A Randomized, Double Blind, Placebo Controlled, Parallel Group, Multiple Dose, Induction Study to Evaluate the Safety, Tolerability and Optimal Dose of ABX464 Compared With Placebo in Patients With Moderate to Severe Ulcerative Colitis Who Have Inadequate Response, Loss of Response, or Intolerance With at Least One of the Following Agents: Immunosuppressant Treatment (i.e. Azathioprine, 6-mercaptopurine, Methotrexate), Tumor Necrosis Factor Alpha [TNF-α] Inhibitors, Vedolizumab, JAK Inhibitors and/or Corticosteroid Treatment
Phase: PHASE2
Conditions: Ulcerative Colitis
Sponsor: Abivax S.A.

 
 
 
 
 
 
 
 
 
 
CLINICAL STUDY PROTOCOL 
ABX464-103 
 
Sponsor: 
ABIVAX 
 
5, rue de la Baume 
 
 75008 Paris 
 
FRANCE 
 
Investigational medicinal product: 
 
Not Available  
Product code: 
 
ABX464 
Study Title: 
 
A randomized, double blind, placebo controlled, parallel group, multiple 
dose, induction study to evaluate the safety, tolerability and optimal dose of 
ABX464 compared with placebo in patients with moderate to severe 
ulcerative colitis who have inadequate response, loss of response, or 
intolerance with at least one of the following agents: immunosuppressant 
treatment (i.e. azathioprine, 6-mercaptopurine, methotrexate), tumor 
necrosis factor alpha [TNF-α] inhibitors, vedolizumab, JAK inhibitors and/or 
corticosteroid treatment. 
EudraCT number: 
 
2018-003558-26 
IND Number: 
 
 
141.396 
Study code: 
 
 
ABX464-103 
 
Version number: 
 
3.0 
Release date:  
 
June 01st, 2020 
 
CONFIDENTIALITY STATEMENT 
Information and data contained herein are proprietary and confidential. 
This information should not be disclosed to any third party without the prior written consent of ABIVAX 
 
 

ABIVAX 
Clinical Study Protocol 
Study code: ABX464-103 
 
01- June -2020 
V3.0 
Page 2 / 64 
 
CLINICAL STUDY PROTOCOL 
Study code 
ABX464-103 
Investigational medicinal 
product code 
ABX464 
EudraCT number 
2018-003558-26 
IND Number  
141.396 
Detailed Title 
A randomized, double blind, placebo controlled, parallel group, multiple 
dose, induction study to evaluate the safety, tolerability and optimal dose of 
ABX464 compared with placebo in patients with moderate to severe 
ulcerative colitis who have inadequate response, loss of response, or 
intolerance with at least one of the following agents: immunosuppressant 
treatment (i.e. azathioprine, 6-mercaptopurine, methotrexate), tumor 
necrosis factor alpha [TNF-α] inhibitors, vedolizumab, JAK inhibitors and/or 
corticosteroid treatment. 
Study Phase 
Phase IIb 
Coordinating Investigator 
Prof. Severine Vermeire 
University Hospitals Leuven - campus Gasthuisberg 
Gastroenterology 
UZ Herestraat 49 - box 7003 08 
3000 Leuven 
Belgium 
Sponsor 
ABIVAX 
5 rue de la Baume 
75008 Paris 
Tel: +33 (0) 1 53 83 08 41 
Fax: +33 (0) 1 53 83 07 48 
Date/Version 
June 01st, 2020 / Version 3.0 
 

ABIVAX 
Clinical Study Protocol 
Study code: ABX464-103 
 
01- June -2020 
V3.0 
Page 3 / 64 
CONTACTS 
Sponsor 
ABIVAX 
5 rue de la Baume 
75008 PARIS - France 
 
VP, Chief Medical Officer 
Tel: +
 
 
VP, Clinical Operations 
Tel: +
 
 
Coordinating investigator 
Prof. Severine Vermeire 
University Hospitals Leuven - campus Gasthuisberg 
Gastroenterology 
Herestraat 49 - box 7003 08 
3000 Leuven - Belgium 
Central Laboratory 
Eurofins Central Laboratory  
Bergschot 71  
4817 PA Breda - The Netherlands 
Imaging Central Review 
Bioclinica  
72 Hammersmith Road, 6th Floor  
London, W14 8UD- United Kingdom 
Study Conduct, Data management 
and Statistical Analysis 
IQVIA 
151-161 Boulevard Victor Hugo 
93588 Saint Ouen Cedex - France 
miRNA-124 determination  
Biogazelle 
Technologiepark-Zwijnaarde 82,  
9052 Gent - Belgique 
Histopathology (RHI) 
Cerba Research (Histalim) 
126, rue Emile Baudot 
Le Millénaire – 34000 Montpellier -France 
Pharmacokinetics  
Charles River (Bioanalyses) 
ZI de Brais 
1 Rue Graham Bell 
BP 40309 44605 Saint-Nazaire - France 
Pharmacovigilance 
IntuVigilance Limited 
Scotsbridge House, Scots Hill 
Rickmansworth WD3 3BB 
Hertfordshire, UK 
 
 

ABIVAX 
Clinical Study Protocol 
Study code: ABX464-103 
 
01- June -2020 
V3.0 
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INVESTIGATOR AGREEMENT PAGE 
 
EudraCT number 
 
2018-003558-26 
IND Number 
 
 
141.396 
 
Detailed Title:  
A randomized, double blind, placebo controlled, parallel group, multiple 
dose, induction study to evaluate the safety, tolerability and optimal 
dose of ABX464 compared with placebo in patients with moderate to 
severe ulcerative colitis who have inadequate response, loss of 
response, or intolerance with at least one of the following agents: 
immunosuppressant treatment (i.e. azathioprine, 6-mercaptopurine, 
methotrexate), tumor necrosis factor alpha [TNF-α] inhibitors, 
vedolizumab, JAK inhibitors and/or corticosteroid treatment. 
 
I have carefully read all the pages of this clinical study protocol and I agree to the following:  
• 
To conduct the study as outlined in the protocol, any mutually agreed future protocol amendments 
and with all the terms and conditions set out by ABIVAX. 
• 
Not to implement any changes in the procedures described in the protocol without the prior approval 
of the sponsor and prior to review and written approval by the Ethics Committee and/or Regulatory 
Authorities, unless instructed otherwise by the Regulatory Authorities or the wellbeing of patients is 
jeopardized. 
• 
To conduct the study in accordance with the ICH GCP (R2) guidelines, US 21 Code of Federal 
Regulations dealing with clinical studies (including parts 50 and 56 concerning informed consent 
and IRB regulations), the European Union Clinical Trials Directive 2005/28/EC, EudraLex GMP 
guidelines Annex 13, the provisions of the Helsinki Declaration and relevant legislation in force.  
• 
I am thoroughly aware of the study drug specifications and adverse events as described in the 
protocol and the current Investigator’s Brochure and any other information provided by the Sponsor. 
• 
To ensure that sub-investigator(s) and other relevant members of my staff involved in the study are 
fully aware of their responsibilities regarding this study and will conduct the study according to the 
protocol.  
 
Investigator’s Name:   
 
________________________________________ 
Investigator’s Signature:  
 
________________________________________ 
Date:   
 
 
 
________________________________________ 
 
 

ABIVAX 
Clinical Study Protocol 
Study code: ABX464-103 
 
01- June -2020 
V3.0 
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TABLE OF CONTENTS 
CONTACTS 
3 
SYNOPSIS 
8 
1. 
INTRODUCTION AND STUDY RATIONALE 
17 
1.1. 
ULCERATIVE COLITIS (UC) 
17 
1.1.1. 
DISEASE 
17 
1.1.2. 
MANAGEMENT OF PATIENTS 
17 
1.2. 
ABX464 RATIONALE 
17 
1.2.1. 
INVESTIGATIONAL TREATMENT DESCRIPTION 
17 
1.2.2. 
INVESTIGATIONAL MEDICINAL PRODUCT DESCRIPTION 
18 
1.2.3. 
INVESTIGATIONAL MEDICINAL PRODUCT MODE OF ACTION 
18 
1.2.4. 
RATIONALE FOR THE DEVELOPMENT OF ABX464 IN ULCERATIVE COLITIS 
18 
1.2.5. 
PRECLINICAL DATA OF ABX464 
22 
1.2.5.1. 
NON-CLINICAL BACKGROUND INFORMATION 
22 
1.2.5.2. 
PREVIOUS CLINICAL EXPERIENCE WITH ABX464 
22 
1.3. 
RATIONALE FOR THE CLINICAL STUDY AND STUDY DESIGN 
23 
2. 
STUDY OBJECTIVES AND ENDPOINTS 
24 
2.1. 
PRIMARY OBJECTIVE 
24 
2.2. 
SECONDARY OBJECTIVES 
24 
2.3. 
PRIMARY ENDPOINT 
24 
2.4. 
SECONDARY ENDPOINTS 
24 
3. 
INVESTIGATIONAL PLAN 
26 
3.1. 
STUDY DESIGN 
26 
3.1.1. 
DESIGN AND METHODOLOGY 
26 
3.1.2. 
DOSE LIMITING TOXICITY (DLT) 
27 
3.1.3. 
DATA SAFETY MONITORING BOARD 
27 
3.2. 
DURATION OF STUDY PARTICIPATION 
27 
4. 
STUDY POPULATION 
28 
4.1. 
NUMBER OF PATIENTS/CENTERS 
28 
4.2. 
ELIGIBILITY CRITERIA 
28 
4.2.1. 
INCLUSION CRITERIA 
28 
4.2.2. 
EXCLUSION CRITERIA 
29 
5. 
STUDY ASSESSMENTS AND PROCEDURES 
31 
5.1. 
STUDY FLOW CHART 
31 
5.2. 
STUDY CONDUCT 
31 
5.2.1. 
SCREENING VISIT (WITHIN 28 ± 3 DAYS PRIOR TO DAY 1) 
31 
5.2.2. 
BASELINE (FIRST DOSING DAY / DAY 1) 
32 
5.2.3. 
DAY 8, DAY 29, DAY 85 VISITS 
32 
5.2.4. 
DAY 57 AND DAY 113 VISITS 
33 
5.2.5. 
END OF STUDY VISIT  (WITHIN A WEEK AFTER LAST DOSE ± 2 DAYS) 
33 
5.3. 
DETAIL OF THE STUDY ASSESSMENTS 
35 
5.3.1. 
PHYSICAL EXAMINATION AND VITAL SIGNS 
35 
5.3.2. 
ADVERSE EVENTS OF INTEREST 
35 
5.3.3. 
PREGNANCY 
35 
5.3.4. 
ECG 
35 
5.3.5. 
IBD QUESTIONNAIRE (IBDQ) 
35 
5.3.6. 
MODIFIED MAYO SCORE - STOOL AND RECTAL BLEEDING FREQUENCY 
36 
5.3.7. 
SIGMOIDOSCOPY WITH RECTAL/SIGMOIDAL BIOPSIES 
36 
5.3.8. 
HEMATOLOGY AND BIOCHEMISTRY 
36 
5.3.9. 
CYTOKINES ANALYSIS 
37 
5.3.10. 
MIRNA MODULATION 
37 
5.3.11. 
PHARMACOKINETICS 
37 
5.4. 
SUMMARY OF BLOOD SAMPLES 
38 
6. 
INVESTIGATIONAL MEDICINAL PRODUCT(S) 
39 
6.1. 
DESCRIPTION OF INVESTIGATIONAL TREATMENT 
39 
6.2. 
DESCRIPTION OF INVESTIGATIONAL MEDICINAL PRODUCT 
39 
6.2.1. 
ACTIVE INVESTIGATIONAL MEDICINAL PRODUCT (ABX464) 
39 
6.2.2. 
PLACEBO 
39 
6.3. 
ADMINISTRATION AND DOSING 
40 
6.3.1. 
ADMINISTRATION OF THE INVESTIGATIONAL MEDICINAL PRODUCT 
40 
6.3.2. 
GUIDELINES FOR TREATMENT POSTPONEMENT AND DOSE MODIFICATIONS 
40 
6.4. 
METHOD OF ASSIGNING PATIENTS TO TREATMENT ARMS 
40 
6.5. 
BLINDING AND BREAKING THE STUDY BLIND 
40 
6.6. 
PACKAGING 
40 
6.7. 
STORAGE 
40 
6.8. 
PRODUCT ACCOUNTABILITY 
40 
6.9. 
PRIOR AND CONCOMITANT MEDICATION 
41 
6.9.1. 
ALLOWED CONCOMITANT TREATMENT 
41 
6.9.2. 
PROHIBITED CONCURRENT MEDICATIONS 
41 

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01- June -2020 
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7. 
PATIENT COMPLETION AND WITHDRAWAL 
42 
7.1. 
PATIENT COMPLETION 
42 
7.2. 
PREMATURE TRIAL DISCONTINUATION 
42 
7.3. 
STUDY DISCONTINUATION 
42 
7.4. 
SCREEN AND BASELINE FAILURES 
42 
8. 
ADVERSE EVENTS (AE) AND SERIOUS ADVERSE EVENTS (SAE) 
44 
8.1. 
DEFINITIONS 
44 
8.1.1. 
DEFINITION OF AN AE 
44 
8.1.2. 
ADVERSE DRUG REACTIONS (ADR) 
44 
8.1.3. 
DEFINITION OF A SAE OR SERIOUS ADVERSE DRUG REACTION (SADR) 
44 
8.2. 
A SUSPECTED UNEXPECTED SERIOUS ADVERSE REACTION (SUSAR) 
45 
8.3. 
EVENTS AND/OR OUTCOMES NOT QUALIFYING AS SAES 
45 
8.4. 
EVENTS OR OUTCOMES QUALIFYING AS AES OR SAES 
45 
8.4.1. 
CLINICAL LABORATORY PARAMETERS 
45 
8.4.2. 
PREGNANCY REPORT 
45 
8.5. 
TIME PERIOD, AND FREQUENCY OF DETECTING AES AND SAES 
46 
8.6. 
RECORDING AES AND SAES 
46 
8.7. 
REPORTING OF SAES TO ABIVAX OR ITS DESIGNEE 
47 
8.8. 
REPORTING OF SAES TO REGULATORY AUTHORITIES 
47 
9. 
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS 
49 
9.1. 
STATISTICAL AND ANALYTICAL PLANS 
49 
9.1.1. 
PROTOCOL DEVIATIONS 
49 
9.1.2. 
DEFINITION OF STUDY ANALYSIS SETS 
49 
9.1.3. 
PATIENTS/PATIENTS DISPOSITION 
49 
9.1.4. 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
49 
9.1.5. 
TREATMENT COMPLIANCE 
49 
9.2. 
EFFICACY ANALYSIS 
49 
9.2.1. 
PHARMACOKINETICS 
50 
9.3. 
SAFETY ANALYSES 
51 
9.3.1. 
CLINICAL LABORATORY EVALUATION 
52 
9.4. 
DETERMINATION OF SAMPLE SIZE 
52 
10. 
STUDY CONDUCT CONSIDERATION 
53 
10.1. 
REGULATORY AND ETHICAL CONSIDERATIONS 
53 
10.1.1. 
GENERAL REQUIREMENTS 
53 
10.1.2. 
INDEPENDENT ETHICS COMMITTEE/INSTITUTIONAL REVIEW BOARD 
53 
10.1.3. 
PATIENT INFORMED CONSENT 
53 
10.1.4. 
COMPENSATION TO PATIENTS 
54 
11. 
STUDY MANAGEMENT 
55 
11.1. 
REMOTE DATA ENTRY 
55 
11.2. 
DATA MANAGEMENT 
55 
11.3. 
DATA CODING 
55 
11.4. 
RANDOMIZATION 
55 
11.5. 
STUDY MONITORING 
55 
11.6. 
RECORDS RETENTION 
56 
11.7. 
QUALITY ASSURANCE AND INSPECTION BY AUTHORITIES 
56 
11.8. 
STUDY AND SITE CLOSURE 
57 
11.9. 
STUDY REPORT AND PUBLICATION 
57 
11.10. 
OWNERSHIP AND CONFIDENTIALITY 
57 
12. 
REFERENCES 
58 
13. 
APPENDICES 
59 
 
 

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Study code: ABX464-103 
 
01- June -2020 
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ABBREVIATIONS 
Abbreviation or Term 
Definition 
AE 
adverse event 
ALT/SGPT 
alanine aminotransferase/serum glutamic pyruvate transaminase 
AST/SGOT 
aspartate aminotransferase/serum glutamic oxaloacetic transaminase 
AUC0-24 
area under the plasma concentration-versus-time curve from zero to 24 hours 
AUC0-∞ 
area under the plasma concentration-versus-time curve from zero to infinity 
AUC0-t 
area under the plasma concentration-versus-time curve from time zero to the time of the last quantifiable concentration 
BMI 
Body Mass Index  
CBC 
Cap Binding Complex 
CI 
Confidence Interval 
Cmax 
peak plasma concentration 
CMV 
Cytomegalovirus 
CNS 
Central Nervous System 
CRF 
Case Report Form 
CRP 
C Reactive Protein 
CTC-AE 
Common Terminology Criteria for Adverse Events, version 5.0 
CTFG 
Clinical Trial Facilitation Group 
CYP 
Cytochrome 
DBP 
Diastolic Blood Pressure  
DSMB 
Data and Safety Monitoring Board 
DSS 
Dextran Sulfate Sodium 
ECG 
electrocardiogram 
ECCO 
European Crohn’s and Colitis Organisation 
EDTA 
ethylenediaminetetraacetic acid 
GCP 
good clinical practice 
GGT 
gamma-glutamyl transferase 
GM 
Geometric Mean 
H 
hours 
HIV 
Human Immunodeficiency Virus 
HR 
heart rate 
IB 
Investigator’s Brochure 
IBD 
IBDQ 
Inflammatory Bowel Disease 
Inflammatory Bowel Disease Questionnaire 
ICF 
informed consent form  
ICH 
International Conference on Harmonization 
IEC 
IgG 
IgM 
Independent Ethics Committee 
Immunoglobulin G 
Immunoglobulin M  
IL-22 
Interleukine 22 
IMP 
Investigational Medicinal Product 
JAK 
Janus Kinase 
Max 
maximum 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
Min 
minimum 
miR 
micro-RNA 
mL 
milliliter 
mmHg 
millimeters of mercury 
NOAEL 
No Observed Adverse Effect Level 
MMS 
Modified Mayo Score 
o.d. 
Once Daily 
PCSA 
potentially clinically significant abnormalities 
PD 
pharmacodynamics 
PK 
pharmacokinetics 
pMMS 
Partial Modified Mayo Score 
PT 
Preferred Term 
QTc 
heart-rate–corrected QT interval (time between the start of the Q wave and the end of the T wave in the heart's electrical cycle) using 
Bazett’s formula 
R 
Accumulation ratio 
RHI 
Robarts Histopathology Index 
SAE 
serious adverse event 
SBP 
systolic blood pressure 
SD 
standard deviation 
SEM 
standard error of the mean 
SF-36 
Quality of Life Questionnaire 
SmPC 
Summary of Product Characteristics  
SOC 
system organ class 
t1/2 
terminal half-life 
TB 
Tuberculosis 
TEAE 
treatment emergent adverse event 
tmax 
time to peak plasma concentration 
TMS 
Total Mayo Score 
TNF 
Tumor Necrosis Factor 
UC 
Ulcerative Colitis 
ULN 
Upper Limit Normal 
Vd/F 
volume of distribution 
vs. 
versus 
 
 

ABIVAX 
Clinical Study Protocol 
Study code: ABX464-103 
 
01- June -2020 
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Study n° 
ABX464-103 
Clinical Phase 
IIb 
 
 
Type of Study 
Safety, Efficacy, Dose-Ranging Study 
patients with previous exposure to biological drugs or JAK inhibitors. 
The proportion of patients with previous exposure to biologics or JAK inhibitors will be limited 
to 60%, including a maximal proportion of patients with previous treatment with vedolizumab 
of 20%. The maximal proportion of patients with previous exposure with JAK inhibitors will be 
limited to 10%. 
Patients will be treated for 16 Weeks in this induction study. All endoscopies (videos) will be 
centrally reviewed. E-Diaries will be used to collect frequency of stools, rectal bleedings, 
number of capsules taken and the intake time. 
From Day 1 onwards, randomized patients will be seen at the investigational site on a regular 
basis (cf. flow-chart). 
Flexible sigmoidoscopy with rectal and sigmoidal (if the sigmoidal is inflamed) biopsies will 
be performed at screening, at Day 57 +/- 4 days (week 8) and at Day 113 +/- 4 days (week16). 
The Day 113 measurement will only be performed if patient does not experience endoscopic 
improvement at Day 57 (i.e.: endoscopy sub-score of 2 or 3). 
From Week 8 onwards, in the event of clinical progression of the disease defined as at least 
a 2-point increase from the screening in partial Modified Mayo Score (pMMS) with a Modified 
Mayo Score ≥ 4 confirmed by an endoscopy sub score of 2 points or higher, the patient will 
exit definitively the study. 
Approximately 244 patients will be randomized in this study (i.e. 61 patients per study 
treatment arm). 
Study 
Objectives 
Primary Objective 
The primary objective of the study is to determine an optimal ABX464 dose to be used in 
moderate to severe active ulcerative colitis patients who have failed or are intolerant to 
immunomodulators, Anti-TNFα, vedolizumab, JAK inhibitors and/or corticosteroids by 
comparing the mean change from baseline in the MMS at week 8 between each ABX464 
group and placebo. 
Secondary Objectives 
The secondary objectives are: 
▪ 
To evaluate the effect of the different dose groups of ABX464 on Modified Mayo Score 
at Week 16 (if available) and on partial Modified Mayo Score at every study visit versus 
placebo. 
▪ 
To evaluate the global effect of ABX464 on Modified Mayo Score at Week 8 and Week 
16 (if available) and on partial Modified Mayo Score at every study visit versus placebo. 
▪ 
To evaluate the effect of the different dose groups of ABX464 on clinical remission at 
Week 8 and at Week 16 (if available) versus placebo. 
▪ 
To evaluate the effect of the different dose groups of ABX464 on clinical response at 
week 8 and at Week 16 (if available) versus placebo. 
▪ 
To evaluate the effect of the different dose groups of ABX464 on endoscopic 
improvement and endoscopic remission, by segment, at Week 8 and Week 16 (if 
available) versus placebo. 
▪ 
To evaluate the effect of the different dose groups of ABX464 on mucosal healing, at 
Week 8 and Week 16 (if available) versus placebo. 
▪ 
To evaluate the effect of the different dose groups of ABX464 on stool and rectal 
bleeding frequency at every study visit versus placebo. 
▪ 
To evaluate the effect of the different dose groups of ABX464 on fecal calprotectin and 
CRP levels at Week 8 and Week 16 versus placebo. 
▪ 
To evaluate the effect of the different dose groups of ABX464 on miR-124 expression 
in tissue (RNA later) at Week 8 and Week 16 (if available) and in total blood at every 
timepoint versus placebo. 
▪ 
To evaluate the effect of the different dose groups of ABX464 versus placebo on the 
rectal/sigmoidal infiltrates using the Robarts Histopathology Index (RHI), the Geboes 
and Nancy Histology Scoring Scales at Week 8 and Week 16 (if available) versus 
placebo. 

ABIVAX 
Clinical Study Protocol 
Study code: ABX464-103 
 
01- June -2020 
V3.0 
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Study n° 
ABX464-103 
Clinical Phase 
IIb 
 
 
Type of Study 
Safety, Efficacy, Dose-Ranging Study 
▪ 
To evaluate the effect of the different dose groups of ABX464 on Quality of Life (QoL) 
measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 8 and 
Week 16 versus placebo. 
▪ 
To evaluate the effect of the different dose groups of ABX464 on IL-6, TNFα, IL-1b, IL-
10 plasma concentrations at every timepoint versus placebo. 
▪ 
To assess the pharmacokinetics of the ABX464 and its main active metabolite ABX464-
N-Glu after oral administration of different daily doses of ABX464 using population 
approach. 
▪ 
To evaluate the safety profile of the different dose groups of ABX464 versus placebo. 
Study 
Endpoints 
 
Primary Endpoint: 
▪ 
Reduction from baseline in Modified Mayo Score at Week 8. 
Secondary Endpoints: 
The secondary endpoints are: 
▪ 
Number and rate of patients in clinical remission at Week 8, per each 
intervention/treatment group. Clinical remission, based on the Mayo Scoring system, is 
defined as stool frequency subscore = 0 or 1 and rectal bleeding subscore = 0 and 
endoscopy subscore = 0 or 1 (modified to exclude friability). 
▪ 
Combined number and rate of patients in clinical remission at Week 8 and at Week 16, 
per each intervention/treatment group. 
▪ 
Number and rate of patients with clinical response at Week 8 and Week 16 per 
intervention/treatment group. Clinical Response is defined as a reduction in Mayo Score 
of at least 2 points and greater than or equal to 30 percent from baseline with an 
accompanying decrease in rectal bleeding sub-score of greater than or equal to 1 point 
or absolute rectal bleeding sub-score of less than or equal to 1 point. 
▪ 
Number and rate of patients with endoscopic improvement, by segment, and number 
and rate of patients with endoscopic remission, by segment, at Week 8 and at Week 16 
(if available) per intervention/treatment group. Endoscopic improvement is defined as a 
Mayo endoscopic sub score of ≤1 (excluding friability) and endoscopic remission 
defined as sub score of 0. 
▪ 
Number and rate of patients with mucosal healing. Mucosal healing is defined as both 
endoscopic remission and histological remission (Geboes score < 2.0) 
▪ 
Reduction relative to baseline in stool and rectal bleeding frequency at every study visit 
by ABX464 dose group and versus placebo. 
▪ 
Reduction relative to baseline in partial Modified Mayo Score at every study visit and 
Modified Mayo Score at Week 16 (if available) by ABX464 dose group and versus 
placebo. 
▪ 
Reduction relative to baseline in fecal calprotectin and CRP levels at Week 8 and Week 
16 by intervention/treatment group. 
▪ 
Change relative to baseline in miRNA-124 expression in rectal/sigmoidal biopsies at 
Week 8 and Week 16 and in total blood at every timepoints by intervention/treatment 
group. 
▪ 
The scores and changes from baseline in IBDQ at Week 8 and Week 16 per intervention 
treatment group. 
▪ 
Reduction relative to baseline of infiltrate/histopathology (rectal/sigmoidal biopsies) 
using the Robarts Histopathology Index (RHI), the Geboes and Nancy Histology 
Scoring Scales at Week 8 and Week 16 (if available) per intervention/treatment group. 
▪ 
Change relative to baseline in IL-6, TNFα, IL-1b, IL-10 plasma concentrations at every 
timepoints by intervention/treatment group. 
▪ 
Serum concentration of ABX464 and N-Glu ABX464 according to dose group. 
▪ 
Number and rate of all adverse events, causally-related adverse events, all SAE and 
causally-related SAEs classified by severity per intervention/treatment group. 
▪ 
Incidence of treatment-emergent serious adverse event per intervention/treatment 
group. 
▪ 
Incidence of adverse events leading to investigational medicinal product discontinuation 
per intervention/treatment group. 

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Clinical Study Protocol 
Study code: ABX464-103 
 
01- June -2020 
V3.0 
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Study n° 
ABX464-103 
Clinical Phase 
IIb 
 
 
Type of Study 
Safety, Efficacy, Dose-Ranging Study 
▪ 
The number of clinically-significant laboratory abnormalities per intervention/treatment 
group. 
Main Selection 
Criteria 
 
Inclusion criteria: 
A patient will be eligible to participate in this study if ALL the following criteria are met: 
▪ 
Men or women age 18 - 75 years; 
▪ 
Diagnosis of moderate to severe active UC (including ulcerative proctitis if proximal 
extension of disease occurs beyond 10 cm) confirmed by endoscopy and histology at 
least 12 Weeks prior to screening visit. Moderate to severe active UC defined by 
Modified Mayo Score (MMS) of 5 to 9 inclusive (on a scale of 0-9). Moderate to severe 
active UC should be confirmed at screening visit with a centrally read endoscopy sub-
score of at least 2 (on a scale of 0-3); 
▪ 
Patients having either a documented inadequate response, no response, a loss of 
response, or an intolerance (defined as the occurrence of at least one Adverse Reaction 
leading to treatment discontinuation) to either immunosuppressant treatment (i.e., 
azathioprine, 6-mercaptopurine, methotrexate), tumor necrosis factor [TNF] inhibitors, 
vedolizumab, JAK inhibitors and/or corticosteroid treatment. Inadequate response, no 
response, loss of response is defined as: 
o Active disease or relapse in spite of thiopurines or methotrexate given at an 
appropriate dose for at least 3 months (i.e. azathioprine 2–2.5 mg/kg/day or 
mercaptopurine 1–1.5 mg/kg/day in the absence of leukopenia), and/or 
o Active disease despite corticosteroids treatment (prednisolone up to 0.75 
mg/kg/day) over a period of 4 Weeks, and/or 
o Active disease or relapse in spite of adequate treatment (as defined in the SmPC) 
with tumor necrosis factor [TNF] inhibitors or vedolizumab, and/or 
o Active disease or relapse in spite of adequate treatment with JAK inhibitors over 
a period of at least 6 Weeks. 
▪ 
Patients receiving oral corticosteroids must have been on a stable dose of prednisone 
or prednisone equivalent (≤20 mg/day) or on beclomethasone diproprionate (≤5mg/day) 
or on budesonide MMX (≤9 mg/day) for at least 2 Weeks prior to the screening visit; 
▪ 
Topical corticosteroids and topical 5-aminosalicylic acid preparations must have been 
withdrawn at least 2 Weeks prior to the screening visit; 
▪ 
Patients who are on oral 5-aminosalicylic acid must have been on a stable dose for at 
least 4 Weeks prior to the screening visit; 
▪ 
Patients who are receiving immunosuppressants in the form of azathioprine, 6-
mercaptopurine, or methotrexate needed to be on a stable dose for at least 4 Weeks 
prior to screening visit. Patients taking methotrexate also are advised to take folic acid 
1 mg/day (or equivalent) supplementation if there is no contraindication; 
▪ 
Patients on probiotics (e.g., Culturelle® [Lactobacillus GG, i-Health, Inc.], 
Saccharomyces boulardii) must be on stable doses for at least 2 Weeks prior to the 
screening visit; 
▪ 
Patients on antidiarrheals (e.g., loperamide, diphenoxylate with atropine) must be on 
stable doses for at least 2 Weeks prior to the screening visit; 
▪ 
Patients who have received tumor necrosis factor [TNF] inhibitors, vedolizumab or other 
biologics must have discontinued therapy at least 8 Weeks prior to the screening visit 
due to lack or insufficient efficacy or intolerance; 
▪ 
Patients previously treated with cyclosporine, tacrolimus or JAK inhibitors must have 
discontinued therapy at least 4 Weeks prior to the screening visit due to lack or 
insufficient efficacy or intolerance; 
▪ 
Patients previously treated with tube feeding, defined formula diets, or parenteral 
alimentation/nutrition must have discontinued treatment 3 Weeks before the screening 
visit and must be able to take, orally, appropriate amount of food (calories) and liquids 
to maintain body weight; 
▪ 
Patients with surveillance colonoscopy defined as per ECCO guidelines; 
▪ 
Patients with the following hematological and biochemical laboratory parameters 
obtained at screening: 
o 
Hemoglobin > 9.0 g dL-1; 

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Study n° 
ABX464-103 
Clinical Phase 
IIb 
 
 
Type of Study 
Safety, Efficacy, Dose-Ranging Study 
o 
Absolute neutrophil count ≥ 750 mm-3; 
o 
Platelets ≥ 100,000 mm-3; 
o 
Total serum creatinine ≤ 1.3 x ULN (upper limit of normal); 
o 
Creatinine clearance > 90 mL min-1 by the Cockcroft-Gault equation within 
60 days prior to baseline; 
o 
Total serum bilirubin < 1.5 x ULN; 
o 
Alkaline phosphatase, AST (SGOT) and ALT (SGPT) < 2 x ULN; 
▪ 
Patients are able and willing to comply with study visits and procedures as per protocol; 
▪ 
Patients should understand, sign and date the written voluntary informed consent form 
at the screening visit prior to any protocol-specific procedures are performed; 
▪ 
Patients should be affiliated to a social security regimen (for French sites only); 
▪ 
Females and males receiving the study treatment (potentially in combination with 
immunosuppressant) and their partners must agree to use a highly effective 
contraceptive method during the study and for 6 months after end of study or early 
termination. Contraception should be in place at least 2 Weeks prior to study 
participation. Women must be surgically sterile or if of childbearing potential must use 
a highly effective contraceptive method. Women of childbearing potential (WOCBP) will 
enter the study after confirmed menstrual period and a negative pregnancy test. Highly 
effective methods of contraception include true abstinence, intrauterine device (IUD) or 
hormonal contraception aiming at inhibition of ovulation, intrauterine hormone releasing 
system, bilateral tubal ligation, vasectomized partner. True abstinence is defined when 
this is in line with the preferred and usual lifestyle of the Patient. In each case of delayed 
menstrual period (over one month between menstruations) confirmation of absence of 
pregnancy is required. This recommendation also applies to WOCBP with an infrequent 
or irregular menstrual cycle. Female and male patients must not be planning pregnancy 
during the trial and for 6 months post completion of their participation in the trial. In 
addition, male participants should use condoms and not donate sperm as long as 
contraception is required. 
Exclusion Criteria: 
Patients who meet any of the following exclusion criteria will be excluded from the 
study: 
▪ 
Patients with Crohn's Disease (CD) or presence or history of fistula, indeterminate 
colitis (IC), infectious/ischemic colitis or microscopic colitis (lymphocytic and 
collagenous colitis); 
▪ 
History of toxic megacolon, abdominal abscess, symptomatic colonic stricture or stoma; 
history or imminent colectomy, colonic malignancy; 
▪ 
History or current evidence of colonic dysplasia or adenomatous colonic polyps. Patient 
with severe gastrointestinal complications; e.g., short bowel syndromes, recent or 
planned bowel surgery, Ileostomy and/or colostomy, recent bowel perforation; 
▪ 
History of more than one episode of herpes zoster or a history (single episode) of 
disseminated zoster; 
▪ 
Patients with active infections at screening such as infected abdominal abscess, 
Clostridium difficile (stool antigen and toxin required), CMV [(positive immunoglobulin 
M (IgM)], TB and recent infectious hospitalization; 
▪ 
Patients previously treated with ABX464; 
▪ 
Acute, chronic or history of clinically relevant pulmonary, cardiovascular, hepatic, 
pancreatic or renal functional abnormality, encephalopathy, neuropathy or unstable 
CNS pathology such as seizure disorder, angina or cardiac arrhythmias, active 
malignancy or any other clinically significant medical problems as determined by 
physical examination and/or laboratory screening tests and/or medical history; 
▪ 
Acute, chronic or history of immunodeficiency or autoimmune disease; 
▪ 
History of malignancy excluding patients considered cured (5 years disease free 
survivors); 
▪ 
Serious illness requiring systemic treatment and/or hospitalization within 3 Weeks prior 
to baseline; 
▪ 
Pregnant or breast-feeding women; 

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Study n° 
ABX464-103 
Clinical Phase 
IIb 
 
 
Type of Study 
Safety, Efficacy, Dose-Ranging Study 
▪ 
Illicit drug or alcohol abuse or dependence; 
▪ 
Patients who received live vaccine 30 days or fewer before first dose of study treatment 
and/or who’s planning to receive such a vaccine during the study duration; 
▪ 
Use of any investigational or non-registered product within 3 months or within 5 half-
lives preceding baseline, whichever is longer and during the study; 
▪ 
Any condition, which in the opinion of the investigator, could compromise the patient's 
safety or adherence to the study protocol. 
Medications 
Allowed Concomitant Medications: 
▪ 
Corticosteroids at stable dose of prednisone or prednisone equivalent ≤20 mg/day; 
beclomethasone diproprionate (≤5mg/day) or budesonide MMX (≤9 mg/day); 
▪ 
Oral 5-aminosalicylic acid at stable dose; 
▪ 
Immunosuppressants in the form of azathioprine, 6-mercaptopurine, or methotrexate at 
stable dose; 
▪ 
Antidiarrheals (e.g., loperamide, diphenoxylate with atropine) at stable dose. 
Prohibited Concomitant Medications: 
▪ 
Tumor necrosis factor [TNF] inhibitors, vedolizumab or others biologic therapies with a 
wash-out period of at least 8 Weeks prior to the screening visit; 
▪ 
JAK inhibitors with a wash-out period of at least 4 Weeks prior to the screening visit; 
▪ 
Topical corticosteroids and topical 5-aminosalicylic acid preparations with a wash-out 
period of at least 2 Weeks prior to the screening visit; 
▪ 
Cyclosporine and tacrolimus with a wash-out period of at least 4 Weeks prior to the 
screening visit; 
▪ 
Vaccination with live components during the study and up to 8 Weeks after the last 
dosing; 
▪ 
Drugs that could interact with ABX464 should be avoided especially the CYP1A2 
substrates (cf. Appendix #1). The following CYP1A2 substrates with a narrow 
therapeutic margin are prohibited during the whole course of the study (Clozapine, 
theophylline, ropinirol, warfarin and methadone). In case of concomitant treatment with 
ondansetron the maximal daily dose must be limited to 8 mg; 
▪ 
Drugs that inhibit or induce CYP1A2 (cf. Appendix #1). 
▪ 
Drugs that inhibit UGTIA9 activity and inhibitors of OATP1B1/1B3 transporters (cf. 
Appendix #1). 
▪ 
Use of any investigational or non-registered product within 3 months or within 5 half-
lives preceding baseline, whichever is longer and during the study. 
Premature trial 
discontinuatio
n 
Patient’s premature trial discontinuation could occur for the following reasons: 
▪ 
Investigator’s decision; patient that would experience a treatment failure during the 
study may be withdrawn at any time. S/he will have to be treated according to 
standard of care as soon as s/he is off from study treatment; 
▪ 
An Adverse Event or an intercurrent condition that preclude continuation of 
treatment; 
o 
Specifically, an increase ≥ 3.0 x ULN in liver transaminases (AST/SGOT 
and/or ALT/SGPT) or an increase ≥ 2.0 x ULN in Alkaline phosphatase or 
in total bilirubin requires close observation with repeating liver enzymes 
and serum bilirubin tests two times weekly and clinical investigation to 
understand the etiology of this elevation. Frequency of retesting can 
decrease to once a month if the abnormality stabilizes after this initial two 
weeks of follow-up and if the patient is asymptomatic. Discontinuation of 
the study treatment should occur if: 
▪ 
 ALT or AST > 8xULN 
▪ 
ALT or AST >5xULN for more than 2 weeks 
▪ 
ALT or AST > 3xULN and total bilirubin > 2xULN or INR>1.5 
▪ 
ALT or AST > 3xULN with appearance of fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, rash, 
and/or eosinophilia (>5%). 

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Study n° 
ABX464-103 
Clinical Phase 
IIb 
 
 
Type of Study 
Safety, Efficacy, Dose-Ranging Study 
▪ 
Worsening of the UC defined, from Week 8 onwards, as a 2-point increase in the 
pMMS, with pMMS ≥ 4 on 2 separate occasions 7 day-apart and confirmed by an 
endoscopy sub-score of 2 points or higher; 
▪ 
Major protocol violation; 
▪ 
Patient’s decision; 
▪ 
Withdrawal of consent. 
Patient Follow-
up  
On Day 113 +/- 4 days, eligible patients willing to continue study treatment will be able to take 
part in an Open Label Extension study (ABX464-104). In this extension study, all patients will 
be dosed with ABX464 50mg QD. ABX464-104 maintenance study is a separate clinical study 
requiring health authorities and ethics committees’ approvals. 
Data Safety 
Monitoring 
Board (DSMB)  
A Data Safety Monitoring Board with expertise and experience in the management in UC will 
review the safety of the trial every two months during the entire study period. 
The DSMB will oversee the adequate balance of baseline characteristics (gender, disease 
duration, fecal calprotectin level, tobacco use) among the treatment groups. 
In addition, DSMB will be review all potential causally-related Serious Adverse Events within 
7 days of the initial report. 
Sample Size 
calculation 
The primary endpoint is the change in the Modified Mayo Score (MMS) from Baseline to 
Week 8. The primary endpoint will be compared between subjects who received ABX464 and 
placebo for each ABX464 dose group separately. 
For sample size calculation the following assumptions were made: 
• 
mean reduction in MMS (ABX464): 2.5 
• 
mean reduction in MMS (placebo): 1.0 
• 
pooled standard deviation of reduction in MMS: 2.1 
• 
Type 1 error: 5% two-sided. 
• 
Treatment testing to use a sequential, gate-keeping strategy, where treatments will 
be tested in the following order: ABX464 50mg vs. placebo, ABX464 100mg vs. 
placebo, ABX464 25mg vs. placebo. Subsequent tests will only be performed only 
if prior test(s) are significant (p<0.05). 
• 
>90% power 
• 
Two-sample t-test 
• 
5% dropout rate prior to Week 8 MMS assessment (all treatment arms) 
• 
1:1:1:1 (ABX464 100mg: ABX464 50mg: ABX464 25mg: placebo) study treatment 
allocation ratio.  
If the above assumptions hold true, then a total sample size of 232 subjects will be required 
to be randomized (58 subjects randomized to each study treatment arm). 
Due to the SARS Cov-2 pandemic the drop-out rate of the study is expected to be somewhat 
higher than originally estimated. Therefore, an additional 12 subjects are planned to be 
recruited in the study, leading to an overall sample size of 244 patients (61 subjects 
randomized to each study treatment arm). 
Statistical 
Methods 
 
Analysis of efficacy data will be carried out using the Full Analysis Set.  
The primary efficacy endpoint of the study is the change in the Modified Mayo Score (MMS) 
from Baseline to Week 8. This change will be compared between subjects who received 
ABX464 and placebo for each ABX464 treatment arm separately using an ANCOVA model 
adjusting for randomized study treatment arm, US vs non-US, previous biological or JAK 
inhibitors treatment use (i.e. randomization strata), and baseline MMS.  
The dose testing will commence with comparing the ABX464 50mg dose with placebo. If this 
is significant at a 5% two-sided level (i.e. p<0.05) a comparison against placebo will be carried 
out at the ABX464 100mg dose. Again, if significance at a 5% level for this test is observed 
the procedure will be repeated at the ABX464 25mg dose. In this closed procedure no 
adjustment for multiple comparison is needed.  Should the data warrant it, testing between 
doses may also be conducted. 
In addition, descriptive statistics will be presented by treatment arm for all secondary efficacy 
variables for each measurement timepoint. 
These statistics include: 

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Study n° 
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Clinical Phase 
IIb 
 
 
Type of Study 
Safety, Efficacy, Dose-Ranging Study 
• 
Continuous variables: mean, standard deviation, minimum and maximum, 95% 
Confidence intervals for the mean, median and quartiles will be presented. 
• 
Categorical variables: counts, rates and 95% confidence intervals for the rates will 
be calculated. 
In addition to descriptive statistics, the following analyses will also be carried out for the 
variables indicated below: 
• 
The global (combined) ABX464 treatment effect vs. placebo in the change from 
Baseline in Modified Mayo Score at Week 8. 
• 
Mixed model analysis of covariance will be conducted for the following 
measurements: 
o 
The change from baseline in miRNA-124 levels in total blood (PAXgene®) at 
Week 1, Week 4, Week 8 and Week 16 and in tissue (RNA later) at Week 8 and 
Week 16 (if available). 
o 
The change from baseline in fecal calprotectin and CRP levels at Week 8 and 
Week 16. 
o 
The change from screening in the histopathology/infiltrate (rectal/sigmoidal 
biopsies) assessed by the Robarts Histopathology Index (RHI), the Geboes and 
Nancy Histology Scoring Scales at Week 8 and Week 16 (if available). 
o 
The change from screening in partial Modified Mayo scores during the study. 
In this model, treatments and stratum will be fixed effects, subject will be random effect and 
baseline values of the respective measurements will be covariates. Other explanatory 
variables will also be allowed to be included in the model. To normalize eventual skewed 
distributions, transformation of the data will also be considered. Study treatment groups will 
be compared within this model framework. All p-values will be interpreted in a descriptive 
manner. 
The following subgroups will be analyzed: 
• 
Gender 
• 
Age 
• 
Country 
• 
US vs non-US 
• 
Baseline MMS 
• 
With/without previous biological or JAK inhibitors treatment 
• 
Week 16 ABX464-NGlu AUC0-12 level above/below 7 000 h*ng/mL (vs. placebo). 
• 
Concomitant UC medications. 
Safety: 
Analysis of safety will be performed on the safety data set consisting in all patients who 
received at least one dose of ABX464 or placebo in the study. The assessment of safety will 
be based on the frequency of adverse events (with and without regard to causality) graded 
according to the “CTC-AE” (Version 5.0) and also, the review of individual values for clinical 
laboratory data, vital signs and ECG focusing on the detection of abnormal values and 
potentially clinically significant abnormalities (PCSAs) as determined upon investigator 
considerations. 
Adverse events will be tabulated (counts and percentages) by dose groups. All adverse 
events will be listed and the data will be tabulated by body system/organ class. Adverse event 
tabulations will include all treatment emergent adverse events, which will be further classified 
by severity, and relationship to treatment. 
Clinical laboratory parameters, vital signs, ECG will be summarized by using descriptive 
statistics (n, mean, SD, SEM, median, minimum and maximum). The number of patients with 
at least one abnormal value will be tabulated (counts and percentages) for each parameter 
in summary shift tables by dose groups. 
Population Pharmacokinetics: 
Blood samples will be collected in all patients for PK assessment. Sampling will be performed 
on Day 1 and on the last day of study treatment. Two elementary sampling designs will be 
used to limit the number of samples in each patient: 

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Study n° 
ABX464-103 
Clinical Phase 
IIb 
 
 
Type of Study 
Safety, Efficacy, Dose-Ranging Study 
• 
Group 1:  
o 
Day 1: 0.5, 1.5, 3h (and 6 h and/or 10 h if possible) 
o 
Last day (Day 113): predose, 1, 2, 4h and if possible 48h (Day 115). D115 
will only be taken if the subject is not transitioning to the ABX464-104 study. 
• 
Group 2:  
o 
Day 1: 1, 2, 4h (and 8 h and/or 12 h if possible) 
o 
Last day (Day 113): predose, 0.5, 1.5, 3h and if possible 48h (Day 115). 
D115 will only be taken if the subject is not transitioning to the ABX464-
104 study. 
In addition to these sampling time points, predose concentrations will be collected at the study 
visit day 8, 29, 85. Patient data will be pooled with data obtained in previous clinical studies 
in order to build a population pharmacokinetic models for ABX464 and its metabolite. 

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1. INTRODUCTION AND STUDY RATIONALE 
1.1. Ulcerative Colitis (UC)  
1.1.1. Disease 
Ulcerative colitis (UC) is a chronic inflammatory condition causing continuous mucosal inflammation of 
the colon without granulomas on biopsy, affecting the rectum and a variable extent of the colon in 
continuity, which is characterized by a relapsing and remitting course. 
UC is a lifelong disease arising from an interaction between genetic and environmental factors, observed 
predominantly in the developed countries of the world. 
The precise etiology is unknown and therefore medical therapy to cure the disease is not yet available. 
1.1.2. Management of patients 
Patients may live with a considerable symptom burden despite medical treatment (66% describe 
interference with work and 73% with leisure activities) [1] in the hope that the etiology of ulcerative colitis 
will be elucidated and a cure developed. 
Although most patients present with mild-to-moderate UC, 10% of patients initially present with severe 
disease. Additionally, approximately 15% of patients will develop a severe flare during the course of 
their lifetime. Both the American College of Gastroenterology practice guidelines and the European 
Crohn's and Colitis Organization position statements define severe colitis as the passage of six or more 
stools per day with evidence of systemic toxicity (e.g., fever, tachycardia, anemia or elevated ESR) [2,3]. 
Patients with acute severe UC require hospitalization for optimal management owing to the seriousness 
of their illness. Although rates of death in severe UC have dropped by up to 25% with the adoption of 
more aggressive monitoring and treatment [4] acute severe colitis is still associated with a measurable 
mortality [5]. 
The use of intravenous steroids and improved surgical techniques probably explain much of the 
reduction in mortality associated with acute severe UC observed in the decades since their introduction 
[6] 
Severe UC should be considered a medical emergency, and patients require close monitoring of stool 
frequency and vitals symptoms. Serial abdominal examinations and plain radiographs should be 
performed. 
The cornerstone of management of severe UC remains the use of intravenous corticosteroids, which 
are effective in the induction of remission in the majority of cases. While many patients with acute severe 
ulcerative colitis will respond to a short course of intravenous corticosteroids, up to a third will fail to 
improve. In these patients with steroid-refractory colitis, the choice is between rescue medical therapy 
with ciclosporin, anti-TNF Alpha, vedolizumab, JAK inhibitors or surgery. Anti-tumor necrosis factor 
(TNF) therapy is effective for the treatment of ulcerative colitis (UC).  
Nevertheless, up to 30% of patients show no clinical benefit despite optimal treatment, while another 
40% of patients lose response over time and need to escalate or discontinue anti-TNF therapy within 
one year of treatment. 
Thus, there is an unmet medical need for novel treatment options for patients with moderate to severe 
UC. 
1.2. ABX464 rationale 
1.2.1. Investigational treatment description 
ABX464 is a first-in-class, orally available, small molecule with anti-inflammatory activity which is under 
investigation as a potential treatment for moderate to severe ulcerative colitis and rheumatoid arthritis. 
In-vitro assays revealed that both ABX464 and its primary metabolite, ABX464-N-Glu, induced a 
significant increase in miR-124 expression in PBMCs in a dose dependent manner. 

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Results support the hypothesis that ABX464 and ABX464-N-Glu bind directly to Cap-Binding Complex 
without interfering with cap binding function. Both molecules selectively modulate RNA biogenesis by 
direct binding to the cellular CBC, leading to an increased expression of miR-124 while not affecting 
other cellular RNAs. In inflammatory conditions, miR-124 expression is associated with the down 
regulation of a variety of pro-inflammatory cytokines/mediators and can induce an anti-inflammatory 
effect. Literature reports indicate that miR-124 appears to regulate the expression of signal transducer 
and activator of transcription 3 (STAT3), MCP-1, IL6-R and TNFα.  In the DSS mouse model, a reduction 
in MCP-1, IL6 and TNFα was observed following ABX464 treatment. MCP-1 is a direct target of miR-
124. ABX464 and ABX464-N-Glu up-regulate the production of miR-124 by binding to the CBC. 
ABX464 and ABX464-N-Glu have shown strong anti-inflammatory effects in vivo, in the inflammatory 
bowel disease (IBD) mouse dextran sulfate sodium (DSS)-model. Results from in vivo studies using the 
DSS-induced mouse model showed that DSS-induced weight loss, an established symptom of intestinal 
injury. This weight loss was significantly reduced in mice receiving ABX464.  The model showed that 
ABX464 had no detectable effect on the expression profile of cytokines and chemokine signaling 
pathways in the absence of DSS exposure. However, ABX464 compensated for most of the expression 
differences induced by DSS exposure, suggesting that it can restore normal transcription in this model. 
ABX464-N-Glu demonstrated a similar effect as ABX464 regarding the dampening of body weight loss 
in DSS-induced colitis. 
This mode of action is unlike any currently approved drug. Because of its action on this single splicing 
event, leading to an increase in miR124, ABX464 potentially has broad utility in a variety of diseases.    
In humans, ABX464 is conjugated via glucuronidation to ABX464-N-Glu, which contributes the majority 
of ABX464 plasma exposure. ABX464-N-Glu is pharmacologically active and also binds to the CBC 
leading to an increase in miR124 expression.  
Clinical studies have been completed with ABX464 in healthy volunteers (2 studies) and patients with 
HIV infection (3 studies, including one study with a healthy volunteer cohort).  
Completed and ongoing studies with ABX464 in inflammation are:  
Ulcerative colitis 
• 
Phase 2a program with an 8-week induction (ABX464-101; completed) and a 2-year 
maintenance (ABX464-102; ongoing; 52-week interim analysis completed) studies  
• 
Phase 2b program including the present study a 16-week induction (ABX464-103; ongoing) and 
52-week maintenance (ABX464-104; planned) studies  
Rheumatoid arthritis  
• 
Phase 2a program with a 12-week induction (ABX464-301; ongoing) and 52-week maintenance 
(ABX464-302; ongoing) studies 
1.2.2. Investigational medicinal product description  
The chemical name of ABX464 molecule is 8-chloro-N-[4-(trifluoromethoxy) phenyl]quinolin-2-amine, or 
(8-chloro-quinolin-2-yl)-(4-trifluoromethoxy-phenyl)-amine. Its molecular weight is 338.7. 
The study drug is formulated as hard gelatin, powder-filled capsules (size 1). 
1.2.3. Investigational medicinal product Mode of Action 
ABX464 and ABX464-N-Glu bind the CBC (Cap Binding Complex), comprised of two proteins CBC20 
and CBC80, within the cell nucleus. This binding leads to an increase in a single micro-RNA (miR124) 
expression by impacting the splicing of a single long non-coding RNA. 
1.2.4. Rationale for the development of ABX464 in Ulcerative Colitis 
In-Vitro assays 
▪ 
Modulation of miR-124 by ABX464 

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Study ABX464PHA011 performed in humans PBMCs revealed that both ABX464 and its primary 
metabolite ABX464-N-Glu  induced a significant increase in miR-124 expression. MiR-124 appears to 
regulate the expression of signal transducer and activator of transcription 3 (STAT3). MiR-124 has also 
been shown to be required for the protective role of nicotine in DSS colitis mice. 
▪ 
Bone Marrow Derived Macrophages – LPS Challenge  
Stimulation of BMDMs with LPS induced the expression of IL6, TNFα, and MCP1 (CCL2) but not that of 
IL10 (Figure 1B). The expressions of MCP1 and IL6 persisted for 48 h post LPS-stimulation, whereas 
TNF expression was down-regulated at 12 h (Figure 1B). Strikingly, ABX464-exposed BMDMs displayed 
an increased production of IL-10 at 12 and 24 h post LPS-stimulation but did not alter levels of the pro-
inflammatory cytokines IL6 and TNFα (Figure 1B).  
 
Figure 1. Effect of ABX464 on cytokine secretion (A) Bone marrow isolated cells were cultured for 6 days in the presence of GM-CSF (50ng/ml) to 
differentiate into macrophages. Cells were kept in culture for additional 3 days in the presence of ABX464 (5µM) or vehicle (DMSO) alone and for additional 6 hours stimulated 
with LPS (4µg/ml). Cells were then kept in normal medium for additional 42 hours. Cell aliquots for RNA isolation and supernatants were taken at time 6, 12, 24 and 48 
hours. (B) Culture supernatants of the indicated cell cultures were analyzed by CBA for the content of MCP-1, IL-6, TNFalpha and IL-10. 
In-Vivo assays 
▪ 
DSS mice model 
ABX464 and its primary metabolite, ABX464-N-Glu were tested in a mouse model of colon inflammation. 
This study tested the protective properties of ABX464 in a DSS-induced experimental model of colitis. 
In this model inflammation is specifically induced in the colon via the administration of DSS in drinking 
water for approximately 5-8 days. ABX464 was administered for 8 days via gavage. These results 
showed that DSS-induced weight loss, an established symptom of intestinal injury, was significantly 
reduced in mice receiving ABX464 (Figure 2B). This induced intestinal inflammation is usually strongest 
3 days after the termination of the DSS challenge. The weight of ABX464-treated mice had already 
returned to pre-treatment levels at that time point, and the mice displayed decreased disease 
parameters such as smaller and fewer colonic lesions as well as decreased shrinkage of colon length 
(Figure 2 CDEF). Importantly, ABX464 did not affect the colons of mice not exposed to DSS. Noteworthy, 
the disease dampening influence of ABX464 in DSS-colitis was observed in experiments performed in 
different animal facilities, suggesting that this phenomenon is not dependent on a particular intestinal 
flora. 

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Figure 2: ABX464 treatment suppresses disease severity in DSS-induced colitis. (A) C57BL/6 mice (n=12 each cohort) Patiented to the 
DSS colitis protocol shown received orally once a day ABX464 (50 mg/kg) in methylcellulose or methylcellulose only through gavage. (B) Weight development in ABX464 
and methycellulose (MC) only treated mice during DSS-induced colitis. Control cohorts included mice not exposed to DSS. (C, D, E) At the end of the protocol described in 
A mice were sacrificed and colons were analyzed by histology for colitis severity including number of lesion (C), lesion size (D) and colon size (E). (F) Representative images 
of hematoxylin and eosin staining of paraffin-embedded colon sections prepared as “Swiss rolls”. Single lesions are delimited by black lines. (G) Representative images of 
lesions with different pathological grade according to Hao et al. Grade 1: Immune cell infiltration in lamina propria (LP); intact epithelial barrier and GI structure. Grade 2: 
Immune cell infiltration in LP; crypt distorsion or loss; gobelet cell loss; intact, but abnormal epithelial barrier. Grade 3: Immune cell infiltration in LP and submucosa; epithelial 
barrier loss and ulceration/necrosis.  
ABIVAX tested whether the protective effect of ABX464 is maintained during prolonged DSS exposure 
(Figure 3A), which typically is lethal for mice. However, the daily application of ABX464 allowed the mice 
to be exposed to DSS for at least 63 days. Following a moderate initial body weight loss of approximately 
5%, the mice recovered and maintained their initial body weight (Figure 3B). The mice that received 
ABX464 for only the first 20 days during the prolonged DSS exposure displayed similar body weight 
development and survival rates to those that received ABX464 for the entire study. Nevertheless, the 
colons of these two mouse cohorts displayed significant differences when examined for 
histopathological parameters including lesion size (Figure 3 C D). This finding suggests that the 20-day 
administration of ABX464 provided a partially protective effect that was maintained for the duration of 
the 63-day DSS challenge.   

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(UC) disease because it demonstrates long-lasting control of the HIV-virus in humanized mice as well 
as the critical features of DSS-induced colitis. 
1.2.5. Preclinical data of ABX464 
 
1.2.5.1. 
Non-clinical background information 
The toxicity of ABX464 and ABX464-N-Glu was studied in a range of rodent and nonrodent species 
(rats, rabbits, dogs, cynomolgus and marmoset monkeys, and mini-pigs) with treatment durations 
ranging from 2-weeks to 6/9 months. These studies have demonstrated that ABX464 and ABX464-N-
Glu are overall well tolerated. Vomiting and ptyalism were the major clinical sign, and the main target 
organs of ABX464 toxicity were the gastro-intestinal tract and the liver. The adverse effects noted on 
these organs were essentially mild/moderate but showed reversibility during the recovery phases. 
ABX464 was found to be non-genotoxic. Its main metabolite, the ABX464-N-Glu was not mutagenic as 
assessed by an Ames test, an in vitro and an in vivo micronucleus assay. 
Reproductive toxicity was assessed from fertility to postnatal development, in five studies. In rabbits, the 
maternal NOAEL was considered to be mg/kg od. and the NOAEL for the embryo-fetal development 
less than mg/kg od. In rats, the maternal NOAEL and the NOAEL for pup development and survival is 
considered to be lower than 
mg/kg od. The F1 generation NOAEL is considered to be 40mg/kg od. 
in absence of adverse effect at this dose-level. 
 
  
In minipigs the main adverse finding was 
 
 observed at dose levels of 
mg/kg 
and above. The liver lesions observed in the single animal administered mg/kg od, were not considered 
adverse. Based on this observation, the NOAEL is mg/kg od. 
No signs of hepatotoxicity have been observed in any of the patients treated with ABX464 in the 
previously conducted or on-going clinical trials. ABIVAX and its clinical experts consider that patients 
treated with ABX464 are not at increased risk of developing a drug-induced hepatotoxicity. 
A specific liver function monitoring plan has been implemented in the current clinical study. 
Regarding the other observations made from the pre-clinical toxicology program, please refer to the 
current version of the Investigator’s Brochure. 
1.2.5.2. 
 Previous clinical experience with ABX464 
The effect of ABX464 in humans has been assessed in 5 completed clinical studies in healthy volunteers 
and in patients with HIV as well as in 1 completed study in patients with UC (ABX464-101). In addition, 
there is efficacy and safety data available from an interim analysis of the longer-term maintenance Study 
ABX464-102 in UC. Two further studies in UC (ABX464-103; ABX464-104) and 2 studies in RA 
(ABX464-301; ABX464-302) are ongoing. As of October 31, 2019, 211 subjects have received single 
doses (25 to 200 mg) of ABX464, or repeated doses (50 to 150 mg) up to a maximum duration 
approaching 2 years. An additional 18 subjects have received ABX464 or placebo in ongoing blinded 
studies. 
ABX464 was rapidly absorbed and metabolised into ABX464-N-Glu within about 1 hour of treatment 
whatever the dose. After repeated administrations of ABX464, an initial decrease in ABX464 AUC was 
observed until steady state was reached after 4 weeks of treatment. Exposure to ABX464-N-Glu was 
much higher than to ABX464 in all patients. Food significantly increased ABX464 exposure, at least 2.8-
fold.3. 
Overall, the safety profile of ABX464 is acceptable; 8 serious AEs have been reported with ABX464, 
which were all considered not related to the investigational product. The most frequently reported AEs 
were nausea, vomiting and headache which were of mild to moderate intensity, occurring after treatment 
onset and transient in nature. The anticipated ABX464 adverse events are: Nausea, Vomiting, 
Abdominal pain upper, Abdominal pain, Diarrhea and Headache 

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For further information, please refer to the current Investigator’s Brochure. 
1.3. Rationale for the clinical study and study design 
A Phase IIa study (ABX464-101) aimed at evaluating the efficacy and safety of ABX464 given at a fixed 
dose of 50mg once daily versus Placebo in Patients with Moderate to Severe Active Ulcerative Colitis 
who have failed or are Intolerant to immunomodulators, Anti-TNFα or Corticosteroids was conducted in 
Belgium, France, Germany, Austria, Poland, Hungary. 
32 patients were randomized (23 ABX464 patients/9 placebo). The principal study results are presented 
below. 
A strong efficacy signal was observed with ABX464 50 mg: 
▪ Clinical Remission rate of 35.0 % of ABX464 patients (Placebo = 11.1%) 
▪ Endoscopic improvement rate of 50.0 %* (p=0.03) of ABX464 patients (Placebo = 11.1%) 
▪ Clinical Response rate of 70.0 % of ABX464 patients (Placebo = 33.0%) 
Same results were also observed in Total and Partial Mayo Score, as depicted in the following graphs 
 
 
Figure 5: Mean change in Total and Partial Mayo in ABX464-101 study 
At the end of the completed 2 months induction treatment study, 22 Patients (15 previously treated with 
ABX464 and 7 on placebo) were enrolled into the open-label maintenance study with ABX464 50mg 
daily (ABX464-102) regardless of what treatment they had previously received. An interim analysis of 
this maintenance study was performed after all patients had completed at least 12 months dosing in the 
maintenance study, with a mean ABX464 treatment duration in the maintenance study of 422 days. 
The interim analysis used the Month 12 Per Protocol (M12 PP) dataset which included all subjects that 
had a Month 12 visit. Of the 22 subjects, 3 subjects were excluded from the M12 PP Set: 2 subjects 
from the ABX464 induction group (one who withdrew due to lack of efficacy at M1 of the maintenance 
study and one who was lost to follow-up) and 1 subject from the placebo induction group (grade 2 
headache at month 4), resulting in 19 subjects analyzed in the efficacy M12 PP set at baseline. Of the 
nineteen subjects in the set, sixteen had had a Month 12 endoscopy performed which forms part of the 
Total Mayo score (TMS).  
Clinical remissions obtained at the end of the induction study were durable and the rates further 
improved during the maintenance phase, as additional subjects achieved clinical remission during 12 
months treatment.  
All patients who had an endoscopy performed, had an endoscopic subscore of 0 or 1. 12/16 patients 
were in clinical remission at month 12. 
Mean and median fecal calprotectin and CRP showed continued declines during the maintenance study, 
though the large variability and small patient numbers requires that the results should be interpreted 
with caution.  The measurement of miR124 relative gene expression by qPCR using whole blood 
samples was included in both ABX464-101 and -102.  A total of 19 patients were sampled on day 0, 28, 
56 of ABX464-101 and on day 365 (while in ABX464-102). Statistically significant increases of miR124 
expression were observed at all these time points. 
No severe or serious adverse reactions were reported. Most adverse events were of mild to moderate 
intensity. These efficacy and safety results warrant the continuation of the clinical development of 
ABX464 in this indication. 

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2. STUDY OBJECTIVES AND ENDPOINTS 
2.1. Primary Objective 
The primary objective of the study is to determine an optimal ABX464 dose to be used in moderate to 
severe active ulcerative colitis patients who have failed or are intolerant to immunomodulators, Anti-
TNFα, vedolizumab, JAK inhibitors and/or corticosteroids by comparing the mean change from baseline 
in the MMS at week 8 between each ABX464 group and placebo. 
2.2. Secondary Objectives 
The secondary objectives are: 
▪ To evaluate the effect of the different dose groups of ABX464 on Modified Mayo Score at Week 16 
(if available) and on partial Modified Mayo Score at every study visit versus placebo. 
▪ To evaluate the global effect of ABX464 on Modified Mayo Score at Week 8 and Week 16 (if 
available) and on partial Modified Mayo Score at every study visit versus placebo. 
▪ To evaluate the effect of the different dose groups of ABX464 on clinical remission at Week 8 and 
at Week 16 (if available) versus placebo. 
▪ To evaluate the effect of the different dose groups of ABX464 on clinical response at week 8 and 
at Week 16 (if available) versus placebo. 
▪ To evaluate the effect of the different dose groups of ABX464 on endoscopic improvement and 
endoscopic remission, by segment, at Week 8 and Week 16 (if available) versus placebo. 
▪ To evaluate the effect of the different dose groups of ABX464 on mucosal healing, at Week 8 and 
Week 16 (if available) versus placebo 
▪ To evaluate the effect of the different dose groups of ABX464 on stool and rectal bleeding 
frequency at every study visit versus placebo. 
▪ To evaluate the effect of the different dose groups of ABX464 on fecal calprotectin and CRP levels 
at Week 8 and Week 16 versus placebo. 
▪ To evaluate the effect of the different dose groups of ABX464 on miR-124 expression in tissue 
(RNA later) at Week 8 and Week 16 (if available) and in total blood at every timepoint versus 
placebo. 
▪ To evaluate the effect of the different dose groups of ABX464 versus placebo on the 
rectal/sigmoidal infiltrates using the Robarts Histopathology Index (RHI), the Geboes and Nancy 
Histology Scoring Scales at Week 8 and Week 16 (if available) versus placebo. 
▪ To evaluate the effect of the different dose groups of ABX464 on Quality of Life (QoL) measured 
by the IBDQ at Week 8 and Week 16 versus placebo. 
▪ To evaluate the effect of the different dose groups of ABX464 on IL-6, TNFα, IL-1b, IL-10 plasma 
concentrations at every timepoint versus placebo. 
▪ To assess the pharmacokinetics of the ABX464 and its main active metabolite ABX464-N-Glu after 
oral administration of different daily doses of ABX464 using population approach. 
▪ To evaluate the safety profile of the different dose groups of ABX464 versus placebo. 
2.3. Primary Endpoint 
The primary endpoint is the reduction from baseline in Modified Mayo Score at Week 8. 
2.4. Secondary Endpoints 
The secondary endpoints of this study are: 
▪ Number and rate of patients in clinical remission at Week 8, per each intervention/treatment group. 
Clinical remission, based on the Mayo Scoring system, is defined as stool frequency subscore = 0 
or 1 and rectal bleeding subscore = 0 and endoscopy subscore = 0 or 1 (modified to exclude 
friability). 

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▪ Combined number and rate of patients in clinical remission at Week 8 and at Week 16, per each 
intervention/treatment group. 
▪ Number and rate of patients with clinical response at Week 8 and Week 16 per 
intervention/treatment group. Clinical Response is defined as a reduction in Mayo Score of at least 
2 points and greater than or equal to 30 percent from baseline with an accompanying decrease in 
rectal bleeding sub-score of greater than or equal to 1 point or absolute rectal bleeding sub-score 
of less than or equal to 1 point.  
▪ Number and rate of patients with endoscopic improvement, by segment, and number and rate of 
patients with endoscopic remission, by segment, at Week 8 and at Week 16 (if available) per 
intervention/treatment group. Endoscopic improvement is defined as a Mayo endoscopic sub score 
of ≤1 (excluding friability) and endoscopic remission defined as sub score of 0. 
▪ Number and rate of patients with mucosal healing. Mucosal healing is defined as both endoscopic 
remission and histological remission (Geboes score < 2.0). 
▪ Reduction relative to baseline in stool and rectal bleeding frequency at every study visit by ABX464 
dose group and versus placebo. 
▪ Reduction relative to baseline in partial Modified Mayo Score at every study visit and Modified 
Mayo Score at Week 16 (if available) by ABX464 dose group and versus placebo. 
▪ Reduction relative to baseline in fecal calprotectin and CRP levels at Week 8 and Week 16 by 
intervention/treatment group. 
▪ Change relative to baseline in miRNA-124 expression in rectal/sigmoidal biopsies at Week 8 and 
Week 16 (if available) and in total blood at every timepoints by intervention/treatment group. 
▪ The scores and changes from baseline in IBDQ at Week 8 and Week 16 per intervention treatment 
group. 
▪ Reduction relative to baseline of infiltrate/histopathology (rectal/sigmoidal biopsies) using the 
Robarts Histopathology Index (RHI), the Geboes and Nancy Histology Scoring Scales at Week 8 
and Week 16 (if available) per intervention/treatment group. 
▪ Change relative to baseline in IL-6, TNFα, IL-1b, IL-10 plasma concentrations at every timepoints 
by intervention/treatment group. 
▪ Serum concentration of ABX464 and ABX464-N-Glu according to dose group. 
▪ Number and rate of all adverse events, causally-related adverse events, all SAE and causally-
related SAEs classified by severity per intervention/treatment group. 
▪ The incidence of treatment-emergent serious adverse event per intervention/treatment group. 
▪ The incidence of adverse events leading to investigational medicinal product discontinuation per 
intervention/treatment group. 
▪ The number of clinically-significant laboratory abnormalities per intervention/treatment group. 

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endoscopy sub-score of 2 or 3). 
From Week 8 onwards, in the event of clinical progression of the disease defined as at least a 2-point 
increase from the screening in partial Modified Mayo Score (pMMS) with a Modified Mayo Score ≥ 4 
confirmed by an endoscopy sub score of 2 points or higher, the patient will exit definitively the study. 
Approximately 244 patients will be randomized in this study (i.e. 61 patients per study treatment arm). 
3.1.2. Dose limiting toxicity (DLT) 
A dose limiting toxicity (DLT) is defined as a grade 3 or higher adverse event as defined by the Common 
Terminology Criteria for Adverse Events (CTC-AE V5.0) considered by a safety review board as 
probably or definitely related to study treatment. 
If more than 2 DLTs occur in the first five treated patients for at least 14 days, then the enrolment of 
additional patients in the concerned treatment group will be stopped, otherwise the enrolment of planned 
patients will be confirmed. 
In addition, in case of a life threatening (grade 4) adverse reaction enrolment in the concerned treatment 
group and treatment of ongoing patients will be immediately discontinued. 
In both cases, enrolment will only be resumed upon the decision of the sponsor if the Data Safety 
Monitoring Board can conclude that the causality of the event was unrelated or unlikely related to study 
treatment. 
3.1.3. Data Safety Monitoring Board 
An independent Data Safety Monitoring Board (DSMB), with expertise and experience in the pathology, 
and without direct involvement in the conduct of the trial, will be set up specifically to guarantee effective 
protection of patients, to ensure the ethical conduct of the trial, to evaluate the  benefit/risk ratio of the 
trial, and to ensure the independent review of the scientific results during the trial and at the end of the 
trial. Besides, the DSMB may recommend the early termination of the trial at any time if an unacceptable 
toxicity occurs. The DSMB will meet every 2 months. 
The DSMB will oversee the adequate balance of baseline characteristics (gender, disease duration, 
concomitant treatment with corticosteroids, fecal calprotectin level, tobacco use) among the treatment 
groups. 
In addition, DSMB will be review all potential causally-related Serious Adverse Events within 7 days of 
the initial report. 
The DSMB has only a consultative role. It will inform the Sponsor who will decide whether the DSMB 
recommendation will be followed. A DSMB charter must be available upon submission of the trial (initial 
protocol) to the respective competent authorities. 
3.2. Duration of study participation 
Eligible patients will be enrolled in the present study at the screening visit within 4 Weeks (28±3 days) 
prior to the first dosing, hence the maximum screening period is 31 days. However, patients can be 
randomized anytime within the screening window if all examinations are performed as per their schedule 
and results are available. Patients will be treated for 16 Weeks. At Week 16, regardless of their 
clinical/symptomatic response and the actual treatment/dose received, patients willing to continue the 
study treatment and eligible for enrollment will roll over in an Open Label Extension study (ABX464-
104). In this extension study, all patients will be dosed with ABX464 50mg QD.  
In any other cases, patients will exit the study (EoS visit to be performed within a Week after last dosing) 
and will be treated according to the standard of care.  
Thus, the total duration of the study participation is 21 Weeks. 

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4. STUDY POPULATION 
4.1. Number of Patients/Centers 
Up to 244 patients will be randomized in this study. These patients will be enrolled in approximately 110 
to 150 sites located in Europe, Canada and in the USA. 
4.2. Eligibility Criteria 
4.2.1. Inclusion Criteria 
A patient will be eligible for inclusion in this study only if ALL of the following criteria apply: 
▪ Men or women age 18 - 75 years; 
▪ Diagnosis of moderate to severe active UC (including ulcerative proctitis if proximal extension of 
disease occurs beyond 10 cm) confirmed by endoscopy and histology at least 12 Weeks prior to 
screening visit. Moderate to severe active UC defined by Modified Mayo Score (MMS) of 5 to 9 
inclusive (on a scale of 0-9). Moderate to severe active UC should be confirmed at screening visit 
with a centrally read endoscopy sub-score of at least 2 (on a scale of 0-3); 
▪ Patients having either a documented inadequate response, no response, a loss of response, or an 
intolerance (defined as the occurrence of at least one Adverse Reaction leading to treatment 
discontinuation) to either immunosuppressant treatment (i.e., azathioprine, 6-mercaptopurine, 
methotrexate), tumor necrosis factor [TNF] inhibitors, vedolizumab, JAK inhibitors and/or 
corticosteroid treatment. Inadequate response, no response, loss of response is defined as: 
o Active disease or relapse in spite of thiopurines or methotrexate given at an appropriate dose 
for at least 3 months (i.e. azathioprine 2–2.5 mg/kg/day or mercaptopurine 1–1.5 mg/kg/day 
in the absence of leukopenia), and/or 
o Active disease despite corticosteroids treatment (prednisolone up to 0.75 mg/kg/day) over a 
period of 4 Weeks, and/or 
o Active disease or relapse in spite of adequate treatment (as defined in the SmPC) with tumor 
necrosis factor [TNF] inhibitors or vedolizumab, and/or 
o Active disease or relapse in spite of adequate treatment with JAK inhibitors over a period of 
at least 6 Weeks. 
▪ Patients receiving oral corticosteroids must have been on a stable dose of prednisone or 
prednisone equivalent (≤20 mg/day) or on beclomethasone diproprionate (≤5mg/day) or on 
budesonide MMX (≤9 mg/day) for at least 2 Weeks prior to the screening visit; 
▪ Topical corticosteroids and topical 5-aminosalicylic acid preparations must have been withdrawn 
at least 2 Weeks prior to the screening visit; 
▪ Patients who are on oral 5-aminosalicylic acid must have been on a stable dose for at least 4 
Weeks prior to the screening visit; 
▪ Patients who are receiving immunosuppressants in the form of azathioprine, 6-mercaptopurine, or 
methotrexate needed to be on a stable dose for at least 4 Weeks prior to screening visit. Patients 
taking methotrexate also are advised to take folic acid 1 mg/day (or equivalent) supplementation if 
there is no contraindication; 
▪ Patients on probiotics (e.g., Culturelle® [Lactobacillus GG, i-Health, Inc.], Saccharomyces 
boulardii) must be on stable doses for at least 2 Weeks prior to the screening visit; 
▪ Patients on antidiarrheals (e.g., loperamide, diphenoxylate with atropine) must be on stable doses 
for at least 2 Weeks prior to the screening visit; 
▪ Patients who have received tumor necrosis factor [TNF] inhibitors, vedolizumab or other biologics 
must have discontinued therapy at least 8 Weeks prior to the screening visit due to lack or 
insufficient efficacy or intolerance; 
▪ Patients previously treated with cyclosporine, tacrolimus or JAK inhibitors must have discontinued 
therapy at least 4 Weeks prior to the screening visit due to lack or insufficient efficacy or intolerance; 
▪ Patients previously treated with tube feeding, defined formula diets, or parenteral 
alimentation/nutrition must have discontinued treatment 3 Weeks before the screening visit and 

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must be able to take, orally, appropriate amount of food (calories) and liquids to maintain body 
weight; 
▪ Patients with surveillance colonoscopy defined as per ECCO guidelines; 
▪ Patients with the following hematological and biochemical laboratory parameters obtained at 
screening: 
o 
Hemoglobin > 9.0 g dL-1; 
o 
Absolute neutrophil count ≥ 750 mm-3; 
o 
Platelets ≥ 100,000 mm-3; 
o 
Total serum creatinine ≤ 1.3 x ULN (upper limit of normal); 
o 
Creatinine clearance > 90 mL min-1 by the Cockcroft-Gault equation within 60 days 
prior to baseline; 
o 
Total serum bilirubin < 1.5 x ULN; 
o 
Alkaline phosphatase, AST (SGOT) and ALT (SGPT) < 2 x ULN; 
▪ Patients are able and willing to comply with study visits and procedures as per protocol; 
▪ Patients should understand, sign and date the written voluntary informed consent form at the 
screening visit prior to any protocol-specific procedures are performed; 
▪ Patients should be affiliated to a social security regimen (for French sites only); 
▪ Females and males receiving the study treatment (potentially in combination with 
immunosuppressant) and their partners must agree to use a highly effective contraceptive method 
during the study and for 6 months after end of study or early termination. Contraception should be 
in place at least 2 Weeks prior to study participation. Women must be surgically sterile or if of 
childbearing potential must use a highly effective contraceptive method. Women of childbearing 
potential (WOCBP) will enter the study after confirmed menstrual period and a negative pregnancy 
test. Highly effective methods of contraception include true abstinence, intrauterine device (IUD) 
or hormonal contraception aiming at inhibition of ovulation, intrauterine hormone releasing system, 
bilateral tubal ligation, vasectomized partner. True abstinence is defined when this is in line with 
the preferred and usual lifestyle of the patient. In each case of delayed menstrual period (over one 
month between menstruations) confirmation of absence of pregnancy is required. This 
recommendation also applies to WOCBP with an infrequent or irregular menstrual cycle. Female 
and male patients must not be planning pregnancy during the trial and for 6 months post completion 
of their participation in the trial. In addition, male participants should use condoms and not donate 
sperm as long as contraception is required. 
4.2.2. Exclusion Criteria 
The following criteria should be checked at the time of screening. If ANY exclusion criterion applies, the 
patient will not be included in the study: 
▪ Patients with Crohn's Disease (CD) or presence or history of fistula, indeterminate colitis (IC), 
infectious/ischemic colitis or microscopic colitis (lymphocytic and collagenous colitis); 
▪ History of toxic megacolon, abdominal abscess, symptomatic colonic stricture or stoma; history or 
imminent colectomy, colonic malignancy; 
▪ History or current evidence of colonic dysplasia or adenomatous colonic polyps. Patient with severe 
gastrointestinal complications; e.g., short bowel syndromes, recent or planned bowel surgery, 
Ileostomy and/or colostomy, recent bowel perforation; 
▪ History of more than one episode of herpes zoster or a history (single episode) of disseminated 
zoster; 
▪ Patients with active infections at screening such as infected abdominal abscess, Clostridium 
difficile (stool antigen and toxin required), CMV (positive IgM), TB and recent infectious 
hospitalization; 
▪ Patients previously treated with ABX464; 
▪ Acute, chronic or history of clinically relevant pulmonary, cardiovascular, hepatic, pancreatic or 
renal functional abnormality, encephalopathy, neuropathy or unstable CNS pathology such as 
seizure disorder, angina or cardiac arrhythmias, active malignancy or any other clinically significant 

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medical problems as determined by physical examination and/or laboratory screening tests and/or 
medical history; 
▪ Acute, chronic or history of immunodeficiency or autoimmune disease; 
▪ History of malignancy excluding patients considered cured (5 years disease free survivors); 
▪ Serious illness requiring systemic treatment and/or hospitalization within 3 Weeks prior to baseline; 
▪ Pregnant or breast-feeding women; 
▪ Illicit drug or alcohol abuse or dependence; 
▪ Patients who received live vaccine 30 days or fewer before first dose of study treatment and/or 
who’s planning to receive such a vaccine during the study duration; 
▪ Use of any investigational or non-registered product within 3 months or within 5 half-lives preceding 
baseline, whichever is longer and during the study; 
▪ Any condition, which in the opinion of the investigator, could compromise the patient's safety or 
adherence to the study protocol. 

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▪ Disease extent (proctitis, left-sided or extensive), duration and disease activity, prior treatment and 
smoking status; 
▪ Refractoriness to biologics (primary non-response or loss of response); 
▪ Body weight and height; 
▪ Medical history; 
▪ Clostridium difficile (stool antigen and toxin), CMV (IgG and IgM), TB; 
▪ Physical examination and vital signs; 
▪ Hematology and Biochemistry including pregnancy test for all women of childbearing potential; 
▪ 12 leads ECG; 
▪ Sigmoidoscopy with rectal and sigmoidal (if the sigmoid is inflamed) biopsies (within 14 days prior 
to randomization/baseline); central read results must be available before randomization; 
▪ Record endoscopy sub-score and transfer videos to central reader; 
▪ Partial Modified Mayo Score (within a week prior to endoscopy) and Modified Mayo Score (once 
endoscopy is performed); 
▪ Hand over the e-Diary to the patient and instruct the patient how to use it; e-Diary should be 
collected daily from screening to end of study; 
▪ Record all medications received within 3 months prior to baseline and note if the medication is 
continuing; 
▪ Record all UC medication without time limitation; 
▪ Adverse Event reporting: 
▪ Inclusion/exclusion criteria will be verified. 
5.2.2. Baseline (First dosing day / Day 1) 
▪ Randomization: The Investigator needs to check the inclusion/exclusion criteria (central read of the 
endoscopy and patient’s symptom score from e-diary) with respect to the procedures performed at 
screening visit and if applicable proceed with the patient randomization. Treatment numbers will 
be allocated at randomization via the IWRS and dispensed to the patient; 
▪ IBD Questionnaire (as the patient’s first procedure); 
▪ Physical examination and vital signs; 
▪ Body weight; 
▪ 12 leads ECG; 
▪ Population Pharmacokinetics blood samples at either 0.5, 1.5, 3h (and 6 h and/or 10 h if possible) 
or at 1, 2, 4h (and 8 h and/or 12 h if possible); 
▪ Hematology and Biochemistry including blood pregnancy test for all women of childbearing 
potential, coagulation parameters and troponin; 
▪ Blood sample for miR-124 (PAXgene® tube) and cytokines determination; 
▪ Serum collection for patients with loss of response to previous biologics (i.e. neutralizing 
antibodies); 
▪ Fecal calprotectin dosage; 
▪ Partial Modified Mayo Score; 
▪ Review the patient e-Diary; 
▪ Adverse Events reporting; 
▪ Dispense study treatment to patient and instruct how to take them (First dosing at site); 
▪ Schedule next patient visits. 
5.2.3. Day 8, Day 29, Day 85 Visits 
▪ Physical examination and vital signs; 
▪ Body weight; 
▪ Hematology and Biochemistry including coagulation parameters and troponin; 

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▪ Blood pregnancy test for all women of childbearing potential (D29 and D85 only); 
▪ Blood sample for miR-124 (PAXgene® tube) and cytokines determination at Day 8 and Day 29 
only; 
▪ Check treatment compliance and review the patient e-Diary; 
▪ Partial Modified Mayo Score; 
▪ Population Pharmacokinetics blood samples pre-dose; 
▪ Adverse Events reporting; 
▪ Dispense study treatment (Day 29 and Day 85 only); 
▪ Schedule next patient visits. 
5.2.4. Day 57 and Day 113 Visits  
▪ IBD Questionnaire (as the first visit procedure); 
▪ Physical examination and vital signs; 
▪ Body weight; 
▪ At Day 113, population Pharmacokinetics blood samples at either pre-dose, 1, 2, 4h and if possible 
48 h (Day 115 only) or pre-dose, 0.5, 1.5, 3h and if possible 48 (Day 115 only); 
▪ Hematology and Biochemistry including blood pregnancy test for all women of childbearing 
potential, coagulation parameters and troponin; 
▪ Blood sample for miR-124 dosage (PAXgene® tube) and cytokines determination; 
▪ 12-leads ECG;  
▪ Fecal calprotectin; 
▪ Sigmoidoscopy with rectal/sigmoidal biopsies (Day 113 endoscopy is conditional on the response 
at Day 57); 
▪ Modified Mayo Score at Day 57 (and Day 113 if available; OR pMMS at Day 113 if Day113 
endoscopy not performed); 
▪ Check treatment compliance; 
▪ Adverse Events reporting; 
▪ Study treatment dispensation at Day 57 visit; 
▪ Review the patient e-Diary; 
▪ At Day 113, enrolment of patients willing to take part to the maintenance phase; 
▪ Schedule next patient visits. 
5.2.5. End of Study Visit  (Within a week after last dose ± 2 days) 
This EoS visit applies to all premature discontinued patients and to patients not taking part to the 
maintenance study. Patients will perform an End of Study Visit (EoS) within a Week after last dosing (i.e 
D120 ± 2 days if the patient completed the study and is not taking part in maintenance study). Patients 
will be treated according to the standard of care from the last day of study treatment.  
Following examinations/procedures should be performed: 
▪ Physical examination and vital signs; 
▪ Body weight; 
▪ Hematology and Biochemistry and a follow-up 3 Weeks later; 
▪ Partial Modified Mayo Score; 
▪ 12 leads ECG;  
▪ Fecal calprotectin; 
▪ Adverse Events reporting. 
NB#1: In case of premature discontinuation occurring during the treatment phase (D1-D113), the above 
examinations should be performed as an End of Study Visit 7 days ± 2 days after last dose. 

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NB#2: A biological follow-up, including hematology, biochemistry panel and a pregnancy test (if 
applicable), should be performed according to the central lab manual 3 Weeks after EOS (i.e Day 120 
if the patient completed the study and is not taking part in maintenance study). In case of premature 
discontinuation, this biological follow up should be performed 3 weeks after the last dose. No specific 
study visit is required. Potential Adverse Event or Clinically significant abnormal value should be 
reported according to the section 8.4 of the study protocol. 

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5.3. Detail of the study assessments  
5.3.1. Physical Examination and Vital Signs 
A routine physical examination (including body weight) will be done at each study visit. Physical 
examinations will cover eyes, ears, nose, throat, lungs/thorax, heart/cardiovascular system, abdomen, 
skin and mucosae, nervous system, lymph nodes, musculo-skeletal system, and, if applicable, others. 
Any new clinically relevant finding compared to baseline must be documented as adverse event. 
Measurements of vital signs will be done at each visit (Blood pressure, Heart Rate, Body temperature). 
The patient should rest supine for at least 10 minutes prior to measurements. The measurements can 
be performed either in sitting or supine position of the patient. The right or left arm may be used. 
However, the position and the arm used for measurement should be kept constant throughout the trial 
for an individual patient.  
The investigator should ensure that each parameter outside the normal range is assessed for clinical 
significance. For any deviation assessed clinically significant, the investigator has to document the 
change as an AE in the CRF.  
In addition, it is at the discretion of the investigator to document any change or trend over time in vital 
signs as an AE if he considers the change to be clinically significant, even if the absolute value is within 
the alert limit or reference range. 
5.3.2. Adverse Events of Interest 
Treatment with ABX464 has been associated with the occurrence of mainly mild to moderate Adverse 
Events; more specifically with headache episodes and skin lesions. To collect information regarding 
these Adverse Events of Interest, the following procedure should be applied: 
▪ In case of occurrence of a skin lesion (regardless of its severity), a dermatologist consultation 
should be scheduled to evaluate the type of lesion, its severity and etiology. An anonymized 
medical report shall be provided to the Sponsor. 
▪ In case of occurrence of a headache episode lasting more than a week and refractory to standard 
painkillers (Ibuprofen, acetaminophen, paracetamol, etc.…), a specific questionnaire will be filled 
in by the patients to better characterize the attributes of the event (Appendix #4). 
5.3.3. Pregnancy 
For all female patients of childbearing potential, a blood pregnancy test (beta human chorionic 
gonadotropin [HCG]) will be performed at Day -28, Day 1, Day 29, Day 57, Day 85 and Day 113. In case 
of positive pregnancy testing, detailed procedures can be found in section 8.4.2. 
5.3.4. ECG 
Electrocardiograms will be performed at Day -28, Day 1, Day 57, Day 113 and EoS visit. At least a 12-
lead ECG with recordings of at least 6 action potentials in lead II (paper speed 25mm/s, amplitude 
10mm/mV) will be measured with the patient in a resting position. Prior to the recording the patient 
should be at rest for at least five minutes. Resting ECG is recommended to be performed before any 
examinations. 
The ECG printout will be reviewed by the Investigator and a signed and dated copy of the ECG will be 
attached to the medical file. The original ECG printouts are considered as source data and should be 
stored at site. If thermal paper is used, a copy of the original ECG must also be kept. All abnormal 
findings must be documented in the CRF. Any clinically relevant findings compared to ECG done at Day 
-28 must be documented as adverse events. 
5.3.5. IBD Questionnaire (IBDQ) 
The Inflammatory Bowel Disease Questionnaire (IBDQ) is a widely used questionnaire for HRQoL 
assessment in patients with inflammatory bowel diseases (IBDs). This questionnaire has been adapted 

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and validated into several languages. IBDQ will be filled in by the patients at Day 1, Day 57 and Day 
113 prior to any study procedures. 
5.3.6. Modified Mayo Score - Stool and Rectal Bleeding Frequency 
The Stool and Rectal Bleeding frequency assessment will be based on the Mayo scoring system which 
is the most commonly used index in clinical trials.  
Total Mayo score consists of 4 items: stool frequency, rectal bleeding, flexible sigmoidoscopic 
examination, and a physician global assessment (Appendix #3). Modified Mayo Score (MMS) consists 
of 3 items (stool frequency, rectal bleeding, flexible sigmoidoscopic examination). 
Partial Modified Mayo Score (pMMS) consists of only 2 items (stool frequency, rectal bleeding). 
Although the physician global assessment is performed as part of the patient care, only the pMMS and 
MMS will be assessed as endpoints according to regulatory guidance. Stool frequency and rectal 
bleeding frequency will be recorded from the patient e-Diary at each patient visit by the Investigator. 
Attention: Investigators should train his/her patient how to record stool frequency and rectal bleedings 
in the e-Diary. Instruction booklet, detailing the FDA requirements for Patient Reported Outcomes, will 
be provided to patients and investigators.  
5.3.7. Sigmoidoscopy with rectal/sigmoidal biopsies 
Sigmoidoscopies procedures (or colonoscopies if applicable) will be standardized for optimized video 
acquisition at clinical sites.  Sigmoidoscopies should be performed according to the Central Imaging 
Management System Charter.  
Central Imaging Management System will be provided including a central image database. Once 
uploaded, video data will be analyzed for quality and resolution prior to independent review by an expert 
central reader. 
Study videos will be scored separately using the Mayo Clinic Score (excluding friability) for all time points 
by central readers who are blinded to the treatment and visit sequence of the recordings.  
The central reader’s score at Screening, Day 57 and Day 113 (if available) will be entered directly into 
the eCRF. Screening videos will be evaluated for eligibility and scores communicated to sites within four 
(4) business days. All procedure videos collected for outcome evaluation will be scored and results 
communicated within five (5) business days. 
Two rectal biopsies (plus optionally two sigmoidal biopsies, if the inflammation of the sigmoid is 
observed) will be performed at Screening, at Day 57 and at Day 113 (if applicable). The two (or 4) 
biopsies will be sent to central laboratories for assessment according to Robarts Histopathology Index 
(RHI), the Geboes and Nancy Histology Scoring Scales (please refer to the lab manual) and for miRNA-
124 determination (RNA later). 
RHI score ranges from 0 (no disease activity) to 33 (severe disease activity) and is based on the 
evaluation of four main parameters: chronic inflammatory infiltrate, lamina propria neutrophils and 
eosinophils, neutrophils in the epithelium and erosion/ulceration. Overall, this histological index has 
been reported to be reproducible, responsive and valid and will be used for confirmation of the mucosal 
healing. The patient’s biopsies will be also read according to the Geboes and Nancy Histology Scoring 
Scales for completeness purposes. 
5.3.8. Hematology and biochemistry 
For hematology and biochemistry central laboratory will be used (i.e. Eurofins). All lab dosages will be 
done centrally. Sampling kits and transportation information and devices will be provided by Eurofins. 
Due to the outbreak of the SARS Cov-2 pandemic, some patients may not attend the study site, therefore 
hematology and biochemistry measurements may be done locally to assess the safety. 
Regarding the calprotectin measurement, the local lab might be asked to keep back-up samples at -
80°C till the end of the study. 

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o 
Last day (Day 113): predose, 1, 2, 4 and if possible 48 h (Day 115). D115 will only be 
taken if the subject is not transitioning to the ABX464-104 study. 
• 
Group 2:  
o 
Day 1: 1, 2, 4 (and 8 h and/or 12 h if possible) 
o 
Last day (Day 113): predose, 0.5, 1.5, 3 and if possible 48 h (Day 115). D115 will only 
be taken if the subject is not transitioning to the ABX464-104 study. 
In addition to these sampling time points, pre-dose concentrations could be collected at the study visit 
day 8, 29, 85. Patient data will be pooled with data obtained in previous clinical studies in order to build 
a population pharmacokinetic models for ABX464 and its metabolite. 
5.4. Summary of blood samples 
The Table  below summarizes the volume of blood to be sampled at each study visit. 
Table 3: Blood Volume 
COLLECTION 
TUBE 
SCR D-
28 
BSL 
D1 
D8 
D29 
D57 
D85 
D113 
EOS 
D120 
FU 
TOTAL 
Hematology (Hemoglobin, 
Hematocrit, Red Cell Count, 
MCV, MCHC, Platelets, White 
cell count with diff.) 
EDTA tube 
2.0 
2.0 
2.0 
2.0 
2.0 
2.0 
2.0 
2.0 
2.0 
18.0 
Biochemistry panel incl CRP, 
GLDH, Serum Pregn and 
lipids 
Serum gel tube 
8.5 
8.5 
8.5 
8.5 
8.5 
8.5 
8.5 
8.5 
8.5 
76.5 
Fibrinogen and Prothrombin 
Time 
Na-citrate tube 
 
4.5 
4.5 
4.5 
4.5 
4.5 
4.5 
 
 
27.0 
Troponin (I&T) 
SST tube with gel 
 
3.5 
3.5 
3.5 
3.5 
3.5 
3.5 
 
 
21.0 
CMV IgG and IgM 
Serum gel tube 
3.5 
 
 
 
3.5 
Neutralizing antibodies 
(biologics) 
Serum 2 mL gel 
tube 
 
2.0 
 
 
 
 
 
 
 
2.0 
Quantiferon TB Gold Plus 
4x 1mL tube 
4.0 
 
 
 
4.0 
Cytokines (IL-6, TNFa, IL-1b, 
IL-10) 
Serum gel tube 
 
8.5 
8.5 
8.5 
8.5 
8.5 
8.5 
 
 
51.0 
PAXgene Tube (miRNA) 
PAXgene 
 
5.0 
5.0 
5.0 
5.0 
5.0 
5.0 
 
 
30.0 
PK samples 
Serum tube 
10.0 
2 
2 
 
10.0 
 
24.0 
Total per visit 
18.0 
44.0 
34.0 
34.0 
32.0 
32.0 
42.0 
10.5 
10.5 
257.0 
 

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6. INVESTIGATIONAL MEDICINAL PRODUCT(S) 
All investigational medicinal products to be used in this study have been manufactured, packaged and 
labelled by contract manufacturers for ABIVAX, according to GMP standards and are supplied to 
investigators free of charge. 
6.1. Description of investigational treatment 
The study treatment that will be administrated to patients enrolled in this Phase IIb study consists of 
capsules containing ABX464 or its matching placebo given orally once daily for 113 days. 
6.2. Description of investigational medicinal product 
6.2.1. Active investigational medicinal product (ABX464) 
The ABX464 investigational medicinal product (IMP) is a hard gelatin capsule intended for oral 
administration. 
For the proposed clinical trial, the IMP consists of size 01 capsules containing either 25mg or 50mg of 
ABX464 drug substance in the form of granulate prepared with a number of common excipients 
 It is supplied 
in study specific child-resistant blister cards. 
ABX464 will be manufactured by:  
 
 
 
 
 
Packaging and labelling activities, as well as Qualified Person release of the IMP will be performed at 
the following site: 
 
 
 
 
 
6.2.2. Placebo 
The matching placebo consists of the same hard gelatin, powder-filled capsules (size 01) filled with only 
the same common excipients 
 
 as the active IMP. It is supplied in study specific child resistant blister cards. 
ABX464 matching placebo will be manufactured by: 
 
 
 
 
Packaging and labelling activities, as well as Qualified Person release of the IMP will be performed at 
the following site: 
 
 
 
 
 

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6.3. Administration and Dosing 
6.3.1. Administration of the investigational medicinal product 
Depending on the randomization, patients will be treated with a daily dose of either 25mg, 50mg or 
100mg of ABX464 or matching placebo. All patients regardless of the treatment group will receive 2 
capsules every day. 
Patients will be orally dosed in a fed condition (regular meal) in the morning with a glass of water. 
An e-Diary, in which the patient should report the number of capsules taken and the intake time from 
baseline visit onwards, will be given to the patient at screening.  
6.3.2. Guidelines for treatment postponement and dose modifications 
No intra-patient dose escalation/dose adjustment are allowed.  
6.4. Method of Assigning Patients to Treatment Arms 
All patients will be assigned a unique and incremental Patient Identification (ID) number. Patient IDs will 
be unique (i.e. reallocation of the ID will not be permitted). The format will be a seven-digit number as 
follows: ABX-country/site number (4 digits) – Patient number (3 digits). The latter 3-digit Patient number 
will be assigned according to the patient’s order of inclusion in the center. 
Eligible non-US patients (i.e. those who fulfil all inclusion/exclusion criteria) will be randomized according 
to a 1:1:1:1 ratio to ABX464 100mg: ABX464 50mg: ABX464 25mg: placebo treatment arms. 
Randomization will be performed via IWRS. Treatment numbers will be allocated first at randomization 
and then every month (i.e. D29, D57 and D85). 
In all cases, patient should return his/her used and unused blister cards at each study visit for a 
compliance check. 
6.5. Blinding and breaking the study blind 
Study drug will be packaged in blinded label child resistant blister cards. Blister cards will be numbered 
according to a randomized treatment number list. The content of the labeling is in accordance with the 
required references listed in the Good Manufacturing Practices. 
The investigator, study personnel, and study participants are blinded with respect to treatment (i.e., 
active ABX464 or placebo). Sponsor or delegate will generate the random code list and the 
corresponding treatment number list. 
Investigators may have access to unblinding at any time via the pharmacovigilance hotline. 
6.6. Packaging 
The IMP consists in hard gelatin, powder-filled capsules (size 01) containing 25 or 50 mg of ABX464 
supplied in study specific child-resistant blister cards. 
6.7. Storage 
ABX464/Placebo capsules will be shipped to the investigational site at a temperature not above 
 
 
 
The IMP should not be used beyond the expiration date. Drug supplies are to be stored in a secure, 
limited-access location under the storage conditions required by GCP/GMP guidelines. 
6.8. Product Accountability 

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An accurate and current accounting of the dispensing and return of IMP(s) will be maintained on an 
ongoing basis by the pharmacist and a member of the study site staff in the Accountability Log and case 
report form and will be verified by the study’s monitor. 
6.9. Prior and Concomitant Medication 
6.9.1. Allowed concomitant treatment 
Allowed Concomitant Medications are: 
▪ Corticosteroids at stable dose of prednisone or prednisone equivalent ≤20 mg/day; 
beclomethasone diproprionate (≤5mg/day) or budesonide MMX (≤9 mg/day); 
▪ Oral 5-aminosalicylic acid at stable dose; 
▪ Immunosuppressants in the form of azathioprine, 6-mercaptopurine, or methotrexate at stable 
dose; 
▪ Antidiarrheals (e.g., loperamide, diphenoxylate with atropine) at stable dose. 
Potential other concomitant medications should be kept at constant dose during the course of the study 
and properly reported in the medical file of the patient and the eCRF. 
This information should include the name of the medication (international nonproprietary name), daily 
dosage, duration, indication and the time of last intake before all PK samplings. 
6.9.2. Prohibited concurrent medications 
The following drugs are prohibited during the course of the study.  
▪ Tumor necrosis factor [TNF] inhibitors, vedolizumab or others biologic therapies with a wash-out 
period of at least 8 Weeks prior to the screening visit; 
▪ JAK inhibitors with a wash-out period of at least 4 Weeks prior to the screening visit; 
▪ Topical corticosteroids and topical 5-aminosalicylic acid preparations with a wash-out period of at 
least 2 Weeks prior to the screening visit; 
▪ Cyclosporine and tacrolimus with a wash-out period of at least 4 Weeks prior to the screening visit; 
▪ Vaccination with live components during the study and up to 8 Weeks after the last dosing; 
▪ Drugs that could interact with ABX464 should be avoided especially the CYP1A2 substrates (cf. 
Appendix #1). The following CYP1A2 substrates with a narrow therapeutic margin are prohibited 
during the whole course of the study (Clozapine, theophylline, ropinirol, warfarin and methadone). 
In case of concomitant treatment with ondansetron the maximal daily dose must be limited to 8 
mg; 
▪ Drugs that inhibit or induce CYP1A2 (cf. Appendix #1). 
▪ Drugs that inhibit UGTIA9 activity and inhibitors of OATP1B1/1B3 transporters (cf. Appendix #1). 
▪ Use of any investigational or non-registered product within 3 months or within 5 half-lives preceding 
baseline, whichever is longer and during the study. 
 
 

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7. PATIENT COMPLETION AND WITHDRAWAL 
7.1. Patient Completion 
Treatment with ABX464/Placebo shall continue until Day 113, except if a patient fulfils a premature 
discontinuation criterion (defined below). After Day 113, patients who are willing to carry on the study 
treatment will be able to take part in the long-term maintenance study (ABX464-104).  
In any other case, patients will exit the study (EoS) and will be treated according to the standard of care. 
The ABX464-104 follow-up study is a separate clinical protocol subject to health authorities and ethics 
committee approvals. 
7.2. Premature trial discontinuation 
A patient can be withdrawn at any time from the study for the following reasons: 
▪ Investigator’s decision; patient that would experience a treatment failure during the study may be 
withdrawn at any time. S/he will have to be treated according to standard of care as soon as s/he 
is off from study treatment; 
▪ An Adverse Event or an intercurrent condition that preclude continuation of treatment; 
o 
Specifically, an increase ≥ 3.0 x ULN in liver transaminases (AST/SGOT and/or 
ALT/SGPT) or an increase ≥ 2.0 x ULN in Alkaline phosphatase or in total bilirubin 
requires close observation with repeating liver enzymes and serum bilirubin tests two 
times weekly and clinical investigation to understand the etiology of this elevation. 
Frequency of retesting can decrease to once a month if the abnormality stabilizes after 
this initial two weeks of follow-up and if the patient is asymptomatic. Discontinuation of 
the study treatment should occur if: 
▪ 
 ALT or AST > 8xULN 
▪ 
ALT or AST >5xULN for more than 2 weeks 
▪ 
ALT or AST > 3xULN and total bilirubin > 2xULN or INR>1.5 
▪ 
ALT or AST > 3xULN with appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%). 
▪ Worsening of the UC defined, from Week 8 onwards, as a 2-point increase in the pMMS, with 
pMMS ≥ 4 on 2 separate occasions 7 day-apart and confirmed by an endoscopy sub-score of 2 
points or higher; 
▪ Major protocol violation; 
▪ Patient’s decision; 
▪ Withdrawal of consent; 
A patient who prematurely exits the study will not be replaced.  
7.3. Study Discontinuation 
All patients (Except those transitioning to the ABX464-104 study), regardless of the completion or 
premature discontinuation, should perform the End of Study Visit according to the study flow-chart,. 
7.4. Screen and Baseline Failures 
A patient is considered to be a baseline failure if the patient signs the informed consent but withdraws 
before the baseline visit. All potential patients who are screened for enrolment in this study will be listed 
on the patient Screening Log/Identification List. Reasons for exclusion will be recorded for potential 
patients who do not enter the study. 
A patient who does not fulfil the randomization criteria will be considered as a screen failure. All patient 
data should be entered in the eCRF including the screen failure data.  

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Based on the investigator evaluation and sponsor prior approval, a non-randomized patient can be re-
screened. This re-screening procedure should be documented, the patient should consent again and a 
new unique and incremental patient Identification (ID) number be allocated. 

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8. ADVERSE EVENTS (AE) AND SERIOUS ADVERSE EVENTS (SAE) 
The investigator is responsible for the detection and documentation of events meeting the criteria and 
definition of an AE or SAE. During the study, in case of a safety evaluation, the investigator or site staff 
will be responsible for reporting AEs and SAEs, as detailed in this section of the protocol.  
During the screening period, all adverse events will be collected. 
Any disease progression will be reported in the eCRF both as an adverse event and documented in the 
efficacy section. 
8.1. Definitions 
8.1.1. Definition of an AE 
Any untoward medical occurrence in a patient or clinical investigation patient administered a 
pharmaceutical product and which does not necessarily have to have a causal relationship with this 
treatment. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product, 
whether or not considered related to the medicinal product. 
Note: The official definition also extends to AEs occurring in the placebo arm. Because of regulatory 
requirements, events occurring during pre-and post-treatment periods will also be designated as AEs. 
Therefore, reporting of such events, AEs and SAEs, will commence when the patient is enrolled into the 
study (date of signature of the informed consent) up until 4 Weeks after the end of the treatment visits. 
The period after discontinuing study drug may be extended if there is a strong suspicion that the drug 
has not yet been eliminated. 
8.1.2. Adverse Drug Reactions (ADR) 
A response to a medicinal product which is noxious and unintended. Suggesting that there is at least a 
reasonable possibility or suspicion of a causal relationship between the medicinal product and an 
adverse event. 
8.1.3. Definition of a SAE or Serious Adverse Drug Reaction (SADR) 
A serious adverse event (experience) or reaction is any untoward medical occurrence that, at any dose: 
a) Results in death 
NOTE: Death is an outcome of an AE, and not an AE in itself. Event which led to death should be 
recorded with fatal outcome. 
b) Is life-threatening 
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. 
c) Requires hospitalization or prolongation of existing hospitalization 
NOTE: In general, hospitalization means that the patient has been detained at the hospital or emergency 
ward for observation and/or treatment that would not have been appropriate in the physician’s office or 
out-patient setting. Complications that occur during hospitalization are AEs. If a complication prolongs 
hospitalization or fulfills any other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred, or was necessary, the AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen after informed 
consent was given is not considered serious. 
d) Results in persistent or significant disability/incapacity,  

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NOTE: The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. This definition is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma (e.g. 
sprained ankle) which may interfere or prevent everyday life functions but do not constitute a substantial 
disruption. 
e) Is a congenital anomaly/birth defect 
f) 
Is another medically important condition: This refers to an AE that may not be immediately life-
threatening or results in death or hospitalization but may jeopardize the patient or may require 
intervention to prevent one of the outcomes listed above. Based on medical and scientific 
judgment this should usually be considered serious. 
If there is any doubt about whether or not an AE is serious, the investigator should contact the sponsor. 
8.2. A Suspected Unexpected Serious Adverse Reaction (SUSAR) 
A Suspected Unexpected Serious Adverse Reaction (SUSAR), is a serious adverse reaction (SAR) for which 
a reasonable causal relationship with the medicine use is suspected but not confirmed. Unexpected in this 
context means not consistent with the applicable product information (e.g. investigator’s brochure for an 
unapproved investigational product or Summary of Product Characteristics (SmPC) for an authorized 
product). 
8.3. Events and/or Outcomes Not Qualifying as SAEs 
Any hospitalization, or prolongation of hospitalization due to the circumstances listed below, will not be 
reported as SAE: 
▪ planned medical/surgical procedure; 
▪ planned medical/surgical admission (planned prior to entry into study, appropriate documentation 
required), for the disease under study; 
▪ Administrative or social reasons (e.g. lack of housing, economic inadequacy, care-giver respite, 
family circumstances).  
8.4. Events or Outcomes Qualifying as AEs or SAEs 
8.4.1. Clinical laboratory parameters  
Abnormal laboratory findings (e.g., clinical chemistry, hematology) or other abnormal assessments (e.g. 
vital signs) that are judged by the investigator as clinically significant will be recorded as AEs or SAEs 
if they meet the definitions of sections 8.1.1.. Clinically significant abnormal laboratory findings or other 
abnormal assessments that are detected during the study or are present at informed consent and 
significantly worsen during the study will be reported as AEs or SAEs. Clinically significant abnormal 
laboratory findings or other abnormal assessments that are associated with the disease being studied 
and are present at the start of the study but do not worsen, will not be reported as AEs or SAEs. 
However, if these findings or assessments are judged by the investigator to be more severe than 
expected considering the patient’s condition, then they may be reported as AEs or SAEs. 
8.4.2. Pregnancy report 
Patients who become pregnant at any time will be immediately withdrawn from participation in the study. 
All appropriate withdrawal assessments may be performed at the discretion of the investigator. 
The investigator will collect pregnancy information on any woman patient or partner of a male patient, 
who becomes pregnant and their partner while participating in this study. The investigator will record 
pregnancy information on a specific pregnancy notification form and submit it to ABIVAX or its designee 
within 24 hours after knowledge of a patient's or partner’s pregnancy. The patient or partner will also be 
followed to determine the outcome of the pregnancy, be it full-term or prematurely terminated. 
Information on the status of the mother and child will be forwarded to ABIVAX or its designee. Follow-
up will normally end 6 to 8 Weeks following the estimated delivery date. 

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While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or elective 
termination of a pregnancy for medical reasons will be recorded as an SAE. A spontaneous abortion is 
always considered to be an SAE and will be reported as such. 
The time period for collecting pregnancy information is identical to the time period for collecting AEs, as 
stated in Section 8.5, Time Period, Frequency, and Method of Detecting AEs and SAEs. Pregnancy 
information is collected from the signing of informed consent to 4 Weeks after the last dose. 
8.5. Time Period, and Frequency of Detecting AEs and SAEs 
All AEs and SAEs occurring from the time a patient consents to participate in the study until 4 Weeks 
after he or she has completed or discontinued the investigational medicinal product must be recorded 
in the Patient’s eCRF.  
Moreover, any occurrence of pregnancy within 3 months post stopping dosing must be reported. 
Importantly, SAEs will have to be reported, either by email or by Fax, to IntuVigilance Limited within 24 
hours of awareness of an SAE. 
IntuVigilance Limited 
Scotsbridge House, Scots Hill 
Rickmansworth WD3 3BB 
Hertfordshire, UK 
Hotline phone: 
  
Email Address: 
  
Fax number: 
  
Legislative guidance requires the investigator to also ensure that any related SAEs are reported after 
the patient finished the study if the investigator becomes aware of them. 
8.6. Recording AEs and SAEs 
Severity of AEs will be assessed according to CTC-AE Classification Version 5.0. 
Patients will be asked to report all AEs as part of the procedures performed at each study visit. The site 
personnel will document all AEs in the patient’s medical record. All AEs subsequently must be recorded 
in the appropriate eCRF sections. 
The following points must be recorded for each event: 
▪ A description of the event in medical terms, not as reported by the patient; 
▪ Date of onset (start date); 
▪ Date of resolution (stop date); 
▪ The time of onset with respect to administering the investigational medicinal product; 
▪ The severity of the sign/symptom or clinically significant abnormal laboratory value according to 
CTC-AE Classification (Version 5.0); 
▪ The causal relationship between the investigational medicinal product and the occurrence of each 
AE. This will be assessed by each investigator using clinical judgment. Alternative causes, such 
as natural history of the underlying diseases, concomitant medications, other risk factors and the 
temporal relationship of the event to the investigational medicinal product will have to be 
considered. The causality of all AEs should be assessed by the investigator with the following 
question: Is there a reasonable possibility that the AE may have been caused by the investigational 
medicinal product? And answered “NO” (if not related) and “YES” (if related); 
▪ Action taken regarding the investigational medicinal product:  
o No action; 
o Temporary discontinuation; 
o Permanent discontinuation; 

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o Recovered without sequelae / resolved without sequelae; 
o Recovered with sequelae / resolved with sequelae; 
o Recovering/Resolving; 
o On-going; 
o Fatal (for SAEs only). 
▪ Patient’s outcome. 
If in any one patient, the same AE occurs on several occasions, the AE in question must be documented 
and assessed a new each time. 
8.7. Reporting of SAEs to ABIVAX or its designee 
Throughout the study, the reporting of SAEs to the Sponsor or its designee will be done through the 
SAE forms. 
It is the investigator’s responsibility to ensure that the SAE report is submitted to IntuVigilance Limited 
within 24 hours after knowledge of the event(s).  
The study specific SAE form should be completed as thoroughly as possible, with all the available details 
of the event and signed by the investigator or designee. The investigator will assess causality between 
the study drug and the adverse event (AE) / serious adverse event (SAE) according to the table outlined 
below: 
Related  
A clinical event, including laboratory test abnormality, occurs in a plausible 
time relationship to treatment administration, and which concurrent disease 
or other drugs or chemicals cannot explain.  
Probably related  
A clinical event, including laboratory test abnormality, with a reasonable time 
sequence to administration of the treatment, unlikely to be attributed to 
concurrent disease or other drugs or chemicals.  
Possibly related  
A clinical event, including laboratory test abnormality, with a reasonable time 
sequence to administration of the treatment, but which could also be 
explained by concurrent disease or other drugs or chemicals.  
Unlikely to be 
related  
A clinical event, including laboratory test abnormality, with a temporal 
relationship to treatment administration which makes a causal relationship 
improbable, and in which other drugs, chemicals or underlying disease 
provide plausible explanations.  
Unrelated  
A clinical event, including laboratory test abnormality, with little or no 
temporal relationship with treatment administration. Typically explained by 
extraneous factors (e.g., concomitant disease, environmental factors or 
other drugs or chemicals).  
An assessment of causality should always be provided at the time of the initial report. If the investigator 
or designee does not have all information regarding the SAE, he/she should not wait to receive additional 
information before completing the form and notifying IntuVigilance Limited.  
Additional or follow-up information relating to the initial SAE report, will be requested, if necessary. 
Again, this information is to be completed and submitted through the SAE forms within 24 hours of 
receipt of the information.  
In the rare occasion when the facsimile equipment does not work or in the absence of facsimile, the 
investigator should notify IntuVigilance Limited by telephone within the given timeframe and send a copy 
of the SAE report form by email. 
8.8. Reporting of SAEs to Regulatory Authorities  
ABIVAX has a legal responsibility to notify, as appropriate, both the local regulatory authorities and other 
regulatory agencies about the safety of the investigational medicinal product. It is therefore important 
that the investigator notifies promptly (within 24 hours) ABIVAX or designee of any SAEs, in order for 
legal obligations and ethical responsibilities towards other patients to be met.  

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In addition, the investigator or designee, will comply with the local regulatory requirements (when 
applicable) in reporting of SAEs to the ethics committee and, if required, to the relevant government 
authority. 
Safety reports on adverse events that are serious AND unexpected AND causally associated with the 
investigational medicinal product are prepared according to ABIVAX’s policy and applicable regulations 
and are forwarded to the investigators. These reports are filed with the investigator brochure or other 
appropriate study documentation. It is the Sponsor or its designee and/or investigator’s responsibility to 
notify the IRB or IEC of these reports, if applicable according to local requirements.  

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9. DATA ANALYSIS AND STATISTICAL CONSIDERATIONS 
A summary of the principal features of the statistical analysis of the data will be described here, in the 
statistical section of the protocol. A more technical and detailed elaboration of the principal features 
stated in the protocol will be given in the first version of the statistical analysis plan (SAP). 
Any amendments to the SAP will be clearly documented and signed prior to the final database lock 
including justifications and details of their potential impact on the interpretation of the study results. 
9.1. Statistical and Analytical Plans 
No interim analysis is planned. 
The study analysis will be performed following database lock upon the completion of the last patient or 
upon its early discontinuation whichever occurs first.  
9.1.1. Protocol deviations 
Protocol deviations will be reviewed and classed as major or minor during the blind-review meeting. 
Major protocol deviations are defined as deviations liable to bias the evaluation of the main efficacy 
endpoint. The following deviations will be considered as major (non-exhaustive list):  
▪ Non compliance with the inclusion or exclusion criteria; 
▪ Non compliance with the study treatment; 
▪ Intake of prohibited medication; 
▪ Noncompliance with time window. 
9.1.2. Definition of study analysis sets 
The following datasets will be defined and used for the analyses: 
▪ The Safety dataset (SAF population) is defined as those patients included in the study, who have 
received at least one dose of the study treatment. 
▪ The Full Analysis dataset (FAS population) is defined as those patients included in the study, 
who have received at least one dose of the study treatment, and who have at least one baseline 
data. 
▪ The Per Protocol dataset (PP population) is defined as those patients of the FAS population 
without any major protocol deviation. 
9.1.3. Patients/Patients disposition 
The number and the percentages of patients enrolled and included in each of the populations will be 
tabulated. The reason for patient exclusions from each of the populations will also be listed. In addition, 
the number of discontinued patients with their reason for discontinuation will be tabulated. 
9.1.4. Demographic and other baseline characteristics 
Demographics and other baseline characteristics will be summarized by treatment arm. This analysis 
will be conducted on the FAS population. 
9.1.5. Treatment compliance 
Number of daily doses will be presented on the FAS population. 
9.2. Efficacy Analysis 
Analysis of efficacy data will be carried out in the Full Analysis Set in which subjects who prematurely 
discontinue the study due to adverse reaction(s) will be considered treatment failures.  

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The primary efficacy endpoint of the study is the change in the Modified Mayo Score (MMS) from 
Baseline to Week 8. This change will be compared between subjects who received ABX464 and placebo 
for each ABX464 treatment arm separately using an ANCOVA model adjusting for randomized study 
treatment arm, previous biological or JAK inhibitors treatment use (i.e. randomization strata), and 
baseline MMS.  
The dose testing will commence with comparing the ABX464 50mg dose with placebo. If this is 
significant at a 5% two-sided level (i.e. p<0.05) a comparison against placebo will be carried out at the 
ABX464 100mg dose. Again, if significance at a 5% level for this test is observed the procedure will be 
repeated at the ABX464 25mg dose. In this closed procedure no adjustment for multiple comparison is 
needed. Should the data warrant it, testing between doses may also be conducted. 
In addition, descriptive statistics will be presented by treatment arm for all secondary efficacy variables 
for each measurement timepoint. 
These statistics include: 
▪ Continuous variables: mean, standard deviation, minimum and maximum, 95%  
▪ Confidence intervals for the mean, median and quartiles will be presented. 
▪ Categorical variables: counts, rates and 95% confidence intervals for the rates will be calculated. 
In addition to descriptive statistics, the following analyses will also be carried out for the variables 
indicated below: 
▪ The global (combined) ABX464 treatment effect vs. placebo in the change from Baseline in 
Modified Mayo Score at Week 8   
▪ The proportion of subjects with clinical remission at Week 8 will be compared across study 
treatment arms using a stratified Mantel-Haenszel test.  
▪ Mixed model analysis of covariance will be conducted for the following measurements: 
o The change from baseline in microRNA-124 levels in total blood (PAXgene®) at Week 1, 
Week 4, Week 8 and Week 16 and in tissue (RNA later). 
o The change from baseline in fecal calprotectin levels at Week 8 and Week 16. 
o The change from screening in the histopathology/infiltrate (rectal/sigmoidal biopsies) 
assessed by the Robarts Histopathology Index, the Geboes and Nancy Histology Scoring 
Scales at Week 8 and Week 16 (if available). 
o The change from screening in Modified Mayo scores and Partial Mayo scores during the 
study. 
In this mixed model, treatments and stratum will be fixed effects, subject will be random effect and 
baseline values of the respective measurements will be covariates. Other explanatory variables will also 
be allowed to be included in the model. To normalize eventual skewed distributions transformation of 
the data will also be considered. Study treatment groups will be compared within this model framework. 
All p-values will be interpreted in a descriptive manner. 
The following subgroups will be analyzed: 
▪ Gender 
▪ Age 
▪ Country 
▪ US vs non-US 
▪ Baseline MMS 
▪ With/without previous biological or JAK inhibitors treatment 
▪ Week 16 ABX464-NGlu AUC0-12 level above/below 7 000 h*ng/mL (vs. placebo) 
▪ Concomitant UC medications. 
9.2.1. Pharmacokinetics 
Population PK data analysis will be performed via three steps: 
▪ 
Data preparation and exploratory: The analysis dataset will be created and formatted according 
to MONOLIX or NONMEM requirement using SAS®. An exploratory analysis by visual inspection 

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of PK profiles/dose normalized PK profiles in natural and semi-log scale will be performed in order 
to anticipate the type of PK model (number of compartments, linear or saturable elimination, etc) 
▪ 
 Population PK model development: A PopPK model consists of four basic components: 
o 
The structural PK model, which defines the PK parameters and describes the plasma 
concentration-time profiles of ABX464 and its metabolite. 
o 
The inter-individual variability model component, which describes the inter-individual 
variability of PK parameters in the population 
o 
The residual error model component, which describes the underlying distribution of the error 
in the measured concentrations. 
o 
The covariate model component, which describes the influence of covariates such as 
demographic data on PK parameters. 
The search for the final model will follow the following strategy: 
o 
Selection of the simplest structural model, which predicts the plasma concentration as a 
function of time and dose, based on smallest objective function and by the pattern in the 
residual plots. The best estimation method, the most appropriate inter-individual 
variability (IIV) models, and the residual error model, are identified. The resulting model 
is called BASE model. 
o 
Test of influence of selected covariates. 
o 
Refinement of inter-individual variability model and residual error models 
▪ 
Model validation: Goodness of fit plots will be assessed for each important step of model 
building. For the final model, a visual predictive check (an evaluation graph based on simulation) 
will be provided. 
Data will be prepared using SAS version 9.2. Population analysis will be performed using MONOLIX 
version 2018 R1 or NONMEM version 7.2. Graphs will be provided using SAS. 
9.3. Safety Analyses 
Adverse events will be coded using the standard dictionary (MedDRA) down to the lower level term 
(LLT). 
An overall summary table will be presented (Any adverse event, any treatment emergent adverse event 
(TEAE), any serious adverse event (SAE), death, any grade 3 or higher adverse events from baseline 
to the end of Study. This analysis will be conducted on SAF population. 
Two periods will be defined for TEAE: 
▪ Any adverse event which occurs or worsens from first dosing to Day 113; 
▪ Any adverse event which occurs after Day 113. 
Adverse events will be described by primary system organ class and preferred term. Numbers and 
percentage of patients, and number of occurrences of adverse event will be presented for: 
▪ TEAE; 
▪ Serious TEAE; 
▪ TEAE leading to drug discontinuation; 
▪ TEAE of grade 3 or 4; 
▪ TEAE for which relationship with the study drug is recorded as possible or probable; 
▪ TEAE leading to death. 
The assessment of safety will be based on the frequency of adverse events (with and without regard to 
causality) graded according to the CTC-AE Classification and also, the review of individual values for 
clinical laboratory data, vital signs and ECG focusing on the detection of abnormal values and PCSAs 
as determined upon investigator considerations. 
Adverse events will be tabulated (counts and percentages) by group. All adverse events will be listed 
and the data will be tabulated by body system/organ class. Adverse event tabulations will include all 
treatment emergent adverse events, which will be further classified by severity, and relationship to 
treatment and dose level. 

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Clinical laboratory parameters, vital signs, ECG will be summarized by using descriptive statistics (n, 
mean, SD, SEM, median, minimum and maximum). Number of patients with at least one abnormal 
values will be tabulated (counts and percentages) for each parameter in summary shift tables, by group 
and dose. 
9.3.1. Clinical laboratory evaluation 
Descriptive statistics for laboratory parameters will be computed at each scheduled assessment. If 
relevant for some parameter, change from baseline will also be tabulated. 
In addition, shift tables from baseline will be presented. 
9.4. Determination of Sample Size 
The primary endpoint is the change in the Modified Mayo Score (MMS) from Baseline to Week 8. The 
primary endpoint will be compared between subjects who received ABX464 and placebo for each 
ABX464 treatment arm separately. 
For the sample size calculation, the following assumptions were made: 
• 
mean reduction in MMS (ABX464): 2.5 
• 
mean reduction in MMS (placebo): 1.0 
• 
pooled standard deviation of reduction in MMS: 2.1 
• 
Type 1 error: 5% two-sided. 
• 
Treatment testing to use a sequential, gate-keeping strategy, where treatment arms will be 
tested in the following order: ABX464 50mg vs. placebo, ABX464 100mg vs. placebo, ABX464 
25mg vs. placebo. Subsequent tests will only be performed only if prior test(s) are significant 
(p<0.05). 
• 
>90% power 
• 
Two-sample t-test 
• 
5% dropout rate prior to Week 8 MMS assessment (all treatment arms) 
• 
1:1:1:1 (ABX464 100mg: ABX464 50mg: ABX464 25mg: placebo) study treatment arm 
allocation ratio. 
 
If the above assumptions hold true, then a total sample size of 232 subjects will be required to be 
randomized (58 subjects randomized to each study treatment arm). 
Due to the SARS Cov-2 pandemic the drop-out rate of the study is expected to be somewhat higher 
than originally estimated. Therefore, an additional 12 subjects are planned to be recruited in the study 
leading to an overall sample size of 244 patients (61 subjects randomized to each study treatment arm). 

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10. 
STUDY CONDUCT CONSIDERATION 
10.1. 
Regulatory and Ethical Considerations 
10.1.1. General Requirements 
The study will be conducted in compliance with the study protocol, ABIVAX / IQVIA Standard Operating 
Procedures and in accordance with any local regulatory requirements, to ensure adherence to Good 
Clinical Practice (GCP) as described in the following documents: 
▪ ICH Harmonized Tripartite Guidelines for Good Clinical Practice (ICH E6 (R2)). 
▪ US 21 Code of Federal Regulations dealing with clinical studies (including parts 50 and 56 
concerning informed consent and IRB regulations). 
▪ Directive 2005/28/EC on the approximation of the laws, regulations and administrative provisions 
of the Member States relating to the implementation of good clinical practice in the conduct of 
clinical studies on medicinal products for human use and its guidance. 
▪ Declaration of Helsinki and its amendments. 
▪ EudraLex GMP guidelines Annex 13 related to shipment, storage and handling of investigational 
medicinal products. 
Upon signing the protocol, the investigator agrees to adhere to the instructions and procedures 
described in it and thereby to adhere to the principles of Good Clinical Practice that it conforms to. 
Written informed consents will be obtained for each patient before he or she can participate in the study.  
ABIVAX will obtain favorable opinion/approval to conduct the study from the appropriate regulatory 
agencies in accordance with any applicable country-specific regulatory requirements prior to a site 
initiating the study in that country. 
10.1.2. Independent Ethics Committee/Institutional Review Board 
Prior to the start of the study, the study protocol and amendments if applicable as well as other 
appropriate study-related documents will be submitted to an independent Institutional Review Board 
(IRB) or independent Ethics Committee (IEC). 
For each center it will be individually specified, who (investigator or sponsor) will be responsible for 
informing the IRB or IEC, respectively of any protocol amendments or new relevant information that 
require an ethical reconsideration of the study protocol. 
If the investigator is responsible for obtaining approval, he/she should also obtain a statement from the 
IRB or IEC, respectively that it is organized and operates according to GCP and applicable laws and 
regulations. 
10.1.3. Patient Informed Consent 
It is the responsibility of the investigator to give each patient full and adequate verbal and written 
information regarding the aims, methods, anticipated benefits and potential hazards. The patient must 
be informed that participation is voluntary, and that they are free to withdraw from the study at any time 
without any disadvantages for their subsequent care. Although a patient is not obliged to give her/his 
reason(s) for withdrawing prematurely from the trial, the investigator should make a reasonable effort to 
ascertain the reason(s), while fully respecting the patient's rights. Written consent (signed and dated by 
the patient and the investigator) must be obtained prior to admission. The patient must be provided with 
a copy of the patient information and informed consent.  
The data collected in this study will be processed anonymously at ABIVAX. Patients should be informed 
about the purpose of the planned computer data processing and the publication of the data (e.g. at 
scientific meetings). The patient must give consent to the computer processing and to the publishing of 
anonymous data.  
The patient must be informed of and consent in writing that personal data relating to the trial may be 
subject to audits by Health Authorities and the sponsor. However, personal data will be kept strictly 
confidential and will not be made publicly available. 

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10.1.4. Compensation to Patients 
Insurance coverage will be provided for all patients enrolled in the study from the time of the patient’s 
inclusion in the study (i.e. date of signing the ICF). The insurance coverage will be provided by the 
Sponsor and will be in line with GCP guidance and legal requirements, but also in accordance with local 
regulations. A confirmation of insurance and corresponding insurance conditions should be archived in 
the Investigator File. 
Besides, due to the cumbersome procedures related to the study (number of visits, sigmoidoscopies…) 
patients could be financially compensated by the Sponsor in accordance with the national regulations 
and the approval of the Ethics Committees. 

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11. 
STUDY MANAGEMENT 
11.1. 
Remote Data Entry 
An electronic case report form (eCRF) will be used to record all data required by the protocol. Remote 
Data Entry (RDE) will be used for data collection, i.e. the Patient’s information pertaining to the study, 
will be entered into the eCRF via a computer at the investigational site. 
Prior to the start of the study, the investigator will complete a "Investigator site staff signature and task 
delegation log" form, showing the signatures and initials of any person who is authorized to make or 
change entries in the eCRF and any person authorized to electronically sign the eCRF. 
The eCRF used for this study is validated and fulfils the International Conference on Harmonization 
(ICH) Good Clinical Practice (GCP) requirements, European and FDA (21 CFR Part 11) regulations.  
Training sessions will be held for all the participants who will use this tool (e.g. investigators, ABIVAX 
staff and contract research organization [CRO] staff, including project managers, CRAs and data 
managers). 
Several supports are available to help all users with this tool including eCRF User Guide and five days 
a Week / working hours helpdesk (support line). 
All of the information will be recorded through transcription from source documents into the eCRF by an 
authorized person.  
The investigator is responsible for the management and accuracy of the information in the eCRF. At 
each monitoring visit, the patient medical files should be at the clinical research associate's (CRA) 
disposal for review. 
11.2. 
Data management 
Data management will be outsourced to a Contract Research Organization (CRO). The data managers 
will issue electronic edit checks via EDC, and modification of the data will be permitted by the investigator 
to achieve accuracy with source documents and eliminate all inconsistencies in the data.  
The data will be reviewed for completeness and logical consistency. Automated validation programs will 
identify missing data, out of range data and other data inconsistencies at the time of entry. 
All new/updated information will be reviewed and verified by the appointed monitor.  
11.3. 
Data coding 
Adverse events, concomitant diseases, medical/surgical histories will be coded using the Medical 
Dictionary for Regulatory Activities (MedDRA). Concomitant medication will be coded using the WHO-
DRUG dictionary. 
11.4. 
Randomization 
Randomization will be centrally managed. It will be performed via the IWRS. The bottle numbers to be 
used for a specific patient will be assigned according to a pre-defined randomization list by the vendor 
in charge of drug supplies. This information will be provided to the site by fax or by email.  
11.5. 
Study Monitoring 
The study will be conducted in accordance with the ICH Note for Guidance on GCP (ICH, Topic 6, 1996). 
The appointed monitor will contact the site prior to the start of the study to review with the site staff the 
protocol, study requirements, and their responsibilities to satisfy regulatory, ethical, and ABIVAX 
requirements. Throughout the study, the monitor will arrange visits to the study center at appropriate 
intervals to assess the progress of the study and review the completed eCRFs.  
During the monitoring visits, the monitor will: 

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▪ Ensure that the safety and the rights of patients are being protected; 
▪ Check that the data are authentic, accurate, and complete and discuss any inconsistencies; 
▪ Ensure that all study materials are correctly stored and dispensed with particular emphasis to the 
investigational medicinal product; 
▪ Verify that the site staff and facilities continue to be adequate for the proper conduct of the study; 
▪ Ensure that the study is conducted in accordance with the currently approved protocol and any 
other study agreements, GCP, and all applicable regulatory requirements; 
▪ Help resolve any problems that may have arisen. 
In line with ICH GCP guidelines, monitoring will include verification of data entered in the CRF against 
the original patient records. Therefore, for the purpose of monitoring review, direct access to all study-
related site and source documents is mandatory. Data items for which the eCRF will serve as the source 
document will be identified, agreed upon and documented. The investigator must also ensure provision 
of sufficient time, space and qualified personnel for the monitoring visits. 
11.6. 
Records Retention 
Following closure of the study, the investigator or the head of the medical institution (where applicable) 
must maintain all site study records, except for those required by local regulations to be maintained by 
someone else, in a safe and secure location. The records must be maintained to allow easy and timely 
retrieval, when needed (e.g., audit or inspection), and, whenever feasible, to allow any subsequent 
review of data in conjunction with assessment of the facility, supporting systems, and staff. 
ABIVAX will inform the investigator/institution of the required time period for retaining these records in 
order to be compliant with all applicable regulatory requirements. The minimum retention time will meet 
the strictest standard applicable to that study site, as dictated by ICH GCP E6 Section 4.9, any 
institutional requirements or local laws and regulations, or ABIVAX standards/procedures; otherwise, by 
default the retention period will be 15 years. 
The investigator must notify ABIVAX of any changes in the archival arrangements, including, but not 
limited to, the following: archival at an off-site facility, transfer of ownership of the records in the event 
the investigator leaves the site. In addition, the investigator should seek the written approval of the 
Sponsor prior to disposing any of the archived records. 
11.7. 
Quality Assurance and Inspection by Authorities 
To ensure compliance with GCP and all applicable regulatory requirements, ABIVAX may conduct 
quality assurance audits. Regulatory agencies may also conduct a regulatory inspection of this study. 
Such audits/inspections can occur at any time during or after completion of the study. By signing the 
protocol agreement page, the investigator agrees to permit drug regulatory agencies and ABIVAX 
audits. If an audit or inspection occurs, the investigator and institution will allow the auditor/inspector 
direct access to all relevant documents and to allocate his/her time and the time of his/her staff to the 
auditor/inspector to discuss findings and any relevant issues. Items of particular interest in case of an 
audit are, but not limited to, the following: 
▪ IRB/IEC and regulatory authority approvals; 
▪ Informed consent forms of the patients; 
▪ Approved study protocol and amendments and investigator brochure; 
▪ Treatment accountability; 
▪ Safety reporting; 
▪ Study file; 
▪ Study personnel; 
▪ Log of monitoring visits and monitoring process; 
▪ Medical records and other source documents; 
▪ Site facilities; 
▪ Reports to the IRB/IEC and the sponsor; 

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▪ Record retention. 
11.8. 
Study and Site Closure 
If the study is terminated prematurely or suspended for any reason, the investigator/institution should 
promptly inform the study patients and should assure appropriate therapy and follow-up for the patients 
ABIVAX reserves the right to temporarily suspend or prematurely discontinue this study, at any time for 
reasons including, but not limited to, safety or ethical issues or severe non-compliance. For multicenter 
studies, this can occur at one or more or at all sites. If such action is required, the Sponsor will discuss 
this with the investigator or the head of the medical institution (where applicable), including the reasons 
for taking such action, at that time. Advance notification will be provided to the site(s) when feasible, on 
the impending action prior to it taking effect. 
All investigators and/or medical institutions conducting the study will be informed in writing should the 
Sponsor decide to suspend or prematurely discontinue the study for safety reasons. The regulatory 
authorities will also be informed of the suspension or premature discontinuation of the study and the 
reason(s) for the action. If required by local regulations, the investigator must inform the IRB/IEC 
promptly and provide the reason for the suspension or premature discontinuation. 
Upon premature discontinuation of the study, the monitor will conduct site closure activities with the 
investigator or site staff, as appropriate, in accordance with applicable regulations, GCP, and ABIVAX 
procedures. All data must be returned to ABIVAX. Arrangements will be made for any unused 
investigational medicinal product based on the relevant ABIVAX procedures for the study. 
11.9. 
Study report and Publication 
Upon conclusion of the study, an integrated clinical and statistical study report will be written by the 
Sponsor in consultation with the Coordinating Investigator. This report will be based on the items 
detailed in this study protocol. When the clinical study report is completed, ABIVAX will provide the 
investigators with a full summary of the study results. The investigators are encouraged to share the 
summary results with the patients, as appropriate. 
The first resulting publication will be a full publication of all data from all participating sites, coordinated 
by ABIVAX. Any secondary publications by the investigators (abstracts in journals, oral presentations 
etc.) will reference the original publication and will require pre-submission review by the Sponsor. Note 
that the Sponsor is entitled to delay any proposed secondary publication, in order to obtain patent 
protection, if required. 
The Coordinating Investigator as well as other members of the study committee will be authors on the 
first publication. The principal investigator of the trial will be the first author. Authorship for other 
investigators will be assigned on the basis of their recruitment contribution, as well as intellectual and 
administrative input. Ranking will be according to the number of patients randomized as well as 
contribution to the study conduct and preparation of final manuscript.  
11.10. 
Ownership and Confidentiality 
All information provided by ABIVAX and all data and information generated by the sites, as parts of the 
study (excluding the patients’ medical records) are property of ABIVAX.  
All potential investigators must be aware of and agree in writing (confidentiality agreement) to the 
confidential nature of the information pertaining to this study. Furthermore, all information provided by 
ABIVAX and all data and information generated by the sites during the study must be kept confidential 
by the investigator and other site staff and may not be used for any purpose other than conducting this 
study.

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References  
1. 
Ghosh S. Mitchell R. Results of the European Federation of Crohn's and Colitis Associations (EFCCA) 
Patient survey: prevalence and impact on quality of life Gut  55 Suppl V 2006 A72. 
2. 
Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults (update): American College of 
Gastroenterology, Practice Parameters Committee. Am. J. Gastroenterol. 99(7), 1371–1385 (2004). 
3. 
Travis SPL, Stange EF, Lémann M et al. European evidence-based consensus on the management of 
ulcerative colitis: current management. J. Crohn's Colitis (2), 24–62 (2008). 
4. 
Truelove SC, Witts LJ. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br. Med. J. 2(4947), 
1041–1048 (1955). 
5. 
Jess T, Riis L, Vind I et al. Changes in clinical characteristics, course, and prognosis of inflammatory bowel 
disease during the last 5 decades: a population-based study from Copenhagen, Denmark. Inflamm. Bowel 
Dis. 13(4), 481–489 (2007). 
6. 
Sonnenberg A. Time trends of mortality from Crohn's disease and ulcerative colitis. Int. J. Epidemiol. 36(4), 
890–899 (2007). 
 

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12. 
APPENDICES 
Appendix 1: 
CYPIA2 substrates/inhibitors/inducers (in bold: prohibited concomitant medications) 
Substrates: 
Alosetron, Duloxetine, Ramelteon, Tasimelteon, Amitriptyline, Clomipramine, Imipramine, 
Agomelatine, Clozapine, Olanzapine, Haloperidol, Ropivacaine, Theophylline, Zolmitriptan, 
Tamoxifen, 
Erlotinib, 
Cyclobenzaprine, 
Mexiletine, 
Naproxen, 
Ondansetron, 
Phenacetin, 
Paracetamol, Propranolol, Tacrine, Tizanidine, Verapamil, Warfarin, Zileuton, Ropinirole, 
Methadone. 
Inhibitors: 
Artemisinin, Atazanavir, Ciprofloxacin, Enoxacin, Ethinyl Estradiol, Fluvoxamine, Mexiletine, 
Tacrine, Thiabendazole, Zileuton 
Inducers: 
Montelukast, Phenytoin, Rifampin, Ritonavir, Teriflunomide 
OATB1B1/1B3 inhibitors (prohibited concomitant medications) 
Inhibitors: 
Cyclosporine, Eltrombopag, Lapatinib, Lopinavir, Rifampin, Ritonavir 
UGT1A9 inhibitors (prohibited concomitant medications) 
Inhibitors: 
Regorafenib, Fosphenytoin, Phenytoin, Eltrombopag, Mefenamic acid, Diflunisal, Niflumic 
acid, Sorafenib, Isavuconazole, Deferasirox, Morniflumat, Rifampicin 
 
 

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Appendix 3: Mayo Score (Ulcerative Colitis) 
 
 

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Appendix 4: Headache Questionnaire 
 

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