A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Clinical Efficacy and Safety of VTX002 in Subjects With Moderately to Severely Active Ulcerative Colitis
Phase: PHASE2
Conditions: Colitis, Ulcerative
Sponsor: Oppilan Pharma Ltd



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Protocol VTX002-201 Version 6.0 Final 21JUL2023 
 
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Protocol Amendment Summary of Changes  
 
DOCUMENT HISTORY 
Document 
Date 
Protocol V1.0 
24 June 2021 
Protocol V2.0* 
17 January 2022 
Protocol V3.0 
01 June 2022 
Protocol V4.0 
19 January 2023 
Protocol V5.0 
09 May 2023 
Protocol V6.0 
21 July 2023 
*Protocol V2.0 was submitted only to the FDA. 
Version 6.0 dated 21 July 2023 
Overall Rationale for the Amendment 
The overall rationale for the protocol amendment Version 6.0 is to make the following changes 
and administrative updates:  
• 
Clarify the sample size calculation 
• 
Update and clarify endpoint definitions 
• 
Update the follow-up period for partner pregnancy outcomes  
• 
Update address for Sponsor’s Clinical Lead 
This protocol amendment Version 6.0 is considered Substantial by the Sponsor, in accordance with 
international regulations. 
 

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per treatment group will be sufficient to achieve at least 80.1% power. Adding a 
10% inflation for dropouts results in 60 63 participants per treatment group and 180 
189 in total. 
Appendix 5 Collection of 
Pregnancy Information 
Pregnant partners should be followed until 12 months after their delivery date for 
outcomes of both the mother and child. Generally, the follow up will be no longer 
than 6 to 8 weeks following the estimated delivery date. 
To update the follow-up period for 
partner pregnancy outcomes based 
on FDA feedback 
 
 
 

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TABLE OF CONTENTS 
TABLE OF TABLES ...............................................................................................................9 
TABLE OF FIGURES .............................................................................................................9 
1.0 
PROTOCOL SUMMARY ........................................................................................10 
1.1 
Synopsis ...........................................................................................................10 
1.2 
Schedule of Activities .....................................................................................22 
2.0 
INTRODUCTION......................................................................................................42 
2.1 
Study Rationale ..............................................................................................42 
2.2 
Background ....................................................................................................42 
2.2.1 
Nonclinical Findings .........................................................................43 
2.2.2 
Clinical Findings ...............................................................................44 
2.3 
Benefit/Risk Assessment ................................................................................46 
3.0 
OBJECTIVES AND ENDPOINTS ..........................................................................49 
3.1 
Objectives........................................................................................................49 
3.2 
Endpoints ........................................................................................................49 
3.3 
Endpoint Definitions ......................................................................................51 
4.0 
STUDY DESIGN ........................................................................................................53 
4.1 
Overall Design ................................................................................................53 
4.1.1 
Screening Period ................................................................................53 
4.1.2 
Induction Treatment Period ...............................................................53 
4.1.3 
Long-Term Extension Treatment Period ...........................................54 
4.1.4 
Open-Label Extension Treatment Period ..........................................54 
4.1.5 
Follow-Up Period ..............................................................................55 
4.2 
Schema ............................................................................................................55 
4.3 
Scientific Rationale for Study Design ...........................................................56 
4.4 
Justification for Dose .....................................................................................56 
4.5 
End of Study Definition .................................................................................57 
5.0 
STUDY POPULATION ............................................................................................58 
5.1 
Inclusion Criteria ...........................................................................................58 
5.2 
Exclusion Criteria ..........................................................................................60 
5.3 
Lifestyle Considerations ................................................................................63 
5.4 
Screen Failures ...............................................................................................63 
6.0 
STUDY TREATMENT .............................................................................................65 
6.1 
Study Treatment Description........................................................................65 
6.2 
Induction Treatment ......................................................................................66 

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6.2.1 
Induction Treatment Week 0 .............................................................66 
6.2.2 
Induction and Long-Term Extension Treatment Weeks 1 to 52
 ...........................................................................................................66 
6.3 
Open-Label Extension Treatment ................................................................66 
6.3.1 
Open-Label Extension Dose Titration ...............................................66 
6.3.2 
Open-Label Extension Study Drug Supplies .....................................67 
6.4 
Additional Dosing Instructions .....................................................................67 
6.4.1 
Missed Dose Instructions ..................................................................67 
6.4.2 
Dose Interruption ...............................................................................67 
6.5 
Guidance for Cardiac Monitoring Following Treatment Initiation 
or Reinitiation.................................................................................................68 
6.5.1 
First-Dose Cardiac Monitoring ..........................................................68 
6.5.2 
Study Treatment Discontinuation Related to Postdose Cardiac 
Monitoring .........................................................................................70 
6.5.3 
Cardiac Monitoring Upon Treatment Reinitiation Following 
Dose Interruption ...............................................................................71 
6.6 
Guidance for Hepatic Monitoring ................................................................71 
6.7 
Preparation/Handling/Storage/Accountability ...........................................72 
6.8 
Measures to Minimize Bias: Randomization and Blinding........................72 
6.8.1 
Emergency Unblinding Procedure ....................................................73 
6.9 
Study Treatment Compliance .......................................................................73 
6.10 
Prior and Concomitant Therapy ..................................................................74 
6.10.1 
Allowed Medications for the Treatment of Ulcerative Colitis ..........74 
6.10.2 
Prohibited Medications ......................................................................75 
6.11 
Treatment After the End of the Study .........................................................76 
7.0 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ................................................................77 
7.1 
Discontinuation of Study Treatment ............................................................77 
7.2 
Follow-Up Period ...........................................................................................79 
7.3 
Lost to Follow-Up ...........................................................................................79 
7.4 
Participant Discontinuation/Withdrawal ....................................................80 
8.0 
STUDY ASSESSMENTS AND PROCEDURES ....................................................81 
8.1 
Screening and Eligibility ...............................................................................81 
8.2 
Virtual/Hybrid Visits .....................................................................................82 
8.3 
Efficacy Assessments .....................................................................................83 
8.3.1 
Mayo Clinic Scores ...........................................................................83 
8.3.2 
Endoscopic Biopsies ..........................................................................86 
8.3.3 
Efficacy-Related Biomarkers ............................................................86 
8.3.4 
Exploratory Efficacy-Related Biomarkers ........................................87 
8.3.5 
Quality of Life ...................................................................................88 
8.4 
Safety Assessments .........................................................................................89 
8.4.1 
Physical Examinations .......................................................................89 
8.4.2 
Vital Signs .........................................................................................89 
8.4.3 
Electrocardiograms ............................................................................89 

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8.4.4 
Holter ECG Monitoring .....................................................................90 
8.4.5 
Pulmonary Function Tests .................................................................91 
8.4.6 
Ophthalmoscopy and Optical Coherence Tomography.....................91 
8.4.7 
Tuberculosis Screening and Chest X-Ray .........................................91 
8.4.8 
Clinical Safety Laboratory Assessments ...........................................92 
8.5 
Adverse Events ...............................................................................................92 
8.5.1 
Time Period and Frequency for Collecting AE and SAE 
Information ........................................................................................93 
8.5.2 
Method of Detecting AEs and SAEs .................................................93 
8.5.3 
Follow-Up of AEs and SAEs ............................................................93 
8.5.4 
Regulatory Reporting Requirements for SAEs .................................94 
8.5.5 
Pregnancy ..........................................................................................94 
8.5.6 
Adverse Events of Special Interest ....................................................95 
8.6 
Treatment of Overdose ..................................................................................95 
8.7 
Pharmacokinetics ...........................................................................................95 
8.7.1 
Collection of Blood Samples for VTX002 Concentration 
Determination in Plasma ...................................................................95 
8.7.2 
Determination of Drug Concentration ...............................................96 
8.8 
Biomarkers .....................................................................................................97 
8.8.1 
Determination of Biomarkers ............................................................97 
8.9 
Genetics ...........................................................................................................97 
9.0 
STATISTICAL CONSIDERATIONS .....................................................................98 
9.1 
General Considerations .................................................................................98 
9.2 
Determination of Sample Size .......................................................................98 
9.3 
Analysis Sets ...................................................................................................98 
9.4 
Statistical Analyses.........................................................................................99 
9.4.1 
Efficacy Analyses ............................................................................100 
9.4.2 
Analysis of LTE Treatment Period and OLE Treatment Period
 .........................................................................................................101 
9.4.3 
Safety Analyses ...............................................................................102 
9.4.4 
Other Analyses ................................................................................102 
9.4.5 
Missing Data ....................................................................................103 
9.4.6 
Sensitivity Analyses ........................................................................103 
9.4.7 
Timing of Analyses .........................................................................103 
9.5 
Data Monitoring Committee .......................................................................103 
10.0 
REFERENCES .........................................................................................................105 
11.0 
APPENDICES ..........................................................................................................106 
Appendix 1 
Abbreviations .................................................................................107 
Appendix 2 
Regulatory, Ethical, and Study Oversight Considerations ........111 
Regulatory and Ethical Considerations ..........................................................111 
Financial Disclosure.......................................................................................111 
Insurance ........................................................................................................112 
Informed Consent Process .............................................................................112 

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Data Protection...............................................................................................112 
Dissemination of Clinical Study Data............................................................113 
Data Quality Assurance .................................................................................113 
Source Documents .........................................................................................114 
Study and Study Center Closure ....................................................................114 
Publication Policy ..........................................................................................115 
Appendix 3 
Clinical Laboratory Tests .............................................................116 
Appendix 4 
Adverse 
Events: 
Definitions 
and 
Procedures 
for 
Recording, Evaluating, Follow-Up, and Reporting ..................................119 
Appendix 5 
Collection of Pregnancy Information ..........................................123 
Appendix 6 
Mayo Scoring System for Assessment of Ulcerative Colitis 
Activity – Sample .........................................................................................124 
Appendix 7 
Histological Scoring Indices ..........................................................126 
Appendix 8 
Signature of Sponsor .....................................................................127 
Appendix 9 
Signature of Investigator ..............................................................128 
 

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TABLE OF TABLES 
Table 1 
Schedule of Activities for the Double-Blind Induction Treatment 
Period ...............................................................................................................22 
Table 2 
Schedule of Activities in the Long-Term Extension Treatment Period ...........27 
Table 3  
Schedule of Activities in the Open-Label Extension Treatment Period 
from OLE Week 0 to OLE Week 13 ...............................................................30 
Table 4  
Schedule of Activities in the Open-Label Extension Treatment Period 
from OLE Week 18 to OLE Week 39 .............................................................33 
Table 5  
Schedule of Activities for the Open-Label Extension Treatment Period 
Year 2 ...............................................................................................................36 
Table 6 
Schedule of Activities for the Open-Label Extension Treatment Period 
Year 3 ...............................................................................................................39 
Table 7 
Study Treatment Description ...........................................................................65 
Table 8 
Dose Titration in the Induction Treatment Period ...........................................66 
Table 9 
Cardiac Assessments to Be Performed ............................................................69 
Table 10 
Blood Samples for Pharmacokinetics ..............................................................96 
Table 11 
Clinical Laboratory Tests ...............................................................................116 
 
TABLE OF FIGURES 
Figure 1 
Study Schema...................................................................................................55 
 

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1.0 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol Title: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, 
Parallel-Group Study to Evaluate the Clinical Efficacy and Safety of VTX002 in Subjects with 
Moderately to Severely Active Ulcerative Colitis 
Short Title: VTX002 versus Placebo for the Treatment of Moderately to Severely Active 
Ulcerative Colitis 
Rationale 
Ulcerative colitis (UC) is a chronic recurrent, remittent, or progressive inflammatory condition 
that affects the colonic mucosa and is associated with an increased risk for colon cancer. Existing 
standard of care agents for UC primarily work by treating the acute symptoms of UC, inducing 
remission in the majority of cases, with approximately 60% to 70% of patients achieving remission 
with first-line corticosteroid therapy. Of the patients who receive second-line therapy such as 
biologics, about 30% to 40% of patients do not respond to treatment despite optimal therapy, while 
another 23% to 46% of patients lose response over time or discontinue treatment, resulting in 
limited clinical benefits. There remains meaningful unmet medical need, including a significant 
underserved set of patients who will not respond or become unresponsive to current therapies. 
VTX002 (formerly known as OPL-002) is an oral small molecule compound being developed for 
the treatment of moderately to severely active UC. VTX002 is a selective sphingosine-1-phosphate 
receptor (S1PR) modulator. The sphingosine-1-phosphate (S1P) signal transduction through the 
S1PRs plays an important role in a series of responses, including inflammation and repair 
processes, which play an important role in several immune-mediated inflammatory diseases. The 
available nonclinical and clinical data support the initiation of a Phase 2 study of VTX002 in 
participants with moderate to severe UC. This Phase 2 study aims to evaluate the efficacy and 
safety of VTX002 tablets for daily oral administration in participants with moderately to severely 
active UC. 
Overall Design 
This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy 
and safety of VTX002 30 mg and 60 mg in participants with moderately to severely active UC 
following daily oral administration of VTX002 as a tablet. Approximately 189 eligible participants 
will be randomized in a 1:1:1 ratio to receive VTX002 30 mg, VTX002 60 mg, or matching 
placebo, once daily (approximately 63 participants per treatment group). 
The target patient population will include: 
• Patients who have had an inadequate response, loss of response, or intolerance to 
conventional therapy and are naïve to biologic/Janus kinase (JAK) inhibitors 
(conventional failed). 
• Patients who have had an inadequate response, loss of response, or intolerance to a 
biologic/JAK inhibitor (biologic/JAK inhibitor failed). Patients in this category may have 
received prior conventional therapy. It is expected that approximately 35% of participants 
in the study will have had an inadequate response to biologics.  

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The study consists of a 28-day Screening Period, a 13-week double-blind Induction Treatment 
Period (including 7 days of titration followed by 12 weeks of treatment at the assigned dose), a 
Long-Term Extension (LTE) Treatment Period of up to 39 weeks, an Open-Label Extension (OLE) 
Treatment Period of up to 143 weeks, and a 2-week Follow-Up Period. The maximal duration of 
treatment including the Induction Period, LTE and OLE will be 36 months. 
A study schema is presented below. 
 
The duration of study participation for each participant is planned to be approximately 162 weeks, 
and the total duration of the study is planned to be approximately 60 months. Approximately 
120 study centers in 15 countries are expected to participate.  
Objectives  
Primary Objective 
• Assess the efficacy of VTX002 when administered for 13 weeks on clinical remission  
Secondary Objectives 
• Assess the efficacy of VTX002 when administered for 13 weeks on endoscopic changes, 
symptomatic response and remission, histology, and mucosal healing  
• Assess the safety and tolerability of VTX002  
• Assess the pharmacokinetics (PK) of VTX002  

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Long-Term and Open-Label Extension Objectives 
• Assess the efficacy of VTX002 through the LTE and OLE Treatment Periods on 
endoscopic changes, symptomatic response and remission, histology, and mucosal 
healing  
• Assess the safety of VTX002 through the LTE and OLE Treatment Periods 
Exploratory Objectives 
• Assess the effect of VTX002 on health-related quality of life (HRQoL) outcomes and 
biomarkers 
Endpoints 
The primary and four key secondary endpoints will be tested for superiority of VTX002 60 mg vs 
placebo and VTX002 30 mg vs placebo. The remaining endpoints will be presented descriptively.  
Primary Endpoint 
• The proportion of participants with clinical remission at Week 13 using modified Mayo 
score (MMS) 
Key Secondary Endpoints 
• The proportion of participants with endoscopic improvement at Week 13 
• The proportion of participants with symptomatic remission at Week 13 
• The proportion of participants with histologic remission at Week 13 
• The proportion of participants with endoscopic improvement-histologic remission at 
Week 13 
Other Secondary Endpoints 
• The proportion of participants with clinical response using MMS at Week 13 
• The proportion of participants with endoscopic remission at Week 13 
• The proportion of participants with endoscopic and histologic remission at Week 13 
• The proportion of participants with endoscopic and clinical remission at Week 13 
• The proportion of participants with endoscopic, histologic, and clinical remission at 
Week 13 
• The proportion of participants with symptomatic remission at Weeks 4, 8, 10 
• The proportion of participants with symptomatic response at Weeks 4, 8, 10, 13 
• The proportion of participants with clinical remission using total Mayo Clinic score 
(MCS) at Week 13 
• The proportion of participants with clinical response using total MCS at Week 13 
• The proportion of participants with histologic improvement at Week 13 
• Proportion of participants with any decrease from baseline in Geboes Index score at 
Week 13 
• The proportion of participants with histologic-endoscopic mucosal improvement (HEMI) 
at Week 13 
• The proportion of participants with UC-related hospitalizations 

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• The proportion of participants requiring UC-related surgeries, including colectomy 
• Plasma concentrations of VTX002, assessed from samples collected predose at Weeks 0, 
1, 4, 8, and 13 in the Induction Treatment Period, and Weeks 18, 26, 36, and 52 in the 
LTE Treatment Period; at the 1-Week and 2-Week Follow-Up visits; and at 2, 4, and 
6 hours (± 15 minutes) postdose at Week 0 
Safety Endpoints 
• Incidence and severity of adverse events  
• Incidence and severity of laboratory abnormalities, and change from baseline in 
laboratory values (eg, hematology and serum chemistry) 
• Incidence of clinically significant vital sign abnormalities and changes from baseline 
Exploratory Endpoints 
The endpoints described here will be analyzed separately for the Induction Treatment Period, 
LTE Treatment Period, and OLE Treatment Period. OLE analyses will be described in detail in 
the Statistical Analysis Plan (SAP). 
• Proportion of participants with clinical remission after 52 weeks of treatment 
• Proportion of participants with clinical remission after 13 and 52 weeks of treatment 
• Proportion of participants with symptomatic remission at Weeks 18, 26, 36, and 52 
• Proportion of participants with endoscopic and histologic remission after 52 weeks of 
treatment 
• Proportion of participants with endoscopic improvement-histologic remission after 
52 weeks of treatment 
• Proportion of participants with endoscopic and clinical remission after 52 weeks of 
treatment 
• Proportion of participants with endoscopic, histologic, and clinical remission after 
52 weeks of treatment 
• Proportion of participants with HEMI after 52 weeks of treatment 
• Proportion of participants with clinical response after 52 weeks of treatment 
• Proportion of participants with symptomatic response at Weeks 18, 26, 36, and 52 
• Proportion of participants with symptomatic response at OLE Week 13, and at each 
additional OLE visit 
• Proportion of participants with any decrease from baseline in Geboes Index score at 
Week 52 
• Change from baseline in fecal calprotectin (FCP) at Weeks 1, 4, 8, 13, 26, 36, 52, and at 
visits during the OLE 
• Change from baseline in C-reactive protein (CRP) at Weeks 1, 4, 8, 13, 26, 36, 52, and at 
visits during the OLE 
• Change from baseline in partial Mayo score (PMS) at Weeks 4, 8, 13, 18, 26, 36, 52, and 
at visits during the OLE 
• Change from baseline in total MCS at Week 52 
• Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) score at 
Weeks 13 and 52 

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• Change and percentage change from baseline in lymphocyte counts at Weeks 1, 4, 8, 13, 
26, 36, and 52 
Inclusion Criteria 
Participants must meet ALL of the following inclusion criteria to be eligible for enrollment into 
the study: 
1. Men or women, 18 to 80 years of age, inclusive, at the time of consent 
2. Capable of giving signed informed consent, which includes compliance with the 
requirements and restrictions listed in the Informed Consent Form 
Disease-Specific 
3. Diagnosed with UC ≥ 3 months prior to Screening. The diagnosis of UC must be confirmed 
by endoscopic and histologic evidence. The endoscopy and histology report should be 
present in the source documents; however, if not available, the Screening endoscopy and 
histology may serve as such. 
4. Active UC confirmed by endoscopy with ≥ 10 cm rectal involvement. Participants with 
proctitis only at baseline who meet the other eligibility criteria for inclusion, including the 
endoscopic and rectal bleeding criteria for moderate to severe disease, will be capped at 10% 
of the total participants enrolled. 
5. Moderately to severely active UC, defined as an MMS of 5 to 9, including an endoscopic 
subscore (ES) ≥ 2 and a rectal bleeding (RB) subscore ≥ 1 
6. Surveillance colonoscopy (performed according to local standard) within 12 months before 
baseline to rule out dysplasia in participants with pancolitis > 8 years duration or participants 
with left-sided colitis > 12 years duration. Participants without a surveillance colonoscopy 
within the prior 12 months will have a colonoscopy at Screening (ie, in place of Screening 
proctosigmoidoscopy). Any adenomatous polyps must be removed per local standard of care 
prior to the first dose of study drug. 
Prior Treatment Failure 
7. Demonstrated inadequate response to, loss of response to, or intolerance to at least 1 of the 
following therapies: 
a. Conventional therapy: 
i. 
Oral 5-aminosalicylic acid (5-ASA) compounds 
ii. Corticosteroids 
iii. Thiopurines (eg, azathioprine or 6-mercaptopurine) 
b. Biologic therapy or JAK inhibitor therapy: 
i. 
Anti-tumor necrosis factor alpha (TNFα) antibodies (eg, infliximab, adalimumab, or 
golimumab) 
ii. Anti-interleukin (anti-IL)12/23 (eg, ustekinumab) 
iii. Anti-integrin antibodies (eg, vedolizumab) 

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iv. JAK inhibitors (eg, tofacitinib, upadacitinib) 
Note: The medication used to qualify the participant for entry into this category of 
biologic therapy or JAK inhibitor therapy must be approved for the treatment of UC in 
the country of use. 
General Safety 
8. Adequate hepatic function, defined as a total bilirubin level of ≤ 1.5 × upper limit of normal 
(ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels of 
≤ 2.0 × ULN. Participants with Gilbert’s syndrome who have an isolated total bilirubin and 
normal AST and ALT levels may participate. 
9. Adequate renal function, defined as an estimated glomerular filtration rate 
≥ 60 mL/min/1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration equation 
at Screening 
Concomitant Medications 
10. Participants are permitted to receive the following concomitant medications: 
a. Oral 5-ASA compounds at a stable dose or discontinued for ≥ 2 weeks prior to Screening 
endoscopy 
b. Oral corticosteroid therapy at a stable dose or discontinued for ≥ 2 weeks prior to 
Screening endoscopy (prednisone at a stable dose ≤ 20 mg/day, budesonide at a stable 
dose ≤ 9 mg/day) 
c. Probiotics, provided the dose has been stable for ≥ 2 weeks prior to Screening endoscopy 
Contraception 
11. Women must meet either a or b of the following criteria and men must meet criterion c to 
qualify for the study: 
a. A woman who is not of childbearing potential must meet 1 of the following: 
i. 
Postmenopausal, defined as no menses for 12 months without an alternative medical 
cause 
ii. Permanent sterilization procedure, such as hysterectomy, bilateral salpingectomy, or 
bilateral oophorectomy 
b. A nonpregnant woman of childbearing potential must agree to use a highly effective 
contraception method that can achieve a failure rate of less than 1% per year when used 
consistently and correctly. The highly effective contraception must be used through the 
duration of the study and for 30 days after the last dose of study treatment. The following 
are considered highly effective birth control methods: 
i. 
Combined (estrogen- and progesterone-containing) hormonal contraception 
associated with inhibition of ovulation, which may be oral, intravaginal, or 
transdermal. 
ii. Progesterone-only hormonal contraception associated with inhibition of ovulation, 
which may be oral, injected, or implanted 
iii. Intrauterine device  

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iv. Intrauterine hormone-releasing system 
v. Bilateral tubal occlusion 
vi. Vasectomized partner, provided that the partner is the sole sexual partner of the 
woman of childbearing potential study participant and the vasectomized partner has 
received medical assessment of the surgical success 
vii. Sexual abstinence (complete sexual abstinence, defined as refraining from 
heterosexual intercourse for the entire period of risk associated with study 
treatments). The reliability of sexual abstinence needs to be evaluated in relation to 
the duration of the clinical study and the preferred and usual lifestyle of the 
participant. Periodic abstinence (calendar, symptothermal, postovulation methods) 
is not acceptable. 
c. A man with a pregnant or nonpregnant partner who is a woman of childbearing potential 
must agree to use condoms through the duration of the study and for 30 days after the last 
dose of study treatment. 
Exclusion Criteria 
Participants will be excluded from the study if any of the following criteria apply: 
Inflammatory Bowel Disease and Gastrointestinal Conditions 
1. Severe extensive colitis as evidenced by: 
a. Physician judgment that the participant is likely to require surgery (surgical intervention 
of any kind for UC [eg, colectomy]) within 12 weeks of baseline 
b. Current evidence of fulminant colitis or toxic megacolon, or recent history (within last 
6 months) of toxic megacolon or bowel perforation 
c. Previous total colectomy 
2. Diagnosis of Crohn’s disease or indeterminate colitis or the presence or history of a fistula 
consistent with Crohn’s disease 
3. Diagnosis of microscopic colitis, ischemic colitis, or infectious colitis 
4. Positive assay or stool culture for pathogens (ova and parasite examination, bacteria) or 
positive test for Clostridium difficile at Screening. Note: If C. difficile or pathogen test is 
positive, the participant may be treated and retested ≥ 4 weeks after completing treatment. 
General Safety 
5. Pregnancy, lactation, or a positive serum β-hCG measured during Screening 
6. Clinically relevant hematologic, hepatic, neurological, pulmonary, ophthalmological, 
endocrine, metabolic (including, but not limited to, hypo- and hyperkalemia), psychiatric, or 
other major systemic disease that will make implementation of the protocol or interpretation 
of the study difficult or will put the participant at risk 
7. Forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) < 70% of 
predicted values and FEV1/FVC ratio < 0.70 at Screening 

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8. Have any of the following conditions or receiving treatments that may affect cardiovascular 
function: 
a. Myocardial infarction, unstable angina, stroke/transient ischemic attack, decompensated 
heart failure requiring hospitalization, or Class III/IV heart failure within ≤ 6 months prior 
to or during the Screening Period 
b. Screening or prerandomization vital signs (taken in the sitting position) with a heart rate 
(HR) < 50 bpm OR systolic blood pressure (BP) < 90 mmHg OR diastolic BP < 55 mmHg. 
Vital signs may be repeated up to 3 times during a visit to confirm abnormal readings. 
c. Screening or prerandomization electrocardiogram (ECG) with PR interval > 200 msec or 
Fridericia’s corrected QT interval (QTcF) ≥ 450 msec in men or ≥ 470 msec in women 
d. History of any of the following unless treated with an implanted pacemaker or an 
implanted cardioverter-defibrillator with pacing: 
i. 
History or presence of recurrent symptomatic bradycardia 
ii. Second- or third-degree atrioventricular block 
iii. Periods of asystole > 3 seconds 
iv. History of sick sinus syndrome or recurrent cardiogenic syncope 
e. Start, stop, or change in dosage of any Class I-IV anti-arrhythmic drugs ≤ 1 week prior to 
dose titration starting at randomization and up to 1 week after titration to the assigned 
dose. This criterion also applies to the OLE Treatment Period titration: 1 week prior to 
and 1 week after the dose titration period. 
9. Uncontrolled diabetes as determined by hemoglobin A1c (HbA1c) > 9%, or participants with 
diabetes with significant comorbid conditions, such as retinopathy 
10. History or presence of macular edema or retinopathy 
11. History of cancer within the last 5 years, including solid tumors and hematological 
malignancies (except basal cell and in situ squamous cell carcinomas of the skin that have 
been excised and resolved) or precancerous conditions such as colonic mucosal dysplasia, 
cervical dysplasia, and cervical intraepithelial neoplasia 
12. History of lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorder, 
or multiple myeloma 
13. History of alcohol or drug abuse within 1 year prior to randomization 
14. Any of the following laboratory abnormalities during the Screening Period: 
a. Absolute white blood cell (WBC) count < 3500/μL 
b. Neutrophils < 1500/μL 
c. Absolute lymphocyte count < 800/μL 
d. Platelet count < 100,000/μL 
e. Hemoglobin < 8 g/dL 

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Infection Risk 
15. Active or latent tuberculosis (TB) infection at Screening. History of untreated or 
inadequately treated latent TB infection. The following are EXCEPTIONS to this exclusion 
criterion: 
a. Participants with latent TB, who have been ruled out for active TB, have completed an 
appropriate course of TB prophylaxis treatment per national/local medical guidelines or 
WHO guidelines, have a chest radiograph without changes suggestive of active TB 
infection, and have not had recent close contact with a person with active TB are eligible 
to enroll in the study. It is the responsibility of the Investigator to verify the adequacy of 
previous TB treatment and provide appropriate documentation of treatment compliance.  
b. Participants diagnosed with latent TB at Screening, ruled out for active TB and have 
received at least 4 weeks of an appropriate TB prophylaxis regimen may be rescreened for 
enrollment. Participant will complete their prophylactic regimen during the trial. 
16. Known active bacterial, viral, fungal, mycobacterial, or other infection (including TB or 
atypical mycobacterial disease) or any major episode of infection that required 
hospitalization or treatment with intravenous (IV) antibiotics within 30 days of Screening or 
oral antibiotics within 14 days prior to Screening. Fungal infection of nail beds is allowed. 
17. Human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) or 
positive test for HIV antibodies at Screening 
18. Acute or chronic hepatitis B infection or test positive for hepatitis B virus (HBV) at 
Screening (positive for hepatitis B surface antigen [HBsAg], or negative for HBsAg and 
positive for anti-hepatitis B core antibody in conjunction with detectable HBV 
deoxyribonucleic acid [DNA]) 
19. Current hepatitis C infection or test positive for hepatitis C virus (HCV) at Screening, as 
defined by positive hepatitis C antibody and detectable HCV ribonucleic acid  
20. History of an opportunistic infection (eg, Pneumocystis jirovecii, cryptococcal meningitis), 
progressive multifocal leukoencephalopathy (PML), or history of disseminated herpes zoster 
or disseminated herpes simplex 
21. History of currently active primary or secondary immunodeficiency 
Previous or Concomitant Treatment  
22. Hypersensitivity to VTX002 or any of the excipients or placebo compounds 
23. Treatment with an investigational therapy ≤ 3 months prior to randomization 
24. Treatment with cyclosporine, tacrolimus, sirolimus, methotrexate, or mycophenolate mofetil 
≤ 8 weeks prior to Screening 
25. Prior treatment with S1P receptor modulators including but not limited to fingolimod, 
siponimod, ozanimod, ponesimod, and etrasimod 
26. Treatment with a biologic agent (ie, anti-TNFs, anti-integrins, and anti-IL-12/23) meeting the 
following criteria: 
a. Treatment with infliximab, adalimumab, golimumab, or vedolizumab ≤ 60 days prior to 
randomization 

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b. Treatment with ustekinumab ≤ 90 days prior to randomization 
c. Treatment with any other approved biologic agent ≤ 5 half-lives prior to randomization 
Note: A trough drug level can be obtained during Screening to confirm absence of biologic 
drug levels in lieu of the washout periods 
27. Treatment with JAK inhibitors ≤ 4 weeks prior to randomization 
28. Use of IV corticosteroids and/or topical steroids ≤ 2 weeks prior to Screening endoscopy. 
Alternative forms of steroids require consultation with the Medical Monitor. 
29. Use of immunosuppressant drugs including thiopurines ≤ 2 weeks prior to Screening 
endoscopy 
30. Prior treatment failure with ≥ 3 biologic agents with different mechanisms of action or 
≥ 2 biologics with different mechanisms of action plus a JAK inhibitor approved for the 
treatment of UC 
31. Treatment with topical rectal 5-ASA or short-chain fatty acid enemas ≤ 2 weeks prior to 
Screening endoscopy 
32. Receipt of a live vaccine ≤ 4 weeks prior to randomization and until 2 weeks post last dose. 
Approved nonlive vaccines, including severe acute respiratory syndrome coronavirus 2 
(SARS-CoV-2), can be administered according to local vaccination standards. 
33. Previous treatment with natalizumab 
34. Previous treatment with lymphocyte-depleting therapies (eg, anti-CD4, cladribine, rituximab, 
ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow 
transplantation, alemtuzumab, daclizumab) 
35. Previous treatment with D-penicillamine, thalidomide, dimethyl fumarate, or pyrimidine 
synthesis inhibitors 
36. Treatment with IV immune globulin or plasmapheresis ≤ 3 months prior to randomization 
Study Periods 
Participant eligibility will be determined during a 4-week (28-day) Screening Period. Entry criteria 
will be based on confirmation of moderately to severely active UC, defined by an MMS of 5 to 9 
with an ES ≥ 2 and RB ≥ 1.  
On Day 1, eligible participants will be randomized in a 1:1:1 ratio to receive VTX002 30 mg, 
VTX002 60 mg, or matching placebo orally once a day (approximately 63 participants per 
treatment group). During the first week of the Induction Treatment Period, participants will 
undergo a 7-day dose titration up to the full assigned double-blind treatment dose. At the end of 
the 13-week Induction Treatment Period, all participants will be evaluated for efficacy and safety.  
Participants who complete the Induction Week 13 visit, and meet criteria for clinical response at 
Induction Week 13, will continue into the blinded LTE Period at their previously assigned 
treatment for up to an additional 39 weeks. Participants who complete the Week 52 visit of the 
LTE may continue into the OLE. If at any time after Week 13, a participant experiences loss of 
response, the participant will have the option to enroll into the OLE.  

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Participants who enter the OLE from the LTE will undergo a 7-day titration period and remain in 
the OLE for a possible total of 36 months of treatment (including the 13-week Induction Period, 
plus the duration in the LTE and the duration in the OLE).  
Participants who complete the Induction Week 13 visit, and do not meet the criteria for clinical 
response at Induction Week 13, will have the option to enroll into the OLE for up to an additional 
143 weeks of treatment (which includes a 7-day titration period followed by treatment with 
VTX002 60 mg for up to 142 weeks). 
Regardless of previous blinded treatment during the Induction Period, if a participant’s condition 
worsens or does not improve after 13 weeks in the OLE with VTX002 60 mg, the participant will 
be discontinued from the study. 
The Sponsor may consider potential expansion of open-label access beyond the 36-month period, 
when the primary analysis results are available. 
For all participants, Follow-Up visits will be performed at 1 and 2 weeks after the last dose of 
study treatment, as indicated in the Schedule of Activities (SoA). All participants who discontinue 
the study prematurely will be asked to return to the clinic for the Early Termination (ET) visit. If 
an ET visit is ≥ 1 week after the last dose of study treatment, the 1-Week Follow-Up visit is not 
required; however, the 2-Week Follow-Up visit should be scheduled and completed.  
If the absolute peripheral lymphocyte count is not within normal limits at the 2-Week Follow-Up 
visit, participants should return for a complete blood count (CBC) with differential according to 
local standard of care (captured as a subsequent Follow-Up visit or unscheduled visit). 
Statistical Methods 
The primary efficacy analysis will be completed based on the Full Analysis Set (FAS) for the study 
drug. The primary endpoint is the proportion of participants with clinical remission at 13 weeks.  
The testing will be done using a Cochran-Mantel-Haenszel test (CMH) test with biologic/JAK 
inhibitor prior use status (Yes or No), baseline corticosteroid use (Yes or No), and baseline disease 
activity (MMS 4-6 or 7-9) as the stratification factors. The CMH chi-square p-value and stratified 
risk differences with 95% confidence interval (CI) using the Newcombe method will be provided 
for pairwise comparisons between each dose group and placebo. Only the two treatment groups – 
VTX002 60 mg and placebo – will be included in the primary analysis of the primary endpoint.  
Key secondary endpoints will be analyzed similarly to the primary endpoint, using the CMH test 
with similar stratification factors. Comparisons between VTX002 60 mg and placebo for all key 
secondary endpoints will be considered key secondary analyses. Comparisons between VTX002 
30 mg and placebo for the primary endpoint and the key secondary endpoints will be considered 
key secondary analyses. The family-wise Type I error rate across the primary analysis of the 
primary efficacy endpoint and all key secondary analyses will be maintained at α = 0.05 using a 
sequentially rejective method. Details will be provided in the SAP. 
Categorical exploratory endpoints will be analyzed similarly to the primary endpoint.  
Continuous exploratory endpoints will be analyzed using a general linear model (analysis of 
covariance [ANCOVA]) with fixed effects for treatment, biologic/JAK inhibitor prior use status 
(Yes or No), baseline corticosteroid use (Yes or No), and baseline disease activity (MMS 4-6 or 
7-9). 

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Symptomatic response and symptomatic remission at Weeks 4, 8, 10, 13, 18, 26, 36, and 52 will 
be analyzed using an appropriate categorical repeated measurements methodology. Change from 
baseline in FCP and CRP at Weeks 1, 4, 8, 13, 26, 36, and 52; and also for change from baseline 
in PMS at Weeks 4, 8, 13, 18, 26, 36, and 52 will be analyzed using an appropriate continuous 
repeated measurements methodology. Details will be provided in the SAP, and will include a 
specification of how the results will be reported. 
All the exploratory endpoints collected during the LTE Treatment Period and the OLE Treatment 
Period will be summarized with appropriate summary statistics over time, using the same 
definitions given above. 
All safety data (eg, Holter ECG monitoring, 12-lead ECG, optical coherence tomography [OCT], 
pulmonary function test [PFT], and physical examination) will be listed and summarized using 
descriptive statistics.

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x. PK samples will be collected (measuring trough concentrations) after completion of vital sign assessments and ECGs. When study drug is administered at the 
clinic, PK sample will be collected predose. On Day 1 only, PK samples will also be collected at 2, 4, and 6 hours (± 10 minutes) postdose (see Table 10). 
y. Sigmoidoscopy is sufficient at both Screening and Visit 7. Colonoscopy can be performed if a surveillance colonoscopy is needed or based on the clinical 
judgment of the Investigator. 
z. Participants will begin eDiary entries beginning on the first day of Screening after diary training is completed. The eDiary should be completed daily to 
capture data, including daily SF and RB (the 2 patient-reported outcome measures of the MMS), and study drug administration. Study center personnel 
should review the diary data at every visit at the timepoints in the table and in between visits via EDC to confirm compliance with eDiary completion. In 
addition, the RB score should be assessed during the Screening Period to ensure the RB score will meet eligibility criteria prior to performing the endoscopy. 
aa. The MMS will be calculated electronically during Screening for eligibility and at Visit 7 for determination of clinical response. The subscores for RB and SF 
are derived from the participant eDiary entries using the scores from the 3 most recent consecutive days within the 7 days prior to the day of bowel 
preparation, averaged and rounded to the nearest integer.  
bb. When endoscopy is performed (see footnote y) and colonic biopsy is collected, samples are sent to the central laboratory. If there is no histologic report 
present at the time of Screening corroborating the diagnosis, additional colonic samples should be taken and sent to a local laboratory for confirmation of the 
diagnosis. Colonic biopsy may be used for histology 
 Biopsy samples will be processed by a central laboratory, and histopathologic 
scoring using the Geboes, Robarts, and Nancy histopathology indices will be performed by a blinded central reader (Appendix 7). 
cc. If and when available in the appropriate local language. 
 

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h. For women of childbearing potential, all pregnancy testing will be performed using a urine dipstick pregnancy test. Home urine pregnancy test kits may be 
provided to the participant for any virtual/hybrid visit or to perform a pregnancy test at home during non-visit months, if permitted by local 
regulations. Participants will confirm the performance of a monthly pregnancy test in the eDiary, if performed at home, and provide the results to the study 
site. Any positive urine pregnancy test result will be confirmed with a serum β-hCG test by a central laboratory. 
i. 
Coagulation panel to be performed at an unscheduled visit in case of elevated ALT/AST. 
j. 
Complete physical examination at Visit 12/ET visit and brief physical examinations during the study. A complete physical examination will include 
evaluation of heart, lung, head and neck, abdomen, neurological function, skin, and extremities. An interim (or brief) physical examination will include 
areas with previously noted abnormalities and/or that are associated with any new complaints from the participant. 
k. Pulmonary function includes assessment of FEV1 and FVC. If the pulmonary function test results are not within normal range, the results should be verified 
by a pulmonologist, and potential confounding factors identified. If the participant has a decline in pulmonary function test values, the participant should be 
evaluated by a pulmonologist. If values (FEV1 and/or FVC) decline below 50% of the predicted values, treatment should be discontinued with follow-up 
evaluation initiated as appropriate. At sites where available, DLCO measurements will also be performed. The ET visit assessment is required only if results 
from the Visit 12 or last on-treatment visit are abnormal. Visit 10 (Week 26) assessment will be performed if clinically indicated.  
l. 
A general ophthalmologist can perform the examination, although a retinal specialist would be preferred wherever possible. A complete ophthalmoscopy 
and OCT assessment should be performed according to the SoA. Site should retain a copy of the OCT result and the ophthalmologist report. For participants 
with a suspicion of new onset of macular edema and/or retinopathy, along with evaluation using ophthalmoscopy and OCT, additional testing should be 
considered at the discretion of the ophthalmologist (eg, general retinal examinations, including eye history, visual acuity, dilated ophthalmoscopy).  
m. Participants will receive a stool sampling kit at a previous visit and be asked to collect a stool sample within 24 hours of the visit. Participants are to bring 
stool samples to the clinic. 
 
 
o. PK samples will be collected (measuring trough concentrations) after completion of vital sign assessments and ECGs. When study drug is administered at 
the clinic, PK sample will be collected predose (see Table 10). 
p. Endoscopy at ET visit is required only for participants who discontinue the study at or after Week 26. 
q. The eDiary should be completed daily to capture data, including daily SF and RB, and study drug administration. Study center personnel should review the 
diary data at every visit at the timepoints in the table and in between visits via EDC to confirm compliance with eDiary completion. 
r. 
The MMS will be calculated electronically at the Week 52/ET visit. The subscores for RB and SF are derived from the participant eDiary entries using the 
scores from the 3 most recent consecutive days within the 7 days prior to the day of bowel preparation, averaged and rounded to the nearest integer.  
s. 
Partial Mayo Score will include SF, RB and PGA assessments, and will be used to determine loss of response as described in Section 8.3.1.5.  
t. 
When endoscopy is performed (see footnote p) and colonic biopsy is collected, samples are sent to the central laboratory. Colonic biopsy may be used for 
histology 
 Biopsy samples will be processed by a central laboratory, and histopathologic scoring using the Geboes, Robarts, and 
Nancy histopathology indices will be performed by a blinded central reader (Appendix 7). 
u. If and when available in the appropriate local language. 
 

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i. 
An increase in AST or ALT > 3 × ULN should be followed by repeat testing within 72 hours of receiving results to confirm the abnormality and determine 
whether AST or ALT is increasing or decreasing. 
j. 
For women of childbearing potential, all pregnancy testing will be performed using a urine dipstick pregnancy test. Home urine pregnancy test kits may be 
provided to the participant for any virtual/hybrid visit or to perform a monthly pregnancy test at home during non-visit months, if permitted by local 
regulations. Participants will confirm the performance of a monthly pregnancy test in the eDiary, if performed at home, and provide the results to the study 
site. Any positive urine pregnancy test result will be confirmed with a serum β-hCG test by a central laboratory. 
k. Coagulation panel to be performed at an unscheduled visit in case of elevated ALT/AST. 
l. 
Complete physical examination at OLE Visit 17/ET visit (see Table 6) and brief physical examinations during the study. A complete physical examination 
will include evaluation of heart, lung, head and neck, abdomen, neurological function, skin, and extremities. An interim (or brief) physical examination will 
include areas with previously noted abnormalities and/or that are associated with any new complaints from the participant. 
m. Pulmonary function includes assessment of FEV1 and FVC. If the pulmonary function test results are not within normal range, the results should be verified 
by a pulmonologist, and potential confounding factors identified. If the participant has a decline in pulmonary function test values, the participant should be 
evaluated by a pulmonologist. If values (FEV1 and/or FVC) decline below 50% of the predicted values, treatment should be discontinued with follow-up 
evaluation initiated as appropriate. At sites where available, DLCO measurements will also be performed.  
n. A general ophthalmologist can perform the examination, although a retinal specialist would be preferred wherever possible. A complete ophthalmoscopy 
and OCT assessment should be performed according to the SoA. Site should retain a copy of the OCT result and the ophthalmologist report. For participants 
with a suspicion of new onset of macular edema and/or retinopathy, along with evaluation using ophthalmoscopy and OCT, additional testing should be 
considered at the discretion of the ophthalmologist (eg, general retinal examinations, including eye history, visual acuity, dilated ophthalmoscopy).  
o. Participant will receive a stool sampling kit at a previous visit and be asked to collect a stool sample within 24 hours before the next visit. Participants are to 
bring stool samples to the clinic. 
 
 
q. PK samples will be collected (measuring trough concentrations) after completion of vital sign assessments and ECGs. When study drug is administered at 
the clinic, PK sample will be collected predose. At OLE Visit 1 (OLE Day 1), PK samples will be collected predose and also at 2, 4, 6, and 24 hours 
(± 10 minutes) postdose (24 hours postdose is an optional timepoint and applies only to participants who consent to return to the clinic on OLE Day 2). At 
OLE Visit 2 and OLE Visit 3, PK samples will be collected predose and at 2, 4, 6, and 24 hours (± 10 minutes) postdose (postdose timepoints are optional, 
but all 4 timepoints are required for participants who consent) (see Table 10). 
r. 
The eDiary should be completed daily to capture data, including daily SF and RB, and study drug administration. Study center personnel should review the 
diary data at every visit at the timepoints in the table and in between visits via EDC to confirm compliance with eDiary completion. Symptomatic response, 
using RB and SF scores, will be assessed by the Investigator at OLE Week 13 only for participants who failed to achieve clinical response at the end of the 
Induction Period (Table 1, Week 13). 
s. 
Partial Mayo Score will include SF, RB and PGA assessments, and will be used to determine loss of response as described in Section 8.3.1.5. 

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35 
h. An increase in AST or ALT > 3 × ULN should be followed by repeat testing within 72 hours of receiving results to confirm the abnormality and determine 
whether AST or ALT is increasing or decreasing. 
i. 
For women of childbearing potential, all pregnancy testing will be performed using a urine dipstick pregnancy test. Home urine pregnancy test kits may be 
provided to the participant for any virtual/hybrid visit or to perform a monthly pregnancy test at home during non-visit months, if permitted by local 
regulations. Participants will confirm the performance of a monthly pregnancy test in the eDiary, if performed at home, and provide the results to the study 
site. Any positive urine pregnancy test result will be confirmed with a serum β-hCG test by a central laboratory. 
j. 
Coagulation panel to be performed at an unscheduled visit in case of elevated ALT/AST. 
k. Complete physical examination at OLE Visit 17/ET visit (see Table 6) and brief physical examinations during the study. A complete physical examination 
will include evaluation of heart, lung, head and neck, abdomen, neurological function, skin, and extremities. An interim (or brief) physical examination will 
include areas with previously noted abnormalities and/or that are associated with any new complaints from the participant. 
l. 
Pulmonary function includes assessment of FEV1 and FVC. If the pulmonary function test results are not within normal range, the results should be verified 
by a pulmonologist, and potential confounding factors identified. If the participant has a decline in pulmonary function test values, the participant should be 
evaluated by a pulmonologist. If values (FEV1 and/or FVC) decline below 50% of the predicted values, treatment should be discontinued with follow-up 
evaluation initiated as appropriate. At sites where available, DLCO measurements will also be performed. The ET visit assessment is required only if results 
from the last on-treatment visit are abnormal. 
m. A general ophthalmologist can perform the examination, although a retinal specialist would be preferred wherever possible. A complete ophthalmoscopy 
and OCT assessment should be performed according to the SoA. Site should retain a copy of the OCT result and the ophthalmologist report. For participants 
with a suspicion of new onset of macular edema and/or retinopathy, along with evaluation using ophthalmoscopy and OCT, additional testing should be 
considered at the discretion of the ophthalmologist (eg, general retinal examinations, including eye history, visual acuity, dilated ophthalmoscopy). 
n. Participants will receive a stool sampling kit at a previous visit and be asked to collect a stool sample within 24 hours of the visit. Participants are to bring 
stool samples to the clinic. 
 
 
p. PK samples will be collected (measuring trough concentrations) after completion of vital sign assessments and ECGs. When study drug is administered at 
the clinic, PK sample will be collected predose (see Table 10). 
q. Endoscopy is not required if ET visit is before OLE Week 13 (Table 3). 
r. 
The eDiary should be completed daily to capture data, including daily SF and RB, and study drug administration. Study center personnel should review the 
diary data at every visit at the timepoints in the table and in between visits via EDC to confirm compliance with eDiary completion. 
s. 
The MMS will be calculated electronically at OLE Week 39/ET visit. The subscores for RB and SF are derived from the participant eDiary entries using the 
scores from the 3 most recent consecutive days within the 7 days prior to the day of bowel preparation, averaged and rounded to the nearest integer.  
t. 
Partial Mayo Score will include SF, RB and PGA assessments, and will be used to determine loss of response as described in Section 8.3.1.5. 
u. When endoscopy is performed (see footnote q) and colonic biopsy is collected, samples are sent to the central laboratory. Colonic biopsy may be used for 
histology 
 Biopsy samples will be processed by a central laboratory, and histopathologic scoring using the Geboes, Robarts, and 
Nancy histopathology indices will be performed by a blinded central reader (Appendix 7). 
v. If and when available in the appropriate local language. 

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j. Complete physical examination at OLE Visit 17/ET visit (Table 6) and brief physical examinations during the study. A complete physical examination will 
include evaluation of heart, lung, head and neck, abdomen, neurological function, skin, and extremities. An interim (or brief) physical examination will 
include areas with previously noted abnormalities and/or that are associated with any new complaints from the participant. 
k. Pulmonary function includes assessment of FEV1 and FVC. If the pulmonary function test results are not within normal range, the results should be verified 
by a pulmonologist, and potential confounding factors identified. If the participant has a decline in pulmonary function test values, the participant should be 
evaluated by a pulmonologist. If values (FEV1 and/or FVC) decline below 50% of the predicted values, treatment should be discontinued with follow-up 
evaluation initiated as appropriate. At sites where available, DLCO measurements will also be performed. The ET visit assessment is required only if results 
from the last on-treatment visit are abnormal. 
l. A general ophthalmologist can perform the examination, although a retinal specialist would be preferred wherever possible. A complete ophthalmoscopy and 
OCT assessment should be performed according to the SoA. Site should retain a copy of the OCT result and the ophthalmologist report. For participants with 
a suspicion of new onset of macular edema and/or retinopathy, along with evaluation using ophthalmoscopy and OCT, additional testing should be 
considered at the discretion of the ophthalmologist (eg, general retinal examinations, including eye history, visual acuity, dilated ophthalmoscopy). 
m. Participants will receive a stool sampling kit at a previous visit and be asked to collect a stool sample within 24 hours of the visit. Participants are to bring 
stool samples to the clinic. 
n. PK samples will be collected (measuring trough concentrations) after completion of vital sign assessments and ECGs. When study drug is administered at 
the clinic, PK sample will be collected predose (see Table 10). 
o. Endoscopy is an optional assessment in OLE Years 2-3. 
p. In OLE Years 2-3, the eDiary will be completed daily for a minimum of 2 weeks prior to each scheduled visit to capture daily SF and RB, and study drug 
administration. Study center personnel should review the diary data during schedule visits. 
q. If endoscopy is performed, the MMS will be calculated electronically at OLE Week 91/ET visit. The subscores for RB and SF are derived from the 
participant eDiary entries using the scores from the 3 most recent consecutive days within the 7 days prior to the day of bowel preparation, averaged and 
rounded to the nearest integer.  
r. Partial Mayo Score will include SF, RB and PGA assessments, and will be used to determine loss of response as described in Section 8.3.1.5. 
s. If endoscopy is performed (see footnote p) and colonic biopsy is collected, samples are sent to the central laboratory. Colonic biopsy may be used for 
histology 
 Biopsy samples will be processed by a central laboratory, and histopathologic scoring using the Geboes, Robarts, and 
Nancy histopathology indices will be performed by a blinded central reader (Appendix 7). 
 
 

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41 
i. Coagulation panel to be performed at an unscheduled visit in case of elevated ALT/AST. 
j. Complete physical examination at OLE Visit 17/ET visit and brief physical examinations during the study. A complete physical examination will include 
evaluation of heart, lung, head and neck, abdomen, neurological function, skin, and extremities. An interim (or brief) physical examination will include areas 
with previously noted abnormalities and/or that are associated with any new complaints from the participant. 
k. Pulmonary function includes assessment of FEV1 and FVC. If the pulmonary function test results are not within normal range, the results should be verified by 
a pulmonologist, and potential confounding factors identified. If the participant has a decline in pulmonary function test values, the participant should be 
evaluated by a pulmonologist. If values (FEV1 and/or FVC) decline below 50% of the predicted values, treatment should be discontinued with follow-up 
evaluation initiated as appropriate. At sites where available, DLCO measurements will also be performed. The ET visit assessment is required only if results 
from the last on-treatment visit are abnormal. 
l. A general ophthalmologist can perform the examination, although a retinal specialist would be preferred wherever possible. A complete ophthalmoscopy and 
OCT assessment should be performed according to the SoA. Site should retain a copy of the OCT result and the ophthalmologist report. For participants with a 
suspicion of new onset of macular edema and/or retinopathy, along with evaluation using ophthalmoscopy and OCT, additional testing should be considered at 
the discretion of the ophthalmologist (eg, general retinal examinations, including eye history, visual acuity, dilated ophthalmoscopy). 
m. Participants will receive a stool sampling kit at a previous visit and be asked to collect a stool sample within 24 hours of the visit. Participants are to bring 
stool samples to the clinic. 
n. PK samples will be collected (measuring trough concentrations) after completion of vital sign assessments and ECGs (see Table 10). 
o. Endoscopy is an optional assessment in OLE Years 2-3. 
p. In OLE Years 2-3, the eDiary will be completed daily for a minimum of 2 weeks prior to each scheduled visit to capture daily SF and RB, and study drug 
administration. Study center personnel should review the diary data during schedule visits. 
q. If endoscopy is performed, the MMS will be calculated electronically at OLE Week 143/ET visit. The subscores for RB and SF are derived from the 
participant eDiary entries using the scores from the 3 most recent consecutive days within the 7 days prior to the day of bowel preparation, averaged and 
rounded to the nearest integer. 
r. Partial Mayo Score will include SF, RB and PGA assessments, and will be used to determine loss of response as described in Section 8.3.1.5. 
s. If endoscopy is performed (see footnote p) and colonic biopsy is collected, samples are sent to the central laboratory. Colonic biopsy may be used for histology 
 Biopsy samples will be processed by a central laboratory, and histopathologic scoring using the Geboes, Robarts, and Nancy 
histopathology indices will be performed by a blinded central reader (Appendix 7). 
 

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2.0 
INTRODUCTION 
2.1 
Study Rationale 
Ulcerative colitis (UC) is a chronic recurrent, remittent, or progressive inflammatory condition 
that affects the colonic mucosa and is associated with an increased risk for colon cancer.1 Existing 
standard of care agents for UC primarily work by treating the acute symptoms of UC, inducing 
remission in the majority of cases, with approximately 60% to 70% of patients achieving remission 
with first-line corticosteroid therapy.2 Of the patients who receive second-line therapy such as 
biologics, about 30% to 40% of patients do not respond to treatment despite optimal therapy, while 
another 23% to 46% of patients lose response over time or discontinue treatment, resulting in 
limited clinical benefits.3 There remains meaningful unmet medical need, including a significant 
underserved set of patients who will not respond or become unresponsive to current therapies. 
VTX002 (formerly known as OPL-002) is an oral small molecule compound being developed for 
the treatment of moderately to severely active UC. VTX002 is a selective sphingosine-1-phosphate 
receptor (S1PR) modulator. The sphingosine-1-phosphate (S1P) signal transduction through the 
S1PRs plays an important role in a series of responses, including inflammation and repair 
processes, which play an important role in several immune-mediated inflammatory diseases. The 
available nonclinical and clinical data support the initiation of a Phase 2 study of VTX002 in 
participants with moderate to severe UC. This Phase 2 study aims to evaluate the efficacy and 
safety of VTX002 tablets for daily oral administration in participants with moderately to severely 
active UC. 
2.2 
Background 
Ulcerative colitis is a chronic disease of unknown etiology that is characterized by inflammation 
of the rectum and colon. Symptoms include diarrhea, rectal bleeding (RB), urgency, and tenesmus. 
Ulcerative colitis has a relapsing-remitting course, which means that many patients have 
intermittent disease flares that are interspersed with periods of remission. 
The treatment goals for UC include acute treatment of symptoms (ie, induction of clinical 
remission) and prevention of flare-ups (maintenance of remission). Medications currently 
available in the market for UC include 5-aminosalicylic acid (5-ASA)-containing medications, 
corticosteroids, immunomodulators such as azathioprine (AZA) and 6-mercaptopurine (6-MP) 
(off-label use), biologic medications (eg, anti-tumor necrosis factor [TNF] and anti-integrins), and 
Janus kinase (JAK) inhibitor therapy. As many patients do not fully respond to available treatment, 
there continues to be an unmet medical need for the development of easily administered, oral 
targeted therapies for the acute symptomatic and maintenance treatment of UC, particularly as 
most patients treated with biologics experience inadequate response. Moreover, many patients who 
receive biologics lose responsiveness over time, even though their initial response may have been 
positive.4 

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VTX002 is an oral small molecule compound being developed for the treatment of moderately to 
severely active UC. VTX002 is a selective S1PR modulator. The S1P signal transduction through 
the S1PRs plays an important role in a series of responses, including inflammation and repair 
processes, which play an important role in several immune-mediated inflammatory diseases. 
2.2.1 Nonclinical Findings 
A series of studies in mouse, rat, dog, and monkey show potent activity of VTX002 as a S1P1 
receptor modulator with modest activity against S1P5 and selectivity over S1P2, S1P3, and S1P4 
receptor subtypes. These primary and secondary pharmacology studies have demonstrated that 
oral dosing of VTX002 leads to a robust and persistent reduction in circulating lymphocyte levels 
that correlates with the plasma concentration of VTX002. In addition, rapid recovery of normal 
lymphocyte trafficking is observed when VTX002 dosing is terminated. In the rat, doses of 
3 mg/kg and above showed significant suppression of circulating lymphocytes. In mouse, dog, and 
primate, approximately 80% suppression of circulating lymphocytes was attained with doses of 
10 mg/kg. In a trinitrobenzene sulfonic acid-induced acute UC model in the rat, efficacy was 
evident at doses ranging from 1 to 10 mg/kg. These data suggest a therapeutic effect can be 
obtained at a human equivalent dose of 0.48 to 1.67 mg/kg. These studies have also demonstrated 
that VTX002 has low central nervous system penetration and brain levels upon oral administration. 
VTX002 was found to have no significant secondary pharmacological effects when screened at a 
concentration of 10 µM against a panel of receptors, ion channels, enzymes, and neurotransmitter 
transporters. VTX002 had no effect on human sodium channel (Nav1.5) at concentrations up to 
10 µM and caused a small reduction (14%) in human calcium channel (Cav1.5) currents at 10 µM. 
This interaction is not considered to be physiologically significant as plasma concentrations 
required to elicit a Cav1.5 response are not expected to be attained following therapeutic doses. 
Core battery safety pharmacology studies conducted with VTX002 showed a modest effect on the 
hERG current with an IC50 of 3.5 µM. The no effect level was 0.1 µM. 
In a cardiovascular function study in telemetered dogs, there was no increase in QT interval (QT 
or QTc) at doses up to 30 mg/kg/day and corresponding peak plasma concentrations of 
4600 ng/mL (8.4 µM). There was also no effect on blood pressure (BP), electrocardiogram (ECG) 
intervals, and body temperature, and no effects on respiratory function. Detailed analysis of heart 
rate (HR) showed no physiologically relevant changes and no transient decreases in HR in the dog, 
which has been reported with other S1P receptor modulators.5 VTX002 also had no effect on 
central and peripheral nervous system function in the rat. 
In summary, primary and secondary pharmacology studies show potent activity of VTX002 as a 
S1P1 receptor modulator with modest activity against S1P5 and selectivity over S1P2, S1P3, and 
S1P4 receptor subtypes and no other significant off target interactions. S1P1 receptor modulation 
resulted in reduced circulating lymphocytes in vivo, and efficacy was demonstrated in a model of 

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colitis in the rat. Safety pharmacology studies demonstrate no effects of oral dosing of VTX002 
on cardiovascular, respiratory, and central and peripheral nervous systems. 
2.2.2 Clinical Findings 
2.2.2.1 Phase 1 Study 
Safety findings from the Phase 1 study showed that VTX002 was safe and generally well tolerated 
when administered orally as an oral suspension (VTX002 SDD) at single (up to 40 mg) and 
multiple (up to 45 mg) ascending oral doses to healthy adult male participants for 21 to 28 days.6 
2.2.2.2 Pharmacokinetics 
Exposure to VTX002 following single doses of the reconstituted powder ranging from 2.5 to 
40 mg increased with dose. The exposure values increased in a somewhat more than 
dose-proportional manner with respect to the increase in VTX002 doses administered. 
However, when the multiple-dose study dose proportionality of plasma VTX002 was performed 
on the pharmacokinetic (PK) parameters maximum concentration (Cmax) and AUC from time zero 
to 24 hours [AUC(0-24)] following administrations of 10 mg VTX002 on Day 8, 20 mg VTX002 on 
Day 9, 35 mg VTX002 on Day 8, and 45 mg VTX002 on Day 8, each after a 7-day dose titration, 
the results indicated that exposure to VTX002 increased statistically proportional with increased 
VTX002 doses. Similarly, the dose proportionality analysis results following 13, 14, or 21 days of 
once daily (QD) dosing indicated that exposure to VTX002 increased in proportion to increases in 
the VTX002 dose. Steady-state analyses of plasma VTX002 concentrations following the 
administration of 10 mg VTX002 QD on Days 8 through 21 and 20 mg VTX002 QD on Days 9 
through 21 indicated that steady state was attained on Day 11 and Day 12, respectively. Moreover, 
steady-state analysis of plasma VTX002 concentrations following the administration of 35 mg 
VTX002 QD and 45 mg VTX002 QD on Days 8 through 28 showed that steady state had been 
achieved by Day 14. The results from the multiple-dose administration showed that the PK of 
VTX002 is linear (ie, it is invariant with respect to time). The accumulation test results showed 
that exposure to VTX002 increased more than the 2-fold following 21 days of multiple VTX002 
dosing. 
Food effect was also assessed in this Phase 1 study and did not affect the exposure to VTX002, as 
the geometric mean ratio values of Cmax and AUC were similar (differences were < 2.4%). There 
was an apparent 2-hour delay in the time to reach Cmax (Tmax) under fed conditions. However, this 
difference did not reach statistical significance (p-value > 0.05). 
2.2.2.3 Pharmacodynamics 
There was a dose-related mean reduction in absolute lymphocyte counts (ALC), as measured by 
percent change from baseline, following all single and multiple oral doses of VTX002 compared 
with placebo. Maximum mean percent change from baseline across all treatments occurred at 

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approximately 3 to 8 hours after dosing. Based on maximum mean percent change from baseline 
following a single oral dose of VTX002, the greatest reduction in ALC (65.4%) was associated 
with the largest plasma VTX002 Cmax value attained following the 40 mg VTX002 dose. Similarly, 
the largest reductions in ALC were associated with the highest plasma VTX002 trough 
concentration values following multiple oral VTX002 QD doses. At steady state, the mean percent 
reductions in ALC were similar for the 35 and 45 mg QD VTX002 doses (62% and 65%, 
respectively), as were the mean maximum observed reductions in ALC for the 35 and 45 mg QD 
VTX002 doses (75% and 74%, respectively). 
2.2.2.4 Cardiodynamics 
Assessment of QT intervals through linear regression of corrected QT using Fridericia’s formula 
(QTcF) versus RR indicated adequacy of QTcF. QTcF versus time profiles were similar across all 
VTX002 doses, with slightly greater mean values noted following 25 mg VTX002 (single 
ascending dose [SAD]) and 10 mg VTX002 (multiple ascending dose [MAD]). All participants in 
the SAD and MAD cohorts exhibited QTcF intervals ≤ 450 msec, and there were no participants 
with change from baseline values > 30 msec. 
2.2.2.5 Heart Rate Analysis 
In the SAD cohorts, there was a dose-related decrease in HR after dosing with VTX002 compared 
with placebo, with the maximum HR decrease from baseline (defined as the interval time between 
-1 hour to dose) occurring during Hour 1 (defined as the interval time between 1 and 2 hours 
postdose) with rapid increase after the nadir, returning to baseline by Hour 3 (defined as the 
interval time between 3 and 4 hours postdose). The maximum decrease from baseline 
of -21.2 beats per minute (bpm) (-30.80%) occurred during Day 1, Hour 1 (defined as the interval 
time between 1 and 2 hours postdose) among participants in the 40 mg VTX002 cohort. 
In the MAD cohorts, after a 7-day titration, there was no clinically significant decrease in HR after 
the administration of the target VTX002 dose. On the first day of the target dose administration, 
the maximum HR changes from predose occurred during Hour 1 (defined as the interval time 
between 1 and 2 hours postdose) and were -3.5 bpm in the 35 mg VTX002 QD cohort and -3.3 bpm 
in the 45 mg VTX002 QD cohort.  
2.2.2.6 Safety 
Single Ascending Dose Cohorts 
There were no deaths, serious adverse events (SAEs), or participant discontinuations due to 
adverse events (AEs) in the SAD part of this study. Overall, 18 (30%) participants dosed reported 
28 treatment-emergent adverse events (TEAEs) under fasted conditions (active drug or placebo) 
and an additional 5 TEAEs occurred in the food effect cohort under fed conditions. Adverse events 
incidence did not increase with rising VTX002 level. The most common TEAE was headache, 
experienced by 3 (5%) participants in the fasted cohorts and 1 (13%) participant in the food effect 

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cohort of the study. One participant in the 40 mg cohort reported an AE of Mobitz Type 1 
second-degree AV block. Overall, 32 TEAEs (27 in the fasted cohorts and 5 in the fed cohort) 
were mild (Grade 1) in severity and 1 (headache, pooled placebo, fasted) was moderate (Grade 2) 
in severity. No treatment- or dose-related trends were observed regarding vital sign, ECG, physical 
examination (PE), ophthalmic examination, or pulmonary function test (PFT) results with respect 
to participant safety in the SAD cohorts. 
Multiple Ascending Dose Cohorts 
There were no deaths or SAEs in the MAD cohorts in this study. Three participants were 
discontinued from the study due to AEs (including 1 event of urticaria, 1 event of first-degree AV 
block, and 1 event of Mobitz Type I second-degree atrioventricular [AV] block) that were 
considered drug related. The event of second-degree AV block led to temporary 1-day dosing 
holiday during the dose titration phase of the study for the 20 mg VTX002 MAD cohort. Overall, 
35 (88%) participants reported a total of 82 TEAEs, with similar numbers of participants reporting 
AEs across all cohorts. The most frequently reported TEAE was mild (Grade 1) contact dermatitis 
secondary to placement of Holter ECG electrode leads, experienced by 31 (78%) participants. 
Eighty-one TEAEs were mild (Grade 1) in severity and 1 (Mobitz Type 1 second-degree AV block, 
20 mg VTX002 once daily [QD]) was moderate (Grade 2) in severity. No treatment- or 
dose-related trends were observed regarding vital sign, ECG, PE, ophthalmic examination, or PFT 
results with respect to participant safety in the MAD cohorts. 
2.2.2.7 Relative Bioavailability Study 
Recently, a tablet formulation was developed for VTX002, and a relative bioavailability study was 
performed comparing the relative bioavailability of the 20 mg tablet to 20 mg of the free base 
suspension used in the Phase 1 study. The ratio of the AUC0-t for the tablet compared with the 
suspension was 
. For the low dose in this study of 30 mg daily, that is equivalent to 
 
of the free base suspension used in the Phase 1 study, and the high dose of 60 mg daily is equivalent 
to 
 of the free base suspension. Based on the similarity in PK characteristics (Cmax and 
AUC) of the suspension and tablet formulation and a half-life of approximately 20 hours, it is 
presumed that as with the suspension formulation, there would be minimal effect of food on 
exposure to the VTX002 tablet formulation. 
2.3 
Benefit/Risk Assessment 
VTX002 may benefit patients with moderately to severely active UC whose disease has progressed 
or is unresponsive to currently approved standard of care agents. Nonclinical results suggest that 
VTX002 administration would result in reduced circulating lymphocytes in vivo, and efficacy was 
demonstrated in a model of colitis in the rat. Results from the Phase 1 study demonstrated a strong 
relationship between dose, exposure, and lowering of circulating lymphocyte levels. 
 

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Potential risks for study participation have been associated with VTX002 include the following: 
Decreased Heart Rate and/or Atrioventricular Conduction 
• Guidance for cardiac monitoring is provided, including first dose and extended cardiac 
monitoring postdose as needed. On Day 1 and OLE Day 1 (OLE Week 0/OLE Visit 1), 
following the first dose of study drug, participants will remain in the clinic for 6 hours to 
monitor vital signs and cardiac conduction. Upon release from the clinic, participants will be 
monitored closely throughout study participation (see Section 6.5). 
• A dose titration schedule will be implemented to minimize the risk for cardiovascular events 
related to administration of the first dose of study treatment (Section 6.2). 
• Availability of emergency equipment should be within close proximity to study site. 
Personnel experienced in the use of advanced life support must be readily accessible during 
the first-dose monitoring and reinitiation of treatment, as well as in case of an emergency 
(see Section 6.5). 
• Criteria for study treatment discontinuation are outlined in Section 7.0. 
Infections 
• Given the mechanism of action of decreased peripheral lymphocytes, VTX002 may increase 
the risk of infections, including opportunistic infections. Participants should be monitored for 
signs and symptoms of infection during the study and throughout the Follow-Up Period. 
Participants with active acute or chronic infection should not be enrolled. Participants who 
develop an active infection during the study should be monitored and may need to have study 
treatment temporarily discontinued (Section 7.0). 
Macular Edema 
• Although not observed in any of the VTX002 preclinical safety or clinical Phase 1 studies, 
treatment with agents in the same class have been associated with cases of macular edema, 
with or without visual symptoms. As described in Section 8.4.6 of the protocol, participants 
should be monitored for visual symptoms during the study, and, if symptoms develop, an 
ophthalmologic evaluation and optical coherence tomography (OCT) should be performed.  
Decrease in Pulmonary Function 
• Although not observed in any of the VTX002 preclinical safety studies or clinical Phase 1 
studies, treatment with agents in the same class have been associated with a decrease in 
pulmonary function. As described in Section 8.4.5 of the protocol, participants should be 
monitored for dyspnea and other pulmonary symptoms, and, if pulmonary symptoms 
develop, a PFT, including diffusing capacity of lung for carbon monoxide, should be 
performed.  

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Drug-Drug Interactions  
In vitro studies suggested that VTX002 may be an inhibitor of P-glycoprotein (P-gp) and breast 
cancer resistance protein (BCRP) transporters. As described in Section 6.10.2, therapies that are 
substrates or inhibitors of P-gp and BCRP are prohibited. 
In addition, risk for reproductive and developmental toxicity cannot be excluded; thus, 
inclusion/exclusion criteria regarding pregnancy are noted to mitigate this risk (see Section 5.0). 
The risk for reproductive and developmental toxicity has also been observed for all other approved 
S1P receptor modulators. 
Results from preclinical safety studies showed that VTX002 has a low risk of phototoxicity. 
Participants may be evaluated for any signs of phototoxicity as part of the PE. 
The Sponsor will immediately notify the Investigator if any additional safety or toxicology 
information becomes available during the study.  
Other risks for study participation may include treatment with placebo and a potentially ineffective 
treatment, and delay of treatment with other approved medicinal products. For vulnerable 
populations as geriatric patients, risks for study participation should be considered, given the 
potential higher number of comorbidities and concomitant medications that may be present in this 
population. Ultimately, the Investigator should consider if the benefits outweigh the risks for 
patients to participate in this study. 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of VTX002 may be found in the Investigator’s Brochure.7 

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3.0 
OBJECTIVES AND ENDPOINTS 
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group study 
to evaluate the clinical efficacy and safety of VTX002 in participants with moderately to severely 
active UC. 
3.1 
Objectives 
Primary Objective 
• Assess the efficacy of VTX002 when administered for 13 weeks on clinical remission  
Secondary Objectives 
• Assess the efficacy of VTX002 when administered for 13 weeks on endoscopic changes, 
symptomatic response and remission, histology, and mucosal healing  
• Assess the safety and tolerability of VTX002  
• Assess the PK of VTX002  
Long-Term and Open-Label Extension Objectives 
• Assess the efficacy of VTX002 through the Long-Term Extension (LTE) and Open-Label 
Extension (OLE) Treatment Periods on endoscopic changes, symptomatic response and 
remission, histology, and mucosal healing  
• Assess the safety of VTX002 through the LTE and OLE Treatment Periods 
Exploratory Objectives 
• Assess the effect of VTX002 on health-related quality of life (HRQoL) outcomes and 
biomarkers 
3.2 
Endpoints 
The endpoints for the study are listed below, and definitions are provided in Section 3.3. The 
primary and four key secondary endpoints will be tested for superiority of VTX002 60 mg vs 
placebo and VTX002 30 mg vs placebo. The remaining endpoints will be presented descriptively. 
Details of the statistical plan are presented in Section 9.0.  
Primary Endpoint 
• The proportion of participants with clinical remission at Week 13 using modified Mayo 
score (MMS)  
Key Secondary Endpoints 
• The proportion of participants with endoscopic improvement at Week 13 
• The proportion of participants with symptomatic remission at Week 13  

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• The proportion of participants with histologic remission at Week 13 
• The proportion of participants with endoscopic improvement-histologic remission at 
Week 13  
Other Secondary Endpoints 
• The proportion of participants with clinical response using MMS at Week 13 
• The proportion of participants with endoscopic remission at Week 13 
• The proportion of participants with endoscopic and histologic remission at Week 13 
• The proportion of participants with endoscopic and clinical remission at Week 13 
• The proportion of participants with endoscopic, histologic, and clinical remission at 
Week 13 
• The proportion of participants with symptomatic remission at Weeks 4, 8, 10  
• The proportion of participants with symptomatic response at Weeks 4, 8, 10, 13 
• The proportion of participants with clinical remission using total Mayo Clinic score 
(MCS) at Week 13 
• The proportion of participants with clinical response using total MCS at Week 13 
• The proportion of participants with histologic improvement at Week 13 
• Proportion of participants with any decrease from baseline in Geboes Index score at 
Week 13 
• The proportion of participants with histologic-endoscopic mucosal improvement (HEMI) 
at Week 13 
• The proportion of participants with UC-related hospitalizations 
• The proportion of participants requiring UC-related surgeries, including colectomy 
• Plasma concentrations of VTX002, assessed from samples collected predose at Weeks 0, 
1, 4, 8, and 13 in the Induction Treatment Period, and Weeks 18, 26, 36, and 52 in the 
LTE Treatment Period; at the 1-Week and 2-Week Follow-Up visits; and at 2, 4, and 
6 hours (± 15 minutes) postdose at Week 0 
Safety Endpoints 
• Incidence and severity of AEs  
• Incidence and severity of laboratory abnormalities, and change from baseline in 
laboratory values (eg, hematology and serum chemistry) 
• Incidence of clinically significant vital sign abnormalities and changes from baseline 
Exploratory Endpoints 
The endpoints described here will be analyzed separately for the Induction Treatment Period, 
LTE Treatment Period, and OLE Treatment Period. OLE analyses will be described in detail in 
the Statistical Analysis Plan (SAP). 
• Proportion of participants with clinical remission after 52 weeks of treatment 
• Proportion of participants with clinical remission after 13 and 52 weeks of treatment 
• Proportion of participants with symptomatic remission at Weeks 18, 26, 36, and 52 
• Proportion of participants with endoscopic and histologic remission after 52 weeks of 
treatment 

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• Proportion of participants with endoscopic improvement-histologic remission after 
52 weeks of treatment 
• Proportion of participants with endoscopic and clinical remission after 52 weeks of 
treatment 
• Proportion of participants with endoscopic, histologic, and clinical remission after 
52 weeks of treatment 
• Proportion of participants with HEMI after 52 weeks of treatment 
• Proportion of participants with clinical response after 52 weeks of treatment 
• Proportion of participants with symptomatic response at Weeks 18, 26, 36, and 52 
• Proportion of participants with symptomatic response at OLE Week 13, and at each 
additional OLE visit 
• Proportion of participants with any decrease from baseline in Geboes Index score at 
Week 52 
• Change from baseline in fecal calprotectin (FCP) at Weeks 1, 4, 8, 13, 26, 36, 52, and at 
visits during the OLE 
• Change from baseline in C-reactive protein (CRP) at Weeks 1, 4, 8, 13, 26, 36, 52, and at 
visits during the OLE 
• Change from baseline in partial Mayo score (PMS) at Weeks 4, 8, 13, 18, 26, 36, 52, and 
at visits during the OLE 
• Change from baseline in total MCS at Week 52 
• Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) score at 
Weeks 13 and 52 
• Change and percentage change from baseline in lymphocyte counts at Weeks 1, 4, 8, 13, 
26, 36, and 52 
3.3 
Endpoint Definitions 
Clinical remission: stool frequency (SF) subscore = 0 or 1, RB subscore = 0, and endoscopic 
subscore (ES) ≤ 1 (excluding friability) 
Clinical response using MMS: A ≥ 2-point and ≥ 30% decrease from baseline in MMS, and a 
≥ 1-point decrease from baseline in RB subscore or an absolute RB subscore ≤ 1  
Clinical remission using total MCS: Total MCS ≤ 2 points with no individual subscore > 1 
point (SF subscore = 0 or 1, RB subscore = 0, ES ≤ 1 [excluding friability], Physician Global 
Assessment [PGA] ≤ 1, and SF + RB + ES + PGA ≤ 2) 
Clinical response using total MCS: A ≥ 3-point and ≥ 30% decrease from baseline in total 
MCS, and a ≥ 1-point decrease from baseline in RB subscore or an absolute RB ≤ 1. 
Endoscopic improvement: ES ≤ 1 (excluding friability)  
Endoscopic remission: ES = 0  
Histologic improvement: Geboes Index score < 3.1. Histology will also be assessed by the 
Robarts Histopathology Index and Nancy Index.  

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Histologic remission: Geboes Index score < 2.0. Histology will also be assessed by the Robarts 
Histopathology Index and Nancy Index.  
Endoscopic improvement-histologic remission: ES ≤ 1 (excluding friability) and histologic 
remission measured by a Geboes Index score < 2.0 
Endoscopic and histologic remission: ES = 0 and histologic remission measured by a Geboes 
Index score < 2.0 
Histologic-endoscopic mucosal improvement (HEMI): ES ≤ 1 (excluding friability) and 
histologic remission measured by a Geboes Index score < 3.1  
Symptomatic remission: SF subscore = 0 or 1 and RB subscore = 0  
Symptomatic response: Decrease from baseline ≥ 30% of the combined RB and SF subscores 
Endoscopic and clinical remission: SF subscore ≤ 1, RB subscore = 0, and ES = 0 
Endoscopic, histologic, and clinical remission: SF subscore ≤ 1, RB subscore = 0, ES = 0, and 
histologic remission measured by a Geboes Index score < 2.0  

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4.0 
STUDY DESIGN 
4.1 
Overall Design 
This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy 
and safety of VTX002 30 mg and 60 mg in participants with moderately to severely active UC 
following daily oral administration of VTX002 as a tablet. Approximately 189 eligible participants 
will be randomized in a 1:1:1 ratio to receive VTX002 30 mg, VTX002 60 mg, or matching 
placebo, once daily (approximately 63 participants per treatment group). 
The target patient population will include the following categories: 
• Patients who have had an inadequate response, loss of response, or intolerance to 
conventional therapy and are naïve to biologic/JAK inhibitors (conventional failed) 
• Patients who have had an inadequate response, loss of response, or intolerance to a 
biologic/JAK inhibitor (biologic/JAK inhibitor failed). Patients in this category may have 
received prior conventional therapy. It is expected that approximately 35% of participants in 
the study will have had an inadequate response to biologics.  
Participant randomization will be stratified based on (a) biologic/JAK inhibitor prior use status 
(Yes or No) and (b) baseline corticosteroid use (Yes or No), and (c) baseline disease activity 
(MMS 5-6 or 7-9). 
As shown in Figure 1, the study consists of a 28-day Screening Period, a 13-week double-blind 
Induction Treatment Period (including 7 days of titration followed by 12 weeks of treatment at the 
assigned dose), an LTE Treatment Period of up to 39 weeks, an OLE Treatment Period of up to 
143 weeks, and a 2-week Follow-Up Period. The maximal duration of treatment including the 
Induction Period, LTE and OLE will be 36 months.  
The duration of study participation for each participant is planned to be approximately 162 weeks, 
and the total duration of the study is planned to be approximately 60 months. Approximately 
120 study centers in 15 countries are expected to participate in this study.  
The Schedule of Activities (SoA) for the study is provided in Section 1.2. 
4.1.1 Screening Period 
Participant eligibility will be determined during a 4-week (28-day) Screening Period. Entry criteria 
will be based on confirmation of moderately to severely active UC, defined by an MMS of 5 to 9 
with an ES ≥ 2 and RB ≥ 1. 
4.1.2 Induction Treatment Period 
On Day 1, eligible participants will be randomized in a 1:1:1 ratio to receive VTX002 30 mg, 
VTX002 60 mg, or matching placebo orally once a day (approximately 63 participants per 

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treatment group). During the first week of the Induction Treatment Period, participants will 
undergo a 7-day dose titration up to the full assigned double-blind treatment dose (see Section 6.2 
for more information). 
At the end of the 13-week Induction Treatment Period, all participants will be evaluated for 
efficacy and safety.  
4.1.3 Long-Term Extension Treatment Period 
Participants who complete the Induction Week 13 visit, and meet criteria for clinical response at 
Induction Week 13, will continue into the blinded LTE Period at their previously assigned 
treatment for up to an additional 39 weeks. 
Participants in the LTE who lose response after Week 13 will have the option to enroll into the 
OLE. Loss of response in LTE will be assessed by the Investigator according to the criteria below: 
• Increase in UC disease activity as defined by an increase in PMS ≥ 2 points compared to 
PMS at Week 13 with an absolute PMS ≥ 4, based on 3 most recent consecutive days of 
diary entries within 7 consecutive days, AND 
• Exclusion of other causes of an increase in disease activity unrelated to underlying UC 
(eg, C. difficile infection, change in medication) 
Participants who complete the Week 52 visit of the LTE may continue into the OLE. 
4.1.4 Open-Label Extension Treatment Period 
Participants who complete the Induction Week 13 visit, and do not meet the criteria for clinical 
response at Induction Week 13, will have the option to enroll into the OLE for up to an additional 
143 weeks of treatment (which includes a 7-day titration period followed by treatment with 
VTX002 60 mg for up to 142 weeks).  
Participants who enter the OLE from the LTE will undergo a 7-day titration period (see 
Section 6.3.1)and remain in the OLE for a possible total of 36 months of treatment (including the 
13-week Induction Period, plus the duration in the LTE and the duration in OLE).  
Participants who were nonresponders at the end of the Induction Period (Week 13) will be assessed 
again for response at OLE Week 13. At OLE Week 13, participants who fail to achieve 
symptomatic response (defined as decrease from baseline ≥ 30% of the combined RB and SF 
scores) will be discontinued from the study drug. However, participants who respond to treatment 
by OLE Week 13 will continue treatment with VTX002 60 mg in the OLE Treatment Period for 
up to an additional 130 weeks (until a total treatment duration of 36 months). 

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4.5 
End of Study Definition 
A participant will be considered to have completed the study after completing all pertinent phases 
of the study including the Follow-Up visits. Further details will be provided in the SAP. 
A participant is considered to end the study when he/she completes the study or withdraws from 
the study for any reason prior to completion. 
The end of the whole study is defined as the date of the last visit of the last participant in the study 
or last scheduled procedure shown in the SoA (Section 1.2) for the last participant in the study 
globally. 

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5.0 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion Criteria 
Participants must meet ALL of the following inclusion criteria to be eligible for enrollment into 
the study: 
1. Men or women, 18 to 80 years of age, inclusive, at the time of consent 
2. Capable of giving signed informed consent, which includes compliance with the 
requirements and restrictions listed in the Informed Consent Form (ICF) 
Disease-Specific 
3. Diagnosed with UC ≥ 3 months prior to Screening. The diagnosis of UC must be confirmed 
by endoscopic and histologic evidence. The endoscopy and histology report should be 
present in the source documents; however, if not available, the Screening endoscopy and 
histology may serve as such. 
4. Active UC confirmed by endoscopy with ≥ 10 cm rectal involvement. Participants with 
proctitis only at baseline who meet the other eligibility criteria for inclusion, including the 
endoscopic and RB criteria for moderate to severe disease, will be capped at 10% of the total 
participants enrolled. 
5. Moderately to severely active UC, defined as an MMS of 5 to 9, including an ES ≥ 2 and an 
RB subscore ≥ 1 
6. Surveillance colonoscopy (performed according to local standard) within 12 months before 
baseline to rule out dysplasia in participants with pancolitis > 8 years duration or participants 
with left-sided colitis > 12 years duration. Participants without a surveillance colonoscopy 
within the prior 12 months will have a colonoscopy at Screening (ie, in place of Screening 
proctosigmoidoscopy). Any adenomatous polyps must be removed per local standard of care 
prior to the first dose of study drug. 
Prior Treatment Failure 
7. Demonstrated inadequate response to, loss of response to, or intolerance to at least 1 of the 
following therapies: 
a. Conventional therapy: 
i. 
Oral 5-ASA compounds 
ii. Corticosteroids 
iii. Thiopurines (eg, AZA or 6-MP) 
b. Biologic therapy or JAK inhibitor therapy: 
i. 
Anti-tumor necrosis factor alpha (TNFα) antibodies (eg, infliximab, adalimumab, or 
golimumab) 
ii. Anti-interleukin (anti-IL)12/23 (eg, ustekinumab) 

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iii. Anti-integrin antibodies (eg, vedolizumab) 
iv. JAK inhibitors (eg, tofacitinib, upadacitinib) 
Note: The medication used to qualify the participant for entry into this category of 
biologic therapy or JAK inhibitor therapy must be approved for the treatment of UC in 
the country of use. 
General Safety 
8. Adequate hepatic function, defined as a total bilirubin level of ≤ 1.5 × upper limit of normal 
(ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels of 
≤ 2.0 × ULN. Participants with Gilbert’s syndrome who have an isolated total bilirubin and 
normal AST and ALT levels may participate. 
9. Adequate renal function, defined as an estimated glomerular filtration rate 
≥ 60 mL/min/1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration equation 
at Screening 
Concomitant Medications 
10. Participants are permitted to receive the following concomitant medications: 
a. Oral 5-ASA compounds at a stable dose or discontinued for ≥ 2 weeks prior to Screening 
endoscopy 
b. Oral corticosteroid therapy at a stable dose or discontinued for ≥ 2 weeks prior to 
Screening endoscopy (prednisone at a stable dose ≤ 20 mg/day, budesonide at a stable 
dose ≤ 9 mg/day) 
c. Probiotics, provided the dose has been stable for ≥ 2 weeks prior to Screening endoscopy 
Contraception 
11. Women must meet either a or b of the following criteria and men must meet criterion c to 
qualify for the study: 
a. A woman who is not of childbearing potential must meet 1 of the following: 
i. 
Postmenopausal, defined as no menses for 12 months without an alternative medical 
cause 
ii. Permanent sterilization procedure, such as hysterectomy, bilateral salpingectomy, or 
bilateral oophorectomy 
b. A nonpregnant woman of childbearing potential must agree to use a highly effective 
contraception method that can achieve a failure rate of less than 1% per year when used 
consistently and correctly. The highly effective contraception must be used through the 
duration of the study and for 30 days after the last dose of study treatment. The following 
are considered highly effective birth control methods: 
i. 
Combined (estrogen- and progesterone-containing) hormonal contraception 
associated with inhibition of ovulation, which may be oral, intravaginal, or 
transdermal. 
ii. Progesterone-only hormonal contraception associated with inhibition of ovulation, 
which may be oral, injected, or implanted 

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iii. Intrauterine device 
iv. Intrauterine hormone-releasing system 
v. Bilateral tubal occlusion 
vi. Vasectomized partner, provided that the partner is the sole sexual partner of the 
woman of childbearing potential study participant and the vasectomized partner has 
received medical assessment of the surgical success 
vii. Sexual abstinence (complete sexual abstinence, defined as refraining from 
heterosexual intercourse for the entire period of risk associated with study 
treatments). The reliability of sexual abstinence needs to be evaluated in relation to 
the duration of the clinical study and the preferred and usual lifestyle of the 
participant. Periodic abstinence (calendar, symptothermal, postovulation methods) 
is not acceptable. 
c. A man with a pregnant or nonpregnant partner who is a woman of childbearing potential 
must agree to use condoms through the duration of the study and for 30 days after the last 
dose of study treatment. 
5.2 
Exclusion Criteria 
Participants will be excluded from the study if any of the following criteria apply: 
Inflammatory Bowel Disease and Gastrointestinal Conditions 
1. Severe extensive colitis as evidenced by: 
a. Physician judgment that the participant is likely to require surgery (surgical intervention 
of any kind for UC [eg, colectomy]) within 12 weeks of baseline 
b. Current evidence of fulminant colitis or toxic megacolon, or recent history (within last 
6 months) of toxic megacolon or bowel perforation 
c. Previous total colectomy 
2. Diagnosis of Crohn’s disease or indeterminate colitis or the presence or history of a fistula 
consistent with Crohn’s disease 
3. Diagnosis of microscopic colitis, ischemic colitis, or infectious colitis 
4. Positive assay or stool culture for pathogens (ova and parasite examination, bacteria) or 
positive test for Clostridium difficile at Screening. Note: If C. difficile or pathogen test is 
positive, the participant may be treated and retested ≥ 4 weeks after completing treatment. 
General Safety 
5. Pregnancy, lactation, or a positive serum β-hCG measured during Screening 
6. Clinically relevant hematologic, hepatic, neurological, pulmonary, ophthalmological, 
endocrine, metabolic (including, but not limited to, hypo- and hyperkalemia), psychiatric, or 
other major systemic disease that will make implementation of the protocol or interpretation 
of the study difficult or will put the participant at risk 
7. Forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) < 70% of 
predicted values and FEV1/FVC ratio < 0.70 at Screening 

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8. Have any of the following conditions or receiving treatments that may affect cardiovascular 
function: 
a. Myocardial infarction, unstable angina, stroke/transient ischemic attack, decompensated 
heart failure requiring hospitalization, or Class III/IV heart failure within ≤ 6 months prior 
to or during the Screening Period 
b. Screening or prerandomization vital signs (taken in the sitting position) with a HR < 50 bpm 
OR systolic BP < 90 mmHg OR diastolic BP < 55 mmHg. Vital signs may be repeated up to 
3 times during a visit to confirm abnormal readings. 
c. Screening or prerandomization ECG with PR interval > 200 msec or Fridericia’s 
corrected QT interval (QTcF) ≥ 450 msec in men or ≥ 470 msec in women 
d. History of any of the following unless treated with an implanted pacemaker or an 
implanted cardioverter-defibrillator with pacing: 
i. 
History or presence of recurrent symptomatic bradycardia 
ii. Second- or third-degree AV block 
iii. Periods of asystole > 3 seconds 
iv. History of sick sinus syndrome or recurrent cardiogenic syncope 
e. Start, stop, or change in dosage of any Class I-IV anti-arrhythmic drugs ≤ 1 week prior to 
dose titration starting at randomization and up to 1 week after titration to the assigned 
dose. This criterion also applies to the OLE Treatment Period titration: 1 week prior to 
and 1 week after the dose titration period. 
9. Uncontrolled diabetes as determined by hemoglobin A1c (HbA1c) > 9%, or participants with 
diabetes with significant comorbid conditions, such as retinopathy 
10. History or presence of macular edema or retinopathy 
11. History of cancer within the last 5 years, including solid tumors and hematological 
malignancies (except basal cell and in situ squamous cell carcinomas of the skin that have 
been excised and resolved) or precancerous conditions such as colonic mucosal dysplasia, 
cervical dysplasia, and cervical intraepithelial neoplasia 
12. History of lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorder, 
or multiple myeloma 
13. History of alcohol or drug abuse within 1 year prior to randomization 
14. Any of the following laboratory abnormalities during the Screening Period: 
a. Absolute white blood cell (WBC) count < 3500/μL 
b. Neutrophils < 1500/μL 
c. Absolute lymphocyte count < 800/μL 
d. Platelet count < 100,000/μL 
e. Hemoglobin < 8 g/dL 

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Infection Risk 
15. Active or latent TB infection at Screening. History of untreated or inadequately treated latent 
TB infection. The following are EXCEPTIONS to this exclusion criterion: 
a. Participants with latent TB, who have been ruled out for active TB, have completed an 
appropriate course of TB prophylaxis treatment per national/local medical guidelines or 
WHO guidelines, have a chest radiograph without changes suggestive of active TB 
infection, and have not had recent close contact with a person with active TB are eligible 
to enroll in the study. It is the responsibility of the Investigator to verify the adequacy of 
previous TB treatment and provide appropriate documentation of treatment compliance.  
b. Participants diagnosed with latent TB at Screening, ruled out for active TB and have 
received at least 4 weeks of an appropriate TB prophylaxis regimen may be rescreened for 
enrollment. Participant will complete their prophylactic regimen during the trial. 
16. Known active bacterial, viral, fungal, mycobacterial, or other infection (including TB or 
atypical mycobacterial disease) or any major episode of infection that required 
hospitalization or treatment with intravenous (IV) antibiotics within 30 days of Screening or 
oral antibiotics within 14 days prior to Screening. Fungal infection of nail beds is allowed. 
17. Human immunodeficiency virus (HIV) / acquired immune deficiency syndrome (AIDS) or 
positive test for HIV antibodies at Screening 
18. Acute or chronic hepatitis B infection or test positive for hepatitis B virus (HBV) at 
Screening (positive for hepatitis B surface antigen [HBsAg], or negative for HBsAg and 
positive for anti-hepatitis B core antibody in conjunction with detectable HBV 
deoxyribonucleic acid [DNA]) 
19. Current hepatitis C infection or test positive for hepatitis C virus (HCV) at Screening, as 
defined by positive hepatitis C antibody and detectable HCV ribonucleic acid 
20. History of an opportunistic infection (eg, Pneumocystis jirovecii, cryptococcal meningitis), 
progressive multifocal leukoencephalopathy (PML), or history of disseminated herpes zoster 
or disseminated herpes simplex 
21. History of currently active primary or secondary immunodeficiency 
Previous or Concomitant Treatment  
22. Hypersensitivity to VTX002 or any of the excipients or placebo compounds 
23. Treatment with an investigational therapy ≤ 3 months prior to randomization 
24. Treatment with cyclosporine, tacrolimus, sirolimus, methotrexate, or mycophenolate mofetil 
≤ 8 weeks prior to Screening 
25. Prior treatment with S1P receptor modulators including but not limited to fingolimod, 
siponimod, ozanimod, ponesimod, and etrasimod 
26. Treatment with a biologic agent (ie, anti-TNFs, anti-integrins, and anti-IL-12/23) meeting the 
following criteria: 
a. Treatment with infliximab, adalimumab, golimumab, or vedolizumab ≤ 60 days prior to 
randomization 

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b. Treatment with ustekinumab ≤ 90 days prior to randomization 
c. Treatment with any other approved biologic agent ≤ 5 half-lives prior to randomization 
Note: A trough drug level can be obtained during Screening to confirm absence of biologic 
drug levels in lieu of the washout periods 
27. Treatment with JAK inhibitors ≤ 4 weeks prior to randomization 
28. Use of IV corticosteroids and/or topical steroids ≤ 2 weeks prior to Screening endoscopy. 
Alternative forms of steroids require consultation with the Medical Monitor. 
29. Use of immunosuppressant drugs including thiopurines ≤ 2 weeks prior to Screening 
endoscopy 
30. Prior treatment failure with ≥ 3 biologic agents with different mechanisms of action or 
≥ 2 biologics with different mechanisms of action plus a JAK inhibitor approved for the 
treatment of UC 
31. Treatment with topical rectal 5-ASA or short-chain fatty acid enemas ≤ 2 weeks prior to 
Screening endoscopy 
32. Receipt of a live vaccine ≤ 4 weeks prior to randomization and until 2 weeks post last dose. 
Approved nonlive vaccines, including severe acute respiratory syndrome coronavirus 2 
(SARS-CoV-2), can be administered according to local vaccination standards. 
33. Previous treatment with natalizumab 
34. Previous treatment with lymphocyte-depleting therapies (eg, anti-CD4, cladribine, rituximab, 
ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow 
transplantation, alemtuzumab, daclizumab) 
35. Previous treatment with D-penicillamine, thalidomide, dimethyl fumarate, or pyrimidine 
synthesis inhibitors 
36. Treatment with IV immune globulin or plasmapheresis ≤ 3 months prior to randomization 
5.3 
Lifestyle Considerations 
There are no restrictions regarding lifestyle. 
5.4 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomly assigned to study treatment/entered in the study. A minimal set of 
screen failure information is required to ensure transparent reporting of screen failure participants 
to meet the Consolidated Standards of Reporting Trials publishing requirements and to respond to 
queries from regulatory authorities. Minimal information includes demography, screen failure 
details, eligibility criteria, and any SAEs. 
Individuals who do not meet the criteria for participation in this study (screen failures) may be 
rescreened. If a participant is being considered to be rescreened more than once, please contact the 

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Medical Monitor. Rescreened participants should not be assigned the same participant number as 
for the initial screening. 
If a participant is considered for rescreening, the need for repeat testing should be discussed with 
the Medical Monitor. Upon approval by the Medical Monitor, if a participant is rescreened within 
6 months a repeat chest X-ray is not required. If a participant is rescreened within 3 months, OCT 
does not need to be repeated if the participant does not have any visual symptoms, and PFTs do 
not need to be repeated if the participant does not have any respiratory symptoms. 

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6.0 
STUDY TREATMENT 
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, or 
medical device(s) intended to be administered to a participant according to the study protocol. 
6.1 
Study Treatment Description 
The physical descriptions of study drug treatments are provided in Table 7. 
VTX002 tablets will be manufactured, quality control tested, and released in accordance with 
Good Manufacturing Practice. 
Table 7 
Study Treatment Description 
Study Drug 
VTX002 
Placebo 
Dosage Formulation 
3 mg, 7 mg, 10 mg, and 20 mg Tablets  
Matching placebo for 3 mg, 7 mg, 10 mg, 
and 20 mg Tablets 
Dosage Level(s) 
30 mg, 60 mg 
Not applicable 
Route of Administration  
Oral 
Oral 
Dosing Instructions 
 
Study drug should be taken by 
participants with approximately 240 mL 
(one cup) of water. The study drug can be 
taken with or without food. All doses on 
clinical days should be administered in 
the clinic. 
Study drug should be taken by 
participants with approximately 240 mL 
(one cup) of water. The study drug can 
be taken with or without food. All doses 
on clinical days should be administered 
in the clinic. 
Packaging and Labeling 
Study treatment will be provided as orange 
tablets in weekly blister cards for 
Induction and LTE Periods (Weeks 0-52) 
of blinded treatment. Blister packs for dose 
titration for Weeks 0 and OLE Week 0 
will have each day of the regimen labeled. 
Blister packs for assigned dose for 
Induction and LTE Periods (Weeks 1-52) 
will contain 7 rows of 4 tablets. Open-label 
bottles of 30 × 20 mg tablets or 
100 × 20 mg tablets will be provided after 
conclusion of OLE Week 0 dose titration. 
Each blister/bottle will be labeled as 
required per country requirement. 
Study treatment will be provided as 
orange tablets in weekly blister cards for 
Induction and LTE Periods (Weeks 0-52) 
of blinded treatment. Blister packs for 
assigned dose for Induction and LTE 
Periods (Weeks 1-52) will contain 7 rows 
of 4 tablets. Each blister will be labeled as 
required per country requirement. 
Storage  
15°C to 25°C 
59°F to 77°F 
15°C to 25°C 
59°F to 77°F 
 

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6.2 
Induction Treatment  
6.2.1 Induction Treatment Week 0 
Participants randomized to study drug will undergo a 7-day dose titration to receive their respective 
double-blinded drug doses (Days 1 to 7) in accordance to Table 8 below. Although dose titration 
is not applicable for placebo and VTX002 30 mg after Day 6, the same number of tablets will be 
given to all participants to simulate dose titration and maintain blinding. 
Table 8 
Dose Titration in the Induction Treatment Period 
Study 
treatment 
Day 1 
(Visit 2) 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Day 8 
and 
Onwards 
(Visit 3) 
VTX002 30 mg 
3 mg 
7 mg 
10 mg 
14 mg 
20 mg 
30 mg 
30 mg 
30 mg 
VTX002 60 mg 
3 mg 
7 mg 
10 mg 
14 mg 
20 mg 
30 mg 
50 mg 
60 mg 
Placebo 
Placebo 
Placebo 
Placebo 
Placebo 
Placebo 
Placebo 
Placebo 
Placebo 
 
Blister cards for Week 0 will contain 9 rows and up to 4 columns. Participants will take one tablet 
from each blister in the row for that day.  
6.2.2 Induction and Long-Term Extension Treatment Weeks 1 to 52 
Dosing configuration for Weeks 1-52 will contain 4 rows with 7 columns. Participants will take 
all tablets from each blister in the column for that day. 
In the case where a participant attends a virtual visit (see Section 8.2) and requires additional study 
treatment to continue on the study, study treatment may be dispensed and delivered by an approved 
courier where permitted by local law and regulation. Alternatively, a future supply of study 
treatment may be dispensed to the participant at an onsite visit or an unscheduled dispensation visit 
to cover study treatment to be dispensed at the next planned virtual visit. Advanced planning and 
communication will be needed to dispense future supply of study treatment at an earlier onsite 
visit. Shipping guidelines and instruction will be provided separately. 
6.3 
Open-Label Extension Treatment 
6.3.1 Open-Label Extension Dose Titration 
Participants entering the OLE Treatment Period will undergo a 7-day dose titration 
(OLE Days 1 to 8) to receive VTX002 60 mg following the same titration schedule for the 
VTX002 60 mg as shown in Table 8. Although dose titration would not be needed for participants 
who received VTX002 60 mg during the Induction Period/LTE Period, all participants entering 
the OLE Treatment Period will go through a full dose titration regimen to maintain the blind of 
the Induction Period/LTE treatment assignments. 

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6.3.2 Open-Label Extension Study Drug Supplies 
Following titration to 60 mg, participants will be dispensed a sufficient number of bottles 
containing 30 or 100 tablets of VTX002 20 mg to provide drug until the next study visit. 
Participants will be instructed to take 3 tablets (60 mg) at the same time each day.  
6.4 
Additional Dosing Instructions 
Study treatment should be taken at approximately the same time each day, preferably in the 
morning. Tablets should be taken with approximately 240 mL of water and can be taken with or 
without food. On study visit days, participants should wait and take their dose at the study site 
after all predose assessments and procedures have been completed, including blood draws for 
predose PK. The time of PK sample collection and last dosing prior to the PK sample should be 
documented. At Week 13 (Visit 8), study treatment administration should be performed in the 
clinic as part of the initial LTE visit.  
6.4.1 Missed Dose Instructions 
Participants should be instructed that if they forget to take a dose, they can take the dose within 
8 hours of the normal dosing time; otherwise, they should take their next dose at the regular time 
on the following day. Participants who vomit a tablet should be instructed not to take another dose 
on the same day, but to take the next dose at the regular time on the following day. Participants 
will record their daily dose in a provided electronic diary (eDiary). Missed doses that occur at any 
time during a week prior to PK sampling should be recorded in the electronic Case Report Form 
(eCRF). Participants should be instructed to contact the Investigator if they miss more than 
2 consecutive doses. 
6.4.2 Dose Interruption 
Decisions regarding dose interruptions will be made by the Investigator in consultation with the 
Medical Monitor based on the clinical evaluation of the participant. 
If the Investigator deems it necessary to withhold study treatment, temporary withholding is 
permitted for up to 4 days without obtaining prior approval from the Medical Monitor. If study 
treatment interruption for ≥ 5 days is required due to a medical reason, the Investigator must 
contact the Medical Monitor.  
The first-dose cardiac monitoring, as outlined in Section 6.5.1, and dose titration as outlined in 
Section 6.2.1, should be performed when study treatment dosing is interrupted as follows: 
•  Missed treatment ≥ 2 consecutive days within the first week of treatment or 
•  Missed treatment ≥ 5 consecutive days after the first week of treatment 

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6.5 
Guidance for Cardiac Monitoring Following Treatment Initiation or Reinitiation 
Prerandomization (ie, predose on Day 1) ECG should be performed and assessed prior to 
randomization. 
Following treatment initiation or reinitiation, participants will remain in the clinic for at least 
6 hours after study drug administration for safety assessments. 
Prerandomization (ie, predose on Day 1) vital signs (ie, pulse, systolic and diastolic BP, 
temperature, and respiratory rate) will be used as baseline measurements. Pulse and BP will be 
measured using calibrated equipment (as appropriate) after the participant has been sitting for at 
least 5 minutes.  
Atropine and epinephrine should be readily available at all study sites. Availability of emergency 
equipment should be within close proximity to study site. Personnel experienced in the use of 
advanced life support must be readily accessible during the first-dose monitoring (Week 0 
[Day 1/Visit 2] and OLE Week 0 [OLE Day 1/OLE Visit 1]) and reinitiation of treatment, as well 
as in case of an emergency. A member of the Investigator team should be available to monitor the 
participant for the 6-hour monitoring period and report any abnormalities to the Investigator. 
6.5.1 First-Dose Cardiac Monitoring 
Participants will undergo in-clinic monitoring for at least 6 hours on Day 1 and OLE Day 1, with 
measurements taken prior to dose and at 1, 2, 4, and 6 hours (± 10 minutes) following study drug 
administration. Cardiac assessments should be performed as shown in Table 9. 
Participants experiencing a cardiovascular treatment-related symptomatic event (eg, chest pain, 
dizziness, palpitations, lightheadedness, shortness of breath, or syncope) associated with a 
clinically significant reduction of HR or associated with clinically relevant ECG changes at any 
time during the 6-hour monitoring period should be discontinued from treatment. 
Participants will be released from the clinical site after dosing on Day 1 (Week 0/Visit 2) and OLE 
Day 1 (OLE Week 1/OLE Visit 1) when they fulfill the discharge criteria outlined in 
Section 6.5.1.1, but no sooner than 6 hours postdose. 

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Table 9 
Cardiac Assessments to Be Performed 
Procedure 
Clinic 
Ambulatory 
Predose 
1, 2, 4, and 6 hours 
postdoseb 
From 6 to 24 
hours postdose 
Vital signsa 
X 
X 
 
12-lead ECG 
X 
X 
 
Holter ECG monitoringc 
X 
X 
X 
Adverse events 
X 
X 
 
Assess discharge criteria 
 
Xd 
 
Abbreviations: BP = blood pressure; ECG = electrocardiogram 
Note: The order of assessments should be rest for 5 minutes (sitting), vital signs (sitting), 12-lead ECG (supine), and 
then blood draws as applicable. 
a. 
Participants must be at rest for at least 5 minutes in sitting position. After the participant has been sitting for at 
least 5 minutes, pulse and BP will be measured.  
b. Measurements may be taken within ± 10 minutes of the scheduled time. 
c. 
Holter ECG monitoring will begin 1 hour predose and continue through 24 hours postdose. Participants who 
meet the discharge criteria (Section 6.5.1.1) at 6 hours postdose will be sent home for continued Holter ECG 
monitoring from 6 to 24 hours postdose. 
d. Discharge criteria assessed only at 6 hours postdose. 
 
6.5.1.1 Discharge Criteria After Cardiac Monitoring 
After 6 hours of cardiac monitoring postdose, participants who meet the following discharge 
criteria will be released: 
• No presence of bradycardia, defined as HR < 50 bpm or no more than 10 bpm lower than the 
predose (baseline) value 
Note: If the HR at 6 hours postdose is at the lowest value postdose, participants should 
undergo extended cardiac monitoring. 
• No evidence of second-degree AV block or higher 
• No cardiac symptoms (eg, chest pain, dizziness, palpitations, lightheadedness, shortness of 
breath, or syncope) 
First-dose cardiac monitoring should be repeated on Day 8/OLE Day 8 if cardiac safety issues 
were observed on Day 1/OLE Day 1.  
Note: Participants should have written instructions on when to return to the clinic and a 24-hour 
contact phone number to call in the event of any new (eg, chest pain, dizziness, palpitations, 
syncope, nausea, vomiting) or worsened cardiovascular symptoms. 

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6.5.1.2 Extended Cardiac Monitoring 
Participants who do not meet the discharge criteria at 6 hours postdose will require extended 
cardiac monitoring, as described below: 
• Vital signs will be assessed hourly and 12-lead ECG may be performed, as clinically 
indicated, until the participant meets the discharge criteria (Section 6.5.1.1). 
• Should a participant require pharmacologic intervention for symptomatic bradycardia, 
continuous overnight ECG monitoring in a medical facility should be instituted, and the first 
dose monitoring strategy should be repeated after the second dose of VTX002. 
• Should postdose bradycardia (eg, HR < 50 bpm) or potentially related symptoms (eg, 
dizziness) occur, then initiate appropriate medical management, assess vital signs, begin 
continuous ECG monitoring, and continue observation until the symptoms have resolved. 
• The Medical Monitor should be contacted if the participant does not meet the discharge 
criteria after ≥ 6 hours of extended cardiac monitoring. 
• Any participant who requires extended monitoring on Day 1 (Week 0/Visit 2) or OLE Day 1 
(OLE Week 0/OLE Visit 1) must return on the following day for the second dose and will be 
remonitored as on Day 1 (Week 0/Visit 2) or OLE Day 1 (OLE Week 0/OLE Visit 1), 
respectively. These participants will be discontinued from study treatment if they do not meet 
the discharge criteria at 6 hours after the second dose. Extended cardiac monitoring should be 
continued until the participant meets the discharge criteria (Section 6.5.1.1). 
• Participants experiencing a symptomatic event (eg, chest pain, dizziness, palpitations, 
lightheadedness, shortness of breath, or syncope) during the 6-hour monitoring period that is 
not associated with either a reduction in HR or clinically relevant change in 12-lead ECG, and 
who continue to experience symptoms during the extended cardiac monitoring period, may be 
discharged provided the symptoms are not associated with a reduction in HR or clinically 
relevant changes in ECG during the extended cardiac monitoring period, and the Investigator 
deems it appropriate; however, these participants must return on Day 2/OLE Day 2 for the 
second dose and will be remonitored as on Day 1 (Week 0/Visit 2) or OLE Day 1 
(OLE Week 0/OLE Visit 1). These participants should be discontinued from treatment if they 
do not meet the discharge criteria at 6 hours after the second dose on Day 2/OLE Day 2 or if 
they experienced the symptoms (eg, chest pain, dizziness, palpitations, lightheadedness, 
shortness of breath, or syncope) on Day 2/OLE Day 2, and extended cardiac monitoring 
should be continued until the participant meets the discharge criteria (Section 6.5.1.1). 
6.5.2 Study Treatment Discontinuation Related to Postdose Cardiac Monitoring 
A complete list of reasons for study treatment discontinuation is provided in Section 7.1. All 
treatment discontinuations should be discussed with the Medical Monitor. 

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Reasons for study treatment discontinuation specific to postdose cardiac monitoring include the 
following: 
• Participants who have a cardiovascular treatment-related symptomatic event (eg, chest pain, 
dizziness, palpitations, lightheadedness, shortness of breath, or syncope) associated with a 
clinically significant reduction of HR or associated with clinically relevant 12-lead ECG 
changes at any time during the 6-hour monitoring period on Day 1/OLE Day 1 or 
Day 2/OLE Day 2 (as applicable). 
• Participants who have not met the discharge criteria on Day 1 (Week 0/Visit 2) or OLE Day 1 
(OLE Week 0/OLE Visit 1) after ≥ 6 hours of extended monitoring and on Day 2/OLE Day 2 
by 6 hours postdose (see Section 6.5.1.2). 
6.5.3 Cardiac Monitoring Upon Treatment Reinitiation Following Dose Interruption 
Participants should undergo the same first-dose cardiac monitoring, as outlined in Section 6.5.1, 
and dose titration, as outlined in Section 6.2.1, procedures as the original treatment initiation when 
study treatment dosing is interrupted as follows: 
•  Missed treatment ≥ 2 consecutive days within the first week of treatment or 
•  Missed treatment ≥ 5 consecutive days after the first week of treatment 
6.6 
Guidance for Hepatic Monitoring 
An increase in AST or ALT > 3 × ULN should be followed by repeat testing within 72 hours of 
receiving results to confirm the abnormality and determine whether AST or ALT is increasing or 
decreasing. 
Discontinuation of study treatment for abnormal liver function should be considered by the 
Investigator when a participant meets one of the conditions outlined below or if the Investigator 
believes that it is in best interest of the participant. See also Section 7.1 for more information. 
• ALT or AST > 8 × ULN 
• ALT or AST > 5 × ULN for > 2 weeks 
• ALT or AST > 3 × ULN and total bilirubin > 2 × ULN or international normalized ratio 
(INR) > 1.5 
• ALT or AST > 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (> 5%) 
All events of ALT or AST > 3 × ULN and total bilirubin > 2 × ULN (> 35% direct bilirubin), or 
ALT or AST > 3 × ULN and INR > 1.5, if INR measured, which may indicate severe liver injury 
(possible Hy’s Law), must be reported as an SAE. See Section 8.5 for follow-up and reporting of 
SAEs. 

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Because transient fluctuations of ALT or AST are common, and progression to severe 
drug-induced liver injury or acute liver failure is uncommon, automatic discontinuation of study 
treatment upon finding a greater than 3 × ULN elevation of ALT or AST may be unnecessary. 
6.7 
Preparation/Handling/Storage/Accountability 
The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study treatments received, and any discrepancies must be reported 
and resolved before use of the study treatment. 
Only participants enrolled in the study may receive study treatment. The study treatment should 
be dispensed by the Investigator or by a qualified individual under the Investigator’s supervision, 
according to the procedures described in this study protocol. All study treatments must be stored 
in a secure, environmentally controlled, and monitored (manual or automated) area in accordance 
with the labeled storage conditions with access limited to the Investigator and authorized study 
center staff. 
The Investigator, institution, or the head of the medical institution (where applicable) is responsible 
for study treatment accountability, reconciliation, and record maintenance (ie, receipt, 
reconciliation, and final disposition records). The Study Monitor will ensure that all unused study 
treatment and all medication containers are returned or destroyed on site. Study treatment can be 
destroyed on site as long as proper documentation is available and permitted by local law. 
Further guidance and information for the final disposition of unused study treatment and all the 
medication containers can be found in the Study Manual. 
The Investigator, a designated member of the study center staff, or a hospital pharmacist must 
maintain an adequate record of the receipt and distribution of all study treatment using the Drug 
Accountability Form. These forms must be available for inspection at any time. 
6.8 
Measures to Minimize Bias: Randomization and Blinding 
The study will employ a double-blind design for the Induction Treatment Period. Participants, 
Investigators, study center staff, persons performing the assessments, and the Sponsor are to 
remain blinded to the identity of the Induction Period treatment from the time of randomization 
until the interim database lock for the study. 
All participants will be centrally assigned to randomized study treatment using an Interactive Web 
Response System (IWRS). Before the study is initiated, the log in information and directions for 
the IWRS will be provided to each study center. Participants will be randomized to a study 
treatment via stratified block randomization. The following will be used for stratification: 
(a) biologic/JAK inhibitor prior use status (Yes or No), (b) baseline corticosteroid use (Yes or No), 
and (c) baseline disease activity (MMS 5-6 or 7-9). 

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The study treatment and placebo tablets will be identical in physical appearance. There will be 
limited access to the randomization codes for the Induction Treatment Period. The treatment each 
participant will receive will not be disclosed to the Investigator, study center staff, participant, 
Sponsor, or study vendors (eg, central readers). The treatment codes will be held by the Clinical 
Supplies Department of the contract research organization (CRO). The IWRS will be programmed 
with blind-breaking instructions. 
Investigators, study center staff, participants, and study vendors not engaged in data analysis 
associated with the interim database lock for the Induction Treatment Period will remain blinded 
to the identity of the LTE Period treatment. The Sponsor will be unblinded to study treatment for 
the LTE Period after the interim database lock and unblinding for the Induction Treatment Period. 
Lymphocyte, neutrophils, 
 CRP, and FCP are 
considered markers for the mechanism of action for VTX002 or efficacy. For Investigators, study 
center staff, participants, and study vendors, total WBC, differentials, lymphocyte, neutrophils, 
 CRP, and FCP results will be blinded during the double-blind Induction Treatment Period, 
LTE Treatment Period, and the first 4 weeks of the OLE Treatment Period (see Section 8.3.4). 
These results will also be blinded to the Sponsor in the same manner until the interim database 
lock and unblinding for the Induction Treatment Period is completed. Then, the Sponsor will be 
unblinded to total WBC, differentials, lymphocyte, neutrophil, 
 CRP and FCP. 
6.8.1 Emergency Unblinding Procedure 
The participant’s treatment group assignment blind will not be broken until the end of the study 
unless medical treatment of that participant depends upon knowing whether the participant is 
receiving active study treatment. In case of an emergency, the Investigator has the sole 
responsibility for determining if unblinding of a participant’s treatment assignment is warranted. 
Participant safety must always be the first consideration in making such a determination. If the 
Investigator decides that unblinding is warranted, the Investigator should make every effort to 
contact the Medical Monitor or their designee prior to unblinding a participant’s treatment 
assignment unless this can delay emergency treatment of the participant. If a participant’s 
treatment assignment is unblinded, the Sponsor must be notified within 24 hours after breaking 
the blind. The date and reason that the blind was broken must be recorded in the source 
documentation and eCRF, as applicable. 
6.9 
Study Treatment Compliance 
The prescribed dosage, timing, and mode of administration may not be changed, except as defined 
in Section 6.4.2. Any departures from the assigned regimen must be recorded in the eCRFs. 
Study treatment compliance will be measured by tablet count. At each visit, prior to dispensing 
the study treatment, the Investigator will retrieve the previously dispensed study treatment and 
assess compliance.  

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Overall, study noncompliance is defined as taking less than 80% or more than 120% of study 
treatment during the Induction Treatment Period and LTE Treatment Period. Participants will 
record tablet intake in the eDiary, which will be reviewed periodically by site staff and the Study 
Team. At each visit, the Investigator will collect the previously dispensed study treatment tablets 
and assess compliance. If there is a discrepancy between the compliance recorded in the eDiary 
and the tablet count, it should be discussed with the participant and noted in the source documents.  
Participants exhibiting poor compliance should be counseled on the importance of good 
compliance to the study dosing regimen. Participants who are persistently noncompliant (< 80% 
or > 120%) should be discussed with the Medical Monitor to determine whether they should be 
withdrawn from the study. 
Details of VTX002 study treatment administration will be documented in the eDiary. The 
participant will be provided with an eDiary to allow, at minimum, documentation of the date and 
time of the dose, date(s) of missed doses or partial dose administered while not in the clinic. This 
information will be transcribed into the participants’ eCRF, as appropriate. Participants will be 
instructed to not take study drug prior to their clinic visits (except for the visits when study drug 
is not to be administered at the clinic), as predose samples will need to be collected prior to dose 
administration. While in the clinic, the date/time of doses administered in the clinic will be 
documented in the eCRF and eDiary. The time and date of study drug administration and the 
participant’s most recent ingestion of food will also be recorded. 
6.10 Prior and Concomitant Therapy 
All concomitant medications, including over-the-counter or prescription medicines, blood 
products, vaccines, vitamins, holistic products, and radiotherapy, will be collected from Screening 
through the 2-Week Follow-Up visit and recorded in the eCRF. Any medication given for a 
study-related AE should be recorded from the time of informed consent.  
The Medical Monitor should be contacted if there are any questions regarding concomitant or prior 
therapy. Medication history should be collected for at least 4 weeks prior to Screening. 
6.10.1 Allowed Medications for the Treatment of Ulcerative Colitis 
Oral 5-ASA, oral corticosteroids, or medicinal probiotics are allowed at the time of Screening; 
however, these products should not be started during Screening or during the treatment period in 
participants who are not already receiving them. 
Immunosuppressive agents such as oral AZA or 6-MP must be discontinued > 2 weeks prior to 
Screening endoscopy. 
Participants receiving 5-ASA or medicinal probiotics should maintain a stable dose throughout the 
Screening Period and study and can only be discontinued or reduced in dose if Investigator 
judgment requires it because of toxicity or medical necessity. 

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6.10.1.1 Corticosteroid Therapy 
Oral corticosteroid therapy (prednisone at a stable dose of ≤ 20 mg/day, budesonide at a stable 
dose of ≤ 9 mg/day, or equivalent steroid) is allowed to be continued during the 13-week Induction 
Treatment Period provided the dose has been stable for the 2 weeks immediately prior to the 
Screening endoscopy assessment. 
Participants entering the LTE Treatment Period will be tapered from corticosteroids. Participants 
entering the OLE Treatment Period may be tapered after 13 weeks of treatment in the OLE. The 
recommended tapering schedule for oral corticosteroids (other than budesonide extended release 
tablets [budesonide MMX]) is as follows: 
• Dose > 10 mg/day prednisone or equivalent: taper daily dose by 5 mg/week until receiving 
10 mg/day, and then continue tapering by 2.5 mg/week until 0 mg/day 
• Dose ≤ 10 mg/day prednisone or equivalent: taper daily dose by 2.5 mg/week until 0 mg/day 
The recommended tapering schedule for participants receiving oral budesonide MMX 9 mg/day is 
to reduce tablets to 9 mg two days out of three for 2 weeks, followed by 9 mg one day out of three 
for 2 weeks, and then discontinue. 
For participants who cannot tolerate the corticosteroid taper without recurrence of clinical 
symptoms of either UC or steroid withdrawal, the corticosteroid dose may be increased (up to the 
dose at study entry if required), but tapering should be attempted again within 2 weeks. 
6.10.2 Prohibited Medications 
In vitro studies suggested that VTX002 may be an inhibitor of P-gp and breast cancer resistance 
BCRP transporters (Section 2.3). Any necessary concomitant use of any of the following must be 
discussed with Medical Monitor. 
• P-gp transporter substrates or inhibitors: amiodarone, carvedilol, clarithromycin, 
cyclosporine, dabigatran etexilate, digoxin, dronedarone, fexofenadine, itraconazole, 
ketoconazole, lapatinib, loperamide, lopinavir, propafenone, quinidine, ranolazine, reserpine, 
ritonavir, saquinavir, tacrolimus, talinolol, telaprevir, tipranavir, verapamil, vinblastine 
• BCRP transporter substrates or inhibitors: coumestrol, curcumin, cyclosporine A, daidzein, 
dantrolene, eltrombopag, estrone-3-sulfate, genistein, novobiocin, prazosin, rosuvastatin, 
sulfasalazine 
The following concomitant medications/therapy are prohibited for the entire duration of the study: 
• Treatments for UC other than those listed in the eligibility criteria (see Section 5.1 and 5.2) 
• Chronic nonsteroidal anti-inflammatory drug (NSAID) use (Note: Occasional use of NSAIDs 
and aspirin up to 325 mg/day is permitted) 
• Marketed biologic therapies 

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• Immunosuppressive agents (eg, AZA, 6-MP, tofacitinib) 
• Any per rectum therapy including enemas (eg, 5-ASA, corticosteroid), other than that 
required for endoscopy preparation 
• Treatment with cyclosporine, tacrolimus, sirolimus, methotrexate, or mycophenolate mofetil  
• Cholestyramine or other drug interfering with enterohepatic circulation unless the dose has 
been stable for > 6 months prior to Screening 
• S1P receptor modulators including but not limited to fingolimod, siponimod, ozanimod, 
ponesimod, and etrasimod 
• Receipt of a live vaccine from 4 weeks prior to randomization and/or until 2 weeks post last 
dose. Nonlive vaccines, including SARS-CoV-2, can be administered according to local 
vaccination standards. 
• Treatment with lymphocyte-trafficking inhibitors  
• Treatment with lymphocyte-depleting therapies (eg, alemtuzumab, anti-CD4, cladribine, 
rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone 
marrow transplantation, daclizumab) 
• Treatment with D-penicillamine, or thalidomide, dimethyl fumarate, or pyrimidine synthesis 
inhibitors 
• Start, stop or change in dosage of any Class I-IV anti-arrhythmic drugs ≤ 1 week prior to 
dose titration starting at randomization and up to 1 week after titration to the assigned dose. 
This criterion also applies to the OLE Treatment Period titration: 1 week prior to and up to 
1 week after the dose titration period.  
The following concomitant procedures are prohibited during the study: 
• Major elective surgery 
• Immunoadsorption columns 
• Intravenous immunoglobulin or plasmapheresis 
• Blood donations during the study and for 14 days after the last dose of study treatment 
• Sperm or oocyte donations during the study and for 30 days after the last dose of study 
treatment. 
6.11 Treatment After the End of the Study 
The Sponsor will not provide any additional care to participants after they leave the study because 
such care should not differ from what is normally expected for patients with the medical condition. 

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7.0 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of Study Treatment 
A participant’s study treatment may be discontinued for any of the following reasons: 
• Worsening of disease, defined as: 
− Induction Treatment Period:  
 Based on Investigator’s decision, administration of prohibited medication for 
treatment of UC during the Induction Period 
− LTE Treatment Period: 
 Based on Investigator’s decision, administration of prohibited medication for 
treatment of UC during the LTE Treatment Period 
− OLE Treatment Period: 
 Participant fails to achieve symptomatic response by OLE Week 13 (among 
participants who had no clinical response at the end of the Induction Period) 
 Participant experiences loss of response 
• AE, see Appendix 4:  
− A participant may be discontinued from the study drug if, in the judgment of the 
Investigator, the participant develops an AE such as an intercurrent illness or complication 
that is not consistent with the protocol requirements or that, in any way, justifies 
withdrawal from the study. 
• Discontinuation of study treatment for abnormal liver function should be considered by the 
Investigator when a participant meets one of the conditions outlined below or if the 
Investigator believes that it is in best interest of the participant. 
− ALT or AST > 8 × ULN 
− ALT or AST > 5 × ULN for > 2 weeks 
− ALT or AST > 3 × ULN and total bilirubin > 2 × ULN or INR > 1.5 
− ALT or AST > 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (> 5%). 
• Other, non-AE 
A participant’s study treatment must be discontinued temporarily (treatment interruption) for any 
of the following reasons: 
• New onset QTcF interval prolongation 
− If an ECG shows a new onset QTcF interval > 450 msec in men and > 470 msec in women 
during the treatment period, a repeated ECG is required. If this abnormal finding is 

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confirmed, study treatment must be temporarily discontinued. Reinitiation of study 
treatment can be considered per criteria described in Section 8.4.3. 
• Lymphopenia (ie, severe decrease in ALC) 
− If the ALC is confirmed to be below the 200 cells/µL limit, study treatment should be 
interrupted and should not be reinitiated if the ALC remains below this threshold. In this 
situation, the unblinded Medical Monitor will notify the Investigator and provide 
instructions on additional actions that the Investigator may need to take. When there is at 
least one measurement of ALC < 200 cells/μL, blinded values may be released to treating 
physicians and Investigators as deemed medically necessary to monitor infection and/or 
aid in diagnostic work-up as clinically indicated, and/or as a tool to assess the 
effectiveness of therapeutic interventions for an infection. Investigators will repeat CBC 
with differentials weekly until ALC > 500 cells/μL. 
− Reinitiation of study treatment can be considered only when ALC > 500 cells/μL. 
A participant’s study treatment must be discontinued permanently for any of the following reasons: 
• Study participant is pregnant (see Section 8.5.5) 
• Decline in PFT values (FEV1 and/or FVC) below 50% of the predicted values 
• Confirmed diagnosis of clinically significant macular edema, see Section 8.4.6 
• Confirmed diagnosis of PML: Cases of PML have occurred in patients who have received 
S1P1 modulators. At the first sign or symptom suggestive of PML, withhold VTX002 and 
perform an appropriate diagnostic evaluation. The magnetic resonance imaging findings may 
be apparent before clinical signs or symptoms. Typical symptoms associated with PML are 
diverse, progress over days to weeks, and include progressive weakness on one side of the 
body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and 
orientation leading to confusion and personality changes. The Investigator must notify the 
Medical Monitor of such symptoms. 
• Cardiovascular events: 
− A participant experiencing a cardiovascular treatment-related symptomatic event (eg, 
chest pain, dizziness, palpitations, lightheadedness, shortness of breath, or syncope) 
associated with a clinically significant reduction of the HR or associated with clinically 
relevant 12-lead ECG changes at any time during the 6-hour monitoring period on Day 1 
or Day 2 (as applicable) (Section 8.4.3). See also Section 6.5 for cardiac monitoring 
during treatment initiation or reinitiation. 
− Participants who have not met the discharge criteria on Week 0 (Day 1/Visit 2) or 
OLE Week 0 (OLE Day 1/OLE Visit 1) after ≥ 6 hours of extended monitoring and on 
Day 2/OLE Day 2 by 6 hours postdose (see Section 6.5.1.2). 
• Noncompliance with study treatment (see Section 6.9) 
• Investigator decision 

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• Withdrawal by participant 
• Study termination by Sponsor or regulatory bodies/agency 
The reason for discontinuation of study treatment will be recorded in the clinical records and the 
participant’s eCRF. 
See Section 6.4.2 for dose interruption of study treatment. 
7.2 
Follow-Up Period 
For all participants, a Follow-Up visit will be performed at 1 and 2 weeks after the last dose of 
study treatment as indicated in the SoA. 
All participants who discontinue the study prematurely will be asked to return to the clinic for the 
ET visit. If the ET visit is ≥ 1 week after the last dose of study treatment, the 1-Week Follow-Up 
visit is not required; however, the 2-Week Follow-Up visit should be scheduled and completed. If 
the ET visit is ≥ 2 weeks after the last dose of study treatment, the 2-Week Follow-Up visit is not 
required. 
If the ALC is not within normal limits at the 2-Week Follow-Up visit, participants should return 
for CBC testing with differential according to local standard of care (captured as a subsequent 
Follow-Up visit or unscheduled visit). 
All AEs should be recorded for 30 days after the last administration of study treatment (see 
Section 8.5.1). 
7.3 
Lost to Follow-Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study center. 
The following actions must be taken if a participant fails to return to the clinic for a required study 
visit: 
• The study center must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the participant wishes to and/or should continue in 
the study. 
• Before a participant is deemed lost to follow-up, the Investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, if 
necessary, a certified letter to the participant’s last known mailing address or local equivalent 
methods). These contact attempts should be documented in the participant’s medical record. 
Should the participant continue to be unreachable, he/she will be considered to have withdrawn 
from the study. 

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7.4 
Participant Discontinuation/Withdrawal 
A participant may withdraw from the study at any time at his/her own request or may be withdrawn 
at any time at the discretion of the Investigator for safety, behavioral, compliance, or administrative 
reasons. 
If the participant withdraws consent for disclosure of future information, the Sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the Investigator must document this in the source document. 
Participants who withdraw from the study will not be replaced. See the SoA (Section 1.2) for data 
to be collected at the time of withdrawal (ie, ET visit) and follow-up, and for any further 
evaluations that need to be completed. 
Discontinuation of specific study centers or of the study as a whole are handled as described in 
Appendix 2. 

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8.0 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the SoA (Section 1.2). 
Protocol waivers or exemptions are not allowed. 
Immediate safety concerns should be discussed with the Sponsor immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue study treatment. 
Adherence to the study design requirements, including those specified in the SoA, is essential and 
required for study conduct. 
8.1 
Screening and Eligibility 
Screening procedures must be completed within 28 days prior to receiving the first dose of study 
treatment. The Screening Period may be extended for participants who require additional 
diagnostic testing/consults to determine status of either latent TB or C. difficile infection. If the 
participant is planned to be randomized > 28 days from the signing of the ICF, the Medical Monitor 
should be consulted to see if repeated testing is needed. The 28-day Screening Period may also be 
extended on a case-by-case basis to accommodate reasonable delays in specific screening 
assessments (eg, PFTs, OCT) due to testing availability. The Medical Monitor must be consulted 
prior to extension in each case. 
All Screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. The Investigator will maintain a Screening log to record details of all 
participants screened and to confirm eligibility or record reasons for Screening failure, as 
applicable. 
Procedures conducted as part of the participant’s routine clinical management (eg, blood count) 
and obtained before signing of the ICF may be utilized for Screening or baseline purposes provided 
the procedures met the protocol-specified criteria and were performed within the time frame 
defined in the SoA. 
Repeat or unscheduled blood samples may be taken for safety reasons or for technical issues with 
the samples. 
A social history including the amount and duration of tobacco, alcohol, and caffeine usage will be 
collected.  
A standard urine drug screen will be performed. Participants who test positive will be assessed for 
eligibility for study participation by the Investigator after discussion with the Medical Monitor. 
Consumption of poppy seeds within 48 hours prior to drug screening may cause a positive drug 
screen. Participants should be instructed not to consume food items that contain poppy seeds for 
48 hours prior to the Screening visit. Participants who report that they have consumed poppy seeds 

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within 48 hours of the Screening visit should not be screened. They may return 48 hours after the 
last poppy seed consumption for screening. 
8.2 
Virtual/Hybrid Visits  
Study visits after Day 1 may be conducted via onsite (in person at the study site or specialty lab), 
offsite (home health visit by study staff or designee), virtual (eg, telephone, video conference), or 
hybrid (a combination of aforementioned visit types), depending on the nature of the study 
assessment, technological capability, and acceptability with institutional practices and in 
alignment with local law and regulatory requirements. These may take place on different days 
within the study visit window.  
Certain assessments and/or procedures will not be performed in the home setting (eg, endoscopies, 
OCT, PFT, cardiac monitoring following treatment initiation or reinitiation, and 12-lead ECG).  
Pregnancy testing and central laboratory assessments (eg, blood, stool, and urine samples) can be 
performed by either onsite visit or offsite visit.  
Assessments or procedures that may be conducted virtually, if allowed by local law and regulation, 
include, for example: informed consent process including obtaining written informed consent, 
medical and medication history to assess eligibility criteria, review of demographic information, 
social history, AE query, review of concomitant medications, eDiary training, and compliance 
review/monitoring including study drug administration and questionnaires.  
During a virtual assessment, a participant may report an AE that requires a follow-up 
symptom-focused physical exam or diagnostic test, as determined by the Investigator. In this 
scenario, the Investigator may have the participant return to the study site for an unscheduled study 
visit to perform the assessment.  
For study drug accountability, the study treatment blister cards/bottles and remaining tablets may 
be visually inspected and counted on video conferencing. Participants must return the dispensed 
blister cards/bottles with the remaining tablets along with any empty blister cards/bottles to the 
study site at the next onsite visit. See Section 6.7 for study treatment management.  
Some study visits may be virtual/hybrid, if so designated in the SoA (see Section 1.2). Regardless 
of how a study visit and its associated procedures are conducted, all study procedures should be 
performed by qualified study site staff or qualified individuals as delegated by the Investigator.  
The safety of study participants and site staff is paramount, so it is at the Investigator’s discretion 
whether PFT can be safely administered to study participants during the treatment period. The 
Investigator should evaluate on a case-by-case basis how best to proceed based on the participant’s 
medical history, the Investigator’s clinical judgment, and in consultation with the Medical 
Monitor. All reasonable efforts should be made to ensure safety and adherence to the protocol. 
When available, spirometry may be conducted at the clinical site instead of at the pulmonary 

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laboratory. If the decision is made that it is not appropriate to conduct PFTs due to safety concerns 
(eg, SARS-CoV-2 transmission), then this decision and rationale should be appropriately captured 
in the participant’s source documentation. When available and safe (due to lifting of local 
restrictions, reopening of local PFT labs, or improved safety conditions), the tests should be 
conducted as soon as possible and as close to the timepoints as outlined in the protocol. 
8.3 
Efficacy Assessments 
8.3.1 Mayo Clinic Scores 
This study uses components of the MCS, which includes ES, RB, SF, and PGA, as well as MMS, 
which includes ES, RB, and SF (Appendix 6), to assess UC disease activity in support of the 
primary, secondary, and exploratory endpoints.  
The total score range of the MCS is from 0 to 12, with each component ranging from 0 to 3. The 
total score range of the MMS is from 0 to 9, with each component ranging from 0 to 3. The PMS 
will also be assessed, which includes RB, SF, and PGA, for a total score range from 0 to 9. 
Each component is described in more detail in the following paragraphs. The efficacy endpoint 
definitions using MMS and MCS components are outlined in Section 3.3.  
Endoscopic subscore: Endoscopy will be used to visualize the mucosa to enable calculation of 
the ES. The ES reports the worst appearance of the mucosa on flexible sigmoidoscopy or 
colonoscopy, on a 4-point scale (Appendix 6). Consistent with regulatory advice, this study 
excludes friability from the definition of an ES of 1. The ES will be determined by a blinded central 
reader. 
Rectal bleeding: The RB subscore is a patient-reported measure. This item reports the most severe 
amount of blood passed per rectum for a given day, on a 4-point scale (Appendix 6). The 
participant will record this in their eDiary daily. 
Stool frequency: The SF subscore is a patient-reported measure. This item reports the number of 
patient-reported stools in a 24-hour period, relative to the normal number of stools for that 
participant in the same period (eg, remission), on a 4-point scale (Appendix 6). A stool is defined 
as a trip to the toilet when the participant has either a bowel movement, passage of blood alone, 
passage of blood and mucus, or passage of mucus only. The total number of stools passed in a 
24-hour period will be recorded by the participant in their eDiary daily. The reference “normal” 
SF for that participant will be recorded electronically on the first day of the Screening visit and is 
the number of stools in a 24-hour period when the participant is in remission. If the participant has 
never achieved remission, the reported SF before initial onset of signs and symptoms of UC will 
be used as the reference SF. 
Physician’s Global Assessment: The PGA is a physician-reported measure that is a component 
of the MCS and is used in the calculation of the total MCS and PMS. The PGA summarizes the 

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Investigator’s assessment of the participant’s UC disease activity on a 4-point scale (Appendix 6). 
The Investigator will record the PGA in the electronic data capture database (EDC) at the specified 
study visits (Section 1.2). Consistent with regulatory guidance, the PGA will not be used for 
primary efficacy assessment in this study. 
8.3.1.1 Electronic Diary 
Participants will begin eDiary entries beginning on the first day of Screening after diary training 
is completed. Participant recording will be made each day for the previous 24-hour period. The 
eDiary should be completed daily to capture data, including daily SF and RB (the 
2 patient-reported outcome measures of the MMS) and study drug administration. The 
participant’s eDiary will be reviewed by study site staff to ensure the participant is compliant with 
diary entries through EDC and during each study visit at the times noted in the SoA (Section 1.2). 
The RB score should be monitored to ensure the participant meets eligibility criteria of RB ≥ 1, 
prior to performing the Screening endoscopy. 
The MCS and MMS require daily patient-reported RB and SF subscores; therefore, the importance 
of daily recording of the RB and SF subscores by participants in their eDiary should be stressed by 
the Investigators. 
Detailed description regarding eDiary recordings can be found in the Study Manual. 
8.3.1.2 Endoscopy 
A flexible proctosigmoidoscopy or full colonoscopy, performed with a video endoscope following 
cleansing preparation (oral or rectal cathartic), will be performed as outlined in the SoA 
(Section 1.2). 
Proctosigmoidoscopy/colonoscopy must be performed prior to randomization to treatment to allow 
central reader review (may take approximately 5 to 12 days) and confirmation of eligibility. 
Preferably, proctosigmoidoscopy/colonoscopy should be performed after other criteria for 
inclusion (eg, laboratory criteria) have been met.  
To ensure quality data and standardization, the same endoscopist should be used throughout the 
study wherever possible. Endoscopy images/video will be obtained during each endoscopy and 
will be sent for central reading and determination of the Mayo ES. A detailed image review charter 
from the central reading laboratory will outline the endoscopic procedures, video recordings, and 
equipment.  
For each participant, a video recording of the entire endoscopic procedure will be performed using 
an acceptable storage medium. Investigators are encouraged to send endoscopic recording by the 
following day after endoscopy. The endoscopic recordings will be read centrally in a blinded 
manner for mucosal lesions and endoscopic severity by a qualified gastroenterologist according to 
the image review charter. The ES will be evaluated by the Investigator and the central reader. The 

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central read will be used for determination of efficacy endpoints; however, treatment decisions will 
be made by the treating Investigator. 
Repeat flexible proctosigmoidoscopy may be permitted by the Sponsor when the central reader 
indicates that the video endoscope data were acquired incorrectly or did not meet the minimal 
required quality standards. 
The detailed instructions for endoscopy can be found in the Study Manual. 
8.3.1.3 Determination of MMS Score to Qualify for Randomization 
The MMS will be evaluated on Day 1. The subscores for RB and SF are derived from the 
participant eDiary entries using the scores from the 3 most recent consecutive days within the 
7 days prior to the day of bowel preparation (excluding the day of bowel preparation), averaged 
and rounded to the nearest integer. The scoring will be calculated electronically. Participants who 
do not have 3 consecutive days of eDiary data within that 7-day period and who do not have a 
minimum of 7 days of eDiary data prior to bowel preparation are not eligible for randomization. 
The MMS must be 5 to 9, including an ES ≥ 2 and RB ≥ 1, for the participant to be eligible for 
randomization. 
8.3.1.4 Determination of Clinical Response 
At Visit 7 (Week 13), clinical response will be calculated electronically to determine if the 
participant will continue in the LTE or have the option to enroll in the OLE. The subscores for RB 
and SF are derived from the participant eDiary entries using the scores from the 3 most recent 
consecutive days of diary entries within the 7 days prior to the day of bowel preparation, averaged 
and rounded to the nearest integer. In the rare case that 3 consecutive days of data are not available, 
the most recent 2 days may be used after discussion with the Medical Monitor. 
8.3.1.5 Determination of Loss of Response in LTE 
During the LTE, participants exhibiting loss of response will have the option to enroll in the OLE. 
The Investigator will assess loss of response according to the following criteria: 
• Increase in UC disease activity as defined by an increase in PMS ≥ 2 points compared to 
PMS at Week 13 with an absolute PMS ≥ 4, based on 3 most recent consecutive days of 
diary entries within 7 consecutive days (averaged and rounded to the nearest integer), AND 
• Exclusion of other causes of an increase in disease activity unrelated to underlying UC (eg, 
C. difficile infection, change in medication). 
8.3.1.6 Determination of Symptomatic Response in OLE 
Participants who failed to achieve clinical response at the end of the Induction Period (Week 13) 
and entered the OLE will be assessed again by the Investigator at OLE Week 13 for symptomatic 
response according to the following criteria: decrease from baseline ≥ 30% of the combined RB 

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and SF scores, based on the 3 most recent consecutive days of diary entries within the 7 days prior 
to the visit, averaged and rounded to the nearest integer. 
8.3.2 Endoscopic Biopsies 
Per the inclusion criteria (Section 5.1), a histopathology report supporting the diagnosis of UC 
must be available in the source documents prior to randomization. If a histopathology report is not 
available, the Screening endoscopy may serve as such with histology evaluated at the local 
histology laboratory. 
Biopsies will be obtained at each endoscopy to support assessment of the histopathology endpoints 
 Up to 4 biopsy pairs (ie, total 
of 8) will be collected from the most affected area 15 to 25 cm from the anal verge. For participants 
with proctitis only at baseline, biopsies should be taken 8 to 10 cm from the anal verge. 
The original location (colonic segment) of biopsy specimens acquired at Screening must be clearly 
indicated. Detailed instructions for endoscopic biopsies (eg, number of biopsies, anatomic site, 
normal or inflamed mucosa) can be found in the Laboratory Manual. 
Biopsy samples will be processed by a central laboratory, and histopathologic scoring using the 
Geboes, Robarts, and Nancy histopathology indices will be performed by a blinded central reader 
(Appendix 7). 
Biopsy specimen transfer, processing, slide preparation, and digitization of slides for 
histopathologic scoring procedures will be detailed in a Histopathology Manual. 
 
This will be further 
delineated in the Laboratory Manual. Histopathology results will not be made available to study 
sites. 
8.3.3 Efficacy-Related Biomarkers 
All efficacy-related and exploratory efficacy-related biomarkers will be analyzed by a central 
laboratory. 
Samples for biomarker assessments will be collected according to the SoA (Section 1.2). Blood, 
tissue, and stool samples will be analyzed by the central or specialty laboratory. Details for 
collection, processing, and storage will be provided in the Laboratory Manual. Residual samples 
will be stored and may be used for additional analyses, if the participant has granted consent and 
where allowed by the regulatory authorities and local ethics committees. 
C-reactive protein: Blood will be collected for measurement of CRP. C-reactive protein is an 
acute phase protein expressed by hepatocytes in response to inflammatory cytokines and will be 
assessed using a CRP assay. Investigators will be blinded to the CRP results during the 13-week 

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Induction Treatment Period, the LTE Treatment Period, and first 4 weeks of the OLE Treatment 
Period. 
Fecal calprotectin: Stool samples will be collected for measurement of FCP. Fecal calprotectin is 
a complex consisting of calcium-binding proteins. It is expressed by activated neutrophils (and to 
a lesser extent by macrophages and monocytes), and fecal levels correlate with the number of 
neutrophils in the gut. It is used as a biomarker of intestinal inflammation. Investigators will be 
blinded to the FCP results during the 13-week Induction Treatment Period, the LTE Treatment 
Period, and first 4 weeks of the OLE Treatment Period. 
Lymphocyte count: Blood will be collected for measurement of lymphocyte count. VTX002, 
through modulation of S1P receptors, is postulated to modulate lymphocyte trafficking, resulting 
in a reduction in peripheral lymphocyte count and lymphocyte availability for recruitment to sites 
of inflammation. During the 13-week Induction Treatment Period, the LTE Treatment Period, and 
first 4 weeks of the OLE Treatment Period, Investigators will be blinded to the WBC and 
differential counts results. The Investigator must take care to avoid ordering or viewing any local 
CBC during this time. During this time, the WBC differential results will be assessed by an 
unblinded Medical Monitor (not providing direct medical oversight of study conduct). If either one 
of the following events occurs, the unblinded Medical Monitor will notify the Investigator with 
additional instructions: 
• ANC (absolute neutrophil count) < 1000/μL  
• ALC < 200 cells/μL  
If the ANC is confirmed to be below the 1000/µL limit, the Investigator will be requested to closely 
monitor for risk of serious infection and institute appropriate follow-up at his or her discretion. 
If the ALC is confirmed to be below the 200 cells/µL limit, study treatment should be interrupted 
and should not be reinitiated if the ALC remains below this threshold. In this situation, the 
unblinded Medical Monitor will notify the Investigator and provide instructions on additional 
actions that the Investigator may need to take. When there is at least one measurement of ALC 
< 200 cells/μL, blinded values may be released to treating physicians and Investigators as deemed 
medically necessary to monitor infection and/or aid in diagnostic work-up as clinically indicated, 
and/or as a tool to assess the effectiveness of therapeutic interventions for an infection. 
Investigators will repeat CBC with differentials weekly until ALC > 500 cells/μL. Reinitiation of 
study treatment can be considered only when ALC > 500 cells/μL.  
8.3.4 Exploratory Efficacy-Related Biomarkers 
Samples for exploratory biomarker assessments will be collected according to the SoA 
(Section 1.2). 
 will be analyzed by a central or specialty laboratory. 
Details for collection, processing, and storage will be provided in the Laboratory Manual. Residual 

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samples will be stored and may be used for additional analyses to further understand response to 
treatment and mechanism of action of VTX002 if the participant has granted consent. These 
additional analyses (as appropriate) will be conducted only where allowed by the regulatory 
authorities and local ethics committees. 
Samples may be stored for a maximum of 15 years (or according to local regulations) following 
the last participant’s last visit for the study at a facility selected by the Sponsor to enable further 
analysis of biomarker responses to VTX002, such as proteomics and transcriptomics, if needed. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
8.3.5 Quality of Life 
Patient-reported quality of life assessment will be completed electronically and checked for 
completeness at the study site as indicated in the SoA (Section 1.2) and will be used in support of 
the efficacy outcomes. 
Inflammatory Bowel Disease Questionnaire: The IBDQ is a validated 32-item questionnaire 
used to assess HRQoL in participants with inflammatory bowel disease, including UC and Crohn’s 
disease. Response to each of the questions is graded from 1 to 7 with overall score ranging from 

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32 (very poor HRQoL) to 224 (perfect HRQoL). The IBDQ will be collected if and when available 
in the appropriate local language.  
8.4 
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoA (Section 1.2). 
8.4.1 Physical Examinations 
A complete PE will include evaluation of heart, lung, head and neck, abdomen, neurological 
system, skin, and extremities. An interim (or brief) PE will include areas with previously noted 
abnormalities and/or that are associated with any new complaints from the participant. Please see 
SoA (Section 1.2) for more information. 
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
8.4.2 Vital Signs 
Temperature, pulse, BP, and respiratory rate will be assessed. Vital signs will be measured prior 
to any blood draws that occur at the same study visit. 
Blood pressure and pulse will be assessed in the sitting position with a calibrated automated device. 
Manual techniques will be used only if an automated device is not available. Proper technique 
should be utilized during the measurement of BP to include the following: 
• The participant’s arm should be bare and supported at heart level 
• An appropriately sized cuff (cuff bladder encircling at least 80% of the arm) should be 
utilized. Participant’s legs should not be crossed during the evaluation 
When obtaining the pulse and BP, the participant should rest in the sitting position for at least 
5 minutes before measurement to establish an accurate baseline measurement. After the participant 
has been sitting for at least 5 minutes, pulse and BP will be measured using an automated validated 
device (if available). Blood pressure and pulse are to be collected prior to completion of the ECG 
assessment and before any simultaneously scheduled blood collections. See Section 6.5 for 
guidance for cardiac monitoring. 
8.4.3 Electrocardiograms 
A12-lead ECG will be obtained as outlined in the SoA (see Section 1.2) using an ECG machine 
that automatically calculates the HR and measures PR, QRS, QT, and QTc intervals.  
Electrocardiograms should be preceded by at least 5 minutes of rest in the supine position without 
distractions (eg, television, cell phones) at each timepoint at which an ECG is required.  

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All ECGs will be recorded from a 12-lead ECG machine with the participant in the supine position. 
Every attempt should be made to ensure the participant’s 12-lead ECG readings are obtained using 
the same machine throughout the study. 
Intervals to be provided on the confirmed read for each safety 12-lead ECG are: RR, PR, QRS, QT 
and QTcF. If an ECG shows a new onset QTcF interval > 450 msec in men and > 470 msec in 
women during the treatment period, a repeated ECG is required. If this abnormal finding is 
confirmed, study treatment must be interrupted. Effective diagnostic and therapeutic strategies 
should be employed. 
Reversible causes of prolonged QTc interval (eg, electrolyte abnormalities or hypomagnesemia) 
should be corrected as clinically indicated. When evaluating a participant with new onset QTc 
interval above 500 msec, referral to a cardiologist experienced in treating cardiac conduction 
disorders should be considered. Reinitiation of study treatment can be considered only after all of 
the following have occurred: 
• The QTcF interval is < 450 msec (men) or < 470 msec (women) 
• The QTc prolongation is considered by the Investigator and confirmed by the cardiologist as 
not related to study treatment and likely caused by other factors 
• Individual risk-benefit is favorable (as determined by the Investigator, in agreement with the 
cardiologist), AND 
• After discussion with the Medical Monitor 
The Investigator will be responsible for review and interpretation of 12-lead ECGs on site and 
determining if the 12-lead ECG is normal, abnormal clinically insignificant, or abnormal clinically 
significant. Findings will be documented in the eCRF. All 12-lead ECG recordings will be 
transferred to a central reader for analysis. See Section 6.5 for guidance for cardiac monitoring. 
8.4.4 Holter ECG Monitoring 
Detailed instructions describing the process for recording and transmission of the digital ECGs 
and Holter can be found in the Study Manual and provided to the site before the start of the study. 
Participants should be in the supine position prior to Holter application. 
On Day 1 and OLE Day 1 (OLE Week 0/OLE Visit 1), continuous Holter ECG monitoring will 
be performed for at least 1 hour predose and at least 24 hours postdose using the same device and 
procedure, as outlined in the SoA (see Section 1.2). Participants who meet the discharge criteria 
(Section 6.5.1.1) will be sent home for continued Holter monitoring at least 24 hours postdose. 
Participants will be instructed regarding removal and return of the Holter monitor. All Holter 
recordings will be transferred to a central reader for analysis. 
See Section 6.5 for guidance for cardiac monitoring. 

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8.4.5 Pulmonary Function Tests 
Pulmonary function tests will be performed according to the SoA (Section 1.2) and include FEV1 
and FVC measurements. At sites where available, diffusing capacity of the lungs for carbon 
monoxide (DLCO) measurements will also be performed. These tests will be performed at a 
qualified pulmonary function laboratory or respiratory department. 
If the PFTs are not within normal range, the results should be verified by a pulmonologist, and 
potential confounding factors identified. If the participant has a decline in PFT values, the 
participant should be evaluated by a pulmonologist. If values (FEV1 and/or FVC) decline below 
50% of the predicted values, treatment should be discontinued with follow-up evaluation initiated 
as appropriate. An inability to perform a test for DLCO should be discussed with the Sponsor. 
The safety of study participants and site staff is paramount, so it is at the Investigator’s discretion 
whether PFT can be safely administered to study participants during the treatment period. The 
Investigator should evaluate on a case-by-case basis how best to proceed based on the participant’s 
medical history, the Investigator’s clinical judgment, and in consultation with the Medical 
Monitor. All reasonable efforts should be made to ensure safety and adherence to the protocol. 
When available, spirometry may be conducted at the clinical site instead of at the pulmonary 
laboratory. If the decision is made that it is not appropriate to conduct PFTs due to the safety 
concerns (eg, SARS-CoV-2 transmission), then this decision and rationale should be appropriately 
captured in the participant’s source documentation. When available and safe (due to lifting of local 
restrictions, reopening of local PFT labs, or improved safety conditions), the tests should be 
conducted as soon as possible and as close to the timepoints as outlined in the protocol. 
8.4.6 Ophthalmoscopy and Optical Coherence Tomography 
Ophthalmoscopy and OCT will be performed according to the SoA (Section 1.2). A general 
ophthalmologist can do the OCT examination, although a retinal specialist would be preferred to 
do the examinations, wherever possible. 
For participants with abnormal OCT findings, with visual signs or symptoms of new onset macular 
edema, or a suspicion of new onset macular edema or worsening macular edema following 
initiation of treatment, general retinal examinations, including eye history, visual acuity, and 
dilated ophthalmoscopy should be obtained along with OCT. Additional testing should be 
considered at the discretion of the ophthalmologist. 
8.4.7 Tuberculosis Screening and Chest X-Ray 
All participants will complete TB screening to determine eligibility (see Exclusion Criterion 15).  
A positive diagnostic TB test is defined as: 
• A positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests OR 

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• A tuberculin skin test reaction ≥ 10 mm (≥ 5 mm in participants receiving the equivalent 
of > 15 mg/day prednisone), if a QuantiFERON test is not available 
Chest X-ray is to be performed at the time of Screening if not done in the previous 6 months. 
Participants with active or latent TB infection at Screening, and history of untreated or 
inadequately treated latent TB infection will be excluded from the study. The following are 
EXCEPTIONS to this exclusion criterion: 
a. Participants with latent TB, who have been ruled out for active TB, have completed an 
appropriate course of TB prophylaxis treatment per national/local medical guidelines or 
WHO guidelines, have a chest radiograph without changes suggestive of active TB 
infection, and have not had recent close contact with a person with active TB are eligible 
to enroll in the study. It is the responsibility of the Investigator to verify the adequacy of 
previous TB treatment and provide appropriate documentation of treatment compliance.  
b. Participants diagnosed with latent TB at Screening, ruled out for active TB and have 
received at least 4 weeks of an appropriate TB prophylaxis regimen may be rescreened for 
enrollment. Participants will complete their prophylactic regimen during the trial. 
8.4.8 Clinical Safety Laboratory Assessments 
See Appendix 3 for the list of clinical laboratory tests to be performed and the SoA (Section 1.2) 
for the timing and frequency. 
The Investigator must review the laboratory report, document this review, and record any clinically 
relevant changes occurring during the study in the AE section of the eCRF. The laboratory reports 
must be filed with the source documents. Clinically significant abnormal laboratory findings are 
those that are not associated with the underlying disease, unless judged by the Investigator to be 
more severe than expected for the participant’s condition. 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within 14 days after the last dose of study treatment should be repeated until the 
values return to normal or baseline or are no longer considered clinically significant by the 
Investigator or Medical Monitor. 
If such values do not return to normal/baseline within a period of time judged reasonable by the 
Investigator, the etiology should be identified, and the Sponsor or their designee notified. All 
protocol-required laboratory assessments, as defined in Appendix 3, must be conducted in 
accordance with the Laboratory Manual and the SoA (Section 1.2). If laboratory values from 
nonprotocol-specified laboratory assessments performed at the institution’s local laboratory 
require a change in participant management or are considered clinically significant by the 
Investigator (eg, SAE or AE), then the results must be recorded in the eCRF. 
8.5 
Adverse Events 
The definitions of an AE and SAE can be found in Appendix 4. 

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Adverse events will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant’s legally authorized representative). 
The Investigator and their designees or site staff are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study treatment or study procedures, or that 
caused the participant to discontinue the study treatment (see Section 7.0). 
8.5.1 Time Period and Frequency for Collecting AE and SAE Information 
All AEs and SAEs will be collected from the signing of the ICF to 30 days after last study treatment 
administration. Medical occurrences that begin before the start of study treatment but after 
obtaining informed consent will be recorded on the Medical History/Current Medical Conditions 
section of the eCRF, not the AE section. 
All SAEs will be recorded and reported to the Sponsor or designee within 24 hours of learning of 
a participant’s SAE, as indicated in Appendix 4. The Investigator will submit any updated SAE 
data to the Sponsor or designee within 24 hours of becoming aware. 
Investigators are not obligated to actively seek AE or SAE data after conclusion of the study 
participation. However, if the Investigator learns of any SAE, including death, at any time after a 
participant has been discharged from the study, and he/she considers the event to be reasonably 
related to the study treatment or study participation, the Investigator must promptly notify the 
Sponsor. 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 4. 
8.5.2 Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.5.3 Follow-Up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow up on each AE 
at subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the event is 
otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). Further 
information on follow-up procedures is given in Appendix 4. 
In addition to appropriate reporting of these events as an AE or SAE, supplementary detailed 
information may be collected from the Investigator. 

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8.5.4 Regulatory Reporting Requirements for SAEs 
Prompt notification by the Investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a study 
treatment under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. The Sponsor 
will comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, Institutional Review Board (IRB)/Independent Ethics Committee (IEC), and 
Investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSARs) according to local regulatory requirements and Sponsor policy, and forwarded to 
Investigators as necessary. The term SUSAR refers to an AE that occurs in a participant and which 
is assessed by the Sponsor and/or Investigator as being unexpected (ie, not listed in the 
Investigator’s Brochure or not listed at the specificity or severity that has been observed), serious, 
and as having a reasonable possibility of a causal relationship with the study drug (ie, related to 
the study drug per causality assessment in Appendix 4). Reports of these reactions are participant 
to expedited submission to regulatory authorities. 
An Investigator who receives an Investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will review and then file it 
along with the Investigator’s Brochure and will notify the IRB/IEC, if appropriate according to 
local requirements. 
8.5.5 Pregnancy 
Reports of all pregnancies in female participants and, if indicated, female partners of male 
participants will be collected after the start of study treatment and until 30 days after the 
participant’s last dose of study drug. 
The first pregnancy test at Screening is a serum β-hCG test that is evaluated by a central laboratory. 
All subsequent pregnancy testing will be performed using a urine dipstick pregnancy test that may 
be performed at the site or at home, if a virtual visit is performed as indicated in the SoA 
(Section 1.2). During non-visit months, participants will be provided with a home urine pregnancy 
test kit (as permitted by local regulations). Participants will confirm the performance of a monthly 
pregnancy test in the eDiary, if performed at home, and provide the results to the study site. If not 
permitted by local regulations, a pregnancy test will be performed at an unscheduled visit at the 
site during non-visit months. Any positive urine pregnancy test result will be confirmed with a 
serum β-hCG test. 
If a pregnancy is reported in a female study participant, study treatment should be discontinued at 
once and the Investigator should inform the Sponsor or designee within 24 hours of learning of the 

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pregnancy, following the procedures outlined in Appendix 5. If a pregnancy is reported in the 
female partner of a male study participant, the pregnancy will be reported and followed the same 
way, but the study participant may continue with study treatment. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs. 
8.5.6 Adverse Events of Special Interest 
Based on the mechanism of action of VTX002 and prior experience with other agents acting via a 
similar mechanism, potential AESIs may be identified.  
See reasons for study treatment discontinuation in Section 7.1 for more information. 
8.6 
Treatment of Overdose 
An overdose is any dose of study treatment given to a participant or taken by a participant that 
exceeds the dose described in the protocol. There is no information yet regarding overdose with 
VTX002. 
Any overdose, with or without associated AEs, must be promptly reported to the Sponsor or 
designee. Overdoses do not need to be recorded as AEs in the eCRF; only overdoses associated 
with an AE should be reported on relevant AE/SAE sections in the eCRF. 
8.7 
Pharmacokinetics  
8.7.1 Collection of Blood Samples for VTX002 Concentration Determination in Plasma 
Blood samples will be collected for measurement of plasma concentrations of VTX002 as 
specified in the SoA (Section 1.2) and as shown in Table 10 below. Blood samples may be taken 
either by direct venipuncture or an indwelling cannula inserted in a forearm vein. 

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Table 10 
Blood Samples for Pharmacokinetics 
 
Pre-dosea 
2, 4, and 6 
hours postdose  
(± 10 minutes) 
24 hours 
postdose  
(± 10 minutes) 
Trough PK 
Induction Visit 2 (Day 1) 
X 
X 
 
 
Induction Visits 3-5 and 7 
X 
 
 
 
LTE Visits 9-12 
X 
 
 
 
OLE Visit 1 (OLE Day 1) 
X 
X 
X (Optional)b 
 
OLE Visits 2 and 3 
X 
X (Optional)c 
X (Optional)c 
 
OLE Visits 4-9, 13, and 17/EOT 
X 
 
 
 
ET and FU 
 
 
 
X 
Abbreviations: EOT = end of treatment; ET = Early Termination; FU = Follow-Up 
a. When study drug is administered at the clinic, PK sample will be collected predose and after completion of vital 
sign assessments and ECGs. 
b. Applies only to participants who consent to return to the clinic on OLE Day 2 
c. Postdose timepoints are optional, but all 4 timepoints (2, 4, 6, and 24 hours postdose) are required for participants 
who consent 
Blood samples for measurement of plasma concentrations of VTX002 will be collected predose at 
all study visits, and also at a few timepoints postdose in some visits. When timepoints are specified 
as optional, samples will be collected only from participants who consent for such samples. 
Additional detailed instructions for the blood collection, processing, storage, and shipment to the 
bioanalytical laboratory will be detailed in the Laboratory Manual. The actual date and time 
(24-hour clock time) of each sample will be recorded, along with the date and time of the 
administration of study treatment. 
8.7.2 Determination of Drug Concentration 
Samples for the determination of VTX002 in plasma will be analyzed using an appropriate 
validated bioanalytical method. Full details of the bioanalytical methods and batch performance 
will be described in a separate Bioanalytical Report that will be included in the final Clinical Study 
Report. 
Samples will be analyzed in accordance with the bioanalytical laboratory’s standard operating 
procedures and the validated method. As bioanalytical concentrations have the potential to unblind 
a study, the concentration results will only be transferred from the bioanalytical laboratory in 
accordance with the Data Transfer Specifications. 
Remaining plasma samples may be subjected to further analysis by the Sponsor or designee for 
the purpose of the development of additional bioanalytical assays and/or for VTX002 metabolite 
identification in human plasma, if warranted based on emerging data and if the participant gives 
consent for this purpose. Samples collected for analyses of VTX002 concentrations may also be 
used to evaluate safety or efficacy aspects related to concerns arising during or after the study. 

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8.8 
Biomarkers 
Biomarkers for efficacy or exploratory efficacy analyses are provided in Sections 8.3.3 and 8.3.4. 
Instructions for the collection and handling of biological samples will be provided in the 
Laboratory Manual. The actual date and time (24-hour clock time) of each sample will be recorded. 
8.8.1 Determination of Biomarkers 
All efficacy-related and exploratory efficacy-related biomarkers will be analyzed by a central 
laboratory. Additional details can be found in the Laboratory Manual. 
 
 
  

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9.0 
STATISTICAL CONSIDERATIONS 
9.1 
General Considerations 
All data listings, summaries, and analyses will be performed under the guidance and approval of 
the Sponsor. 
Descriptive statistics will be used for all variables, as appropriate. Continuous variables will be 
summarized by the number of observations, mean, standard deviation (SD), median, first quartile, 
third quartile, minimum, and maximum. In addition to the aforementioned summary statistics, 
geometric mean and geometric CV will be calculated for certain PK parameters. Categorical 
variables will be summarized by frequency counts and percentages for each category. Unless 
otherwise stated, percentages will be calculated out of the total population for each treatment group 
and hypothesis tests will use a two-sided alpha = 0.05. 
For change from baseline efficacy analyses (including the primary efficacy analysis), only 
participants with a baseline and at least one nonmissing postbaseline measurement will be 
included. 
For primary analysis purposes, all efficacy endpoints will be analyzed using the Full Analysis Set 
(FAS). For sensitivity analysis purposes, the primary and key secondary endpoints will also be 
analyzed using the modified Full Analysis Set (mFAS) and Per Protocol Set, using the same 
statistical methodology as described in Section 9.4.1 and Section 9.4.3. 
Additional details about the statistical methods will be provided in the SAP, which will be prepared 
as a separate document. 
9.2 
Determination of Sample Size 
The study is powered to show superiority of VTX002 60 mg to placebo with respect to clinical 
remission. Based on literature data review, the expected proportion of clinical remission at 
Week 13 is 28% for VTX002 60 mg and 8% for placebo.8,9 Under these assumptions and with a 
1:1 randomization ratio, two-group chi-squared test, and two-sided significance level of 5%, a 
sample of 57 participants per treatment group will be sufficient to achieve at least 80% power. 
Adding a 10% inflation for dropouts results in 63 participants per treatment group and 189 in total. 
All sample size calculations were conducted in SAS® (v9.4, SAS Institute Inc., Cary, NC). 
9.3 
Analysis Sets 
The following analysis sets for the Induction Treatment Period are defined as follows: 
Full Analysis Set (FAS): The FAS consists of all randomized participants who received at least 
one dose of study treatment. Participants will be analyzed according to the treatment to which they 
were randomized. 

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Modified Full Analysis Set (mFAS): For a given analysis, mFAS consists of all randomized 
participants who received at least 1 dose of study treatment, and have at least one non-missing 
post-baseline assessment(s) relevant to the analysis. Participants will be analyzed according to the 
treatment to which they were randomized. 
Per Protocol Set: The Per Protocol Set consists of all participants in the mFAS who do not have 
a significant protocol deviation having a major effect on the primary efficacy evaluation. 
Safety Set: The Safety Set consists of all randomized participants who received at least 1 dose of 
study treatment (VTX002 or placebo). For this population, participants are analyzed according to 
the treatment received, regardless of randomization. The Safety Set will be used for all safety 
analyses. 
Pharmacokinetics Set: The Pharmacokinetics Set consists of all participants who receive 
VTX002, have at least 1 measured concentration at a scheduled PK timepoint after start of dosing 
for VTX002. 
Biomarker Set: The Biomarker Set consists of all participants in the Safety Set who have at least 
1 measured biomarker value at a scheduled timepoint after start of dosing for study treatment. The 
Biomarker Set will be used for all biomarker analyses. 
The following analysis sets for the OLE Treatment Period are subsets of the analysis sets of the 
Induction Treatment Period, as defined below: 
FAS-Extension Treatment (FAS-ET) Set: The FAS-ET Set consists of all randomized 
participants who received at least 1 dose of study treatment in the LTE or the OLE Treatment 
Periods. Under this approach, the original treatment groups as assigned at randomization will be 
used. 
Safety-Extension Treatment (Safety-ET) Set: The Safety-ET Set includes all participants who 
received at least 1 dose of study treatment in the LTE or the OLE Treatment Periods. The 
Safety-ET Set will be used for all safety analyses. Participants will be analyzed according to 
treatments received in the LTE or the OLE Treatment Periods. 
9.4 
Statistical Analyses 
The SAP will be developed and finalized before the interim database lock (see Section 9.4.7) for 
the purpose of primary analysis and will describe the participant analysis sets to be included in the 
analyses and the procedures for accounting for missing, unused, and spurious data. This section is 
a summary of the planned statistical analyses of the primary and secondary endpoints. 
All analyses, summaries, and listings will be performed using SAS (version 9.4 or higher). 

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The following descriptive statistics will be used as applicable to summarize the study data unless 
otherwise specified: 
• Continuous variables: number of observations (n), mean, SD, median, first quartile, third 
quartile, minimum (min), and maximum (max) 
• Categorical variables: frequencies and percentages 
• Pharmacokinetic data will be presented in terms of number of participants (N), number of 
observations (n), arithmetic mean, SD, CV, median, first quartile, third quartile, minimum, 
and maximum value. In addition, geometric mean and geometric CV may also be presented. 
Individual participant data will be presented in listings. 
9.4.1 Efficacy Analyses 
The study is designed to have a capability to show superiority of VTX002 60 mg to placebo for 
the primary endpoint. Apart from the primary analysis, four key secondary endpoints are defined 
for this study. Further on, comparing two different dose levels of VTX002 vs placebo brings a 
total number of inferential analyses in the study up to 10. The family-wise Type I error rate across 
the primary analysis of the primary efficacy endpoint and all key secondary analyses will be 
maintained at α = 0.05 using a sequentially rejective method. Details will be provided in the SAP. 
Additional details about secondary and exploratory efficacy analyses will be included in the SAP, 
which will be finalized before the interim database lock. 
9.4.1.1 Primary Efficacy Analysis 
The primary analysis of the primary efficacy endpoint will be completed based on the FAS, and 
will be a comparison between VTX002 60 mg and placebo. The primary efficacy endpoint is the 
proportion of participants with clinical remission at Week 13. The following null hypothesis: 
H0: pVTX002 – pplacebo = 0 
will be tested against a two-sided alternative: 
HA: pVTX002 – pplacebo ≠ 0. 
The hypothesis will be tested at a 5% level of significance. Testing will be done using a 
Cochran-Mantel-Haenszel test (CMH) test with biologic/JAK inhibitor prior use status (Yes or 
No), baseline corticosteroid use (Yes or No), and baseline disease activity (MMS 4-6 or 7-9) as 
the stratification factors. The CMH chi-square p-value and stratified risk differences with 95% CI 
using the Newcombe method will be provided for pairwise comparisons between each dose group 
and placebo. Only the two treatment groups – VTX002 60 mg and placebo – will be included in 
the primary analysis of the primary endpoint.  

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9.4.1.2 Key Secondary Analyses 
Key secondary endpoints will be analyzed similarly to the primary endpoint, using the CMH test 
with similar stratification factors. Comparisons between VTX002 60 mg and placebo for all key 
secondary endpoints will be considered key secondary analyses. Comparisons between VTX002 
30 mg and placebo for the primary endpoint and the key secondary endpoints will be considered 
key secondary analyses. 
9.4.1.3 Exploratory Analyses 
Categorical exploratory endpoints will be analyzed similarly to the primary endpoint.  
Continuous exploratory endpoints will be analyzed using a general linear model (analysis of 
covariance [ANCOVA]) with fixed effects for treatment, biologic/JAK inhibitor prior use status 
(Yes or No), baseline corticosteroid use (Yes or No), and baseline disease activity (MMS 4-6 or 
7-9). 
Repeated measures Induction/LTE data on clinical remission, endoscopic response, endoscopic 
remission, histologic improvement (Geboes), and histologic remission (Geboes) at Weeks 4, 8, 10, 
13, 18, 26, 36, and 52 will be analyzed. This will be done using repeated measurements logistic 
regression specifying the distribution as binomial, the link function as logit and randomization 
stratification factors added as covariates in addition to randomized treatment.  
Change from baseline in FCP and CRP at Weeks 1, 4, 8, 13, 26, 36, and 52; and also for change 
from baseline in PMS at Weeks 4, 8, 13, 18, 26, 36, and 52 will be analyzed using an appropriate 
continuous repeated measurements methodology. Details will be provided in the SAP, and will 
include a specification of how the results will be reported. 
For clinical remission, endoscopic response, endoscopic remission, histologic improvement 
(Geboes), and histologic remission (Geboes) at Week 13, separate logistic regression models with 
stepwise selection will be built to assess the impact of the following covariates measured at 
baseline: 
• ALC derived from blinded hematology laboratory results 
• FCP 
• CRP 
The alpha level for both entering and removing a covariate will be 0.10. Point estimates and the 
corresponding 95% confidence intervals for the odds ratios will be calculated. 
9.4.2 Analysis of LTE Treatment Period and OLE Treatment Period 
All the exploratory endpoints collected during the LTE Treatment Period and the OLE Treatment 
Period will be summarized with appropriate summary statistics over time, using the same 
definitions given above. 

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9.4.3 Safety Analyses 
All safety data (eg, Holter ECG monitoring, 12-lead ECG, OCT, PFT, and PE) will be listed and 
summarized using descriptive statistics. Separate summaries of safety data will be provided for the 
Induction, the LTE, and the OLE Treatment Periods. Additional details regarding analyses of the 
safety data (eg, Holter ECG monitoring, 12-lead ECG, OCT, PFT, and PE) will be provided in the 
SAP. 
Treatment-emergent AEs are defined as AEs that first occurred or worsened in severity after the 
first administration of study treatment and prior to 30 days after the last administration of study 
treatment. 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities. For each 
study treatment, numbers of TEAEs and incidence rates will be tabulated by Preferred Term and 
System Organ Class. 
Treatment-emergent AEs by maximum severity, TEAEs by relationship to study treatment, SAEs, 
TEAEs leading to death, and TEAEs leading to discontinuation of study treatment will be tabulated 
for each treatment group. Commonly occurring TEAEs in either treatment group will be 
summarized using descriptive statistics. 
All central laboratory test results, vital signs measurements, ECG results, and weight 
measurements will be summarized for each treatment group using descriptive statistics at each 
visit for raw numbers and change from baseline. The incidence of treatment-emergent abnormal 
laboratory, vital sign, and ECG values will also be summarized using descriptive statistics. 
Incidence of AEs including pulmonary dysfunction and macular edema, as well as abnormalities 
in clinical laboratory assessments, vital signs, Holter ECG monitoring, 12-lead ECG, and PE will 
also be summarized.  
9.4.4 Other Analyses 
9.4.4.1 Pharmacokinetics Analyses 
Full details of PK analysis will be provided in a PK Analysis Plan. 
9.4.4.2 Biomarker Analyses 
Biomarker analyses refer to assessment of efficacy-related (Section 8.3.3) and exploratory 
efficacy-related biomarkers (Section 9.4.1.3) as it relates to treatment with VTX002. Observed 
biomarker results and change from baseline results will be summarized by treatment and scheduled 
time, where appropriate, for the biomarker analysis set(s). Graphic presentations of biomarker 
results (and/or change from baseline results) by treatment and scheduled time may be prepared for 
select biomarkers of interest. Treatment differences in biomarker response may also be explored 

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using inferential analyses, if warranted by the data. Further details on any planned biomarker 
analyses and graphic presentations will be provided in the Biomarker Analysis Plan. 
9.4.4.3 Subgroup Analyses 
Subgroup analyses using biologic/JAK inhibitor prior status (Yes or No), baseline corticosteroid 
use (Yes or No), and baseline disease activity (MMS 4-6 or 7-9) will be performed. 
All other subgroup analyses will be further described in the SAP. 
9.4.5 Missing Data 
Participants who discontinue treatment will be followed up as participants who do not discontinue 
treatment, unless consent is withdrawn. A detailed discussion of estimands, intercurrent events, 
and handling of missing data will be presented in the SAP. 
9.4.6 Sensitivity Analyses 
Sensitivity and supportive analyses based on estimands, intercurrent events, and missing data 
imputation methods are discussed in the SAP. 
9.4.7 Timing of Analyses 
After all randomized participants either complete the Induction Treatment Period or discontinue 
study drug, an interim database lock, treatment unblinding, and subsequent interim statistical 
analysis will be triggered. All data for the 13-week double-blind Induction Treatment Period will 
be analyzed following an interim database lock (Induction Period Analysis). As the primary 
efficacy endpoint and all the key secondary efficacy endpoints are measured at Week 13, the 
Induction Period Analysis will be the final analysis of the primary efficacy and key secondary 
efficacy endpoints. 
After the last participant completes the study, data accumulated over the entire study will be 
presented in summaries and listings.  
Detailed descriptions of the primary, supportive, and sensitivity analyses for each unique database 
lock will be given in the SAP. 
9.5 
Data Monitoring Committee 
An independent Data Monitoring Committee (DMC) will be utilized to monitor the safety of 
participants and to enhance the integrity and credibility of the study. The roles and responsibilities 
of the DMC are described in detail in the DMC Charter. 
The DMC will abide by the principles set forth in the FDA Guidance for Industry, Clinical Trial 
Sponsors, Establishment and Operation of Clinical Trial Data Monitoring Committees 
(FDA 2006). As part of its role, the DMC will conduct reviews of accumulating safety and efficacy 

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data at specified intervals during the conduct of the trial, according to the guidelines detailed in 
the DMC Charter. DMC recommendations to the Study Team will be communicated in a blinded 
fashion (ie, treatment assignment for individual participants will not be shared). To ensure the 
scientific integrity of the study, members of the DMC will not be directly involved in the ongoing 
management of the study. 
In addition to members of the DMC, an independent statistician responsible for interacting with 
the DMC will have access to unblinded study data. This statistician will not be directly involved 
in the conduct of the study.  
 

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10.0 REFERENCES 
1. Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol. 
2010;28:573-621. 
2. Mowat C, Cole A, Windsor A, et al. Guidelines for the management of inflammatory bowel 
disease in adults. Gut. 2011;60(5):571-607. 
3. Roda G, Jharap B, Neeraj N, Colombel J. Loss of response to anti-TNFs: definition, 
epidemiology, and management. Clin Transl Gastroenterol. 2016;7(1): e135. 
4. Ungar B, Kopylov U. Advances in the development of new biologics in inflammatory bowel 
disease. Ann Gastroenterol. 2016;29(3):243-8. 
5. Camm J, Hla T, Bakshi R, Brinkmann V. Cardiac and vascular effects of fingolimod: 
mechanistic basis and clinical implications. Am Heart J. 2014;168(5):632-44.  
6. Phase 1 Clinical Study Report. A Phase 1, Single-Center, Double-Blind, Placebo-Controlled, 
Safety and Pharmacokinetics Study of OPL002 in Healthy Volunteers. Version 1.0, 
30 September 2019. 
7. Investigator’s Brochure for OPL002 [now VTX002], version 2.2, dated 11 July 2020. 
8. Sandborn WJ, Feagan BG, Wolf DC, et al. Ozanimod induction and maintenance treatment 
for ulcerative colitis. N Engl J Med. 2016;374;1754-62. 
9. Sandborn WJ, Peyrin-Biroulet L, Zhang J, et al. Efficacy and safety of etrasimod in a Phase 2 
randomized trial of patients with ulcerative colitis. Gastroenterol. 2020;158;550-61. 
10. Geboes K, Riddell R, Öst A, Jensfelt B, Persson T, Löfberg R. A reproducible grading scale 
for histological assessment of inflammation in ulcerative colitis. Gut. 2000;47(3):404-9. 
11. Marchal-Bressenot A, Salleron J, Boulagnon-Rombi C, et al. Development and validation of 
the Nancy histological index for UC. Gut. 2017;66(1):43-9. 
12. Mosli MH, Feagan BG, Zou G, et al. Development and validation of a histological index for 
UC. Gut. 2017;66(1):50-8. 

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11.0 APPENDICES 
 
 

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Appendix 1 
Abbreviations 
Abbreviation 
Definition 
β-hCG 
beta-human chorionic gonadotropin 
5-ASA 
5-aminosalicylic acid 
6-MP 
6 mercaptopurine 
AE 
adverse event 
AESI 
adverse event of special interest 
AIDS 
acquired immune deficiency syndrome 
ALC 
absolute lymphocyte count 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
ANCOVA 
analysis of covariance 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
AUC(0–24) 
area under the concentration-time curve of the analyte in the sampled 
matrix from zero (predose) to 24 hours 
AUC(0-t) 
area under the concentration-time curve of the analyte in the sampled 
matrix from zero (predose) to time ‘t’ 
AUC(0–∞) 
area under the concentration-time curve of the analyte in the sampled 
matrix from zero (predose) to infinity 
AV 
atrioventricular 
AZA 
azathioprine 
BCRP 
breast cancer resistance protein 
BP 
blood pressure 
bpm 
beats per minute 
CBC 
complete blood count 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
Cmax 
observed maximum analyte concentration in the sampled matrix 
CMH 
Cochran-Mantel-Haenszel 
CRO 
contract research organization 
CRP 
C-reactive protein 
CV 
coefficient of variation 
DLCO 
diffusing capacity of the lungs for carbon monoxide 

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Abbreviation 
Definition 
DMC 
Data Monitoring Committee 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
eCRF 
electronic Case Report Form 
EDC 
electronic data capture database 
eDiary 
electronic diary 
eGFR 
estimated glomerular filtration rate 
EOT 
end of treatment  
ES 
endoscopic subscore 
ET 
early termination 
FAS 
Full Analysis Set 
FAS-ET 
Full Analysis Set-Extension Treatment 
FCP 
fecal calprotectin 
FEV1 
forced expiratory volume in 1 second 
FVC 
forced vital capacity 
GCP 
Good Clinical Practice 
HbA1c 
hemoglobin A1c 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HEMI 
histologic-endoscopic mucosal improvement 
HIV 
human immunodeficiency virus 
HR 
heart rate 
HRQoL 
health-related quality of life 
IBDQ 
Inflammatory Bowel Disease Questionnaire 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
Ig 
immunoglobulin 
IL 
interleukin 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
IV 
intravenous 

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Abbreviation 
Definition 
IWRS 
interactive web response system 
JAK 
Janus kinase 
LTE 
Long-Term Extension 
MAD 
multiple ascending dose 
MCS 
Mayo Clinic score 
mFAS 
modified Full Analysis Set 
MMS 
modified Mayo score 
MMX 
extended release tablets 
NSAID 
nonsteroidal anti-inflammatory drug 
OCT 
optical coherence tomography 
OLE 
Open-Label Extension 
 
 
PE 
physical examination 
PFT 
pulmonary function test 
PGA 
Physician’s Global Assessment 
P-gp 
P-glycoprotein 
PK 
pharmacokinetic 
PML 
progressive multifocal leukoencephalopathy 
PMS 
partial Mayo score 
QD 
once daily 
QTcF 
Fridericia’s corrected QT interval 
RB 
rectal bleeding 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
S1P 
sphingosine-1-phosphate 
S1PR 
sphingosine-1-phosphate receptor  
SAD 
single ascending dose 
SAE 
serious adverse event 
Safety-ET 
Safety-Extension Treatment 
SAP 
Statistical Analysis Plan 
SD 
standard deviation 
SF 
stool frequency 
SoA 
Schedule of Activities 
SUSAR 
suspected unexpected serious adverse reaction 

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Abbreviation 
Definition 
TB 
tuberculosis 
 
 
TEAE 
treatment-emergent adverse event 
Tmax 
time of maximum analyte concentration (Cmax) 
TNF 
tumor necrosis factor  
UC 
ulcerative colitis 
ULN 
upper limit of normal 
WBC 
white blood cell 

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Appendix 2 
Regulatory, Ethical, and Study Oversight Considerations 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the Declaration 
of Helsinki and Council for International Organizations of Medical Sciences International 
Ethical Guidelines. 
• Applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) 
Guidelines. 
• Applicable laws and regulations. 
The protocol, protocol amendments, ICF, Investigator Brochure, and other relevant documents 
(eg, advertisements) must be submitted to an IRB/IEC by the Investigator and reviewed and 
approved by the IRB/IEC before the study is initiated. 
Any amendments to the protocol will require IRB/IEC and regulatory authority approval, when 
applicable, before implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to participants. 
The Investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by the 
IRB/IEC. 
• Notifying the IRB/IEC of SAEs or other significant safety findings as required by IRB/IEC 
procedures. 
• Providing oversight of the conduct of the study at the study center and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/IEC, 
European regulation 536/2014 for clinical studies (if applicable), and all other applicable 
local regulations. 
After reading the protocol, each Investigator will sign the protocol signature page (Appendix 9). 
The study will not start at any study center at which the Investigator has not signed the protocol. 
Financial Disclosure 
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 

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Insurance 
The Sponsor has obtained liability insurance, which covers this study as required by local law 
and/or national regulations and/or ICH guidelines, whichever is applicable. The terms of the 
insurance will be kept in the study files. 
Informed Consent Process 
The Investigator or his/her authorized representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions regarding the 
study. 
Participants must be informed that their participation is voluntary. Participants or their legally 
authorized representative will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act requirements, where applicable, and the IRB/IEC or study center. 
The medical record must include a statement that written informed consent was obtained before 
the participant was entered in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
Participants must be re-consented to the most current version of the ICF(s) as applicable during 
their participation in the study. 
A copy of the ICF(s) must be provided to the participant or the participant’s legally authorized 
representative. 
Participants who are rescreened are required to sign a new ICF. 
The ICF will contain a separate section that addresses the use of remaining mandatory samples for 
optional exploratory research. The Investigator or authorized designee will explain to each 
participant the objectives of the exploratory research. Participants will be told that they are free to 
refuse to participate and may withdraw their consent at any time and for any reason during the 
storage period. A separate signature will be required to document a participant’s agreement to 
allow any remaining specimens to be used for exploratory research. Participants who decline to 
participate in this optional research will not provide this separate signature. 
Data Protection 
Participants will be assigned a unique identifier by the Sponsor. Any participant records or datasets 
that are transferred to the Sponsor will contain the identifier only; participant names or any 
information which would make the participant identifiable will not be transferred. 

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The participant must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant. 
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by appropriate 
IRB/IEC members, and by inspectors from regulatory authorities. 
Dissemination of Clinical Study Data 
The results of the study should be reported within 1 year from the end of the clinical study. 
Irrespective of the outcome, the Sponsor will submit to the European Union database a summary 
of the results of the clinical study within 1 year from the end of the clinical study. It shall be 
accompanied by a summary written in a manner that is understandable to laypersons. 
Data Quality Assurance 
All participant data relating to the study will be recorded on printed or eCRFs unless transmitted 
to the Sponsor or designee electronically (eg, laboratory data). The Investigator is responsible for 
verifying that data entries are accurate and correct by physically or electronically signing the 
eCRF. 
The Investigator must maintain accurate documentation (source data) that supports the information 
entered in the eCRF. 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
The Sponsor or its representative may conduct audits at the investigative sites including, but not 
limited to, drug supply, presence of required documents, the informed consent process, and 
comparison of eCRFs with source documents. All medical records (progress notes) must be 
available for audit. The Investigator agrees to participate with audits conducted at a convenient 
time in a reasonable manner. 
Government regulatory authorities may also inspect the Investigator during or after the study. The 
Investigator or designee should contact the Sponsor/CRO immediately if this occurs. He/she must 
cooperate fully with regulatory authorities or other audits conducted at a convenient time in a 
reasonable manner. The purpose of an audit is to assess whether ethics, regulatory, and quality 
requirements are fulfilled. 
Study monitors will perform ongoing source data verification to confirm that data entered into the 
eCRF by authorized study center personnel are accurate, complete, and verifiable from source 

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documents; that the safety and rights of participants are being protected; and that the study is being 
conducted in accordance with the currently approved protocol and any other study agreements, 
ICH GCP, and all applicable regulatory requirements. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the Investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the Sponsor. No records may be transferred to 
another location or party without written notification to the Sponsor. 
Source Documents 
The Investigator/institution should maintain adequate and accurate source documents and study 
records that include all pertinent observations on each of the study center’s participants. Source 
data should be attributable, legible, contemporaneous, original, accurate, and complete. Changes 
to source data should be traceable, should not obscure the original entry, and should be explained 
if necessary (eg, via an audit trail). 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the Investigator’s study center. 
Data entered in the eCRF that are transcribed from source documents must be consistent with the 
source documents or the discrepancies must be explained. The Investigator may need to request 
previous medical records or transfer records, depending on the study. Also, current medical records 
must be available. 
Definition of what constitutes source data can be found in the Study Manual. 
Study and Study Center Closure 
The Sponsor designee reserves the right to close the study center or terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Study centers will be closed upon study 
completion. A study center is considered closed when all required documents and study supplies 
have been collected and a study center closure visit has been performed. 
The Investigator may initiate study center closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study center by the Sponsor or Investigator may include but are 
not limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the Sponsor’s procedures, or GCP guidelines. 
• Inadequate recruitment of participants by the Investigator. 
• Discontinuation of further study treatment development. 

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Publication Policy 
The data generated by this study are confidential information of the Sponsor. The Sponsor will 
make the results of the study publicly available. The publication policy with respect to the 
Investigator and study center will be set forth in the Clinical Trial Agreement. 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the Investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. 
This allows the Sponsor to protect proprietary information and to provide comments. 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual study center data. In this case, a 
Coordinating Investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 

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Appendix 3 
Clinical Laboratory Tests 
The tests detailed in Table 11 will be performed by the central laboratory. 
Local laboratory results are only required in the event that the central laboratory results are not 
available in time for either study drug administration and/or response evaluation. If a local sample 
is required, it is important that the sample for central analysis is obtained at the same time. 
Additionally, if the local laboratory results are used to make either a study treatment decision or 
response evaluation, the results must be entered into the eCRF. 
Protocol-specific requirements for inclusion or exclusion of participants are detailed in Section 5.0 
of the protocol. 
Additional tests may be performed at any time during the study as determined necessary by the 
Investigator or required by local regulations. All laboratory tests with values considered clinically 
significantly abnormal during participation in the study or within 14 days after the last dose of 
study treatment should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the Investigator or Medical Monitor. 
Investigators must document their review of each laboratory safety report. 
Laboratory/analyte results that can unblind the study will not be reported to study centers or other 
blinded personnel until the study has been unblinded. 
Table 11 
Clinical Laboratory Tests 
SCREENING Only 
Virology 
HIV, HBsAg, HCV (RIBA), QuantiFERON 
Stool Sample 
Bacterial culture, ova and parasites, C. difficile 
Drug of Abuse 
Amphetamine, barbiturates, benzodiazepines, cocaine, methadone, methamphetamine, 
methylenedioxymethamphetamine, opiate, oxycodone, phencyclidine, if and where available 
Others  
Hemoglobin A1c 
PREGNANCY TESTING 
Pregnancy Testing 
Serum pregnancy test for β-hCG – Screening, and if any urine pregnancy test is positive 
Urine β-hCG (only for woman of childbearing potential), including home pregnancy testing, as applicable 

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a) 
Total WBC, differentials, lymphocyte, neutrophil, 
, fecal calprotectin, and CRP will be blinded as defined in 
Section 6.8. Total WBC, neutrophil, lymphocyte, CD4 T-cell counts, fecal calprotectin, and CRP will be reviewed by an 
unblinded Medical Monitor who will provide instructions to the site Investigator in the event of significant lymphopenia 
(Section 8.3.3). Participants, Investigators, study staff, and study vendors are to remain blinded to the identity of the 
treatment during the double-blind Induction Treatment Period, LTE Treatment Period, and the first 4 weeks of the OLE 
Treatment Period. The Sponsor are blinded to the blinded results until the interim database lock and unblinding for the 
Induction Treatment Period is completed. 
b) 
Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping or monitoring 
event are given in Section 6.6. An increase in AST or ALT > 3 × ULN should be followed by repeat testing within 72 hours 
of receiving results to confirm the abnormality and determine whether AST or ALT is increasing or decreasing. All events 
of ALT or AST > 3 × ULN and total bilirubin > 2 × ULN (> 35% direct bilirubin), or ALT or AST > 3 × ULN and 
INR > 1.5, if INR measured, which may indicate severe liver injury (possible Hy’s Law), must be reported as an SAE. 
c) 
eGFR will be calculated each time the serum creatinine is tested. 
 
 
  

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Appendix 4 
Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting 
See Section 8.5 for additional information regarding AEs and SAEs. 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a participant, temporally associated with the use of 
study treatment, whether or not considered related to the study treatment. 
• 
NOTE: 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 
study treatment. 
Events Meeting the AE Definition  
• 
Any abnormal laboratory test results (hematology, clinical chemistry, coagulation, or urinalysis) or 
other safety assessments (eg, ECG, radiological scans, vital signs measurements), including those that 
worsened from baseline, considered clinically significant in the medical and scientific judgment of the 
Investigator (ie, not related to progression of underlying disease) 
• 
Exacerbation of a chronic or intermittent preexisting condition including either an increase in 
frequency and/or intensity of the condition 
• 
New conditions detected or diagnosed after study drug administration even though it may have been 
present before the start of the study 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study treatment or a 
concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an intentional 
overdose taken with possible suicidal/self-harming intent. Such overdoses should be reported 
regardless of sequelae. 
• 
“Lack of efficacy” or “failure of expected pharmacological action” per se will not be reported as an AE 
or SAE. Such instances will be captured in the efficacy assessments. However, the signs, symptoms, 
and/or clinical sequelae resulting from lack of efficacy will be reported as AE or SAE if they fulfill the 
definition of an AE or SAE. 
Events NOT Meeting the AE Definition  
• 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments which are 
associated with the underlying disease, unless judged by the Investigator to be more severe than 
expected for the participant’s condition. Medical occurrences that begin before the start of study 
treatment but after obtaining informed consent will be recorded on the Medical History/Current 
Medical Conditions section of the eCRF, not the AE section. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of the disease/disorder 
being studied, unless more severe than expected for the participant’s condition 
• 
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the 
procedure is the AE 
• 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital) 
• 
Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present or detected at the 
start of the study that do not worsen 
 

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Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
An SAE is defined as any untoward medical occurrence that, at any dose: 
a) Results in death 
b) Is life-threatening 
The term “life-threatening” in the definition of “serious” refers to an event in which the participant 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 inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or outpatient 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 preexisting condition that did not worsen from baseline is not 
considered an AE. 
d) Results in persistent disability/incapacity 
• 
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 (eg, sprained 
ankle), which may interfere with or prevent everyday life functions but do not constitute a substantial 
disruption. 
e) Is a congenital anomaly/birth defect 
f) 
Other situations: 
• 
Medical or scientific judgment should be exercised in deciding whether SAE reporting is appropriate 
in other situations, such as important medical events that may not be immediately life-threatening or 
result in death or hospitalization but may jeopardize the participant or may require medical or surgical 
intervention to prevent one of the other outcomes listed in the above definition. These events should 
usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive treatment in an emergency 
room or at home for allergic bronchospasm, blood dyscrasias, convulsions that do not result in 
hospitalization, or development of drug dependency or drug abuse. 

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Recording and Follow-Up of AE and/or SAE 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all documentation (eg, 
hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
• 
The Investigator will then record all relevant AE/SAE information in the eCRF. Each event must be 
recorded separately. 
• 
It is not acceptable for the Investigator to send photocopies of the participant’s medical records to the 
Sponsor in lieu of completion of the AE/SAE eCRF page. 
• 
There may be instances when copies of medical records for certain cases are requested by the Sponsor. 
In this case, all participant identifiers, with the exception of the participant number, will be redacted on 
the copies of the medical records before submission to the Sponsor. 
• 
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, and/or 
other clinical information. Whenever possible, the diagnosis (not the individual signs/symptoms) will 
be documented as the AE/SAE. 
Assessment of Severity 
The Investigator will make an assessment of severity for each AE and SAE reported during the study 
according to the Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v5.0): 
• 
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention 
not indicated. 
• 
Grade 2: Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate 
instrumental activities of daily living (ADL). 
• 
Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling, limiting self-care ADL (eg, preparing meals, 
shopping for groceries or clothes, using the telephone, managing money). 
• 
Grade 4: Life-threatening consequences, urgent intervention indicated. 
• 
Grade 5: Death related to AE. 
An event is defined as “serious” when it meets at least one of the predefined outcomes as described in the 
definition of an SAE, NOT when it is rated as severe. 
Assessment of Causality 
• 
The relationship of each AE to the investigational products will be assessed by the Investigator or 
Sub-Investigator on the basis of his/her clinical judgment and the following definitions: 
o 
Related: 
 
The AE follows a reasonable temporal sequence from investigational product 
administration and cannot be reasonably explained by the participant’s clinical state 
or other factors (eg, disease under study, concurrent diseases, or concomitant 
medications). 
 
The AE follows a reasonable temporal sequence from investigational product 
administration and represents a known reaction to the investigational product or 
other drugs in its class or is predicted by the known pharmacological properties of 
the drug. 
 
The AE resolves with discontinuation of the investigational product and/or recurs 
with re-challenge, if applicable. 
o 
Not Related: 
 
The AE does not follow a reasonable temporal sequence from investigational product 
administration or can be reasonably explained by the participant’s clinical state or 

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other factors (eg, disease under study, concurrent diseases, and concomitant 
medications). 
• 
The Investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as well 
as the temporal relationship of the event to study drug administration will be considered and 
investigated. 
• 
The Investigator will also consult the Investigator’s Brochure and/or Product Information, for 
marketed products, in his/her assessment. 
• 
For each AE/SAE, the Investigator must document in the medical notes that he/she has reviewed the 
AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred and the Investigator has minimal information to 
include in the initial report to the Sponsor. However, it is very important that the Investigator always 
make an assessment of causality for every event before the initial transmission of the SAE data to the 
Sponsor. 
• 
The Investigator may change his/her opinion of causality in light of follow-up information and send an 
SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
Follow-Up of AEs and SAEs 
• 
The Investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by the Sponsor or designee to elucidate the 
nature and/or causality of the AE or SAE as fully as possible. This may include additional laboratory 
tests or investigations, histopathological examinations, or consultation with other health care 
professionals. 
• 
If a participant dies during participation in the study or during a recognized Follow-Up Period, the 
Investigator will provide the Sponsor or designee with a copy of any postmortem findings, including 
histopathology. 
• 
New or updated information will be recorded in the originally completed eCRF. 
• 
The Investigator will submit any updated SAE data to the Sponsor or designee within 24 hours of 
receipt of the information. 
Reporting of SAEs 
SAE Reporting to the Sponsor or designee via an Electronic Data Collection Tool 
• 
The primary mechanism for reporting an SAE to the Sponsor or designee will be the electronic data 
collection tool. If the electronic system is unavailable for more than 24 hours, then the study center 
will use the paper SAE data collection tool. 
• 
The study center will enter the SAE data into the electronic system as soon as it becomes available. 
• 
After the study is completed at a given study center, the electronic data collection tool will be taken 
off-line to prevent the entry of new data or changes to existing data. 
• 
If a study center receives a report of a new SAE from a participant or receives updated data on a 
previously reported SAE after the electronic data collection tool has been taken off-line, then the study 
center can report this information on a paper SAE form or to the Sponsor or designee by telephone.  
• 
After the whole study is completed or terminated, an SAE should be reported directly to the Sponsor.  
• 
Contacts for SAE reporting can be found in the Study Manual. 

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Appendix 5 
Collection of Pregnancy Information 
Male participants with partners who become pregnant 
The Investigator will attempt to collect pregnancy information on any male participant’s female 
partner who becomes pregnant while the male participant is in this study.  
After obtaining the necessary signed informed consent from the pregnant female partner directly, 
the Investigator will record pregnancy information on the appropriate form and submit it to the 
Sponsor within 24 hours of learning of the partner’s pregnancy. The female partner will also be 
followed to determine the outcome of the pregnancy. Information on the status of the mother and 
child will be forwarded to the Sponsor. Pregnant partners should be followed until 12 months after 
their delivery date for outcomes of both the mother and child. Any termination of the pregnancy 
will be reported regardless of fetal status (presence or absence of anomalies) or indication for the 
procedure. 
Female participants who become pregnant 
The Investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate form 
and submitted to the Sponsor or designee within 24 hours of learning of a participant’s pregnancy. 
The participant will be followed to determine the outcome of the pregnancy and for 1 year after 
delivery for evaluation of outcomes of both the mother and child. The Investigator will collect 
follow-up information (may be conducted by telephone) on the mother and child and the 
information will be forwarded to the Sponsor. Any termination of pregnancy will be reported, 
regardless of fetal status (presence or absence of anomalies) or indication for the procedure. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous abortion is 
always considered to be an SAE and will be reported as such. 
Any poststudy pregnancy-related SAE considered reasonably related to the study treatment by the 
Investigator will be reported to the Sponsor as described in Section 8.5.5. While the Investigator 
is not obligated to actively seek this information in former participants, he or she may learn of an 
SAE through spontaneous reporting. 
Any female participant who becomes pregnant while participating in the study will discontinue 
study treatment or be withdrawn from the study. 

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Appendix 6 
Mayo Scoring System for Assessment of Ulcerative Colitis 
Activity – Sample 
The Mayo score ranges from 0 to 12, with higher scores indicating more severe disease. 
Stool frequency: Each participant serves as his or her own control to establish the degree of 
abnormality of the SF. 
0 = Normal number of stools for this participant 
1 = 1 to 2 stools more than normal 
2 = 3 to 4 stools more than normal 
3 = 5 or more stools more than normal 
Subscore: 0 to 3 
Rectal bleeding: The daily bleeding score represents the most severe bleeding of the day. 
0 = No blood seen 
1 = Streaks of blood with stool less than half the time 
2 = Obvious blood with stool most of the time 
3 = Blood alone passes 
Subscore: 0 to 3 
Findings on endoscopy: The endoscopy subscore will be determined by qualified personnel at a 
central laboratory. 
0 = Normal or inactive disease 
1 = Mild disease (erythema, decreased vascular pattern) 
2 = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions) 
3 = Severe disease (spontaneous bleeding, ulceration) 
Subscore: 0 to 3 
Physician’s Global Assessment: The Physician’s Global Assessment acknowledges the 3 other 
criteria, the participant’s daily recollection of abdominal discomfort and general sense of 
well-being, and other observations, such as physical findings and the participant’s performance 
status. 
0 = Normal 

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1 = Mild disease 
2 = Moderate disease 
3 = Severe disease 
Subscore: 0 to 3 

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Appendix 7 
Histological Scoring Indices 
Geboes Grading System 
The Geboes Grading System is a stepwise grading system used for the evaluation of microscopic 
inflammation and histopathologic disease activity in UC. The microscopic appearance of the 
mucosa is categorized into 6 grades. A decrease of the Geboes Score grading system to Grade zero 
(0) or one (1) indicates mucosal healing.10 
Nancy Histological Index 
The Nancy Histological Index is a validated index for assessing histological disease activity in UC. 
It is composed of 3 histological items defining 5 grades of disease activity: absence of significant 
histological disease (Grade 0), chronic inflammatory infiltrate with no acute inflammatory 
infiltrate (Grade 1), mildly active disease (Grade 2), moderately active disease (Grade 3), and 
severely active disease (Grade 4). The presence of ulceration on the biopsy specimen corresponds 
to severely active disease (Grade 4). If there is no ulceration, acute inflammatory cells infiltrate 
(presence of neutrophils) is assessed. Moderate or severe acute inflammatory cells infiltrate 
corresponds to moderately active disease (Grade 3), while mild acute inflammatory cells infiltrate 
correspond to mildly active disease (Grade 2). If there is no acute inflammatory cells infiltrate, 
assessment of chronic inflammatory infiltrate (lymphocytes and plasmacytes) is made. A biopsy 
specimen showing moderate or marked chronic inflammatory infiltrate corresponds to moderate 
or marked chronic acute inflammatory infiltrate (Grade 1). A biopsy specimen showing mild or no 
chronic inflammatory infiltrate corresponds to absence of significant histological disease 
(Grade 0).11 
Robarts Histopathology Index 
The Robarts Histopathology Index (RHI) is an evaluative index, derived from the Geboes score, 
that is designed to be reproducible and responsive to clinically meaningful change in disease 
activity over time. The total RHI score ranges from 0 (no disease activity) to 33 (severe disease 
activity) and is calculated as follows: RHI = 1 × Chronic inflammatory infiltrate + 2 × Lamina 
propria neutrophils + 3 × Neutrophils in epithelium + 5 × Erosion or ulceration.12 

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Appendix 9 
Signature of Investigator 
PROTOCOL TITLE: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, 
Parallel-Group Study to Evaluate the Clinical Efficacy and Safety of VTX002 in Subjects with 
Moderately to Severely Active Ulcerative Colitis 
PROTOCOL NO: 
VTX002-201 
VERSION:  
 
Protocol Version 6.0 
This protocol is a confidential communication of Oppilan Pharma, Ltd. I confirm that I have read 
this protocol, I understand it, and I will work according to this protocol. I will also work 
consistently with the ethical principles that have their origin in the Declaration of Helsinki and that 
are consistent with Good Clinical Practices and the applicable laws and regulations. Acceptance 
of this document constitutes my agreement that no unpublished information contained herein will 
be published or disclosed without prior written approval from Ventyx Biosciences, Inc. 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
 
 
 
 
Investigator signature 
 
Date 
 
 
Printed name, title, and study center