A Phase 2, Randomized, Double-blind, Placebo-controlled, Multi-center Study to Evaluate GB004 in Adult Subjects With Mild-to-moderate Active Ulcerative Colitis
Phase: PHASE2
Conditions: Ulcerative Colitis
Sponsor: GB004, Inc.

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Protocol GB004-2101, Version 3.0, Amendment 2.0, 15 December 2021 
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CLINICAL STUDY PROTOCOL 
 
Protocol Title:  
A Phase 2, randomized, double-blind, placebo-controlled, multi-center 
study to evaluate GB004 in adult subjects with mild-to-moderate active 
ulcerative colitis 
Short Title: 
GB004 in adult subjects with active ulcerative colitis 
Protocol Number:  
GB004-2101 
Compound Number:  
GB004 
Study Phase:  
Phase 2 
 
Sponsor Name: 
GB004, Inc. 
Legal Registered 
Address: 
3013 Science Park Road 
San Diego, CA 92121, USA 
Regulatory Agency 
Identifier Number(s): 
IND Number: 133519 
EudraCT: 
2020-002306-12 
Version: 
3.0, Amendment 2.0 
Approval Date: 
15 December 2021 
 
Confidential 
This document contains proprietary and confidential information of GB004, Inc. Acceptance of 
this document constitutes agreement by the recipient that no previously unpublished information 
contained herein will be published or disclosed without the prior written approval of GB004, Inc. 
The following exceptions may occur under the condition that the party has agreed to keep this 
information confidential: 1) disclosure of information to the extent necessary to obtain informed 
consent, 2) disclosure of the document to study personnel under your supervision who need to 
know the contents for conducting the study, and 3) disclosure of the document to appropriate 
Institutional Review Boards (IRB)/Independent Ethics Committees (IEC). The foregoing shall not 
apply to disclosure required by governmental regulations or laws; however, GB004, Inc. shall be 
promptly notified of any such disclosure. 
 

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INVESTIGATOR AGREEMENT 
GB004-2101: A Phase 2, randomized, double-blind, placebo-controlled, multi-center study to 
evaluate GB004 in adult subjects with mild-to-moderate active ulcerative colitis. 
I, the undersigned, have read this protocol and agree to conduct this protocol in accordance with 
ethical principles as outlined in the International Council for Harmonisation (ICH) guidelines on 
Good Clinical Practice (GCP), any applicable laws and requirements and any additional 
conditions mandated by a regulatory authority and/or Institutional Review Board/Independent 
Ethics Committee (IRB/IEC). 
I acknowledge that I am responsible for the overall study conduct and I agree to personally 
conduct or supervise the described clinical study. 
I agree to ensure that the confidential information contained in this document will not be used for 
any purpose other than the evaluation or conduct of the clinical investigation without the prior 
written consent of GB004, Inc. 
 
 
 
 
Signature 
 
 
 
Name of Investigator 
 
Date 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
Amendment 2.0 (v3.0) 
15 December 2021 
Amendment 1.0 (v2.0) 
21 October 2020 
Original Protocol (v1.0) 
27 July 2020 
Amendment 2.0 (v3.0, 15 December 2021) 
Overall Rationale for the Amendment: 
The purpose of this amendment is primarily to make updates to Section 6.8 (Concomitant 
Medications) and Appendix 6 (Prohibited Medications). 
Table 1: 
Summary of Changes 
Section # and Name 
Description of Change 
Brief Rationale 
6.8 Concomitant Therapy 
 
Guidance has been added 
regarding the use of sensitive 
clinical substrates of OCT2 
and CYP2C8 with GB004. 
Results from in vitro studies indicate 
that a glucuronide metabolite of 
GB004, GBD242, may be an inhibitor 
of OCT2 and CYP2C8.  
Appendix 6 
Added dofetilide and 
sensitive substrates of 
CYP2C8 to Prohibited 
Medications.  
Concomitant use of dofetilide, which is 
contraindicated when used with OCT2 
inhibitors, is prohibited in this study. 
Concomitant use of sensitive substrates 
of CYP2C8 (eg, repaglinide, 
rosiglitazone, pioglitazone, and 
loperamide) is prohibited in this study. 
1.3.2 Open-Label Extension 
– Schedule of Activities   
Added Physician’s Global 
Assessment (PGA) at the 
OLE Follow-up visit. 
This assessment should occur at the 
OLE Follow-up visit. 
1.2 Study Schema 
Edited text in study schema 
for consistency with protocol 
text.  
For overall clarity and alignment with 
protocol text. 
4.1.2 OLE (24 Weeks) 
Added text “(if last dose of 
PCP IP has not been taken 
earlier in the day)” to the 
second sentence of the second 
paragraph. 
The change was made for clarity. 
5.2 Exclusion Criterion #22 
Estimated glomerular 
filtration rate (eGFR) was 
corrected to read 
< 60 mL/min/1.73 m2. 
Change was made to correct an earlier 
oversight.  

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9.4.1.1 Efficacy Analysis, 
Secondary Endpoints 
The second sentence was 
updated to read: Histologic 
remission at PCP Week 12 
and mucosal healing at PCP 
Week 12 will be evaluated 
among subjects with Baseline 
lamina propria neutrophils 
and neutrophils in epithelium 
RHI subscores > 0. 
Change was made to correct an earlier 
oversight.  
9.5 Interim Analysis 
1.1 Synopsis 
4.1.1 Placebo-Controlled 
Period (36 weeks) 
Text related to the optional, 
unblinded interim analysis 
was removed. 
The interim analysis is no longer 
planned.  
4.1.1 Placebo-Controlled 
Period (36 weeks) 
Removed the following 
sentence: “Subjects who 
permanently discontinue IP or 
withdraw from study during 
the PCP will not be eligible to 
enter the OLE.” 
The sentence was removed for clarity 
and because Section 4.1.2 clearly 
describes who is eligible for the OLE.  
4.1.1 Placebo-Controlled 
Period (36 weeks) 
Added text “without enrolling 
in the OLE” to the paragraphs 
discussing subjects who 
permanently discontinue IP 
and subjects who withdraw 
from the PCP. 
These changes were made for clarity. 
7.1 Discontinuation 
Added text “if the subject is 
not enrolling in the OLE” to 
the paragraph discussing 
Discontinuation of IP during 
the PCP. 
This change was made for clarity. 
Other minor corrections to grammatical or typographical errors were made that did not affect content. 

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TABLE OF CONTENTS 
INVESTIGATOR AGREEMENT...................................................................................................3 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................4 
TABLE OF CONTENTS .................................................................................................................6 
LIST OF TABLES .........................................................................................................................10 
1. 
PROTOCOL SUMMARY ..........................................................................................11 
1.1. 
Synopsis ......................................................................................................................11 
1.2. 
Study Schema .............................................................................................................15 
1.3. 
Schedule of Activities (SoA) ......................................................................................16 
1.3.1. 
Placebo-Controlled Period – Schedule of Activities ..................................................16 
1.3.2. 
Open-Label Extension - Schedule of Activities .........................................................21 
2. 
INTRODUCTION ......................................................................................................23 
2.1. 
Study Rationale ...........................................................................................................23 
2.2. 
Background .................................................................................................................23 
2.3. 
Benefit/Risk Assessment ............................................................................................25 
2.3.1. 
Benefit Assessments ...................................................................................................25 
2.3.2. 
Risk Assessments ........................................................................................................25 
2.3.3. 
Overall Benefit and Risk Conclusion .........................................................................26 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................27 
3.1. 
Placebo-Controlled Period Objectives and Endpoints ................................................27 
3.2. 
Open-Label Extension (OLE) Objectives and Endpoints ...........................................30 
3.3. 
Efficacy Endpoint Definitions ....................................................................................31 
4. 
STUDY DESIGN .......................................................................................................32 
4.1. 
Overall Study Design ..................................................................................................32 
4.1.1. 
Placebo-Controlled Period (36 weeks) .......................................................................32 
4.1.2. 
OLE (24 weeks) ..........................................................................................................33 
4.2. 
Scientific Rationale for Study Design ........................................................................33 
4.2.1. 
Study Population .........................................................................................................34 
4.2.2. 
Endpoint Selection ......................................................................................................34 
4.2.3. 
Placebo Rationale .......................................................................................................34 
4.3. 
Justification for Dose ..................................................................................................34 
4.4. 
Study Duration ............................................................................................................36 

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4.5. 
End of Study Definition ..............................................................................................36 
4.5.1. 
Placebo-Controlled Period ..........................................................................................36 
4.5.2. 
OLE .............................................................................................................................36 
5. 
ELIGIBILITY CRITERIA .........................................................................................36 
5.1. 
Inclusion Criteria ........................................................................................................36 
5.2. 
Exclusion Criteria .......................................................................................................37 
5.3. 
UC Disease Activity Criteria ......................................................................................39 
5.4. 
Screen Failures ............................................................................................................40 
6. 
INVESTIGATIONAL PRODUCT ............................................................................40 
6.1. 
Investigational Product(s) Administered ....................................................................40 
6.2. 
Preparation/Handling/Storage/Accountability ............................................................42 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................42 
6.3.1. 
Assignment of a Subject Number ...............................................................................42 
6.3.2. 
Randomization and Stratification ...............................................................................42 
6.3.3. 
Investigational Product Numbers ...............................................................................42 
6.3.4. 
Blinding ......................................................................................................................42 
6.3.5. 
Unblinding of an Individual Subject ...........................................................................43 
6.4. 
Investigational Product Compliance ...........................................................................43 
6.5. 
Dose Modification ......................................................................................................44 
6.5.1. 
Investigational Product ...............................................................................................44 
6.5.2. 
Background UC Therapy ............................................................................................44 
6.6. 
Continued Access to Investigational Product After the End of the Study ..................45 
6.7. 
Treatment of Overdose ...............................................................................................45 
6.8. 
Concomitant Therapy .................................................................................................46 
6.8.1. 
Prohibited Medications Prior to the Screening Visit and Throughout the Study .......46 
7. 
DISCONTINUATION OF INVESTIGATIONAL PRODUCT AND 
SUBJECT WITHDRAWAL FROM STUDY ............................................................47 
7.1. 
Discontinuation of Investigational Product, Subject Withdrawal from the 
Study and Stopping Rules ...........................................................................................47 
7.1.1. 
Hemoglobin, Nausea, and Dizziness Stopping Criteria ..............................................48 
7.1.2. 
QTcF Stopping Criteria ..............................................................................................48 
7.1.3. 
Liver Function: Actions and Follow-up Assessments ................................................48 
7.1.4. 
Pregnancy ...................................................................................................................48 

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7.1.5. 
Introduction of New UC Therapy Stopping Criteria ..................................................49 
7.2. 
Lost to Follow-up .......................................................................................................49 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................49 
8.1. 
Efficacy Assessments .................................................................................................50 
8.1.1. 
Clinical, Endoscopic and Histologic Assessment .......................................................50 
8.1.2. 
Mayo Score and Modified Mayo Score ......................................................................50 
8.1.3. 
Robarts Histopathology Index (RHI) Score, Geboes Score and Ulcerative 
Colitis Index-100 ........................................................................................................52 
8.2. 
Safety Assessments .....................................................................................................52 
8.2.1. 
Physical Examinations ................................................................................................52 
8.2.2. 
Vital Signs ..................................................................................................................53 
8.2.3. 
Electrocardiograms .....................................................................................................53 
8.2.4. 
Clinical Safety Laboratory Assessments ....................................................................53 
8.3. 
Adverse Events and Serious Adverse Events .............................................................54 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE Information .......................54 
8.3.2. 
Method of Detecting Aes and SAEs ...........................................................................54 
8.3.3. 
Follow-up of Aes and SAEs .......................................................................................54 
8.3.4. 
Regulatory Reporting Requirements for SAEs ...........................................................55 
8.3.5. 
Pregnancy ...................................................................................................................55 
8.3.6. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as 
Aes or SAEs ................................................................................................................55 
8.4. 
Pharmacokinetics ........................................................................................................55 
8.5. 
Pharmacodynamics and Biomarkers ...........................................................................56 
8.6. 
Pharmacogenetic .........................................................................................................56 
9. 
STATISTICAL CONSIDERATIONS .......................................................................56 
9.1. 
Statistical Hypotheses .................................................................................................56 
9.1.1. 
Placebo-Controlled Period ..........................................................................................56 
9.1.2. 
OLE .............................................................................................................................56 
9.2. 
Sample Size Determination ........................................................................................57 
9.2.1. 
Placebo-Controlled Period ..........................................................................................57 
9.2.2. 
OLE .............................................................................................................................57 
9.3. 
Populations for Analyses ............................................................................................57 
9.3.1. 
Placebo-Controlled Period ..........................................................................................57 

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9.3.2. 
OLE .............................................................................................................................57 
9.4. 
Statistical Analyses .....................................................................................................58 
9.4.1. 
PCP Week 12 Analysis ...............................................................................................58 
9.4.2. 
PCP Final Analysis .....................................................................................................59 
9.4.3. 
OLE Final Analysis ....................................................................................................59 
9.5. 
Interim Analyses .........................................................................................................60 
9.5.1. 
Data Review Committee .............................................................................................60 
10. 
APPENDICES ............................................................................................................61 
APPENDIX 1. REGULATORY, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS ..................................................................................................61 
APPENDIX 2. CLINICAL LABORATORY TESTS ................................................................65 
APPENDIX 3. ADVERSE EVENTS: DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ......................67 
APPENDIX 4. CONTRACEPTIVE GUIDANCE AND COLLECTION OF 
PREGNANCY INFORMATION ...............................................................................72 
APPENDIX 5. PHARMACOGENETICS ..................................................................................76 
APPENDIX 6. PROHIBITED MEDICATIONS ........................................................................77 
APPENDIX 7. LIVER SAFETY – ACTIONS AND FOLLOW-UP ASSESSMENTS ............78 
APPENDIX 8. INSTRUCTIONS FOR CALCULATING MAYO SCORE FOR UC 
DISEASE ACTIVITY CRITERIA ASSESSMENT ..................................................81 
APPENDIX 9. GUIDANCE TO ADDRESS A PANDEMIC OR OTHER GLOBAL 
HEALTH EMERGENCIES AND POTENTIAL IMPACT ON THE 
CLINICAL STUDY ...................................................................................................82 
APPENDIX 10. LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..................85 
APPENDIX 11. PROTOCOL AMENDMENT HISTORY ........................................................89 
11. 
REFERENCES ...........................................................................................................91 
 

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LIST OF TABLES 
Table 1: 
Summary of Changes ....................................................................................................4 
Table 2: 
Efficacy Endpoint Definitions ....................................................................................31 
Table 3: 
Investigational Product Formulation by Treatment Group .........................................41 
Table 4: 
Protocol-Required Safety Laboratory Assessments ...................................................65 
Table 5: 
Liver Safety Laboratory Assessments ........................................................................66 
Table 6: 
Liver Chemistry Criteria Requiring Additional Monitoring with Possible 
Dose Modification of Investigational Product ............................................................78 
Table 7: 
Liver Chemistry Criteria Requiring Investigational Product Interruption and 
Additional Monitoring ................................................................................................79 
Table 8: 
Instructions for Calculating Mayo Score For UC Disease Activity Criteria 
Assessments (at or after PCP Week 12 visit and prior to PCP Week 36 visit) ..........81 
 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A Phase 2, randomized, double-blind, placebo-controlled, multi-center study to 
evaluate GB004 in adult subjects with mild-to-moderate active ulcerative colitis 
Short Title: GB004 in adult subjects with active ulcerative colitis 
Rationale 
GB004 (formerly AKB-4924) is a novel small molecule in development for the treatment of 
inflammatory bowel disease (IBD). The novel approach of GB004 is based on evidence that 
hypoxia inducible factor 1 alpha (HIF-1α), a member of the hypoxia inducible factor (HIF) 
transcription factor family, has a crucial role in the maintenance of epithelial barrier integrity and 
in the modulation of the innate inflammatory response in mouse models of IBD. 
Small molecule prolyl hydroxylase inhibitors (PHDi’s) stabilize HIF-1α protein and have shown 
efficacy in multiple mouse models of IBD that include trinitrobenzene sulfonic acid (TNBS) and 
dextran sulfate sodium (DSS)-induced colitis models and the tumor necrosis factor alpha 
(TNFα)-driven terminal ileitis model (Ablin, 1999; Minaiyan, 2012). Prolyl hydroxylases (PHDs) 
are key regulators of the HIF pathway (Eltzschig, 2014). These findings support PHD inhibition 
as a target for treating ulcerative colitis (UC). 
GB004, a HIF-1α stabilizer, is being developed as an oral therapeutic, gut-targeted treatment for 
UC with higher intestinal than systemic exposure. The relatively low oral bioavailability (< 20%) 
and preferential distribution to the gastrointestinal (GI) tissues observed in nonclinical studies, 
combined with its mechanism of action in gut lumen and positive effects on gut healing and 
inflammation in animal models of colitis, provide rationale for further development in human 
subjects. 
GB004 has been shown in studies of both healthy volunteers (AKB-4924-CI-1001, 
AKB-4924-CI-1002, and GB004-1902) and patients with UC (GB004-1101) to be a gut-targeted 
treatment with higher intestinal than systemic exposure. In addition, the GB004-1101 study, 
although limited by only 4 weeks of dosing, showed trends in improvement in clinical and 
histologic outcomes in UC patients. GB004, Inc. has developed tablet formulations with 2 release 
profiles, tablets and delayed-release (DR) tablets, which have distinct systemic profiles with both 
delivering GB004 to the colonic tissue.  
This 2-part study, comprising of a 36-week placebo-controlled period and a 24-week open-label 
extension period, will assess the efficacy and safety of GB004 when added to background UC 
therapy of 5-aminosalicylate (5-ASA) with or without systemic steroids.  

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Objectives and Endpoints 
Placebo-Controlled Period (PCP) (Primary, Secondary and Safety Objectives and 
Endpoints) 
Objectives 
Endpoints 
Primary 
• 
To evaluate the effect of GB004 
compared to placebo on clinical 
remission at PCP Week 12  
• 
Proportion of subjects with clinical remission at PCP 
Week 12, defined as a Modified Mayo score ≤ 2, with 
a Rectal bleeding subscore of 0, Stool frequency 
subscore of 0 or 1 (with a ≥ 1 point decrease from 
baseline), and Endoscopic subscore of 0 or 1 
Secondary 
• 
To evaluate the effect of GB004 
on clinical response, histologic 
remission, endoscopic 
improvement, mucosal healing at 
PCP Week 12 
 
• 
Proportion of subjects with clinical response at PCP 
Week 12, defined as reduction in the Modified Mayo 
score of ≥ 2 points and ≥ 35 percent reduction from 
baseline, including a decrease in Rectal bleeding 
subscore of ≥1 or absolute Rectal bleeding subscore 
of ≤ 1 
• 
Proportion of subjects with histologic remission at 
PCP Week 12, defined as Robarts Histopathology 
Index (RHI) ≤ 3 with lamina propria neutrophils 
subscore = 0 and neutrophils in epithelium subscore = 
0  
• 
Proportion of subjects with endoscopic improvement 
at PCP Week 12, defined as endoscopic subscore of 0 
or 1 
• 
Proportion of subjects with mucosal healing at PCP 
Week 12, defined as endoscopic improvement and 
histologic remission  
• 
To evaluate the effect of GB004 
on clinical remission, clinical 
response, histologic remission, 
endoscopic improvement, and 
mucosal healing at PCP Week 36 
• 
Proportion of subjects with clinical remission at PCP 
Week 36 
• 
Proportion of subjects with clinical response at PCP 
Week 36 
• 
Proportion of subjects with histologic remission at 
PCP Week 36 
• 
Proportion of subjects with endoscopic improvement 
at PCP Week 36 
• 
Proportion of subjects with mucosal healing at PCP 
Week 36 
Safety 
• 
To evaluate the safety and 
tolerability of GB004  
• 
Incidence of treatment-emergent adverse events 
(TEAEs) 

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Open-Label Extension (OLE) (Primary) 
Objectives 
Endpoints 
Primary 
• 
To evaluate the safety and 
tolerability of GB004 
• 
Incidence of TEAEs 
Overall Design 
This is a 2-part study in adult subjects with mild-to-moderate active UC who have disease activity 
despite treatment with 5-ASA with or without systemic steroids: 
• The Placebo-Controlled period (PCP) is a randomized, placebo-controlled, multi-
center, 36-week study evaluating the efficacy, safety, tolerability and pharmacokinetics 
(PK) of 2 dose regimens of GB004; the initial 12 weeks of treatment will be double-
blind. 
• The OLE is an open-label, multi-center, 24-week study evaluating the safety and 
tolerability of GB004 twice per day (BID) dose regimen  
Subjects who complete the Week 36 visit on IP and subjects who meet the predefined UC Disease 
Activity criteria at or after PCP Week 12 visit and prior to PCP Week 36 visit on IP can enter the 
OLE (for details refer to Section 5.3). 
All subjects participating in the study will be required to maintain a stable dose of 5-ASA 
throughout the study. Subjects on systemic corticosteroids must remain on a stable dose during the 
initial 12 weeks of the PCP (for details refer to Section 6.5.2). After the PCP Week 12 visit, a 
standardized taper from systemic corticosteroids may be attempted at any time. 
All subjects will attend a Follow-up visit at the clinic 4 weeks after last dose of IP. 
A data review committee (DRC) will periodically convene to review unblinded overall safety and 
emerging efficacy results (Section 9.5.1). 
A schematic of the study design is presented in Section 1.2. 
Placebo-Controlled Period (36 weeks) 
After signing an informed consent form (ICF), subjects will be screened for study eligibility over 
a Screening period of up to 5 weeks. During the Screening period, subjects will capture stool 
frequency and rectal bleeding symptoms in a provided electronic diary (eDiary) on a daily basis. 
Flexible sigmoidoscopy or colonoscopy will be performed at screening. Subjects not meeting the 
eligibility criteria will be deemed screen failures and will not continue participation in the study.  
On Day 1/Week 0, eligible subjects will be randomized 1:1:1 to receive the following treatments 
for 36 weeks: 
• GB004 480 mg BID 
• GB004 480 mg once daily (QD) 
• Placebo 

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2. 
INTRODUCTION 
2.1. 
Study Rationale 
GB004 (formerly AKB-4924) is a novel small molecule in development for the treatment of 
inflammatory bowel disease (IBD). The novel approach of GB004 is based on evidence that 
hypoxia inducible factor 1 alpha (HIF-1α), a member of the hypoxia inducible factor (HIF) 
transcription factor family, has a crucial role in the maintenance of epithelial barrier integrity and 
in the modulation of the innate inflammatory response in mouse models of IBD. 
Small molecule prolyl hydroxylase inhibitors (PHDi’s) stabilize HIF-1α protein and have shown 
efficacy in multiple mouse models of IBD that include trinitrobenzene sulfonic acid (TNBS) and 
dextran sulfate sodium (DSS)-induced colitis models and the tumor necrosis factor alpha (TNFα)-
driven terminal ileitis model (Ablin, 1999; Minaiyan, 2012). Prolyl hydroxylases (PHDs) are key 
regulators of the HIF pathway (Eltzschig, 2014). These findings support PHD inhibition as a 
target for treating ulcerative colitis (UC). 
GB004, a HIF-1α stabilizer, is being developed as an oral therapeutic, gut-targeted treatment for 
UC with higher intestinal than systemic exposure. The relatively low oral bioavailability (< 20%) 
and preferential distribution to the gastrointestinal (GI) tissues observed in nonclinical studies, 
combined with its mechanism of action in gut lumen and positive effects on gut healing and 
inflammation in animal models of colitis, provide rationale for further development in human 
subjects. 
GB004 has been shown in studies of both healthy volunteers (AKB-4924-CI-1001, 
AKB-4924-CI-1002, and GB004-1902) and patients with UC (GB004-1101) to be a gut-targeted 
treatment with higher intestinal than systemic exposure. In addition, the GB004-1101 study, 
although limited by only 4 weeks of dosing, showed trends in improvement in clinical and 
histologic outcomes in UC patients. GB004, Inc. has developed tablet formulations with 2 release 
profiles, tablets and delayed-release (DR) tablets, which have distinct systemic profiles with both 
delivering GB004 to the colonic tissue.  
This 2-part study, comprising of a 36-week placebo-controlled period and a 24-week open-label 
extension period, will assess the efficacy and safety of GB004 when added to background UC 
therapy of 5-aminosalicylate (5-ASA) with or without systemic steroids. 
2.2. 
Background 
UC is the result of an unrelenting, severe inflammatory response mounted against an 
environmental trigger in a genetically susceptible host. The inflammatory response, in turn, causes 
a breach in intestinal barrier integrity which allows influx of luminal antigens setting up a vicious 
cycle of inflammation and epithelial injury that perpetuates the disease process. 
UC symptoms include rectal bleeding and diarrhea (Schroeder, 1987). Consistently, UC is 
associated with a significantly reduced quality of life and recent data indicate increased mortality 
especially among patients diagnosed at early ages. Despite the improved efficacy of UC treatment 
with anti-tumor necrosis factor (anti-TNF) agents and anti-integrin agents (eg, vedolizumab), 
there remains a large subset of patients who either do not respond adequately to conventional 

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therapy or biologic therapy and do not achieve long-term remission. Perhaps the best indicator of 
the inadequacy of current therapy is that surgery is required for about 23-46% of patients with UC 
(Shen, 2008). Considering the worldwide increase in UC, novel approaches to managing UC are 
urgently needed. (Bernstein, 2012; Kaplan, 2012; Singh, 2015). 
The overall goal of treatment for patients with active UC is to induce and maintain remission and 
to induce and maintain mucosal healing (de Mattos, 2015; Heyman, 2005; Jain, 2019; 
Lamb, 2019; Ng, 2009; Singh, 2019). Treatment of UC consists of anti-inflammatory and 
immunosuppressive therapies that are chosen to maximize efficacy while avoiding toxicity. The 
therapy chosen is therefore dependent on the patient’s disease severity and their response to 
therapy (Jain, 2019; Kelsen, 2020; Ko, 2019; Kornbluth, 2010; Ng, 2009). While agents used to 
treat mild to moderate UC are generally well tolerated, as the severity of UC increases, so do the 
potential toxicities of the medications required to manage the disease. In mild to moderate UC 
patients unresponsive to local therapy or in patients with more severe or more extensive disease, 
systemic treatment with an oral 5-ASA, such as mesalamine, olsalazine, sulfasalazine, and 
balsalazide, is commonly required (Jain, 2019; Ng, 2009; Turner, 2011; Whaley, 2019). After 
patients fail 5-ASA therapy, the next recommended add-on therapy is oral systemic or locally 
acting steroids (Ko, 2019). While >90% of UC patients in population-based cohorts receive 
5-ASA therapy within 1 year of diagnosis, 50% will also be prescribed steroids during the course 
of their disease (Singh, 2019). Therapies indicated for moderate to severe UC after steroids are 
either oral immunomodulators or biologics. These therapies are associated with higher rates of 
clinical remission, but also with higher risk of adverse events such as infection or malignancy 
(Kirchgesner, 2018). Biologics are typically employed after the failure of 5-ASAs due to the 
associated risks of these therapies, lack of durable response due to immunogenicity, and 
requirement of parental administration. There is an ongoing unmet medical need for an oral UC 
treatment that is highly effective in achieving long-term remission and mucosal healing with 
limited side effects in these patients with 5-ASA failure and prior to biologics (Levesque, 2015). 
GB004, a HIF-1α stabilizer, is being developed as an oral therapeutic, gut-targeted treatment for 
UC. The GB004 mechanism of action in gut lumen, positive effects on gut healing and 
inflammation in animal models of colitis, trends in improvement in disease related outcomes such 
as histologic remission, mucosal healing, rectal bleeding, and safety and tolerability results over 4 
weeks of treatment in the Phase 1b GB004-1101 study, provide rationale for further development 
of GB004 in UC subjects. 

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2.3. 
Benefit/Risk Assessment 
More detailed safety findings from completed and ongoing studies may be found in the 
Investigator’s Brochure (IB). 
2.3.1. 
Benefit Assessments 
Development of GB004 for UC is supported by its mechanism of action, which stabilized HIF-1α 
in Phase 1, and the evidence that GB004 show enhanced healing and decreased inflammation in 
animal models of colitis. 
The potential benefits of GB004 treatment for subjects in this study were shown in the 
GB004-1101 Phase 1b Study and included trends in improvement with GB004 compared to 
placebo in histologic remission, rectal bleeding, and mucosal healing; however, the study was 
limited by the 28 days of dosing and small sample size. This longer Phase 2 clinical study is 
designed to evaluate the impact of GB004 on these efficacy endpoints and provide sufficient time 
for the initial improvement of the clinical signs and symptoms of ulcerative colitis, and then the 
longer-term impact on clinical remission and mucosal healing. This study will also allow for 
subjects in the PCP to transition to OLE at or after PCP Week 12 and before PCP Week 36 and 
receive GB004 480 mg BID if they meet the predefined UC disease activity criteria (Section 5.3). 
2.3.2. 
Risk Assessments 
As of May 27, 2020, a total of 117 subjects, comprising 94 healthy volunteers and 23 subjects 
with active UC, have received GB004. GB004 Powder for Oral Solution has been studied in 
healthy volunteers receiving single and multiple doses up to 240 mg daily for 8 days (AKB-4924-
CI-1001 and AKB-4924-CI-1002) and in subjects with active UC receiving 120 mg daily for 28 
days (GB004-1101). GB004 formulations (Powder for Oral Solution and tablets) have been 
studied in healthy volunteers receiving doses up to 240 mg daily for 7 days (GB004-1902). There 
are no identified risks of GB004. There are 2 potential risks of GB004. 
These potential risks are: 
• Nausea: The overall incidence of nausea was 18.8% (22/117) in GB004-treated 
subjects versus none in placebo-treated subjects. Nausea in GB004-treated subjects 
was generally characterized as: mild, occurring more frequently with GB004 doses of 
120 mg or greater, first occurring within the first hour after the first dose and lasting 1 
day, without concurrent vomiting, and of low clinical impact with infrequent 
discontinuations of GB004 (1 subject). 
• Dizziness: The overall incidence of dizziness was 11.1% (13/117) in GB004-treated 
subjects versus 4.9% (2/41) in placebo-treated subjects. Dizziness in GB004-treated 
subjects was generally characterized as: mild, occurred more frequently with GB004 
doses of 120 mg or greater, first occurring within 1 day after first dose and lasting 1 
day, without impairment of function, and with no discontinuation of GB004. 
Preliminary safety results from the study of GB004 tablet formulations (GB004-1902) show that 
nausea and dizziness were reported  less frequently than were previously reported with the 
solution formulation. GB004 formulations have been studied in a Phase 1 study (GB004-1902) in 
healthy volunteers receiving daily doses of 120 mg solution or placebo, or up to 240 mg tablet, 

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delayed-release tablet, or placebo for 7 days. Overall, TEAEs were reported by 9 of 32 (28%) 
subjects who received GB004 and 3 of 10 (30%) subjects who received placebo. All TEAEs were 
mild in severity. TEAEs reported in more than one subject in the GB004 group included nausea 
(9% GB004; none in placebo), headache (9% GB004; 10% placebo), diarrhea (6% GB004; 
20% placebo), and liver function test elevation (6% GB004; none in placebo). Preliminary safety 
results from this study suggest that GB004 formulations of 120 mg solution and up to 240 mg 
tablet, and 240 mg DR tablet are generally well tolerated in healthy subjects. 
GB004 Powder for Oral Solution has been studied in subjects with active UC receiving daily 
doses of 120 mg in a Phase 1b study (GB004-1101). The majority of adverse events (AEs) were 
reported as Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or 2 in severity 
and were considered not related. The most common (≥ 10%) TEAEs reported in GB004-treated 
subjects included nausea (21.7% GB004; 0% placebo) and dysgeusia (13% GB004; 0% placebo). 
Preliminary results suggest that GB004 Powder for Oral Solution 120 mg daily is generally well 
tolerated in subjects with active UC. 
2.3.3. 
Overall Benefit and Risk Conclusion 
Given the potential benefits for subjects and the potential benefit of identifying a new therapeutic 
for UC and the potential risks of GB004, the benefit versus risk ratio for GB004 is considered 
favorable. 

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3. 
OBJECTIVES AND ENDPOINTS 
3.1. 
Placebo-Controlled Period Objectives and Endpoints 
Objectives 
Endpoints 
(see definitions for efficacy endpoints in Section 3.3) 
Primary 
• To evaluate the effect of GB004 
compared to placebo on clinical 
remission at PCP Week 12 
• Proportion of subjects with clinical remission at 
PCP Week 12, defined as a Modified Mayo 
score ≤ 2, with a Rectal bleeding subscore of 0, 
Stool frequency subscore of 0 or 1 (with a ≥ 1 
point decrease from baseline), and Endoscopic 
subscore of 0 or 1 
Secondary 
• To evaluate the effect of GB004 
on clinical response, histologic 
remission, endoscopic 
improvement and mucosal 
healing at PCP Week 12   
• Proportion of subjects with clinical response at 
PCP Week 12, defined as reduction in the 
Modified Mayo score of ≥ 2 points and ≥ 35 
percent reduction from baseline, including a 
decrease in Rectal bleeding subscore of ≥1 or 
absolute Rectal bleeding subscore of ≤ 1 
• Proportion of subjects with histologic remission 
at PCP Week 12, defined as Robarts 
Histopathology Index (RHI) ≤ 3 with lamina 
propria neutrophils subscore = 0 and 
neutrophils in epithelium subscore = 0 
• Proportion of subjects with endoscopic 
improvement at PCP Week 12, defined as 
endoscopic subscore of 0 or 1 
• Proportion of subjects with mucosal healing at 
PCP Week 12, defined as endoscopic 
improvement and histologic remission  
• To evaluate the effect of GB004 
on clinical remission, clinical 
response, histologic remission, 
endoscopic improvement, and 
mucosal healing at PCP Week 36 
• Proportion of subjects with clinical remission at 
PCP Week 36 
• Proportion of subjects with clinical response at 
PCP Week 36 
• Proportion of subjects with histologic remission 
at PCP Week 36 
• Proportion of subjects with endoscopic 
improvement at PCP Week 36 

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Objectives 
Endpoints 
(see definitions for efficacy endpoints in Section 3.3) 
• Proportion of subjects with mucosal healing at 
PCP Week 36 
Safety 
• To evaluate the safety and 
tolerability of GB004 
• Incidence of treatment emergent adverse events 
(TEAEs) 
Exploratory 
• To evaluate other safety 
outcomes 
• Change from Baseline in laboratory, vital signs, 
and electrocardiogram (ECG) parameters 
• To explore other measures of the 
effect of GB004 on disease 
activity over time 
• Proportion of subjects with resolution of Rectal 
bleeding  
• Proportion of subjects with histologic response  
• Proportion of subjects with Geboes score ≤ 2  
• Proportion of subjects with steroid-free clinical 
remission at PCP Week 36 
• Proportion of subjects with clinical remission 
by Mayo score and resolution of rectal bleeding  
• Proportion of subjects with clinical remission 
by Mayo score  
• Proportion of subjects with clinical response by 
Mayo score  
• Proportion of subjects with Modified Mayo 
score of ≤ 2, with no individual subscore > 1  
• Proportion of subjects with disease clearance  
• Proportion of subjects with symptomatic 
remission  
• Proportion of subjects with modified 
symptomatic remission  
• Proportion of subjects with Partial Mayo 
remission 
• Proportion of subjects with reduction of ≥ 2 
points from baseline in partial Mayo score  

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Objectives 
Endpoints 
(see definitions for efficacy endpoints in Section 3.3) 
• Proportion of subjects with a 6-point Mayo 
score clinical remission  
• Change from Baseline in Modified Mayo score  
• Change from Baseline in Mayo score  
• Change from Baseline in Partial Mayo score 
over time 
• Change from Baseline in Mayo subscores over 
time 
• Change from Baseline in RHI score  
• Change from Baseline in the UC-100 Index  
• To explore the PK of GB004 
• Plasma and colon tissue concentrations of 
GB004 
• To explore target engagement 
(TE) and pharmacodynamic 
(PD) response 
• Change from baseline in tissue and blood 
markers of target engagement, eg, HIF-1α, 
EGLN1-2-3, etc. 
• Change from baseline in markers of 
pharmacodynamics, eg, fecal calprotectin, fecal 
lactoferrin, and neutrophil activity 
(myeloperoxidase) 
• Change from baseline in tissue, blood, and stool 
in downstream genes and proteins, eg, CAIX, 
MPO, c-reactive protein (CRP), TJP, CLDN1, 
etc. as a function of exposure (Cmax, Tmax, 
AUC), efficacy endpoints (eg, clinical 
remission, clinical response), and/or safety 
endpoints 
• To explore baseline markers with 
response to treatment with 
GB004 
• Relationship between tissue, blood, and stool 
baseline markers (eg, HIF-1α, EGLN1-2-3, 
calprotectin, etc.) and response to treatment, as 
measured by efficacy endpoints (eg, clinical 
remission, clinical response), and/or safety 
endpoints 
• To explore pharmacogenetics 
(PGx)  
• Effect of naturally occurring genetic variation 
on the efficacy (eg, clinical remission, clinical 
response), safety, and/or PK profile (Cmax, Tmax, 

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Objectives 
Endpoints 
(see definitions for efficacy endpoints in Section 3.3) 
AUC) and tissue concentrations associated with 
treatment with GB004 
3.2. 
Open-Label Extension (OLE) Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
• To evaluate the safety and 
tolerability of GB004 
• Incidence of TEAEs 
Exploratory 
• To evaluate other safety 
outcomes 
• Change from GB004 baseline in laboratory, vital 
signs, and ECG parameters 
• To explore measures of the 
effect of GB004 on disease 
activity over time 
• Proportion of subjects with resolution of Rectal 
bleeding at OLE Week 24 
• Proportion of subjects with partial Mayo score 
of ≤2 with no individual subscore >1 over time 
• Proportion of subjects with reduction of ≥2 
points from GB004 baseline in partial Mayo 
score over time 
• Change from GB004 baseline in partial Mayo 
score over time 
• Proportion of subjects with a 6-point Mayo 
score clinical remission at OLE Week 24 
• To explore PD response 
• Change from GB004 baseline in fecal 
calprotectin 
• Change from GB004 baseline in blood, and 
stool in downstream markers, included but not 
limited to CRP 
 

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3.3. 
Efficacy Endpoint Definitions 
Table 2: 
Efficacy Endpoint Definitions 
Note: For the purposes of the endpoint definitions, refer to Section 9.4 for baseline definitions. 
Endpoint 
Definitions 
Clinical remission 
Modified Mayo score ≤ 2, with a Rectal bleeding subscore of 0, Stool 
frequency subscore of 0 or 1 (with ≥1 point decrease from baseline), and 
Endoscopic subscore of 0 or 1 (refer to Section 8.1.2 for Modified Mayo 
score) 
Clinical response 
Reduction in the Modified Mayo score of ≥ 2 points and ≥ 35% from 
baseline, including a decrease in Rectal bleeding subscore of ≥1 or 
absolute Rectal bleeding subscore of ≤ 1  
Histologic remission 
RHI ≤ 3 with lamina propria neutrophils subscore = 0 and neutrophils in 
epithelium subscore = 0 (refer to Section 8.1.3) 
Endoscopic improvement 
Endoscopic subscore 0 or 1 
Mucosal healing 
Endoscopic improvement and histologic remission 
Resolution of Rectal 
bleeding 
Rectal bleeding subscore = 0 
Histologic response 
Decrease from baseline in RHI of ≥ 7 (refer to Section 8.1.3) 
Steroid-free remission 
Clinical remission with no systemic corticosteroid use among subjects 
who were using systemic corticosteroids at baseline 
Clinical remission by 
Mayo score 
Mayo score ≤ 2, with no Mayo individual subscores >1 (refer to 
Section 8.1.2 for Mayo score) 
Clinical response by 
Mayo score 
Reduction in the Mayo score of ≥ 3 points and ≥ 30% from baseline, 
including a decrease in Rectal bleeding subscore of ≥ 1 or absolute Rectal 
bleeding subscore of ≤1 
Disease clearance 
Clinical remission and histologic remission (Danese, 2020) 
Symptomatic remission 
Mayo score of ≤ 2, with no individual subscore > 1 and both Rectal 
bleeding and Stool frequency subscores of 0 
Modified symptomatic 
remission 
Endoscopic improvement, resolution of Rectal bleeding and Stool 
frequency subscore of 0 
Partial Mayo remission 
Partial Mayo score of ≤ 2 with no individual subscore >1 (refer to 
Section 8.1.2 for partial Mayo score) 
6-point Mayo score 
clinical remission 
6- point Mayo score < 2 with a Rectal bleeding subscore of 0 and Stool 
frequency subscore of 0 or 1 (with ≥ 1 point decrease from baseline) 
(Lewis, 2008) (refer to Section 8.1.2 for 6-point Mayo score) 
Abbreviations: RHI, Robarts Histopathology Index. 

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4. 
STUDY DESIGN 
4.1. 
Overall Study Design 
This is a 2-part study in adult subjects with mild-to-moderate active UC who have disease activity 
despite treatment with 5-ASA with or without systemic steroids: 
• The Placebo-Controlled period (PCP) is a randomized, placebo-controlled, multi-
center, 36-week study evaluating the efficacy, safety, tolerability and pharmacokinetics 
(PK) of 2 dose regimens of GB004; the initial 12 weeks of treatment will be double-
blind  
• The OLE is an open-label, multi-center, 24-week study evaluating the safety and 
tolerability of GB004 twice per day (BID) dose regimen  
Subjects who complete the Week 36 visit on IP and subjects who meet the predefined UC Disease 
Activity criteria at or after PCP Week 12 visit and prior to PCP Week 36 visit on IP  can enter the 
OLE (for details refer to Section 5.3). 
All subjects participating in the study will be required to maintain a stable dose of 5-ASA 
throughout the study. Subjects on systemic corticosteroids must remain on a stable dose during the 
initial 12 weeks of the PCP (for details refer to Section 6.5.2). After the PCP Week 12 visit, a 
standardized taper from systemic corticosteroids may be attempted at any time. 
All subjects will attend a Follow-up visit at the clinic 4 weeks after last dose of IP. 
A data review committee (DRC) will periodically convene to review unblinded overall safety and 
emerging efficacy results (Section 9.5.1). 
A schematic of the study design is presented in Section 1.2. 
4.1.1. 
Placebo-Controlled Period (36 weeks) 
After signing an informed consent form (ICF), subjects will be screened for study eligibility over 
a Screening period of up to 5 weeks. During the Screening period, subjects will capture stool 
frequency and rectal bleeding symptoms in a provided electronic diary (eDiary) on a daily basis. 
Flexible sigmoidoscopy or colonoscopy will be performed at screening. Subjects not meeting the 
eligibility criteria will be deemed screen failures and will not continue participation in the study. 
On Day 1/Week 0, eligible subjects will be randomized 1:1:1 to receive the following treatments 
for 36 weeks: 
• GB004 480 mg BID 
• GB004 480 mg once daily (QD) 
• Placebo 
Randomization will be stratified by systemic corticosteroid use at baseline (yes/no). 
All subjects will dose investigational product (IP) BID to maintain the blind (for details refer to 
Section 6.1). The first dose of IP will be administered in the clinic on Day 1/Week 0 with food. 
All subsequent doses will be taken at home with food, with the exception of the morning doses at 

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the Week 2, 4, 8, 12, and 36 visits where IP will be administered in the clinic, with food, after 
predose blood collection as specified in the Schedule of Activities (SoA) in Section 1.3.1 – PCP. 
After initiation of IP on Day 1/Week 0, subjects will return to the clinic and will be evaluated as 
specified in the SoA, see Section 1.3.1. A flexible sigmoidoscopy with biopsies will be performed 
at the PCP Week 12 and Week 36 visits (and at the Unscheduled UC Disease Activity Criteria 
Assessment visit(s) and at the Early Withdrawal from Study visit, if applicable). 
Subjects who permanently discontinue IP without enrolling in the OLE will be encouraged to 
continue in the PCP and will complete the Early Discontinuation of IP visit at the time of IP 
discontinuation and then complete the remaining PCP study visits per the SoA. At subsequent 
visits, all study procedures will be completed per the SoA excluding dispensation/return and 
accountability of IP. 
Subjects who withdraw from the PCP without enrolling in the OLE, regardless of the reason, will 
be requested to return to the clinic to complete the Early Withdrawal from Study visit and will be 
asked to return for a Follow-up visit approximately 4 weeks after their last dose of IP to assess 
safety. 
For dose modifications refer to Section 6.5.1. 
4.1.2. 
OLE (24 weeks) 
Subjects may participate in the 24-week OLE if in the opinion of the Investigator they have been 
compliant with study procedures and: 
• Completed the Week 36 visit on IP; or 
• Met the predefined UC Disease Activity criteria any time after PCP Week 12 visit and 
prior to PCP Week 36 visit on IP (refer to Section 5.3) 
Beginning at the OLE Enrollment visit, all subjects will receive GB004 480 mg BID for 24 
weeks. All doses will be taken at home with food with the exception of the morning dose at the 
OLE Enrollment visit (if last dose of PCP IP has not been taken earlier in the day), OLE Week 2, 
12 and End of OLE visit/Early termination (ET) visit where IP will be administered in the clinic, 
with food, after predose blood collection as specified in the SoA (Section 1.3.2 – OLE). 
Subsequently, subjects will return to the clinic and be evaluated as specified in the SoA 
(Section 1.3.2 - OLE). 
Consideration should be given to discontinuing IP for subjects who do not show clinical 
improvement per Investigator’s judgement by OLE Week 12. Subjects who permanently 
discontinue IP during the OLE will be withdrawn from the study, complete the End of OLE/ET 
visit and will be asked to return for a Follow-up visit approximately 4 weeks after their last dose 
of IP to assess safety. 
4.2. 
Scientific Rationale for Study Design 
The PCP is designed as a randomized, placebo-controlled study to evaluate the efficacy and safety 
of 2 dose regimens of GB004 relative to placebo over a 36-week treatment period. The first 12 
weeks will be double-blind. 

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The OLE is designed to primarily evaluate the safety and tolerability of GB004 BID over a 
24-week treatment period and allows subjects who originally were assigned to placebo in the PCP 
to have an opportunity to be treated with GB004. 
4.2.1. 
Study Population 
The target population is adult subjects with mild-to-moderate active UC and have disease activity 
despite treatment with 5-ASA with or without prednisone (or equivalent), beclomethasone, 
budesonide, or budesonide-MMX. Mild-to-moderate active UC will be defined as a Mayo score of 
5-10, inclusive, with an Endoscopic subscore of ≥ 2, a Stool frequency subscore ≥ 1, and a Rectal 
bleeding subscore ≥ 1. 
4.2.2. 
Endpoint Selection 
Clinical remission has been chosen as the primary endpoint based on its clinical and regulatory 
importance in UC and the GB004 mechanism of action, which may lead to restoration of 
epithelial barrier function and resolution of inflammation and symptoms. This Phase 2 study is 
designed to evaluate the impact of GB004 on a set of efficacy endpoints while allowing sufficient 
time for the initial improvement of the clinical signs and symptoms of UC. Safety will be 
evaluated throughout with AE monitoring and other safety assessments. 
4.2.3. 
Placebo Rationale 
The study will compare the impact of adding GB004 versus placebo to background therapy for 
UC. Placebo will be used as a comparator to assess any differences in treatment effect or 
perception of response due to participation in the study. A placebo-controlled design is necessary 
because UC is a disease that waxes and wanes over time and is measured by endpoints with 
subjective components. It is important to be able to differentiate the biological activity of GB004 
compared to the “placebo effect,” which may be as high as 15 to 20% depending on the endpoint 
chosen. Comparisons between the GB004 and placebo treatment groups will facilitate 
differentiation of the GB004 safety profile from that of the background UC therapy. 
4.3. 
Justification for Dose 
Phase 1 studies have shown GB004 to be a gut-targeted treatment with higher intestinal than 
systemic exposure with trends in improvement in histologic remission, rectal bleeding, and 
mucosal healing in subjects with UC. The previous Phase 1b study in subjects with UC 
(GB004-1101) was limited by 4 weeks of dosing with a low dose (GB004 Powder for Oral 
Solution 120 mg QD) and by the number of subjects evaluated. Colonic concentrations were 
variable but frequently below target concentrations based on efficacy predictions from nonclinical 
animal models of colitis. Therefore, higher doses (480 mg QD and 480 mg BID) are planned in 
this Phase 2 study (refer to study schema in Section 1.2). This Phase 2 study is designed to 
evaluate the impact of GB004 on a set of efficacy endpoints while allowing sufficient time for the 
initial improvement of the clinical signs and symptoms of ulcerative colitis, and then to assess (at 
36 weeks) the longer term impact on clinical remission and mucosal healing. 
The PCP will evaluate 2 dose regimens of GB004, 480 mg (240 mg GB004 tablets and 240 mg 
GB004 DR tablets) administered BID or QD, compared to placebo. Subjects will be dosed under 

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fed conditions. These doses and the longer treatment duration are supported by completed 
nonclinical toxicology and clinical studies based on the following considerations: 
• Tolerability and safety profile of GB004 from the SAD and MAD studies, and 
evidence of target engagement from colon tissue biopsies from the MAD study. 
• Preliminary tolerability, safety, PK profile with minimal observed accumulation of 
GB004 following QD dosing for 28 days, and trends in improvement in disease-related 
outcomes such as histologic remission and mucosal healing in the Phase 1b GB004-
1101 study in subjects with active UC. 
• Preliminary tolerability, safety, and PK profile of GB004 tablets and GB004 DR 
tablets in the Phase 1a GB004-1902 study in healthy male and female volunteers, 
which demonstrated tablet plasma exposures that enable dosing at the proposed 
Phase 2 dose levels with a combination of GB004 tablets and GB004 DR tablets. The 
maximum observed concentration at steady-state (Cmax) and AUClast of GB004 tablets 
were similar to those with GB004 Powder for Oral Solution. When subjects were given 
GB004 tablets when fed, steady-state Cmax and AUC0-24 of GB004 appeared to be 
generally similar to subjects given GB004 tablets when fasted after normalization to 
dose. Given the rapid elimination of GB004 from systemic circulation, the steady-state 
Cmax of GB004 following BID dosing is expected to be similar to that following QD 
dosing, while daily AUC are expected to double following BID dosing compared to 
QD dosing. GB004 DR tablets when given fasted had a lower Cmax and AUClast than 
GB004 tablets fasted or GB004 solution. 
Based on the current safety and PK results with GB004 tablets at doses up to 240 mg, adequate 
safety margins of the projected human 480 mg GB004 (240 mg GB004 tablets and 240 mg 
GB004 DR tablets) BID treatment arm exposure values, and the selected doses taken with food, 
the proposed Phase 2 doses are expected to be tolerated. 
The OLE will evaluate GB004 480 BID because this dose is expected to inform long-term safety 
of GB004 at doses at or below this maximum dose in the study. 
The 9-month nonclinical toxicology results, and clinical safety, tolerability, PK and target 
engagement data, along with the preliminary evidence of clinical activity of GB004 in subjects 
with UC, support evaluating GB004 480 mg administered BID or QD under fed conditions for up 
to 60 weeks. 

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5. Colonoscopy within the past 2 years (or during the Screening period) to screen for 
dysplasia (unless otherwise recommended by local and national guidelines) if the subject 
has had UC for 8 or more years duration. 
Allowed UC Therapy 
6. Currently receiving treatment for UC, on a stable dose for at least 2 weeks prior to flexible 
sigmoidoscopy or colonoscopy, with oral 5-ASA (eg, mesalamine, sulfasalazine) alone or 
with one of the following oral treatments: 
a. prednisone ≤ 20 mg/day or equivalent or 
b. beclomethasone ≤ 5 mg/day or 
c. budesonide or budesonide multi-matrix (MMX) of ≤ 9 mg/day 
Body Mass Index (BMI) 
7. BMI 18 to 35 kg/m2. 
Pregnancy and Contraception 
Contraception use by men or women should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies. 
8. Women meeting the definition of non-childbearing potential or women of childbearing 
potential must agree to the contraceptive guidance (see Appendix 4). 
9. Men must agree to the contraceptive guidance (see Appendix 4). 
Informed Consent 
10. Capable of giving signed informed consent which includes compliance with the 
requirements and restrictions listed in the ICF and in this protocol. 
5.2. 
Exclusion Criteria 
Subjects are excluded from the study if any of the following criteria apply: 
Excluded Prior Therapy 
1. Prior approved biologic therapy used for the treatment of UC. 
2. Enemas or suppository formulations of steroids or 5-aminosalicylates within 2 weeks of 
screening flexible sigmoidoscopy/colonoscopy. 
3. Tofacitinib, oral cyclosporine, sirolimus or mycophenolate mofetil within 8 weeks of 
Day 1. 
4. Azathioprine, or 6-mercaptopurine within 1 day of Day 1. 
5. Anti-diarrheal medications (e.g., loperamide, diphenoxylate/atropine) during screening. 
6. Epoetin alfa within 8 weeks of Day 1. 
7. Cholestyramine or other drugs interfering with enterohepatic circulation within 14 days of 
Day 1. 

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8. Chronic non-steroidal anti-inflammatory agents (NSAID) use (occasional use of NSAID, 
acetaminophen, or aspirin up to 325 mg/day is allowed). 
9. Treatment with strong cytochrome P450 (CYP) 3A inhibitors and/or CYP3A inducers, and 
inhibitors of uridine-diphosphoglucuronosyl transferase (UGT) within 21 days or within 5 
half-lives, whichever is longer, of the respective medication prior to Day 1 (see 
Appendix 6 for examples). 
Medical Conditions 
10. Diagnosis of Crohn’s disease or indeterminate colitis, pouchitis. 
11. Fulminant colitis, toxic megacolon, or in Investigator’s judgement likely to require 
colectomy or ileostomy within 16 weeks of Day 1. 
12. Stool sample positive for Clostridium difficile (C difficile) toxin, stool pathogens, or ova 
and parasites infection on screening laboratory tests. If positive, subjects may be treated 
and retested. 
13. A current malignancy, current colonic dysplasia or previous history of cancer in remission 
for less than 5 years prior to screening. Subjects will not be excluded if they had localized 
carcinoma of the skin that was resected for cure, cervical dysplasia that has been 
adequately treated, or colonic dysplasia that has been completely removed. 
14. Known pre-existing, unstable liver disease (as defined by the presence of ascites, 
encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices or 
persistent jaundice), cirrhosis, known biliary abnormalities, known pre-existing non-
alcoholic steatohepatitis (NASH), or active infection with Hepatitis B or Hepatitis C. 
15. Immunodeficiency, including that due to human immunodeficiency virus (HIV), other 
than that explained by systemic corticosteroid use. 
16. Other concurrent medical conditions: known, pre-existing clinically significant endocrine, 
autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, cardiovascular, 
respiratory (eg, including active tuberculosis), hematological, or any other system 
abnormalities that are uncontrolled with standard treatment. 
17. Any other medical condition or laboratory abnormality that, in the opinion of the 
Investigator, would prohibit the subject from participating in the study. 
Diagnostic assessments 
18. QTcF ≥ 450 msec for males or QTcF ≥ 470 msec for females at screening by central 
overread. If QTcF is above specified limit and there are no other clinically significant 
abnormalities, repeat assessment is allowed with permission by the Sponsor’s Medical 
Monitor (or designee). 
19. Hemoglobin <7.5 g/dL, platelet count <100,000/µL, absolute neutrophils count < 1200/µL 
at screening. 
20. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 times upper 
limit of normal (ULN) at screening. 

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21. Total bilirubin > ULN at screening, unless likely related to diagnosis of Gilbert’s 
syndrome, in the opinion of the Investigator. 
22.  Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 calculated by chronic 
kidney disease epidemiology collaboration (CKD-EPI). 
Prior Clinical Study Experience 
23. Treatment with an investigational medication or treatments (eg, hyperbaric oxygen 
treatment) within the past 30 days or within 5 half-lives of the medication, whichever is 
longer, prior to screening. (This also includes investigational formulations of marketed 
products.) 
24. Have previously received treatment with GB004/AKB-4924. 
Other Exclusions 
25. A history or suspected history of alcohol misuse or substance abuse, per the discretion of 
the principal investigator, within 12 months prior to screening. 
26. Female subject who is pregnant or breastfeeding. Female subjects should not be enrolled if 
they are planning to become pregnant during the time of study participation. A urine 
pregnancy test is required of all women of child-bearing potential. 
5.3. 
UC Disease Activity Criteria 
Subjects meeting the following predefined UC Disease Activity criteria at or after the PCP 
Week 12 visit and prior to PCP Week 36 visit on IP may enter the OLE and receive GB004 BID 
treatment. Refer to Table 8 for Mayo score calculation instructions in Appendix 8. 
• A Mayo score: 
− with Endoscopic subscore ≥2 using the centrally read endoscopy score from the 
flexible sigmoidoscopy, 
AND 
− greater than or equal to the Mayo score at the PCP Day 1/Week 0 visit 
AND 
• Exclusion of other causes of disease activity unrelated to underlying UC (eg, 
infections), at the discretion of the Investigator 

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5.4. 
Screen Failures 
Subjects will be assigned a subject number at the time of signing the ICF. Subjects who are not 
randomized will be labeled as screen failures. 
A minimal set of screen failure information is required to ensure transparent reporting of screen 
failure subjects to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities. Minimal information includes 
informed consent date, demography, screen failure details (including eligibility criteria), and any 
SAE. 
Subjects who are labelled as screen failures may be eligible to rescreen once upon approval by the 
Sponsor’s Medical Monitor (or designee). A new subject number will be assigned if approved to 
rescreen. 
6. 
INVESTIGATIONAL PRODUCT 
6.1. 
Investigational Product(s) Administered 
Each dose of IP will consist of a combination of GB004 tablets and GB004 delayed-release 
(equivalent term to gastro-resistant) tablets or of matching placebo tablets and will be taken orally 
BID on a fed stomach at approximately the same time each day, 8 to 12 hours apart. 
The GB004 tablets, GB004 delayed-release tablets, and placebo tablets are similar and 
indistinguishable in terms of appearance, odor, and taste, such that the blind is maintained. 

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Table 3: 
Investigational Product Formulation by Treatment Group 
Investigational 
Product Name 
GB004 (Active) 
PCP and OLE 
Placebo (Control) 
PCP only 
Dose Formulation 
GB004 round film-coated tablets 
Matching placebo 
round film-coated 
tablets 
Unit Dose 
Strength 
60 mg per tablet 
Placebo tablet 
Dose regimen 
 
GB004 480 mg BID (PCP and OLE): 
4 tablets + 4 delayed-release tablets, BID 
Placebo: 
8 placebo tablets BID 
GB004 480 mg QD (PCP only): 
• 
4 tablets + 4 delayed-release tablets, QD 
morning 
• 
8 placebo tablets, QD evening 
Route of 
Administration 
Oral, with food 
IP to be taken BID (approximately 8 to 12 hours apart) at approximately the 
same time each day. 
Sourcing 
IP will be provided to the site centrally by the Sponsor or designated 
representative. For exceptions, refer to Appendix 9. 
Packaging 
PCP: GB004 tablets, GB004 delayed-release tablets, and GB004 placebo 
tablets will be packaged in 68 count, 60 cc high-density polyethylene 
(HDPE) bottles, with child-resistant induction-sealed closures. 
OLE: GB004 tablets and GB004 delayed-release tablets will be packaged in 
68 count, 60 cc high-density polyethylene (HDPE) bottles, with child-
resistant induction-sealed closures. 
Bottles will be dispensed in 4-bottle sets supplying 2 weeks of dosing 
(sufficient for 17 days of treatment) consisting of 2 bottles used for morning 
dosing and 2 bottles for evening dosing. Subjects to dose 4 tablets per bottle 
per day.  
Refer to the Pharmacy Manual for additional details. 
Labeling 
Label text will at a minimum include the protocol number, lot number, 
storage conditions, and Sponsor name and address. Labels will comply with 
local regulatory requirements for IPs. 
Storage 
Requirements 
Store at 2°C to 8°C; for more details refer to the Pharmacy Manual. 

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6.2. 
Preparation/Handling/Storage/Accountability 
• Bottles containing GB004 tablets or placebo will be shipped to clinical sites using 
temperature monitoring devices and stored at 2°C to 8°C. The Investigator or designee 
must confirm appropriate temperature conditions have been maintained during transit 
for all IP received and any discrepancies are reported and resolved before use of the IP. 
• Only randomized subjects may receive IP and only authorized site staff may supply IP. 
At the study site, all IP must be stored in a secure, refrigerated (2°C to 8°C), 
environmentally controlled, and monitored (manual or automated) area in accordance 
with the labeled storage conditions with access limited to the Investigator and 
authorized site staff. 
• Subjects will be provided with coolers for transport of IP from the study site to their 
home location. Once at home, IP is to be stored in a refrigerator. 
• The Investigator, institution, or the head of the medical institution (where applicable) 
is responsible for IP accountability, reconciliation, and record maintenance (ie, receipt, 
reconciliation, and final disposition records). 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
6.3.1. 
Assignment of a Subject Number 
At the Screening visit, a unique subject number will be assigned to a subject upon signing of the 
ICF. 
6.3.2. 
Randomization and Stratification 
At PCP Day 1/Week 0 visit, all subjects who meet eligibility criteria will be centrally randomized 
1:1:1 to GB004 480 mg BID, GB004 480 mg QD, or placebo using an interactive response 
technology (IRT) system. 
Before the study is initiated, directions for use of the IRT system will be provided to the sites. 
Randomization will be stratified by systemic corticosteroid use at baseline (yes/no). 
6.3.3. 
Investigational Product Numbers 
IP will be dispensed at the study visits as summarized in the SoA (Section 1.3.1 – PCP and 
Section 1.3.2 – OLE). On PCP Day 1/Week 0 visit, the IRT system will assign IP bottle number(s) 
based on the subject’s randomized treatment group. 
For subsequent visits when IP is dispensed, the IRT system will assign new IP bottle number(s) 
based on the subject’s randomized/assigned treatment group. 
6.3.4. 
Blinding 
Subjects, investigators and site personnel, and the Sponsor (with exceptions described below) will 
be blinded to individual subject treatment assignments in the PCP. All subjects will dose IP BID 
to maintain the blind. 

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The study will be unblinded to the Sponsor at the time of the PCP Week 12 Analysis (see 
Section 9.4). Therefore, the PCP will be double-blind through PCP Week 12 and will remain 
blinded to subjects, investigators, and site staff throughout the PCP. 
Sponsor (or designee) personnel will have access to unblinded individual subject treatment 
assignments for the purposes of study-required activities, including management of IP inventory, 
production of summaries of data for DRC review, and performance of bioanalytical analysis of 
PK and gene/protein concentrations. These personnel will not be directly involved in the conduct 
of the study. 
A DRC will periodically convene to review unblinded overall safety and emerging efficacy results 
(refer to Section 9.5.1). 
6.3.5. 
Unblinding of an Individual Subject 
The IRT system will be programmed with blind-breaking instructions. In case of a medical 
emergency, the Investigator has the sole responsibility for determining if unblinding of a subject’s 
treatment assignment is warranted. Subject safety must always be the first consideration in 
making such a determination. If the Investigator decides that unblinding is warranted, the 
Investigator, when possible, should make every effort to contact the Sponsor to discuss unblinding 
a subject’s treatment assignment unless this could delay medical emergency treatment of the 
subject. If a subject’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. 
Appropriate personnel at the Sponsor will unblind suspected unexpected serious adverse reactions 
(SUSARs) for the purpose of regulatory reporting. The Sponsor will submit SUSARs to Regulatory 
Agencies in blinded or unblinded fashion according to local law. The Sponsor will submit SUSARs to 
Investigators in a blinded fashion. 
6.4. 
Investigational Product Compliance 
The first dose of IP will be administered in the clinic on PCP Day 1/Week 0 with food. All 
subsequent doses will be taken at home with food with the exception of the morning doses at the 
PCP Week 2, 4, 8, 12, and 36 visits and OLE Enrollment, Week 2, 12 and EOT visits where IP 
will be administered in the clinic, with food, after pre-dose blood collection as specified in the 
SoA (Section 1.3.1 – PCP and Section 1.3.2 – OLE). 
After initiation of IP on PCP Day 1/Week 0 visit, subjects will visit the clinic for assessments of 
IP use as specified in the SoA (Section 1.3.1 – PCP and Section 1.3.2 – OLE). IP accountability 
will be assessed by counting returned tablets. Subjects who demonstrate poor IP compliance 
should be re-educated on the importance of taking their medications as prescribed. 
Subjects will be asked to record dosing information on a daily basis in an eDiary. 
For additional details refer to Study Reference Manuals. 

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Guidance for Missed Dose(s) 
If a dose is missed, subjects should be instructed to skip the missed dose if there are less than 6 hours 
before the time of the next dose, resume dosing at their next scheduled dosing time, and document the 
missed dose. 
6.5. 
Dose Modification 
6.5.1. 
Investigational Product 
Dose modification, as described below, may be considered for treatment-related AEs and liver 
chemistry laboratory abnormalities. 
Dose reduction will be prescribed in two steps (as detailed in the Study Reference Manuals): 
• First reduction step: IP dose will be reduced by 2 tablets BID 
• Second reduction step (only if either treatment-related AE or liver function 
abnormality persist for 7 days following initiation of first step of dose reduction): IP 
dose will be reduced further by 1 tablet BID 
Treatment-related AEs (other than liver chemistry laboratory abnormalities described below): 
Dose modification of IP may be undertaken only after consultation and approval from the 
Sponsor’s Medical Monitor (or designee) for AEs assessed by the Investigator as treatment-
related, such as tolerability related AEs. Subjects may be requested to attend an unscheduled visit 
after dose reduction (before potential re-administration of IP at a higher dose as described below), 
to collect blood samples for safety and PK, if possible. 
Liver chemistry laboratory abnormality:  
• Dose modification of IP may be undertaken only after consultation and approval from 
the Sponsor’s Medical Monitor (or designee) for confirmed ALT or AST ≥ 3 × ULN 
and < 5 × ULN meeting the criterion described in Table 6 in Appendix 7.  
• For confirmed ALT or AST ≥3 × ULN meeting criteria in Table 7 in Appendix 7, IP 
should be discontinued. 
In both study periods, following dose reduction, IP may be re-administered at a higher dose in 
consultation with the Sponsor's Medical Monitor (or designee). 
After consultation and approval from the Sponsor’s Medical Monitor (or designee), subjects with 
a dose reduction during the PCP may enter the OLE at the reduced dose (reduced number of 
tablets as specified above) or at full dose (480 mg BID). 
6.5.2. 
Background UC Therapy 
New UC therapies may not be started between 2 weeks prior to the screening flexible 
sigmoidoscopy/colonoscopy and the PCP Week 36 visit. Subjects requiring introduction of new 
therapies to treat UC will be discontinued from IP as described in Section 7.1.5. 

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5-ASA 
Subjects should remain on their stable UC background oral 5-ASA therapy from 2 weeks prior to 
screening flexible sigmoidoscopy/colonoscopy used to assess the baseline Mayo score through the 
duration of their time on study. Any changes in existing UC background therapies should be 
discussed with the Sponsor’s Medical Monitor (or designee), if possible. 
Systemic steroid tapering 
Subjects receiving oral prednisone ≤ 20 mg/day (or equivalent) or beclomethasone ≤ 5 mg/day or 
budesonide or budesonide MMX of ≤ 9 mg/day should remain on their stable dose from 2 weeks 
prior to screening flexible sigmoidoscopy/colonoscopy used to assess the baseline Mayo score 
through the PCP Week 12 visit. At the discretion of the Investigator, systemic steroids may be 
tapered after the PCP Week 12 visit as described below. For subjects who cannot tolerate systemic 
steroid taper without recurrence of clinical symptoms of either UC or steroid withdrawal, the 
systemic steroid dose may be increased (up to the baseline dose if required). 
Prednisone (or equivalent) tapering 
• Subjects receiving prednisone at a dose of > 10 mg/day (or equivalent) should have 
their dose reduced at a rate of 5 mg per week until a 10 mg/day dose is achieved.  
• Subjects receiving prednisone at a dose of 10 mg/day (or equivalent) either or when 
this dose is achieved by tapering during the OLE, are to have their dose reduced at a 
rate of 2.5 mg per week until discontinuation.  
Beclomethasone or Budesonide tapering 
• Subjects receiving beclomethasone should taper their dose of 5 mg every day to 5 mg 
every other day for 2 weeks then discontinue beclomethasone. 
• Subjects receiving budesonide or budesonide MMX should taper their dose of 9 mg 
every day to 9 mg every other day for 2 weeks then discontinue budesonide or 
budesonide MMX. 
6.6. 
Continued Access to Investigational Product After the End of the 
Study 
No additional intervention is planned beyond the OLE EOT visit. 
6.7. 
Treatment of Overdose 
Any dose of IP greater than the prescribed daily dose within the same calendar day will be 
considered an overdose. 
There is no specific treatment recommended to treat an overdose of IP and the subject should 
receive treatment directed towards any symptoms manifested. 
In the event of an overdose, the Investigator should: 
• Contact the Sponsor’s Medical Monitor (or designee) as soon as possible. 

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• Closely monitor the subject for any AE/SAE and laboratory abnormalities. 
• Document the quantity of the excess dose as well as the duration of the overdose in the 
electronic case report form (eCRF). 
Decisions regarding dose interruptions will be made by the Investigator in consultation with the 
Sponsor's Medical Monitor (or designee) based on the clinical evaluation of the subject. 
6.8. 
Concomitant Therapy 
At least a 4-hour interval is required between taking IP tablets and mineral supplements, and 
antacids that contain polyvalent cations (eg, iron, aluminum, and zinc). 
Results from in vitro studies indicate that a glucuronide metabolite of GB004, GBD242, may be 
an inhibitor of OCT2 and CYP2C8.  
If sensitive clinical substrates of OCT2 (such as metformin or dalfampridine) are used 
concomitantly with GB004, refer to the prescribing information of the clinical substrate for 
assessing the benefit and risk of concomitant use. Initiation of sensitive clinical substrates of 
OCT2 is permitted only after discussion with the Sponsor’s Medical Monitor (or designee) and 
consideration of alternatives.  
Concomitant use of sensitive substrates of CYP2C8 (eg, repaglinide, rosiglitazone, pioglitazone, 
and loperamide) is prohibited in this study pending further evaluation of the potential for GBD242 
to inhibit CYP2C8 activity clinically. 
Any medication or vaccine (including over-the-counter [OTC] or prescription medicines, 
vitamins, and/or herbal supplements) that the subject is receiving at the time of enrollment or 
receives during the study must be recorded along with: 
• Reason for use 
• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
The Sponsor's Medical Monitor (or designee) should be contacted if there are any questions 
regarding concomitant or prior therapy.  
6.8.1. 
Prohibited Medications Prior to the Screening Visit and Throughout the Study 
Please refer to Appendix 6 for further details regarding prohibited medications. 

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7. 
DISCONTINUATION OF INVESTIGATIONAL PRODUCT AND 
SUBJECT WITHDRAWAL FROM STUDY 
7.1. 
Discontinuation of Investigational Product, Subject Withdrawal from 
the Study and Stopping Rules 
Discontinuation of IP 
In some instances, it may be necessary for a subject to permanently discontinue IP. 
PCP: Permanent discontinuation of IP does not mean withdrawal from the study, and the subject 
will be encouraged to remain in the study and continue to complete any remaining PCP study 
visits as per the SoA (Section 1.3.1 – PCP) if the subject is not enrolling in the OLE. A follow-up 
visit will be conducted approximately 4 weeks after last dose of IP. The reason for discontinuation 
of IP will be recorded in the eCRF.  
OLE: Subjects who permanently discontinue IP during the OLE will be withdrawn from the study, 
complete the End of OLE/ET visit, and will be asked to return for a Follow-up visit approximately 
4 weeks after their last dose of IP to assess safety. 
Withdrawal from the Study 
Subjects have the right to withdraw from the study at any time and for any reason without 
prejudice to their future medical care by the Investigator or at the institution. The reason for 
subject withdrawal from the study will be recorded in the eCRF. At the time of withdrawal from 
the PCP, an Early Withdrawal from Study visit should be conducted, as shown in the SoA 
(Section 1.3.1 – PCP) and from the OLE, the EOT visit should be conducted as shown in the SoA 
(Section 1.3.2 – OLE). See the SoA for data to be collected at the time of study withdrawal and 
follow-up and for any further evaluations that need to be completed. If a subject withdraws from 
the study, he/she may request destruction of any samples taken and not tested, and the Investigator 
must document this in the site study records. 
A subject may discontinue IP or withdraw from the study for the following reasons: 
• Adverse event 
• Death 
• Lack of efficacy 
• Lost to follow-up 
• Non-compliance with study drug 
• Physician decision 
• Pregnancy 
• Protocol deviation 
• Site terminated by Sponsor 
• Study terminated by Sponsor 

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• Withdrawal by subject 
For stopping criteria related to hemoglobin, nausea, and dizziness, refer to Section 7.1.1. 
For stopping criteria relating to QTcF prolongation, refer to Section 7.1.2. 
For liver chemistry abnormality actions and follow-up assessments, refer to Section 7.1.3 and 
Appendix 7 and for dose modification, refer to Section 6.5.1. 
Pregnancy is a criterion for mandatory permanent discontinuation of IP (see Section 7.1.4). 
For stopping criteria related to introduction of new therapy to treat UC between 2 weeks prior to 
the screening flexible sigmoidoscopy/colonoscopy and the PCP Week 36 visit, refer to 
Section 7.1.5. 
7.1.1. 
Hemoglobin, Nausea, and Dizziness Stopping Criteria 
Individual subjects will be permanently discontinued from IP for any of the following: 
• Hemoglobin increase of > 4 g/dL from baseline and above ULN, and is assessed by the 
Investigator as a related AE.  
• Nausea that prevents daily activity, requires outpatient IV hydration, and is assessed by 
the Investigator as a related AE. 
• Dizziness that prevents daily activity, requires medical intervention, and is assessed by 
the Investigator as a related AE. 
7.1.2. 
QTcF Stopping Criteria 
Subjects must permanently discontinue IP for QTcF >500 msec. 
7.1.3. 
Liver Function: Actions and Follow-up Assessments 
Liver chemistry will be evaluated as specified in the SoA (Section 1.3.1 – PCP and Section 1.3.2 – 
OLE). 
For ALT or AST ≥3 × ULN, refer to Appendix 7 for guidelines on monitoring and criteria for 
possible dose modifications (Section 6.5.1) and temporary interruption of IP with possible 
restarting criteria and actions. 
Any occurrence of a confirmed ALT or AST value ≥3 × ULN will be monitored and evaluated for 
an etiology (for example viral hepatitis, drug and herbal supplements, environmental exposure, 
alcohol use, and other) in consultation with the Sponsor (Appendix 2,  Table 5). 
7.1.4. 
Pregnancy 
A subject must permanently discontinue IP if she becomes pregnant. See Appendix 4 and 
Section 8.3.5 for additional details. 
See the SoA (Section 1.3.1 – PCP and Section 1.3.2 – OLE) for data to be collected at the time of 
IP discontinuation (Early Withdrawal from Study visit in PCP and EOT visit for OLE) and 
follow-up and for any further evaluations that need to be completed. 

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7.1.5. 
Introduction of New UC Therapy Stopping Criteria 
A subject requiring introduction of a new therapy to treat UC between 2 weeks prior to the 
screening flexible sigmoidoscopy/colonoscopy and the PCP Week 36 visit must permanently 
discontinue IP. 
7.2. 
Lost to Follow-up 
A subject will be considered lost to follow-up if he or she repeatedly fails to engage for scheduled 
visits and is unable to be contacted by the study site. 
The following actions must be taken if a subject fails to return to the clinic for a required study 
visit (for exceptions refer to Appendix 9): 
• The site must attempt to contact the subject and reschedule the missed visit as soon as 
possible and counsel the subject on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the subject wishes to and/or should continue in 
the study. 
• Before a subject is deemed lost to follow-up, the Investigator or designee must make 
every effort to regain contact with the subject (where possible, 3 telephone calls and, 
if necessary, a certified letter to the subject’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the subject’s 
medical record. 
• Should the subject continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
Discontinuation of specific sites or of the study as a whole are handled as part of Appendix 1. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the SoA (Section 1.3.1 – PCP and 
Section 1.3.2 – OLE). Protocol waivers or exemptions are not allowed. 
• Immediate safety concerns should be discussed with the Sponsor’s Medical Monitor 
(or designee) immediately upon occurrence or awareness to determine if the subject 
should continue or discontinue IP. 
• Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that potential 
subjects meet all eligibility criteria. The Investigator will maintain a screening log to 
record details of all subjects screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
• In case of natural disasters or pandemics, some visits/study procedures may be done 
via virtual visits or at home visits. Refer to Appendix 9 and Study Reference Manuals 
for more details. 

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8.1. 
Efficacy Assessments 
8.1.1. 
Clinical, Endoscopic and Histologic Assessment 
Throughout the study, subjects will capture Stool frequency and Rectal bleeding symptoms on a 
daily basis in an eDiary. For evaluation of eligibility, the Rectal bleeding and Stool frequency 
subscores of the Mayo score will each be calculated based on the average of the most recent 3 
days with non-missing data within 14 days prior to the PCP Day 1/Week 0, excluding the day of 
and the day after flexible sigmoidoscopy/colonoscopy and the day(s) of bowel preparation, if 
performed. Subjects bowel preparation for flexible sigmoidoscopy/colonoscopy should follow 
standard clinical practice. Subjects will be instructed that a stool is defined as a trip to the toilet 
when the subject has either a bowel movement, or passes blood alone, blood and mucus, or mucus 
only. 
Screening, PCP Week 12, and PCP Week 36 (and at an Unscheduled UC Disease Activity Criteria 
Assessment visit(s) and the Early Withdrawal from Study visit, if applicable) endoscopic 
subscores will be assessed by both a central reader (who is blinded to treatment assignment, visit, 
and subject symptoms) and local endoscopist (who is blinded to treatment assignment). The same 
local endoscopist assesses the endoscopic subscore for a particular subject throughout the study, if 
possible. Differences between the local endoscopist and the central reader will be adjudicated by a 
second blinded central reader as described in the Imaging Charter. Centrally read endoscopic 
subscores will be used for both eligibility determination and efficacy analyses. Histologic scores 
(eg, RHI) will be evaluated by a blinded central reader.  
Flexible sigmoidoscopy/colonoscopy and histology assessments will consist of assessing the 
Endoscopic subscore of the sigmoid colon at approximately 15 to 25 cm from the anal verge. Six 
biopsies will be obtained during the endoscopic procedures from the area that appears to be most 
affected by UC in this sigmoid colon segment.  
Biopsies may also be evaluated for PK, gene expression, and immunohistochemistry signals of 
biological activity. 
8.1.2. 
Mayo Score and Modified Mayo Score 
Mayo score is used for inclusion into the study rather than a Modified Mayo score (used to 
evaluate efficacy) given the limited information available at the study inception regarding 
Modified Mayo score cut points that define a mild-to-moderate patient population. 
The Mayo score is a conventional assessment of UC disease activity and is commonly used in 
clinical studies of UC. The score is composed of four subscores, each ranging from 0 to 3, that are 
summed to give a total score ranging from 0 to 12 points, with higher scores indicating greater 
severity (Adapted from Schroeder, 1987): 
1. Stool frequency: 
0 = Normal number of stools for this subject 
1 = 1 to 2 stools more than normal 
2 = 3 to 4 stools more than normal 
3 = 5 or more stools than normal 

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Each subject serves as his or her own control to establish the degree of abnormality of the 
stool frequency. The control value is the number of stools in a 24-hour period when the 
subject was in remission from UC, or, if the subject does not report having previously 
achieved remission from UC, the number of stools the subject reports per day before 
initial onset of signs and symptoms of UC. 
2. Rectal bleeding: 
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 
The daily bleeding score represents the most severe bleeding of the day. 
3. Findings on endoscopy: 
0 = Normal or inactive disease 
1 = Mild disease (erythema, decreased vascular pattern) 
2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions) 
3 = Severe disease (spontaneous bleeding, ulceration) 
4. Physician’s Global Assessment 
0 = Normal 
1 = Mild disease 
2 = Moderate disease 
3 = Severe disease 
The PGA acknowledges the three other criteria, the subject’s recollection of abdominal 
discomfort and general sense of wellbeing, and other observations, such as physical 
findings and the subject’s performance status. It is recommended that the same physician 
performs the PGA for a particular subject throughout the study. 
The Modified Mayo score is an endpoint measure composed of: Stool frequency, Rectal bleeding, 
and Endoscopic subscores (where the Endoscopic subscore value of 1 does not include friability), 
each ranging from 0 to 3, that are summed to give a total score ranging from 0 to 9 points, with 
higher scores indicating greater severity. 
The Partial Mayo score is an endpoint measure composed of: Stool frequency, Rectal bleeding, 
and PGA subscores, each ranging from 0 to 3, that are summed to give a total score ranging from 
0 to 9 points, with higher scores indicating greater severity. 
The 6-point Mayo score is an endpoint measure composed of: Stool frequency and Rectal 
bleeding subscores, each ranging from 0 to 3, that are summed to give a total score ranging from 0 
to 6 points, with higher scores indicating greater severity. 

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8.1.3. 
Robarts Histopathology Index (RHI) Score, Geboes Score and Ulcerative Colitis 
Index-100 
The RHI is a validated instrument that measures histological disease activity in UC. The RHI 
consists of 4 items: chronic inflammatory infiltrate, lamina propria neutrophils, neutrophils in 
epithelium, and erosion or ulceration. The RHI score ranges from 0-33 and is derived from 
Geboes score (Mosli, 2017). 
RHI =  1 x chronic inflammatory infiltrate level (4 levels) 
+ 2 x lamina propria neutrophils (4 levels)  
+ 3 x neutrophils in epithelium (4 levels) 
+ 5 x erosion or ulceration (4 levels after combining Geboes 5.1 and 5.2)  
The Geboes score is divided into 6 grades: architectural changes [grade 0], chronic inflammatory 
infiltrate [grade 1], lamina propria eosinophils and neutrophils [grade 2A and 2B], neutrophils in 
epithelium [grade 3], crypt destruction [grade 4] and erosions or ulcerations [grade 5]. The Geboes 
score is calculated as the highest grade with a corresponding subgrade score > 0, excluding Geboes 
Grade 2A, and ranges from 0 to 5. 
The Ulcerative Colitis Index-100 (UC-100) score is the composite index (1 + 16 x Stool frequency 
subscore [0 to 3] + 6 x Endoscopic subscore [0 to 3] + 1 x RHI score [0 to 33]) (Jairath, 2019). 
8.2. 
Safety Assessments 
8.2.1. 
Physical Examinations 
A complete physical examination will be performed at timepoints designated in the SoA 
(Section 1.3.1 – PCP and Section 1.3.2 – OLE) and will include: 
• General appearance/inspection 
• Skin 
• Neck 
• Lymphatic 
• Respiratory 
• Cardiovascular 
• Abdominal system 
• HEENT (head, eyes, ears, nose, throat) 
• Other- for those body systems, not listed above considered necessary per PI’s 
discretion 
A symptom-directed physical examination will be conducted if clinically indicated throughout the 
study. Investigators should pay special attention to clinical signs related to previous serious 
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8.2.2. 
Vital Signs 
• Heart rate, respiratory rate, temperature and blood pressure will be assessed. 
• Blood pressure and pulse measurements will be assessed with the subject in a sitting 
position with a completely automated device. Manual techniques will be used only if 
an automated device is not available or if the automated cuff sizes available are not 
large enough for the subject’s arm circumference. 
• Vital signs will be measured after 5 minutes rest and prior to ECG measurements on 
days where the 12-lead ECG will be obtained. 
• Height and weight will also be measured and recorded. Height will only be recorded at 
Screening. 
8.2.3. 
Electrocardiograms 
• 12-lead ECGs will be obtained at timepoints specified in the SoA (Section 1.3.1 – PCP 
and Section 1.3.2 – OLE) using an ECG machine that automatically calculates the 
heart rate and measures PR, QRS, QT, and QTc intervals. 
• Subjects with evidence of a significant abnormality in the 12-lead ECGs obtained at 
screening, including prolongation of the QTc interval, will not be eligible to randomize 
into the study. 
• ECG will be centrally read by the Sponsor’s designee via the electronic portal. 
• Original paper tracings and tracing copies of the ECGs should be stored in the  source 
documents. 
8.2.4. 
Clinical Safety Laboratory Assessments 
• See Appendix 2 for the list of clinical laboratory tests to be performed and the 
SoA (Section 1.3.1 – PCP and Section 1.3.2 – OLE) for the timing and frequency. 
Details for collection, processing, and shipping of samples to the central laboratory are 
provided in a separate Central Laboratory Manual. 
• The Investigator must review and document review of the laboratory report. The 
Investigator must 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. 
• All laboratory tests with values considered clinically significant during participation in 
the study should be repeated as medically indicated until the values return to normal or 
baseline or are no longer considered clinically significant by the Investigator or 
Sponsor’s Medical Monitor (or designee). 
− 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 
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− All protocol-required laboratory assessments, as defined in Appendix 2, must be 
conducted in accordance with the Central Laboratory Manual and the SoA 
(Section 1.3.1 – PCP and Section 1.3.2 – OLE). 
8.3. 
Adverse Events and Serious Adverse Events 
The definitions of an AE and SAE can be found in Appendix 3. 
AEs will be reported by the subject (or, when appropriate, by a caregiver, surrogate, or the 
subject's legally authorized representative). 
The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE. The Investigator and qualified 
designees remain responsible for following AEs that are serious, considered related to the IP or 
study procedures, or that caused the subject to discontinue from IP or from the study (see 
Section 7.1). 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE Information 
AEs and SAEs will be collected beginning at the time of consent through the end of the follow-up 
period (including PCP and OLE). All medical occurrences, with the exception of SAEs, that begin 
after obtaining ICF and before first dose of IP will be recorded on the Medical History section of 
the eCRF and not the AE section. 
All SAEs will be recorded and reported to the Sponsor or designee immediately upon the site 
learning of an event and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The Investigator will submit any updated SAE data to the Sponsor within 24 hours of 
it being available. 
Investigators are not obligated to actively seek AEs or SAEs after conclusion of the study 
participation. However, if the Investigator learns of any SAE, including a death, at any time after 
a subject has been discharged from the study, and he/she considers the event to be reasonably 
related to the IP or study participation, the Investigator must promptly notify the Sponsor. 
8.3.2. 
Method of Detecting AEs and SAEs 
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 3. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the subject is the preferred method to inquire about AE 
occurrences. 
8.3.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each subject at 
subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the event is 
otherwise explained, or the subject is lost to follow-up (as defined in Section 7.2). Further 
information on follow-up procedures is given in Appendix 3. 

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8.3.4. 
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 towards the safety of subjects and the 
safety of an IP 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 an IP under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRB/IEC, and investigators. 
• Investigator Safety Reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and Sponsor policy, and 
then the reports will be forwarded to Investigators as necessary. 
• 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 IB and will notify the IRB/IEC, if appropriate 
according to local requirements. 
8.3.5. 
Pregnancy 
• Details of all pregnancies in female subjects and female partners of male subjects will 
be collected after the start of study IP and until birth. 
• If a pregnancy is reported, the Investigator should inform the Sponsor within 24 hours 
of learning of the pregnancy and should follow the procedures outlined in Appendix 4. 
• Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 
8.3.6. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs 
Worsening of UC will be evaluated by efficacy assessments (Section 8.1) and is a disease-related 
outcome not qualifying as an AE unless the Investigator considers the worsening UC to have met 
the definition of an SAE (Appendix 3). Worsening UC meeting the definition of an SAE will be 
reported in the appropriate eCRF. Worsening UC not meeting the definition of an SAE should not 
be reported as an AE. Worsening UC will be evaluated by efficacy endpoints and by the 
occurrence of SAEs, and will be monitored by the Sponsor on a routine basis. 
8.4. 
Pharmacokinetics 
Blood will be collected and used for the measurement of plasma concentrations of GB004, and 
metabolites of GB004 (glucuronide [GBD242] and glucoside [GBD243]) as specified in the SoA 
(Section 1.3.1 – PCP and Section 1.3.2 – OLE). On the visit day, the subject should be instructed 
to take the dose at the site following the predose blood sample draw. If a subject withdraws early 
from the study, a blood sample may also be taken, if possible. 
Colon tissue samples will be collected during flexible sigmoidoscopy/colonoscopy and may be 
used for measuring concentration of GB004. 

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Additionally, stool samples may be analyzed for levels of GB004. 
Samples may also be used for assay development and characterization of potential metabolites of 
GB004. 
Drug concentration information that may unblind the study will not be reported to investigative 
sites or blinded personnel. 
8.5. 
Pharmacodynamics and Biomarkers 
Blood, stool, and colonic biopsy samples should be collected as designated in the SoA 
(Section 1.3.1 – PCP and Section 1.3.2 – OLE) and may be used for exploratory assessment of 
TE/PD biomarkers, eg, histology, c-reactive protein (CRP), fecal calprotectin, fecal lactoferrin, 
gene expression, and immunohistochemistry, e.g. HIF-1α, EGLN1-2-3, etc. 
Samples may be stored at a facility selected by the Sponsor, to enable further analysis of 
biomarker responses to GB004, for a maximum of 8 years (or according to local regulations) 
following the last subject’s last visit for the study. 
Residual blood, and urine samples may be stored for potential future identification of factors or 
profiles that correlate with measures of response to GB004. 
Please refer to the study specific Central Laboratory Manual for PD biomarker details. 
8.6. 
Pharmacogenetic 
Pharmacogenetic (PGx) analyses may be performed on any bio-sample from subjects who have 
consented for PGx sampling. Subject confidentiality will be maintained. 
Suitable bio-samples should be collected from all subjects, where permitted by law and local 
authorities. Those subjects who are prohibited from participating in the PGx research by law 
and/or local authorities, and those subjects providing a written (documented) opt-out, may still 
participate in the study. 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
9.1.1. 
Placebo-Controlled Period 
The PCP is designed to demonstrate the superiority of each GB004 treatment group to placebo on 
the primary endpoint of the proportion of subjects with clinical remission at PCP Week 12. The 
PCP is also designed to demonstrate the superiority of each GB004 treatment group to placebo on 
the primary endpoint of the proportion of subjects with clinical remission at PCP Week 36. 
9.1.2. 
OLE 
The purpose of the OLE period is to evaluate the long-term safety and tolerability of GB004. No 
formal statistical hypotheses are being tested. 

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9.2. 
Sample Size Determination 
9.2.1. 
Placebo-Controlled Period 
A total sample size of approximately 195 subjects (approximately 65 per treatment group, 
randomized 1:1:1, with stratification by systemic corticosteroid use at baseline [yes/no]) is 
estimated to provide approximately 80% power to detect a difference of 20.4% between each 
GB004 treatment group and placebo for the primary endpoint of proportion of subjects with 
clinical remission at PCP Week 12 based on a chi-squared test at an 0.050 two-sided level of 
significance. This assumes the proportion of subjects with clinical remission at PCP Week 12 is 
10% in the placebo group and 30.4% in each GB004 treatment group and a dropout rate by PCP 
Week 12 of approximately 8%. Subjects with missing clinical remission status at PCP Week 12 
will be considered as having not met the primary endpoint. 
Using the same sample size assumptions as above for the primary endpoint of proportion of 
subjects with clinical remission at PCP Week 12 (ie, a difference of 20.4% between each GB004 
treatment group and placebo, with a 10% proportion in the placebo group), there will be 
approximately 80% power for the secondary endpoint of the proportion of subjects with clinical 
remission at PCP Week 36 based on a chi-squared test at an 0.050 two-sided level of significance. 
Subjects with missing clinical remission status at PCP Week 36 will be considered as having not 
met the endpoint. 
9.2.2. 
OLE 
There is no formal sample size calculation for this period of the study. This is an extension of the 
PCP. Subjects must complete at least 12 weeks of treatment in the PCP prior to dosing in the 
OLE. Therefore, the maximum number of subjects potentially eligible to participate in the OLE 
will not be greater than the total number of subjects randomized in the PCP (approximately 195 
subjects). 
9.3. 
Populations for Analyses 
9.3.1. 
Placebo-Controlled Period 
The following major analysis populations are defined for the PCP: 
• Intent-to-treat (ITT) Population: All subjects who are randomized and receive at least 1 
dose of IP, with subjects grouped according to randomized treatment. 
• Safety Population: All subjects who receive at least 1 dose of IP, with subjects grouped 
according to their actual treatment. 
9.3.2. 
OLE 
The following major analysis populations are defined for the OLE: 
• OLE Safety Population: All subjects who receive at least one dose of IP in the OLE. 
• GB004-treated Safety Population: All subjects who receive at least one dose of GB004 
in PCP and/or OLE. 

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9.4. 
Statistical Analyses 
Three separate formal statistical analyses will be performed:   
• The PCP Week 12 Analysis will be conducted after all subjects either complete the 
PCP Week 12 visit or withdraw from the study prior to completion of the PCP Week 
12 visit. This analysis will evaluate endpoints at or up through PCP Week 12. 
• The PCP Final Analysis will be conducted after all subjects either complete the PCP  
or withdraw from the study prior to completion of the PCP;  This analysis will evaluate 
all PCP endpoints. 
• The OLE Final Analysis will be conducted after all subjects either complete the OLE 
period or withdraw from the study prior to completion of the OLE period. 
The study will be unblinded to the Sponsor at the time of the PCP Week 12 Analysis. Therefore, 
the PCP will be double-blind through PCP Week 12 and will remain blinded to subjects, 
investigators, and site staff throughout the PCP. 
In general, continuous variables will be summarized using the number of subjects with non-
missing data, mean, standard deviation, standard error (where appropriate), median, minimum, 
and maximum. Categorical variables will be summarized using counts and percentages.  
For the PCP Week 12 Analysis and the PCP Week 36 Analysis, baseline will be defined as the last 
non-missing value prior to first dose of IP in the PCP. For the OLE Analysis, GB004 baseline will be 
defined as the last non-missing value prior to the first dose of GB004 in the study. 
This section is a summary of the planned statistical analyses of the primary, secondary, and safety 
endpoints. 
9.4.1. 
PCP Week 12 Analysis 
9.4.1.1. 
Efficacy Analyses 
The ITT population will be utilized for efficacy analyses. 
Primary Endpoint  
The primary endpoint of the proportion of subjects with clinical remission at PCP Week 12 will 
be compared between each GB004 treatment group and placebo by a Cochran-Mantel Haenszel 
(CMH) chi-squared test (Mantel, 1959) stratified by systemic corticosteroid use at baseline 
(yes/no) with a two-sided 0.050 level of significance. If stratum cell sizes are too small based on 
the Mantel-Fleiss criterion (Mantel, 1980), Pearson’s chi-squared test will be used instead. 
For the comparison of each GB004 treatment group versus placebo, the p-value from the CMH 
chi-squared test will be reported, along with the estimated Mantel-Haenszel common odds ratio 
across strata and corresponding 95% CI. The number and proportion of subjects meeting the 
primary endpoint and corresponding 95% Wilson (Score) CIs (Wilson, 1927) will be summarized 
by treatment group. The absolute difference in proportion between each GB004 treatment group 
and placebo will also be summarized, with the 95% CI for the absolute difference based on the 
Newcombe continuity-corrected method (Newcombe, 1998). 

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In the primary analysis of the primary endpoint, subjects with missing clinical remission status at 
PCP Week 12 will be considered as having not met the primary endpoint. The primary endpoint 
will also be analyzed using various other methodological approaches for handling subjects with 
missing data as sensitivity analyses. 
Secondary Endpoints 
The secondary endpoints of the proportion of subjects with clinical response at PCP Week 12, the 
proportion of subjects with histologic remission at PCP Week 12, the proportion of subjects with 
endoscopic improvement at PCP Week 12, and the proportion of subjects with mucosal healing at 
PCP Week 12 will be analyzed using the same approach as the primary endpoint. Histologic 
remission at PCP Week 12 and mucosal healing at PCP Week 12 will be evaluated among 
subjects with Baseline lamina propria neutrophils and neutrophils in epithelium 
RHI subscores > 0. 
These secondary endpoints will be assessed at a two-sided level of significance of 0.050 for the 
comparison of each GB004 treatment group and placebo. 
9.4.1.2. 
Safety Analyses 
All safety analyses will be performed using the Safety Population. Safety data will be listed by 
subject. 
Safety analyses will be focused on treatment-emergent AEs, defined as an AE with onset on or 
after the start of study treatment. The incidence of AEs will be summarized by treatment group, 
including the incidence by system organ class and preferred term, severity, and relationship to 
study drug, the incidence of SAEs, the incidence of AEs that lead to discontinuation of study drug, 
and the incidence of AEs that lead to withdrawal from study. 
9.4.2. 
PCP Final Analysis 
The PCP Final Analysis will be performed using the same methodological approaches as the PCP 
Week 12 Analysis. 
9.4.3. 
OLE Final Analysis 
The OLE Safety population will be used as the primary analysis population for safety analyses, 
which will be based on data from the OLE period. 
Select safety analyses will summarize the safety experience of all subjects treated with GB004 in 
the PCP or the OLE period, using the GB004-Treated Safety population, with data combined 
across the PCP and OLE. 
Additionally, in order to inform assessment of whether there appear to be any new or worsening 
safety signals in the OLE period, select safety analyses will summarize the placebo-controlled 
safety experience in the PCP side-by-side with the continuing GB004 safety experience in the 
OLE period (using subjects in the OLE Safety population who were previously treated with 
GB004). 
Safety analyses will be focused on TEAEs, defined as an AE with onset on or after the start of 
study treatment in the respective analysis. The incidence of AEs will be summarized by treatment 

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group, including the incidence by system organ class and preferred term, severity, and relationship 
to study drug, the incidence of SAEs, the incidence of AEs that lead to discontinuation of study 
drug, and the incidence of AEs that lead to withdrawal from study. The incidence of AEs and 
SAEs by system organ class and preferred term may also be presented by time intervals. Incidence 
rates of AEs adjusted for time on study (eg, number of subjects per 1000 subject-years) may also 
be presented. 
9.5. 
Interim Analyses 
During the OLE, interim analyses will be performed as needed for regulatory reporting, safety 
updates, publications, or as otherwise required by the Sponsor. 
9.5.1. 
Data Review Committee 
A DRC, comprised of Sponsor representatives not directly involved in the conduct of the study, 
and external expert physician(s), will regularly monitor overall safety and emerging efficacy 
results on an unblinded basis, as well as general aspects of study conduct, to ensure that the 
benefits and risks of study participation remain acceptable. 
Based on these regular reviews of emerging results, the DRC will recommend continuation, 
modification, or termination of the study. 
Composition of the DRC, meeting structure, schedule, and procedures, the content and format of 
DRC reports, and other relevant details will be determined in consultation with DRC members 
and detailed in a separate DRC charter. 

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10. 
APPENDICES 
APPENDIX 1. 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 (CIOMS) International Ethical Guidelines 
− Applicable ICH Good Clinical Practice (GCP) Guidelines 
− Applicable laws and regulations 
• The protocol, protocol amendments, ICF, IB, 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 approval before implementation 
of changes made to the study design, except for changes necessary to eliminate an 
immediate hazard to study subjects. 
• 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 site and adherence to 
requirements of 21 Code of Federal Regulation (CFR), ICH guidelines, the 
IRB/IEC, European regulation 536/2014 for clinical studies (if applicable), and all 
other applicable local regulations 
Informed Consent Process 
• The Investigator or his/her representative will explain the nature of the study to the 
subject 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 (HIPAA) requirements, where 
applicable, and the IRB/IEC or study center. 

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• The medical record must include a statement that written informed consent was 
obtained before the subject was enrolled 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) during their 
participation in the study. 
• A copy of the ICF(s) must be provided to the subject or the subject’s legally authorized 
representative. 
• Subjects 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 subject 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 subject'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 subject records or 
datasets that are transferred to the Sponsor will contain the identifier only; subject 
names or any information which would make the subject identifiable will not be 
transferred. 
• The subject 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 subject. 
• The subject 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 
A clinical study report will be developed by the Sponsor at completion of data analysis. This 
report will be a clinical and statistical integrated report, according to the ICH E3 guidelines. 
Data Quality Assurance 
• All subject data relating to the study will be recorded on eCRF 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 electronically 
signing the eCRF. 

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• 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. 
• Monitoring details describing strategy (eg, risk-based initiatives in operations and 
quality such as Risk Management and Mitigation Strategies and Analytical Risk-Based 
Monitoring), methods, responsibilities and requirements, including handling of 
noncompliance issues and monitoring techniques (central, remote, or on-site 
monitoring) are provided in the Monitoring Plan. 
• The Sponsor or designee is responsible for the data management of this study 
including quality checking of the data. 
• The Sponsor assumes accountability for actions delegated to other individuals (eg, 
Contract Research Organizations). 
• Study monitors will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of subjects 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 per ICH-GCP and local regulations or institutional 
policies. 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 
• Source documents provide evidence for the existence of the subject and substantiate 
the integrity of the data collected. Source documents are filed at the Investigator’s site. 
• 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. 
• Source documents are original documents, data, and records from which the subject’s 
eCRF data are obtained. These include but are not limited to hospital records, clinical 
and office charts, laboratory and pharmacy records, diaries, microfiches, radiographs, 
and correspondence. 

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Study and Site Closure 
The Sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The Investigator may initiate study-site 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 site 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 subjects by the Investigator 
• Discontinuation of further IP development 
Publication Policy 
The publication policy for this study is located within the Clinical Study Agreement with the 
Investigator and/or Institution. 

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• 
Urine Pregnancy Test 
The additional tests listed in Table 5 will be collected only as part of liver safety actions and 
follow-up (see Section 7.1.3). 
Table 5: 
Liver Safety Laboratory Assessments 
• 
Hepatitis A immunoglobulin M (IgM) antibody 
• 
HBsAg 
• 
Hepatitis C virus antibody 
• 
Hepatitis E IgM antibody 
• 
Cytomegalovirus IgM antibody 
• 
Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, heterophile antibody or 
monospot testing) 
• 
Anti-nuclear antibody 
• 
Anti-smooth muscle antibody 
• 
Type 1 anti-liver kidney microsomal antibodies 
• 
Quantitative total immunoglobulin G (IgG) or gamma globulins 
• 
Serum acetaminophen assay 
• 
Serum creatine phosphokinase (CPK) 
• 
Lactate dehydrogenase (LDH) 
• 
Complete Blood Count with differential 
• 
Obtain blood sample for pharmacokinetic (PK) analysis 
The above assessments will be conducted only if required. 
 

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APPENDIX 4. CONTRACEPTIVE GUIDANCE AND COLLECTION OF 
PREGNANCY INFORMATION 
1. Definitions 
Women of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of IP, additional evaluation should be considered. 
Women in the following categories are not considered WOCBP: 
1. Premenarchal 
2. Premenopausal female with one of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, Mullerian agenesis, androgen insensitivity), Investigator discretion should be applied 
to determining study entry. 
Note: Documentation can come from review of the subject’s medical records, medical 
examination, or medical history interview. 
3. Postmenopausal female 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
− A high follicle stimulating hormone (FSH) level in the postmenopausal range may 
be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, confirmation with more than one FSH measurement is 
required. 
• Female subjects on HRT and whose menopausal status is in doubt will be required to 
use one of the non-estrogen hormonal highly effective contraception methods if they 
wish to continue their HRT during the study. Otherwise, they must discontinue HRT to 
allow confirmation of postmenopausal status before baseline into the study. 

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2. Contraception Guidance 
Male Participants: 
Male subjects are eligible to participate if they agree to the following from consent through at 
least 90 days after the last dose of IP: 
• Refrain from donating sperm 
PLUS either: 
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent 
OR 
• Must agree to use contraception/barrier (condom) 
Female Participants: 
A female subject is eligible to participate if she is not pregnant or breastfeeding, and at least one 
of the following conditions applies: 
• Is not a woman of childbearing potential (WOCBP) 
OR 
• Is a WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of <1% per year), preferably with low user dependency, as described in the 
table below, from 30 days prior to screening, during the study period, and for 30 days 
after the last dose of IP and agrees not to donate eggs (ova, oocytes) for the purpose of 
reproduction during this period. The Investigator should evaluate the effectiveness 
of the contraceptive method in relationship to the first dose of IP. 
• A WOCBP must have a negative highly sensitive pregnancy test 
within 24 hours before the first dose of IP. If the urine test is positive or cannot be 
confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In 
such cases, the subject must be excluded from participation if the serum pregnancy 
result is positive. 

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Highly Effective Methodsa That Have Low User Dependency 
• Implantable progestogen-only hormone contraception associated with inhibition 
of ovulationb  
• Intrauterine device (IUD)  
• Intrauterine hormone-releasing system (IUS)b  
• Bilateral tubal occlusion  
• Vasectomized partner 
(Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the woman of childbearing potential and the 
absence of sperm has been confirmed. If not, an additional highly effective method of 
contraception should be used. Spermatogenesis cycle is approximately 90 days.)  
Highly Effective Methodsa That Are User Dependent 
• Combined (estrogen- and progestogen-containing) hormonal contraception 
associated with inhibition of ovulation 
− oral 
− intravaginal 
− transdermal 
− injectable  
• Progestogen-only hormone contraception associated with inhibition of ovulationb 
− oral 
− injectable  
• Sexual abstinence 
(Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the IP. The reliability of sexual abstinence needs to be evaluated in relation to 
the duration of the study and the preferred and usual lifestyle of the subject.)  
Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive 
methods for those participating in clinical studies. 
a. Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those when 
used consistently and correctly. 
b. Acceptable contraceptive methods are limited to those which inhibit ovulation as the primary mode of action. 
Note: Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception for this 
study. Male condom and female condom should not be used together (due to risk of failure with friction). 

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3. Collection of Pregnancy Information 
Male subjects with partners who become pregnant 
The Investigator will attempt to collect pregnancy information on any male subject’s female 
partner who becomes pregnant while the male subject is 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. Follow-up must be conducted at least until birth 
or termination of the pregnancy. 
Female subjects who become pregnant 
The Investigator will collect pregnancy information on any female subject who becomes pregnant 
while participating in this study. Information will be recorded on the appropriate form and 
submitted to the Sponsor within 24 hours of learning of a subject's pregnancy. 
The subject will be followed to determine the outcome of the pregnancy. The Investigator will 
collect follow-up information on the subject and the neonate and the information will be 
forwarded to the Sponsor. Follow-up must be conducted at least until birth or termination of the 
pregnancy. 
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 post-study pregnancy related 
SAE considered reasonably related to the IP by the Investigator will be reported to the Sponsor as 
described in Appendix 3. While the Investigator is not obligated to actively seek this information 
in former study subjects, he or she may learn of an SAE through spontaneous reporting. 
Any female subject who becomes pregnant while participating in the study will 
discontinue IP or be withdrawn from the study. 

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APPENDIX 5. PHARMACOGENETICS 
Use and Analysis of DNA 
• Germ line variation may impact a subject’s response to IP, susceptibility to, and severity 
and progression of disease. Variable response to IP may be due to genetic determinants 
that impact drug absorption, distribution, metabolism, and excretion; mechanism of action 
of the drug; disease etiology; and/or molecular subtype of the disease being treated. 
Therefore, where local regulations and IRB/IEC allow, a biosample may be collected for 
analysis from subjects. 
• Samples may be analyzed for genetic variations in genes which dramatically affect the 
pharmacokinetics of GB004, the safety, and/or efficacy profile. Often times, a large 
variability in the plasma concentration–time profiles of any medicine can be linked to loss 
of function mutations in the drug metabolizing enzymes and/or transporters. For example, 
substantial efforts have been made in reducing the risk of drug–drug interactions related to 
cytochrome P450 enzymes and variability caused by polymorphic expression of 
metabolizing enzymes (eg, UGT1A1, UGT1A6, UGT2B7). The effects of single 
nucleotide polymorphisms (SNPs) on the PK of GB004 uncovered in the course of this 
study may help guide future clinical studies and regulatory review of GB004. Additional 
pharmacogenetic analyses may be conducted if it is hypothesized that doing so may help 
resolve issues with the clinical data (eg, safety and/or pharmacodynamic observations) 
during the study. 
• The results of these analyses may be reported in a separate study summary. 
• The Sponsor will store the DNA samples in a secure storage space with adequate measures 
to protect confidentiality. 
• The samples will be retained while research on GB004 continues but no longer than 
8 years or other period as per local requirements. 
• The Sponsor may elect to measure the naturally occurring variation across a range of 
relevant pharmacogenetic markers using modern laboratory assays, eg, the ThermoFisher 
DMET™ Plus Solution. This assay, for example, would cover 1,936 genetic variants 
across 231 relevant genes, using a single array, and would include many genetic variants 
that cannot easily be detected using other assays, eg, SNPs and indels with secondary 
polymorphisms in close proximity, triallelic markers, and variants from multi-gene 
families. Particular emphasis would, in this case, be placed on covering the PharmaADME 
“Core ADME Genes” (32 genes) and PharmaADME “Core Markers” (185 variants). If the 
Sponsor finds it necessary, it may move beyond the PharmaADME core content to cover 
common and functional variants associated with the mechanism of action of GB004, 
hepatic detoxification pathways, and/or other markers associated with adverse drug events 
eg, CYP3A4 (392A>G), structural variants in transporter genes – an important 
pharmaceutical target eg, ABCG2 (421C>A), enrichment for mutations in absorption, 
distribution, metabolism, elimination (ADME) regulatory genes eg, PPARD, inclusion of 
many population specific markers eg, VKORC1. 

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APPENDIX 6. PROHIBITED MEDICATIONS 
The following medications are prohibited throughout the study: 
• Azathioprine 
• 6-mercaptopurine 
• Any per rectum therapy (eg, enemas or suppository formulations of steroids or 
5-aminosalicylates) except those required for flexible sigmoidoscopy preparation 
• Marketed biologic therapies for any condition such as adalimumab, infliximab, 
vedolizumab, rituximab, golimumab, ustekinumab 
• Tofacitinib, oral cyclosporine, sirolimus, mycophenolate mofetil 
• Epoetin alfa 
• Cholestyramine or other drugs interfering with enterohepatic circulation 
• Any investigational agent other than GB004 
• Chronic NSAID use (occasional use of NSAID, acetaminophen, or aspirin up to 
325 mg/day is allowed) 
• Anti-diarrheal medications (eg, loperamide, diphenoxylate/atropine) 
• 
Strong CYP3A inhibitors and/or CYP3A inducers (eg, boceprevir, cobicistat, conivaptan, 
danoprevir, ritonavir, elvitegravir, grapefruit juice, indinavir, itraconazole, ketoconazole, 
lopinavir, paritaprevir, ombitasvir, dasabuvir, posaconazole, saquinavir, telaprevir, 
tipranavir, troleandomycin, voriconazole, clarithromycin, diltiazem, idelalisib, nefazodone, 
nelfinavir, (carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John’s wort) 
• 
Inhibitors of UGT (eg, atazanavir; oral cannabidiol [≥5 mg/kg/day]; elbasvir and 
grazoprevir; encorafenib; epirubicin; oral fluconazole; fostamatinib; glecaprevir and 
pibrentasvir; isavuconazole; nelfinavir; ombitasvir and paritaprevir and ritonavir and 
dasabuvir; pazopanib; regorafenib; valproic acid).  
• 
Dofetilide 
• Sensitive CYP2C8 substrates (eg, repaglinide, rosiglitazone, pioglitazone, loperamide). 
 
 
 
 

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APPENDIX 7. LIVER SAFETY – ACTIONS AND FOLLOW-UP 
ASSESSMENTS 
Liver assessments performed as part of the standard clinical chemistry evaluations will be 
evaluated as specified in the SoA (Section 1.3.1 – PCP and Section 1.3.2 – OLE) and Appendix 2 
(Table 5). Parameters will include ALT, AST, GGT, ALP, total bilirubin, and direct bilirubin. 
For subjects with ALT or AST ≥ 2 × ULN and < 3 × ULN, confirm the value within 72 hours. 
Contact the Sponsor's Medical Monitor (or designee) to determine if additional liver monitoring is 
indicated. Blood sample for pharmacokinetic (PK) analysis should also be obtained. 
For liver chemistry abnormalities actions and follow-up assessments refer to Section 7.1.3, and for 
dose modification refer to Section 6.5.1. The criteria requiring additional liver monitoring with 
possible IP interruption is provided in Table 6. 
Table 6: 
Liver Chemistry Criteria Requiring Additional Monitoring with Possible Dose 
Modification of Investigational Product  
Criteria 
Actions 
ALT or AST ≥ 3 ULN and 
< 5 ULN 
AND bilirubin ≤ 2 ULN 
AND without symptoms 
believed to be related to liver 
injury or hypersensitivitya 
AND who can be monitored 
weekly for 4 weeks 
• 
Notify the Sponsor's Medical Monitor (or designee) within 24 
hours of learning of the abnormality to discuss subject safety. 
“Liver Safety Laboratory Assessment” in Table 5 may be 
requested by the Sponsor's Medical Monitor (or designee). 
• 
Confirm values within 24-48 hours via repeat laboratories 
(include ALT, AST, GGT, ALP, total bilirubin, direct bilirubin, 
and INR). 
• 
If unable to obtain repeat laboratories within 24-48 hours, 
decision to continue or interrupt IP will be determined by the 
Investigator in consultation with the Sponsor's Medical Monitor 
(or designee). 
• 
If repeat laboratories confirm that criteria are met, the dose of 
IP may be reduced, with approval from the Sponsor's Medical 
Monitor (or designee), to doses mentioned in Section 6.5.1. 
• 
Subject must return weekly or more frequently for repeat liver 
chemistry tests (ALT, AST, GGT, ALP, total bilirubin, direct 
bilirubin, and INR) until the abnormalities resolve, stabilize or 
return to baseline. 
• 
If at any time the subject meets liver chemistry interruption 
criteria (as specified in Table 7), then follow the instructions in 
“Liver Chemistry – Investigational Product Interruption 
Criteria” in Table 7 and in consultation with the Sponsor's 
Medical Monitor (or designee) initiate relevant assessment 
procedures. 
a New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or hypersensitivity (such as fever, rash or eosinophilia). 

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Table 7: 
Liver Chemistry Criteria Requiring Investigational Product Interruption and 
Additional Monitoring 
Liver Chemistry – IP Interruption Criteria 
ALT/AST (single occurrence) 
ALT or AST ≥ 5 ULN 
ALT/AST 
ALT or AST ≥ 3 ULN persists for ≥ 4 weeks 
+ Bilirubin a,b 
ALT or AST ≥ 3 ULN and 
bilirubin > 2 ULN (> 35% direct bilirubin) 
+ INR b 
ALT or AST ≥ 3 ULN and 
international normalized ratio (INR) > 1.5, if INR measured 
+ Cannot Monitor 
ALT or AST ≥ 3 ULN and cannot be monitored weekly for 4 weeks 
+ Symptomatic c 
ALT or AST ≥ 3ULN associated with symptoms (new or 
worsening) believed to be related to liver injury or hypersensitivity 
ACTIONS 
• 
Immediately interrupt IP. 
• 
Report the event to the Sponsor's Medical Monitor (or designee) within 24 hours. 
• 
Repeat liver chemistry tests (include ALT, AST, GGT, ALP, total bilirubin, direct bilirubin, 
and INR) and perform the Liver Safety Laboratory Assessments (Table 5) within 24 hours. 
• 
If the repeat liver chemistry test confirms the criteria are met, monitor the subject until liver 
chemistry test abnormalities resolve, stabilize, or return to baseline after discussion with the 
Sponsor's Medical Monitor (or designee) (see MONITORING). 
• 
Do not restart IP unless Sponsor's Medical Monitor (or designee) approval is granted. If 
restart is granted, IP may be restarted at modified dose (Section 6.5.1). 
• 
If restart not granted, permanently discontinue IP and continue subject in the study for any 
protocol specified follow up assessments. 
• 
Complete an SAE data collection tool if the event also met the criteria for an SAE.b 
• 
Liver imaging (ultrasound, magnetic resonance, or computerized tomography), liver biopsy, 
and/or specialist consultation to evaluate liver disease may be requested by the Sponsor. 
MONITORING 
If ALT or AST ≥ 3 ULN AND bilirubin > 
2 ULN or INR > 1.5: 
• 
Monitor subject twice weekly until liver 
chemistry test abnormalities resolve, 
stabilize, or return to baseline. 
If ALT or AST ≥ 3 ULN AND bilirubin ≤ 2 
ULN and INR ≤ 1.5: 
• 
Monitor subjects weekly until liver chemistry 
abnormalities resolve, stabilize, or return to 
baseline. 
a Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue IP if ALT or AST ≥ 3 × ULN and bilirubin > 2 × ULN. Additionally, if serum 
bilirubin fractionation testing is unavailable, record the absence/presence of detectable urinary bilirubin on 
dipstick which is indicative of direct bilirubin elevations suggesting liver injury. 
b All events of ALT or AST ≥ 3 × ULN and bilirubin > 2 × ULN (> 35% direct bilirubin) or ALT or AST ≥ 3 × ULN 
and INR > 1.5 may indicate severe liver injury (possible ‘Hy’s Law’) and must be reported as an SAE 
(excluding studies of hepatic impairment or cirrhosis). The INR stated threshold value will not apply to subjects 
receiving anticoagulants. INR is not part of routine laboratory assessments in this study. 

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c New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or hypersensitivity (such as fever, rash or eosinophilia) 

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APPENDIX 8. INSTRUCTIONS FOR CALCULATING MAYO SCORE 
FOR UC DISEASE ACTIVITY CRITERIA ASSESSMENT  
Table 8 provides instructions for calculating the Mayo score for assessing the predefined UC 
disease activity criteria at or after the PCP Week 12 visit and prior to the PCP Week 36 visit 
(Section 5.3) while the subject is receiving IP. 
Table 8: 
Instructions for Calculating Mayo Score For UC Disease Activity Criteria 
Assessments (at or after PCP Week 12 visit and prior to PCP Week 36 visit) 
Timepoint 
Instructions 
At PCP Week 12 visit (post 
endoscopy) 
• Use PCP Week 12 visit Mayo score and centrally 
read Endoscopic subscore  
At PCP post-Week 12 visit and 
prior to PCP Week 36 visit 
• Use 
− Updated centrally read Endoscopic subscore 
(unscheduled) if previous flexible sigmoidoscopy 
was conducted > 4 weeks prior, otherwise use PCP 
Week 12 centrally read Endoscopic subscore 
− Updated Stool frequency subscore, Rectal 
bleeding subscore, and PGA 
Notes:  
• 
If, after the PCP Week 12 visit and prior to the PCP Week 36 visit, the investigator becomes aware of an 
increase in UC disease activity outside the normal visit schedule in a subject on IP, then a subject may also be 
evaluated at an Unscheduled UC Disease Activity Criteria Assessment visit as specified in the SoA 
(Section 1.3.1).  
• 
Endoscopic subscores will be assessed by both a central reader (who is blinded to treatment assignment, visit, 
and subject symptoms) and local endoscopist (who is blinded to treatment assignment). Differences between the 
local endoscopist and the central reader will be adjudicated by a second blinded central reader as described in 
the Imaging Charter. 

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APPENDIX 9. 
GUIDANCE TO ADDRESS A PANDEMIC OR OTHER GLOBAL 
HEALTH EMERGENCIES AND POTENTIAL IMPACT ON THE 
CLINICAL STUDY 
In the occurrence of a global health emergency affecting the conduct of the ongoing study, such as the 
COVID-19 pandemic, study conduct may be adjusted due to subjects being in self-
isolation/quarantine, limited access to public places (including hospitals) due to the risk of spreading 
infections, and health care professionals being committed to critical tasks. 
Adjustments to the GB004-2101 protocol may be made as described below, in line with global 
regulatory authorities guidance in order to ensure the safety of study participants, maintain compliance 
with GCP, and minimize the risks to study integrity during the COVID-19 pandemic (EMA, April 
2020; FDA, March 2020; Health Canada, 03 April 2020; MHRH, 22 April 2020). Member states 
within the National Competent Authorities may issue their own guidance requiring country specific 
recommendations to be followed. 
Informed Consent 
• If written consent by the study subject is not possible (for example because of physical 
isolation due to COVID-19 or other global health emergencies), consent could be given 
orally by the study subject. 
• Study subjects and the person obtaining consent could sign and date separate ICFs. 
• In case a written informed consent cannot be obtained at the clinical site, electronic 
informed consent can be obtained remotely. Alternatively, the consent form may be 
sent to the subject or the subject’s legally authorized representative by facsimile or 
e-mail, and the consent interview may then be conducted by telephone/teleconference 
when the subject or subject’s legally authorized representative can read the consent 
form during the discussion; the subject or subject’s legally authorized representative 
will be requested to sign and date a blank piece of paper with a written statement 
affirming that they agree to participate in the study. 
• If re-consent is necessary for the implementation of new urgent changes in study 
conduct (mainly expected for reasons related to global health emergencies or important 
safety issues for other studies), alternative ways of obtaining may include contacting 
the study subject via phone or video-calls and obtaining oral consents, to be 
documented in the study subjects’ medical records, supplemented with e-mail 
confirmation. 
• The informed consent procedure is to remain compliant with the study protocol as well 
as local regulatory requirements. All relevant records should be archived in the 
investigator's site master file. A correctly signed and dated informed consent form 
should be obtained from the study subjects later, as soon as possible. 
Study Visits and Procedures 
• COVID-19 screening procedures that may be mandated by the health care system in 
which a clinical study is being conducted do not need to be reported as an amendment 
to the protocol even if done during clinical study visits. The Investigator in 

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consultation with the Sponsor will decide if it is in the best interest of COVID-positive 
subjects to remain in the study. 
• In the case of missed visits due to global health emergencies (or other health pandemic) 
related reasons: 
− The site should make every effort to contact the study subject to confirm and 
document the reason for the missed visit, and at minimum evaluate AEs/SAEs, and 
concomitant medications in order to assess subject safety. 
− The study subject should continue to collect the daily diary responses on the 
eDiary. 
• In order to maintain the integrity of the study, alternative methods of collecting study 
procedures may be considered where possible: 
− In cases where global health emergencies-related circumstances preclude a visit to 
the investigative site, remote visits (eg, by telemedicine or phone contact) will be 
allowed for relevant study procedures. 
− In certain situations, with Sponsor approval, and according to site business 
continuity plans, home visits may be used to collect laboratory samples and 
assessments as required by the protocol.  
− In certain situations, with Sponsor approval, a local laboratory may be used to 
collect laboratory samples as required by the protocol. Local analysis can be used 
for safety decisions. In addition, local laboratory can be used for study endpoints if 
samples drawn at the local laboratory cannot be shipped to the central laboratory. 
− Study assessments will only be conducted in a remote manner if they can be done 
without affecting the wellbeing of the subject during the study and with the same 
level of scientific integrity as assessments conducted in a physical study center.  
− Remote study assessments can be completed via online technology. The subject 
may interact with study personnel using online communication tools which 
incorporate telemedicine.  
− Serum pregnancy tests can be performed if urine pregnancy cannot be performed. 
− For flexible sigmoidoscopy assessments in the PCP at the PCP Week 12 visit, PCP 
Week 36 visit, Unscheduled UC Disease Activity Criteria Assessment visit(s) and 
Early Withdrawal from Study visit, other options such as mobile endoscopy may 
be considered with Sponsor’s approval. 
− If a subject is unable to complete the PCP Week 12 and/or Week 36 flexible 
sigmoidoscopy within the required timeframe (per SoA), there is flexibility to 
conduct the endoscopy up to 14 days beyond the visit window for the planned 
Week 12 and/or Week 36 timepoint while continuing on IP (if the subjects has not 
previously permanently discontinued IP); in this case, an unscheduled visit will be 
conducted at the planned Week 12 and/or Week 36 timepoint remotely (eg, by 
telemedicine) to collect AEs and concomitant medication (additional IP will be 

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dispensed as needed); the Week 12 and/or Week 36 visit assessments will be 
required at the clinic within 3 days post-endoscopy. 
Supply of Investigational Product 
• Alternative methods of supplying IP to enrolled study subjects (eg, direct-to-patient 
shipment from site) may be considered where possible. 
• Additional IP will not be released to the subject without an evaluation of subject 
safety, including protocol-required laboratory results (at a minimum hematology, 
clinical chemistries and pregnancy for WOCBP), and clearance communicated to 
the subject. Subjects must also consent for IP shipment. 
Monitoring and Audits 
• Certain Sponsor oversight responsibilities, such as monitoring and quality assurance 
activities need to be re-assessed and temporarily, alternative proportionate mechanisms of 
oversight may be required. On-site audits will be avoided or postponed, and if permitted 
under local regulations, social distancing restrictions should apply. 
• Cancelling or postponing of on-site monitoring visits and extending of the period between 
monitoring visits will be allowed. 
• To the extent on-site monitoring remains feasible, it should take into account national, 
local and/or organizational social distancing restrictions. 
• Centralized monitoring can be considered for data acquired by electronic data capture 
systems (eg, eCRFs, central laboratory or ECG / imaging data, electronic patient reported 
outcomes, etc.) that are in place or could be put in place provides additional monitoring 
capabilities that can supplement and temporarily replace on-site monitoring through a 
remote evaluation of ongoing and/or cumulative data collected from trial sites, in a timely 
manner. 
• Off-site monitoring can be conducted and will include phone calls, video visits, e-mails or 
other online tools in order to discuss the study with the investigator and site staff. Remote 
monitoring should be focused on review of critical study site documentation and 
source data. These activities could be used to get information on the clinical study 
progress, to exchange information on the resolution of problems, review of procedures, 
study subject status as well as to facilitate remote site selection and investigator training 
for critical study procedures. 
Risk Mitigation 
• The Sponsor will continually assess whether the limitations imposed by the COVID-19 
public health emergency on protocol implementation pose new safety risks to study 
subjects, and whether it is feasible to mitigate these risks by amending study processes 
and/or procedures. 

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APPENDIX 10. LIST OF ABBREVIATIONS AND DEFINITIONS OF 
TERMS 
The terms IP and study drug are used interchangeably throughout this document.  
LIST OF ABBREVIATIONS  
DEFINITIONS OF TERMS 
5-ASA 
5-aminosalicylate 
ADME  
absorption, distribution, metabolism, elimination 
AE 
adverse event 
ALT 
alanine aminotransferase 
anti-TNF 
anti-tumor necrosis factor 
AST 
aspartate aminotransferase 
AUC 
area under the drug concentration versus time curve 
AUC(0-τ) 
area under the curve during a dose interval 
BID 
twice per day 
BMI 
body mass index 
CFR 
Code of Federal Regulations 
Cmax 
maximum observed concentration 
CI 
confidence interval 
CL/F 
total body clearance corrected for bioavailability 
CIOMS 
Council for International Organizations of Medical Sciences 
CKD-EPI 
chronic kidney disease epidemiology collaboration 
CMC 
carboxy methyl cellulose 
CMH 
Cochran-Mantel-Haenszel 
CONSORT 
Consolidated Standards of Reporting Trials 
CPK 
creatine phosphokinase  
CRP 
c-reactive protein 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
coefficient of variation 
CYP 
cytochrome P450 
DNA 
deoxyribonucleic acid 
DR 
delayed-release or gastro-resistant 
DRC 
Data Review Committee 
DSS 
dextran sulfate sodium 
ECG 
electrocardiogram 

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LIST OF ABBREVIATIONS  
DEFINITIONS OF TERMS 
eCRF 
electronic case report form 
eDiary 
electronic diary 
eGFR 
estimated glomerular filtration rate 
EPO 
erythropoietin 
ET 
early termination 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase  
GI 
gastrointestinal 
HBsAg 
hepatitis B surface antigen 
HDPE 
high-density polyethylene 
HIF 
hypoxia inducible factor 
HIF-1α  
hypoxia inducible factor 1 alpha 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
HPβCD 
2-hydroxypropyl-beta-cyclodextrin 
HRT 
hormone replacement therapy 
IB 
Investigator’s brochure 
IBD 
inflammatory bowel disease 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee  
IgG 
immunoglobulin G  
IgM 
Immunoglobulin M 
INR 
international normalized ratio  
IP 
investigational product 
IRB 
Institutional Review Board  
IRT 
interactive response technology 
ITT 
intent-to-treat 
IUD 
intrauterine device 
IUS 
intrauterine hormone-releasing system 
MAD 
multiple ascending dose 

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LIST OF ABBREVIATIONS  
DEFINITIONS OF TERMS 
MMX 
multi-matrix 
NASH 
non-alcoholic steatohepatitis  
NOAEL 
no observed adverse effect level 
NSAID 
non-steroidal anti-inflammatory agents 
OLE 
open-label extension 
OTC 
over-the-counter 
PCP 
placebo-controlled period 
PD 
pharmacodynamics 
PGA 
Physician’s Global Assessment 
PGx 
pharmacogenetics 
PHD 
prolyl hydroxylase 
PHDi 
prolyl hydroxylase inhibitor 
PK 
pharmacokinetic 
QD 
once daily 
QTc 
corrected QT interval 
QTcF 
QT interval corrected for heart rate using Fridericia’s formula 
RHI 
Robarts Histopathology Index 
RNA 
ribonucleic acid 
SAD 
single ascending dose 
SAE 
serious adverse event 
SNP 
single nucleotide polymorphism 
SoA 
Schedule of Activities  
SNP 
single nucleotide polymorphism 
SUSAR 
suspected unexpected serious adverse reactions 
t1/2 
apparent terminal half-life 
Tmax 
time of occurrence of maximum observed concentration 
TE 
target engagement 
TEAE 
treatment-emergent adverse events 
TNBS 
trinitrobenzene sulfonic acid  
TNF-α 
tumor necrosis factor alpha  
UC 
ulcerative colitis 
UC-100 Index 
Ulcerative colitis 100 index 

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LIST OF ABBREVIATIONS  
DEFINITIONS OF TERMS 
UGT 
uridine-diphosphoglucuronosyl transferase 
ULN 
upper limit of normal 
Vd/F 
oral apparent volume of distribution corrected for 
bioavailability 
VEGF 
vascular endothelial growth factor 
WBC 
white blood cells 
WOCBP 
women of childbearing potential  

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APPENDIX 11. PROTOCOL AMENDMENT HISTORY 
Amendment 1.0 (v2.0, 21 October 2020) 
Overall Rationale for the Amendment: 
The rationale for changes in this amendment includes primarily updates that extend the duration 
of the placebo-control period of the study and incorporate an open-label extension.  
Table 1: Summary of Changes 
Section # and Name 
Description of Change 
Brief Rationale 
Global change affecting all 
protocol sections, including, 
but not limited to: 
1 Protocol summary 
3 Objectives/endpoints 
4 Study design 
5 Eligibility criteria 
6 Investigational product 
7 Discontinuation of IP 
8. Study procedures 
9 Statistical consideration 
Extend the duration of 
placebo-controlled period 
(PCP) to 36 weeks and add a 
24-week open-label extension 
To evaluate the benefit-risk profile of 
GB004 compared to placebo with 
longer term dosing up to 36 weeks in 
terms of efficacy, safety, and 
tolerability, and to obtain further safety 
experience with the higher dose of 
GB004 (BID) in an open-label 
extension study 
1.1 Protocol synopsis 
1.3.1 SoA 
4.1 Overall study design 
Extend duration of screening 
period to 5 weeks 
To provide adequate time to complete 
all screening assessments 
2.3.2 Risk assessment 
Update risks 
To reflect emerging data and to align 
with the investigator’s brochure 
5.1 Inclusion criteria 
• 
Clarify age for inclusion 
• 
Add beclomethasone as 
allowed UC background 
therapy 
• 
To comply with different country 
regulations 
• 
To expand list of permitted 
background steroid therapy 
5.2 Exclusion criteria 
Exclude pregnant/lactating 
women 
To reflect that pregnant/lactating 
women should be excluded 
5.3 UC disease activity 
criteria 
Appendix 8 Instructions for 
calculating Mayo score for 
UC disease activity criteria 
assessment 
Add sections 
Part of modifying the study design 
(mentioned above) 
6.5.2 Background UC 
therapy 
Add tapering instructions for 
systemic steroids after PCP 
Week 12 
Part of modifying the study design 
(mentioned above) 

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Section # and Name 
Description of Change 
Brief Rationale 
6.8 Concomitant therapy 
Delete section on CYP3A4 
Per emerging in vitro data suggesting 
that GB004 and its glucuronide 
metabolite have a low potential to 
inhibit CYP3A4 substrates 
8.1.3 RHI Score, Geboes 
Score and UC Index-100 
Add RHI calculation 
For clarity 
8.2.1 Physical examination 
Clarify and differentiate 
between complete and 
symptom-directed physical 
examination 
For clarity 
Appendix 9 Guidance to 
address a pandemic or other 
global health emergencies 
Update 
To reflect updated guidance by 
regulatory agencies 
General 
Minor clarifications 
throughout protocol 
Update list of abbreviations, 
formatting, hyperlinks 
For consistency and accuracy 
throughout protocol 

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11. 
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