relapsed and only 2/67 patients had HBsAg loss, 
21% had ALT >10x ULN and another 10% ALT >5x ULN. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 55 of 123 
 
 
 
Overall given the high need to improve functional HBV cure rates with a finite treatment 
and the observations of oral QD doses of EYP001a to be well tolerated, with a 
dose-dependent signal on HBsAg reduction after only 4 weeks therapy, the exploration of 
an EYP001a prolonged treatment on top of NA seems justified. The study EYP001-201was 
initially designed to test the safety and the antiviral effect of 400 mg QD EYP001a when 
administered in combination with stable NA therapy over 16 weeks on HBsAg in CHB 
patients who are virologically suppressed on a stable NA therapy1. 
Nevertheless, in light of preliminary findings in ongoing EYP001-202 NASH phase 2a and 
in the EYP001-107 phase 1 NASH trials (Section 1.4.3.3) the dosage has been modified to 
200mg QD (1x200mg tablet) which generates a similar plasma exposure as 400mg QD 
(2x200mg ) capsules, previously tested and well tolerated dose. 
1.5.2. Benefit-Risk Assessment 
EYP001a is a synthetic, small, non-bile salt agonist of the nuclear FXR, which plays a 
pivotal role in BA metabolism. EYP001a is in early stage development and has no proven 
clinical efficacy.  
Overall at the current stage of development, EYP001a is considered safe and well tolerated 
for oral doses of 500 mg QD over 15 days (study EYP001 C01), 400 mg QD and 200 mg 
BID over 29 days (study EYP001 103).  
Refer to Sections 1.4.2 and 1.4.3 for summary of nonclinical and clinical experience with 
EYP001a, respectively. 
In line and within the range of reported changes for other investigational FXR agonists, as 
well as the FDA- and European Medicines Agency-approved FXR agonist OCALIVA® 
(synthetic bile salt), EYP001a may modify lipid blood profiles in the long term. This 
appears to be a class effect with an unknown risk in the long term and requires monitoring 
in patients considered for chronic treatment with FXR agonist. The potential risks of 
long-term high density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol 
profile modifications need to be weighed against the possible therapy benefits – additional 
information from ongoing and future studies will be sought for a complete and accurate 
determination of this potential risk. In addition, patients should be monitored for 
liver-related adverse reactions and pruritus. 
Overall, based on available nonclinical and clinical data, and prior knowledge with FXR 
agonist showing favourable effect on liver growth and regeneration and prevention or 
resolution of liver fibrosis, and the possible favourable effect on HBsAg reduction, the 
risk-benefit profile of EYP001a is judged as acceptable for the further exploration in 
chronically infected HBV patients. 
 
 
1 Note: an independent 2nd phase 2a study named EYP001-203 will be conducted in parallel for 
treatment naïve virally not suppressed patients (i.e. HBV DNA >20’000 IU/mL) assessing 
EYP001a effect combined with NA and peg-IFN. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 56 of 123 
 
 
 
2. 
Study Objectives and Endpoints 
2.1. 
Study Objectives 
2.1.1. Primary Objective 
• To determine the effect of EYP001a on top of NA (SOC therapy) on HBsAg plasma 
levels 
2.1.2. Secondary Objectives 
• To establish the effect of EYP001a on top of NA on HBsAg responder rate at the 
end of the 16-week EYP001a treatment and at 24-week of follow-up (Week 40).  
• To establish the effect of EYP001a on top of NA on HBsAg loss rate at the end of 
the 16-week EYP001a treatment and at 24-week of follow-up (Week 40). 
• To establish the HBV virologic failure rate (breakthrough)2 during the 24-weeks 
follow-up period after stopping EYP001a with ongoing NA. 
• To determine HBV viral response, HBV pgRNA, HBcrAg, HBeAg, anti-HBe and 
anti-HBs at the end of the 16-week EYP001a treatment and Week 40 of follow-up. 
• To explore the safety profile of EYP001a treatment in combination with NA. 
• To determine the plasma concentration of EYP001a and PD markers (plasma C4 
[7α-hydroxy-4-cholesten-3-one]), FgF19 and BAs. 
2.2. 
Study Endpoints 
2.2.1. Primary Endpoint 
• Efficacy assessed as HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment 
2.2.2. Secondary Endpoints 
• Efficacy assessed as: 
o HBsAg responder rate (decrease from baseline ≥ 1.0 on the log10 scale) at Week 
16 of treatment and Weeks 20, 28 and 40 of follow up. 
o HBsAg responder rate (decrease from baseline ≥ 0.5 on the log10 scale) at 
Weeks 12 and 16 of treatment and Weeks 20, 28 and 40 of follow up. 
o HBsAg loss rate (% patients with HBsAg < LLOQ) at Week 16 of treatment 
and Weeks 20, 28 and 40 of follow-up. 
o HBsAg loss rate (Proportion of results that are Target Not Detected versus 
Target Detected) at Week 16 of treatment and Weeks 20, 28 and 40 of follow-up 
o Relapse rate HBsAg (% patients who became negative [HBsAg < LLOQ], then 
increased with HBsAg > LLOQ) at Week 16 of treatment period and Weeks 20, 
28 and 40 during follow-up period 
 
 
2 Breakthrough is defined by quantifiable HBV DNA increase of ≥ 1 log10 HBV DNA copies/mL 
above LLOQ. Breakthrough samples will be further assessed for resistance assessments, 
including both for the nucleos(t)ide analogue as well as for EYP001a (e.g., sequence analysis of 
FXR response elements in HBV genome). Details will be described in the Laboratory manual. 
Also refer footnote no. 9 below. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 57 of 123 
 
 
 
o Virologic failure rate (breakthrough) 3  of HBV-DNA (% patients with a 
confirmed quantifiable HBV DNA increase of ≥ 1log10 HBV DNA copies/mL 
above LLOQ4) assessed at Week 16 of treatment period and Weeks 20, 28 and 
40 during follow-up period 
o HBV-pgRNA decline (Δ log10) from Day 1 to Weeks 4, 8, 12, 16 of treatment 
period and Week 40 of maintenance period 
o HBcrAg decline (Δ log10) from Day 1 to Weeks 4, 8, 12, 16 of treatment period 
and Week 40 of maintenance period 
o HBeAg quantification for HBeAg pos patients and changes at Week 16 of 
treatment and Week 40 of follow-up 
o Fibroscan VCTE change from screening value to Weeks 16 and 40 or ET value 
• Safety and Tolerability assessed as: 
o Treatment-emergent adverse events (TEAEs) (including SAEs) 
o All-cause mortality  
o Clinical laboratory tests 
o Pruritus assessment 
o Vital signs (blood pressure, heart rate, respiratory rate, and temperature) 
o Concomitant medications 
o Physical examinations 
o 12-lead ECG 
• PK assessed as: 
o Plasma concentration of EYP001a or any relevant active metabolites (as 
identified in an ongoing phase 1 study) 
• PD biomarkers: 
o Plasma C4 (7α-hydroxy-4-cholesten-3-one) 
o FGF19 
o Plasma primary and secondary BAs 
3. 
Study Plan 
3.1. 
Description of Overall Study Design and Plan 
This is a prospective, multi-centre, randomized, double-blind, placebo controlled, Phase 2a 
experimental study of oral FXR modulator EYP001a/placebo combined with NA in 
virologically suppressed CHB patients to improve functional cure rates. 
 
 
3 Breakthrough samples will be further assessed for resistance assessments, including both for 
the nucleos(t)ide analogue as well as for EYP001a (e.g., sequence analysis of FXR response 
elements in HBV genome). Details will be described in the Laboratory manual. 
4 HBV DNA results <LLOQ will be reported as either <LLOQ/Detected (i.e. LLOQ/TD) or 
<LLOQ/Target Not Detected (i.e. LLOQ/TND), both are considered LLOQ. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 58 of 123 
 
 
 
In total 49 eligible patients will be enrolled and randomized at approximately 14 study 
sites. Patients will be randomized prior to study drug (EYP001a or placebo and NA) 
administration on Day 1 in the ratio of 3:1 into 2 arms: 
• Experimental Arm: EYP001a 200 mg QD + NA daily (37 patients) 
• Control Arm: Placebo + NA daily (12 patients) 
Patients will also be stratified per HBeAg status, based on medical history HBeAg value 
or established during screening, to obtain a balanced randomization to both study arms. 
The maximum total engagement duration for eligible patients in this study is up to 370 
days: 90 days screening, 112 days (16 weeks) treatment period and 168 days (24 weeks) 
follow-up. 
Patients enrolled in the study will be assessed as outpatients. Patient screening will occur 
no more than 90 days prior to the Day 1 visit. Eligible patients will undergo further 
assessments on Day 1 to qualify for study drug administration on Day 1. 
A diagrammatic representation of the study design is presented in Figure 7: 
Figure 7 
Study Design 
 
 
 
 
The visits during the study are planned as below: 
• Screening visit: 12 weeks (90 days) 
• 16 weeks treatment period: 
o Treatment Visit 1 (Week 1 [Day 1]) 
o Treatment Visit 2 (Week 2 [Day 14 ±3 days]) 
o Treatment Visit 3 (Week 4 [Day 28 ±3 days]) 
o Treatment Visit 4 (Week 6 [Day 42 ±3 days]) 
o Treatment Visit 5 (Week 8 [Day 56 ±3 days]) 
o Treatment Visit 6 (Week 10 [Day 70 ± 3 days]) 
o Treatment Visit 7 (Week 12 [Day 84 ± 3 days]) 
o Treatment Visit 8 (Week 14 [Day 98 ± 3 days]) 
o Treatment Visit 9 (Week 16 [Day 112±3 days]) 
• 24 weeks safety follow-up period: 
o Follow-up Visit 1 (Week 20 [Day 140 ±7 days]) 
o Follow-up Visit 2 (Week 28 [Day 196 ±7 days]) 
o Follow-up Visit 3 (Week 40 [Day 280 ±7 days]) 
Note: during follow-up patients are kept on NA until the end of the trial: Week 40 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 59 of 123 
 
 
 
(consolidation Phase). 
• Post study consolidation period: after Week 40, the investigator can continue or 
stop NA therapy provided the following recommended plan is respected at the end 
of the study: after cessation of antiviral therapy, there is a transition of HBV care 
to a local provider for continued monitoring every 3 months with clinical and 
ALT/AST assessments for at least one year to monitor eventual HBV flares. 
Please refer to Section 6 for planned assessments/activities at each study visit. 
Safety, tolerance, PK /PD and efficacy of EYP001a will be established in an outpatient 
setting. An external, independent Data Safety Monitoring Committee (DSMC) will review 
all available unblinded preliminary virology, safety, PK and PD results when any stopping 
rules (Section 4.6) are met in two or more subjects and on two occasions for a scheduled 
interim analysis. Please refer to Section 3.3 for details. 
3.2. 
Rationale for Study Design  
This study is designed to test the effect of 200 mg QD EYP001a over 16 weeks on HBsAg 
in CHB patients who are virally suppressed while on stable NA therapy. The study will 
employ a randomized, double blind, placebo-controlled design. 
In EYP001a Phase 1 trials the physiological FXR engagement has been confirmed, both in 
healthy subjects and CHB patients via the analysis of two PD markers reflecting FXR 
activation: FGF19 and the BA biosynthesis precursor C4. Overall FXR led to considerable 
interest as a therapeutic target for the treatment of metabolic and hepatobiliary diseases, 
such as CHB. 
Randomized, double-blind placebo-controlled designs are generally acknowledged as 
standard for minimizing the risk of biased estimates of subjective endpoints such as safety, 
tolerability and efficacy. For rationale of dose selection, please refer Section 5.4. 
Both male and female participants are included because CHB, a potential clinical indication 
for EYP001a, affects both genders. 
In order to minimize the risk to study patients and maximize the information gained from 
the study for further development, an independent DSMC will review all available 
unblinded preliminary virology, safety, PK, and PD results when any stopping rules are 
met in two or more subjects and on two occasions for a scheduled interim analysis. 
3.3. 
Data Safety Monitoring Committee (DSMC) 
An external, independent DSMC will review all available unblinded preliminary virology, 
safety, PK, and PD results when any stopping rules are met in two or more subjects 
(Stopping rules details are described in the protocol Section 4.6.). DSMC will also review 
on two scheduled occasions for an interim analysis: 
1. First interim analysis on all available unblinded preliminary safety study data:  
Safety assessment when 50% (n=25) patients reach week 8 resulting in a decision 
on continuation of the study based on safety (Go/No go decision); enrolment would 
remain ongoing during this review 
2. Second interim analysis on all available unblinded preliminary virology, safety, PK 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 60 of 123 
 
 
 
and PD study data: 
Safety & futility when 50% (n=25) patients reached week 12, resulting in a decision 
on continuation of the study (Go/No go decision) based on safety & evidence of a 
benefit of EYP001 (HBsAg, other secondary viral markers); enrolment is ongoing 
during this review 
The interim analyses will be performed on all available primary and secondary endpoints 
according to the SAP and DSMC charter, which describes the overall guidelines, 
composition, roles, and responsibilities of the independent DSMC for the EYP001-201 
study, including the selection of DSMC members, timing of meetings, methods of 
providing information to and from the DSMC, frequency and format of meetings, data 
analysis recommendations, and DSMC relationships with other parties participating in the 
conduct of this study.  
The futility assessment will be performed by the DSMC according to the futility rules 
detailed in Section 11.5, to determine if EYP001 has no benefit at a point when 50% of 
subjects have reached 12 weeks of dosing. The study will not stop for efficacy at Week 12 
interim analyses, even if efficacy boundary is crossed. The stopping of the study for futility 
will be considered by the DSMC by applying these rules. The criteria are not binding and 
DSMC can overrule if other interim results show beneficial results. 
3.4. 
End of Study Definition 
A participant is considered to have completed the study if he/she has completed all study 
visits, including the last Visit or the last scheduled procedure required for statistical 
analysis or safety follow-up. 
The end of this study is defined as the date when the last Visit of the last participant occurs 
or the date at which the last data point required for statistical analysis or safety follow-up 
is received from the last participant, whichever occurs later. 
Follow-up Visit 3 planned in Week 40 on Day 280 ±7 days is considered as EoS visit. An 
early termination (ET) Visit is planned for patients who discontinue early from the study 
for any reason. This visit is planned for a follow-up approximately one week after 
administration of their last dose of any study medication, regardless of how many days the 
patient was in the study. 
4. 
Study Population 
4.1. 
Number of Participants 
The study is open to chronic HBV carriers with no recent (3 months) history of any 
clinically significant conditions, which, in the opinion of the investigator, would jeopardize 
the safety of the patient or impact the validity of the study results. 
Diagnosed CHB is defined by the following values established during screening period: 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 61 of 123 
 
 
 
• HBV virally suppressed with HBV DNA <LLOQ 5 and on stable single NA 
treatment of at least 12 months duration (ETV or TDF)6 
• All genotypes, stratified A vs. non-A7 
• HBeAg negative or positive (expected ratio 7/3): stratification across study arms 
• HBsAg plasma levels >100 IU/mL8. 
4.2. 
Inclusion Criteria 
Patients must satisfy all of the following criteria during screening to be enrolled in the 
study: 
1. Has given voluntary written informed consent before performance of any study 
related procedure. 
2. Must be 18 to 65 years of age, inclusive 
3. Are on stable NA therapy at least 12 months from the screening date (ETV or TDF)9 
4. Has virally suppressed CHB: 
a. HBV DNA <LLOQ and serum HBsAg >100 IU/mL 
5. Has liver imaging to screen for hepatocellular carcinoma or concomitant 
pancreaticobiliary disease either in the prior 6 months or at screening. 
6. Has liver tests during the Screening Period defined as follows: 
a. The baseline values (i.e. two measurements at least 3 days apart: one can be 
 
 
5 The performance characteristics of the quantitative HBV DNA assay will be reported in the 
laboratory manual. The same assay will be used for all study visits. An FDA approved test will be 
used such as Abbott Realtime HBV Assay or COBAS HBV Test.  
6 Or equivalent effective NA: Lamivudine, adefovir dipivoxil, ETV, telbivudine and TDF have been 
approved in most Asia Pacific countries. Patients will be switched to ETV 0.5 mg or Tenofovir 
Disopropil 245 mg or Tenofovir Disoproxil Fumarate (TDF) 300 mg during screening period if they 
are not already taking this drug with the same dosage or equivalent. 
7 Genotype information will be collected from medical history, if not available best effort to assess 
in virologically appropriate plasma sample will be used. 
8 The performance characteristics of the HBsAg quantitative assay will be reported in the 
laboratory manual. The same assay will be used for all study visits. A validated test will be used 
(such as Quest Diagnostics quantitative HBsAg or DIASORIN LIAISON® XL HBsAg Quant 
([REF] 310250). 
Rational: HBsAg level <100 IU/mL predictive for sustained response 2 years after EOT. The role 
of HBsAg levels in the current management of chronic HBV infection [Höner et al, 2014]. 
9 Cross resistance has been described between lamivudine and ETV, as well as telbivudine. In 
case of previous therapy with lamivudine or telbivudine and current treatment with ETV, a 
possible cross resistance must be documented as to be unlikely by appropriate in vitro testing 
(mutational analysis M204V/I, rtT184, rtS202, or rtM250), else history of previous Lamivudine 
therapy leads to exclusion. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 62 of 123 
 
 
 
from medical history if not older than 12 months and one during screening 
period) with both measurements of ALT or AST are ≤ 2 × ULN 
b. Normal or clinically not relevant levels of ALP (≤ 1.5 ULN) 
c. Has total bilirubin (TBL) ≤ 22.2 μmol/L, which corresponds to ≤ 1.3 mg/dL  
d. Has conjugated (direct) bilirubin of ≤ 0.3 mg/dL (i.e. 5.1 μmol/L) 
e. Has normal or clinically not relevant levels of GGT (≤ 2.0 ULN) 
f. International normalized ratio ≤ 1.2 x ULN, unless on anticoagulant therapy 
g. Platelet count ≥ 100 G/L 
h. Has albumin ≥3.5 g/dL. 
7. Is not of childbearing potential or, if of childbearing potential, is not pregnant as 
confirmed by a negative serum human chorionic gonadotropin test at screening and 
is not planning a pregnancy during the course of the study. 
8. Women of childbearing potential (WOCBP) and male patients with WOCBP 
partners must agree to use a dual method of contraception as defined in the study 
protocol or practice complete abstinence from sexual intercourse if this is the 
patient’s usual and preferred lifestyle throughout the duration of the study and for 
90 days after stopping study drug. Patients who are using hormonal contraceptives 
should be instructed to use an additional contraceptive measure during the study. 
Note: A woman is considered of childbearing potential following menarche and 
until becoming postmenopausal unless permanently sterile. A postmenopausal state 
is defined as no menses for >12 consecutive months without an alternative medical 
cause. 
A follicle-stimulating hormone level in the postmenopausal range will be used to 
confirm a postmenopausal state in women <55 years of age. Permanent sterilization 
methods 
include 
hysterectomy, 
bilateral 
salpingectomy, 
and 
bilateral 
oophorectomy. 
4.3. 
Exclusion Criteria 
A patient who meets any of the following exclusion criteria will be excluded from 
participation in the study: 
1. Is an employee of a contract research organization (CRO), vendor, or Sponsor 
involved with this study. 
2. Has known hepatocellular carcinoma or pancreaticobiliary disease.  
3. Neutropenia (defined by two confirmed values within screening period of 
<1500/μL). 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 63 of 123 
 
 
 
4. Has Gilbert syndrome. 
5. Shows evidence of worsening liver function, defined as either a confirmed (two 
assessments at least 3 days apart) increase >2 ULN ALT or AST or an increase of 
>1.5 × first assessed value of TBL or associated with clinical signs or symptoms of 
liver impairment. 
6. Has known or suspected non-CHB liver disease, including, but not limited to, 
Hepatitis D virus co-infection, alcoholic liver disease, non-alcoholic steatohepatitis 
diagnosed with liver biopsy, autoimmune disease, human immunodeficiency virus, 
active hepatitis C virus (HCV10), Wilson disease, hemochromatosis, hepatocellular 
carcinoma (normal AFP at screening required) or suspected or known other liver 
cancer, primary biliary cholangitis, primary sclerosing cholangitis, drug-induced 
liver injury (DILI), bile duct obstruction. 
7. History of cirrhosis or liver decompensation, including ascites, hepatic 
encephalopathy, or presence of oesophageal varices. 
8. Probable or possible F3 stage with a vibration controlled transient elastography 
(VCTE). Patients with normal baseline ALT and VCTE >8.8 kPa are excluded. 
Patients with baseline ALT >ULN (but <2ULN per EC5) and who have VCTE 
>10.5 kPa at baseline are excluded 11. 
9. Has known history of alcohol abuse or daily heavy alcohol consumption (females: 
>14 units of alcohol per week; males: >21 units of alcohol per week [1 unit of 
alcohol is equivalent to a half pint of beer {285 mL}, 1 measure of spirits {25 mL}, 
or 1 glass of wine {125 mL}]). Has an Alcohol Use Disorders Identification 
Test-Concise (AUDIT-C) score of >3 points for men and women AND a full 
Alcohol Use Disorders Identification Test (AUDIT) score of >8 points at screening. 
Note: Only patients with AUDIT-C scores >3 points at screening will receive the 
full AUDIT and will be excluded if they score >8 points on the full AUDIT. Patients 
with AUDIT-C scores <3 points will not receive the full AUDIT. 
10. Is pregnant or breastfeeding. 
11. Has clinically relevant immunosuppression, including, but not limited to, 
immunodeficiency conditions such as common variable hypogammaglobulinemia. 
 
 
10 Note: HCV antibody (HCV Ab) positive individuals are not eligible, with the following 2 
exceptions: (a) Patients previously treated with a registered drug for viral hepatitis C with at least 
a 1-year period since documented sustained virologic response may be eligible if HCV ribonucleic 
acid (RNA) is below the lower limit of quantification (LLOQ) and if all other eligibility criteria are 
met, and (b) patients with presence of HCV Ab if HCV RNA is below the LLOQ at screening 
without treatment (i.e., spontaneous clearance) may be eligible if all other eligibility criteria are 
met. 
11 Tapper et al., 2015, Liang, 2017, Marcellin et al., 2009, Chon et al., 2012 and Chan et al., 2009 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 64 of 123 
 
 
 
12. Has a known pre-existing medical or psychiatric condition that could interfere with 
the patient’s ability to provide informed consent or participate in study conduct, or 
that may confound study findings. 
13. Has known dyslipidaemia with higher cardio-vascular risk from worsening lipid 
parameters (history of clinically significant cardiovascular or cerebrovascular 
disease during 12 months prior to study entry). 
14. Has, in the opinion of the Investigator, clinically significant cardiovascular or 
cerebrovascular disease within 12 months prior to the first study drug 
administration, including, but not limited to, myocardial infarction, acute coronary 
syndrome, revascularization (percutaneous coronary intervention or coronary 
artery bypass grafting) or ischemic stroke, or implanted defibrillator or pacemaker. 
15. Has participated in any study with administration of an investigational drug in the 
past 30 days, or 5 half-lives, whichever is longer, prior to the first study drug 
administration in the current study. 
16. Has had major visceral or orthopaedic surgery within 30 days prior to the first study 
drug administration in the current study. 
17. Has a hypersensitivity to the study drug or to any of the excipients or placebo. 
18. Has a history of relevant drug and/or food allergies. The term “relevant” applies if 
any of the following allergy conditions are met: 
a. Has had several episodes of drug-induced urticaria. 
b. Immediate allergic signs (e.g. rhinoconjunctivitis, respiratory) with 2 or 
more episodes (at whatever time in medical history) due to an identified 
drugs or food (seasonal rhinoconjunctivitis is not an exclusion). 
c. Has ongoing urticaria episodes (attributed to whatever allergen) or has other 
active (current) immediate type reaction allergies (e.g. allergic 
rhinoconjunctivitis, allergic asthma, or latex allergy). 
d. Has had a moderate or severe allergic reaction (Grade 2 per the World 
Allergy Organization reference table, i.e., isolated non-drug induced 
urticaria of Grade 1 is not relevant). 
e. Has any allergic condition that might require an emergency epinephrine 
injection (similar to the EpiPen® Auto-Injector). 
19. Has used anti-HBV medications other than NAs within 90 days prior to screening. 
20. Is using any of the following disallowed medications within 30 days or 5 half-lives 
prior to screening whichever is longer, or planned use later during study 
participation: vitamin K antagonists such as warfarin, anticancer (except 
anti-hormonal 
which 
are 
allowed) 
drug(s), 
immunomodulator(s), 
or 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 65 of 123 
 
 
 
immunosuppressant(s) or any drug with known liver toxicity for >2 weeks in the 
year prior to screening (e.g. amiodarone, methotrexate, systemic glucocorticoids, 
tetracyclines, estrogens at doses greater than those used for hormone replacement, 
anabolic steroids, or valproic acid or other known hepatotoxins at the Investigator 
or Medical Monitor’s discretion), ursodeoxycholic acid, or obeticholic acid within 
90 days prior to screening. Agents (including over-the-counter weight loss 
preparations) or medications known to significantly impact body weight within 
30 days prior to screening (e.g. sibutramine, phenetamine, and orlistat). 
21. Is using lipid lowering drugs such as statins (other than rosuvastatin, atorvastatin, 
simvastatin, pravastatin, fluvastatin or lovastatin). 
22. Has planned major visceral, orthopaedic or neuro surgery during the study period. 
23. Has uncontrolled type 1 diabetes mellitus or type 2 diabetes mellitus (T2DM) 
(haemoglobin A1c >9.5%). 
24. Has any of the following exclusionary laboratory results at screening: 
a. Estimated glomerular filtration rate <60 mL/min/1.73 m2 (the Modification 
of Diet in Renal Disease formula). 
b. Thyroid-stimulating hormone >1.5× ULN or abnormal free triiodothyronine 
or free thyroxine. 
Note: Unless otherwise specified, repeat testing may be performed in consultation 
with the Medical Monitor if any of the above laboratory abnormalities are found. 
25. Has a history of clinically significant gastrointestinal disease, especially peptic 
ulcerations, gastrointestinal bleeding, inflammatory bowel disease, bariatric 
surgery, renal, neurologic, hematologic, endocrine, oncologic, pulmonary, 
immunologic, or cardiovascular disease or any other condition, which, in the 
opinion of the Investigator, would jeopardize the safety of the patient or impact the 
validity of the study results. 
4.4. 
Prohibitions and Restrictions in the study 
Potential patients must be willing to adhere to the following prohibitions and restrictions 
during the course of the study: 
1. Must restrict consumption of caffeinated drinks to 2 per day during the study and 
refrain from any consumption for at least 12 hours prior to study visits 
2. Must refrain from undertaking any strenuous exercise 48 hrs before all Visits  
3. Must refrain from alcohol and/or drug substance abuse during the course of the 
study 
4.5. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 66 of 123 
 
 
 
but are not subsequently enrolled in the study. A minimal set of screen failure information 
is required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials publishing requirements and to respond to 
queries from regulatory authorities. Minimal information includes demography, screen 
failure details, eligibility criteria, and any SAE. 
Individuals who do not meet the criteria for participation in this study (screen failure) may 
be rescreened. Re-screening will be allowed within the screening period of 90 days. Screen 
failures related to laboratory results will only be considered for re-screening. Rescreened 
participants should be assigned the same participant number as for the initial screening. 
4.6. 
Stopping Rules 
Dosing for a patient will be discontinued for any of the following events: 
1. One occurrence of an SAE assessed to be definitely, probably or possibly related to 
dosing with the study drug. 
2. One occurrence of a Grade 4 AE (i.e. life-threatening) assessed to be considered 
“possibly related” or “probably related” to the study drug 
3. One occurrence a Grade 3 rash or higher or acute systemic allergic reaction. 
4. Confirmation of any of the study drug discontinuation criteria as described in 
Section 8.3. 
5. Occurrence of any condition that, in the opinion of the Investigator, significantly 
jeopardizes the wellbeing and safety of the patient and is assessed to be probably 
related to dosing with the study drug. 
6. Clinically significant changes in vital signs or ECGs (such as arrhythmias) assessed 
to be considered “possibly related” or “probably related” to the study drug (i.e., no 
alternative explanation likely).  
7. Clinically significant changes in the safety laboratory tests assessed to be 
considered “probably related” to the study drug (i.e., no alternative explanation 
likely).  
8. A subject experiences a breakthrough (defined by quantifiable HBV DNA increase 
of ≥ 1 log10 HBV DNA copies/mL above LLOQ) the subject should return to the 
study site for a confirmatory measurement within two weeks, and if virologic 
breakthrough is confirmed, EYP001a or placebo dosing should be stopped and NA 
treatment should be continued or modified at the investigator’s discretion. 
If two or more patients meet study drug stopping criteria #1, or #3 to #8, recruitment and 
dosing should be suspended or terminated for the remaining patients, pending the outcome 
of a DSMC review. The DSMC must review all safety data and provide clearance prior to 
dosing any additional patients. 
If one patient meets study drug stopping criteria #2, recruitment and dosing should be 
suspended or terminated for the remaining patients, pending the outcome of a DSMC 
review. 
If one patient experiences a Grade 5 common terminology criteria for adverse event 
(CTCAE) toxicity (based on CTCAE, version 5.0), or if more than 2 patients develop a 
Grade 3 CTCAE toxicity in the same category, the study will be paused, and safety reports 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 67 of 123 
 
 
 
will be submitted to the DSMC for review and clearance prior to dosing any additional 
patients. 
In other situations, re-initiation of study drug may be considered after consultation with the 
Medical Monitor. 
4.7. 
Participant withdrawal criteria 
Each participant has the right to withdraw from the study at any time. In addition, the 
Investigator may discontinue a participant from the study at any time if the Investigator 
considers it necessary for any reason, including the occurrence of an AE or noncompliance 
with the protocol. 
Participants who withdraw from the study for any reason will not be replaced unless it is 
mutually agreed upon, in writing, by the Investigator, the medical monitor, and Sponsor. 
If a participant withdraws or is discontinued from the study, the reason(s) for the 
discontinuation from the study and primary reason will be recorded. An ET Visit is planned 
for a follow-up approximately one week after administration of their final last dose of study 
medication, regardless of how many days the patient was in the study. 
If a participant is discontinued from the study with an ongoing AE or an unresolved 
laboratory result that is significantly outside the reference range, the Investigator will 
attempt to provide follow-up until a satisfactory clinical resolution of the laboratory result 
or AE is achieved.  
4.8. 
Study Termination 
ENYO Pharma may terminate this study prematurely, for reasonable cause, provided that 
written notice is submitted in advance of the intended termination. The Investigator may 
also terminate the study for reasonable cause, after providing written notice to ENYO 
Pharma in advance of the intended termination. Advance notice is not required by either 
party if the study is stopped due to safety concerns. If ENYO Pharma terminates the study 
for safety reasons, ENYO Pharma will immediately notify the Investigator by telephone 
and subsequently provide written instructions for study termination. 
5. 
Treatments 
5.1. 
Identity of Investigational Product 
EYP001a is a white to off-white immediate-release (IR) tablet containing 200 mg of drug 
substance.  
Placebo tablets will be of identical appearance as the active EYP001a. The number of 
placebo tablets to be administered will be adjusted as may be necessary to match the 
number of EYP001a tablets administered.  
NA treatment: ETV 0.5 mg daily or Tenofovir Disoproxil Fumarate (TDF) 300 mg daily 
which is equivalent to 245 mg of tenofovir disoproxil per country specific label will be 
provided as the SOC. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 68 of 123 
 
 
 
5.1.1. Packaging and Labelling 
EYP001a tablets (200 mg) or placebo will be packaged as 7 tablets in an aluminium 
polyvinyl chloride (PVC)/polyethylene (PE)/polyvinylidene chloride (PVDC) blister pack.  
The study doses to be administered to a patient will be labelled according to the PIC/S 
Guide to Good Manufacturing Practice for Medicinal Products. The detail on the labels 
will include, but not be limited to: 
• The notation- ‘For Clinical Trial Use Only’; 
• Protocol number; 
• Investigator/site identification; 
• Trial participant number; 
• Name of sponsor; 
• Route of administration; 
• Batch number; 
• Retest date/expiry date. 
Detailed instructions for the labelling, supply and dispensing instructions of EYP001a are 
described in the study pharmacy manual. 
5.1.2. Storage 
EYP001a tablets are stable when packaged in blisters composed of PVC/PE/PVDC with 
aluminium foil backing at 15-25ºC. 
EYP001a will be supplied dispensed ready for patient dosing by a designated drug depot 
distributor for the sponsor. Study drug supplies will be stored securely under the 
appropriate conditions at the study site according to the applicable regulatory requirements. 
Based on available stability data, EYP001a tablets should be stored at room temperature 
(15-25oC). Refer to the Directions for Use for additional storage requirements in the study 
pharmacy manual. The clinical site must ensure that the products are stored in a secure area 
under recommended storage conditions. It is the responsibility of the investigator to ensure 
that the integrity of packaged investigational products not be jeopardized prior to 
dispensing. 
All materials supplied are for use only in this clinical study and should not be used for any 
other purpose. 
All investigational products will be administered in accordance with the investigator’s 
prescription and it is the investigator’s responsibility to ensure that an accurate record of 
“investigational product issued and returned” is maintained. 
Only participants enrolled in the study may receive the investigational products, in 
accordance with all applicable regulatory requirements. Only authorized and trained site 
staff may supply or administer the investigational products. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 69 of 123 
 
 
 
5.1.3. Description 
Table 2 provides a comprehensive summary of the study drug to be administered in this 
study. 
 
Table 2 
Comprehensive Details of EYP001a / placebo 
 
Investigational Product 
Product Name: 
EYP001a 
Matching placebo 
Dosage Form: 
Tablet 
Tablet 
Unit Dose 
200 mg  
1 
Route of Administration 
Oral 
Oral 
Physical Description 
White to off-white tablet 
White to off-white tablet 
Manufacturer 
of 
Drug 
Substance 
PCAS (France) 
NA 
Formulation/Manufacturing 
of Drug Product 
Catalent (Germany) 
Catalent (Germany) 
For a complete list of excipients, please refer to the study pharmacy manual. 
NA treatment (ETV or TDF) will be provided in combination with EYP001a and placebo 
as a SOC per the dosing guidelines presented in the country-specific label(s). Entecavir 
(ETV) 0.5 mg daily (or per country specific label) or Tenofovir Disoproxil Fumarate (TDF) 
300 mg daily which is equivalent to 245 mg of tenofovir disoproxil will be given per 
country specific label). Patients will continue to receive NA treatment during the follow-up 
phase as well. 
5.2. 
Treatments Administered 
A single daily dose of 200 mg of EYP001a, using one 200 mg tablet, will be orally 
administered in the morning fed or fasted with plain water. 
The investigator is responsible for the education of study staff in the correct dispensing of 
the study drug. The investigator/designee is responsible for the education of study patients 
in the correct administration of the study drug when dosing at home. 
Note: On each treatment visit the study drug should be administered after PK/PD blood 
sampling. 
5.3. 
Method of Assigning Participants to Treatment Groups 
Sequential screening numbers will be assigned to participants at the time of informed 
consent signing. As they are enrolled into the study, participants will be assigned to a 
unique randomization number which are randomly assigned to treatment according to the 
specified randomization scheme. 
The randomization schedule will be computer-generated before the start of the study. 
An Interactive Web Response System (IWRS) will be employed to manage patient 
randomization and treatment assignments. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 70 of 123 
 
 
 
5.4. 
Dose Rationale and Selection of Doses in the Study 
EYP001a Phase 1 data in healthy subjects showed that EYP001a was well tolerated after 
single and multiple oral administration from 30 to 800 mg (single ascending doses) and 
from 60 to 500 mg (multiple ascending doses). For all dosing conditions despite similar 
rapid EYP001a elimination, FGF19 and C4 showed a prolonged FXR target engagement 
up to at least 24 hours, which was not influenced by fasting or fed condition or by morning 
or evening administration (Study EYP001-102). EYP001a was safe in chronically infected-
HBV patients treated over 4 weeks with doses of 100 mg QD, 150 mg BID, 200 mg QD, 
200 mg BID, 300 mg QD, and 400 mg QD, EYP001a. The most frequent TEAEs were 
headache, pruritus, abdominal pain, and diarrhea. Pruritus was mostly seen with BID 
administration and was of mild or moderate intensity and lasting from 5 to 36 days. In 
addition, the QD doses showed better tolerance with few pruritus TEAEs. 
Overall, EYP001a was safe and well tolerated over the dose range of 100 mg to 500 mg 
QD and 200 mg BID but was better tolerated with the QD regimen than with BID dosing. 
This is an early stage Phase 2a exploratory study to determine if adding EYP001a 16-week 
treatment on top of NA can induce a clinically meaningful and statistically significant 
reduction of HBsAg plasma levels after 16 weeks of combined treatment. An initial dose 
strength of 400 mg QD EYP001a capsules was selected because it was the so far highest 
tested dose over 4 weeks and was well tolerated by CHB patients. It also showed an 
apparent dose-dependent signal on HBsAg reduction. 
However in an ongoing phase 2a trial (EYP001-202, 24 NASH subjects enrolled as of 18 
December 2019) and in an ongoing phase 1 trial (EYP001-107, 9NASH and 4 healthy 
subjects enrolled as of 18 December 2019), 100mg and 200mg EYP001a oral tablets were 
tested at the dose levels 100mg BID, 200mg QD and 400mg QD. These are the preliminary 
findings: 
PK profile of EYP001 tablet:  
● The oral EYP001a tablet formulation appears to have higher bioavailability 
compared to the oral capsule formulation previously used in EYP001 phase 1 
studies in healthy and subjects with NASH.  
● The similar exposure seen in NASH subjects with the 200mg QD (1x200mg tablet) 
and the 400mg QD (2x200mg tablets) suggests a saturation phenomenon with 
exposure reaching a plateau over the 200mg dose level  
● A similar EYP001 plasma concentrations were obtained in simulations performed 
for CHB subjects for the 200mg QD (1x200mg tablet) compared to concentrations 
after administration of the 400mg QD (2x200mg capsules). The later was 
previously tested and well tolerated in study EYP001-103 in CHB subjects. 
● Finally the differences of the PK parameters after administration of 200mg, 400mg 
QD repeated oral EYP001a doses either as capsules or tablet  
 
Safety & Tolerance:  


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 71 of 123 
 
 
 
● Pruritus: In an ongoing study EYP001-202 , NASH subjects treated during 12 
weeks (with EYP001a 100mg BID or 200mg QD or 400mg QD or Placebo tablets) 
had an overall pruritus frequency of 15/24 (64%) subjects, all mild or moderate 
episodes, except for three Grade 3. Five pruritus episodes led to early treatment 
termination. This is in contrast with previous experience in study EYP001-103, in 
which CHB subjects were treated during 4 weeks with EYP001a capsules, and had 
mostly mild or moderate pruritus episodes: 1 subject of 7 to 9 (11% to 14%) in each 
of the EYP001 arms (100 mg, 200 mg and 400 mg QD) but increased to 6 of 9 
(67%) subjects treated with 200 mg BID. One subject terminated early because of 
pruritus. 
● ALT/AST: In study EYP001-202, two grade 3 cases of isolated transient ALT/AST 
increases, with no signs of liver impairment, occurred around Day 56 of treatment. 
No Hy’s law cases occurred (no confirmed DILI). The designation by the Primary 
Investigators (PIs) of the liver enzyme elevations did not consider these as clinically 
significant, with a variance over time with few outliers, overall not unexpected in 
the NASH patient population. This compares and is in line with previous phase 1 
trials results, where ALT and AST values were within the normal range following 
EYP001a administration in healthy subjects and in study EYP001-103 after 4 
weeks of administration of EYP001a to CHB subjects, 5 subjects had Grade 3 (n=4) 
or 4 (n=1) ALT/AST increases without signs of liver impairment. The changes were 
interpreted as hepatic flares or typical of those seen in subjects with underlying 
chronic viral HBV liver disease. 
Taken together, these PK and safety/tolerance preliminary findings in the ongoing NASH 
and phase 1 trial obtained with the EYP001a tablet formulation do not support the use of 
the 400mg daily EYP001 dose as a tablet. The reduction to 200mg QD (1x200mg tablet) 
will generate an exposure similar to previously tested and well tolerated 400mg QD 
(2x200mg capsules). EYP001a 200mg tablet QD dose can be assessed safely in CHB 
subjects over the planned 16 week treatment period.  
For more details, please refer to IB memorandum dated 16 January 2020 (IB Memo, 2020). 
5.5. 
Selection and Timing of Dose for each Participant 
The study drug will be administered to patients randomized in the study based on the 
assigned treatment arm: 
• Experimental Arm: EYP001a 200 mg QD + NA daily (37 patients) 
• Control Arm: Placebo + NA daily (12 patients)  
5.6. 
Contraindications 
Although there is no indication from dose-ranging studies that EYP001a has an effect on 
embryo-foetal development in rats and rabbits, and there are no data in humans, pregnancy 
should be avoided in women receiving this compound. Women of childbearing potential 
(WOCBP) should undergo pregnancy testing prior to initiation of EYP001a and 
periodically during treatment. In addition, adequate contraceptive methods should be 
consistently used by males and females during and for 90 days after stopping treatment 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 72 of 123 
 
 
 
with EYP001a. Patients should be counselled on the use of contraception before beginning 
treatment with EYP001a. 
EYP001a is also contraindicated in nursing mothers, as it is not known if EYP001a or any 
of its metabolites are excreted in breast milk. 
EYP001a should also be contraindicated in patients with clinically significant 
hypersensitivity to any components of its formulation.  
5.7. 
Potential Risks and Adverse Reactions  
EYP001a may lead to mild or moderate GI symptoms observed in trial subjects (including 
dyspepsia, nausea, hypersalivation, diarrhea, vomiting and abdominal pain). These are 
transient, short-lasting and self-limited, no specific treatment or measure is required. Other 
observed possible drug-related TEAEs were mild pruritus, headache, dizziness, muscular 
symptoms, increased hepatic enzymes, and skin reactions. 
EYP001a may lead to HDL decrease and/or LDL increase. Although this is in line and 
within the range of reported changes for other FXR agonists under development or the 
approved synthetic bile salt OCALIVA®, and it appears as a likely class effect with an 
unknown risk in the long term. It requires monitoring in patients considered for chronic 
treatment with FXR agonist. The potential risks of a long-term cholesterol profile 
modifications need to be weighed against the possible therapy benefits. 
For more details, please refer to Section 6 of the IB [IB, 2019]. 
5.8. 
Dose Interruptions and Reductions 
Dosages for study drug should be maintained constant during the study. However, safety 
criteria for stopping doses (temporarily or permanently) for individual patients is described 
in Section 4.6.  
5.8.1. Pruritus management: guidance to investigators  
 
Self-limited pruritus mostly mild to moderate has been observed in clinical trials with 
EYP001 and in higher a proportion of patients who received twice daily dosing regimens. 
Pruritus has also been reported with other FXR agonists and in patients with NASH as part 
of the disease natural symptomatology and independent of any pharmacological treatment. 
Tolerance to pruritus may develop over continuous uninterrupted dosing of EYP001. 
 
The following three level therapeutic approach to pruritus can be applied:  
 
1. 
Topical non-pharmacological or over the counter interventions to improve pruritus 
may be tried and can be advised to patients. These include application of 
moisturizers, cooling agents, antihistamines, taking cool showers/showering in the 
morning, using clear/gentle soaps and laundry detergents, application of cold packs 
or fabric strips soaked in cold water, avoidance of wool or other irritating fabrics, 
wearing loose-fitting clothing. 
2. 
With likely no improvement of severe pruritus, a drug holiday of 2 to maximum 5 
days may be considered and in such cases, we would encourage to contact the 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 73 of 123 
 
 
 
Medical Monitor 
3. 
In situation where pruritus prevails and requires systemic oral pharmacological 
treatment, the following drugs may be considered at the investigator’s judgment 
and taking into account individual clinical situation, pruritus severity and 
concomitant medications and comorbidities: antihistamines, hydroxyzine, opioid 
antagonists, gabapentin (note that the concomitant use of opioid agonists and 
gabapentin is not recommended). 
 
5.9. 
Blinding 
Study site personnel, including the Investigator and study team, as well as the study 
patients, will remain blinded to the treatment assignment throughout the course of the 
study.  
Blinding of study treatment will be managed by the packaging and labelling vendor and 
should be maintained by the clinical investigative site’s pharmacy in accordance with the 
Pharmacy Manual. In the event of a medical emergency where breaking the blind is 
required to provide medical care to the patient, the investigator may obtain treatment 
assignment for that patient.  
IWRS should be used as the primary method of breaking the blind. If IWRS cannot be 
accessed, the investigator should contact the Sponsor medical monitor to break the blind. 
Treatment assignment should remain blinded unless that knowledge is necessary to guide 
patient emergency medical care. The investigator is requested to notify the Medical 
Monitor and Sponsor including the medically compelling justification to unblind a patient’s 
treatment assignment. 
Blinding of study treatment is critical to the integrity of this clinical trial and therefore, if 
a patient’s treatment assignment is disclosed to the investigator, the patient will have study 
treatment discontinued. All patients will be followed until study completion unless consent 
to do so is specifically withdrawn by the patient. 
The Sponsor or designee may independently unblind cases for expedited reporting of 
SUSARs as required by regulators. 
5.10. 
Prior and Concomitant Therapy 
Prior medication will be defined as any medication taken within 30 days prior to screening 
and stopped prior to the first dose of study drug. 
Concomitant medication will be defined as any medication taken during the study between 
the date of the first dose of study drug and the date of the EoS/ET Visit. Any medications 
started after the EoS/ET will not be considered concomitant medications. 
Alcohol and drug substance abuse and any other IPs/devices are prohibited during the 
course of the study.  
Therapies considered necessary for the patient’s well-being may be given at the discretion 
of the investigator and should be documented on the electronic case reported form (eCRF). 
Other concomitant medications, except for analgesics, chronic treatments for concomitant 
medical conditions, or agents required for life-threatening medical problems, should be 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 74 of 123 
 
 
 
avoided. Herbal and complementary therapies should not be encouraged because of 
unknown side effects and potential drug interactions, but any taken by the patient should 
be documented appropriately on the eCRF.  
Drugs transported by OATP1B1 have potential for drug-drug interaction with EYP001a. 
Therefore, use of lipid lowering drugs such as statins (other than rosuvastatin, atorvastatin, 
simvastatin, pravastatin, fluvastatin or lovastatin) need Sponsor’s approval. 
Any change in regimen for any concomitant medication, including restricted concomitant 
medications, must be reported to the Sponsor in a timely manner. 
Details of concomitant medications from Screening through (EoS) participation should be 
recorded in the patient’s source documents and in the eCRF. In addition, medications taken 
within the past 30 days prior to Screening should also be recorded. 
5.11. 
Treatment Compliance 
The study drug (EYP001a/Placebo and NA) will be dispensed to the patients by the 
Investigator or study site personnel dedicated to the study on the treatment visits 1, 3, 5, 7 
and 9 (for EYP001a/Placebo dispensation is only at visits 1 and 5, as each boxe is for 8 
weeks of treatment). Please note 16 weeks of treatment (EYP001a/Placebo and NA) with 
8 weeks treatment units will be dispensed. Should the patient “loose” treatment units the 
check on sufficient treatment can be made at each fortnightly visit. Patient diary will be 
provided on the treatment visits 1, 2, 3, 4, 5, 6, 7, 8 and 9. NA will also be dispensed along 
with patient diary, on the follow up visits 1 and 2. Patients will administer the study drug 
(EYP001a/placebo and NA) outside the study sites (at home) during the treatment period 
(Week 1 to Week 16) and follow-up period (Week 17 to Week 40) as instructed by 
Investigator or study-site personnel and will record the dosing details in the patient diary 
to document compliance.  
Data pertaining to tablet count for the study drug will be collected on the treatment visits 
2, 3, 4, 5, 6, 7, 8 and 9; on all follow-up visits and on ET visit. If a patient’s drug 
administration and site-related procedures are not conducted as defined in the protocol, the 
Investigator will make note of ensuring compliance to the protocol for future activities.  
The date and time of each study drug administration and accompanying activity recorded 
in the patient diary will be transcribed in the eCRF. Detailed instructions for the dispensing 
instructions of EYP001a are described in the study pharmacy manual. 
5.12. 
Drug Accountability  
The PI or appropriately trained designee will maintain an accurate record of the receipt of 
the study drug shipment, including the date and quantity received. Refer to the Pharmacy 
Manual for further information. 
In addition, an accurate drug dispensing record will be kept that specifies the amount 
dispensed to each patient and the date of dispensing.  
A drug accountability inventory record to account for all dispending and return of any used 
and unused study drug must be maintained and available by the site staff for inspection at 
any time. At the end of the study, the study drug will be reconciled, and copies of the 
complete record of study drug accountability will be provided to the Sponsor. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 75 of 123 
 
 
 
5.13. 
Investigational Product Handling and Disposal 
The study drug will be sent to the study site under appropriate storage conditions. Upon 
receipt of study drug, study staff are to open the shipment and verify that the amount and 
identity of the contents match that stated in the enclosed shipping form. The Sponsor (or 
designee) is to be notified immediately about any irregularities, discrepancies, or damage. 
The Investigator must not supply the study drug to any person except those named as 
Sub-Investigators or designated staff. They must not dispense any study drug from the 
designated study to non-study patients or individuals. Site personnel must not re-label or 
give study drug to individuals not enrolled in the study. 
The Investigator must ensure that all study drug received at the study site is inventoried 
and accounted for and that dispensed study drug is recorded in the eCRF and in the Study 
Medication Log. The Site Monitor will verify study drug accountability during monitoring 
visits. The study staff will maintain a full record of study drug accountability as described 
in Section 5.12. 
Upon completion of the study, used and unused study drug are to be returned to the Sponsor 
(or designee) or, if prior Sponsor approval is obtained, disposed of in accordance with 
applicable site procedures. ENYO Pharma (Sponsor) or its designee will provide 
instructions for the return or destruction of study drug. 
Study staff must maintain documentation of any missing or unreturned study drug. The 
final disposition of all study drug received at the site is to be documented. 
Detailed instructions for the handling and disposal instructions of EYP001a are described 
in the study pharmacy manual. 
6. 
Study Assessments and Procedures 
6.1. 
Informed Consent 
Written informed consent to use or disclose protected health information, must be obtained 
from a prospective participant before any study-specific procedures are performed for that 
individual. SOC assessments performed before informed consent is obtained may be 
utilized to screen for study eligibility. Participants will read the informed consent form 
(ICF), after being explained about the study. Before signing the ICF, participants will have 
an opportunity to discuss the contents of the ICF with study centre staff. Participants will 
be made aware that they may withdraw from the study at any time. Participants who agree 
to participate in the study will sign the most recently approved ICF and will be provided 
with a copy of the fully executed documents. The original, executed ICF will be maintained 
in the respective participant’s clinical study file.  
Refer to Section 13: Ethical Considerations. The schedule of events for the study is 
described below and in Section 19: Appendices for more details. 
6.2. 
Schedule of assessments  
Schedule of assessments are presented in Section 19.1 and discussed below. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 76 of 123 
 
 
 
6.2.1. Screening Evaluations 
Patients will be assigned screening numbers (Format: three-digit site number ‘-‘three-digit 
participant number e.g. 001-001, 001-002, etc.) consecutively by the Investigator or 
designee at the time the patient signs the ICF. For all patients screened, the Investigator or 
designee will record the eligibility criteria assessment in the medical record. A screening 
and enrolment log will capture the screening number for each patient, the date of screening 
and a screen fail reason(s) for patients that are not eligible to participate.  
Enrolment for this study is defined as any patient that has received at least one dose of the 
investigational product. The enrolment number of the patient will remain the same as the 
screening number.  
Patient who is first designated as a screen failure prior to being randomized may be 
rescreened upon Sponsor or designee approval. Patients will be randomized into the study 
once all eligibility criteria are confirmed. 
All screening tests must be performed within study Weeks -12 to -1, unless otherwise 
indicated. Procedures to be performed at Screening Visit includes the following: 
• Obtain signed written informed consent prior to screening 
• Check patient’s eligibility 
• Review and record patient’s demographic details 
• Review and record patient’s medical history 
• Review and record patient’s prior and concomitant medications 
• Perform drugs of abuse screen12 
• Record patient’s height and body weight 
• Calculate body mass index (BMI) 
• Perform complete physical examination 
• Perform vital signs (systolic/diastolic blood pressure [BP], heart rate, temperature, 
respiratory rate) evaluation 
• Perform AUDIT-C 
• Perform clinical laboratory analysis including haematology, serum chemistry 
panel, coagulation tests, lipid and metabolic profile and TSH. 
• Perform serum pregnancy test (for WOCBP only) 
• Perform Dipstick urinalysis for all male and female patients 
• Perform 12-Lead ECG 
• Sampling for analysis of HBV response markers 
• Perform Fibroscan VCTE 
• Perform Liver imaging (unless done within 6 months prior screening) 
 
All screening Viral serology tests must be performed within study Weeks -12 to -8, unless 
 
 
12 For drugs such as amphetamines, methamphetamine, barbiturates, benzodiazepines, cocaine, 
methadone, opiates, phencyclidine, tricyclic antidepressants and THC (cannabis). 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 77 of 123 
 
 
 
otherwise indicated and test to be performed at Screening Visit includes the following: 
• Perform Viral serology: anti-HIV, anti-HCV13, anti-HDV, quantitative HBV-DNA, 
quantitative HBsAg, anti-HBs, anti-HBe. 
Note: all the PD and PK samplings during the study must be performed before study drug 
administration.  
6.2.2. Treatment Period (Week 1 to Week 16) 
The treatment period begins with the administration of study drug and the study procedures 
are allocated on Treatment Visits 1 (Week 1 [Day 1]), 2 (Week 2 [Day 14 ± 3 days]), 3 
(Week 4 [Day 28 ± 3 days]), 4 (Week 6 [Day 42 ± 3 days]), 5 (Week 8 [Day 56 ± 3 days]), 
6 (Week 10 [Day 70 ± 3 days]), 7 (Week 12 [Day 84 ± 3 days]), 8 (Week 14 [Day 98 ± 3 
days]) and 9 (Week 16 [Day 112±3 days]). The patients will be outpatient during the 
treatment period. Please refer Section 19.1 for overall activities planned for the treatment 
period. 
6.2.2.1. 
Treatment Visit 1 (Week 1 [Day 1]) 
The treatment Visit 1 is planned on Day 1. Following activities are planned for the visit: 
• Confirm patient’s eligibility prior to randomization  
• Review and record patient’s prior and concomitant medications 
• Perform drugs of abuse screen pre-dose 
• Record patient’s body weight 
• Calculate BMI 
• Perform symptom-directed physical examination 
• Perform vital signs (systolic/diastolic BP, heart rate, temperature, respiratory rate) 
evaluation pre-dose 
• Perform AUDIT-C 
• Randomization 
• Pruritus assessment 
• AE monitoring 
• Perform clinical laboratory analysis including haematology, serum chemistry 
panel (including liver safety testing: ALT, AST, Alkaline Phosphatase, Gamma 
Glutamyl Transferase (GGT), Total Bilirubin and Albumin), coagulation tests and 
lipid and metabolic profile 
• Perform urine pregnancy test (for WOCBP only) 
• Perform Dipstick urinalysis for all male and female patients 
• Perform 12-Lead ECG 
• Sampling for analysis of HBV response markers14 
 
 
13 For positive HCV antibody-test results only, a PCR-based quantitative HCV viral load 
assessment will also be performed.   
14 All subjects must have the blood samples collected at pre-dose for quantitative HBV tests: 
HBsAg, HBV-DNA, HBV-pgRNA, HBcrAg and HBeAg (the later only for anti-HBe positives 
subjects).  


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 78 of 123 
 
 
 
• PD biomarker sampling 
• Liver fibrosis and inflammation assessment 
• PK Sampling 
• Dispense patient diary and explain use 
• Dispense EYP001a or placebo and NA (choice between ETV or TFV is at the 
Investigator discretion)  
6.2.2.2. 
Treatment Visit 2 (Week 2 [Day 14 ± 3 days]) 
The treatment Visit 2 is planned on Day 14 ± 3 days in Week 2. Following activities are 
planned for the visit: 
● Review and record patient’s prior and concomitant medications 
● Perform vital signs (systolic/diastolic BP, heart rate, temperature, respiratory rate) 
evaluation pre-dose 
● Pruritus assessment 
● AE monitoring 
● Perform clinical laboratory analysis only liver safety testing: ALT, AST, ALP, 
GGT, total bilirubin, thrombocytes and albumin 
● Sampling for analysis of HBV response markers 
● PD biomarker sampling 
● PK Sampling 
● Review returned patient diary and dispense new diary 
● Collect used/unused study drug and assess compliance 
6.2.2.3. 
Treatment Visit 3 (Week 4 [Day 28 ± 3 days]) 
The treatment Visit 3 is planned on Day 28 ± 3 days in Week 4. Following activities are 
planned for the visit: 
● Review and record patient’s prior and concomitant medications 
● Record patient’s body weight 
● Calculate BMI 
● Perform symptom-directed physical examination 
● Perform vital signs (systolic/diastolic BP, heart rate, temperature, respiratory rate) 
evaluation pre-dose 
● Pruritus assessment 
● AE monitoring 
● Perform clinical laboratory analysis including haematology, serum chemistry 
panel, coagulation tests, lipid and metabolic profile and TSH.  
● Perform urine pregnancy test (for WOCBP only) 
● Perform Dipstick urinalysis for all male and female patients 
● Perform 12-Lead ECG 
● Sampling for analysis of HBV response markers 
● PD biomarker sampling 
● Liver fibrosis and inflammation assessment 
● PK Sampling 
● Review returned patient diary and dispense new diary 
● Dispense NA 
● Collect used/unused study drug and assess compliance 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 79 of 123 
 
 
 
6.2.2.4. 
Treatment Visit 4 (Week 6 [Day 42 ± 3 days]) 
The treatment Visit 4 is planned on Day 42 ± 3 days in Week 6. Following activities are 
planned for the visit: 
● Review and record patient’s prior and concomitant medications 
● Perform vital signs (systolic/diastolic BP, heart rate, temperature, respiratory rate) 
evaluation pre-dose 
● Pruritus assessment 
● AE monitoring 
● Perform clinical laboratory analysis only liver safety testing: ALT, AST, ALP, 
GGT, total bilirubin, thrombocytes and albumin 
● Sampling for analysis of HBV response markers 
● PD biomarker sampling 
● PK Sampling 
● Review returned patient diary and dispense new diary 
● Collect used/unused study drug and assess compliance 
6.2.2.5. 
Treatment Visit 5 (Week 8 [Day 56 ±3 days]) 
The treatment Visit 5 is planned on Day 56 ± 3 days in Week 8. Following activities are 
planned for the visit: 
● Review and record patient’s prior and concomitant medications 
● Record patient’s body weight 
● Calculate BMI 
● Perform symptom-directed physical examination 
● Perform vital signs (systolic/diastolic BP, heart rate, temperature, respiratory rate) 
evaluation pre-dose 
● Pruritus assessment 
● AE monitoring 
● Perform clinical laboratory analysis including haematology, serum chemistry 
panel, coagulation tests, lipid and metabolic profile and TSH. 
● Perform urine pregnancy test (for WOCBP only) 
● Perform Dipstick urinalysis for all male and female patients 
● Perform 12-Lead ECG 
● Sampling for analysis of HBV response markers 
● PD biomarker sampling 
● Liver fibrosis and inflammation assessment 
● PK Sampling 
● Review returned patient diary and dispense new diary 
● Dispense EYP001a or placebo and NA 
● Collect used/unused study drug and assess compliance 
6.2.2.6. 
Treatment Visit 6 (Week 10 [Day 70 ± 3 days]) 
The treatment Visit 6 is planned on Day 70 ± 3 days in Week 10. Following activities are 
planned for the visit: 
● Review and record patient’s prior and concomitant medications 
● Perform vital signs (systolic/diastolic BP, heart rate, temperature, respiratory rate) 
evaluation pre-dose 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 80 of 123 
 
 
 
● Pruritus assessment 
● AE monitoring 
● Perform clinical laboratory analysis only liver safety testing: ALT, AST, ALP, 
GGT, total bilirubin, thrombocytes and albumin 
● Sampling for analysis of HBV response markers 
● PD biomarker sampling 
● PK Sampling 
● Review returned patient diary and dispense new diary 
● Collect used/unused study drug and assess compliance 
6.2.2.7. 
Treatment Visit 7 (Week 12 [Day 84 ± 3 days]) 
The treatment Visit 7 is planned on Day 84 ± 3 days in Week 12. Following activities are 
planned for the visit: 
● Review and record patient’s prior and concomitant medications 
● Record patient’s body weight 
● Calculate BMI 
● Perform symptom-directed physical examination 
● Perform vital signs (systolic/diastolic BP, heart rate, temperature, respiratory rate) 
evaluation pre-dose 
● Pruritus assessment 
● AE monitoring 
● Perform clinical laboratory analysis including haematology, serum chemistry 
panel, coagulation tests, lipid and metabolic profile and TSH 
● Perform urine pregnancy test (for WOCBP only) 
● Perform Dipstick urinalysis for all male and female patients 
● Perform 12-Lead ECG 
● Sampling for analysis of HBV response markers 
● PD biomarker sampling 
● Liver fibrosis and inflammation assessment 
● PK Sampling 
● Review returned patient diary and dispense new diary 
● Dispense NA 
● Collect used/unused study drug and assess compliance 
6.2.2.8. 
Treatment Visit 8 (Week 14 [Day 98 ± 3 days]) 
The treatment Visit 8 is planned on Day 98 ± 3 days in Week 14. Following activities are 
planned for the visit: 
● Review and record patient’s prior and concomitant medications 
● Perform vital signs (systolic/diastolic BP, heart rate, temperature, respiratory rate) 
evaluation pre-dose 
● Pruritus assessment 
● AE monitoring 
● Perform clinical laboratory analysis only liver safety testing: ALT, AST, ALP, 
GGT, total bilirubin, thrombocytes and albumin 
● Sampling for analysis of HBV response markers 
● PD biomarker sampling 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 81 of 123 
 
 
 
● PK Sampling 
● Review returned patient diary and dispense new diary 
● Collect used/unused study drug and assess compliance 
6.2.2.9. 
Treatment Visit 9 (Week 16 [Day 112 ±3 days]) 
The treatment Visit 9 is planned on Day 112 ± 3 days in Week 16. Following activities are 
planned for the visit: 
● Review and record patient’s prior and concomitant medications 
● Record patient’s body weight 
● Calculate BMI 
● Perform symptom-directed physical examination 
● Perform vital signs (systolic/diastolic BP, heart rate, temperature, respiratory rate) 
evaluation pre-dose 
● Pruritus assessment 
● AE monitoring 
● Perform clinical laboratory analysis including haematology, serum chemistry 
panel, coagulation tests, lipid and metabolic profile and TSH. 
● Perform urine pregnancy test (for WOCBP only) 
● Perform Dipstick urinalysis for all male and female patients 
● Perform 12-Lead ECG 
● Sampling for analysis of HBV response markers 
● PD biomarker sampling 
● Liver fibrosis and inflammation assessment 
● Perform Fibroscan VCTE 
● PK Sampling 
● Review returned patient diary and dispense new diary 
● Dispense NA 
● Collect used/unused study drug and assess compliance 
6.2.3. Follow-up Period (Week 17 to Week 40) 
The study procedures during the follow-up period are allocated on Follow-up Visits 1 
(Week 20 [Day 140 ± 7 days]), 2 (Week 28 [Day 196 ± 7 days]) and 3 (Week 40 [Day 280 
± 7 days]). The patients will be outpatient during the follow-up period. Please refer Section 
19.1 for overall activities planned for the follow-up period. 
6.2.3.1. 
Follow-up Visit 1 (Week 20 [Day 140 ± 7 days]) 
The follow-up Visit 1 is planned on Day 140 ± 3 days in Week 20. Following activities are 
planned for the visit: 
• Review and record patient’s prior and concomitant medications 
• Record patient’s body weight 
• Calculate BMI 
• Perform symptom-directed physical examination 
• Perform vital signs (systolic/diastolic BP, heart rate, temperature, respiratory rate) 
evaluation pre-dose 
• Pruritus assessment 
• AE monitoring 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 82 of 123 
 
 
 
• Perform clinical laboratory analysis including haematology, serum chemistry 
panel, coagulation tests and lipid and metabolic profile 
• Sampling for analysis of HBV response markers 
• PD biomarker sampling 
• Liver fibrosis and inflammation assessment 
● Review returned patient diary and dispense new diary 
● Dispense NA 
• Collect used/unused study drug and assess compliance 
6.2.3.2. 
Follow-up Visit 2 (Week 28 [Day 196 ± 7 days]) 
The follow-up Visit 2 is planned on Day 196 ± 3 days in Week 28. Following activities are 
planned for the visit: 
• Review and record patient’s prior and concomitant medications 
• Record patient’s body weight 
• Calculate BMI 
• Perform symptom-directed physical examination 
• Perform vital signs (systolic/diastolic BP, heart rate, temperature, respiratory rate) 
evaluation pre-dose 
• Perform pruritus assessment 
• AE monitoring 
• Perform clinical laboratory analysis including haematology, serum chemistry 
panel, coagulation tests and lipid and metabolic profile 
● Sampling for analysis of HBV response markers 
● PD biomarkers sampling 
● Liver fibrosis and inflammation assessment 
● Review returned patient diary and dispense new diary 
● Dispense NA 
• Collect used/unused study drug and assess compliance 
6.2.3.3. 
Follow-up Visit 3/EoS Visit (Week 40 [Day 280 ± 7 days]) 
The follow-up Visit 3/EoS Visit is planned on Day 280 ± 3 days in Week 40. Following 
activities are planned for the visit: 
• Review and record patient’s prior and concomitant medications 
• Record patient’s body weight 
• Calculate BMI 
• Perform symptom-directed physical examination 
• Perform vital signs (systolic/diastolic BP, heart rate, temperature, respiratory rate) 
evaluation pre-dose 
• Perform pruritus assessment 
• AE monitoring 
• Perform clinical laboratory analysis including haematology, serum chemistry 
panel, coagulation tests and lipid and metabolic profile 
• Sampling for analysis of HBV response markers 
• PD biomarkers sampling 
• Liver fibrosis and inflammation assessment 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 83 of 123 
 
 
 
• Perform Fibroscan VCTE 
• 
Review returned patient diary  
• Collect used/unused study drug and assess compliance 
• Perform liver imaging to screen patient for HCC. For patients with risk factors for 
HCC, i.e. any of these: family history with HCC, >40 years of age, male sex, born 
in Sub-Saharan Africa, Metabolic syndrome (obesity, diabetes), smoking, 
ALT>ULN, HBV DNA (>2,000 IU/mL), HBeAg-negative, Genotype C) during 
follow-up phase liver imaging is also performed at week 40. 
 
6.2.4. Early Termination (ET) Visit 
The ET Visit is planned for patients who discontinue early from the study for any reason, 
for a follow-up approximately one week after administration of their final last dose of any 
study medication, regardless of how many days the patient was in the study. Please refer 
Section 19.1 for the collection of data based on the following activities planned for the 
visit: 
• Review and record patient’s prior and concomitant medications 
• Record patient’s body weight 
• Calculate BMI 
• Perform symptom-directed physical examination 
• Perform vital signs (systolic/diastolic BP, heart rate, temperature, respiratory rate)  
• Pruritus assessment 
• AE monitoring 
• Perform clinical laboratory analysis including haematology, serum chemistry 
panel, coagulation tests and lipid and metabolic profile 
• Perform serum pregnancy test (for WOCBP only) 
• Perform Dipstick urinalysis for all male and female patients 
• Perform 12-Lead ECG 
• Sampling for analysis of HBV response markers 
• PD biomarker sampling 
• Liver fibrosis and inflammation assessment 
• Perform Fibroscan VCTE 
• PK sampling 
• Review returned patient diary 
• Collect used/unused study drug and assess compliance 
6.3. 
Appropriateness of Measurements 
Standard efficacy, PK, PD, statistical, clinical and laboratory procedures will be utilized in 
this study.  
7. 
Efficacy Variables 
The efficacy of EYP001a will be assessed via the following efficacy variables: 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 84 of 123 
 
 
 
7.1. 
Definitions 
Primary efficacy variables 
The primary efficacy variables are: 
• HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment period 
Secondary efficacy variables 
The secondary efficacy variables are as follows: 
• HBsAg responder rate (decrease from baseline ≥ 1.0 on the log10 scale) at Week 16 
of treatment and Weeks 20, 28 and 40 of follow up. 
• HBsAg responder rate (decrease from baseline ≥ 0.5 on the log10 scale) at Weeks 
12 and 16 of treatment and Weeks 20, 28 and 40 of follow up. 
• HBsAg loss rate (% patients with HBsAg < LLOQ) at Weeks 16 of treatment period 
and Weeks 20, 28 and 40 of follow-up. 
• HBsAg loss rate (proportion of results that are Target Not Detected versus Target 
Detected) at Weeks 16 of treatment period and Weeks 20, 28 and 40 of follow-up. 
• relapse rate HBsAg (% patients who became negative [HBsAg < LLOQ], then 
increased with HBsAg > LLOQ) at Week 16 of treatment period and Weeks 20, 28 
and 40 during follow-up period. 
• Virologic failure rate (breakthrough)15 of HBV DNA (% patients with a confirmed 
quantifiable HBV DNA increase of ≥ 1log10 HBV DNA copies/mL above LLOQ16) 
assessed at Week 16 of treatment period and Weeks 20, 28 and 40 during follow-up 
period 
• HBV pgRNA decline (Δ log10) from Day 1 to Weeks 4, 8, 12 and 16 of treatment 
period and Week 40 of maintenance period 
• HBcrAg decline (Δ log10) from Day 1 to Weeks 4, 8, 12 and 16 of treatment period 
and Week 40 of maintenance period 
• HBeAg quantification for HBeAg pos patients and changes at Week 16 of treatment 
and Week 40 of follow-up 
• Fibroscan VCTE change from screening to Weeks 16 and 40 or ET 
Analysis of HBV response markers:  
• Samples for analysis of quantitative HBsAg and quantitative HBV-DNA will be 
collected at pre-dose on all study visits during treatment period and Weeks 20, 28 
and 40 of follow-up or at the ET visit. 
• Samples for analysis of quantitative HBV pgRNA and HBcrAg will be collected at 
pre-dose on all study visits during treatment period and Week 40 of maintenance 
during follow-up period or at the ET visit. 
 
 
15 Breakthrough samples will be further assessed for resistance assessments, including both for 
the nucleos(t)ide analogue as well as for EYP001a (e.g., sequence analysis of FXR response 
elements in HBV genome). Details will be described in the Laboratory manual. 
16 HBV DNA results <LLOQ will be reported as either <LLOQ/Detected (i.e. LLOQ/TD) or 
<LLOQ/Target Not Detected (i.e. LLOQ/TND), both are considered LLOQ. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 85 of 123 
 
 
 
• Sample for analysis of HBeAg, anti-HBe and anti-HBs will be collected at 
screening or Day 1, then pre-dose at Week 16, Week 40 (EoS visit) or ET Visit. 
7.2. 
Drug Concentration Measurements 
The analysis of IP (EYP001a) in serum samples, as well as the analysis of biomarkers, will 
be performed at a Bioanalytical Laboratory using validated or qualified methods. The 
bioanalytical reports for the determinations will be included in the clinical study report 
(CSR). 
8. 
Safety Assessments 
The safety and tolerability of EYP001a will be assessed throughout the study. 
Safety and tolerability will be determined by evaluating medical history (including 
evaluation of AEs and concomitant medication use) and assessments will include the 
monitoring of adverse events (AEs) and Serious Adverse Events (SAEs), and findings from 
physical examinations, vital signs, 12-lead ECGs, and clinical laboratory parameters.  
Clinical laboratory assessments will include: 
• Haematology: red blood cell count, white blood cell count and differential; 
quantitatively - leukocytes, erythrocytes, haemoglobin, haematocrit; partial 
automated differentiation - thrombocytes, lymphocytes, monocytes, eosinophils, 
basophils, neutrophils, and platelets. 
Coagulation: quantitatively - prothrombin time (reported in seconds and as INR), 
activated partial thromboplastin time, and fibrinogen 
● Serum chemistry: ALT, albumin, ALP, amylase, AST, blood urea nitrogen, 
calcium, creatine kinase, creatinine phosphokinase (CPK), creatinine, Estimation 
of glomerular filtration rate, GGT, glucose, lactate dihydrogenase, potassium, 
sodium, total bilirubin (if >ULN, add conjugated bilirubin), total protein, uric acid. 
• Additional chemistry: Alpha 2 macroglobulin, autotaxin, cardiac troponin I, 
ferritin, phosphate and TSH. These markers will be assessed at the end of study on 
existing chemistry plasma aliquots collected on Day 1, Day 112 and Day 280, only 
if relevant improvements in liver inflammation or fibrosis are apparent. 
• Lipid and metabolic profiles: branched-chain amino acid concentrations as liver 
function test, haemoglobin A1c, homeostatic model assessment for insulin 
resistance (morning fasting glucose and insulin), lipoprotein insulin resistance 
index by nuclear magnetic resonance based on serum cholesterol, HDL-C, LDL-C, 
triglycerides, apolipoprotein B, small dense LDL, and lipoprotein(a). 
Lipoprotein particle size; small LDL particle number, small very low-density 
lipoprotein (VLDL) particle number, VLDL size 
• Urinalysis (dipstick qualitatively): bilirubin, nitrite, blood, pH, glucose, protein, 
haemoglobin, specific gravity, ketones, urobilinogen, and leukocytes); 
• Pregnancy testing. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 86 of 123 
 
 
 
Laboratory parameters combined with AE, ECG and clinical assessments will be 
established at each study visit. They are considered appropriate measures for the following 
reasons: 
• EYP001a Phase 1 studies showed pharmacological effects related to target FXR 
engagement as expected in the digestive system and lipid metabolism. From the 
available data no off-target effect has been evidenced. No dose-related or clinically 
significant changes in haematology or clinical chemistry laboratory values were 
evidenced so far. 
• The study population will be adequately monitored through ECG, the safety lab, in 
particular liver enzymes, CPK, and cardiac troponin I, which aids in the risk 
stratification of patients with potentially unstable angina or non-ST segment 
elevation acute coronary syndromes with increased probability of ischemic events 
requiring urgent revascularization procedures. 
• Patients with cirrhotic liver disease are excluded from this study. 
8.1. 
Adverse Events and Adverse Event Reactions 
Adverse Event (AE): Any untoward medical occurrence in a subject or clinical 
investigation subject administered a pharmaceutical product and which does not 
necessarily have to have a causal relationship with this treatment.  
An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding, for example), symptom or disease temporally associated with the use 
of a medicinal product, whether or not considered related to the medicinal product. 
Adverse Drug Reaction (ADR): In the pre-approval, clinical experience with a new 
medicinal product or its new usages, particularly as the therapeutic dose(s) may not be 
established: all noxious and unintended responses to a medicinal product related to any 
dose should be considered ADRs. 
The phrase "responses to a medicinal products" means that a causal relationship between a 
medicinal product and an AE is at least a reasonable possibility, i.e., the relationship cannot 
be ruled out. 
Unexpected ADR: An adverse reaction, the nature and severity of which is not consistent 
with the applicable product information (e.g. IB for an unapproved medicinal product). 
8.1.1. Recording of Adverse Events 
All AEs during the course of the trial will be reported in the appropriate section in the 
eCRF. The investigator will give his or her opinion as to the relationship of the adverse 
event to the investigational product. The Investigator should attempt to establish a 
diagnosis of the AE based on signs, symptoms, and/or other clinical information. In such 
cases, the diagnosis should be documented as the AE verbatim term rather than individual 
signs/symptoms.  
All AEs regardless of relationship to the study drug during the period starting from the time 
the participant signed the ICF through 7 days after the last study drug dose will be recorded 
in the eCRF.  


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 87 of 123 
 
 
 
8.1.2. Follow-up of Adverse Events 
All events will be followed to resolution or stabilization or until 30 days after the patient 
completes the study. A final assessment of outcome will be made at that time. 
8.1.3. Relationship to the Study Drug 
The relationship of each AE to study drug is to be assessed by the Investigator according 
to categories in in Table 3. 
Table 3 
Criteria for Determination of AE Relationship to Study Drug 
Unrelated 
The event is definitely not associated with the study drug. Other conditions 
including concurrent illness, progression or expression of the disease state, or 
reaction to a concurrent medication explain the reported AE. 
Unlikely 
The temporal association, subject history and/or circumstances are such that the 
study drug is not likely to have had an association with the observed event. Other 
conditions including concurrent illness, progression or expression of the disease 
state, or reaction to a concurrent medication, appear to explain the reported AE. 
Possibly 
Related 
The event follows a reasonable temporal sequence from study drug but could 
have been produced by the subject’s clinical state or other therapies administered 
to the subject. 
Probably 
Related 
The event follows a reasonable temporal sequence from the study drug abates 
upon discontinuation of the study drug and cannot be reasonably explained by 
known characteristics of the subject’s clinical state 
Definitely 
Related 
The event follows a reasonable temporal sequence from the study drug abates 
upon discontinuation or cannot be explained by known characteristics of the 
subject’s clinical state. 
8.1.4. Intensity Assessment 
The intensity of each AE is to be assessed by the Investigator according to the CTCAE, 
version 5.0; please refer Table 4. 
Table 4 
CTCAE Severity grade description 
Grade 1  
Mild 
Asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
Grade 2  
Moderate 
Minimal, local or non-invasive intervention indicated; 
limiting age-appropriate instrumental activities of daily 
living* 
Grade 3  
Severe 
Severe or medically significant but not immediately 
life-threatening; 
Hospitalization or prolongation of hospitalization indicated; 
disabling; limiting self-care activities of daily living**. 
Note: An experience may be severe but may not be serious, 
(e.g. severe headache). 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 88 of 123 
 
 
 
8.1.5. Abnormal Laboratory Values 
All laboratory results must be filed in the participant’s medical record and monitored. The 
Investigator or designee must review laboratory results in a timely manner demonstrated 
by 
signature/date 
and 
assignment 
of 
clinical 
significance 
assessment. 
Non-clinically-significant laboratory abnormalities, i.e., minor deviations from the normal 
range, are expected and it is likely that no medical intervention will be required. Abnormal 
laboratory results should not be considered AEs unless they are associated with a diagnosis. 
Any grade laboratory abnormality that is considered to be clinically significant by the 
Investigator will be recorded on the AE eCRF. An abnormal test result will be considered 
as an AE if it is not associated with an already reported AE, diagnosis, or pre-existing 
condition; if there is a change in concomitant medication or intervention is needed, in direct 
response to a Grade 3 or 4 laboratory result and if investigator considers the laboratory 
result to be clinically significant 
All such laboratory abnormalities should be repeated and reassessed for ‘seriousness’ by 
the Investigator or designee as soon as possible. If a result meets the regulatory definition 
of ‘serious’, it should be reported as an SAE following regulatory and protocol 
requirements. Repeat laboratory tests should be performed regularly to monitor patient 
status. 
8.1.6. Pre-Existing Medical Conditions 
A pre-existing medical condition is one that is present at the start of the trial. Such 
conditions should be recorded on the Medical History eCRF. A pre-existing medical 
condition should be recorded as an AE or SAE only if the frequency, severity, or character 
of the condition worsens during the trial. When recording such events on an SAE Report 
Form and/or AE eCRF, it is important to convey the concept that the pre-existing condition 
has changed by including applicable descriptors. 
8.2. 
Serious Adverse Events  
8.2.1. Definition 
An SAE (experience) or reaction is any untoward medical occurrence that at any dose:  
• results in death 
• is life-threatening  
Grade 4  
Life-Threatening 
Life-threatening 
consequences; 
urgent 
intervention 
indicated. 
Grade 5  
Fatal 
Death related to AE. 
Note: A semi-colon indicates ‘or’ within the description of the grade.  
*Instrumental activities of daily living refer to preparing meals, shopping for groceries or clothes, using 
the telephone, managing money, etc.  
**Self-care activities of daily living refer to bathing, dressing and undressing, feeding self, using the toilet, 
taking medications and not bedridden. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 89 of 123 
 
 
 
NOTE: The term "life-threatening" in the definition of "serious" refers to an event in 
which the patient was at risk of death at the time of the event; it does not refer to an 
event which hypothetically might have caused death if it were more severe.  
• requires in-patient hospitalization or prolongation of existing hospitalization 
NOTE: inpatient hospital admission refers to an overnight stay in a health care facility 
• results in persistent or significant disability/incapacity 
• is a congenital anomaly/birth defect 
• is an important medical event described as an event that may not result in death, be 
life-threatening, or require hospitalization but may be considered an SAE when, based 
upon appropriate medical judgment, it may jeopardize the subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in the definitions 
for SAEs. Examples of such medical events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias or convulsions 
that do not result in inpatient hospitalization, or the development of drug dependency 
or drug abuse. 
Hospitalization: Treatment within or admission to the following facilities will not meet 
the hospitalization criteria (however, if any other seriousness criteria as specified above are 
met, the event will be considered an SAE and reported immediately): 
• Hospital visit of <24 hours duration (e.g. patient presented to emergency room, but not 
admitted to ward) 
• Hospitalization of subjects to receive study treatment  
• Subjects admitted to a hospice or nursing home for elective non-specific, general care 
or social reasons  
• Hospitalization for prescheduled or elective procedures (such as for pain management, 
disease staging/restaging procedures or protocol specific procedures). 
Suspected unexpected serious adverse reaction (SUSAR), is defined as any AE for 
which there is a reasonable possibility that the study drug caused the AE of which the 
specificity or severity is not consistent with those noted in the current protocol and/or IB 
and meets one of the above criteria for serious. This refers to any AE that has not been 
previously observed, (e.g. included in the IB), rather than from the perspective of such an 
event not being anticipated from the pharmacological properties of the product. 
Unexpected Adverse Event is defined as an adverse reaction, the nature or severity of 
which is not consistent with the applicable product information (e.g. IB for an unapproved 
IP).  
8.2.2. Reporting of Serious Adverse Events  
All SAEs regardless of relationship to the study drug during the period starting from the 
time the patient signed the ICF through 7 days after the last study drug dose, will be 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 90 of 123 
 
 
 
recorded in the eCRF. Once the Investigator becomes aware of an SAE, he/she must report 
the SAE to the Sponsor safety representative within 24 hours of knowledge of the event.  
Safety Contact Information: 
Pharmalex: 
Telephone: +34 976 204 400 
Fax: +34 976 204 402 
Email: EnyoSafety@pharmalex.com 
A written SAE report must include a full description of the event including the below 
parameters (include any protocol specific requirements): 
• Diagnosis or description of event  
• Onset date  
• Severity assessment 
• Causal relationship to the investigational product  
• Assessment of seriousness of the event  
• Corrective treatment administered for the SAE 
• Action taken related to study drug include the following: dose interruption, dose 
delay, dose reduction, or study drug discontinuation  
• Outcome of event and end date 
Follow-up information for SAEs and information on non-serious AEs that become serious 
should also be reported to Sponsor Safety representative within 24 hours of receipt of 
follow-up information. 
The Investigator must update the SAE form and submit any supporting documentation (eg, 
patient discharge summary or autopsy reports) to the ENYO safety designee via fax or 
email. 
The Investigator is responsible for reporting all SAEs to the appropriate Institutional 
Review Board/Institutional Ethics Committee (IRB/IEC) in accordance with local laws and 
regulations. The Investigator is responsible for maintaining documentation in the study file 
that indicates the IRB/IEC has been properly notified. 
8.2.3. Follow-up of Serious Adverse Events  
All events will be followed to resolution or stabilization or until 30 days after the patient 
completes the study. A final assessment of outcome will be made at that time. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 91 of 123 
 
 
 
8.3. 
Drug-Induced Liver Injury 
8.3.1. Normal values at baseline 
Drug-induced liver injury (DILI) monitoring in patients with normal liver transaminases 
and bilirubin at baseline should be performed throughout the study according to the 
procedures summarized below: 
• If patients with normal baseline liver indices develop elevations of aspartate 
aminotransferase (AST) or alanine aminotransferase (ALT) >2 upper limit of 
normal (ULN) or total bilirubin (TBL) >1.5 ULN values during the study, repeat 
testing should be performed within 48 hours. 
• If there are persistent elevations (ALT or AST >2 ULN or TBL >1.5 ULN) upon 
repeat testing, close observation (testing and physical examination 2 to 3 times per 
week) should be implemented. An important purpose of the close observation is to 
gather additional clinical information to seek other possible causes of the observed 
liver test abnormalities, such as 1 of the following: acute viral hepatitis, alcoholic 
and autoimmune hepatitis, hepatobiliary disorders, cardiovascular causes, or 
concomitant treatments. Discontinuation of study drug should be considered. 
Study drug should be discontinued, and the patient should be followed until resolution of 
signs or symptoms, in the following situations: 
• ALT or AST >8 ULN. 
• ALT or AST >5 ULN for more than 2 weeks. 
• ALT or AST >3 ULN and (TBL >2 ULN or international normalized ratio [INR] 
>1.5). 
• ALT or AST >3 ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%). 
For any patients who present with a constellation of syndromes indicative of liver disease 
as per the Investigator’s overall assessment (i.e., fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia [>5%]), perform liver function 
tests to determine if liver disease is worsening. 
Re-initiation of study drug may be considered after consultation with the Medical Monitor. 
 
 
 
 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 92 of 123 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 8 
Normal liver transaminase and bilirubin at baseline 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 93 of 123 
 
 
 
 
ALT: alanine aminotransferase; AST: aspartate aminotransferase; INR: international normalized ratio; TBL: total 
bilirubin; ULN: upper limit of normal. 
 
 
8.3.2. Elevated values at baseline 
Drug-induced liver injury (DILI) monitoring in patients with elevations in liver 
transaminases or bilirubin at baseline should be performed throughout the study 
according to the procedures summarized below: 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 94 of 123 
 
 
 
• If patients with abnormal baseline liver indices develop elevations of AST or ALT 
>2 baseline average or TBL >1.5 baseline average values during the study, repeat 
testing should be performed within 48 hours. 
• If there are persistent elevations (ALT or AST >2 baseline average or TBL>1.5 
baseline average values) upon repeat testing, then close observation (testing and 
physical examination 2 to 3 times per week) should be implemented and 
discontinuation of study drug should be considered. 
Study drug should be discontinued, and the patient should be followed until resolution of 
signs or symptoms, in the following situations: 
• Baseline average measurements were <2 × ULN and ALT or AST increases to >5 
× baseline measurements. 
• ALT or AST increase >2 × baseline average measurements AND the increase is 
accompanied by a concomitant increase in TBL to >2 × baseline average 
measurements or the INR concomitantly increases by >0.2. 
For any patients who present with a constellation of syndromes indicative of liver disease 
as per the Investigator’s overall assessment (i.e., fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia [>5%]), perform liver function 
tests to determine if liver disease is worsening. 
Re-initiation of study drug may be considered after consultation with the Medical Monitor. 
 
 
 
 
 
 
 
 
 
Figure 9 
Elevated liver transaminase and bilirubin at baseline 
 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 95 of 123 
 
 
 
 
ALT: alanine aminotransferase; AST: aspartate aminotransferase; INR: international normalized ratio; TBL: total 
bilirubin; ULN: upper limit of normal. 
 
 
8.3.3. General Considerations 
For all patients, close observation for suspected drug-induced liver injury includes the 
following: 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 96 of 123 
 
 
 
• Repeating liver enzyme (ALT, AST, and alkaline phosphatase) and serum bilirubin 
tests 2 or 3 times weekly. 
• The frequency of repeat testing can decrease to once a week or less if abnormalities 
stabilize or the study drug has been discontinued and the patient is asymptomatic. 
• Obtaining a more detailed history of symptoms and prior or concurrent diseases. 
• Obtaining a history of concomitant drug use (including non-prescription 
medications and herbal and dietary supplement preparations), alcohol use, 
recreational drug use, and special diets. 
• Ruling out acute viral hepatitis types A, B, C, D, and E; autoimmune or alcoholic 
hepatitis; non-alcoholic steatohepatitis; hypoxic/ischemic hepatopathy; and biliary 
tract disease. 
• Obtaining a history of exposure to environmental chemical agents. 
• Obtaining additional tests to evaluate liver function, as appropriate (e.g. INR, direct 
bilirubin). 
• Considering gastroenterology or hepatology consultations. 
8.4. 
Pruritus Assessment 
Pruritus will be assessed using a visual analog scale and a 5-D (degree, duration direction, 
disability, and distribution) itch scale (Refer Section 19.2, Appendix B) at each study visit 
after screening. 
8.5. 
Pregnancy 
Pregnancy testing must be performed in all WOCBP as specified in the Schedule of 
Assessments table, and the results of all pregnancy tests (positive or negative) are to be 
recorded on the eCRF. If the pregnancy test is positive, the patient will be immediately 
discontinued from study treatment. 
In addition, all WOCBP should be instructed to contact the Investigator immediately if they 
suspect they might be pregnant (e.g. missed or late menstrual period) at any time during 
the study. Male patients should contact the Investigator immediately if they suspect they 
may have fathered a child during the study. When possible, partner’s pregnancies should 
be followed (to term) to determine the outcome.  
If a patient becomes pregnant while enrolled in the trial, a Pregnancy Form should be 
completed and sent to the Sponsor Safety Representative expeditiously, irrespective of 
whether or not it meets the criteria for expedited reporting. Abortions (spontaneous, 
accidental, or therapeutic) must also be reported to the Sponsor Safety Representative. 
Congenital anomalies/birth defects always meet SAE criteria, and should therefore be 
expeditiously reported as an SAE, using the previously described process for SAE 
reporting. A Pregnancy Form should also have been previously completed and will need to 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 97 of 123 
 
 
 
be updated to reflect the outcome of the pregnancy. The Investigator must report any 
pregnancy (including the pregnancy of a male patient’s partner), even if no AE has 
occurred, on a Pregnancy Report Form within 24 hours of the Investigator becoming aware 
of the pregnancy. 
9. 
PK and PD Methods 
9.1. 
Pharmacokinetics 
EYP001a PK parameters to be determined include:  
• Plasma concentration of EYP001a or any relevant active metabolites (as identified 
in an ongoing phase 1 study). 
Fasting plasma samples will be collected at all study visits pre-dose in the morning on Day 
1 and at Weeks 2, 4, 6, 8, 10, 12, 14 and 16 and in the morning at the ET Visit. 
If by error patient has taken study medication on study Visit days prior to coming to the 
clinic the accurate time of last dosing and blood draw will be recorded. 
Plasma will be stored at -80°C until analysis. Plasma samples will be analysed for EYP001a 
and any active metabolites using a validated liquid chromatography/mass spectrometry 
(LC-MS/MS) method. 
9.2. 
Pharmacodynamics 
EYP001a PD parameters to be determined include: 
• Plasma C4 (7α-hydroxy-4-cholesten-3-one) 
• FGF19 
• Plasma primary and secondary BAs  
Plasma C4, FGF19; BAs (total, primary, and secondary BAs (such as chenodeoxycholic 
acid [CDCA], deoxycholic acid [DCA], lithocholic acid, and/or others as appropriate) 
sampling will occur pre-dose paired with PK sampling at all visits during treatment period. 
A sample will also be collected at the Weeks 28 and 40 (EoS) or ET Visits.  
Samples for BAs will be collected and stored centrally frozen for subsequent assessment 
after the EoS pending ongoing BA profiling related to EYP001a pharmacology. 
10. Data Quality Assurance 
The study may be audited by the Quality Assurance Department at CRO to assess 
adherence to the clinical study protocol and Quality System. During the conduct of the 
study, process related audits may be performed. An audit certificate will be provided in the 
appendices of the final CSR outlining any audits and other related activities performed. 
The clinical research site will be monitored by the study monitor to ensure correct 
performance of the study procedures and assure that the study will be conducted according 
to the relevant regulatory requirements.  
The eCRF entries will be verified with the source documentation.  
The study monitor identifies any data to be recorded directly on the eCRF (i.e., no prior 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 98 of 123 
 
 
 
written or electronic record of data), and to be considered to be source data. 
Regulatory authorities, the IRB/IEC and/or the Sponsor’s clinical quality assurance group 
may request access to all source documents, eCRFs, and other study documentation for 
on-site audit or inspection. Direct access to these documents must be guaranteed by the 
Investigator, who must provide support at all times for these activities. 
Quality control principles will be applied throughout the performance of this study. Review 
procedures will be followed by the CRO for all documents that are generated in relation 
with the study. Essential study activities of personnel will be checked by other CRO 
colleagues during execution, and each of them will sign off the documentation for 
execution or checking of the activities. 
An explanation will be given for all missing, unused and spurious data in the relevant 
sections of the CSR. 
11. Statistical Methods and Determination of Sample Size 
11.1. 
Statistical Analysis Plan and General Statistical Methods 
All data will be handled and processed according to the sponsor’s representative (Novotech 
[Australia] Pty Ltd) SOPs, which are written based on the principles of GCP. 
A Statistical Analysis Plan (SAP) containing the detailed planned statistical methods will 
be finalized prior to locking of the study database for the interim and final analysis and will 
form the basis for the programming of the displays and analyses of the final study data. All 
statistical calculations will be performed using SAS® (SAS Institute Inc., Cary, NC, USA) 
or similar software. 
The statistical analyses will consist of both inferential and descriptive statistics. In general, 
the data will be presented by dose group. All collected and derived data will be included in 
the patient data listings. 
All inferential analyses will be conducted at a one-sided 0.05 level of significance. Unless 
otherwise specified, all inferential testing will be one-sided in nature.  
Continuous data, other than PK data, will be summarized by treatment group and time point 
using the number of observations, arithmetic mean, standard deviation, median, minimum 
and maximum. The coefficient of variance, geometric means and geometric coefficient of 
variance will also be presented for the concentration-related PK data. Categorical data will 
be summarized by the number and percentage of patients in each category. Unless 
specifically stated otherwise, the number of patients in the treatment group (for the specific 
analysis set) will be used as the denominator for all percentage calculations. 
Baseline is defined as the last available non-missing value collected prior to the first 
administration of IP. 
Change from baseline values will be calculated as the difference between the result at a 
specific time point, and the baseline value for the specific endpoint. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 99 of 123 
 
 
 
Missing, unused, or spurious data will be handling in the following manner: 
• 
There will be no imputations or substitution made for missing safety data points. 
• 
For the PK analyses, imputations will be made for missing data points. 
11.2. 
Definition of Analysis Sets 
The following analysis sets are defined for this study. 
11.2.1. Intention-To-Treat (ITT) Set 
The ITT set will include all randomized patients, irrespective of whether a patient receives 
any study drug. This set will be based on randomized treatment. The ITT set will be used 
for the baseline, demographic summaries and efficacy summaries. 
11.2.2. Modified Intention-To-Treat (mITT) Set 
The mITT set will include all randomized patients, who received any amount of study drug, 
have a measurable baseline HBsAg assessment and a 16-week post baseline efficacy 
assessment. This set will be based on randomized treatment. The mITT set will be used for 
efficacy analyses. 
11.2.3. Per Protocol (PP) Set 
The PP set is defined as the set of patients who meet the mITT set requirements and were 
not associated with a major protocol violation. This set will be identified before the start of 
the final analysis and will be used to support the analysis conducted for the primary efficacy 
endpoint. Patients will be analysed based on the actual treatment received. 
11.2.4. Safety Analysis Set (SAS) 
The Safety analyses set will be defined as all patients who receive at least one confirmed 
dose of the study drug and will be based on actual treatment received. The SAS will be 
used for all safety and tolerability analyses. 
11.2.5. Pharmacokinetic Set 
The PK set will consist of all patients who received any study drug administration and that 
have sufficient and interpretable EYP001a concentrations data. Patients with missing 
sample concentrations will be included in the PK set provided that the PK parameters can 
be adequately characterized based upon the remaining data. Protocol violations and 
individual patient profiles will be assessed on a case-by-case basis to determine if the 
patient, or specific concentration values, should be excluded from the PK set. 
11.2.6. Pharmacodynamic Set 
All patients included in the SAS with a measurable baseline PD assessment and at least 
one measurable post baseline PD assessment, will be included in the PD set. 
11.3. 
Statistical Methods 
11.3.1. Patient Disposition 
Patient disposition will be summarised using counts and percentages. The number and 
percentage of enrolled patients, patients discontinued from the study, the primary reason 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 100 of 123 
 
 
 
for discontinuation as well as the number and percentage of patients included in each 
analysis set will be summarised by treatment group. 
11.3.2. Demographic and Baseline Characteristics 
Demographic and baseline information including treatment history, HBV genotype, age, 
gender, BMI, weight, and height will be summarised by treatment group using the ITT set. 
11.3.3. Efficacy Analyses 
All Efficacy analyses will be based on the ITT set unless otherwise specified. All efficacy 
data will be summarised by study visit and treatment group. 
11.3.3.1. 
Primary Efficacy 
The primary endpoint, HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment will 
be analysed using a general linear model for repeated measures, using the stratification 
factors as independent variables in the model (A Genotype [yes, no] and HBeAg pos [yes, 
no]). The primary analysis will be based on the ITT set. The analysis will be repeated based 
on the mITT and PP sets, as sensitivity analyses. 
The analysis will be based on a one-sided test at a 5% level of significance. 
Note that the sample size calculations are based on a t-test, as power calculations based on 
a repeated measures model require information about within-patient correlation structures, 
which is not available. However, using a repeated measures model, better power is 
expected compared to a t-test. A t-test, imputing missing data at 16 weeks as zero difference 
versus baseline, will be carried out as a sensitivity analysis.  
11.3.3.2. 
Secondary Efficacy 
HBsAg responder rate (decrease from baseline ≥ 1.0 on the log10 scale and decrease from 
baseline ≥ 0.5 on the log10 scale) and HBsAg loss rate (proportion of HBsAg<LLOQ) at 
Week 16 of treatment and Week 20, Week 28 and Week 40 of follow-up will be analysed 
as key secondary endpoints at 16 weeks, and 40 weeks. Proportion of patients of Target 
not detected will be analysed as exploratory endpoint. HBsAg responder rate (decrease 
from baseline ≥ 0.5 on the log10 scale) will also be analysed at Week 12 of treatment. At 
16 and 40 weeks, these endpoints will be analysed taking into account multiplicity by a 
combination of a hierarchical fixed test procedure and a Hochberg procedure (See Section 
11.4.2), using a this Pearson Chi-square test. At other timepoints, analyses for these two 
endpoints will be descriptive.  
Relapse rate HBsAg (% patients who became negative [HBsAg< LLOQ], then increased 
with HBsAg > LLOQ) at Week 16 of treatment period and Weeks 20, 28 and 40 during the 
follow-up period will be summarized by frequency counts and percentages. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 101 of 123 
 
 
 
Virologic failure rate (breakthrough) 17 of HBV DNA (% patients with a confirmed 
quantifiable HBV DNA increase of ≥ 1log10 HBV DNA copies/mL above LLOQ18) 
assessed at Weeks 16 of treatment, 20, 28 and 40 during follow up period will be 
summarized by frequency counts and percentages. 
HBV-pgRNA decline (Δ log10) and HBcrAg decline (Δ log10) from Day 1 to Weeks 4, 8, 
12 and 16 of the treatment period and Week 40 of maintenance period, HBeAg 
quantification for HBeAg positive patients and changes at Week 16 of treatment and Week 
40 of follow-up and Fibroscan VCTE change from screening value to the Weeks 16 and 40 
or ET visit will be summarized through descriptive statistics. 
11.3.4. PK Analyses 
The PK analysis will be based on the PK set. 
Individual plasma concentrations and trough levels of EYP001a and any active metabolites 
will be listed for each patient and summarised by nominal sampling time point and 
treatment group with descriptive statistics. All concentrations below the limit of 
quantification will be labelled as such in the concentration data listings. Listings of 
individual patient plasma concentrations and actual blood sampling times and graphs of 
concentration versus time will be prepared. Plasma concentrations will be summarized 
using descriptive statistics. The actual PK sampling timepoints will be used for the PK 
analysis. Appropriate validated PK software (eg, Phoenix WinNonlin v6.3) will be used. 
A non-compartmental analysis will not be performed. 
EYP001a PK parameters to be determined include:  
• Plasma concentration of EYP001a or any relevant active metabolites (as identified 
in an ongoing phase 1 study). 
PK parameters will be summarized by treatment group using descriptive statistics. 
Statistical analysis will be performed on the pharmacokinetic parameters using validated 
statistical software. 
11.3.5. PD Analyses 
The PD analysis will be based on the PD set. 
PD marker parameters will be summarized using descriptive statistics and will also be 
presented graphically per treatment group. 
The following PD markers will be assessed: 
 
 
17 Breakthrough samples will be further assessed for resistance assessments, including both for 
the nucleos(t)ide analogue as well as for EYP001a (e.g., sequence analysis of FXR response 
elements in HBV genome). Details will be described in the Laboratory manual. 
18 HBV DNA results <LLOQ will be reported as either <LLOQ/Detected (i.e. LLOQ/TD) or 
<LLOQ/Target Not Detected (i.e. LLOQ/TND), both are considered LLOQ. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 102 of 123 
 
 
 
• 
Plasma C4 (7α-hydroxy-4-cholesten-3-one) 
• 
FGF19 
• 
Plasma primary and secondary BAs 
11.3.6. Safety Analyses 
Listings and summaries for all safety data will be presented using the Safety Set. Safety 
endpoints will be summarised by treatment group. 
The following data presentations and summaries will be performed. No formal inferential 
statistics will be performed on safety assessments. 
All AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA®). 
All AE summaries will be restricted to TEAEs only and will be summarised by treatment 
group. Summary tables will include the number of patients (%) experiencing an event and 
the number of events. Patients will be counted only once at each system organ class and 
preferred term (PT) level of summary. 
The TEAE summaries may include but not be limited to: 
• 
TEAE summary by SOC and PT 
• 
TEAE summary of serious events by SOC and PT 
• 
TEAE summary by severity by SOC and PT 
• 
TEAE summary by causality by SOC and PT 
All AEs will be listed and will include verbatim term, preferred term (PT), system organ 
class, treatment, severity, causality, seriousness, and action taken with regards to the study 
drug. Separate listings will be created for SAEs and events leading to treatment 
discontinuation. 
Clinical laboratory results will be summarised by treatment group and will include changes 
from baseline and counts of number of values out of normal range at each scheduled time 
point. Shift tables (categorical parameters) may also be used, as appropriate. Individual 
vital signs assessments will be listed for each patient. Summaries of vital signs by treatment 
group will include changes from baseline for each parameter at each scheduled time point. 
Individual ECG results will be listed for each patient. Summaries of ECGs by treatment 
group will include changes from baseline for each parameter at each scheduled time point. 
Physical examination findings will be listed for each patient and any changes described in 
the text of the final report. 
Exposure to study drug and concomitant medications will be listed by patient and coded 
using the most current WHO drug dictionary available at the Sponsor. The number and 
percentage of patients who used prior and/or concomitant medications will be summarised 
by Anatomic Therapeutic Chemical (ATC) classification levels and treatment group. At 
each level of ATC classification, patients will be counted once. Concomitant medications 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 103 of 123 
 
 
 
are medications defined as any medications taken after first study drug administration. 
Prior medications are medications stopped prior to first study drug administration. 
11.4. 
Determination of Sample Size 
11.4.1. Sample size calculations for the primary endpoint 
The primary endpoint is HBsAg reduction. Improvement of 1.0 on a log10 scale at 16 weeks 
is considered to be clinically significant. The expected accrual rate is 2 to 4 patients per 
week but does not affect sample calculation. Note that the accrual rate will not affect 
sample size calculations. All assumptions are given in Table 5. 
The primary analysis will be performed using a general linear model for repeated measures, 
using the stratification factors as independent variables in the model (A Genotype [yes, no] 
and HBeAg pos [yes, no]). The primary analysis will be done on the ITT population. The 
mITT and PP population, will be analysed as a sensitivity analysis. 
Table 5 
Assumptions for primary endpoint 
Primary Endpoint 
HBsAg reduction vs baseline on a log10 scale 
(“Chg”) 
Null hypothesis 
H0: Chgexp – Chgctrl = 0 
Alternative hypothesis 
Ha: Chgexp - Chgctrl = -1.0 
SD of change vs baseline in experimental 
arm 
1.08 
SD of change vs baseline in control arm 
1.08 
Drop-out 
10% over total study duration 
Randomization ratio 
3:1 for experimental:control (i.e. nE/nC=3) 
Power 
80% 
Type I error rate (1-sided) 
0.05 
Chg: Change vs baseline; Ctrl: Control arm; Exp: Experimental arm; H0: Null Hypothesis; Ha: Alternative 
Hypothesis; SD: Standard Deviation 
As the ITT population will be analysed, patients who have dropped out, will be assumed 
to have a zero-difference vs baseline for conservativeness. To take this into account, the 
assumed effect of -1.0 on a log10 scale, will be multiplied by 0.9, resulting in an assumed 
effect of -0.9. Using these assumptions, based on a test, 49 patients will need to be enrolled. 
Calculations are based on a t-test.  
Note that the final analysis will be done, using a general linear model for repeated 
measures. Using this type of model, a better power is expected, thus sample size 
calculations can be considered conservative.  
11.4.2. Testing strategy and power for key secondary endpoints 
Multiplicity is taken into account by using a combination of a hierarchical fixed test 
procedure and a Hochberg procedure.  
Only in case the primary endpoint is significant at 16 weeks, the key secondary endpoint 
“HBsAg loss rate” will be tested at the same one-sided α level of 0.05, using a Hochberg 
procedure. This procedure goes as follows: the p-values will be ordered from small to large 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 104 of 123 
 
 
 
p(1) ≤ p(2). largest p-value p(2) will be compared to α=0.05. If significant, then both 
hypotheses will be rejected. If not, the smallest p-value is compared to α/2=0.025. If 
significant, then only the hypothesis corresponding to the smallest p-value is rejected.  
At 40 weeks, the key secondary endpoints HBsAg responder rate and HBsAg loss rate will 
be tested a one-sided α level of 0.05, using a Hochberg procedure. 
To calculate the power to detect a difference in HBsAg loss rate, we assumed a proportion 
of 0.5% in the placebo arm, and of 10% in the experimental arm. A trial including 49 
patients results in a power of about 55% for this endpoint (using an un-pooled estimate of 
the variance), using a one-sided α of 0.05.  
11.5. 
Interim Analyses 
An unscheduled interim analysis of all available unblinded preliminary safety study data 
will be conducted when any stopping rules (Section 4.6) are met in two or more subjects. 
 
Two interim analysis are scheduled: 
 
1. First interim analysis on all available unblinded preliminary safety study data:  
Safety assessment when 50% (n=25) patients reach week 8 resulting in a decision on 
continuation of the study based on safety (Go/No go decision); enrolment would remain 
ongoing during this review. 
2. Second interim analysis on all available unblinded preliminary virology, safety, PK and 
PD study data:  
Safety and futility when 50% patients (n=25) reached week 12, resulting in a decision 
on continuation of the study (Go/No go decision) based on safety and evidence of a 
benefit of EYP001a (HBsAg, other secondary viral markers); enrolment is ongoing 
during this review. 
The interim analyses will be performed on all available primary and secondary endpoints 
according to the SAP and DSMC charter, which describes the overall guidelines, 
composition, roles, and responsibilities of the independent DSMC for the EYP001-201 
study, including the selection of DSMC members, timing of meetings, methods of 
providing information to and from the DSMC, frequency and format of meetings, data 
analysis recommendations, and DSMC relationships with other parties participating in the 
conduct of this study.  
The futility assessment will be performed to determine if EYP001 has no benefit at a point 
when 50% of subjects have reached 12 weeks of dosing. The futility assessment will be 
performed by the DSMC according to the following rules: 
• A treatment effect of -1.0 on a log10 scale of HBsAg for the primary endpoint at 16 
weeks, and a common standard deviation of 1.08 was assumed and the treatment effect 
would be -0.5 after 12 weeks of treatment, with common standard deviation of 0.7 Using 
a one-sided alpha of 0.05 and 80% power, a group sequential design, incorporating a 
futility and efficacy O’Brien-Fleming analysis when 50% of patients have reached 12 
weeks of treatment, needs inclusion of 49 patients.  


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 105 of 123 
 
 
 
• Table 6 gives the probability of stopping early under the null and alternative hypothesis, 
at the time of the interim analysis.  
The probability of stopping correctly for futility is 40%. The probability of stopping 
wrongly for futility is only 3.5%.  
Table 6 
Probability of different decisions at the interim analysis 
Under H0 
Under Ha 
Efficacy 
Futility 
Efficacy 
Futility 
0.001 
0.4 
0.073 
0.035 
H0: Null Hypothesis; Ha: Alternative Hypothesis 
• The efficacy boundary is crossed when the 12-week p-value is less than 0.001, or the 
difference is less than -0.971 on a log scale. The futility boundary is crossed when the 
12-week p-value is higher than 0.603, or the difference is more than 0.085 on a log 
scale.  
The stopping of the study for futility will be considered by the DSMC by applying these 
rules. The study will not stop for efficacy at Week 12 interim analyses, even if efficacy 
boundary is crossed. The criteria are not binding and DSMC can overrule if other interim 
results show beneficial results.  
Data will be summarized and presented by treatment group and time point in summary 
tables. Descriptive statistics including number of patients (N), means, standard deviations, 
medians, and minimum and maximum values will be presented for continuous variables. 
Counts and percentages will be presented for categorical variables. In addition, by- patient 
listing for all safety and efficacy data will be presented.  
Note that all interim analyses will be descriptive. The study design does not include any 
formal statistical guidelines for use at interim analysis.  
11.6. 
Other Analysis 
ENYO is developing a mathematical computational HBV disease model. The results from 
EYP001-201 will serve as clinical data for the calibration of in silico HBV patients 
simulating the effect of combinational treatments that will eventually support designing 
later trials. With its different sub-models (HBV replication and excretion, BAs metabolism, 
cholesterol metabolism, immune system, fibrosis, blood virus related changes, and 
EYP001a, ETV and PEG-IFNα2a drug models) the disease model of chronic HBV 
infection will be used to predict quantitative efficacy on relevant endpoints (DNA HBV in 
blood, HBsAg) in a representative virtual population. The computational model is a system 
of ordinary differential equations (ODEs) which integrates more than 300 biological 
variables and more than 1000 parameters. It will be used to explore the effect of 
combinations of different treatments regimens including EYP001a, ETV and PEG-IFNα2a. 
Iterations of the validated model will serve for the exploration of alternative arms in the 
EYP001-203 study (conducted in parallel EYP001-201, with treatment naive or 
virologically non-suppressed patients treated with EYP001a combined with NA and peg-
IFN), by simulating different doses and treatment regimens. Disease model simulations 
will support future explorations of development strategies, with the upcoming EYP001a 
pivotal study designs. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 106 of 123 
 
 
 
12. Protocol Amendments, other Changes in Study Conduct 
12.1. 
Protocol Amendments 
Any additional amendments proposed by the Sponsor will be submitted to the Investigator 
and IRB/IEC for review and approval prior to implementation by the Investigator. In 
addition, the Investigator must provide the signed protocol amendment page to the Sponsor. 
If the protocol is amended to eliminate or reduce the risk to participants, the amendment 
may be implemented before IRB/IEC review and approval. However, the IRB/IEC must 
be informed in writing of such an amendment, and approval must be obtained within 
reasonable time limits. 
12.2. 
Other Changes in Study Conduct 
Protocol waivers will not be allowed. 
Protocol deviations brought to the attention of the Sponsor after their occurrence will only 
be recognized and assessed for ethical, medical, scientific, and regulatory implications and 
for impact on the participant’s participation in the study and will be documented. Such 
deviations cannot be waived. 
Protocol violations (which are deviations that have a major impact on the participant’s 
rights, safety, or well-being or the integrity and authenticity of the study data) can never be 
waived. 
13. Ethical Considerations 
13.1. 
Independent Ethics Committee/Institutional Review Board 
It is the responsibility of the Investigator to obtain the approval of the IRB/IEC before the 
start of the study. A copy of the approval letter will be supplied to the Sponsor, along with 
a roster of IRB/IEC members. During the course of the study, the Investigator or designee 
will provide timely and accurate reports to the IRB/IEC on the progress of the study at 
appropriate intervals [not to exceed 1 year] and at the completion of the study. Investigator 
or designee will notify the IRB/IEC of SAEs or other important safety findings. The study 
protocol, ICF, information sheet advertisements (if any), and amendments (if any) will be 
approved by the IRB at each study centre in conformance Code of Federal Regulations 
(CFR), Title 21, Part 56.  
13.2. 
Ethical Conduct of the Study 
This study will be performed in accordance with the protocol, current ethical principles 
that have their origins in the Declaration of Helsinki, the ICH Harmonized Tripartite 
Guideline for GCP, and all applicable local regulatory requirements.  
The procedures set out in this study protocol are also designed to ensure that the Sponsor 
and Investigator abide by the principles of the GCP guidelines of the ICH and in keeping 
with local legal requirements. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 107 of 123 
 
 
 
13.3. 
Participant Information and Consent 
Before the start of any study-related procedures are undertaken, the Investigator or 
designee must obtain written, informed consent from each participant in accordance with 
US federal regulations (21 CFR §50) and the ICH document “Guidance for Industry – E6 
Good Clinical Practice: Consolidated Guidance”. Informed consent will be obtained by 
discussing with the participant the purpose of the study, the risks and benefits, the study 
procedures, and any other information relevant to the participant. 
The Investigator or designee must explain to the participant that for purposes of evaluating 
the study results, that participant’s private health information obtained during the study 
may be shared with the Sponsor, regulatory agencies, and IRBs/IECs, before enrolling that 
participant into the study. The participant or his/her legal representative will document 
his/her informed consent by signing the current version of the written, IRB/IEC approved 
ICF. The person who conducted the informed consent discussion with the participant 
and/or participant’s legal representative (if applicable) must also sign the ICF. The 
participant is given a fully executed copy of the ICF bearing all appropriate signatures, and 
the original must be maintained in the clinical master files at the site. 
The Investigator, or designee, is responsible for the content of the ICF, but the original and 
any updated versions must be approved by the Sponsor prior to submission to the IRB/IEC. 
The ICF should also include any additional information required by local laws relating to 
institutional review. All active participants participating on the protocol must be 
re-consented each time the ICF is updated and re-approved by the IRB/IEC. 
13.4. 
Compensation Arrangements 
If the participant is physically injured as a direct result of this study or study procedure 
improperly performed under the plan for this study and it is not due to a pre-existing 
medical condition or underlying disease, the Sponsor will reimburse the participant for the 
reasonable medical expenses for the treatment of that injury which are not covered by 
another payor, their own insurance or health care program. No other compensation is 
available from the Sponsor if any injury occurs. 
13.5. 
Protected Health Information 
Data collected during this study may be used to support the development, registration or 
marketing of this investigational product. All data collected during the study will be 
controlled by the Sponsor (or designee) and the Sponsor will abide by all relevant data 
protection laws. After a participant has consented to take part in the study, their medical 
records and the data collected during the study will be reviewed by representatives of the 
Sponsor and/or the company organizing the research on the Sponsor’s behalf to confirm 
that the data collected are accurate and for the purpose of analysing the results. These 
records and data may additionally be reviewed by auditors or by regulatory authorities. The 
participant’s name, however, will not be disclosed outside the hospital. They will be known 
by a unique participant number. The results of this study may be used in other countries 
throughout the world that have ensured an adequate level of protection for personal data. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 108 of 123 
 
 
 
14. Data Handling and Record Keeping 
Data collection will involve the use of the Sponsor Electronic Data Capture (EDC) system, 
to which only authorized personnel will have access.  
In addition to periodic monitoring occurring within the system by Sponsor personnel or 
representative, programmatic edit checks will be used to review the data for completeness, 
logic, and adherence to study protocol. As a result of this monitoring and these checks, 
queries may be issued electronically to the clinical study centre and answered electronically 
by that study centre. The identifying information (assigned username, date, and time) for 
both the originator of the query (if created during the monitoring process) and the originator 
of the data change (if applicable), as well as the Investigator’s approval of all changes 
performed on his or her participants’ data, will be collected. 
All data collected in the context of this study will be stored and evaluated according to 
regulatory requirements and applicable guidance for electronic records. Data will be stored 
and evaluated in such a way as to guarantee participant confidentiality in accordance with 
the legal stipulations applying to confidentiality of data. Study records (e.g. patient diaries, 
copies of eCRFs, regulatory documents, etc.) will be retained at the study centre, along 
with adequate source documentation, according to FDA and ICH requirements. All study 
records must be available for inspection by the Sponsor, its authorized representatives, and 
FDA officials. 
The PI must maintain the documentation relating to this study. If the Sponsor, the FDA, or 
another regulatory authority wishes to review any documentation relating to the study, the 
PI must permit access to such records. 
The PI must retain a copy of all records that support the CRFs for this study (e.g. ICFs, 
clinical laboratory reports, source documents, investigational product dispensing records) 
for a period of at least 15 years after study completion unless local regulations or study 
centre policies require a longer retention period or otherwise notified in writing by the 
Sponsor. 
If the PI retires, relocates, or for other reasons withdraws from the responsibility of keeping 
the study records, custody must be transferred to a suitable alternate custodian employee 
of the study centre or to a suitably qualified and responsible third party. The Sponsor must 
be notified in writing of the name and address of the new custodian before such transfer is 
made. 
No study records shall be destroyed without notifying and giving the Sponsor the 
opportunity to arrange long-term storage for such study records or to authorize in writing 
the destruction of records after the required retention period. 
15. Financing & Insurance 
In the event of injury resulting from participation in this study, any medical treatment 
deemed necessary will be provided to study participants to assist in recovery from the 
injury.  
Study participants will not be charged for this care beyond that covered by the study 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 109 of 123 
 
 
 
participant’s health insurance. This agreement to provide free medical treatment does not 
include treatment for illnesses experienced during the study if the illness is not the direct 
result of study participation. No compensation will be provided for study-related injury 
other than free medical treatment. 
16. Financial Disclosure 
The Investigator will be required to disclose any financial arrangement whereby the value 
of the compensation for conducting the study could be influenced by the outcome of the 
study; any significant payments of other sorts from the Sponsor, such as a grant to fund 
ongoing research, compensation in the form of equipment, retainer for ongoing 
consultation, or honoraria; any proprietary interest in the study; any significant equity 
interest in the Sponsor, as defined in the US CFR (21 CFR 54 2[b]). 
In consideration of participation in the study, the Sponsor will pay the Investigator, study 
site or nominated payee the sums set out in the payment schedule attached to the 
Investigator Agreement. 
17. Reporting & Publication 
17.1. 
Clinical Study Report  
The data and information collected during this study will be reported in a study report 
prepared by the CRO. The final report may be used for the further development of the 
investigational product as considered necessary by the Sponsor.  
17.2. 
Confidentiality and Intellectual Property Rights of Study Data  
Any confidential information relating to the investigational product or the study, including 
any data and results from the study will be the exclusive property of the Sponsor. The 
Investigator and any other persons involved in the study will protect the confidentiality of 
this proprietary information belonging to the Sponsor.  
17.3. 
Publication Policy 
The Sponsor encourages publication of results derived from the clinical research. 
Publications include a paper in a peer reviewed medical journal, abstract submission with 
a poster or oral presentation at a scientific meeting or making results public by some other 
means. The Sponsor will retain the right to review all material prior to presentation or 
submission for publication and neither institution(s) nor Study Co-chairs/PI(s) are 
permitted to publish/present the results of the study, in part or in their entirety, without the 
written authorization of the Sponsor. The review is aimed at protecting the Sponsor’s 
pre-existing proprietary information and commercial interests. 
 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 110 of 123 
 
 
 
18. References 
Alexopoulou A and Karayiannis P. HBeAg negative variants and their role in the natural 
history of chronic hepatitis B virus infection. World J Gastroenterol 2014 June 28; 20(24): 
7644-7652 
Ali AH, Carey EJ, Lindor KD. Recent advances in the development of farnesoid X receptor 
agonists. Ann Transl Med. 2015;3(1):5. 
Belloni L, Pollicino T, De Nicola F, et al. Nuclear HBx binds the HBV minichromosome 
and modifies the epigenetic regulation of cccDNA function. Proc. Natl. Acad. Sci. 
2009;106:19975–19979. 
Chan H.L.Y. et al. Alanine aminotransferase-based algorithms of liver stiffness 
measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B. 
Journal of Viral Hepatitis, 2009, 16, 36–44. 
Chon Y.E. et al. Performance of Transient Elastography for the Staging of Liver Fibrosis 
in Patients with Chronic Hepatitis B: A Meta-Analysis. PLoS One. 2012;7(9):e44930.  
De Ridder F, Sonneveld M, Lenz O, Janssen HL, Talloen W, Hansen BE. Mean week 24 
HBsAg declines predict subsequent rate of HBsAg seroclearance and could be a valuable 
endpoint for early development HBV trials. AASLD, Washington DC, USA, 2017. 
Decorsière A, Mueller H, van Breugel PC, et al. Hepatitis B virus X protein identifies the 
Smc5/6 complex as a host restriction factor. Nature. 2016;531:386–389. 
European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines 
on the management of hepatitis B virus infection. Journal of hepatology. 2017;67(2):370-
98. 
EYP001-102. Clinical Study Report. A Phase 1, Open-Label, Randomized, 4-Way 
Crossover Study in Subjects with Chronic Hepatitis B Virus Infection to Assess 
Pharmacokinetics (Fasted/Fed), Safety, Tolerability And Pharmacodynamics of Single 
Oral Doses of Farnesoid X Receptor Agonist EYP001a. 
EYP001-103. A Randomized, Double-Blind, Placebo-Controlled Study to Determine the 
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the FXR Agonist 
EYP001a in Chronically HBV Infected Subjects. Interim analysis and preliminary results. 
15 November 2018. 
EYP001-C01. Clinical Study Report. A Phase 1, Randomized, Double-Blind, 
Placebo-Controlled, Escalating Single- and Multiple-Dose Study to Evaluate the Safety, 
Tolerability and Pharmacokinetics of EYP001a in Healthy Male Subjects. 
Fiorucci S, Rizzo G, Antonelli E, et al. Cross-talk between farnesoid-X-receptor (FXR) 
and peroxisome proliferator-activated receptor gamma contributes to the antifibrotic 
activity of FXR ligands in rodent models of liver cirrhosis. J Pharmacol Exp Ther. 
2005;315(1):58-68. 
Guo F, Xu Z, Zhang Y, Jiang P, et al. FXR induces SOCS3 and suppresses hepatocellular 
carcinoma. Oncotarget. 2015;6(33):34606-34616. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 111 of 123 
 
 
 
Hensel KO, Cantner F, Bangert F, Wirth S, Postberg J. Episomal HBV persistence within 
transcribed host nuclear chromatin compartments involves HBx. Epigenetics Chromatin. 
2018;11:34. 
Höner zu Siederdissen C and Cornberg M. The role of HBsAg levels in the current 
management of chronic HBV infection. Ann Gastroenterol. 2014;27(2):105-112. 
Hyams KC. Risks of chronicity following acute hepatitis B virus infection: a review. Clin 
Infect Dis. 1995;20(4):992-1000. 
Investigator’s brochure Edition 4.1 dated 06 March 2019. EYP001a. ENYO Pharma. 
Investigator’s brochure memorandum dated 16 January 2020. EYP001a. ENYO Pharma. 
Lamontagne RJ, Bagga S, Bouchard MJ. Hepatitis B virus molecular biology and 
pathogenesis. Hepatoma Res. 2016;2:163-186. 
Lampertico P, Agarwal K, Berg T, et al. EASL 2017 Clinical Practice Guidelines on the 
management of hepatitis B virus infection. J Hepatol. 2017;67(2):370-398. 
Liang XE, Chen YP. Clinical Application of Vibration Controlled Transient Elastography 
in Patients with Chronic Hepatitis B. J Clin Transl Hepatol. 2017;5(4):368–375. 
Marcellin P. et al. Non-invasive assessment of liver fibrosis by stiffness measurement in 
patients with chronic hepatitis B. Liver International 2009; 29: 242-247. 
Marcellin P, et al.Combination of tenofovir disoproxil fumarate and peginterferon a-2a 
increases loss of hepatitis B surface antigen in patients with chronic hepatitis B. 
Gastroenterology 2016;150:134–144. 
Misra VL, Khashab M, Chalasani N. Nonalcoholic fatty liver disease and cardiovascular 
risk. Curr Gastroenterol Rep. 2009;11(1):50-5. 
Moreau P, Cournac A, Palumbo GA, et al. Tridimensional infiltration of DNA viruses into 
the host genome shows preferential contact with active chromatin. Nat. Commun. 
2018;9:4268. 
Mouzannar K, Fusil F, Lacombe B, et al. Farnesoid X receptor-α is a proviral host factor 
for hepatitis B virus that is inhibited by ligands in vitro and in vivo. FASEB J. 
2018;fj.201801181R. 
Niu Y, Xu M, Slagle BL, et al. Farnesoid X receptor ablation sensitizes mice to hepatitis b 
virus X protein–induced hepatocarcinogenesis. Hepatology. 2017;65:893–906. 
Oehler N, Volz T, Bhadra OD, et al. Binding of hepatitis B virus to its cellular receptor 
alters the expression profile of genes of bile acid metabolism. Hepatol. Baltim. Md. 
2014;60:1483–1493. 
OCALIVA (obeticholic acid) US Package Insert (USPI). New York, NY. Intercept 
Pharmaceuticals 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207999s000lbl.pdf (accessed 
26 July 2018). 
Radreau P, Porcherot M, Ramière C, Mouzannar K, Lotteau V, André P. Reciprocal 
regulation of farnesoid X receptor α activity and hepatitis B virus replication in 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
 
Confidential 
Page 112 of 123 
 
 
 
differentiated HepaRG cells and primary human hepatocytes. FASEB J. 2016; 30:3146–
3154. 
Radreau-Pierini P. Effects of EYP001 on HBV infection in PHH cells. 2016. 
Ramière C, Scholtès C, Diaz O, et al. Transactivation of the hepatitis B virus core promoter 
by the nuclear receptor FXRalpha. J Virol. 2008 Nov;82(21):10832-40. 
Sanyal AJ. NASH: A global health problem. Hepatol Res. 2011 Jul;41(7):670-674. 
Schaap FG, Trauner M, Jansen PL. Bile acid receptors as targets for drug development. 
Nat Rev Gastroenterol Hepatol. 2014;11(1):55-67. 
Slijepcevic D, Kaufman C, Wichers CGK, et al. Impaired uptake of conjugated bile acids 
and hepatitis b virus pres1-binding in na+-taurocholate cotransporting polypeptide 
knockout mice. Hepatology. 2015;62:207–219. 
Tan A., Koh S., Bertoletti B. Immune Response in Hepatitis B Virus Infection. Cold Spring 
Harb Perspect Med 2015;5:a021428.  
Tapper EB, Castera L, Afdhal NH. FibroScan (vibration-controlled transient elastography): 
where does it stand in the United States practice. Clin Gastroenterol Hepatol. 
2015;13(1):27-36. 
Urban S, Schulze A, Dandri M, Petersen J. The replication cycle of hepatitis B virus. J 
Hepatol. 2010;52(2):282-4. 
WHO 2014 World Health Organization. Fact sheet N°204 - Hepatitis B. 
www.who.int/mediacentre/factsheets/fs204/en/ (accessed 5 August 2016). 
World Health Organization (WHO). WHO Fact Sheet - Hepatitis B. 
http://www.who.int/news-room/fact-sheets/detail/hepatitis-b (Accessed 26 July 2018).  
Yan H, Zhong G, Xu G, et al. Sodium taurocholate cotransporting polypeptide is a 
functional receptor for human hepatitis B and D virus. Elife. 2012;1:e00049. 
Zhang Y et al. HBsAg seroclearance or seroconversion induced by peg-interferon alpha 
and lamivudine or adefovir combination therapy in chronic hepatitis B treatment: a meta-
analysis and systematic review. Rev Esp Enferm Dig. 2016;108:263-270. 
 
 
 


ENYO Pharma SA 
                                                                                                                                    Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
                                                                                                                         Confidential                                                                                 Page 113 of 123 
 
 
 
19. Appendices 
19.1. 
Appendix A - Schedule of Assessment* 
Assessment 
Screen
ing 
Visit1 
Treatment Period 
(Week 1 to Week 16) 
Follow-up Period 
(Week 17 to Week 40) 
ET 
Visit2 
 
Week -
12 
to -1 
(Day -
90 to 
Day -
1) 
Treat
ment 
Visit 1 
Week 
1 
(Day 
1) 
Treat
ment 
Visit 2 
Week 
2 
(Day 
14 ± 3 
days) 
Treat
ment 
Visit 3 
Week 
4 
(Day 
28 ± 3 
days) 
Treat
ment 
Visit 4 
Week 
6 
(Day 
42 ± 3 
days) 
Treat
ment 
Visit 5 
Week 
8 
(Day 
56 ± 3 
days) 
Treat
ment 
Visit 6 
Week 
10 
(Day 
70 ± 3 
days) 
Treat
ment 
Visit 7 
Week 
12 
(Day 
84 ± 3 
days) 
Treat
ment 
Visit 8 
Week 
14 
(Day 
98 ± 3 
days) 
Treat
ment 
Visit 9 
Week 
16 
(Day 
112 ± 3 
days) 
Follow
-up 
Visit 1 
Week 
20 
(Day 
140 ± 7 
days) 
Follow
-up 
Visit 2 
Week 
28 
(Day 
196 ± 7 
days) 
Follow
-up 
Visit 3 
Week 
40 
(Day 
280 ± 7 
days) 
(EoS) 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria 
X 
X3 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior and 
Concomitant 
Medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Drugs of abuse 
screen5 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Height6 and body 
weight 
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
BMI Calculation 
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 


ENYO Pharma SA 
                                                                                                                                    Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
                                                                                                                         Confidential                                                                                 Page 114 of 123 
 
 
 
Assessment 
Screen
ing 
Visit1 
Treatment Period 
(Week 1 to Week 16) 
Follow-up Period 
(Week 17 to Week 40) 
ET 
Visit2 
 
Week -
12 
to -1 
(Day -
90 to 
Day -
1) 
Treat
ment 
Visit 1 
Week 
1 
(Day 
1) 
Treat
ment 
Visit 2 
Week 
2 
(Day 
14 ± 3 
days) 
Treat
ment 
Visit 3 
Week 
4 
(Day 
28 ± 3 
days) 
Treat
ment 
Visit 4 
Week 
6 
(Day 
42 ± 3 
days) 
Treat
ment 
Visit 5 
Week 
8 
(Day 
56 ± 3 
days) 
Treat
ment 
Visit 6 
Week 
10 
(Day 
70 ± 3 
days) 
Treat
ment 
Visit 7 
Week 
12 
(Day 
84 ± 3 
days) 
Treat
ment 
Visit 8 
Week 
14 
(Day 
98 ± 3 
days) 
Treat
ment 
Visit 9 
Week 
16 
(Day 
112 ± 3 
days) 
Follow
-up 
Visit 1 
Week 
20 
(Day 
140 ± 7 
days) 
Follow
-up 
Visit 2 
Week 
28 
(Day 
196 ± 7 
days) 
Follow
-up 
Visit 3 
Week 
40 
(Day 
280 ± 7 
days) 
(EoS) 
 
Physical 
Examination7 
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
Vital Signs8,9 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AUDIT-C10 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization11 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Pruritus assessment 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse event 
monitoring 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Viral serology12 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chemistry 
X13 
X 
X23 
X 
X23 
X 
X23 
X 
X23 
X 
X 
X 
X 
X 
Haematology, 
coagulation, lipid 
and metabolic 
profile 
X 
X 
X23 
X 
X23 
X 
X23 
X 
X23 
X 
X 
X 
X 
X 
Pregnancy test (for 
WOCBP only)14 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 


ENYO Pharma SA 
                                                                                                                                    Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
                                                                                                                         Confidential                                                                                 Page 115 of 123 
 
 
 
Assessment 
Screen
ing 
Visit1 
Treatment Period 
(Week 1 to Week 16) 
Follow-up Period 
(Week 17 to Week 40) 
ET 
Visit2 
 
Week -
12 
to -1 
(Day -
90 to 
Day -
1) 
Treat
ment 
Visit 1 
Week 
1 
(Day 
1) 
Treat
ment 
Visit 2 
Week 
2 
(Day 
14 ± 3 
days) 
Treat
ment 
Visit 3 
Week 
4 
(Day 
28 ± 3 
days) 
Treat
ment 
Visit 4 
Week 
6 
(Day 
42 ± 3 
days) 
Treat
ment 
Visit 5 
Week 
8 
(Day 
56 ± 3 
days) 
Treat
ment 
Visit 6 
Week 
10 
(Day 
70 ± 3 
days) 
Treat
ment 
Visit 7 
Week 
12 
(Day 
84 ± 3 
days) 
Treat
ment 
Visit 8 
Week 
14 
(Day 
98 ± 3 
days) 
Treat
ment 
Visit 9 
Week 
16 
(Day 
112 ± 3 
days) 
Follow
-up 
Visit 1 
Week 
20 
(Day 
140 ± 7 
days) 
Follow
-up 
Visit 2 
Week 
28 
(Day 
196 ± 7 
days) 
Follow
-up 
Visit 3 
Week 
40 
(Day 
280 ± 7 
days) 
(EoS) 
 
TSH intermittent 
monitoring 
X 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
Dipstick Urinalysis 
all male and 
females15 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
12-Lead ECG9 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
HBV response 
markers16 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD biomarker 
sampling17 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Liver fibrosis and 
inflammation 
assessment18 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
Fibroscan VCTE 
X 
 
 
 
 
 
 
 
 
X 
 
 
X 
X 
Liver imaging  
X19 
 
 
 
 
 
 
 
 
 
 
 
X19 
 
PK Sampling 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
Dispense patient 
diary and review20 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 


ENYO Pharma SA 
                                                                                                                                    Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
                                                                                                                         Confidential                                                                                 Page 116 of 123 
 
 
 
Assessment 
Screen
ing 
Visit1 
Treatment Period 
(Week 1 to Week 16) 
Follow-up Period 
(Week 17 to Week 40) 
ET 
Visit2 
 
Week -
12 
to -1 
(Day -
90 to 
Day -
1) 
Treat
ment 
Visit 1 
Week 
1 
(Day 
1) 
Treat
ment 
Visit 2 
Week 
2 
(Day 
14 ± 3 
days) 
Treat
ment 
Visit 3 
Week 
4 
(Day 
28 ± 3 
days) 
Treat
ment 
Visit 4 
Week 
6 
(Day 
42 ± 3 
days) 
Treat
ment 
Visit 5 
Week 
8 
(Day 
56 ± 3 
days) 
Treat
ment 
Visit 6 
Week 
10 
(Day 
70 ± 3 
days) 
Treat
ment 
Visit 7 
Week 
12 
(Day 
84 ± 3 
days) 
Treat
ment 
Visit 8 
Week 
14 
(Day 
98 ± 3 
days) 
Treat
ment 
Visit 9 
Week 
16 
(Day 
112 ± 3 
days) 
Follow
-up 
Visit 1 
Week 
20 
(Day 
140 ± 7 
days) 
Follow
-up 
Visit 2 
Week 
28 
(Day 
196 ± 7 
days) 
Follow
-up 
Visit 3 
Week 
40 
(Day 
280 ± 7 
days) 
(EoS) 
 
Check amount of 
study medication 
and dispense 
accordingly 
EYP001a/placebo 
and/or NA21 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
 
 
Collect 
used/unused study 
drug and assess 
compliance22 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AUDIT-C: Alcohol Use Disorders Identification Test-Concise; BMI: Body Mass Index; ECG: Electrocardiogram; EoS: End of Study; ET: Early Termination; 
HIV: Human Immunodeficiency Virus; VCTE: Vibration Controlled Transient Elastography; WOCBP: Women of Childbearing Potential 
* 3-day window is acceptable for treatment visits and a 7 days window for Follow-Up visits. 
1 Patient who is first designated as a screen failure prior to being randomized may be rescreened upon Sponsor or designee approval.  
2 Patients who discontinue early from the study for any reason, will be requested to return to the clinic for a follow-up Visit approximately one week after 
administration of their final last dose of any study medication, regardless of how many days the patient was in the study. 
3 Confirm eligibility prior to randomization 
4 Genotype information will be collected from medical history. Genotyping will be requested via central lab only if information is not available through medical 
history. 
5 Drugs of abuse test at Screening and Day 1 pre-dose only for drugs such as amphetamines, methamphetamine, barbiturates, benzodiazepines, cocaine, 
methadone, opiates, phencyclidine, tricyclic antidepressants and THC (cannabis). 
6 Height to be recorded only on Screening visit 


ENYO Pharma SA 
                                                                                                                                    Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
                                                                                                                         Confidential                                                                                 Page 117 of 123 
 
 
 
7 A complete physical examination (including general appearance; eyes, ears, nose, and throat; head and neck; chest and lungs; cardiovascular; abdomen; 
musculoskeletal; lymphatic; dermatological; neurological systems; mental status; and extremities) will be performed at screening. Brief, symptom-directed 
physical examinations will be performed on all other study visits. 
8 Vital signs include systolic and diastolic blood pressure, heart rate, respiratory rate, and body temperature and will be performed with the patient in the sitting 
position after 5 minutes of rest and before any blood draws. Site staff will use a mercury sphygmomanometer or automatic blood pressure device with an 
appropriately sized cuff with the bladder centred over the brachial artery. Site staff will record the arm used for the measurement and use the same arm 
throughout the study. Site staff will measure and record the blood pressure. Blood pressure will be recorded to the nearest 2 mmHg mark on the manometer or to 
the nearest whole number on an automatic device.. 
9 The following schedule will be utilized to measure vital signs (Heart Rate, Blood Pressure, Temperature): Blood pressure and pulse: 
screening, pre-dose on Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 28 and 40 (EoS) or ET. Blood pressure will be taken in a sitting position after 5 minutes rest. ECG 
will be performed prior to vital signs assessments. 
10 Patients with AUDIT-C scores 3 points at screening will receive the full AUDIT and will be excluded if they score 8 points on the full AUDIT. Patients with 
AUDIT C scores <3 points will not receive the full AUDIT. 
11 Can occur after eligibility check on Day -3 at the earliest and prior to dosing on Day 1 at the latest 
12 Anti-HIV, anti-HCV, anti-HDV, quantitative HBV-DNA, quantitative HBsAg, anti-HBs, anti-HBe on screening visit. For positive HCV antibody-test results 
only, a PCR-based quantitative HCV viral load assessment will also be performed. 
13 Alpha Foeto Protein (AFP) at screening normal 
14 A serum hCG test will be performed at Screening and ET Visits in WOCBP only. Urine hCG tests will be performed at all other visits. If a urine hCG test is 
positive, a serum hCG test will be performed. 
15 Urinalysis will be evaluated from a fresh urine sample by dipstick. Further analysis for urine sediment or urine microscopy will be performed when there are 
any abnormalities on any of the following 3 dipstick results: leukocyte esterase, blood, or nitrite, and if judged clinically significant by the Investigator. 
16 HBV DNA, HBsAg, HBV RNA, HBcrAg, HBeAg and anti-HBe. 
Analysis of HBV response markers: 
• 
Samples for analysis of quantitative HBsAg and quantitative HBV-DNA will be collected at pre-dose on all study visits during treatment period and 
Weeks 20, 28 and 40 of follow-up or at the ET visit. 
• 
Samples for analysis of quantitative HBV pgRNA and HBcrAg will be collected at pre-dose on all study visits during treatment period and at week 40 of 
follow-up or at the ET visit. 
• 
Sample for analysis of HBeAg, anti-HBe and anti-HBs will be collected at screening or Day 1, then pre-dose at Week 16, Week 40 (EoS visit) or ET 
Visit. 
• A subject who experiences a breakthrough (defined by quantifiable HBV DNA increase of ≥ 1log10 HBV DNA copies/mL above LLOQ) should return to the 
study site for a confirmatory measurement within two weeks. If virologic breakthrough is confirmed stopping rule (Section 4.6. applies) 
17 PD biomarker samples: 
Plasma C4, FGF19; BAs (total, primary, and secondary BAs [such as CDCA, DCA, LCA, and/or others as appropriate {Samples for BAs will be collected and 
stored centrally frozen for subsequent assessment after the EoS pending ongoing BA profiling related to EYP001a pharmacology}]) sampling will occur 
pre-dose paired with PK sampling at all visits during treatment period. A sample will also be collected at the EoS or ET Visits. 


ENYO Pharma SA 
                                                                                                                                    Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
                                                                                                                         Confidential                                                                                 Page 118 of 123 
 
 
 
18 Liver fibrosis and inflammation parameters include ALT, AST, AST/ALT ratio, high sensitivity C-reactive protein, interleukin 6, tumour necrosis factor alpha, 
procollagen type III N terminal peptide (Pro C3), tissue inhibitor of metalloproteinases-1 (and derived enhanced liver fibrosis score). This is a provisional list 
with some fibrosis markers that can be added. 
19 Unless done within 6 months prior screening liver imaging is performed at screening. For liver imaging ultrasonography (US) is preferred, alternately 
computed tomography (CT) or magnetic resonance imaging (MRI) can be used. For patients with risk factors for of hepatocellular carcinoma (HCC), i.e. any of 
these: family history with HCC, >40 years of age, male sex, born in Sub-Saharan Africa, Metabolic syndrome (obesity, diabetes), smoking, ALT>ULN, HBV 
DNA (>2,000 IU/mL), HBeAg-negative, Genotype C) during follow-up phase liver imaging is performed at week 40, i.e. after 6 months of follow-up 
maintenance treatment.. 
20 During the treatment period, patient diary will be dispensed to record study drug (EYP001a/Placebo and NA) administration and will be reviewed to assess 
compliance to study drug. During the follow-up period, patient diary will be dispensed to record NA administration and will be reviewed to assess compliance to 
NA.  
21 EYP001a/Placebo will be dispensed throughout the treatment period. NA will be dispensed throughout the treatment period and follow-up Visits 1 and 2 
(Weeks 20 and 28, respectively). Please note 16 weeks of treatment (EYP001a/Placebo and NA) with 4 weeks treatment units will be dispensed. This implies that 
no extra treatment units will be dispensed. Should patient “loose” treatment units the check on sufficient treatment can be made at each fortnightly visit. 
On each treatment visit study drug (EYP001a/Placebo and NA) should be administered after PK/PD blood sampling.  
22 During the treatment period, used/unused study drug (EYP001a/Placebo and NA) will be collected to assess compliance to study drug. During the follow-up 
period, used/unused NA will be collected to assess compliance to NA. 
23 Liver safety testing: ALT, AST, Alkaline Phosphatase, Gamma Glutamyl Transferase (GGT), Total Bilirubin, Thrombocytes and Albumin. 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
Confidential 
          Page 119 of 123 
 
 
 
19.2. 
Appendix B: Pruritus Scale 
 
Pruritus Visual Analog Scale 
 
 
 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
Confidential 
          Page 120 of 123 
 
 
 
 
 
 
 
 
 
 
 
 
 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
Confidential 
          Page 121 of 123 
 
 
 
19.3. 
Appendix C: Alcohol Use Disorders Identification Test-Concise 
 
The Alcohol Use Disorders Identification Test-Concise (AUDIT-C) has 3 questions and is 
scored on a scale of 0 to 12. Read the questions as written and circle the letter that 
corresponds to the answer. Each AUDIT-C question has 5 answer choices valued from 0 
to 4 points. In men, a score of 4 or more is considered positive, optimal for identifying 
hazardous drinking or active alcohol use disorders. In women, a score of 3 or more is 
considered positive. Generally the higher the score, the more likely it is that a person’s 
drinking is affecting his or her safety.  
 
See answer module on the next page.  


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
Confidential 
          Page 122 of 123 
 
 
 
Answer Module  
Question 1: How often do you have a drink containing alcohol?  
 
Question 2: How many standard drinks containing alcohol do you have on a typical day?  
 
Question 3: How often do you have six or more drinks on one occasion?  
 
 
 
 
 


ENYO Pharma SA 
 
Protocol No: EYP001-201 
 
 
Version/date: 3.0 / 22 January 2020 
Confidential 
          Page 123 of 123 
 
 
 
19.4. 
Appendix D: The Alcohol Use Disorders Identification Test: Interview 
Version 
Read questions as written. Read answers carefully. Begin the AUDIT by saying “Now I 
am going to ask you some questions about your use of alcoholic beverages during this past 
year.” Explain what is meant by “alcoholic beverages” by using local examples of beer, 
wine, vodka, etc. Code answers in terms of “standard drinks.” Place the correct answer 
number in the box at the right. Total scores of 8 are recommended as indicators of 
hazardous and harmful alcohol use.  
 

SAP_001.pdf: 
Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 1 of 52 
 
 
 
 
The information in this document is confidential and proprietary to Novotech Pty Ltd and its 
clients. The information may only be used by the entities to which it was disclosed for the purpose 
it was disclosed. To the maximum extent permissible by law, the information must not be 
disclosed to any third parties without the prior written consent of Novotech. 
STATISTICAL ANALYSIS PLAN 
A PHASE 2a, RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED 
STUDY OF ORAL FXR MODULATOR EYP001a COMBINED WITH 
NUCLEOS(T)IDE ANALOGUES (NA) IN VIROLOGICALLY SUPPRESSED 
CHRONIC HEPATITIS B PATIENTS TO IMPROVE FUNCTIONAL CURE 
RATES 
 
PROTOCOL NO.: 
EYP001-201 
 
PRODUCT CODE: EYP001a 
 
PREPARED FOR: 
ENYO Pharma SA 
 
60 avenue Rockefeller, 
 
Bâtiment Bioserra B. 
 
69008 
 
Lyon, 
 
France 
 
PREPARED BY: 
Novotech (Australia) Pty Ltd 
 
Level 3, 235 Pyrmont Street 
 
Pyrmont, NSW, 2009  
 
Australia  
 
DATE OF ISSUE: 
2021-08-13 
 
VERSION/STATUS: 
Version 3.0 (2021-08-13) 
 
VERSION HISTORY:  Version 2.1 (2021-08-11) 
                                         Version 1.5 (2021-05-31) 
                                        Version 1.4 (2021-05-21) 
                                        Version 1.3 (2021-05-13) 
                                          Version 1.2 (2021-04-28) 
                                          Version 1.1 (2021-04-20) 
                                          Version 1.0 (2021-03-10) 
                                          Version 0.6 (2021-03-05) 
                                      Version 0.5 (2021-02-18) 
                                      Version 0.4 (2021-01-22) 
                                      Version 0.3 (2020-12-14) 
                                      Version 0.2 (2020-10-07) 
 
Version 0.1 (2020-02-07) 
 
 
AUTHOR: 
Jan Steyn/ Ella Liu 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 2 of 52 
 
SAP APPROVAL 
 
By my signature, I confirm that this SAP has been reviewed by ENYO Pharma SA and has been approved 
for use on the EYP001-201 study: 
 
Name 
Title / Company 
Signature 
Date 
 
 
 
 
Hugo Girma 
Biostatistician, Data-Manager / 
Enyo Pharma 
 
 
 
 
 
 
Jan Steyn 
Senior Manager Biostatistics / 
Novotech 
On behalf of Jan Steyn 
 
Ella Liu 
Senior Biostatistician / 
Novotech 
 
 
 
 
 
 
 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 3 of 52 
 
Table of contents 
 
1. 
INTRODUCTION 
7 
2. 
PROJECT OVERVIEW 
8 
2.1 
Study Design 
8 
2.2 
Objectives 
8 
2.3 
Endpoints 
9 
2.4 
Sample Size 
10 
2.5 
Randomization 
11 
3. 
STATISTICAL CONSIDERATIONS 
12 
3.1 
General Considerations 
12 
3.2 
Key Definitions 
13 
3.3 
Inferential Analyses 
14 
3.4 
Multiple Comparisons and Multiplicity Adjustments. 
17 
3.5 
Handling of Missing Data 
17 
3.6 
Coding of Events and Medications 
19 
3.7 
Treatment Groups/Treatment Sequence 
19 
4. 
ANALYSIS SETS 
20 
4.1 
Population Descriptions 
20 
5. 
PARTICIPANT DISPOSITION AND ANALYSIS POPULATIONS 
21 
6. 
PROTOCOL DEVIATIONS 
22 
7. 
DEMOGRAPHIC AND BASELINE INFORMATION 
23 
7.1 
Demographics 
23 
7.2 
Medical history 
23 
7.3 
Viral Serology 
23 
7.4 
Drugs of Abuse 
23 
8. 
TREATMENT EXPOSURE AND COMPLIANCE 
24 
9. 
PRIOR AND CONCOMITANT MEDICATIONS 
25 
10. 
PHARMACOKINETICS 
26 
11. 
PHARMACODYNAMICS 
27 
12. 
EFFICACY 
28 
12.1 
Inferential Analyses 
29 
12.2 
Other Analyses 
29 
13. 
SAFETY 
30 
13.1 
Adverse Events 
30 
13.2 
Safety Laboratory Assessments 
30 
13.3 
Vital Signs 
33 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 4 of 52 
 
13.4 
12-Lead Electrocardiogram (ECG) 
34 
13.5 
Pruritus Assessment 
34 
13.6 
Physical Examinations 
35 
13.7 
Liver Fibrosis and inflammation Assessment 
35 
13.8 
Liver Imaging 
36 
13.9 
Pregnancy Test Results 
36 
14. 
IMMUNOGENICITY 
37 
15. 
CHANGES TO THE PLANNED ANALYSIS 
38 
16. 
INTERIM AND FINAL ANALYSIS 
39 
16.1 
Interim Analysis (DSMC Review meeting) 
39 
16.2 
Final Analysis (End of Study) 
40 
17. 
SOFTWARE 
41 
18. 
TABLES 
42 
19. 
LISTINGS 
46 
20. 
FIGURES 
49 
21. 
REFERENCES 
52 
 
 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 5 of 52 
 
List of Abbreviations 
 
Abbreviation 
Description 
 
 
AE 
Adverse Event 
Anti-HBe  
Antibody to Hepatitis B e antigen  
Anti-HBs  
Antibody to Hepatitis B surface antigen  
ATC 
Anatomical Therapeutic Class 
BA 
Bile Acid 
BMI 
Body Mass Index 
BP 
Blood Pressure 
CHB 
Chronic Hepatitis B 
CS 
Clinically Significant 
CSR 
Clinical Study Report 
CTU 
Clinical Trial Unit 
DBP 
Diastolic blood pressure 
 
DNA 
Deoxyribonucleic Acid  
ECG 
12-Lead Electrocardiogram  
eCRF 
Electronic Case Report Form 
EoS 
End of Study 
ET 
Early Termination 
ETV 
Entecavir  
FDA 
Food and Drug Administration 
FGF19 
Fibroblast Growth Factor 
FU 
Follow Up 
FXR 
Farnesoid X Receptor 
GCP 
Good Clinical Practice 
HBcrAg 
Hepatitis B core-related antigen 
HBeAg 
Hepatitis B Surface e-Antigen 
HBsAg  
Hepatitis B Surface Antigen  
HBV  
Hepatitis B virus  
HCV  
Hepatitis C virus  
HIV 
Human Immunodeficiency Virus 
IA 1 
Interim Analysis 1 
IA 2 
Interim Analysis 2 
ICH 
International Council for Harmonization 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
IP 
Investigational Product 
ITT 
Intent-to-Treat 
IWRS 
Interactive Web Response System 
LLOQ 
Lower Limit Of Quantification 
LS 
Least Square 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intention-To-Treat 
NA 
Nucleos(t)ide analogues 
N/A 
Not Applicable 
NCS 
Not Clinically Significant 
NK 
Not Known 
PD 
Pharmacodynamic 
pgRNA 
Pg/Precore Ribonucleic Acid  
PK 
Pharmacokinetic 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 6 of 52 
 
PP 
Per Protocol 
PT 
Preferred Term 
QD 
Once Daily 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SBP 
Systolic blood pressure 
SD 
Standard Deviation 
S.I. 
International System of Units 
SOC 
Standard of Care 
SOC2 
System Organ Class 
SOP 
Standard Operating Procedure 
TD  
Target Detected 
TDF  
Tenofovir Disoproxil Fumarate  
TEAE 
Treatment Emergent Adverse Event 
TFL 
Tables, Figures and Listings 
TND 
Target not detected 
VAS 
Visual Analog Scale 
VCTE 
Vibration Controlled Transient Elastography  
WHO-DD 
World Health Organization Drug Dictionary 
 
 
 
 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 7 of 52 
 
1. 
INTRODUCTION 
The following Statistical Analysis Plan (SAP) provides the outline for the statistical analysis of the data 
collected from the EYP001-201 study (protocol version 3.0 dated 22 January 2020). 
The planned analyses identified in this SAP may be included in clinical study reports (CSRs), regulatory 
submissions, or future manuscripts. Also, post hoc exploratory analyses not necessarily identified in this 
SAP may be performed to further examine study data. Any post hoc, or unplanned, exploratory analyses 
performed will be clearly identified as such in the final CSR. 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 8 of 52 
 
2. 
PROJECT OVERVIEW 
2.1 
Study Design 
This is a prospective, multi-centre, international randomized, double-blind, placebo controlled, Phase 2a 
experimental study of oral FXR modulator EYP001a/placebo combined with Nucleos(t)ide analogues 
(NA) in virologically suppressed CHB patients to improve functional cure rates.  
In total 49 eligible patients will be enrolled and randomized at approximately 14 study sites in 4 
countries. Patients will be randomized prior to study drug (EYP001a or placebo and NA) administration 
on Day 1 in the ratio of 3:1 into 2 arms:  
● 
Experimental Arm: EYP001a 200 mg once daily (QD) + NA daily (37 patients)  
● 
Control Arm: Placebo + NA daily (12 patients)  
Patients will also be stratified per HBeAg status, based on medical history HBeAg value or established 
during screening, to obtain a balanced randomization to both study arms.  
The maximum total engagement duration for eligible patients in this study is up to 370 days: 90 days 
screening, 112 days (16 weeks) experimental treatment period and 168 days (24 weeks) follow-up on 
NA standard of care therapy (SOC) only.  
Patients enrolled in the study will be assessed as outpatients. Patient screening will occur no more than 
90 days prior to the Day 1 visit. Eligible patients will undergo further assessments on Day 1 to qualify 
for study drug administration on Day 1. 
Figure 1: 
Study Design 
 
2.2 
Objectives 
2.2.1 
Primary objective 
The primary objective of this study is: 
● 
To determine the effect of EYP001a on top of NA (standard of care (SOC) therapy) on Hepatitis 
B Surface Antigen (HBsAg) plasma levels. 
2.2.2 
Secondary objective(s) 
The secondary objectives of this study are: 
● 
To establish the effect of EYP001a on top of NA on HBsAg responder rate at the end of the 16-
week EYP001a treatment and at 24-week of follow-up (Week 40).  
● 
To establish the effect of EYP001a on top of NA on HBsAg loss rate at the end of the 16-week 
EYP001a treatment and at 24-week of follow-up (Week 40).  
● 
To establish the Hepatitis B virus (HBV) virologic failure rate (breakthrough) during the 24-weeks 
follow-up period after stopping EYP001a with ongoing NA.  
● 
To determine HBV viral response, HBV Pg/Precore Ribonucleic Acid (pgRNA), Hepatitis B core-
related antigen (HBcrAg) and Hepatitis B Surface e-Antigen (HBeAg), Antibody to Hepatitis B e 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 9 of 52 
 
antigen (Anti-HBe) and Antibody to Hepatitis B surface antigen (Anti-HBs) at the end of the 16-
week EYP001a treatment and Week 40 of follow-up.  
● 
To explore the safety profile of EYP001a treatment in combination with NA.  
● 
To determine the plasma concentration of EYP001a and pharmacodynamic (PD) markers (plasma 
C4 (7α-hydroxy-4-cholesten-3-one)), fibroblast growth factor (FGF) 19 and BAs. 
2.3 
Endpoints 
2.3.1 
Primary endpoint(s) 
● 
Efficacy assessed as HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment.  
2.3.2 
Secondary endpoints(s) 
Efficacy will be assessed as follows: 
● 
HBsAg responder rate (decrease from baseline ≥ 1.0 on the log10 scale) at Week 16 of treatment 
and Weeks 20, 28 and 40 of follow up. 
● 
HBsAg responder rate (decrease from baseline ≥ 0.5 on the log10 scale) at Weeks 12 and 16 of 
treatment and Weeks 20, 28 and 40 of follow up.  
● 
HBsAg loss rate (% patients with HBsAg < Lower Limit of Quantification (LLOQ/TND) at Week 
16 of treatment and Weeks 20, 28 and 40 of follow-up. 
● 
HBsAg loss rate (% patients with HBsAg < Lower Limit of Quantification (LLOQ/TD) at Week 
16 of treatment and Weeks 20, 28 and 40 of follow-up. 
● 
HBsAg loss rate (Proportion of results that are Target Not Detected versus Target Detected) at 
Week 16 of treatment and Weeks 20, 28 and 40 of follow-up.  
● 
Relapse rate HBsAg (% patients who became negative [HBsAg < LLOQ], then increased with 
HBsAg > LLOQ) at Week 16 of treatment period and Weeks 20, 28 and 40 during follow-up 
period. 
● 
Virologic failure rate (breakthrough) of Hepatitis B virus Deoxyribonucleic Acid (HBV-DNA) (% 
patients with a confirmed quantifiable HBV DNA increase of ≥ 1log10 HBV DNA copies/mL 
above LLOQ) assessed at Week 16 of treatment period and Weeks 20, 28 and 40 during follow-
up period.  
● 
% patients with HBV DNA < Lower Limit of Quantification (LLOQ/TND) at baseline, Week 4, 
8, 12 and 16 of treatment and Weeks 20, 28 and 40 of follow-up 
● 
% patients with HBV DNA < Lower Limit of Quantification (LLOQ/TD) at baseline, Week 4, 8, 
12 and 16 of treatment and Weeks 20, 28 and 40 of follow-up 
● 
HBV-pgRNA decline (Δ log10) from Day 1 to Weeks 4, 8, 12, 16 of treatment period and Week 
40 of maintenance period.  
● 
HBcrAg decline (Δ log10) from Day 1 to Weeks 4, 8, 12, 16 of treatment period and Week 40 of 
maintenance period.  
● 
HBeAg quantification for HBeAg pos patients and changes at Week 16 of treatment and Week 40 
of follow-up.  
● 
Fibroscan Vibration Controlled Transient Elastography (VCTE) change from screening value to 
Weeks 16 and 40 or Early Termination (ET) value.  
Safety and Tolerability will be assessed as: 
● 
Treatment-emergent adverse events (TEAEs) (including Serious Adverse Event (SAEs))  
● 
All-cause mortality  


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 10 of 52 
 
● 
Clinical laboratory tests  
● 
Pruritus assessment (VAS and Q5D) 
● 
Vital signs (blood pressure, heart rate, respiratory rate, and temperature)  
● 
Concomitant medications  
● 
Physical examinations  
● 
12-lead Electrocardiogram (ECG). 
Pharmacokinetics (PK) assessed will be as: 
● 
Plasma concentration of EYP001a or any relevant active metabolites (as identified in an ongoing 
phase 1 study). 
PD biomarkers will be assessed as:  
● 
Plasma C4 (7α-hydroxy-4-cholesten-3-one) 
● 
FGF19 
● 
Plasma primary and secondary BAs. 
2.4 
Sample Size 
The primary endpoint is HBsAg reduction. Improvement of 1.0 on a log10 scale at 16 weeks is considered 
to be clinically meaningful. The expected accrual rate is 2 to 4 patients per week but does not affect the 
sample size calculation. Note that the accrual rate will not affect sample size calculations. All 
assumptions are given in Table 1. 
Table 1 Assumptions for primary endpoint  
Primary Endpoint 
HBsAg reduction vs baseline on a log10 scale (“Chg”) 
Null hypothesis  
H0: Chgexp – Chgctrl = 0  
Alternative hypothesis  
Ha: Chgexp - Chgctrl = -1.0  
SD of change vs baseline in experimental 
arm  
1.08  
SD of change vs baseline in control arm  
1.08  
Drop-out  
10% over total study duration  
Randomization ratio  
3:1 for experimental:control (i.e. nE/nC=3)  
Power  
80%  
Type I error rate (1-sided)  
0.05  
Chg: Change vs baseline; Ctrl: Control arm; Exp: Experimental arm; H0: Null Hypothesis; Ha: Alternative Hypothesis; SD: 
Standard Deviation 
Patients who have dropped out, will be assumed to have a zero-difference vs baseline for 
conservativeness. To take this into account, the assumed effect of -1.0 on a log10 scale, will be multiplied 
by 0.9, resulting in an assumed effect of -0.9. Using these assumptions, based on a test, 49 patients will 
need to be enrolled. Calculations are based on a t-test.  
Note that the final analysis will be done, using a general linear model for repeated measures. Using this 
type of model, a better power is expected, thus sample size calculations can be considered conservative. 
To calculate the power to detect a difference in HBsAg loss rate, we assumed a proportion of 0.5% in 
the placebo arm, and of 10%in the experimental arm. A trial including 49 patients results in a power of 
about 55% for this endpoint (using an un-pooled estimate of the variance), using a one-sided α of 0.05. 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 11 of 52 
 
2.5 
Randomization 
Sequential screening numbers will be assigned to patients at the time of informed consent signing. As 
they are enrolled into the study and after eligibility on Day -3 at the earliest and prior to dosing on Day 
1 at the latest, patients will be assigned to a unique randomization number which are randomly assigned 
to treatment according to the specified randomization scheme.  
The randomization schedule will be computer-generated before the start of the study.  
An Interactive Web Response System (IWRS) will be employed to manage patient and treatment 
assignments. 
Patients will be randomized prior to study drug (EYP001a or placebo and NA) administration on Day 1     
in the ratio of approximately 3:1 (37:12) into 2 arms: 
● 
Experimental Arm: EYP001a 200 mg QD + NA daily (37 patients) 
● 
Control Arm: Placebo + NA daily (12 patients) 
The ratio will be controlled through block randomization. 
Patients will also be stratified per HBeAg status, based on medical history HBeAg value or established 
during screening, to obtain a balanced randomization to both study arms. 
 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 12 of 52 
 
3. 
STATISTICAL CONSIDERATIONS 
Data will be handled and processed per the sponsor’s representative (Novotech) Standard Operating 
Procedures (SOPs), which are written based on the principles of good clinical practice (GCP).  
3.1 
General Considerations 
All data collected on the electronic case report form (eCRF) will be presented in the data listings and 
will be listed and sorted by treatment arm, participant number and visit, where applicable. All descriptive 
summaries will be presented by treatment group and nominal visit/time point (where applicable).  
Unless otherwise stated, the following methods will be applied: 
● 
Continuous variables: Descriptive statistics will include the number of non-missing values (n), 
arithmetic mean, standard deviation (SD), median, minimum and maximum values.  
The minimum and maximum values will be displayed to the same decimal precision as the source 
data, the arithmetic mean, SD and median values will be displayed to one more decimal than the 
source data for the specific variable. 
95% Confidence Intervals (CIs), mean differences (among treatments and from baseline) and 
least-square (LS-Means) values will be displayed to one more decimal than the source data for a 
specific variable. P-values will be displayed to 3 decimal places. 
The appropriate precision for derived variables will be determined based on the precision of the 
data on which the derivations are based, and statistics will be presented in accordance with the 
above-mentioned rules. 
● 
Figures based on continuous summary data:  
o 
X-axis will represent the linear scheduled time expressed as -Day x for screening values 
and +Day y on treatment values 
o 
Y-axis will represent the Mean (+/-SD) and be presented as box-plots (median 
interquartile) parameter value (unit). 
● 
Categorical variables: Descriptive statistics will include counts and percentages per category. The 
denominator in all percentage calculations will be the number of participants in the relevant 
analysis population with non-missing data, unless specifically stated otherwise. Percentages will 
be displayed to one decimal place. Proportions will be displayed to 3 decimal places. 
95% Confidence Intervals (CIs), difference in proportions, odds ratio’s and other categorical 
parameters will be displayed to one decimal place for percentages. Proportions will be displayed 
to 3 decimal places. P-values will be displayed to 3 decimal places. 
● 
Repeat/unscheduled assessments: Only values collected at scheduled study visits/time points will 
be presented in summary tables.      If a repeat assessment was performed, the result from the 
original assessment will be presented as the result at the specific visit/time point. All collected 
data will be included in the data listings. 
● 
Assessment windows: All assessments will be included in the data listings and no visit windows 
will be applied to exclude assessments that were performed outside of the protocol specified 
procedure windows. 
● 
Result display convention: Results will be center aligned in all summary tables and listings. 
Participant identifiers visit and parameter labels may be left-aligned if required. 
● 
Date and time display conventions: The following display conventions will be applied in all 
outputs where dates and/or times are displayed: 
Date only: YYYY-MM-DD 
Date and time: YYYY-MM-DD HH:MM 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 13 of 52 
 
If only partial information is available, unknown components of the date or time will be presented as 
‘NK’ (not known), i.e., ‘2016-NK-NK’. Times will be reported in military time. 
● 
End of Study (EoS) vs Early Termination (ET) 
For any analyses based on safety data, efficacy and PD data, EOS and ET assessment will be summarized 
separately. 
 
3.2 
Key Definitions 
The following definitions will be used: 
● 
Baseline: The baseline value is defined as the last available valid (quantifiable continuous or 
categorical value), non-missing observation for each participant prior to first study drug 
administration. Repeat and unscheduled assessments will be included in the derivation of the 
baseline values.  
For HBsAg, ALT, AST, ALP, and total Bilirubin (TBL), the baseline value is defined as the 
average of screening and day 1 pre-dose. 
For HBeAg, the Baseline value is value taken at screening visit. 
● 
Change from Baseline: The change from baseline value is defined as the difference between the 
result collected/derived at a post-baseline visit/time point and the baseline value. 
The change from baseline value at each post-baseline visit/time point will be calculated for all 
continuous parameters using the following formula: 
Change from Baseline Value = Result at Visit/Time Point – Baseline Value 
The change from baseline value will only be calculated if the specific post-baseline visit/time point 
result and the baseline value for the parameter are both available and will be treated as missing 
otherwise. 
● 
Percent Change from baseline: The percent change from baseline at each post-baseline visit/time 
point will be calculated for all continuous parameters using the following formula: 
% Change from Baseline = 100 X [(Post-Dose Visit Value – Baseline) / Baseline] 
● 
Study day: The study day of an event is defined as the relative day of the event starting with the 
date of the first study drug administration (reference date) as Day 1 (there will be no Day 0). 
The study day of events occurring before the first study drug administration will be calculated as: 
Study Day = (Date of Event - Date of First Study Drug Administration) 
For events occurring on or after Day 1, study day will be calculated as: 
Study Day = (Date of Event - Date of First Study Drug Administration) + 1 
Study days will only be calculated for events with complete dates and will be undefined for 
events that are ‘Ongoing’ at the end of the study. 
Relative days compared to an alternative reference point will be calculated similarly, but the 
alternative starting reference start date will be used instead of the date of the first study drug 
dosing. 
     Please note that for this study, first study drug dosing is considered to occur on Day 1. 
● 
Breakthrough: Quantifiable HBV DNA increase of ≥ 1 log10 HBV DNA copies/mL above LLOQ.  
● 
Lower limit of quantification (LLOQ): HBV DNA results i.e HBsAg < LLOQ will be reported as 
either <LLOQ/Detected (i.e. LLOQ/TD) or <LLOQ/Target Not Detected (i.e. LLOQ/TND), both 
are considered LLOQ. HBsAg loss rates will be further subdivided accordingly. 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 14 of 52 
 
● 
HBsAg decline: Change from Baseline in HBsAg on the log10 scale. Negative values indicate a 
decline.  
● 
HBsAg loss: Patients with HBsAg < LLOQ/TND.  
● 
HBsAg responder A: A decrease from baseline ≥ 1.0 on the log10 scale, i.e. a change from baseline 
of ≤ -1.0. HBsAg results <LLOQ/Target Not Detected will be reported as  0.015 [log10(0.015) = 
-1.852 and HBsAg < LLOQ/Target Detected will be reported as midpoint between LLOQ/Target 
Not Detected and LLOQ/Target Detected, i.e. 0.04IU/mL = log10 (0.04)= -1.4. Also, HBsAg 
above LLOQ will be reported as the raw data is reported.  
● 
HBsAg responder B: A decrease from baseline ≥ 0.5 on the log10 scale, i.e. a change from baseline 
of ≤ -0.5.  HBsAg results <LLOQ/Target Not Detected will be reported as 0.015 [log10(0.015) = 
-1.852 and HBsAg < LLOQ/Target Detected will be reported as midpoint between LLOQ/Target 
Not Detected and LLOQ/Target Detected, i.e. 0.04IU/mL = log10 (0.04)= -1.4. Also, HBsAg 
above LLOQ will be reported as the raw data is reported.   
● 
HBsAg Relapse Rate: Patients who became negative (HBsAg<LLOQ), then increased with 
HBsAg > LLOQ.  HBsAg results <LLOQ/Target Not Detected will be reported as  0.015 
[log10(0.015) = -1.852 and HBsAg < LLOQ/Target Detected will be reported as midpoint between 
LLOQ/Target Not Detected and LLOQ/Target Detected, i.e. 0.04IU/mL = log10 (0.04)= -1.4. Also, 
HBsAg above LLOQ will be reported as the raw data is reported.  
● 
Virologic failure: Patients with a confirmed quantifiable HBV DNA increase of ≥ 1log10 HBV 
DNA copies/mL above LLOQ. HBV DNA results < LLOQ/Target Not Detected will be reported 
as  10 [log10(10) = 1) and HBV DNA < LLOQ/Detected will be reported as midpoint between 
LLOQ/Target Not Detected, i.e. 20IU/mL = log10 (20)= 1.3. Also, HBV DNA above LLOQ will 
be reported as the raw data is reported. 
● 
HBV-pgRNA decline: Change from Baseline in HBV-pgRNA on the log10 scale. Negative values 
indicate a decline.  
● 
HBcrAg decline: Change from Baseline in HBcrAg on the log10 scale. Negative values indicate a 
decline.  
● 
Prior Medications: Prior medications are defined as any medication where the use was stopped 
prior to the first administration of the study medication. 
● 
Concomitant Medications: Concomitant medications are defined as any medication (other than 
the study drug) that was used at least once after the first administration of the study drug. 
Medications that were stopped on the same date as the first study drug administration will be 
defined as concomitant medications. If a clear determination cannot be made (partial medication 
end dates) the medication will be classified as concomitant 
● 
Treatment Emergent Adverse Events (TEAEs) are defined as adverse events that occurred 
following the first administration of study medication. 
3.3 
Inferential Analyses 
Descriptive statistics will be used to summarize the safety and PK data. No formal hypothesis testing is 
planned. All efficacy analyses (unless otherwise specified) will be performed at a one-sided 5% level of 
significance. 
● 
HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment (primary) 
o 
Hypothesis:  
H01: Adjusted Mean for experimental arm at Week xx minus Adjusted Mean 
for control arm at Week xx = 0, where xx = 2, 4, 6, 8, 10, 12, 14, and 16 
H11: Adjusted Mean for experimental arm at Week xx minus Adjusted Mean 
for control arm at Week xx = -1, where xx = 2, 4, 6, 8, 10, 12, 14, and 16. 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 15 of 52 
 
o 
Time Points: Change from baseline until to Week 16 of treatment. 
o 
A general linear model for repeated measures will be used to assess HBsAg decline (Δ 
log10), using the stratification factors as independent variables in the model (HBeAg pos 
[yes, no]). Baseline HBsAg level will be included as a covariate. The analysis will be based 
on a one-sided test at a 5% level of significance. Degrees of freedom calculation will be 
based on the Kenward-Roger method. The unstructured covariance matrix structure to 
model the within-patient errors will be selected initially. If the unstructured covariance 
structure leads to non-convergence, covariance matrix structure will be selected through the 
maximum likelihood method. The final model will then we rerun by using the reduced 
maximum likelihood method. 
The following covariates will be included for this model: 
i. 
Baseline HBsAg level 
ii. 
HBeAg positive [yes, no] 
iii. 
Treatment Group 
iv. 
Study visit 
v. 
Interaction between treatment group and study visit 
o 
The least-squares mean change from baseline, along with corresponding 95% CI and SE for 
treatment arms and experimental arm versus control arm at the one-sided 0.05 level will be 
provided for Week 2, 4, 6, 8 , 10 , 12, 14 and 16 for the ITT population (with  Multiple imputation). 
This will be repeated for ITT (with no imputation), mITT (with Multiple imputation), mITT (with 
no imputation), PP set (with Multiple imputation) and PP set (no imputation). 
o 
If applicable, this model will be re-analyzed with the genotype covariate as “sensitivity analysis”. 
 
● 
Liver Fibrosis and inflammation change from baseline from Day 1 to Week 16 of treatment  
o 
Hypothesis:  
H0: Adjusted Mean for experimental arm at Week xx minus Adjusted Mean 
for control arm at Week xx = 0, where xx = 4, 8, 12 and 16 
H1: Adjusted Mean for experimental arm at Week xx minus Adjusted Mean 
for control arm at Week xx ≠ 0, where xx = 4, 8, 12 and 16. 
o 
Time Points: Change from baseline until to Week 16 of treatment. 
o 
A general linear model for repeated measures will be used to assess Liver Fibrosis and 
inflammation parameters including ALT, AST, AST/ALT ratio, high sensitivity C-reactive 
protein, interleukin 6, tumour necrosis factor alpha, procollagen type III N terminal peptide 
(Pro C3), tissue inhibitor of metalloproteinases-1, using the stratification factors as 
independent variables in the model (HBeAg pos [yes, no]). Baseline Liver Fibrosis and 
inflammation parameters value will be included as a covariate. The analysis will be based 
on a two-sided test at a 5% level of significance. Degrees of freedom calculation will be 
based on the Kenward-Roger method. The unstructured covariance matrix structure will be 
selected initially. If the unstructured covariance structure leads to non-convergence, 
covariance matrix structure will be selected through the maximum likelihood method. The 
final model will then we rerun by using the reduced maximum likelihood method. 
The following covariates will be included for this model: 
i. 
Baseline liver fibrosis and inflammation parameters value 
ii. 
HBeAg positive [yes, no] 
iii. 
Treatment Group 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 16 of 52 
 
iv. 
Study visit 
v. 
Interaction between treatment group and study visit 
o 
The least-squares mean change from baseline, along with corresponding 95% CI and SE for 
treatment arms and experimental arm versus control arm at the two-sided 0.05 level will be 
provided for Week 4, 8, 12 and 16 for the Safety Set.  
o 
If applicable, this model will be re-analyzed with the genotype covariate as “sensitivity 
analysis”. 
 
● 
HBsAg responder rate (decrease from baseline ≥ 1.0 on the log10 scale) at Week 16 of treatment 
and Weeks 40 of follow up. (secondary) 
o 
Hypothesis: H0: Treatment is not associated with endpoint  
HA: Treatment is associated with endpoint 
o 
Time Points: Week 16 and Week 40. 
o 
The Pearson Chi-squared test will be used to compare the differences in proportions 
between the treatment groups at Week 16 and Week 40. At Week 16 and Week 40, this 
endpoint will consider multiplicity by a combination of a hierarchical fixed test procedure 
and a Hochberg procedure (see section 3.4 for more detail). The analysis will be based on 
a one-sided test at a 5% level of significance. 
● 
HBsAg responder rate (decrease from baseline ≥ 0.5 on the log10 scale) at 16 of treatment and 
Weeks 40 of follow up.  
o 
Hypothesis: H0: Treatment is not associated with endpoint  
HA: Treatment is associated with endpoint 
o 
Time Points: Week 16 and Week40. 
o 
The Pearson Chi-squared test will be used to compare the differences in proportions 
between the treatment groups at Week 16 and Week 40. At Week 16 and Week 40, this 
endpoint will consider multiplicity considering multiplicity by a combination of a 
hierarchical fixed test procedure and a Hochberg procedure (see section 3.4 for more detail). 
The analysis will be based on a one-sided test at a 5% level of significance. 
● 
HBsAg loss rate (% patients with HBsAg < Lower Limit of Quantification (LLOQ)/TND) at Week 
16 of treatment and Week 40 of follow-up. 
o 
Hypothesis: H0: Treatment is not associated with endpoint  
HA: Treatment is associated with endpoint 
o 
Time Points: Week 16 and Week40. 
o 
The Pearson Chi-squared test will be used to compare the differences in proportions 
between the treatment groups at Week 16, and Week 40. At Week 16 and Week 40, this 
endpoint will consider multiplicity by a combination of a hierarchical fixed test procedure 
and a Hochberg procedure (see section 3.4 for more detail). The analysis will be based on 
a one-sided test at a 5% level of significance. 
● HBsAg loss rate (% patients with HBsAg < Lower Limit of Quantification (LLOQ)/TD) at Week 
16 of treatment and Week 40 of follow-up. 
o Hypothesis: H0: Treatment is not associated with endpoint  
HA: Treatment is associated with endpoint 
o Time Points: Week 16 and Week 40. 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 17 of 52 
 
o The Pearson Chi-squared test will be used to compare the differences in proportions 
between the treatment groups at Week 16, and Week 40. At Week 16 and Week 40, this 
endpoint will consider multiplicity by a combination of a hierarchical fixed test 
procedure and a Hochberg procedure (see section 3.4 for more detail). The analysis will 
be based on a one-sided test at a 5% level of significance. 
3.4 
Multiple Comparisons and Multiplicity Adjustments. 
For the analysis of secondary endpoints during the final analysis, multiplicity will be considered by using 
a combination of a hierarchical fixed test procedure and a Hochberg procedure. 
Only if the primary endpoint is significant at 16 weeks, the key secondary endpoints “HBsAg loss rate  
(<LLOQ/TND and <LLOQ/TD)” and “HBsAg responder rates (B and A see section 3.2)” will be tested 
at the same one-sided α level of 0.05, using a Hochberg procedure at Week 16. This procedure goes as 
follows: the p-values will be ordered from small to large p(1) ≤ p(2) ≤ (p3) ≤ (p4). The largest p-value 
p(4) will then be compared to α=0.05. If significant, then all hypotheses will be rejected. If not, the next 
largest p-value p(3) is compared to α/2=0.025. If significant, then these hypotheses corresponding to 
p(1) , p(2) and (p3) are rejected. If not, the next largest p-value p(2) is compared to α/3=0.017. If 
significant, then both hypotheses corresponding to p(1) and p(2) are rejected. If not, the smallest p-value 
is compared to α/4=0.0125. If significant, then only the hypothesis corresponding to the smallest p-value 
is rejected.  
At 40 weeks, the key secondary endpoints HBsAg responder rates (B and A) and HBsAg loss rate will 
be tested a one-sided α level of 0.05, using a Hochberg procedure.  
To calculate the power to detect a difference in HBsAg loss rate, we assumed a proportion of 0.5% in 
the placebo arm, and of 10% in the experimental arm. A trial including 49 patients results in a power of 
about 55% for this endpoint (using an un-pooled estimate of the variance), using a one-sided α of 0.05. 
3.5 
Handling of Missing Data 
For the classification of Treatment emergent adverse event (TEAE) and Concomitant medication, the 
following will be applied in the following order: 
a. 
If all dates/times (start and stop) missing, the event/medication will automatically be classified as 
a TEAE/Concomitant medication. 
b. 
For AEs with a missing start date/time, if the event end date/time is prior to first study drug 
administration, the event will not be classified as a TEAE. 
c. 
If only the AE start year/ medication end year is present and is the same or is after the first study 
drug administration year unit, the event/medication will be classified as a TEAE/Concomitant 
medication. 
d. 
If the AE start month and year/medication end month and year are present and are the same or 
after the first study drug administration month and year units, the event/medication will classified 
as a TEAE/Concomitant medication. 
For the efficacy analysis of values that are below the LLOQ, the following imputations will be made for 
continuous data analyses:      
● 
HBsAg LLOQ/TND values will be set to 0.015[log10(0.015) = -1.852]  
● 
HBsAg LLOQ/TD values will be set to the midpoint between LLOQ/TND and LLOQ/TD. 
● 
HBV DNA LLOQ/TND values will be set to 10 (log10(10) = 1).  
● 
HBV DNA LLOQ/TD (< 1.30 log IU/mL) values will be set to the midpoint of LLOQ/TND  (the 
midpoint =  1.15) 
● 
HBV DNA = “insufficient sample” will be set to missing. 
● 
HBcrAg LLOQ/TND values will be set to 30 (log10(30) = 1.5).  


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 18 of 52 
 
● 
HBcrAg LLOQ/TD (<3.0 log U/mL)  values will be set to 2.25 (log U/mL)       
● 
HBcrAg = “insufficient sample” will be set to missing. 
● 
HBV-pgRNA = “insufficient sample” will be set to missing. 
● 
HBV-pgRNA LLOQ/TND values will be set to 100 (log10(100) = 2).  
● 
HBV-pgRNA values = “<4.04” will be set to 3.02 log C/mL 
● 
HBV-pgRNA LLOQ/TD values will be set to the midpoint of LLOQ/TND (the midpoint = 3.02 
log C/mL)  
      
For the handling of missing primary efficacy data (excluding LLOQ/TND and LLOQ/TD), missing 
primary efficacy data (HBsAg) will be imputed using multiple imputation process (MI SAS procedure) 
with MAR pattern. For completeness, analysis will be repeated under the scenario of no imputation.  
The Multiple imputation will be performed as follows: 
• 
Missing data will be imputed using multiple imputation technique with Markov chain 
Monte Carlo method assuming MAR and multivariate normality. 
• 
This is carried out by using the SAS procedure PROC MI with the MCMC option, the 
seed number will be 20201113. The number of burn-in iterations will be 200, which is 
the default value. Nevertheless, if diagnosis plots show that the convergence has not yet 
occurred, this will be adjusted. 
• 
Imputation will be repeated N=1000 times. The log 10(HBsAg) will then be calculated 
for each of the data set. 
SAS Code: 
             Proc mi data=new nimpute = 1000 out= mi_mvn seed= 20201113; 
               mcmc nbiter =200 plots=trace ; 
               By Treatment; 
               Var Baseline log10(HBsAg);  
 Run; 
 
• 
The difference in HBsAg (Δ log10) from Day 1 to Week 16 between treatment and 
placebo will be analysed using a general linear model for repeated measures for each 
imputation. 
SAS Code: 
                            Proc mixed data= mi_mvn ; 
                              By _imputation_; 
    Class  ID TRT VISIT  HBeAg;  
    Model CHG = Baseline  HBeAg TRT VISIT TRT*VISIT /      
    SOLUTION CL; 
   DDFM=KenwardRoger; 
  Repeated VISIT /SUBJECT = ID TYPE = UN ; 
   Lsmeans TRT*VISIT / DIFF CL; 
Run; 
 
• 
The parameter estimates obtained from the above are then combined and reported using 
SAS - Proc mianalyze procedure.  
Conversion of categorical values 
In some instances, continuous variables are expressed as a range (i.e. < 10). In such cases, values may 
be converted to the range boundary (upper or lower limit as applicable). As an example, a value of <10 
may be converted to 10. Such substitutions will be clearly documented in the footnotes of relevant 
outputs.  


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 19 of 52 
 
There will be no imputations or substitution made for missing safety data points.  
3.6 
Coding of Events and Medications 
Medical history and AE verbatim terms will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) using the latest version available at the time of study commencement. Terms will 
be coded to the full MedDRA hierarchy, but the system organ class (SOC) and preferred terms (PT) will 
be of primary interest for the analysis. 
Prior and concomitant medications will be coded using the World Health Organization Drug Dictionary 
using the latest version available at the time of study commencement. Medications will be mapped to 
the full WHO-DD Anatomical Therapeutic Chemical (ATC) class hierarchy, but PTs will be of primary 
interest in this analysis. 
3.7 
Treatment Groups/Treatment Sequence 
TFLs will be presented by treatment arms, and for all study patients in the given analysis set, where 
applicable.   
The following order will be used for all summary outputs (with the treatment arm displayed, as applicable 
to the output): 
● 
EYP001a 200 mg QD + NA daily (N=37)  
● 
EYP001a 200 mg QD + NA daily HBeAg+ (N=xx) 
● 
EYP001a 200 mg QD + NA daily HBeAg- (N=xx) 
● 
Placebo + NA daily (N=12)  
● 
Placebo HBeAg+ (N=xx) 
● 
Placebo HBeAg- (N=xx) 
● 
All HBeAg+ (N=xx) 
● 
All HBeAg- (N=xx) 
● 
All Study Patients (N=49) 
The following treatment group labels will be used for all by-participant listings: 
● 
EYP001a 200 mg QD + NA daily HBeAg+  
● 
EYP001a 200 mg QD + NA daily HBeAg-  
● 
Placebo HBeAg+  
● 
Placebo HBeAg-  
 
 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 20 of 52 
 
4. 
ANALYSIS SETS  
In this study 5 analysis populations are defined: Intention-To-Treat (ITT) Analysis Set, Modified 
Intention-To-Treat (mITT) Analysis Set, Safety Analysis Set (SAS), PK Analysis Set, the PD Analysis 
Set and the Per Protocol (PP) Analysis Set. 
Furthermore, any additional exploratory analysis not identified in the SAP will be identified in the final 
CSR as exploratory post hoc analyses, including analyses for additional study populations or subgroups 
of interest. 
4.1 
Population Descriptions 
4.1.1 
Intention-To-Treat (ITT) Analysis Set 
The ITT set will include all randomized patients, irrespective of whether a patient receives any study 
drug. This set will be based on randomized treatment. The ITT set will be used for the baseline, 
demographic summaries and efficacy summaries. 
4.1.2 
Modified Intention-To-Teat (mITT) Analysis Set 
The mITT set will include all randomized patients, who received any amount of study drug, have a 
measurable baseline HBsAg assessment and a 16-week post baseline efficacy assessment. This set will 
be based on randomized treatment. The mITT set will be used for efficacy analyses. 
4.1.3 
Safety Analysis Set (SAS) 
The Safety analyses set will be defined as all patients who receive at least one confirmed dose of the 
study drug and will be based on actual treatment received. The SAS will be used for all safety and 
tolerability analyses. 
4.1.4 
Pharmacokinetic (PK) Analysis Set (will be done by Calvagone) 
The PK set will consist of all patients who received any study drug administration and that have sufficient 
and interpretable EYP001a concentrations data. Protocol violations and individual patient profiles will 
be assessed on a case-by-case basis to determine if the patient, or specific concentration values, should 
be excluded from the PK set.  
4.1.5 
Pharmacodynamic (PD) Analysis Set 
All patients included in the SAS with a measurable baseline PD assessment and at least one measurable 
post baseline PD assessment, will be included in the PD set. 
4.1.6 
Per Protocol (PP) Analysis Set 
The PP set is defined as the set of patients who meet the mITT set requirements and were not associated 
with a major protocol violation. This set will be identified before the start of the final analysis and will 
be used to support the analysis conducted for the primary efficacy endpoint. Patients will be analyzed 
based on the actual treatment received and patients with the study drug compliance of <50% will be 
excluded.   
 
 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 21 of 52 
 
5. 
PARTICIPANT DISPOSITION AND ANALYSIS POPULATIONS 
Participant disposition and analysis population analysis will be based on the ITT population. Participant 
disposition and analysis populations will be summarized descriptively as described in section 3.1 
(categorical descriptive analysis). 
5.1.1 
Participant Disposition 
Participant disposition will include the number of participants who completed the study as planned, 
participants withdrawn from the study, as well as the primary reason for early termination. Participant 
disposition will be summarized descriptively. 
A listing of patient disposition with study discontinuation and treatment discontinuation will be 
presented. Whether a patient had any ongoing AEs, the date of last dose (EYP001a/Placebo and NA), 
reason for treatment discontinuation (if applicable), date of last contact (or date of death) and date of 
withdrawal of consent (if applicable) will be included. 
Screening failures and reason for screening failure, will be noted in the listing of eligibility criteria. All 
withdrawals from the study, taking place on or after study drug administration, will be fully documented 
in the body of the clinical study report (CSR). 
5.1.2 
Analysis Populations 
The number of participants included in each study populations will be summarized descriptively. 
In addition, the inclusion of each participant into/from each of the defined analysis populations will be 
presented in the by-participant data listings. 
 
 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 22 of 52 
 
6. 
PROTOCOL DEVIATIONS 
Protocol deviations will be presented for each participant in the by-participant data listings for the 
enrolled set. All data will be listed by treatment group. 
Prior to database lock, all protocol deviations will be reviewed by medical monitors and assigned a status 
of Important if qualifying as such. 
Protocol deviations and important protocol deviations will be categorized as noted in the Protocol 
Deviation Management Plan Version 1.0 dated 2020-01-13. 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 23 of 52 
 
7. 
DEMOGRAPHIC AND BASELINE INFORMATION 
Demographic and baseline information analysis will be based on the ITT population. Summary tables 
may be repeated for the mITT, Safety and PP analysis sets if different from the ITT analysis set. 
Demographic and baseline information will be summarized descriptively as described in section 3.1. 
7.1 
Demographics 
The following demographic parameters will be analyzed: 
Continuous descriptive analysis: 
● 
Age (years) 
● 
Height (cm) 
● 
Weight (kg) 
● 
BMI (kg/m2) 
● 
Audit-C overall score 
Categorical descriptive analysis: 
● 
Sex 
● 
Childbearing Potential  
● 
Race 
● 
Ethnicity 
● 
HBV Genotype  
● 
HBeAg Status (Positive/Negative) 
7.2 
Medical history 
Medical / Surgical history will be coded using MedDRA® currently in effect at Novotech at the time of 
database lock. and will be presented in the by-participant data listings. 
7.3 
Viral Serology 
Hepatitis D virus (anti-HDV), antibody to HIV (anti-HIV), antibody to HCV (anti-HCV), quantitative 
HBsAg, anti-HBs, Anti-HBe, a PCR-based quantitative HCV viral load (for positive HCV antibody-test 
results only), will be presented in the by-participant data listings. 
The viral serology result will be summarized at baseline visit by treatment group. 
7.4 
Drugs of Abuse 
Drugs of abuse results will be presented in the by-participant data listings. 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 24 of 52 
 
8. 
TREATMENT EXPOSURE AND COMPLIANCE 
EYP001a/Placebo administration information (study drug administered (Yes/No), reason for non-
administration date and time of administration, reason for dose adjustment and adjusted dose 
administered will be listed by treatment group. Patient fasting listed will also be noted. 
For NA, treatment administered, reason not administered, date and time of administration, dose taken 
per protocol (Yes/No), reason for dose adjustment and adjusted dose administered will be listed by 
treatment group. NA switching during the screening period will also be listed. 
Missed doses and reason for missed doses along with corresponding AEs will be listed as well. 
EYP001a/Placebo and NA accountability will be listed by treatment group. The following fields will be 
included: number of 200mg tablets dispensed, date dispensed, number of 200mg tablets used, date 
returned, doses missed (Yes/No), patient compliant (Yes/No), if no reason not compliant and the 
percentage of treatment compliance.  
Treatment Compliance is defined as: 
( Total Drug Administered 
Expected Drug Administered) ∗100 
The total drug administered is defined as: 
 (Number of 200mg Tablets Used + Number of NA Tablets Used during treatment period) 
The expected drug administered is defined as: 
The expected drug administered for EYP001a/Placebo + The expected drug administered for NA during 
treatment period 
• 
The expected drug administered for EYP001a/Placebo is defined as: 
Number of treatment days for EYP001a/Placebo × daily dosage (= 1 tablet), where the number of 
treatment days for EYP001a/Placebo will be calculated as: 
Number of treatment Day = (Date of treatment visit 1 - Date of last treatment visit) +1 during treatment 
period. 
• 
The expected drug administered for NA is defined as: 
Number of treatment days for NA × daily dosage (= 1 tablet), where the number of treatment days for 
NA will be calculated as: 
Number of treatment Day = (Date of treatment visit 1 - Date of last treatment visit) +1 during treatment 
period. 
Treatment compliance (including count and percentage with <50% compliance, >=50% and =< 80%, 
and > 80% compliance) will be summarized descriptively as described in section 3.1(categorical 
descriptive analysis) under Safety analysis set. 
 
 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 25 of 52 
 
9. 
PRIOR AND CONCOMITANT MEDICATIONS 
Concomitant medications will be summarized by Anatomical Therapeutic Chemical (ATC) class Level 
3 and PT as noted in section 3.1 (categorical descriptive analysis) using Safety analysis set. Participant 
who used the same medication on multiple occasions will only be counted once in the specific category 
(PT). PTs will be sorted alphabetically. In addition to the summaries by the coded terms, the number of 
participants who used at least one concomitant medication during the study will be presented. 
Prior and concomitant medications will be presented in the by-participant data listings using Safety 
analysis set. 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 26 of 52 
 
10. 
PHARMACOKINETICS 
The PK analysis falls outside the scope of this SAP. 
 
 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 27 of 52 
 
11. 
PHARMACODYNAMICS 
All pharmacodynamic analysis will be based on the PD analysis Set. 
The following PD endpoints will be analyzed: 
● 
Plasma C4 (7α-hydroxy-4-cholesten-3-one) 
● 
FGF19 
● 
Plasma primary and secondary BAs (optional) 
PD endpoints will be summarized descriptively as described in section 3.1 (continuous descriptive 
analysis). 
 
 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 28 of 52 
 
12. 
EFFICACY 
All Efficacy analyses will be based on the ITT analysis set unless otherwise specified.  
     The following Efficacy endpoints will be analyzed: 
● 
HBsAg decline (Δ log10) from Baseline (screen and Day 1 average) to Week 16 of treatment.  
● 
HBsAg responder rate (decrease from baseline ≥ 1.0 on the log10 scale) at Week 16 of treatment 
and Weeks 20, 28 and 40 of follow up.  
● 
HBsAg responder rate (decrease from baseline ≥ 0.5 on the log10 scale) at Weeks 12 and 16 of 
treatment and Weeks 20, 28 and 40 of follow up.  
● 
HBsAg loss rate (% patients with HBsAg < Lower Limit of Quantification (LLOQ)/TND) at Week 
16 of treatment and Weeks 20, 28 and 40 of follow-up.  
● 
HBsAg loss rate (Proportion of results that are Target Not Detected versus Target Detected) at 
Week 16 of treatment and Weeks 20, 28 and 40 of follow-up.  
● 
Relapse rate HBsAg (% patients who became negative [HBsAg < LLOQ], then increased with 
HBsAg > LLOQ) at Week 16 of treatment period and Weeks 20, 28 and 40 during follow-up 
period.  
● 
Virologic failure rate (breakthrough) of Hepatitis B virus Deoxyribonucleic Acid (HBV-DNA) (% 
patients with a confirmed quantifiable HBV DNA increase of ≥ 1log10 HBV DNA copies/mL 
above LLOQ) assessed at Week 16 of treatment period and Weeks 20, 28 and 40 during follow-
up period.  
● 
HBV-pgRNA decline (Δ log10) from Day 1 to Weeks 4, 8, 12, 16 of treatment period and Week 
40 of maintenance period.  
● 
HBcrAg decline (Δ log10) from Day 1 to Weeks 4, 8, 12, 16 of treatment period and Week 40 of 
maintenance period.  
● 
HBeAg quantification for HBeAg pos patients and changes at Week 16 of treatment and Week 40 
of follow-up.  
● 
Fibroscan Vibration Controlled Transient Elastography (VCTE) change from screening value to 
Weeks 16 and 40 or Early Termination (ET) value.  
● 
Anti-HBs: Percent of subjects detectable (reactive) for Anti-HBs at baseline, Week 16 of treatment 
and Week40 of follow-up 
● 
Anti-HBe: Percent of subjects detectable (reactive) for Anti-HBe at baseline, Week 16 of 
treatment and Week40 of follow-up 
Efficacy endpoints at each scheduled visit will be summarized descriptively as described in section 3.1 
(categorical descriptive analysis). All HBV response marker data collected at scheduled and unscheduled 
visits will be included in the listings. 
For HBsAg, and HBV DNA, box plots for actual value and change from baseline value over time by 
treatment group, by HBeAg (positive and negative) and by A Genotype (yes and no) will be generated 
separately. Also, series plots for individual actual value over time and in change from baseline by HBeAg 
and by A genotype will be generated separately. 
Furthermore, HBsAg, HBV-pgRNA, HBcrAg, HBeAg quantification for HBeAg pos patients and 
Fibroscan Vibration Controlled Transient Elastography (VCTE) at each scheduled visit and change from 
baseline values will be summarized descriptively as described in section 3.1 (continuous descriptive 
analysis). Counts (%) of number participants with Anti-HBs and Anti-HBe results at baseline, week 16 
and week40 will also be presented (categorical descriptive analysis). 
 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 29 of 52 
 
12.1 
Inferential Analyses 
The following endpoints will be analyzed as described in sections 3.3: 
● 
HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment 
● 
HBsAg responder rate (decrease from baseline ≥ 1.0 on the log10 scale) at Week 16 of treatment 
and Week 40 of follow up. (secondary) 
● 
HBsAg responder rate (decrease from baseline ≥ 0.5 on the log10 scale) at Weeks 16 of treatment 
and Week 40 of follow up. 
● 
HBsAg loss rate (% patients with HBsAg < Lower Limit of Quantification (LLOQ)/TND) at Week 
16 of treatment and Week 40 of follow-up. 
● 
HBsAg loss rate (% patients with HBsAg < Lower Limit of Quantification (LLOQ)/TD) at Week 
16 of treatment and Week 40 of follow-up. 
12.2 
Other Analyses 
ENYO is developing a mathematical computational HBV disease model. The results from EYP001-201 
will serve as clinical data for the calibration of in silico HBV patients simulating the effect of 
combinational treatments that will eventually support designing later trials. With its different sub-models 
(HBV replication and excretion, BAs metabolism, cholesterol metabolism, immune system, fibrosis, 
blood virus related changes, and EYP001a, ETV and PEG-IFNα2a drug models) the disease model of 
chronic HBV infection will be used to predict quantitative efficacy on relevant endpoints (DNA HBV in 
blood, HBsAg) in a representative virtual population. The computational model is a system of ordinary 
differential equations (ODEs) which integrates more than 300 biological variables and more than 1000 
parameters. It will be used to explore the effect of combinations of different treatments regimens 
including EYP001a, ETV and PEG-IFNα2a. Iterations of the validated model will serve for the 
exploration of alternative arms in future trials and in the EYP001-203 study (conducted in parallel 
EYP001-201, with treatment naive or virologically non-suppressed patients treated with EYP001a 
combined with NA and peg-IFN), by simulating different doses and treatment regimens. Disease model 
simulations will support future explorations of development strategies, with the upcoming EYP001a 
pivotal study designs. 
This analysis is reported in a separate analysis plan (reference : Validation protocol HBV EYP001 
modeling and simulation project) falls outside the scope of the SAP. 
 
 
 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 30 of 52 
 
13. 
SAFETY  
Safety endpoints will be analyzed using the Safety population. Safety endpoints will be summarized 
descriptively as described in section 3.1. 
13.1 
Adverse Events 
All AEs including will be coded using MedDRA. All AE summaries will be restricted to TEAEs only. 
Summary tables will include the number of participants (%) experiencing an event and the number of 
events. Participants will be counted only once for each SOC and PT level (categorical descriptive 
analysis). 
AE and SAE will be analysed taking into account any identified subject with Sars-Cov2 infection during 
and post-pandemic measures phases. Such an analysis will be operated through the independent Data 
Monitoring Committee (DMC). 
The TEAE summaries will include: 
● 
Overall summary of TEAEs. 
o Number of TEAEs 
o Number of TEAEs with Severity ≥ Grade 3 Severe 
o Number of Serious TEAEs 
o Number of Study Drug Related TEAEs (Drug Related: A Possibly, Probably or 
Definitely related TEAE) 
o Number of Entecavir (ETV) Related TEAEs (Drug Related: A Possibly, Probably or 
Definitely related TEAE) 
o Number of Tenofovir Disoproxil Fumarate (TDF) Related TEAEs (Drug Related: A 
Possibly, Probably or Definitely related TEAE) 
o Number of TEAEs leading to study drug withdrawal 
● 
TEAE summary by SOC and PT. 
● 
TEAE summary of serious events by SOC and PT. 
● 
TEAE summary by SOC, PT and Severity. 
● 
TEAE summary by SOC, PT and relationship to study drug. 
● 
TEAE summary by SOC, PT and relationship to ETV. 
● 
TEAE summary by SOC, PT and relationship to TD. 
● 
TEAE summary of events leading to the study drug discontinuation by SOC and PT. 
All AEs will be listed and will include verbatim term, PT, SOC, treatment, causality to study drug, ETV 
and TDF, severity, seriousness, outcome, and action taken with regards to the study drug and AE. 
Separate listings will be created for SAEs and events leading to study drug withdrawal. 
13.2 
Safety Laboratory Assessments 
Blood and urine samples will be collected at the time points specified in the Schedule of Events (refer to 
the Protocol) to conduct hematology, chemistry, coagulation, lipid and metabolic profile and urinalysis 
(including microscopic examinations) analyses. 
The following tests will be performed within each of the specified test panels: 
Hematology: 
● 
Red blood cell count 
● 
White blood cell count  


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 31 of 52 
 
● 
Haemoglobin 
● 
Haematocrit 
● 
Partial automated differentiation 
o Thrombocytes (% and Abs) 
o Lymphocytes (% and Abs) 
o Monocytes (% and Abs),  
o Eosinophils (% and Abs),  
o Basophils (% and Abs),  
o Neutrophils (% and Abs)  
o Platelets (% and Abs).  
Coagulation: 
● 
Prothrombin Time (s) 
● 
INR 
● 
Activated Partial Thromboplastin Time 
● 
Fibrinogen 
Serum Chemistry: 
● 
Albumin 
● 
ALP 
● 
ALT 
● 
Amylase 
● 
Apo A1 
● 
AST 
● 
AST/ALT ratio 
● 
Bilirubin conjugated  (direct bilirubin) 
● 
BUN 
● 
Calcium 
● 
Creatine Kinase 
● 
Creatinine phosphokinase (CPK) 
● 
Creatinine 
● 
C-Reactive Protein-hs 
● 
Estimation of glomerular filtration rate  
● 
GGT 
● 
Glucose 
● 
Insulin 
● 
Lactate dihydrogenase 
● 
Potassium 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 32 of 52 
 
● 
Sodium 
● 
Total Bilirubin (if >ULN, add conjugated bilirubin) 
● 
Total Protein 
● 
Uric Acid 
Lipid Metabolic Profile 
● 
Cholesterol 
● 
Branched-chain amino acid concentrations as liver function test, (analyze done by Labcorp)   
● 
Haemoglobin A1c,  
● 
Homeostatic model assessment for insulin resistance (morning fasting glucose and insulin),  
● 
Lipoprotein insulin resistance index by nuclear magnetic resonance based on serum cholesterol 
(analyze done by Labcorp),  
● 
HDL-C (analyze done by Labcorp),  
● 
LDL-C (analyze done by Labcorp),  
● 
Triglycerides (analyze done by Labcorp),  
● 
Apolipoprotein B,  
● 
Small dense LDL (analyze done by Labcorp),  
Urinalysis (Dipstick) & Microscopic Urinalysis: 
● 
Blood 
● 
Bilirubin 
● 
Glucose  
● 
Ketones 
● 
Leukocytes 
● 
Haemoglobin 
● 
pH 
● 
Protein 
● 
Specific Gravity 
● 
Urobilinogen 
● 
Microscopic Examinations (abnormalities on any of the following 3 dipstick results: leukocyte 
esterase, blood, or nitrite, and if judged clinically significant by the Investigator) 
Immunochemistry 
● 
T4 (free)  
● 
T3 (free)  
● 
TSH  
● 
FSH  
● 
AFP 
● 
IL-6ha 
● 
TNF-alpha hs  


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 33 of 52 
 
All laboratory data collected at scheduled and unscheduled visits will be included in the listings, but only 
results collected as scheduled visits will be included in the summary tables. 
Results for individual parameters may be reported in different units depending on the analyzing 
laboratory. If required, the results (and the corresponding normal range cut-off values) for individual 
parameters may be converted to International System of Units (S.I.) units to summarize the data. 
For all the parameters where a unit value has been reported, the parameter names that will be used in the 
outputs will comprise of the test name and the unit of measure, for example, ‘Albumin (g/L)’. For the 
urinalysis parameters, the parameter name will be the reported test name only. Parameters will be sorted 
alphabetically within tables and listings. 
For all parameters where a normal range limit value was reported, the normal range will be derived based 
on the available lower and upper limit values and any reported mathematical symbols. If both a lower 
and upper limit value is available, the normal range will be presented as ‘(Lower, Upper)’. 
The reported results for each parameter with a defined normal range will be classified (‘Low’, ‘Normal’, 
‘High’) in relation to the defined normal range limits. If a result is equal to the normal range cut-off 
value, the result will be considered ‘Normal’. 
The hematology, coagulation, chemistry and lipid and metabolic profile results tables will present 
summary statistics for each laboratory parameter within the specific test panel. For each parameter, 
summaries will be presented for the baseline and each scheduled post-baseline visit. In addition, 
summaries will be presented for the change from baseline values(and % change from baseline for the 
lipid and metabolic profile results) at each scheduled post-baseline visit (continuous descriptive 
analysis). 
The decimal precision to which the summaries for each parameter will be based on the maximum number 
of decimals to which the reported result or the normal range limits are presented to in the raw data. The 
results and normal ranges will be displayed to the same decimal precision in the listings. 
Additionally, counts (%) of number participants with values out of normal range at each scheduled time 
point will also be presented along with shift tables that will represent the changes in normal range 
categories across post-baseline time points (categorical descriptive analysis). 
For ALT, AST, Total Bilirubin, and GGT tests, individual (for each participant) actual and change from 
baseline values over time will be displayed graphically and box plots over time by treatment group will 
be generated as well. A summary of maximum CTCAE Grades for post treatment assessments will be 
produced. Also, the HBV DNA versus ALT and AST at each visit will be displayed graphically. 
For Lipid parameters-total cholesterol, LDL-C, HDL-C and triglycerides, individual (for each 
participant) actual values over time will be displayed graphically. 
The urinalysis table will present counts and percentages of normal, abnormal clinically significant and 
clinically significant for the reported results at baseline and each post-baseline visit for all parameters 
(categorical descriptive analysis). 
13.3 
Vital Signs 
The following vital signs measurements will be taken at the time points specified in the Schedule of 
Events (refer to the Protocol): 
● 
Heart Rate (beats/min); 
● 
Systolic blood pressure (SBP) (mmHg) 
● 
Diastolic blood pressure (DBP) (mmHg) 
● 
Respiratory rate (breaths/min) 
● 
Temperature (ºC) 
All vital signs data collected at scheduled and unscheduled visits will be included in the listings, but only 
results collected as scheduled visits will be included in the summary tables. 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 34 of 52 
 
The parameter names that will be used in the outputs will comprise of the test name and the unit of 
measure, for example, ‘Systolic Blood Pressure (mmHg)’. Parameters will be sorted in the order that the 
measurements were collected in on the Vital Signs eCRF page within the tables and listings. 
Vital signs measurements will present summary statistics for the results at the baseline and each 
scheduled post-baseline visit for each of the parameters. In addition, summaries will be presented for the 
change from baseline values at each scheduled post-baseline visit (continuous descriptive analysis). 
In the summaries for each parameter one more decimal place will be added to the maximum number for 
the results reported in the eCRF for decimal precision. For example: 2 decimals reported in the eCRF 
will be reported as 3 decimals for precision.  
In addition, parameters with clinically significant findings will be noted in the listings. 
13.4 
12-Lead Electrocardiogram (ECG) 
The following ECG measurements will be taken at the time points specified in the Schedule of Events 
(refer to the Protocol): 
● 
Heart Rate (beats/min) 
● 
PR Interval (msec) 
● 
RR Interval (msec) 
● 
QT Interval (msec) 
● 
QTc Interval (msec) 
● 
QRS Duration (msec) 
● 
Overall Investigator Finding 
All ECG data collected at scheduled and unscheduled visits will be included in the listings, but only 
results collected as scheduled visits will be included in the summary tables. 
The parameter names that will be used in the outputs will comprise of the test name and the unit of 
measure, for example, ‘Ventricular Rate (beats/min)’. Parameters will be sorted in the order that the 
measurements were collected in on the ECG eCRF page within the tables and listings. 
ECG measurements will present summary statistics for the results at the baseline and each scheduled 
post-baseline visit for each of the parameters. In addition, summaries will be presented for the change 
from baseline values at each scheduled post-baseline visit (continuous descriptive analysis). 
The decimal precision for each parameter will be based on the maximum number of decimals to which 
the results were reported on the eCRF. 
The summary of overall interpretation findings table will present counts and percentages for the reported 
results at baseline and each post-baseline visit/time point. Result categories will be ordered as ‘Normal’, 
‘Abnormal Not Clinically Significant (NCS)’, ‘Abnormal Clinically Significant (CS)’ and ‘Not 
Evaluable’ (categorical descriptive analysis). 
The listings of ECG measurements will include all the information collected data. In addition, the 
observations that are used as the baseline record (value) for each parameter will be flagged, and the 
change from baseline values at each post-baseline visit will be presented. For clinically significant 
assessments, cardiologist confirmation (Yes/No) and additional comments will be listed. 
13.5 
Pruritus Assessment 
Pruritus will be assessed using a visual analog scale (VAS) and a 5-D (degree, duration direction, 
disability, and distribution) itch scale at each study visit after screening.  
The 5-D Pruritus Scale is a multidimensional measure that quantifies pruritus.  The scale consists of five 
domains: duration (1 item), degree (1 item), direction (1 item), disability (4 items), and distribution (16 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 35 of 52 
 
locations of itch).  All items of the first four domains were measured on a five-point Likert scale. A total 
score of 4 indicates ‘no Pruritus’ and 35 indicates ‘most sever Pruritus’. 
The scores of each of the five domains are achieved separately and then summed together to obtain a 
total 5-D score.  5-D scores can potentially range between 4 (no pruritus) and 35 (most severe pruritus.) 
Single-item domain scores (duration, degree, and direction) are equal to the value indicated below the 
response choice (range 1-5).  The score for the disability domain is achieved by taking the highest score 
on any of the four items. For the distribution domain, the number of affected body parts is tallied 
(potential sum 0-16) and the sum is sorted into five scoring bins: 
● 
sum of 0-2 = 
1 
● 
sum of 3-5 = 
2 
● 
sum of 6-10 = 
3 
● 
sum of 11-13 = 
4 
● 
sum of 14-16 = 
5. 
The total score including change from baseline to each post baseline will be summarized. Domain and 
total scores along with changes from baseline will be listed. 
In addition, the Pruritus visual analog scale result will be listed and summarized per time point by 
treatment group.  
13.6 
Physical Examinations 
By-participant data listings will be created for all complete physical examination and symptom directed 
assessments and all time points.  
13.7 
Liver Fibrosis and inflammation Assessment 
The following Liver fibrosis and inflammation assessments will be taken at the time points specified in 
the Schedule of Events (refer to the protocol): 
● 
ALT 
● 
AST 
● 
AST/ALT ratio 
● 
High sensitivity C-reactive protein 
● 
Interleukin 6 
● 
Tumour necrosis factor alpha 
● 
Procollagen type III N terminal peptide (Pro C3) 
● 
Tissue inhibitor of metalloproteinases-1 
● 
 ELF score (HA, TIMP-2, PIIINP) 
All liver fibrosis and inflammation data collected at scheduled and unscheduled visits will be included 
in the listings, but only results collected as scheduled visits will be included in the summary tables. 
 
Liver fibrosis and inflammation assessments will present summary statistics for the results at the baseline 
and each scheduled post-baseline visit for each of the parameters. In addition, summaries will be 
presented for the change from baseline values at each scheduled post-baseline visit (continuous 
descriptive analysis). 
13.7.1 Inferential Analyses 
The following endpoint will be analyzed as described in sections 3.3: 
● 
Liver Fibrosis and inflammation change from baseline from Day 1 to Week 16 of treatment  


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 36 of 52 
 
13.8 
Liver Imaging 
Liver imaging assessment will be listed for all time points.      
The assessment of liver imaging table will present counts and percentages for the reported results at 
screening and Week 40 of follow up. Result categories will be ordered as ‘Normal’, ‘Abnormal Not 
Clinically Significant (NCS)’ and ‘Abnormal Clinically Significant (CS)’ (categorical descriptive 
analysis). 
13.9 
Pregnancy Test Results 
All information related to pregnancy testing (urine and serum based) will be presented in the by-
participant data listings. 
 
 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 37 of 52 
 
14. 
IMMUNOGENICITY 
No Immunogenicity analysis is planned for this study. 
 
 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 38 of 52 
 
15. 
CHANGES TO THE PLANNED ANALYSIS 
Safety review will be performed when 20 patients have reached w8 (expected by 1st March 2021 with 
data cut-off point defined to be 5th March 2021, replacing when 50% (n=25) patients reach week 8.   
Sponsor decided on February 17th, 2021 to suspend further enrollments (after approx. 25 
randomizations). 
A request to deviate from the protocol has been initiated and executed by the sponsor and will be 
documented here. The changes to the planned analysis from the protocol are described in the following 
table: 
Protocol 
Key Changes 
Based on the protocol section 11.3.3.1, for the 
primary efficacy endpoints (HBsAg decline), 
imputing missing data at 16 weeks as zero 
difference versus baseline 
 Missing primary efficacy data (HBsAg) will 
be imputed using multiple imputation process 
(MI SAS procedure) with MAR pattern.  
Not in the protocol  
 Inferential Analyses for liver Fibrosis and 
inflammation change from baseline from Day 
1 to Week 16 of treatment  
 To summarize the Maximum CTCAE for 
ALT, AST, BILI and GGT for Post Treatment 
Assessments using CTCAE to do the toxicity 
grading. 
Not in the protocol - The primary efficacy 
variables 
 Additional primary efficacy variable: 
 
Anti-HBs 
 
Anti-HBe. 
Based on the protocol section 11.3.3.1, for the 
primary efficacy endpoints (HBsAg decline), A 
Genotype [yes, no] needs to be included in the 
general linear model 
 A Genotype variable will be removed from the 
general linear model because the CRAs went 
back and cross checked there is no available 
historical genotype available in the medical 
history source other than what is currently in 
the EDC and also for most of the patients, 
there is no virus available in the samples to 
genotype. 
 
 
 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 39 of 52 
 
16. 
INTERIM AND FINAL ANALYSIS 
16.1 
Interim Analysis (DSMC Review meeting) 
An unscheduled DSMC review meeting of all available unblinded preliminary safety study data will be 
conducted when any stopping rules (Protocol Section 4.6) are met in two or more patients. All stopping 
rules will be listed by treatment group. 
Two DSMC Review meeting are scheduled: 
1. 
DSMC Safety Review Meeting on all available unblinded preliminary safety study data:  
Safety assessment when 40.8% (n=20 out of 49) patients reach week 8 resulting in a decision on 
continuation of the study based on safety (Go/No go decision); enrolment would remain ongoing 
during this review. 
2. 
DSMC Safety Review and Futility Analysis Meeting on all available unblinded preliminary 
virology, safety, PK and PD study data:  
Safety and futility when 50% patients (n=25) reached week 12, resulting in a decision on 
continuation of the study (Go/No go decision) based on safety and evidence of a benefit of 
EYP001 (HBsAg, other secondary viral markers); enrolment is ongoing during this review.  
The DSMC review meeting will be performed on all available primary and secondary endpoints 
according to the DSMC charter, which describes the overall guidelines, composition, roles, and 
responsibilities of the independent DSMC for the EYP001-201 study, including the selection of DSMC 
members, timing of meetings, methods of providing information to and from the DSMC, frequency and 
format of meetings, data analysis recommendations, and DSMC relationships with other parties 
participating in the conduct of this study.  
The futility assessment will be performed to determine if EYP001 has no benefit at a point when 50% 
of patients have reached 12 weeks of dosing. The futility assessment will be performed by the DSMC 
according to the following rules:  
● 
A treatment effect of -1.0 on a log10 scale of HBsAg for the primary endpoint at 16 weeks, and a 
common standard deviation of 1.08 was assumed and the treatment effect would be -0.5 after 12 
weeks of treatment, with common standard deviation of 0.7 Using a one-sided alpha of 0.05 and 
80% power (beta = 0.20), a group sequential design, incorporating a futility and efficacy O’Brien-
Fleming analysis when 50% of patients have reached 12 weeks of treatment, needs inclusion of 
49 patients.  
● 
Table 2 gives the probability of stopping early under the null and alternative hypothesis, at the 
time of the interim analysis.  
The probability of stopping correctly for futility is 40%. The probability of stopping wrongly for 
futility is only 3.5%. 
Table 2 Probability of different decisions at the DSMC Safety Review and Futility 
Analysis Meeting 
Under H0 
Under Ha 
Efficacy 
Futility 
Efficacy 
Futility 
0.001 
0.4 
0.073 
0.035 
H0: Null Hypothesis; Ha: Alternative Hypothesis 
● 
     The efficacy boundary is crossed when the 12-week p-value is less than 0.001, or the difference 
is less than -0.971 on a log scale. The futility boundary is crossed when the 12-week p-value is 
higher than 0.603, or the difference is more than 0.085 on a log scale.  
The stopping of the study for futility will be considered by the DSMC by applying these rules. The study 
will not stop for efficacy at Week 12 DSMC Safety Review and Futility Analysis Meeting even if 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 40 of 52 
 
efficacy boundary is crossed. The criteria are not binding and DSMC can overrule after overall 
consideration. 
Data will be summarized and presented by treatment group and time point in summary tables. 
Descriptive statistics including number of patients (N), means, standard deviations, medians, and 
minimum and maximum values will be presented for continuous variables. Counts and percentages will 
be presented for categorical variables. In addition, by- patient listing for all safety and efficacy data will 
be presented.  
Note that all DMSC review meeting will be descriptive, except 2nd scheduled DSMC safety and futility 
review meeting containing mentioned futility testing. 
Based on the protocol clarification letter #13, the first interim analysis as described in the current 
EYP001-201 Study Protocol v3.0 dated 29th January 2020 corresponds to the first planned DSMC 
meeting and is performed on all available preliminary safety study data at the time of database snapshot 
(20 patients reach week 8, expected by 1st March 2021 with data cut-off point defined to be 5th March 
2021,). Safety data only will be evaluated, based upon the review of the individual values (clinical 
significant abnormalities), descriptive statistics (summary tables, graphics) and if needed,). The term 
“first interim analysis” should be replaced by “DSMC Safety Review Meeting”. The “second interim 
analysis” corresponds to the second planned DSMC meeting covering safety review and futility analysis 
and is performed on all available virology, safety, PK and PD study data at the time of database snapshot 
when 25 patients have reached w12 (expected by 16th March 2021 with data cut-off point defined to be 
15th May 20201  Safety and futility will be evaluated, based upon the review of the individual values 
(clinical significant abnormalities), descriptive statistics (summary tables, graphics) and on statistical 
analysis (futility analysis as described in section 11.5 of the study protocol). The term “second interim 
analysis” should be replaced by an interim analysis corresponding to “DSMC Safety and Futility Review 
Meeting” 
There will be an additional database lock performed on all patient visits to Week 16 / Visit 9 for all 
randomised patients. All patients will be unblinded following database lock. Novotech Biostatistician 
will convert the datasets to CDISC format. Novotech data management will provide ENYO with raw 
data and Biostatistician will provide ENYO with CDISC converted datasets.  
16.2 
Final Analysis (End of Study) 
The final analysis will be conducted after all participants have completed the study (at the end of the 
study), the clinical database has been hard locked, the analysis populations have been approved and the 
study has been unblinded. 
The final analysis will be based on the final version of the SAP. Any deviations from the planned analysis 
will be documented in the CSR. 
 
  
 
 
 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 41 of 52 
 
17. 
SOFTWARE 
● 
SAS® Version 9.2 or higher (SAS Institute, Cary, North Carolina, USA).


Protocol Number: EYP001-201                                                                                                                                                                        2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 42 of 52 
 
18. 
TABLES 
Table Number 
Table Title 
Population 
DSMC Safety 
DSMC 
Safety and 
Futility 
 
 
 
 
 
14.1 
Demographics and Other Baseline Characteristics 
 
 
 
14.1.1 
Summary of Participant Enrolment and Disposition 
ITT 
X 
X 
14.1.2.1 
Summary of Demographics and Baseline Characteristics 
ITT 
 
 
14.1.2.2 
Summary of Demographics and Baseline Characteristics 
mITT 
      
 
14.1.2.3 
Summary of Demographics and Baseline Characteristics 
Safety 
X 
X 
14.1.2.4 
Summary of Demographics and Baseline Characteristics 
PP 
 
 
14.1.3.1 
Summary of Viral Serology at Screening 
ITT 
 
      
14.1.3.2 
Summary of Viral Serology at Screening 
mITT 
      
 
14.1.3.3 
Summary of Viral Serology at Screening 
Safety 
      
 
14.1.3.4 
Summary of Viral Serology at Screening 
PP 
      
 
14.1.4 
Summary of Treatment Compliance 
Safety 
X 
X 
14.2 
Efficacy 
 
 
 
14.2.1.1.1 
Summary of HBsAg by A Genotype – Imputation 
ITT 
 
X 
14.2.1.1.2 
Summary of HBsAg by A Genotype – No imputation 
ITT 
 
X 
14.2.1.2.1 
Summary of HBsAg by A Genotype – Imputation 
mITT 
 
 
14.2.1.2.2 
Summary of HBsAg by A Genotype – No Imputation 
mITT 
 
 


Protocol Number: EYP001-201                                                                                                                                                                        2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 43 of 52 
 
14.2.1.3.1 
Summary of HBsAg by A Genotype - Imputation 
PP 
 
 
14.2.1.3.2 
Summary of HBsAg by A Genotype – No Imputation 
PP 
 
 
14.2.2.1.1 
Analysis of HBsAg: Baseline to Week 16 – Imputation 
ITT  
 
X 
14.2.2.1.2 
Analysis of HBsAg: Baseline to Week 16 – No Imputation 
ITT  
 
X 
14.2.2.2.1 
Analysis of HBsAg: Baseline to Week 16 - Imputation 
mITT  
 
 
14.2.2.2.2 
Analysis of HBsAg: Baseline to Week 16 – No Imputation 
mITT  
 
 
14.2.2.3.1 
Analysis of HBsAg: Baseline to Week 16 – Imputation 
PP  
 
 
14.2.2.3.2 
Analysis of HBsAg: Baseline to Week 16 – No Imputation 
PP  
 
 
14.2.3.1 
Summary and Analysis of HBsAg Loss Rate A 
ITT  
 
X 
14.2.3.2 
Summary and Analysis of HBsAg Loss Rate B 
ITT  
 
X 
14.2.4.1 
Summary and Analysis of HBsAg Responder Rate A 
ITT  
 
X 
14.2.4.2 
Summary and Analysis of HBsAg Responder Rate B 
ITT  
 
X 
14.2.5 
Summary of HBsAg Relapse Rate 
ITT  
 
 
14.2.6 
Summary of Virologic Failure Rate of HBV DNA 
ITT  
 
X 
14.2.7 
Summary of HBV-pgRNA 
ITT  
 
X 
14.2.8 
Summary of HBcrAg 
ITT  
 
X 
14.2.9 
Summary of HBeAg 
ITT  (HBeAg+ 
patients) 
 
X 
14.2.10 
Summary of Fibroscan VCTE 
ITT  
 
X 
14.2.11 
Summary of HBsAg Loss Rate (Target not detected vs. Target detected) 
ITT 
 
 


Protocol Number: EYP001-201                                                                                                                                                                        2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 44 of 52 
 
14.2.12 
Summary of Anti-HBs 
ITT  
 
 
14.2.13 
Summary of Anti-HBe 
ITT  
 
 
14.2.14 
Summary of PD Markers 
PD 
 
 
14.3 
Safety 
 
 
 
14.3.1 
Summary of Concomitant Medication 
Safety 
X 
X 
14.3.3 
Adverse Events 
 
 
 
14.3.3.1 
Summary of Overall Treatment Emergent Adverse Events 
Safety 
X 
X 
14.3.3.2 
Summary of Treatment Emergent Adverse Events by SOC and PT 
Safety 
X 
X 
14.3.3.3 
Summary of Serious Treatment-Emergent Adverse Events by SOC and PT 
Safety 
X 
X 
14.3.3.4.1 
Summary of Treatment-Emergent Adverse Events by Relationship to Study Drug 
by SOC and PT 
Safety 
X 
X 
14.3.3.4.2 
Summary of Treatment-Emergent Adverse Events by Relationship to ETV by SOC 
and PT 
Safety 
 
 
14.3.3.4.3 
Summary of Treatment-Emergent Adverse Events by Relationship to TD by SOC 
and PT 
Safety 
 
 
14.3.3.5 
Summary of Treatment-Emergent Adverse Events by SOC, PT and Severity 
Safety 
X 
X 
14.3.3.6 
Summary of Treatment Emergent Adverse Events Leading to Study Drug 
Discontinuation by SOC and PT 
Safety 
X 
X 
14.3.4 
Laboratory Parameters 
 
 
 
14.3.4.1.1 
Summary of Hematology & Coagulation 
Safety 
X 
X 
14.3.4.1.2 
Summary of Hematology & Coagulation Shifts from Baseline 
Safety 
 
 
14.3.4.2.1 
Summary of Serum Chemistry 
Safety 
X 
X 


Protocol Number: EYP001-201                                                                                                                                                                        2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 45 of 52 
 
14.3.4.2.2 
Summary of Serum Chemistry Shifts from Baseline 
Safety 
 
 
14.3.4.3.1 
Summary of Lipid Metabolic Profile  
Safety 
X 
X 
14.3.4.3.2 
Summary of Lipid Metabolic Profile Shifts from Baseline (Low, Normal, High) 
Safety 
 
 
14.3.4.3 
Summary of Urinalysis 
Safety 
X 
X 
14.3.4.4 
Summary of Maximum CTCAE for ALT, AST, BILI and GGT for Post Treatment 
Assessments 
Safety 
 
X 
14.3.5 
Other Safety 
 
 
 
14.3.5.1 
Summary of Vital Signs 
Safety 
X 
X 
14.3.5.2.1 
Summary of 12-Lead ECG 
Safety 
X 
X 
14.3.5.2.2 
Summary of 12-Lead ECG Interpretation 
Safety 
X 
X 
14.3.5.3 
Summary of Pruritus Assessment - 5-D Pruritus Scale 
Safety 
 
 
14.3.5.4 
Summary of Pruritus Assessment - Visual Analogue Scale 
Safety 
X 
X 
14.3.5.5 
Summary of Liver Fibrosis and Inflammation Assessment 
Safety 
 
 
14.3.5.6 
Analysis of Liver Fibrosis and Inflammation Assessment: Baseline to Week 16 
Safety 
 
X 
14.3.5.7 
Summary of Liver Imaging 
Safety 
X 
X 
 
 
 


Protocol Number: EYP001-201                                                                                                                                                                        2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 46 of 52 
 
19. 
LISTINGS 
Listing 
Number 
Listing Title 
Population 
DSMC Safety 
DSMC  
Safety and 
Futility 
 
 
 
 
 
16.2.1 
Subject Disposition 
 
 
 
16.2.1.1 
Analysis Populations 
ITT 
 
X 
16.2.1.2 
Participant Disposition 
ITT 
 
X 
16.2.2 
Protocol Deviations 
 
 
 
16.2.2.1 
Protocol Deviations 
ITT 
 
X 
16.2.4 
Demographic and Other Baseline Data 
 
 
 
16.2.4.1 
Demographics and Baseline Characteristics 
ITT 
 
X 
16.2.4.2 
Medical History 
ITT 
 
X 
16.2.4.3 
Drugs of Abuse Screen 
ITT 
 
X 
16.2.4.4 
AUDIT - Interview Version 
ITT 
 
X 
16.2.4.5 
Serology 
ITT 
 
X 
16.2.4.6 
Eligibility Criteria 
All Screened 
Patients 
 
X 
16.2.5 
Treatment Administration 
 
 
 
16.2.5.1 
Subject Randomization 
ITT 
 
 
16.2.5.2 
Treatment Exposure 
ITT 
 
X 
16.2.5.3 
Study Drug Accountability 
ITT 
 
 


Protocol Number: EYP001-201                                                                                                                                                                        2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 47 of 52 
 
16.2.5.4 
Missed Dose  
ITT 
 
X 
16.2.6  
Efficacy/PK/PD 
 
 
 
16.2.6.1 
HBsAg (IU/mL) 
ITT 
 
X 
16.2.6.2 
HBV DNA (Log IU/mL) 
ITT 
 
X 
16.2.6.3 
HBV-pgRNA (Log IU/mL) 
ITT 
 
X 
16.2.6.4 
HBcrAg (Log IU/mL) 
ITT 
 
X 
16.2.6.5 
HBeAg (PEI U/mL) 
ITT 
 
 
16.2.6.6 
Anti-HBs 
ITT 
 
 
16.2.6.7 
Anti-HBe 
ITT 
 
 
16.2.6.8 
Fibroscan VCTE 
ITT 
 
X 
16.2.6.9 
PD Markers  
ITT 
 
 
16.2.7 
Adverse Events 
 
 
 
16.2.7.1 
Adverse Events 
Safety 
X 
X 
16.2.7.2 
Serious Adverse Events 
Safety 
X 
X 
16.2.7.3 
Adverse Events Leading to Study Drug Withdrawal 
Safety 
X 
X 
16.2.8 
Laboratory Parameters 
 
 
 
16.2.8.1.1 
Hematology & Coagulation 
Safety 
X 
X 
16.2.8.1.2 
Abnormal Haematology & Coagulation 
Safety 
 
 
16.2.8.2.1 
Serum Chemistry 
Safety 
X 
X 
16.2.8.2.2 
Abnormal Serum Chemistry 
Safety 
 
 


Protocol Number: EYP001-201                                                                                                                                                                        2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 48 of 52 
 
16.2.8.3.1 
Lipid and Metabolic Profile 
Safety 
X 
X 
16.2.8.3.2 
Abnormal Lipid and Metabolic Profile 
Safety 
 
 
16.2.8.4.1 
Urinalysis 
Safety 
X 
X 
16.2.8.4.2 
Urine Microscopy 
Safety 
 
 
16.2.9 
Other Safety 
 
 
 
16.2.9.1 
Vital Signs 
Safety 
X 
X 
16.2.9.2 
12-Lead ECG 
Safety 
X 
X 
16.2.9.3 
Physical Examination 
Safety 
X 
X 
16.2.9.4 
Liver Fibrosis and inflammation Assessment 
Safety 
 
 
16.2.9.5 
Liver Imaging 
Safety 
 
 
16.2.9.6 
Pregnancy Test Results  
Safety 
X 
X 
16.2.9.7 
Pruritus Assessments – 5-D Pruritus Scale 
Safety 
 
 
16.2.9.8 
Pruritus Assessments – Visual Analogue Scale 
Safety 
X 
X 
16.2.9.9 
Stopping Rules 
Safety 
X 
X 
16.2.10 
Prior & Concomitant Medication 
 
 
 
16.2.10.1 
Prior Medication 
ITT 
X 
X 
16.2.10.2 
Concomitant Medication 
ITT 
X 
X 
 
 
 
 
 
 
 


Protocol Number: EYP001-201                                                                                                                                                                        2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 49 of 52 
 
20. 
FIGURES  
 
Figure 
Number 
Figure Title 
Population 
DSMC Safety 
DSMC 
Safety and 
Futility 
 
 
 
 
 
14.2  
Efficacy/PK/PD 
 
 
 
14.2.12.1 
Series Plot of Mean Actual Value over Time for PD Markers 
PD 
 
 
14.2.12.2 
Series Plot of Mean Change from Baseline over Time for PD Markers 
PD 
 
 
14.2.12.3 
Series Plot of Mean % Change from Baseline over Time for PD Markers 
PD 
 
 
14.2.12.4.1 
Boxplot of HBsAg (IU/mL) over Time by Treatment 
Safety 
 
 
14.2.12.4.2 
Boxplot of HBsAg (IU/mL) over Time by HBeAg  
Safety 
 
 
14.2.12.4.3 
Boxplot of HBsAg (IU/mL) over Time by A Genotype 
Safety 
 
 
14.2.12.5.1 
Boxplot of HBsAg (IU/mL) Change from Baseline by Treatment 
Safety 
 
X 
14.2.12.5.2 
Boxplot of HBsAg (IU/mL) Change from Baseline by HBeAg 
Safety 
 
 
14.2.12.5.3 
Boxplot of HBsAg (IU/mL) Change from Baseline by A Genotype 
Safety 
 
 
14.2.12.6.1 
Boxplot of HBV DNA (Log IU/mL) over Time by Treatment 
Safety 
 
X 
14.2.12.6.2 
Boxplot of HBV DNA (Log IU/mL) over Time by HBeAg 
Safety 
 
 
14.2.12.6.3 
Boxplot of HBV DNA (Log IU/mL) over Time by A Genotype 
Safety 
 
 
14.2.12.7.1 
Boxplot of HBV DNA (Log IU/mL) Change from Baseline by Treatment 
Safety 
 
 
14.2.12.7.2 
Boxplot of HBV DNA (Log IU/mL) Change from Baseline by HBeAg 
Safety 
 
 
14.2.12.7.3 
Boxplot of HBV DNA (Log IU/mL) Change from Baseline by A Genotype 
Safety 
 
 


Protocol Number: EYP001-201                                                                                                                                                                        2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 50 of 52 
 
14.2.12.8.1 
Series Plot of Individual Actual Value over Time for HBsAg (IU/mL) by HBeAg 
Safety 
 
X 
14.2.12.8.2 
Series Plot of Individual Actual Value over Time for HBsAg (IU/mL) by A 
Genotype 
Safety 
 
 
14.2.12.9.1 
Series Plot of Individual Change from Baseline Value for HBsAg (IU/mL) by 
HBeAg 
Safety 
 
 
14.2.12.9.2 
Series Plot of Individual Change from Baseline Value for HBsAg (IU/mL) by A 
Genotype 
Safety 
 
 
14.2.12.10.1 
Series Plot of Individual Actual Value over Time for HBV DNA (Log IU/mL) by 
HBeAg 
Safety 
 
 
14.2.12.10.2 
Series Plot of Individual Actual Value over Time for HBV DNA (Log IU/mL) by A 
Genotype 
Safety 
 
 
14.2.12.11.1 
Series Plot of Individual Change from Baseline Value for HBV DNA (Log IU/mL) 
by HBeAg 
Safety 
 
 
14.2.12.11.2 
Series Plot of Individual Change from Baseline Value for HBV DNA (Log IU/mL) 
by A Genotype 
Safety 
 
 
14.3 
Laboratory Parameters 
 
 
 
14.3.4.2.3 
Individual ALT over Time  
Safety 
X 
X 
14.3.4.2.4 
Individual ALT Change from Baseline  
Safety 
 
 
14.3.4.2.5 
Boxplot of ALT over Time by Treatment 
Safety 
X 
X 
14.3.4.2.6 
Individual AST over Time  
Safety 
X 
X 
14.3.4.2.7 
Individual AST Change from Baseline  
Safety 
 
 
14.3.4.2.8 
Boxplot of AST over Time by Treatment 
Safety 
X 
X 
14.3.4.2.9 
Individual ALP over Time  
Safety 
X 
X 


Protocol Number: EYP001-201                                                                                                                                                                        2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 51 of 52 
 
14.3.4.2.10 
Individual ALP Change from Baseline  
Safety 
 
 
14.3.4.2.11 
Boxplot of ALP over Time by Treatment 
Safety 
 
 
14.3.4.2.12 
Individual GGT over Time  
Safety 
 
 
14.3.4.2.13 
Individual GGT Change from Baseline  
Safety 
 
 
14.3.4.2.14 
Boxplot of GGT over Time by Treatment 
Safety 
 
 
14.3.4.2.15 
Individual Total Bilirubin over Time  
Safety 
X 
X 
14.3.4.2.16 
Individual Total Bilirubin Change from Baseline  
Safety 
 
 
14.3.4.2.17 
Boxplot of Total Bilirubin over Time by Treatment 
Safety 
 
 
14.3.4.2.18 
Individual Lipid Parameters over Time  
Safety 
 
X 
14.3.4.2.19 
Individual HBV DNA versus ALT at each visit 
Safety 
 
X 
14.3.4.2.20 
Individual HBV DNA versus AST at each visit 
Safety 
 
X 


Protocol Number: EYP001-201 
 
2021-08-13 
Document status: Version 3.0 
 
Novotech - Strictly Confidential 
Page 52 of 52 
 
21. 
REFERENCES 
1) 
Clinical Study Protocol Version 3.0 dated 22 January 2020. 
2) 
EYP001-201 Protocol Clarification Letter #13 dated 27 January 2021. 
3) 
EYP001-201 Protocol Clarification Letter #11 dated 08 January 2021. 
 


Protocol No: EYP001-201 
Document status: Mock EOS Tables, Listings & Figures, Final Version 2.0 
2021-06-01 
 
Novotech – Strictly Confidential 
 
Page 1 of 138 
 
Mock Tables 
Table of Contents 
Table 14.1.1 Summary of Participant Enrolment and Disposition (ITT Set)......................................................................... 6 
Table 14.1.2.x Summary of Demographics and Baseline Characteristics (ITT Set)................................................................... 7 
Table 14.1.2.x Summary of Demographics and Baseline Characteristics (ITT set)................................................................... 8 
Table 14.1.2.x Summary of Demographics and Baseline Characteristics (ITT set)................................................................... 9 
Table 14.1.3.x Summary of Viral Serology at Screening (ITT set)................................................................................ 10 
Table 14.1.3.x Summary of Viral Serology at Screening (ITT set)................................................................................ 11 
Table 14.1.4 Summary of Treatment Compliance (Safety set)...................................................................................... 12 
Table 14.2.1.1.x Summary of HBsAg by A Genotype (ITT Set)...................................................................................... 13 
Table 14.2.2.x Analysis of HBsAg: Baseline to Week 16 (ITT Set)................................................................................ 14 
Table 14.2.3.1 Summary and Analysis of HBsAg Loss Rate A (ITT Set)............................................................................. 15 
Table 14.2.3.2 Summary and Analysis of HBsAg Loss Rate B (ITT Set)............................................................................. 16 
Table 14.2.4.1 Summary and Analysis of HBsAg Responder Rate A (ITT Set)........................................................................ 17 
Table 14.2.4.2 Summary and Analysis of HBsAg Responder Rate B (ITT Set)........................................................................ 18 
Table 14.2.5 Summary of HBsAg Relapse Rate (ITT Set)........................................................................................... 19 
Table 14.2.6 Summary of Virologic Failure Rate of HBV DNA (ITT Set)............................................................................ 20 
Table 14.2.7 Summary of HBV-pgRNA (ITT Set).................................................................................................... 21 
Table 14.2.8 Summary of HBcrAg (ITT Set)....................................................................................................... 22 
Table 14.2.9 Summary of HBeAg (ITT Set and HBeAg Positive Patients)............................................................................ 23 
Table 14.2.10 Summary of Fibroscan VCTE (ITT Set).............................................................................................. 24 
Table 14.2.11 Summary of HBsAg Loss Rate (Target not detected vs. Target detected) (ITT Set)................................................... 25 
Table 14.2.12 Summary of Anti-HBs (ITT Set).................................................................................................... 26 
Table 14.2.13 Summary of Anti-HBe (ITT Set).................................................................................................... 27 
Table 14.2.14 Summary of PD Markers (PD Set)................................................................................................... 28 
Table 14.3.1 Summary of Concomitant Medications (Safety Set)................................................................................... 29 
Table 14.3.3.1 Summary of Overall Treatment Emergent Adverse Events (Safety Set)............................................................... 30 
Table 14.3.3.2 Summary of Treatment Emergent Adverse Events by System Organ Class and Preferred Term (Safety Set).............................. 31 
Table 14.3.3.3 Summary of Serious Treatment Emergent Adverse Events by System Organ Class and Preferred Term (Safety Set)...................... 32 
Table 14.3.3.4.1 Summary of Treatment Emergent Adverse Events by Relationship to Study Drug by System Organ Class, Preferred Term (Safety Set). 33 
Table 14.3.3.4.2 Summary of Treatment Emergent Adverse Events by Relationship to ETV by System Organ Class, Preferred Term (Safety Set)........ 34 
Table 14.3.3.4.3 Summary of Treatment Emergent Adverse Events by Relationship to TD by System Organ Class, Preferred Term (Safety Set)......... 35 
Table 14.3.3.5 Summary of Treatment Emergent Adverse Events by System Organ Class, Preferred Term and Severity (Safety Set).................... 36 
Table 14.3.3.6 Summary of Treatment Emergent Adverse Events Leading to Stud Drug Discontinuation by System Organ Class and Preferred Term  
(Safety Set) .................................................................................................................... 37 
Table 14.3.4.1.1 Summary of Hematology and Coagulation (Safety Set)............................................................................ 38 
Table 14.3.4.1.2 Summary of Hematology and Coagulation Shifts from Baseline (Safety Set)....................................................... 39 
Table 14.3.4.2.1 Summary of Serum Chemistry (Safety Set)....................................................................................... 40 
Table 14.3.4.2.2 Summary of Serum Chemistry Shifts from Baseline (Safety Set).................................................................. 41 
Table 14.3.4.3.1 Summary of Lipid Metabolic Profile (Safety Set)............................................................................... 42 
Table 14.3.4.3.2 Summary of Serum Chemistry Shifts from Baseline (Safety Set).................................................................. 43 
Table 14.3.4.3 Summary of Urinalysis (Safety Set).............................................................................................. 44 
Table 14.3.4.4 Summary of Maximum CTCAE for ALT, AST, BILI and GGT for Post Treatment Assessments (Safety Set)................................. 45 
Table 14.3.5.1 Summary of Vital Signs (Safety Set)............................................................................................. 46 
Table 14.3.5.2.1 Summary of 12-Lead ECG (Safety Set)........................................................................................... 47 
Table 14.3.5.2.2 Summary of 12-Lead ECG Interpretation (Safety Set)............................................................................ 48 
Table 14.3.5.3 Summary of Pruritus Assessment - 5-D Pruritus Scale (Safety Set)................................................................ 49 
Table 14.3.5.4 Summary of Pruritus Assessment - Visual Analogue Scale (Safety Set)............................................................. 50 
Table 14.3.5.5 Summary of Liver Fibrosis and Inflammation Assessment (Safety Set).............................................................. 51 
Table 14.3.5.6 Analysis of Liver Fibrosis and Inflammation Assessment: Baseline to Week 16 (Safety Set)........................................ 52 


Protocol No: EYP001-201 
Document status: Mock EOS Tables, Listings & Figures, Final Version 2.0 
2021-06-01 
 
Novotech – Strictly Confidential 
 
Page 2 of 138 
Table 14.3.5.7 Summary of Liver Imaging (Safety Set)........................................................................................... 53 
Listing 16.2.1.1 Analysis Populations (ITT Set)................................................................................................ 54 
Listing 16.2.1.2 Participant Disposition (ITT Set)............................................................................................. 55 
Listing 16.2.2.1 Protocol Deviation (ITT Set).................................................................................................. 56 
Listing 16.2.4.1 Demographics and Baseline Characteristics (ITT Set)........................................................................... 57 
Listing 16.2.4.2 Medical History (ITT Set)..................................................................................................... 58 
Listing 16.2.4.3 Drugs of Abuse Screen (ITT Set)............................................................................................... 59 
Listing 16.2.4.4 AUDIT – Interview Version (ITT Set)........................................................................................... 60 
Listing 16.2.4.5 Serology (ITT Set)............................................................................................................ 61 
Listing 16.2.4.6 Eligibility Criteria (All Screened Patients).................................................................................. 62 
Listing 16.2.5.1 Participant Randomization (ITT Set)........................................................................................... 63 
Listing 16.2.5.2 Treatment Exposure (ITT Set).................................................................................................. 64 
Listing 16.2.5.3 Study Drug Accountability (ITT Set)........................................................................................... 65 
Listing 16.2.5.4 Missed Dose (ITT Set)......................................................................................................... 66 
Listing 16.2.6.1 HBsAg (IU/mL) (ITT Set)....................................................................................................... 67 
Listing 16.2.6.2 HBV DNA (Log IU/mL) (ITT Set)................................................................................................. 68 
Listing 16.2.6.3 HBV-pgRNA (Log IU/mL) (ITT Set)............................................................................................... 69 
Listing 16.2.6.4 HBcrAg (Log IU/mL) (ITT Set).................................................................................................. 70 
Listing 16.2.6.5 HBeAg (PEI U/ml) (ITT Set).................................................................................................... 71 
Listing 16.2.6.6 Anti-HBs (ITT Set)............................................................................................................ 72 
Listing 16.2.6.7 Anti-HBe (ITT Set)............................................................................................................ 73 
Listing 16.2.6.8 Fibroscan VCTE (ITT Set)...................................................................................................... 74 
Listing 16.2.6.9 PD Markers (ITT Set).......................................................................................................... 75 
Listing 16.2.7.1 Adverse Events (ITT Set)...................................................................................................... 76 
Listing 16.2.7.2 Serious Adverse Events (ITT Set).............................................................................................. 77 
Listing 16.2.7.3 Adverse Events Leading to Study Drug Withdrawal (ITT Set)..................................................................... 78 
Listing 16.2.8.1.1 Hematology and Coagulation (ITT Set)........................................................................................ 79 
Listing 16.2.8.1.2 Abnormal Hematology and Coagulation (ITT Set)............................................................................... 80 
Listing 16.2.8.2.1 Serum Chemistry (ITT Set)................................................................................................... 81 
Listing 16.2.8.2.2 Abnormal Serum Chemistry (ITT Set).......................................................................................... 82 
Listing 16.2.8.3.1 Lipid and Metabolic Profile (ITT Set)....................................................................................... 83 
Listing 16.2.8.3.2 Abnormal Lipid and Metabolic Profile (ITT Set).............................................................................. 84 
Listing 16.2.8.4.1 Urinalysis (ITT Set)........................................................................................................ 85 
Listing 16.2.8.4.2 Urine Microscopy (ITT Set).................................................................................................. 86 
Listing 16.2.9.1 Vital Signs (ITT Set)......................................................................................................... 87 
Listing 16.2.9.2 12-Lead ECG (ITT Set)......................................................................................................... 88 
Listing 16.2.9.3 Physical Examination (ITT Set)................................................................................................ 89 
Listing 16.2.9.4 Liver Fibrosis and Inflammation Assessment (ITT Set).......................................................................... 90 
Listing 16.2.9.5 Liver Imaging (ITT Set)....................................................................................................... 91 
Listing 16.2.9.6 Pregnancy Test Results (ITT Set).............................................................................................. 92 
Listing 16.2.9.7 Pruritus Assessment – 5-D Pruritus Scale (ITT Set)............................................................................ 93 
Listing 16.2.9.8 Pruritus Assessment – Visual Analogue Scale (ITT Set)......................................................................... 94 
Listing 16.2.9.9 Stopping Rule (ITT Set)....................................................................................................... 95 
Listing 16.2.10.1 Prior Medication (ITT Set)................................................................................................... 96 
Listing 16.2.10.2 Concomitant Medication (ITT Set)............................................................................................. 97 
Figure 14.2.12.1 Series Plot of Mean Actual Value over Time for PD Markers (PD Set)............................................................ 98 
Figure 14.2.12.2 Series Plot of Mean Actual Value over Time for PD Markers (PD Set)............................................................ 99 
Figure 14.2.12.3 Series Plot of Mean % Change from Baseline over Time for PD Markers (PD Set)................................................. 100 
Figure 14.2.12.4.1 Boxplot of HBsAg (IU/mL) over Time by Treatment (Safety Set)............................................................... 101 
Figure 14.2.12.4.2 Boxplot of HBsAg (IU/mL) over Time by HBeAg (Safety Set)................................................................... 102 
Figure 14.2.12.4.3 Boxplot of HBsAg (IU/mL) over Time by A Genotype (Safety Set).............................................................. 103 
Figure 14.2.12.5.1 Boxplot of HBsAg (IU/mL) Change from Baseline by Treatment (Safety Set).................................................... 104 
Figure 14.2.12.5.2 Boxplot of HBsAg (IU/mL) Change from Baseline by HBeAg (Safety Set)........................................................ 105 


Protocol No: EYP001-201 
Document status: Mock EOS Tables, Listings & Figures, Final Version 2.0 
2021-06-01 
 
Novotech – Strictly Confidential 
 
Page 3 of 138 
Figure 14.2.12.5.3 Boxplot of HBsAg (IU/mL) Change from Baseline by A Genotype (Safety Set)................................................... 106 
Figure 14.2.12.6.1 Boxplot of HBV DNA (Log IU/mL) over Time by Treatment (Safety Set)......................................................... 107 
Figure 14.2.12.6.2 Boxplot of HBV DNA (Log IU/mL) over Time by HBeAg (Safety Set)............................................................. 108 
Figure 14.2.12.6.3 Boxplot of HBV DNA (Log IU/mL) over Time by A Genotype (Safety Set)........................................................ 109 
Figure 14.2.12.7.1 Boxplot of HBV DNA (Log IU/mL) Change from Baseline by Treatment (Safety Set).............................................. 110 
Figure 14.2.12.7.2 Boxplot of HBV DNA (Log IU/mL) Change from Baseline by HBeAg (Safety Set).................................................. 111 
Figure 14.2.12.7.3 Boxplot of HBV DNA (Log IU/mL) Change from Baseline by A Genotype (Safety Set)............................................. 112 
Figure 14.2.12.8.1 Series Plot of Individual Actual Value over Time for HBsAg (IU/mL) by HBeAg (Safety Set)................................... 113 
Figure 14.2.12.8.2 Series Plot of Individual Actual Value over Time for HBsAg (IU/mL) by A Genotype (Safety Set).............................. 114 
Figure 14.2.12.9.1 Series Plot of Individual Change from Baseline Value for HBsAg (IU/mL) by HBeAg (Safety Set)............................... 115 
Figure 14.2.12.9.2 Series Plot of Individual Change from Baseline Value for HBsAg (IU/mL) by A Genotype (Safety Set).......................... 116 
Figure 14.2.12.10.1 Series Plot of Individual Actual Value over Time for HBV DNA (Log IU/mL) by HBeAg (Safety Set)............................ 117 
Figure 14.2.12.10.2 Series Plot of Individual Actual Value over Time for HBV DNA (Log IU/mL) by A Genotype (Safety Set)....................... 118 
Figure 14.2.12.11.1 Series Plot of Individual Change from Baseline Value for HBV DNA (Log IU/mL) by HBeAg (Safety Set)........................ 119 
Figure 14.2.12.11.2 Series Plot of Individual Change from Baseline Value for HBV DNA (Log IU/mL) by A Genotype (Safety Set)................... 120 
Figure 14.3.4.2.3 Individual ALT over Time (Safety Set)....................................................................................... 121 
Figure 14.3.4.2.4 Individual ALT Change from Baseline (Safety Set)............................................................................ 122 
Figure 14.3.4.2.5 Boxplot of ALT over Time by Treatment (Safety Set).......................................................................... 123 
Figure 14.3.4.2.6 Individual AST over Time (Safety Set)....................................................................................... 124 
Figure 14.3.4.2.7 Individual AST Change from Baseline (Safety Set)............................................................................ 125 
Figure 14.3.4.2.8 Boxplot of AST over Time by Treatment (Safety Set).......................................................................... 126 
Figure 14.3.4.2.9 Individual ALP over Time (Safety Set)....................................................................................... 127 
Figure 14.3.4.2.10 Individual ALP Change from Baseline (Safety Set)........................................................................... 128 
Figure 14.3.4.2.11 Boxplot of ALP over Time by Treatment (Safety Set)......................................................................... 129 
Figure 14.3.4.2.12 Individual GGT over Time (Safety Set)...................................................................................... 130 
Figure 14.3.4.2.13 Individual GGT Change from Baseline (Safety Set)........................................................................... 131 
Figure 14.3.4.2.14 Boxplot of GGT over Time by Treatment (Safety Set)......................................................................... 132 
Figure 14.3.4.2.15 Individual Total Bilirubin over Time (Safety Set).......................................................................... 133 
Figure 14.3.4.2.16 Individual Total Bilirubin Change from Baseline (Safety Set)............................................................... 134 
Figure 14.3.4.2.17 Boxplot of Total Bilirubin over Time by Treatment (Safety Set)............................................................. 135 
Figure 14.3.4.2.18 Individual Lipid Parameters over Time (Safety Set)......................................................................... 136 
Figure 14.3.4.2.19 Individual HBV DNA versus ALT at Each Visit (Safety Set)................................................................... 137 
Figure 14.3.4.2.20 Individual HBV DNA versus AST at Each Visit (Safety Set)................................................................... 138 
 
 
 


Protocol No: EYP001-201 
Document status: Mock EOS Tables, Listings & Figures, Final Version 2.0 
2021-06-01 
 
Novotech – Strictly Confidential 
 
Page 4 of 138 
GENERAL COMMENTS 
 
• 
Where a count is 0, the percentage will not be shown (e.g. 0(0.0%) will be displayed as 0) 
• 
Unless otherwise states, parameters will be listed in alphabetical order. 
• 
The minimum and maximum values will be presented to the same number of decimal places as recorded in the electronic Case Report Form (eCRF) 
• 
Mean, SD, and Median will be presented to one more decimal place than the raw data 
• 
Percentages will be rounded to one decimal place, with the denominator being the number of subjects in the relevant population with non-missing 
data, unless otherwise specified 
• 
Change from Baseline: 
Change from Baseline will be calculated as: 
 
Change from Baseline = post baseline value – baseline value 
• 
Unscheduled visits will be excluded from summary tables but included in all by-participant listings. 
• 
Names and order of Treatment Groups for Table Summaries 
o Group 1 = EYP001a 200 mg QD + NA daily  
o Group 2 = EYP001a 200 mg QD + NA daily HBeAg+  
o Group 3 = EYP001a 200 mg QD + NA daily HBeAg-  
o Group 4 = Placebo + NA daily  
o Group 5 = Placebo HBeAg+  
o Group 6 = Placebo HBeAg-  
o Group 7 = All HBeAg+  
o Group 8 = All HBeAg-  
o Group 9 = All Study Patients  
 
• 
Treatment Display by Page 
Page 1, 3, 5, etc. 
EYP001a 200 mg QD + NA 
daily 
(N=xx) 
= EYP001a 200 mg QD + 
NA daily HBeAg+ 
(N=xx) 
= EYP001a 200 mg QD + 
NA daily HBeAg- 
(N=xx) 
Placebo + NA daily 
(N=xx) 
Page 2, 4, 6, etc. 
Placebo HBeAg+ 
(N=xx) 
Placebo HBeAg- 
(N=xx) 
All HBeAg+ 
(N=xx) 
All HBeAg- 
(N=xx) 
All Study Patients 
(N=xx) 
Section 14.3.1 and Section 14.3.3.x 
Page 1, 3, 5, etc. 


Protocol No: EYP001-201 
Document status: Mock EOS Tables, Listings & Figures, Final Version 2.0 
2021-06-01 
 
Novotech – Strictly Confidential 
 
Page 5 of 138 
Group 1 
(N=xx) 
n (%) m 
Group 2 
(N=xx) 
n (%) m 
Group 3 
(N=xx) 
n (%) m 
Group 4 
(N=xx) 
n (%) m 
Page 2, 4, 6, etc. 
Group 5 
(N=xx) 
n (%) m 
Group 6 
(N=xx) 
n (%) m 
Group 7 
(N=xx) 
n (%) m 
Group 8 
(N=xx) 
n (%) m 
Group 9 
(N=xx) 
n (%) m 
• 
Names and order of Treatment Groups for Listings 
o EYP001a 200 mg QD + NA daily HBeAg+  
o EYP001a 200 mg QD + NA daily HBeAg-  
o Placebo HBeAg+  
o Placebo HBeAg-  
• 
Names of visits 
o Screening (Listing only) 
o Baseline (Table only) 
o Visit 1 = Day 1 
o Visit 2 = Week 2 
o Visit 3 = Week 4 
o Visit 4 = Week 6 
o Visit 5 = Week 8 
o Visit 6 = Week 10 
o Visit 7 = Week 12 
o Visit 8 = Week 14 
o Visit 9 = Week 16 
o Visit 10 = Week 20 (Follow-up Visit 1) 
o Visit 11 = Week 28 (Follow-up Visit 2) 
o Visit 12 = Week 40 (EOS) 
o Early Termination  
o Unscheduled (Listing only) 
 
• 
Column widths and text-wrapping may be altered in final output in order to best present the data. 
• 
Footnotes may be added/amended if required.


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 6 of 138 
Table 14.1.1 Summary of Participant Enrolment and Disposition (ITT Set)  
 
 
Group 1 
(N=xx) 
etc. 
Group x 
(N=xx) 
 
 
 
Intention-to-Treat Set  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Modified Intention-To-Teat Set 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Safety Analysis Set 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Pharmacodynamic Analysis Set 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Per Protocol Analysis Set 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Number of Participants who Completed the Study 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Number of Participants who did not Complete the Study 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Primary Reason for Non-Completion 
 
 
 
Adverse Event 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Death 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Protocol Violation 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Withdrawal by Subject 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Lack of Efficacy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Study Terminated by Sponsor 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Non-compliance with Study Drug  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Lost to Follow Up 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Screen Failure 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Source Listing: 16.2.1.1, 16.2.1.2 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the ITT Set in each treatment group 
(N). 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 7 of 138 
Table 14.1.2.x Summary of Demographics and Baseline Characteristics (ITT Set)  
 
Parameter 
Statistic 
Group 1 
(N=xx) 
etc. 
Group x 
(N=xx) 
 
 
 
Age (years) at Screening 
n 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.x 
xx.x 
xx.x 
Median 
x.x 
x.x 
x.x 
Minimum 
xx 
xx 
xx 
Maximum 
xx 
xx 
xx 
 
 
 
Sex n(%) 
Female 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Male 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Childbearing Potential n(%)* 
Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Race n (%) 
American Indian or Alaskan Native 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Asian 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Black or African American 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Native Hawaiian or Other Pacific Islander 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
White 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Unknown 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Not Reported 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Ethnicity n(%) 
Hispanic or Latino 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Not Hispanic or Latino 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Not Reported 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Unknown 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Source Listing: 16.2.4.1 
SD: Standard Deviation. Percentages are calculated (the denominator used for the calculation) based on the number of participants in the ITT set 
in each treatment group (N).  
*For childbearing potential, percentages are based on the number of female participants. 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 8 of 138 
Table 14.1.2.x Summary of Demographics and Baseline Characteristics (ITT set)  
 
Parameter 
Statistic 
Group 1 
(N=xx) 
etc. 
Group x 
(N=xx) 
 
 
 
Weight (kg) at Screening 
n 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.x 
xx.x 
xx.x 
Median 
xx.x 
xx.x 
xx.x 
Minimum 
xx 
xx 
xx 
Maximum 
xx 
xx 
xx 
 
 
 
Height (cm) at Screening 
n 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.x 
xx.x 
xx.x 
Median 
xx.x 
xx.x 
xx.x 
Minimum 
xx 
xx 
xx 
Maximum 
xx 
xx 
xx 
 
 
 
Body Mass Index(kg/m2) at Screening n 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.x 
xx.x 
xx.x 
Median 
xx.x 
xx.x 
xx.x 
Minimum 
xx 
xx 
xx 
Maximum 
xx 
xx 
xx 
 
 
 
HBeAg Status 
Positive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Negative 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Source Listing: 16.2.4.1 
 
SD: Standard Deviation. Percentages are calculated (the denominator used for the calculation) based on the number of participants in the ITT Set 
in each treatment group (N).  
*For childbearing potential, percentages are based on the number of female participants. 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 9 of 138 
Table 14.1.2.x Summary of Demographics and Baseline Characteristics (ITT set)  
 
Parameter 
Statistic 
Group 1 
(N=xx) 
etc. 
Group x 
(N=xx) 
 
 
 
HBV Genotype 
A 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
B 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
C 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
D 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
E 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
F 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
G 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
H 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
I 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
J 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Audit-C overall score 
n 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.x 
xx.x 
xx.x 
Median 
xx.x 
xx.x 
xx.x 
Minimum 
xx 
xx 
xx 
Maximum 
xx 
xx 
xx 
 
 
 
Source Listing: 16.2.4.1 
 
SD: Standard Deviation. Percentages are calculated (the denominator used for the calculation) based on the number of participants in the ITT Set 
in each treatment group (N).  
*For childbearing potential, percentages are based on the number of female participants. 
 
Programming note: 
- Repeat for table 14.1.2.2 (mITT Set), table 14.1.2.3 (Safety Set) and table 14.1.2.4 (PP Set) 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 10 of 138 
Table 14.1.3.x Summary of Viral Serology at Screening (ITT set)  
 
Parameter 
Category 
Group 1 
(N=xx) 
etc. 
Group x 
(N=xx) 
 
 
 
Hepatitis D virus (anti-HDV) 
n 
xx 
xx 
xx 
Positive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Negative 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Antibody to HIV (anti-HIV) 
n 
xx 
xx 
xx 
Positive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Negative 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Antibody to HCV (anti-HCV), 
n 
xx 
xx 
xx 
Positive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Negative 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
PCR-based Quantitative HCV Viral Load * 
n 
xx 
xx 
xx 
Positive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Negative 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Anti-HBs 
n 
xx 
xx 
xx 
Positive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Negative 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Anti-HBe 
n 
xx 
xx 
xx 
Positive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Negative 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Source Listing: 16.2.4.5 
 
SD: Standard Deviation. Percentages are calculated (the denominator used for the calculation) based on the number of participants in the ITT Set 
in each treatment group (N).  
*For PCR-based Quantitative HCV Viral Load, percentages are based on the number of anti-HCV positive participants. 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 11 of 138 
Table 14.1.3.x Summary of Viral Serology at Screening (ITT set)  
 
Parameter 
Category 
Group 1 
(N=xx) 
etc. 
Group x 
(N=xx) 
 
 
 
Quantitative HBsAg Level 
n 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.x 
xx.x 
xx.x 
Median 
xx.x 
xx.x 
xx.x 
Minimum 
xx 
xx 
xx 
Maximum 
xx 
xx 
xx 
 
 
 
Second Quantitative HBsAg Level 
n 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.x 
xx.x 
xx.x 
Median 
xx.x 
xx.x 
xx.x 
Minimum 
xx 
xx 
xx 
Maximum 
xx 
xx 
xx 
 
 
 
Source Listing: 16.2.4.5 
 
SD: Standard Deviation. Percentages are calculated (the denominator used for the calculation) based on the number of participants in the ITT Set 
in each treatment group (N).  
*For PCR-based Quantitative HCV Viral Load, percentages are based on the number of anti-HCV positive participants. 
 
 
Programming note: 
- Repeat for table 14.1.3.2 (mITT Set), table 14.1.3.3 (Safety Set) and table 14.1.3.4 (PP Set) 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 12 of 138 
Table 14.1.4 Summary of Treatment Compliance (Safety set)  
 
Category 
Group 1 
(N=xx) 
etc. 
Group x 
(N=xx) 
 
 
 
n 
xx 
xx 
xx 
< 50% Compliance 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
>= 50% and =< 80% Compliance 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
> 80% Compliance 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Source Listing: 16.2.5.2, 16.2.5.3 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 13 of 138 
Table 14.2.1.1.x Summary of HBsAg by A Genotype (ITT Set)  
 
Genotype: A 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
Visit 
 Statistics 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Baseline [1] 
 
 
 
 
 
 
N 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Mean 
XX 
N/A 
XX 
N/A 
XX 
N/A 
SD 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Median 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Minimum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Maximum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
 
N 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Week xx 
 
 
 
 
 
 
n 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Source Listing: 16.2.6.1 
 
SD: Standard Deviation. N/A = Not Applicable. 
[1] Baseline is defined as the average of screening and day 1 pre-dose. 
 
Programming Note: 
- Repeat for Genotype: Non A 
- Repeat for table 14.2.1.1.2 (ITT set with no imputation), 14.2.1.2.1 (mITT with imputation), ), 14.2.1.2.2 (mITT with no imputation) , 14.2.1.3.1 (PP set with imputation) 
and 14.2.1.3.2 (PP set with no imputation) . 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 14 of 138 
Table 14.2.2.x Analysis of HBsAg: Baseline to Week 16 (ITT Set) 
 
EYP001a 200 mg QD + NA daily  
(N=XXX) 
Placebo + NA daily  
(N=XXX) 
 
 
Week 2 
 
 
n 
XX 
XX 
Mean change from baseline  
XX 
XX 
LS Mean change from baseline 
XX 
XX 
95% CI on LS mean change from baseline 
XX,XX 
XX,XX 
SE on LS mean change from baseline 
xx.xx 
xx.xx 
p-value 
.xxx 
.xxx 
 
 
 
Difference in change from baseline at Week 10 
 
 
N 
XX 
 
Mean 
XX 
 
LS Mean 
XX,XX 
 
95% on LS Mean 
XX,XX 
 
SE on LS Mean 
xx.xx 
 
  p-value 
.xxx 
 
<Repeat for Week 4,6,8,10,12,14,16> 
 
 
 
 
 
 
Source Listing: 16.2.6.1 
LS mean is derived from a general linear model for repeated measures. The covariates are treatment groups, visit, baseline HBsAG, A Genotype, 
HBeAg positive and the interaction term of treatment group*visit. 
Covariance structure is XXX. 
CI = Confidence Interval. SE = Standard Error. 
 
Programming Note: 
- Repeat for table 14.2.2.1.2 (ITT set with no imputation), 14.2.2.2.1 (mITT with imputation), ), 14.2.2.2.2 (mITT with no imputation) , 14.2.2.3.1 (PP set with imputation) 
and 14.2.2.3.2 (PP set with no imputation) . 
-The SAS code used to implement this analysis is given below: 
                       PROC MIXED DATA=dataset; 
CLASS  ID TRT VISIT HBeAg; 
MODEL CHG = Baseline HBeAg TRT VISIT TRT*VISIT / SOLUTION CL; 
DDFM=KenwardRoger; 
REPEATED VISIT /SUBJECT = ID TYPE = UN ; 
LSMEANS TRT*VISIT / DIFF CL; 
RUN; 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 15 of 138 
 
Table 14.2.3.1 Summary and Analysis of HBsAg Loss Rate A (ITT Set)  
 
Visit 
Category 
Statistics 
EYP001a 200 mg QD + NA daily  
(N=XXX) 
Placebo + NA daily  
(N=XXX) 
 
 
Week 16 
n 
xx 
xx 
HBsAg Loss 
n (%) [1] 
xx (xx.x %) 
xx (xx.x %) 
p-value 
0.XXX 
 
 
 
<Repeat for Week 40> 
 
 
 
 
 
 
 
 
Source Listing: 16.2.6.1 
p-value is based on the Person Chi-squared Test. 
HBsAg Loss is defined as HBsAg value < LLOQ/TND. 
[1] Number of subjects at each visit (Visit n) will be used as the denominator for the calculation of all percentages. 
 
 
Programming Note: 
- Only present Week 16 and Week 40 will consider multiplicity by a combination of a hierarchical fixed test procedure and a Hochberg procedure to adjust p-value. 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 16 of 138 
Table 14.2.3.2 Summary and Analysis of HBsAg Loss Rate B (ITT Set)  
 
Visit 
Category 
Statistics 
EYP001a 200 mg QD + NA daily  
(N=XXX) 
Placebo + NA daily  
(N=XXX) 
 
 
Week 16 
n 
xx 
xx 
HBsAg Loss 
n (%) [1] 
xx (xx.x %) 
xx (xx.x %) 
p-value 
0.XXX 
 
 
 
<Repeat for Week 40> 
 
 
 
 
 
 
 
 
Source Listing: 16.2.6.1 
p-value is based on the Person Chi-squared Test. 
HBsAg Loss is defined as HBsAg value < LLOQ/TD. 
[1] Number of subjects at each visit (Visit n) will be used as the denominator for the calculation of all percentages. 
 
 
Programming Note: 
- Only present Week 16 and Week 40 will consider multiplicity by a combination of a hierarchical fixed test procedure and a Hochberg procedure to adjust p-value. 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 17 of 138 
 
Table 14.2.4.1 Summary and Analysis of HBsAg Responder Rate A (ITT Set)  
 
Decrease from Baseline ≥ 1.0 on the log10 Scale 
Visit 
Category 
Statistics 
EYP001a 200 mg QD + NA daily  
(N=XXX) 
Placebo + NA daily  
(N=XXX) 
 
 
Week 16 
n 
 
 
HBsAg Responder 
n (%) [1] 
 
 
p-value 
 
 
 
 
Week 40 
n 
xx 
xx 
n (%) [1] 
xx (xx.x %) 
xx (xx.x %) 
p-value 
0.XXX 
 
 
 
 
 
Source Listing: 16.2.6.1 
 
p-value is based on the Person Chi-squared Test. 
[1] Number of subjects at each visit (Visit n) will be used as the denominator for the calculation of all percentages. 
 
 
Programming Note: 
- Only to present Week 16 and Week 40 will consider multiplicity by a combination of a hierarchical fixed test procedure and a Hochberg procedure to adjust p-value. 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 18 of 138 
 
Table 14.2.4.2 Summary and Analysis of HBsAg Responder Rate B (ITT Set)  
 
Decrease from Baseline ≥ 0.5 on the log10 Scale 
Visit 
Category 
Statistics 
EYP001a 200 mg QD + NA daily  
(N=XXX) 
Placebo + NA daily  
(N=XXX) 
 
 
Week 16 
n 
xx 
xx 
HBsAg Responder 
n (%) [1] 
xx (xx.x %) 
xx (xx.x %) 
p-value 
0.XXX 
 
 
 
Week 40 
n 
xx 
xx 
n (%) [1] 
xx (xx.x %) 
xx (xx.x %) 
p-value 
0.XXX 
 
 
 
 
 
 
 
Source Listing: 16.2.6.1 
 
p-value is based on the Person Chi-squared Test. 
[1] Number of subjects at each visit (Visit n) will be used as the denominator for the calculation of all percentages. 
 
 
Programming Note: 
- Only to present Week 16 and Week 40 will consider multiplicity by a combination of a hierarchical fixed test procedure and a Hochberg procedure to adjust p-value. 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 19 of 138 
 
Table 14.2.5 Summary of HBsAg Relapse Rate (ITT Set)  
 
Visit 
Category 
Statistics 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
 
 
 
Week 16 
n 
xx 
xx 
xx 
HBsAg Relapse  
n (%) [1] 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
<Repeat for Week 20, 
28, 40> 
n 
xx 
xx 
xx 
HBsAg Relapse  
n (%) [1] 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
 
 
 
Source Listing: 16.2.6.1 
 
HBsAg Relapse is defined as patients who became negative [HBsAg < LLOQ], then increased with HBsAg > LLOQ. 
[1] Number of subjects at each visit (Visit n) will be used as the denominator for the calculation of all percentages. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 20 of 138 
Table 14.2.6 Summary of Virologic Failure Rate of HBV DNA (ITT Set)  
 
Visit 
Category 
Statistics 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
 
 
 
Week 16 
n 
xx 
xx 
xx 
Virologic Failure Rate 
n (%) [1] 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
<Repeat for Week 20, 
28, 40> 
n 
xx 
xx 
xx 
Virologic Failure Rate 
n (%) [1] 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
 
 
 
Source Listing: 16.2.6.2 
 
Virologic Failure Rate of HBV DNA is defined as patients with a confirmed quantifiable HBV DNA increase of ≥ 1log10 HBV DNA copies/mL above LLOQ. 
[1] Number of subjects at each visit (Visit n) will be used as the denominator for the calculation of all percentages. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 21 of 138 
Table 14.2.7 Summary of HBV-pgRNA (ITT Set)  
 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
Visit 
 Statistics 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Baseline [1] 
 
 
 
 
 
 
N 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Mean 
XX 
N/A 
XX 
N/A 
XX 
N/A 
SD 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Median 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Minimum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Maximum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
 
N 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Week xx 
 
 
 
 
 
 
n 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Source Listing: 16.2.6.3 
 
SD: Standard Deviation. N/A = Not Applicable.  
[1] Baseline is defined as the last valid, non-missing assessment prior to first study drug administration. 
 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 22 of 138 
Table 14.2.8 Summary of HBcrAg (ITT Set)  
 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
Visit 
 Statistics 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Baseline [1] 
 
 
 
 
 
 
N 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Mean 
XX 
N/A 
XX 
N/A 
XX 
N/A 
SD 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Median 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Minimum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Maximum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
 
N 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Week xx 
 
 
 
 
 
 
n 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Source Listing: 16.2.6.4 
 
SD: Standard Deviation. N/A = Not Applicable. 
[1] Baseline is defined as the last valid, non-missing assessment prior to first study drug administration. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 23 of 138 
Table 14.2.9 Summary of HBeAg (ITT Set and HBeAg Positive Patients)  
 
Group 2 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
Visit 
 Statistics 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Baseline [1] 
 
 
 
 
 
 
N 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Mean 
XX 
N/A 
XX 
N/A 
XX 
N/A 
SD 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Median 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Minimum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Maximum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
 
 
 
 
 
 
Week 16 
 
 
 
 
 
 
N 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Week 40 
 
 
 
 
 
 
n 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Source Listing: 16.2.6.5 
 
SD: Standard Deviation. N/A = Not Applicable. 
[1] Baseline is defined as the HBeAg value at screening visit.. 
 
Programming Note: 
This table is only for ITT set and HBeAg Positive Patients so that the treatment groups will be presented as below: 
Group 2 = EYP001a 200 mg QD + NA daily HBeAg+   
Group 5 = Placebo HBeAg+  
Group 7 = All HBeAg+  
Group 9 = All Study Patients (HBeAg + only)  
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 24 of 138 
Table 14.2.10 Summary of Fibroscan VCTE (ITT Set)  
 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
Visit 
 Statistics 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Baseline [1] 
 
 
 
 
 
 
N 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Mean 
XX 
N/A 
XX 
N/A 
XX 
N/A 
SD 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Median 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Minimum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Maximum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
 
 
 
 
 
 
Week 16 
 
 
 
 
 
 
N 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Week 40 
 
 
 
 
 
 
n 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Source Listing: 16.2.6.8 
 
SD: Standard Deviation. N/A = Not Applicable. 
[1] Baseline is defined as the last valid, non-missing assessment prior to first study drug administration. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 25 of 138 
Table 14.2.11 Summary of HBsAg Loss Rate (Target not detected vs. Target detected) (ITT Set)  
 
Visit 
Result 
Statistics 
Group 1 
(N=xx) 
etc. 
Group x 
(N=xx) 
 
 
 
Week 16 
n 
xx 
xx 
xx 
TND 
n (%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
TD 
n (%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Week 20 
n 
xx 
xx 
xx 
TND 
n (%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
TD 
n (%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
<Repeat for Week 28, 40> 
 
 
 
 
 
 
Source Listing: 16.2.6.1 
 
TND = Target Not Detected. TD = Target Detected. 
Number of subjects at each visit (Visit n) will be used as the denominator for the calculation of all percentages. 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 26 of 138 
Table 14.2.12 Summary of Anti-HBs (ITT Set)  
 
Visit 
Category 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
 
 
 
 
Baseline[1] 
n 
xx 
xx 
xx 
Non-Reactive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Indeterminate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Reactive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
Week 16 
n 
xx 
xx 
xx 
Non-Reactive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Indeterminate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Reactive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Week 40 
n 
xx 
xx 
xx 
Non-Reactive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Indeterminate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Reactive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Source Listing: 16.2.6.6 
 
Number of subjects at each visit (Visit n) will be used as the denominator for the calculation of all percentages. 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 27 of 138 
 
Table 14.2.13 Summary of Anti-HBe (ITT Set)  
 
Visit 
Category 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
 
 
 
 
Baseline[1] 
n 
xx 
xx 
xx 
Non-Reactive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Indeterminate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Reactive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
Week 16 
n 
xx 
xx 
xx 
Non-Reactive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Indeterminate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Reactive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Week 40 
n 
xx 
xx 
xx 
Non-Reactive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Indeterminate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Reactive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Source Listing: 16.2.6.7 
 
Number of subjects at each visit (Visit n) will be used as the denominator for the calculation of all percentages. 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 28 of 138 
Table 14.2.14 Summary of PD Markers (PD Set)  
 
Parameters: Plasma C4 (7α-hydroxy-4-cholesten-3-one) 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
Visit 
 Statistics 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Baseline [1] 
 
 
 
 
 
 
N 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Mean 
XX 
N/A 
XX 
N/A 
XX 
N/A 
SD 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Median 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Minimum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Maximum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
 
N 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Week xx 
 
 
 
 
 
 
n 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Source Listing: 16.2.6.9 
 
SD: Standard Deviation.  
[1] Baseline is defined as the last valid, non-missing assessment prior to first study drug administration. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 29 of 138 
Table 14.3.1 Summary of Concomitant Medications (Safety Set)  
 
 
Anatomical Therapeutic Class (ATC) [Level 3] 
    Preferred Term (PT) 
Group 1 
(N=xx) 
n (%) m 
etc. 
Group x 
(N=xx) 
n (%) m 
 
 
 
 
Subjects with at least one Concomitant Medication 
xx (xx.x%) x 
xx (xx.x%) x 
xx (xx.x%) x 
 
 
 
 
ATC 1 
xx (xx.x%) x 
xx (xx.x%) x 
xx (xx.x%) x 
    PT 1 
xx (xx.x%) x 
xx (xx.x%) x 
xx (xx.x%) x 
    PT 2 
xx (xx.x%) x 
xx (xx.x%) x 
xx (xx.x%) x 
…. 
xx (xx.x%) x 
xx (xx.x%) x 
xx (xx.x%) x 
 
 
 
 
ATC 2 
xx (xx.x%) x 
xx (xx.x%) x 
xx (xx.x%) x 
    PT 1 
xx (xx.x%) x 
xx (xx.x%) x 
xx (xx.x%) x 
    PT 2 
xx (xx.x%) x 
xx (xx.x%) x 
xx (xx.x%) x 
…… 
 
 
 
 
 
 
 
Source: Listing 16.2.10.2 
 
Concomitant medications are defined as any medication (other than the study drug) that was used at least once after the first administration of 
the study drug. If a participant has multiple occurrences of a concomitant medication, the participant is presented only once in the participant 
count (n) column for a given ATC and PT. Occurrences are counted each time in the mentions/occurrence (m) column. 
 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the safety set in each treatment 
group (N). 
 
World Health Organization-Drug Dictionary (WHO-DD) Version xx, YYYY 
 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 30 of 138 
 
Table 14.3.3.1 Summary of Overall Treatment Emergent Adverse Events (Safety Set)  
 
Group 1 
(N=xx) 
n (%) m 
etc. 
Group x 
(N=xx) 
n (%) m 
 
 
 
Number of Participants Reporting at least: 
 
 
 
  One TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
  One Serious TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
  One TEAE with Common Terminology Criteria for Adverse Events (CTCAE)   
  Toxicity ≥ Grade 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
  One Study Drug Related TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
  One Entecavir (ETV) Related TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
  One Tenofovir Disoproxil Fumarate (TDF) Related TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
  One TEAE Leading to Discontinuation of Study Drug 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
Source: Listing 16.2.7.1 
 
Treatment Emergent Adverse Events (TEAEs) are defined as adverse events that occurred following the first administration of study medication.  
If a participant has multiple occurrences of a TEAE, the participant is presented only once in the Participant count (n) column for a given System 
Organ Class and Preferred Term. Occurrences are counted each time in the mentions/Occurrence (m) column.  
Treatment Related TEAE is defined as any TEAE reported as being “Possibly”, “Probably” or “Definitely” to Study Drug/EV/TDF. 
 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the safety set in each treatment group 
(N). 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 31 of 138 
Table 14.3.3.2 Summary of Treatment Emergent Adverse Events by System Organ Class and Preferred Term (Safety Set)  
 
Group 1 
(N=xx) 
n (%) m 
etc. 
Group x 
(N=xx) 
n (%) m 
 
 
 
Participants with at least one TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
SOC1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   PT1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
….. 
 
 
 
 
 
 
SOC2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   PT1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   PT2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   PT3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   PT4 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
…. 
 
 
 
 
 
 
Source: Listing 16.2.7.1 
 
Treatment Emergent Adverse Events (TEAEs) are defined as adverse events that occurred following the first administration of study medication.  
If a participant has multiple occurrences of a TEAE, the participant is presented only once in the Participant count (n) column for a given System 
Organ Class and Preferred Term. Occurrences are counted each time in the mentions/Occurrence (m) column.  
 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the safety set in each treatment group 
(N). 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 32 of 138 
Table 14.3.3.3 Summary of Serious Treatment Emergent Adverse Events by System Organ Class and Preferred Term (Safety Set)  
 
Group 1 
(N=xx) 
n (%) m 
etc. 
Group x 
(N=xx) 
n (%) m 
 
 
 
Participants with at least one Serious TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
SOC1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   PT1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
….. 
 
 
 
 
 
 
SOC2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   PT1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   PT2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   PT3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   PT4 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
…. 
 
 
 
 
 
 
Source: Listing 16.2.7.2 
 
Treatment Emergent Adverse Events (TEAEs) are defined as adverse events that occurred following the first administration of study medication. 
If a participant has multiple occurrences of a TEAE, the participant is presented only once in the Participant count (n) column for a given System 
Organ Class and Preferred Term. Occurrences are counted each time in the mentions/Occurrence (m) column.  
 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the safety set in each treatment group 
(N). 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 33 of 138 
Table 14.3.3.4.1 Summary of Treatment Emergent Adverse Events by Relationship to Study Drug by System Organ Class, Preferred Term (Safety Set)  
 
Group 1 
(N=xx) 
n (%) m 
etc. 
Group x 
(N=xx) 
n (%) m 
 
 
 
Participants with at least one TEAE related to study drug 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Definitely Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Probably Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Possibly Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Unlikely Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Unrelated 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
SOC1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Definitely Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Probably Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Possibly Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Unlikely Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Unrelated 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
   PT1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Definitely Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Probably Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Possibly Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Unlikely Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Unrelated 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
….. 
 
 
 
 
 
 
Source: Listing 16.2.7.1 
 
Treatment Emergent Adverse Events (TEAEs) are defined as adverse events that occurred following the first administration of study medication.  
If a participant has multiple occurrences of a TEAE, the participant is presented only once in the Participant count (n) column for a given System 
Organ Class and Preferred Term. Occurrences are counted each time in the mentions/Occurrence (m) column.  
 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the safety set in each treatment group 
(N). 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 34 of 138 
Table 14.3.3.4.2 Summary of Treatment Emergent Adverse Events by Relationship to ETV by System Organ Class, Preferred Term (Safety Set)  
 
Group 1 
(N=xx) 
n (%) m 
etc. 
Group x 
(N=xx) 
n (%) m 
 
 
 
Participants with at least one TEAE related to ETV 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Definitely Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Probably Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Possibly Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Unlikely Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Unrelated 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
SOC1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Definitely Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Probably Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Possibly Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Unlikely Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Unrelated 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
   PT1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Definitely Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Probably Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Possibly Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Unlikely Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Unrelated 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
….. 
 
 
 
 
 
 
Source: Listing 16.2.7.1 
 
Treatment Emergent Adverse Events (TEAEs) are defined as adverse events that occurred following the first administration of study medication.  
If a participant has multiple occurrences of a TEAE, the participant is presented only once in the Participant count (n) column for a given System 
Organ Class and Preferred Term. Occurrences are counted each time in the mentions/Occurrence (m) column.  
 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the safety set in each treatment group 
(N). 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 35 of 138 
Table 14.3.3.4.3 Summary of Treatment Emergent Adverse Events by Relationship to TD by System Organ Class, Preferred Term (Safety Set)  
 
Group 1 
(N=xx) 
n (%) m 
etc. 
Group x 
(N=xx) 
n (%) m 
 
 
 
Participants with at least one TEAE related to TD 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Definitely Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Probably Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Possibly Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Unlikely Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Unrelated 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
SOC1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Definitely Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Probably Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Possibly Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Unlikely Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Unrelated 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
   PT1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Definitely Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Probably Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Possibly Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Unlikely Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Unrelated 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
….. 
 
 
 
 
 
 
Source: Listing 16.2.7.1 
 
Treatment Emergent Adverse Events (TEAEs) are defined as adverse events that occurred following the first administration of study medication.  
If a participant has multiple occurrences of a TEAE, the participant is presented only once in the Participant count (n) column for a given System 
Organ Class and Preferred Term. Occurrences are counted each time in the mentions/Occurrence (m) column.  
 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the safety set in each treatment group 
(N). 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 36 of 138 
Table 14.3.3.5 Summary of Treatment Emergent Adverse Events by System Organ Class, Preferred Term and Severity (Safety Set)  
 
Group 1 
(N=xx) 
n (%) m 
etc. 
Group x 
(N=xx) 
n (%) m 
 
 
 
Participants with at least one TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Mild 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Moderate 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Severe 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Life-threatening 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Fatal 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
SOC1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Mild 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Moderate 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Severe 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Life-threatening 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   Fatal 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
   PT1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Mild 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Moderate 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Severe 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Life-threatening 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
      Fatal 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
….. 
 
 
 
 
 
 
Source: Listing 16.2.7.1 
 
Treatment Emergent Adverse Events (TEAEs) are defined as adverse events that occurred following the first administration of study medication.  
If a participant has multiple occurrences of a TEAE, the participant is presented only once in the Participant count (n) column for a given System 
Organ Class and Preferred Term. Occurrences are counted each time in the mentions/Occurrence (m) column.  
 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the safety set in each treatment group 
(N). 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 37 of 138 
Table 14.3.3.6 Summary of Treatment Emergent Adverse Events Leading to Stud Drug Discontinuation by System Organ Class and Preferred Term  
(Safety Set) 
 
Group 1 
(N=xx) 
n (%) m 
etc. 
Group x 
(N=xx) 
n (%) m 
 
 
 
Participants with at least one TEAE Leading to Discontinuation of Study Drug 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
SOC1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   PT1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
….. 
 
 
 
 
 
 
SOC2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   PT1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   PT2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   PT3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
   PT4 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
…. 
 
 
 
 
 
 
Source: Listing 16.2.7.3 
 
Treatment Emergent Adverse Events (TEAEs) are defined as adverse events that occurred following the first administration of study medication. 
If a participant has multiple occurrences of a TEAE, the participant is presented only once in the Participant count (n) column for a given System 
Organ Class and Preferred Term. Occurrences are counted each time in the mentions/Occurrence (m) column.  
 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the safety set in each treatment group 
(N). 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 38 of 138 
Table 14.3.4.1.1 Summary of Hematology and Coagulation (Safety Set)  
 
Parameter: Basophils (unit) 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
Visit 
 Statistics 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Baseline [1] 
 
 
 
 
 
 
N 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Mean 
XX 
N/A 
XX 
N/A 
XX 
N/A 
SD 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Median 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Minimum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Maximum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
 
N 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Week xx 
 
 
 
 
 
 
n 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Source: Listing 16.2.8.1.1 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. SD = Standard Deviation. 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 39 of 138 
Table 14.3.4.1.2 Summary of Hematology and Coagulation Shifts from Baseline (Safety Set)  
 
Parameter: Hemoglobin (unit) 
Baseline [1] 
Visit 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
 
 
 
Baseline  
Week 2 
 
 
 
 Low 
 Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Low 
 Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Low 
 Hight 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Normal 
 Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Normal 
 Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Normal 
 Hight 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 High 
 Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 High 
 Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 High 
 Hight 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Etc. 
Etc. 
 
 
 
 
 
 
Source: Listing 16.2.8.1.1 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
Number of participants at each visit (n) will be used as the denominator for the calculation of all percentages. 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 40 of 138 
Table 14.3.4.2.1 Summary of Serum Chemistry (Safety Set)  
 
Parameter: Basophils (unit) 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
Visit 
 Statistics 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Baseline [1] 
 
 
 
 
 
 
N 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Mean 
XX 
N/A 
XX 
N/A 
XX 
N/A 
SD 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Median 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Minimum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Maximum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
 
N 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Week xx 
 
 
 
 
 
 
n 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Source: Listing 16.2.8.2.1 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
For ALT, AST, ALP, and total Bilirubin (TBL), the baseline value is defined as the average of screening and day 1 pre-dose. 
N/A = Not Applicable. SD = Standard Deviation. 
 
Programming Note: 
- For ALT, AST, ALP, and total Bilirubin (TBL), the baseline value is defined as the average of screening and day 1 pre-dose. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 41 of 138 
Table 14.3.4.2.2 Summary of Serum Chemistry Shifts from Baseline (Safety Set)  
 
Parameter: Basophils (unit) 
Baseline [1] 
Visit 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
 
 
 
Baseline  
Week 2 
 
 
 
 Low 
 Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Low 
 Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Low 
 Hight 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Normal 
 Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Normal 
 Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Normal 
 Hight 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 High 
 Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 High 
 Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 High 
 Hight 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Etc. 
Etc. 
 
 
 
 
 
 
Source: Listing 16.2.8.2.1 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
Number of participants at each visit (n) will be used as the denominator for the calculation of all percentages. 
 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 42 of 138 
Table 14.3.4.3.1 Summary of Lipid Metabolic Profile (Safety Set)  
 
Parameter: HDL-C (unit) 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
Visit 
 Statistics 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Baseline [1] 
 
 
 
 
 
 
N 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Mean 
XX 
N/A 
XX 
N/A 
XX 
N/A 
SD 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Median 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Minimum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Maximum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
 
N 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Week xx 
 
 
 
 
 
 
n 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Source: Listing 16.2.8.3.1 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
For ALT, AST, ALP, and total Bilirubin (TBL), the baseline value is defined as the average of screening and day 1 pre-dose. 
N/A = Not Applicable. SD = Standard Deviation. 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 43 of 138 
Table 14.3.4.3.2 Summary of Serum Chemistry Shifts from Baseline (Safety Set)  
 
Parameter: HDL-C (unit) 
Baseline [1] 
Visit 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
 
 
 
Baseline  
Week 2 
 
 
 
 Low 
 Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Low 
 Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Low 
 Hight 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Normal 
 Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Normal 
 Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 Normal 
 Hight 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 High 
 Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 High 
 Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 High 
 Hight 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Etc. 
Etc. 
 
 
 
 
 
 
Source: Listing 16.2.8.3.1 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
Number of participants at each visit (n) will be used as the denominator for the calculation of all percentages. 
 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 44 of 138 
 
Table 14.3.4.3 Summary of Urinalysis (Safety Set)  
 
Parameter: Glucose (unit) 
 
Visit 
Category 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
 
 
 
 
Baseline[1] 
n 
xx 
xx 
xx 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal, Not Clinically Significant 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal, Clinically Significant 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
Week xx 
n 
xx 
xx 
xx 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal, Not Clinically Significant 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal, Clinically Significant 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Etc. 
Etc. 
 
 
 
Source: Listing 16.2.8.4.1 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
Number of participants at each visit (n) will be used as the denominator for the calculation of all percentages. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 45 of 138 
 
Table 14.3.4.4 Summary of Maximum CTCAE for ALT, AST, BILI and GGT for Post Treatment Assessments (Safety Set)  
 
 
 
Parameters/ grade 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
 
 
 
 
Number of subjects with any CTCAE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
ALT 
 
 
 
No CTCAE (Grade 0) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Grade 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Grade 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Grade 3  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Grade 4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Grade 5 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
< repeat for AST, BILI and GGT > 
 
 
 
Etc. 
 
 
 
Source: Listing 16.2.8.2.1 
 
This table is based on maximum grading using CTCAE version 5.0 
BILI =  Total Bilirubin; GGT= Gamma Glutamyl Transferase; ALT =Alanine Aminotransferase; AST = Aspartate Aminotransferase 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 46 of 138 
Table 14.3.5.1 Summary of Vital Signs (Safety Set)  
 
Parameter: Heart rate (beats/min) 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
Visit 
 Statistics 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Baseline [1] 
 
 
 
 
 
 
N 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Mean 
XX 
N/A 
XX 
N/A 
XX 
N/A 
SD 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Median 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Minimum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Maximum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
 
N 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Week xx 
 
 
 
 
 
 
n 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Source: Listing 16.2.9.1 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. SD = Standard Deviation. 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 47 of 138 
Table 14.3.5.2.1 Summary of 12-Lead ECG (Safety Set)  
 
Parameter: Heart Rate (bpm) 
 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
Visit 
 Statistics 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Baseline [1] 
 
 
 
 
 
 
N 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Mean 
XX 
N/A 
XX 
N/A 
XX 
N/A 
SD 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Median 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Minimum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Maximum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
 
 
 
 
 
 
Week xx 
 
 
 
 
 
 
N 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Source: Listing 16.2.9.2 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. SD = Standard Deviation. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 48 of 138 
Table 14.3.5.2.2 Summary of 12-Lead ECG Interpretation (Safety Set)  
 
Parameter: Overall ECG Interpretation 
 
Visit 
Category 
Group 1 
(N=XXX) 
Group 2 
(N=XXX) 
Group 3 
(N=XXX) 
 
 
 
 
Baseline[1] 
n 
xx 
xx 
xx 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal, Not Clinically Significant 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal, Clinically Significant 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Not Evaluable 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
Week xx 
N 
xx 
xx 
xx 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal, Not Clinically Significant 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal, Clinically Significant 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Not Evaluable 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Etc. 
Etc. 
 
 
 
Source: Listing 16.2.9.2 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
Number of participants at each visit (n) will be used as the denominator for the calculation of all percentages. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 49 of 138 
Table 14.3.5.3 Summary of Pruritus Assessment - 5-D Pruritus Scale (Safety Set)  
 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
Visit 
 Statistics 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Baseline [1] 
 
 
 
 
 
 
N 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Mean 
XX 
N/A 
XX 
N/A 
XX 
N/A 
SD 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Median 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Minimum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Maximum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
 
 
 
 
 
 
Week xx 
 
 
 
 
 
 
N 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Source: Listing 16.2.9.7 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. SD = Standard Deviation. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 50 of 138 
Table 14.3.5.4 Summary of Pruritus Assessment - Visual Analogue Scale (Safety Set)  
 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
Visit 
 Statistics 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Baseline [1] 
 
 
 
 
 
 
N 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Mean 
XX 
N/A 
XX 
N/A 
XX 
N/A 
SD 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Median 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Minimum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Maximum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
 
 
 
 
 
 
Week xx 
 
 
 
 
 
 
N 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Source: Listing 16.2.9.8 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. SD = Standard Deviation. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 51 of 138 
Table 14.3.5.5 Summary of Liver Fibrosis and Inflammation Assessment (Safety Set)  
 
Parameter: ALT (unit) 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
Visit 
 Statistics 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Actual Value 
Change from 
Baseline 
Baseline [1] 
 
 
 
 
 
 
N 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Mean 
XX 
N/A 
XX 
N/A 
XX 
N/A 
SD 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Median 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Minimum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
Maximum 
XX 
N/A 
XX 
N/A 
XX 
N/A 
 
 
 
 
 
 
Week 4 
 
 
 
 
 
 
N 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Week xx 
 
 
 
 
 
 
n 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX 
XX 
XX 
XX 
XX 
XX 
SD 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX 
XX 
XX 
XX 
XX 
XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
Source: Listing 16.2.9.4 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. SD = Standard Deviation. 
 
Programming Note: 
- These parameter (ALT, AST, AST/ALT ratio, high sensitivity C-reactive protein, interleukin 6, tumour necrosis factor alpha, procollagen type III N terminal peptide (Pro 
C3), tissue inhibitor of metalloproteinases-1) will be included. 
For ALT and AST, the baseline value is defined as the average of screening and day 1 pre-dose 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 52 of 138 
Table 14.3.5.6 Analysis of Liver Fibrosis and Inflammation Assessment: Baseline to Week 16 (Safety Set) 
 
Parameter: AST (unit) 
 
EYP001a 200 mg QD + NA daily  
(N=XXX) 
Placebo + NA daily  
(N=XXX) 
 
 
Week 4 
 
 
n 
XX 
XX 
Mean change from baseline  
XX 
XX 
LS Mean change from baseline 
XX 
XX 
95% CI on LS mean change from baseline 
XX,XX 
XX,XX 
SE on LS mean change from baseline 
xx.xx 
xx.xx 
 
 
 
Difference in change from baseline at Week 4 
 
 
N 
XX 
 
Mean 
XX 
 
LS Mean 
XX,XX 
 
95% on LS Mean 
XX,XX 
 
SE on LS Mean 
xx.xx 
 
 
 
<Repeat for Week 8,12,16> 
 
 
 
 
 
 
Source Listing: 16.2.9.4 
 
LS mean is derived from a general linear model for repeated measures. The covariates are treatment groups, visit, baseline value of liver 
fibrosis and inflammation assessment, A Genotype, HBeAg positive and the interaction term of treatment group*visit. 
Covariance structure is XXX. 
CI = Confidence Interval. SE = Standard Error. 
 
Programming note: 
The SAS code used to implement this analysis is given below: 
                       PROC MIXED DATA=dataset; 
CLASS  ID TRT VISIT HBeAg; 
MODEL CHG = Baseline HBeAg TRT VISIT TRT*VISIT / SOLUTION CL; 
DDFM=KenwardRoger; 
REPEATED VISIT /SUBJECT = ID TYPE = UN ; 
LSMEANS TRT*VISIT / DIFF CL; 
RUN; 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 53 of 138 
Table 14.3.5.7 Summary of Liver Imaging (Safety Set)  
 
Parameter: Glucose (unit) 
 
Visit 
Category 
Group 1 
(N=XXX) 
etc. 
Group x 
(N=XXX) 
 
 
 
 
Screening 
n 
xx 
xx 
xx 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal, Not Clinically Significant 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal, Clinically Significant 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
Week 40 
n 
xx 
xx 
xx 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal, Not Clinically Significant 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal, Clinically Significant 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Etc. 
Etc. 
 
 
 
Source: Listing 16.2.9.5 
 
Number of participants at each visit (n) will be used as the denominator for the calculation of all percentages. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 54 of 138 
Listing 16.2.1.1 Analysis Populations (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject 
ID 
Intention-
to-Treat 
Set 
Modified Intention-
to-Treat 
Set 
Safety  
Set 
Pharmacodynamic 
Set 
Per Protocol  
Set 
Reason for Exclusion 
 
 
 
 
 
 
 
XXX 
Yes 
Yes 
Yes 
Yes 
Yes 
 
XXX 
Yes 
Yes 
Yes 
Yes 
Yes 
 
XXX 
Yes 
Yes 
Yes 
Yes 
Yes 
 
XXX 
Yes 
Yes 
No 
Yes 
No 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 55 of 138 
Listing 16.2.1.2 Participant Disposition (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject ID 
Informed Consent 
Did the Participant 
Complete the Study? 
Study Completion/ 
Early Termination Date 
(YYYY-MM-DD) 
Primary Reason for 
Non-completion 
Date for Consent 
Withdrawal 
(YYYY-MM-DD) 
Date  
(YYYY-MM-DD) 
Date for the storage 
and use of blood 
samples  
(YYYY-MM-DD) 
 
 
 
 
 
 
XXX 
YYYY-MM-DD 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
 
 
XXX 
YYYY-MM-DD 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
 
 
XXX 
YYYY-MM-DD 
YYYY-MM-DD 
No 
YYYY-MM-DD 
Withdrawal by Subject 
YYYY-MM-DD 
XXX 
YYYY-MM-DD 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
 
 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 56 of 138 
Listing 16.2.2.1 Protocol Deviation (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject ID 
Date of Deviation 
(YYYY-MM-DD) 
Type of Deviation 
Deviation Description 
Important Deviation 
 
 
 
 
 
XXX 
YYYY-MM-DD 
YYYYYYYYYYYYYYY 
XXXXXXXXXXXXX 
No 
XXX 
YYYY-MM-DD 
YYYYYYYYYYYYYYY 
XXXXXXXXXXXXX 
No 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 57 of 138 
Listing 16.2.4.1 Demographics and Baseline Characteristics (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject 
ID 
Date of 
Informed 
Consent 
(YYYY-MM-DD) 
Date of 
Birth 
(YYYY-MM-
DD) 
Age at 
Informed 
Consent 
(years) 
Sex 
Childbearing 
Potential 
Reason not 
of 
Childbearing 
Potential 
Race 
Ethnicity
Height 
(cm) 
Weight  
(kg)  
Body Mass 
Index 
(kg/m2) 
Audit-C 
overall 
score 
HBV 
Genotype 
HBeAg 
Status 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXX 
YYYY-MM-DD YYYY-MM-DD 
xx 
Female 
No 
Other - 
xxxxx 
Asian 
xxxxx 
xxx 
xx.x 
xx.x 
3 
A 
Positive 
XXX 
YYYY-MM-DD YYYY-MM-DD 
xx 
Male 
N/A 
 
White 
xxxxx 
xxx 
xx.x 
xx.x 
3 
B 
Negative 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N/A = Not Applicable. 
 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 58 of 138 
 
Listing 16.2.4.2 Medical History (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject 
ID 
MH Id 
Medical History Term/ System Organ Class /Preferred Term 
Start Date  
(YYYY-MM-DD) 
End Date  
(YYYY-MM-DD) 
 
 
 
 
 
XXX 
xx 
XXXXXXXXXX/ YYYYYYYYY/ ZZZZZZZZZ 
YYYY-MM-DD 
YYYY-MM-DD 
 
xx 
XXXXXXXXXX/ YYYYYYYYY/ ZZZZZZZZZ 
YYYY-MM-DD 
Ongoing 
….. 
 
 
 
 
 
 
 
 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 59 of 138 
Listing 16.2.4.3 Drugs of Abuse Screen (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject ID 
Visit 
Test Performed / No- 
Reason 
Collection Date/ Time 
(YYYY-MM-DD/ HH:MM) 
Any Positive Result 
Tests Positive 
 
 
 
 
 
 
XXX 
Screening 
Yes 
YYYY-MM-DD/ HH:MM 
Yes 
Amphetamines 
……. 
 
 
 
 
Barbiturates 
 
 
 
 
 
…. 
 
Treatment Visit 1 
Yes 
YYYY-MM-DD/ HH:MM 
No 
 
 
 
 
 
 
 
XXX 
Screening 
No - XXXXXX 
 
 
 
….. 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 60 of 138 
Listing 16.2.4.4 AUDIT – Interview Version (ITT Set)  
 
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject ID 
Visit 
Interview 
Performed 
Administered/ No - 
Reason 
Test Date 
(YYYY-MM-DD) 
Questions 
Result 
 
 
 
 
 
 
XXX 
Screening 
Yes 
YYYY-MM-DD 
How often do you have a drink containing alcohol? 
Never 
 
 
 
 
How many drinks containing alcohol do you have on a 
typical day when you are drinking? 
1 or 2 
 
 
 
 
How often do you have six or more drinks on one occasion? 
Less than monthly 
 
 
 
 
How often during the last year have you found that you 
were not able to stop drinking once you had started? 
Less than monthly 
 
 
 
 
How often during the last year have you failed to do what 
was normally expected from you because of drinking? 
Daily or almost 
daily 
 
 
 
 
How often during the last year have you needed a first 
drink in the morning to get yourself going after a heavy 
drinking session? 
Never 
 
 
 
 
How often during the last year have you had a feeling of 
guilt or remorse after drinking 
Never 
 
 
 
 
How often during the last year have you been unable to 
remember what happened the night before because you had 
been drinking 
Never 
 
 
 
 
Have you or someone else been injured as a result of your 
drinking 
Never 
 
 
 
 
Has a relative or friend or a doctor or another health 
worker been concerned about your drinking or suggested you 
cut down 
Never 
 
 
 
 
AUDIT Overall Score 
6 
 
Day 1 
No - xxxxxxx 
 
How often do you have a drink containing alcohol? 
N/A 
 
 
 
 
Etc. 
 
XXX 
Screening 
Yes 
YYYY-MM-DD 
How often do you have a drink containing alcohol? 
 
….. 
….. 
 
 
Etc. 
 
 
 
 
 
 
 
 
Programming Note: 
- Patients with AUDIT-C scores 3 points at screening will receive the full AUDIT and will be excluded if they score 8 points on the full AUDIT. Patients with AUDIT C 
scores <3 points will not receive the full AUDIT. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 61 of 138 
Listing 16.2.4.5 Serology (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject ID 
Visit 
Collection Date/ Time 
(YYYY-MM-DD/ HH:MM) 
Test Name 
Result 
 
 
 
 
 
XXX 
Screening 
YYYY-MM-DD/ HH:MM 
Hepatitis D Antibody (Anti-HDV) 
Negative 
 
 
 
HIV-1 Antibody/HIV-2 Antibody (Anti-HIV) 
Negative 
 
 
 
Hepatitis B Antibody (Anti-HBsAg) 
Negative 
 
 
 
hepatitis B e-antibody (Anti-HBe) 
Negative 
 
 
 
Quantitative HBsAg 
xx 
 
 
 
Hepatitis C Antibody (Anti-HCV) 
Positive 
….. 
 
 
PCR-based quantitative HCV viral load 
Negative 
 
 
Programming Note: 
- When Anti-HCV is Positive, a PCR-based quantitative HCV viral load assessment will be performed. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 62 of 138 
Listing 16.2.4.6 Eligibility Criteria (All Screened Patients)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject ID 
Visit 
Participant Eligible 
Category Failed 
(Inclusion/ Exclusion) 
Inclusion/ Exclusion  
Criterion not met 
 
 
 
 
 
XXX 
Screening 
No 
Inclusion and 
Exclusion 
Exclusion: xx, xx; Inclusion xx, xx 
 
Day 1 
Yes 
 
 
…. 
…. 
 
 
 
 
 
 
 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 63 of 138 
Listing 16.2.5.1 Participant Randomization (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject ID 
Randomization Date/Time 
(YYYY-MM-DD/ HH:MM) 
Randomization 
Number 
Randomized Treatment  
Received 
 
 
 
 
XXX 
YYYY-MM-DD/ HH:MM 
XXX 
EYP001a 200 mg QD + NA daily  
XXX 
YYYY-MM-DD/ HH:MM 
XXX 
EYP001a 200 mg QD + NA daily  
XXX 
YYYY-MM-DD/ HH:MM 
XXX 
EYP001a 200 mg QD + NA daily  
…. 
 
 
 
 
 
 
 
 
 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 64 of 138 
Listing 16.2.5.2 Treatment Exposure (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject 
ID 
Visit 
Study Drug 
Administered/ 
No - Reason 
Date/Time of 
Administration 
(YYYY-MM-DD/ 
HH:MM) 
Did the subject 
take 200mg as 
per protocol? / 
No – Reason 
Fasting? 
NA 
Administered 
(Treatment)/ 
No - Reason 
Date/Time of 
Administration for 
NA 
(YYYY-MM-DD/ HH:MM) 
Did the subject 
take NA as per 
protocol? / No 
– Reason 
 
 
 
 
 
 
 
 
 
XXX 
Day 1 
Yes 
YYYY-MM-DD/ 
HH:MM 
Yes 
No 
Yes (TD) 
YYYY-MM-DD/ HH:MM 
Yes 
 
Week 2 
Yes 
YYYY-MM-DD/ 
HH:MM 
No - xxxxx 
No 
Yes (ETV) 
YYYY-MM-DD/ HH:MM 
No - xxxx 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXX 
Day 1 
No - xxxxxxxx 
 
 
 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NA = Nucleos(T)ide Analogue. TD = Tenofovir Disopropil. ETV = Entecavir 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 65 of 138 
Listing 16.2.5.3 Study Drug Accountability (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Drug Accountability (EYP001a/Placebo) 
Subject 
ID 
Visit 
Number of 200mg 
Tablets Used 
Date of 
Return  
(YYYY-MM-DD) 
Number of 200mg 
Tablets Dispensed 
Date of 
Dispense 
(YYYY-MM-DD) 
Dose 
Missed 
Was the subject 
compliant with 
EYP001a/Placebo 
Dosing? 
reason for non-
compliance 
 
 
 
 
 
 
 
 
 
XXX 
Day 1 
xx 
YYYY-MM-DD 
xx 
YYYY-MM-DD 
No 
Yes 
 
 
Week 4 
xx 
YYYY-MM-DD 
Xx 
YYYY-MM-DD 
No 
Yes 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXX 
Day 1 
No - xxxxxxxx 
 
 
 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Drug Accountability (NA) 
Subject 
ID 
Visit 
Number of 
Tablets Used 
Date of 
Return  
(YYYY-MM-
DD) 
Drug 
Number of 
Tablets 
Dispensed 
Date of 
Dispense 
(YYYY-MM-DD) 
Dose 
Missed 
Was the subject 
compliant with NA 
Dosing? 
reason for non-
compliance 
 
 
 
 
 
 
 
 
 
 
XXX 
Day 1 
xx 
YYYY-MM-DD 
ETV 
xx 
YYYY-MM-DD 
Yes 
No 
Xxxx,yyy,zzz 
 
Week 4 
xx 
YYYY-MM-DD 
ETV 
Xx 
YYYY-MM-DD 
No 
Yes 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXX 
Day 1 
No - xxxxxxxx 
 
 
 
 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NA = Nucleos(T)ide Analogue. TDF = Tenofovir Disopropil. ETV = Entecavir 
 
 
Programming note: 
- in the reason for non-compliance, to present all that apply and separated by a "," 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 66 of 138 
Listing 16.2.5.4 Missed Dose (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
Subject ID 
Date of Missed 
EYP001a/Placebo Dose 
(YYYY-MM-DD) 
Reason for missed EYP001a/Placebo dose 
Date of Missed 
NA Dose  
(YYYY-MM-DD) 
Reason for missed NA dose 
 
 
 
 
 
XXX 
YYYY-MM-DD 
Patient Forgot 
 
Patient Forgot 
 
YYYY-MM-DD 
AE- xxxxxxx 
 
 Other - xxxxx 
 
 
 
 
 
 
 
 
 
 
XXX 
 
 
 
 
... 
 
 
 
 
 
 
 
 
 
NA = Nucleos(T)ide Analogue.  
 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 67 of 138 
 
 
Listing 16.2.6.1 HBsAg (IU/mL) (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject 
ID 
Visit 
Was HBV Response 
Marker Sample 
Collected / No - 
Reason 
Collection Date/ Time 
(YYYY-MM-DD/ HH:MM) 
Actual Value 
log10 
Actual Value 
Change from 
Baseline [1] 
 
 
 
 
 
 
 
XXX 
Screening 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
N/A 
 
Day 1 [1] 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
N/A 
 
Week 2 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
xx.x 
 
Week 4 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
xx.x 
 
Etc. 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
etc. 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the average of screening and Day 1 pre-dose. 
N/A = Not Applicable. EOS = End of Study. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 68 of 138 
Listing 16.2.6.2 HBV DNA (Log IU/mL) (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject 
ID 
Visit 
Was HBV Response Marker 
Sample Collected / No - 
Reason 
Collection Date/ Time (YYYY-MM-
DD/ HH:MM) 
Actual Value 
Change from 
Baseline [1] 
 
 
 
 
 
 
XXX 
Screening 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
N/A 
 
Day 1 [1] 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
N/A 
 
Week 2 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
 
Week 4 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
 
Etc. 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
 
 
 
 
 
 
etc. 
etc. 
 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. EOS = End of Study. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 69 of 138 
Listing 16.2.6.3 HBV-pgRNA (Log IU/mL) (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject 
ID 
Visit 
Was HBV Response Marker 
Sample Collected / No - 
Reason 
Collection Date/ Time (YYYY-MM-
DD/ HH:MM) 
Actual Value 
Change from 
Baseline [1] 
 
 
 
 
 
 
XXX 
Screening 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
N/A 
 
Day 1 [1] 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
N/A 
 
Week 2 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
 
Week 4 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
 
Etc. 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
 
 
 
 
 
 
etc. 
etc. 
 
 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. EOS = End of Study. 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 70 of 138 
Listing 16.2.6.4 HBcrAg (Log IU/mL) (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject 
ID 
Visit 
Was HBV Response Marker 
Sample Collected / No - 
Reason 
Collection Date/ Time (YYYY-MM-
DD/ HH:MM) 
Actual Value 
Change from 
Baseline [1] 
 
 
 
 
 
 
XXX 
Screening 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
N/A 
 
Day 1 [1] 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
N/A 
 
Week 2 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
 
Week 4 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
 
Etc. 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
 
 
 
 
 
 
etc. 
etc. 
 
 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. EOS = End of Study. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 71 of 138 
Listing 16.2.6.5 HBeAg (PEI U/ml) (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject 
ID 
Visit 
Was HBV Response 
Marker Sample 
Collected / No - 
Reason 
Collection Date/ Time 
(YYYY-MM-DD/ HH:MM) 
Actual Value 
log10 
Actual Value 
Change from 
Baseline [1] 
 
 
 
 
 
 
 
XXX 
Screening [1] 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
N/A 
 
Day 1  
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
N/A 
 
Week 16 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
xx.x 
 
Week 40 (EOS) 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
xx.x 
 
 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
etc. 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as HBeAg value at screening visit. 
EOS = End of Study. 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 72 of 138 
Listing 16.2.6.6 Anti-HBs (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject ID 
Visit 
Was HBV Response Marker 
Sample Collected / No - 
Reason 
Collection Date/ Time (YYYY-MM-DD/ 
HH:MM) 
Actual Value 
 
 
 
 
 
XXX 
Screening 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
 
Day 1 [1] 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
 
Week 16 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
 
Week 40 (EOS) 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
 
 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
 
 
 
 
 
etc. 
etc. 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 73 of 138 
Listing 16.2.6.7 Anti-HBe (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject ID 
Visit 
Was HBV Response Marker 
Sample Collected / No - 
Reason 
Collection Date/ Time (YYYY-MM-DD/ 
HH:MM) 
Actual Value 
 
 
 
 
 
XXX 
Screening 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
 
Day 1 [1] 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
 
Week 16 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
 
Week 40 (EOS) 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
 
 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
 
 
 
 
 
etc. 
etc. 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 74 of 138 
Listing 16.2.6.8 Fibroscan VCTE (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject 
ID 
Visit 
Fibroscan VCTE 
Performed/ No - 
Reason 
Assessment Date/ 
Time (YYYY-MM-DD/ 
HH:MM) 
Liver stiffness 
measure (LSM) result 
(kpa) 
Change from 
Baseline [1] 
Date and Time of Last 
Solid Meal 
(YYYY-MM-DD/ HH:MM) 
 
 
 
 
 
 
 
XXX 
Screening [1] 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
 
YYYY-MM-DD/ HH:MM 
 
Week 16 
Yes 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
YYYY-MM-DD/ HH:MM 
 
Week 40 (EOS) 
No - XXXXXX 
YYYY-MM-DD/ HH:MM 
xx.x 
xx.x 
YYYY-MM-DD/ HH:MM 
 
 
 
 
 
 
 
etc. 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable.EOS = End of Study. 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 75 of 138 
 
Listing 16.2.6.9 PD Markers (ITT Set) 
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Parameter: FGF-19 (unit) 
 
Subject ID 
Visit 
Collection  
Date/ Time  
(YYYY-MM-DD/ HH:MM) 
Actual 
Value 
Change from 
Baseline [1] 
Comments 
 
 
 
 
XXX 
Day 1 [1] 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
 
Week 2 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xxxxxxxx 
Week 4 
YYYY-MM-DD/ HH:MM 
xx 
xx 
 
Week 6 
YYYY-MM-DD/ HH:MM 
xx 
xx 
 
Week 8 
YYYY-MM-DD/ HH:MM 
xx 
xx 
 
…. 
Etc. 
YYYY-MM-DD/ HH:MM 
xx 
xx 
 
 
 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
Lower Limit of Quantitation is xx.xx (unit) 
N/A = Not Applicable. LLOQ = Lower Limit of Quantitation.  
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 76 of 138 
Listing 16.2.7.1 Adverse Events (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject 
ID 
AE 
No. 
Adverse Event Verbatim/ 
System Organ Class/ 
Preferred Term 
Start Date/Time 
End Date/Time  
(YYYY-MM-DD/ 
HH:MM)  
SAE TEAESeverity 
Relationship to Study 
Drug/ETV/TD  
Action 
Taken for 
AE 
Concomitant 
Medication 
Action Taken 
for 
Study 
treatment 
Outcome 
 
 
 
 
 
 
 
 
 
 
XXX 
xx 
XXXXXXXXXXXXXXXXXX 
ZZZZZZZZZZZZZZZZZZ 
YYYYYYYYYYYYYYYYYY 
YYYY-MM-DD/ 
HH:MM 
 YYYY-MM-DD/ 
HH:MM 
Yes Yes 
Mild 
Related/Unlikely/Possibly 
Related 
Medication 
required 
XXXXXX 
Dose Not 
Changed 
Recovered/ 
Resolved 
XXX 
xx 
XXXXXXXXXXXXXXXXXX 
ZZZZZZZZZZZZZZZZZZ 
YYYYYYYYYYYYYYYYYY 
YYYY-MM-DD/ 
HH:MM 
Ongoing 
Yes No Moderate 
Related/Unlikely/Possibly 
Related 
None 
 
N/A 
Recovering 
/ 
Resolving 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAE = Serious Adverse Event. TEAE = A treatment-emergent adverse event. ETV = Entecavir. TD = Tenofovir Disoproxil. 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 77 of 138 
Listing 16.2.7.2 Serious Adverse Events (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject 
ID 
Adverse Event 
Verbatim/ 
System Organ 
Class/ 
Preferred Term 
Start 
Date/Time  
End 
Date/Time  
(YYYY-MM-DD/ 
HH:MM)  
SAE 
SAE 
Criteria TEAE Severity 
Relationship to Study 
Drug/ETV/TD  
Action 
Taken for 
AE 
Concomitant 
Medication 
Action Taken 
for 
Study 
treatment 
Outcome 
 
 
 
 
 
 
 
 
 
 
 
XXX 
XXXXXXXXXXXXXXXXXX 
ZZZZZZZZZZZZZZZZZZ 
YYYYYYYYYYYYYYYYYY 
YYYY-MM-DD/ 
HH:MM 
 YYYY-MM-DD/ 
HH:MM 
Yes 
Life 
Threatening Yes 
Mild 
Related/Unlikely/Possibly 
Related 
Medication 
required 
XXXXXX 
Dose Not 
Changed 
Recovered/ 
Resolved 
XXX 
XXXXXXXXXXXXXXXXXX 
ZZZZZZZZZZZZZZZZZZ 
YYYYYYYYYYYYYYYYYY 
YYYY-MM-DD/ 
HH:MM 
Ongoing 
Yes 
Congenital 
Anomaly or 
Birth 
Defect 
No Moderate 
Related/Unlikely/Possibly 
Related 
None 
 
N/A 
Recovering 
/ 
Resolving 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAE = Serious Adverse Event. TEAE = A treatment-emergent adverse event. ETV = Entecavir. TD = Tenofovir Disoproxil. 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 78 of 138 
Listing 16.2.7.3 Adverse Events Leading to Study Drug Withdrawal (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject 
ID 
Adverse Event 
Verbatim/ 
System Organ Class/ 
Preferred Term 
Start 
Date/Time  
End Date/Time 
(YYYY-MM-DD/ 
HH:MM)  
SAE TEAE Severity 
Relationship to Study 
Drug/ETV/TD  
Action 
Taken for AE 
Concomitant 
Medication 
Action Taken for 
Study treatment 
Outcome 
 
 
 
 
 
 
 
 
 
 
XXX 
XXXXXXXXXXXXXXXXXX 
ZZZZZZZZZZZZZZZZZZ 
YYYYYYYYYYYYYYYYYY 
YYYY-MM-DD/ 
HH:MM 
 YYYY-MM-DD/ 
HH:MM 
Yes Yes 
Mild 
Related/Unlikely/Possibly 
Related 
Medication 
required 
XXXXXX 
Dose Not Changed 
Recovered/ 
Resolved 
XXX 
XXXXXXXXXXXXXXXXXX 
ZZZZZZZZZZZZZZZZZZ 
YYYYYYYYYYYYYYYYYY 
YYYY-MM-DD/ 
HH:MM 
Ongoing 
Yes No Moderate 
Related/Unlikely/Possibly 
Related 
None 
 
N/A 
Recovering 
/ Resolving 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAE = Serious Adverse Event. TEAE = A treatment-emergent adverse event. ETV = Entecavir. TD = Tenofovir Disoproxil. 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 
 
Programming Note: 
- Select action taken for EYO001a/Placebo = “Drug Withdrawn”. 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 79 of 138 
Listing 16.2.8.1.1 Hematology and Coagulation (ITT Set) 
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Parameter: Hemoglobin (unit) 
 
Subject ID 
Visit 
Collection  
Date/ Time  
(YYYY-MM-DD/ HH:MM) 
Actual 
Value 
Change from 
Baseline [1] 
High/Low  
Flag 
Clinically 
Significant 
Comments 
 
 
 
 
 
 
XXX 
Screening 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
 
 
Day 1 [1] 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
H 
NCS 
xxxxxxxx 
Week 2 
YYYY-MM-DD/ HH:MM 
xx 
xx 
 
 
 
Week 4 
YYYY-MM-DD/ HH:MM 
xx 
xx 
H 
 
 
Week 6 
YYYY-MM-DD/ HH:MM 
xx 
xx 
 
 
 
…. 
Etc. 
YYYY-MM-DD/ HH:MM 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. CS = Clinically Significant, NCS = Not Clinically Significant. 
 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 80 of 138 
 
Listing 16.2.8.1.2 Abnormal Hematology and Coagulation (ITT Set) 
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Parameter: Hemoglobin (unit) 
 
Subject ID 
Visit 
Collection  
Date/ Time  
(YYYY-MM-DD/ HH:MM) 
Actual 
Value 
Change from 
Baseline [1] 
High/Low  
Flag 
Clinically 
Significant 
Comments 
 
 
 
 
 
 
XXX 
Day 1 [1] 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
H 
NCS 
xxxxxxxx 
Week 2 
YYYY-MM-DD/ HH:MM 
xx 
xx 
L 
NCS 
 
Week 4 
YYYY-MM-DD/ HH:MM 
xx 
xx 
H 
CS 
 
…. 
Etc. 
YYYY-MM-DD/ HH:MM 
xx 
xx 
H 
NCS 
 
 
 
 
 
 
 
 
 [1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. CS = Clinically Significant, NCS = Not Clinically Significant. 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 81 of 138 
 
Listing 16.2.8.2.1 Serum Chemistry (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Parameter: Sodium (unit) 
 
Subject ID 
Visit 
Collection  
Date/ Time  
(YYYY-MM-DD/ HH:MM) 
Actual 
Value 
Change from 
Baseline [1] 
High/Low  
Flag  
Clinically 
Significant 
Comments 
 
 
 
 
 
 
XXX 
Screening 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
 
 
Day 1 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
H 
NCS 
xxxxxxxx 
Week 2 
YYYY-MM-DD/ HH:MM 
xx 
xx 
 
 
 
Week 4 
YYYY-MM-DD/ HH:MM 
xx 
xx 
H 
 
 
Week 6 
YYYY-MM-DD/ HH:MM 
xx 
xx 
 
 
 
…. 
Etc. 
YYYY-MM-DD/ HH:MM 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. CS = Clinically Significant, NCS = Not Clinically Significant. 
 
Programming note: 
For AST, ALT, total BILI and GGT, to present the CTCAE Grade with High /Low Flag. For example, H – CTCAE Grade 1 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 82 of 138 
Listing 16.2.8.2.2 Abnormal Serum Chemistry (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Parameter: Sodium (unit) 
 
Subject ID 
Visit 
Collection  
Date/ Time  
(YYYY-MM-DD/ HH:MM) 
Actual 
Value 
Change from 
Baseline[1] 
High/Low  
Flag 
Clinically 
Significant 
Comments 
 
 
 
 
 
 
XXX 
Day 1 1 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
H 
NCS 
xxxxxxxx 
Week 2 
YYYY-MM-DD/ HH:MM 
xx 
xx 
L 
 
 
Week 4 
YYYY-MM-DD/ HH:MM 
xx 
xx 
H 
 
 
Week 6 
YYYY-MM-DD/ HH:MM 
xx 
xx 
L 
 
 
…. 
Etc. 
YYYY-MM-DD/ HH:MM 
xx 
xx 
L 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. CS = Clinically Significant, NCS = Not Clinically Significant. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 83 of 138 
 
Listing 16.2.8.3.1 Lipid and Metabolic Profile (ITT Set) 
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Parameter: Serum Cholesterol (unit) 
 
Subject ID 
Visit 
Collection  
Date/ Time  
(YYYY-MM-DD/ HH:MM) 
Actual 
Value 
Change from 
Baseline [1] 
Fasting 
High/Low  
Flag 
Clinically 
Significant 
Comments 
 
 
 
 
 
 
 
XXX 
Screening 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
Yes 
 
 
Day 1 [1] 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
No 
H 
NCS 
xxxxxxxx 
Week 2 
YYYY-MM-DD/ HH:MM 
xx 
xx 
No 
 
 
 
Week 4 
YYYY-MM-DD/ HH:MM 
xx 
xx 
No 
H 
 
 
Week 6 
YYYY-MM-DD/ HH:MM 
xx 
xx 
No 
 
 
 
…. 
Etc. 
YYYY-MM-DD/ HH:MM 
xx 
xx 
No 
 
 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. CS = Clinically Significant, NCS = Not Clinically Significant. 
 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 84 of 138 
 
Listing 16.2.8.3.2 Abnormal Lipid and Metabolic Profile (ITT Set) 
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Parameter: Serum Cholesterol (unit) 
 
Subject ID 
Visit 
Collection  
Date/ Time  
(YYYY-MM-DD/ HH:MM) 
Actual 
Value 
Change from 
Baseline [1] 
Fasting 
High/Low  
Flag 
Clinically 
Significant 
Comments 
 
 
 
 
 
 
 
XXX 
Day 1 [1] 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
No 
H 
NCS 
xxxxxxxx 
Week 2 
YYYY-MM-DD/ HH:MM 
xx 
xx 
No 
H 
NCS 
 
Week 4 
YYYY-MM-DD/ HH:MM 
xx 
xx 
No 
H 
NCS 
 
Week 6 
YYYY-MM-DD/ HH:MM 
xx 
xx 
No 
L 
NCS 
 
…. 
Etc. 
YYYY-MM-DD/ HH:MM 
xx 
xx 
No 
L 
NCS 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. CS = Clinically Significant, NCS = Not Clinically Significant. 
 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 85 of 138 
 
Listing 16.2.8.4.1 Urinalysis (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Parameter: Glucose (unit) 
 
Subject ID 
Visit 
Collection  
Date/ Time  
(YYYY-MM-DD/ HH:MM) 
Actual 
Value 
Clinically Significant 
 
 
 
XXX 
Screening 
YYYY-MM-DD/ HH:MM 
xxxxxxx 
 
Day 1[1] 
YYYY-MM-DD/ HH:MM 
xxxxxxx 
NCS 
Week 4 
YYYY-MM-DD/ HH:MM 
xxxxxxx 
 
Week 8 
YYYY-MM-DD/ HH:MM 
xxxxxxx 
 
…. 
Etc. 
YYYY-MM-DD/ HH:MM 
xxxxxxx 
 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
CS = Clinically Significant, NCS = Not Clinically Significant. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 86 of 138 
Listing 16.2.8.4.2 Urine Microscopy (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Parameter: Parameter (unit) 
 
Subject ID 
Visit 
Collection  
Date/ Time  
(YYYY-MM-DD/ HH:MM) 
Actual 
Value 
Clinically Significant 
 
 
 
XXX 
Screening 
YYYY-MM-DD/ HH:MM 
xxxxxxx 
 
Day 1 
YYYY-MM-DD/ HH:MM 
xxxxxxx 
NCS 
Week 4 
YYYY-MM-DD/ HH:MM 
xxxxxxx 
 
Etc. 
YYYY-MM-DD/ HH:MM 
xxxxxxx 
 
…. 
 
 
 
 
 
 
CS = Clinically Significant, NCS = Not Clinically Significant. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 87 of 138 
Listing 16.2.9.1 Vital Signs (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Parameter: Heart Rate (bpm) 
 
Subject ID 
Visit 
Assessment  
Date/ Time  
(YYYY-MM-DD/ HH:MM) 
Actual 
Value 
Change from 
Baseline[1] 
Clinically Significant 
 
 
 
 
XXX 
Screening 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
 
Day 1 [1] 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
NCS 
Week 2 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
 
Week 4  
YYYY-MM-DD/ HH:MM 
xx 
xx 
 
Week 6 
YYYY-MM-DD/ HH:MM 
xx 
xx 
 
Etc. 
YYYY-MM-DD/ HH:MM 
xx 
xx 
 
…. 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. CS = Clinically Significant, NCS = Not Clinically Significant. 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 88 of 138 
Listing 16.2.9.2 12-Lead ECG (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Parameter: Heart Rate (beats/min) 
 
Subject ID Visit 
Assessment  
Date/ Time  
(YYYY-MM-DD/ HH:MM) 
Actual Value 
Change from 
Baseline[1] 
Abnormal 
Description 
confirmed by a 
cardiologist 
Comments 
 
 
 
 
 
 
XXX 
Screening 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
 
 
 
Day 1 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
 
 
 
Week 4 
YYYY-MM-DD/ HH:MM 
xx 
xx 
 
 
 
Week 8 
YYYY-MM-DD/ HH:MM 
xx 
xx 
 
 
 
Etc. 
YYYY-MM-DD/ HH:MM 
xx 
xx 
 
 
 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. CS = Clinically Significant, NCS = Not Clinically Significant. WCS = Worst Case Scenario. 
 
 
Programming Note: 
-  
- In addition, the ECG finding will be included as a separate parameter. And “Abnormal Description” and “Was the clinically significant abnormality confirmed by a 
cardiologist” will be specified if the result is abnormal. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 89 of 138 
Listing 16.2.9.3 Physical Examination (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject ID 
Visit 
Assessment Date  
(YYYY-MM-DD) 
Body System 
Result 
Description of Abnormality 
 
 
 
 
 
 
XXX 
Screening 
YYYY-MM-DD 
General Appearance 
Normal 
 
 
 
 
EYES/EARS/NOSE/THROAT 
Normal 
 
 
 
 
HEAD AND NECK 
Normal 
 
 
 
 
… 
Normal 
 
 
 
 
EXTREMITIES 
Normal 
 
 
 
 
Other - XXXXXXXX 
Normal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
YYYY-MM-DD 
Symptom Directed Physical 
Examination 
Normal 
 
 
 
 
… 
Normal 
 
 
 
 
 
 
 
… 
Etc. 
 
 
 
 
 
 
 
 
 
 
CS = Clinically Significant, NCS = Not Clinically Significant. 
 
Programming Note: 
- A complete physical examination will be performed at screening. Brief, symptom-directed physical examinations will be performed on all other study visits. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 90 of 138 
Listing 16.2.9.4 Liver Fibrosis and Inflammation Assessment (ITT Set)  
 
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Parameter: XXXX (unit) 
 
Subject 
ID 
Visit 
Assessment Sample Collected/ No - 
Reason   
Assessment Date/ Time 
(YYYY-MM-DD/ HH:MM) 
Actual 
Value 
Change from 
Baseline[1] 
 
 
 
 
 
 
XXX 
Day 1 [1] 
Yes 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
 
Week 4 
 No - xxxxxxxxxxxx 
YYYY-MM-DD/ HH:MM 
xx 
xx 
 
Week 8 
Yes 
YYYY-MM-DD/ HH:MM 
xx 
xx 
 
Etc. 
Yes 
YYYY-MM-DD/ HH:MM 
xx 
xx 
 
 
 
 
 
 
XXX 
Day 1 
Yes 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
….. 
….. 
 
 
 
 
 
 
 
 
 
 
N/A = Not Applicable. 
 
 
Programming Note: 
- These parameter (ALT, AST, AST/ALT ratio, high sensitivity C-reactive protein, interleukin 6, tumour necrosis factor alpha, procollagen type III N terminal peptide (Pro 
C3), tissue inhibitor of metalloproteinases-1) will be included. 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 91 of 138 
Listing 16.2.9.5 Liver Imaging (ITT Set)  
 
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject 
ID 
Visit 
Was liver 
imaging done? / 
No - Reason  
Method 
Assessment Date/ 
Time 
(YYYY-MM-DD/ 
HH:MM) 
Result 
Abnormal 
Description 
Risk factor 
 
 
 
 
 
 
 
 
XXX 
Screening 
Yes 
CT 
YYYY-MM-DD/ HH:MM 
Normal 
 
Xxxx,yyyy,zzzz 
 
Week 40 (EOS) 
 No – xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXX 
Screening 
Yes 
US 
YYYY-MM-DD/ HH:MM 
Abnormal NCS 
xxxxxxx 
 
….. 
….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N/A = Not Applicable. CT = Computed Tomography. US = Ultrasonography. MRI = Magnetic Resonance Imaging.  
CS = Clinically Significant. NCS = Not Clinically Significant. 
 
 
Programming Note: 
- in the risk factor, to present all that apply and separated by a "," 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 92 of 138 
 
Listing 16.2.9.6 Pregnancy Test Results (ITT Set) 
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject ID 
Visit 
Was Test Performed – 
Reason Not Performed 
Collection Date/Time 
(YYYY-MM-DD/ HH:MM) 
Type 
Result 
 
 
 
 
 
 
XXX 
Screening 
Yes 
YYYY-MM-DD/ HH:MM 
Serum 
Negative 
 
Day 1 
Yes 
YYYY-MM-DD/ HH:MM 
Urine 
Negative 
 
Week 4 
No - xxxx 
 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
XXX 
Screening 
Yes 
YYYY-MM-DD/ HH:MM 
Serum 
Negative 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
Programming Note: 
- A serum hCG test will be performed at Screening and EOS/ET Visits in WOCBP only. Urine hCG tests will be performed at all other visits 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 93 of 138 
Listing 16.2.9.7 Pruritus Assessment – 5-D Pruritus Scale (ITT Set)  
 
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Domains: Duration  
 
Subject ID 
Visit 
Assessment Assessed – Reason 
no Performed 
Assessment Date 
(YYYY-MM-DD) 
Actual 
Value 
Change from 
Baseline [1] 
 
 
 
 
XXX 
Day 1 [1] 
Yes 
YYYY-MM-DD 
xx 
N/A 
Week 2 
Yes 
YYYY-MM-DD 
xx 
xx 
Week 4 
No - xxxxx 
YYYY-MM-DD 
xx 
xx 
Etc. 
 
 
 
 
 
 
 
 
…. 
 
 
 
 
 
 
 
 
N/A = Not Applicable. 
 
Programming Note: 
- repeated for 5 domains – Duration, Degree, Direction, disability and distribution and total score.  
- Single-item domain scores (duration, degree, and direction) are equal to the value indicated below the response choice (range 1-5).   
- The score for the disability domain is achieved by taking the highest score on any of the four items.  
 - For the distribution domain, the number of affected body parts is tallied (potential sum 0-16) and the sum is sorted into five scoring bins: 
sum of 0-2 = 
1 
sum of 3-5 = 
2 
sum of 6-10 = 
3 
sum of 11-13 = 
4 
sum of 14-16 = 
5. 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 94 of 138 
Listing 16.2.9.8 Pruritus Assessment – Visual Analogue Scale (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject 
ID 
Visit 
Assessment Assessed – Reason no 
Performed  
Assessment Date 
(YYYY-MM-DD) 
Actual 
Value 
Change from 
Baseline[1] 
 
 
 
 
 
 
XXX 
Day 1 [1] 
Yes 
YYYY-MM-DD 
xx 
N/A 
 
Week 2 
 No - xxxxxxxxxxxx 
 
 
 
 
Week 4 
Yes 
YYYY-MM-DD 
xx 
xx 
 
Week 6 
Yes 
YYYY-MM-DD 
xx 
xx 
 
Etc. 
Yes 
YYYY-MM-DD 
xx 
xx 
 
 
 
 
 
 
XXX 
Day 1 
Yes 
YYYY-MM-DD 
xx 
N/A 
….. 
….. 
 
 
 
 
 
 
 
 
 
 
N/A = Not Applicable. 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 95 of 138 
Listing 16.2.9.9 Stopping Rule (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject ID 
Visit 
Participant Met any of the following 
stopping rules 
Stopping Rules Met 
 
 
 
 
XXX 
Day 1 
Yes 
Stopping rules: 01, 02,xx 
 
Week 2 
Yes 
Stopping rules: 05, 06, 08 
…. 
…. 
 
 
 
 
 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 96 of 138 
 
Listing 16.2.10.1 Prior Medication (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject ID CM Id 
Concomitant Medication Therapy/ 
Anatomical Therapeutic Class (ATC) 
[Level 3]/  
Preferred Term (PT) 
Indication 
Start Date  
(YYYY-MM-DD)  
End Date 
(YYYY-MM-DD) 
Dose 
Unit 
Frequency 
Route 
Reason for Use 
 
 
 
 
 
 
 
 
XXX 
xx 
XXXXXXXXXXXXXXXXXXXXXX/ 
ZZZZZZZZZZZZZZZZZZZZZZ/ 
YYYYYYYYYYYYYYYYYYYYYY 
zzzzzzzz 
YYYY-MM-DD/ 
YYYY-MM-DD 
XX 
Unit 
YYYYYY 
ZZZZZ 
xxx 
xx 
XXXXXXXXXXXXXXXXXXXXXX/ 
ZZZZZZZZZZZZZZZZZZZZZZ/ 
YYYYYYYYYYYYYYYYYYYYYY 
zzzzzzzz 
YYYY-MM-DD/ 
YYYY-MM-DD 
XX 
Unit 
YYYYYY 
ZZZZZ 
xxx 
… 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior medications are defined as any medication where the use was stopped prior to the first administration of the study medication. 
 
World Health Organization-Drug Dictionary (WHO-DD) Version xx, YYYY 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 97 of 138 
Listing 16.2.10.2 Concomitant Medication (ITT Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
Subject ID CM Id 
Concomitant Medication Therapy/ 
Anatomical Therapeutic Class (ATC) 
[Level 3]/  
Preferred Term (PT) 
Indication 
Start Date  
(YYYY-MM-DD)  
End Date 
(YYYY-MM-DD) 
Dose 
Unit 
Frequency 
Route 
Reason for Use 
 
 
 
 
 
 
 
 
XXX 
xx 
XXXXXXXXXXXXXXXXXXXXXX/ 
ZZZZZZZZZZZZZZZZZZZZZZ/ 
YYYYYYYYYYYYYYYYYYYYYY 
zzzzzzzz 
YYYY-MM-DD/ 
YYYY-MM-DD 
XX 
Unit 
YYYYYY 
ZZZZZ 
xxx 
xx 
XXXXXXXXXXXXXXXXXXXXXX/ 
ZZZZZZZZZZZZZZZZZZZZZZ/ 
YYYYYYYYYYYYYYYYYYYYYY 
zzzzzzzz 
YYYY-MM-DD/ 
YYYY-MM-DD 
XX 
Unit 
YYYYYY 
ZZZZZ 
xxx 
… 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medications are defined as any medication (other than the study drug) that was used at least once after the first administration of 
the study drug. 
 
World Health Organization-Drug Dictionary (WHO-DD) Version xx, YYYY 
 
 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 98 of 138 
Figure 14.2.12.1 Series Plot of Mean Actual Value over Time for PD Markers (PD Set)  
 
Parameter: FGF-19 (unit) 
 
 
 
Source Table 14.2.12 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent the mean of PD markers (unit) 
All treatments will be represented on a single page. Each treatment group will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 99 of 138 
Figure 14.2.12.2 Series Plot of Mean Actual Value over Time for PD Markers (PD Set)  
 
Parameter: FGF-19 (unit) 
 
 
 
Source Table 14.2.12 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent the mean of PD markers (unit) 
All treatments will be represented on a single page. Each treatment group will be presented as a distinct line type. 
For baseline visit, the mean of CFB will set to zero. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 100 of 138 
Figure 14.2.12.3 Series Plot of Mean % Change from Baseline over Time for PD Markers (PD Set)  
 
Parameter: FGF-19 (unit) 
 
 
 
Source Table 14.2.12 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent the mean % change from baseline for each PD marker (unit) 
All treatments will be represented on a single page. Each treatment group will be presented as a distinct line type. 
For baseline visit, the mean %of CFB will set to zero. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 101 of 138 
Figure 14.2.12.4.1 Boxplot of HBsAg (IU/mL) over Time by Treatment (Safety Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Table: 14.2.1.3.2 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent the HBsAg (IU/mL) 
Box Plot will show first quartile, median, third quartile, minimum and maximum. 
All participants per treatment group (one page for each treatment group) will be represented on a single page.  
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 102 of 138 
Figure 14.2.12.4.2 Boxplot of HBsAg (IU/mL) over Time by HBeAg (Safety Set)  
 
HBeAg: Positive  
 
 
 
 
 
 
Source Table: 14.2.1.3.2 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent the HBsAg (IU/mL) 
Box Plot will show first quartile, median, third quartile, minimum and maximum. 
All participants per HBeAg status (positive and negative) will be represented on a single page.  
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 103 of 138 
Figure 14.2.12.4.3 Boxplot of HBsAg (IU/mL) over Time by A Genotype (Safety Set)  
 
A Genotype: Yes  
 
 
 
 
 
 
Source Table: 14.2.1.3.2 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent the HBsAg (IU/mL) 
Box Plot will show first quartile, median, third quartile, minimum and maximum. 
All participants per A genotype (Yes /No) will be represented on a single page.  
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 104 of 138 
Figure 14.2.12.5.1 Boxplot of HBsAg (IU/mL) Change from Baseline by Treatment (Safety Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Table: 14.2.1.3.2 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent the HBsAg (IU/mL) change from baseline 
Box Plot will show first quartile, median, third quartile, minimum and maximum. 
All participants per treatment group (one page for each treatment group) will be represented on a single page.  
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 105 of 138 
Figure 14.2.12.5.2 Boxplot of HBsAg (IU/mL) Change from Baseline by HBeAg (Safety Set)  
 
HBeAg: Positive  
 
 
 
 
 
 
Source Table: 14.2.1.3.2 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent the HBsAg (IU/mL) change from baseline 
Box Plot will show first quartile, median, third quartile, minimum and maximum. 
All participants per HBeAg status (positive and negative) will be represented on a single page.  
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 106 of 138 
Figure 14.2.12.5.3 Boxplot of HBsAg (IU/mL) Change from Baseline by A Genotype (Safety Set)  
 
A Genotype: Yes  
 
 
 
 
 
 
Source Table: 14.2.1.3.2 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent the HBsAg (IU/mL) Change from Baseline 
Box Plot will show first quartile, median, third quartile, minimum and maximum. 
All participants per A genotype (Yes /No) will be represented on a single page.  
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 107 of 138 
 
Figure 14.2.12.6.1 Boxplot of HBV DNA (Log IU/mL) over Time by Treatment (Safety Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Listing: 16.2.6.2 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent the HBV DNA (Log IU/mL) 
Box Plot will show first quartile, median, third quartile, minimum and maximum. 
All participants per treatment group (one page for each treatment group) will be represented on a single page.  
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 108 of 138 
Figure 14.2.12.6.2 Boxplot of HBV DNA (Log IU/mL) over Time by HBeAg (Safety Set)  
 
HBeAg: Positive  
 
 
 
 
 
 
Source Listing: 16.2.6.2 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent the HBV DNA (Log IU/mL) 
Box Plot will show first quartile, median, third quartile, minimum and maximum. 
All participants per HBeAg status (positive and negative) will be represented on a single page.  
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 109 of 138 
Figure 14.2.12.6.3 Boxplot of HBV DNA (Log IU/mL) over Time by A Genotype (Safety Set)  
 
A Genotype: Yes  
 
 
 
 
 
 
Source Listing: 16.2.6.2 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent HBV DNA (Log IU/mL) 
Box Plot will show first quartile, median, third quartile, minimum and maximum. 
All participants per A genotype (Yes /No) will be represented on a single page.  
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 110 of 138 
Figure 14.2.12.7.1 Boxplot of HBV DNA (Log IU/mL) Change from Baseline by Treatment (Safety Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Listing: 16.2.6.2 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent the HBV DNA (Log IU/mL) change from baseline 
Box Plot will show first quartile, median, third quartile, minimum and maximum. 
All participants per treatment group (one page for each treatment group) will be represented on a single page.  
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 111 of 138 
Figure 14.2.12.7.2 Boxplot of HBV DNA (Log IU/mL) Change from Baseline by HBeAg (Safety Set)  
 
HBeAg: Positive  
 
 
 
 
 
 
Source Listing: 16.2.6.2 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent the HBV DNA (Log IU/mL) change from baseline 
Box Plot will show first quartile, median, third quartile, minimum and maximum. 
All participants per HBeAg status (positive and negative) will be represented on a single page.  
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 112 of 138 
Figure 14.2.12.7.3 Boxplot of HBV DNA (Log IU/mL) Change from Baseline by A Genotype (Safety Set)  
 
A Genotype: Yes  
 
 
 
 
 
Source Listing: 16.2.6.2 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent the HBV DNA (Log IU/mL) Change from Baseline 
Box Plot will show first quartile, median, third quartile, minimum and maximum. 
All participants per A genotype (Yes /No) will be represented on a single page.  
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 113 of 138 
Figure 14.2.12.8.1 Series Plot of Individual Actual Value over Time for HBsAg (IU/mL) by HBeAg (Safety Set)  
 
HBeAg: Positive 
 
 
 
Source Listing: 16.2.6.1 
 
Programming Note: 
The x-axis will represent the actual study time in days. 
The y-axis will represent the HBsAg (IU/mL) 
All participants per HBeAg status (positive or negative) (one page for HBeAg status) will be represented on a single page. Each subject will be presented as a distinct line 
type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 114 of 138 
Figure 14.2.12.8.2 Series Plot of Individual Actual Value over Time for HBsAg (IU/mL) by A Genotype (Safety Set)  
 
A Genotype: Yes 
 
 
 
Source Listing: 16.2.6.1 
 
Programming Note: 
The x-axis will represent the actual study time in days. 
The y-axis will represent the HBsAg (IU/mL) 
All participants per A Genotype (Yes/No) (one page for A Genotype) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 115 of 138 
Figure 14.2.12.9.1 Series Plot of Individual Change from Baseline Value for HBsAg (IU/mL) by HBeAg (Safety Set)  
 
HBeAg: Positive 
 
 
 
Source Listing: 16.2.6.1 
 
Programming Note: 
The x-axis will represent the actual study time in days. 
The y-axis will represent the HBsAg (IU/mL) Change from baseline 
All participants per HBeAg status (positive or negative) (one page for HBeAg status) will be represented on a single page. Each subject will be presented as a distinct line 
type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 116 of 138 
Figure 14.2.12.9.2 Series Plot of Individual Change from Baseline Value for HBsAg (IU/mL) by A Genotype (Safety Set)  
 
A Genotype: Yes 
 
 
 
Source Listing: 16.2.6.1 
 
Programming Note: 
The x-axis will represent the actual study time in days. 
The y-axis will represent the HBsAg (IU/mL) Change from baseline  
All participants per A Genotype (Yes/No) (one page for A Genotype) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 117 of 138 
Figure 14.2.12.10.1 Series Plot of Individual Actual Value over Time for HBV DNA (Log IU/mL) by HBeAg (Safety Set)  
 
HBeAg: Positive 
 
 
 
Source Listing: 16.2.6.2 
 
Programming Note: 
The x-axis will represent the actual study time in days. 
The y-axis will represent the HBV DNA (Log IU/mL) 
All participants per HBeAg status (positive or negative) (one page for HBeAg status) will be represented on a single page. Each subject will be presented as a distinct line 
type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 118 of 138 
Figure 14.2.12.10.2 Series Plot of Individual Actual Value over Time for HBV DNA (Log IU/mL) by A Genotype (Safety Set)  
 
A Genotype: Yes 
 
 
 
Source Listing: 16.2.6.2 
 
Programming Note: 
The x-axis will represent the actual study time in days. 
The y-axis will represent the HBV DNA (Log IU/mL)  
All participants per A Genotype (Yes/No) (one page for A Genotype) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 119 of 138 
Figure 14.2.12.11.1 Series Plot of Individual Change from Baseline Value for HBV DNA (Log IU/mL) by HBeAg (Safety Set)  
 
HBeAg: Positive 
 
 
 
Source Listing: 16.2.6.2 
 
Programming Note: 
The x-axis will represent the actual study time in days. 
The y-axis will represent the HBV DNA (Log IU/mL) Change from baseline 
All participants per HBeAg status (positive or negative) (one page for HBeAg status) will be represented on a single page. Each subject will be presented as a distinct line 
type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 120 of 138 
Figure 14.2.12.11.2 Series Plot of Individual Change from Baseline Value for HBV DNA (Log IU/mL) by A Genotype (Safety Set)  
 
A Genotype: Yes 
 
 
 
Source Listing: 16.2.6.2 
 
Programming Note: 
The x-axis will represent the actual study time in days. 
The y-axis will represent the HBV DNA (Log IU/mL) Change from baseline  
All participants per A Genotype (Yes/No) (one page for A Genotype) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 121 of 138 
Figure 14.3.4.2.3 Individual ALT over Time (Safety Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Listing: 16.2.8.2.1 
 
Programming Note: 
The x-axis will represent the scheduled and unscheduled study time in days. 
The y-axis will represent the ALT (unit) 
All participants per treatment group (one page for each treatment group) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 122 of 138 
Figure 14.3.4.2.4 Individual ALT Change from Baseline (Safety Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Listing: 16.2.8.2.1 
 
Programming Note: 
The x-axis will represent the scheduled and unscheduled study time in days. 
The y-axis will represent the ALT (unit) 
All participants per treatment group (one page for each treatment group) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 123 of 138 
Figure 14.3.4.2.5 Boxplot of ALT over Time by Treatment (Safety Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Table: 14.3.4.2.1 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent the ALT (unit) 
Box Plot will show first quartile, median, third quartile, minimum and maximum. 
All participants per treatment group (one page for each treatment group) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 124 of 138 
Figure 14.3.4.2.6 Individual AST over Time (Safety Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Listing: 16.2.8.2.1 
 
Programming Note: 
The x-axis will represent the scheduled and unscheduled study time in days. 
The y-axis will represent the AST (unit) 
All participants per treatment group (one page for each treatment group) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 125 of 138 
Figure 14.3.4.2.7 Individual AST Change from Baseline (Safety Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Listing: 16.2.8.2.1 
 
Programming Note: 
The x-axis will represent the scheduled and unscheduled study time in days. 
The y-axis will represent the AST (unit) 
All participants per treatment group (one page for each treatment group) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 126 of 138 
Figure 14.3.4.2.8 Boxplot of AST over Time by Treatment (Safety Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Table: 14.3.4.2.1 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent the AST (unit) 
Box Plot will show first quartile, median, third quartile, minimum and maximum. 
All participants per treatment group (one page for each treatment group) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 127 of 138 
Figure 14.3.4.2.9 Individual ALP over Time (Safety Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Listing: 16.2.8.2.1 
 
Programming Note: 
The x-axis will represent the scheduled and unscheduled study time in days. 
The y-axis will represent the ALP (unit) 
All participants per treatment group (one page for each treatment group) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 128 of 138 
Figure 14.3.4.2.10 Individual ALP Change from Baseline (Safety Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Listing: 16.2.8.2.1 
 
Programming Note: 
The x-axis will represent the scheduled and unscheduled study time in days. 
The y-axis will represent the ALP (unit) 
All participants per treatment group (one page for each treatment group) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 129 of 138 
Figure 14.3.4.2.11 Boxplot of ALP over Time by Treatment (Safety Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Table: 14.3.4.2.1 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent the ALP (unit) 
Box Plot will show first quartile, median, third quartile, minimum and maximum. 
All participants per treatment group (one page for each treatment group) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 130 of 138 
Figure 14.3.4.2.12 Individual GGT over Time (Safety Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Listing: 16.2.8.2.1 
 
Programming Note: 
The x-axis will represent the scheduled and unscheduled study time in days. 
The y-axis will represent the GGT (unit) 
All participants per treatment group (one page for each treatment group) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 131 of 138 
Figure 14.3.4.2.13 Individual GGT Change from Baseline (Safety Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Listing: 16.2.8.2.1 
 
Programming Note: 
The x-axis will represent the scheduled and unscheduled study time in days. 
The y-axis will represent the GGT (unit) 
All participants per treatment group (one page for each treatment group) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 132 of 138 
Figure 14.3.4.2.14 Boxplot of GGT over Time by Treatment (Safety Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Table: 14.3.4.2.1 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent the GGT (unit) 
Box Plot will show first quartile, median, third quartile, minimum and maximum. 
All participants per treatment group (one page for each treatment group) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 133 of 138 
Figure 14.3.4.2.15 Individual Total Bilirubin over Time (Safety Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Listing: 16.2.8.2.1 
 
Programming Note: 
The x-axis will represent the scheduled and unscheduled study time in days. 
The y-axis will represent the Total Bilirubin (unit) 
All participants per treatment group (one page for each treatment group) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 134 of 138 
Figure 14.3.4.2.16 Individual Total Bilirubin Change from Baseline (Safety Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Listing: 16.2.8.2.1 
 
Programming Note: 
The x-axis will represent the scheduled and unscheduled study time in days. 
The y-axis will represent the Total Bilirubin (unit) 
All participants per treatment group (one page for each treatment group) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 135 of 138 
Figure 14.3.4.2.17 Boxplot of Total Bilirubin over Time by Treatment (Safety Set)  
 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Table: 14.3.4.2.1 
 
Programming Note: 
The x-axis will represent the scheduled study time in days. 
The y-axis will represent the Total Bilirubin (unit) 
Box Plot will show first quartile, median, third quartile, minimum and maximum. 
All participants per treatment group (one page for each treatment group) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 136 of 138 
Figure 14.3.4.2.18 Individual Lipid Parameters over Time (Safety Set)  
 
Parameter: total cholesterol 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Listing: 16.2.8.2.1 
 
Programming Note: 
The x-axis will represent the scheduled and unscheduled study time in days. 
The y-axis will represent the lipid parameters (unit) accordingly 
All participants per treatment group (one page for each treatment group) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 137 of 138 
Figure 14.3.4.2.19 Individual HBV DNA versus ALT at Each Visit (Safety Set)  
 
Visit: Screening 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Listing: 16.2.8.2.1 
 
Programming Note: 
The x-axis will represent the HBV DNA (unit). 
The y-axis will represent the ALT (unit)  
All participants per treatment group per scheduled visit will be represented on a single page. Each subject will be presented as a distinct line type. 
Only include the scheduled visits with both HBV DNA and ALT values. 
 
 


Sponsor: Enyo Pharma SA 
Data Cut-Off: YYYY-MM-DD 
Protocol: EYP001-201 
 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 138 of 138 
Figure 14.3.4.2.20 Individual HBV DNA versus AST at Each Visit (Safety Set)  
 
Visit: Screening 
Group 1: EYP001a 200 mg QD + NA daily  
 
 
 
 
 
 
Source Listing: 16.2.8.2.1 
 
Programming Note: 
The x-axis will represent the HBV DNA (unit). 
The y-axis will represent the AST (unit)  
All participants per treatment group per scheduled visit will be represented on a single page. Each subject will be presented as a distinct line type. 
Only include the scheduled visits with both HBV DNA and AST values.