Clinical trial NCT05291689
Conditions: Inflammatory Bowel Diseases Colitis, Ulcerative
Keywords: Ulcerative Colitis (UC) Inflammatory Bowel Disease (IBD) a4b7 Moderately to severely active ulcerative colitis Integrin
Sponsor: Morphic Therapeutic, Inc. (A Wholly Owned Subsidiary of Eli Lilly and Company)
Start date: 2022-05-24; Completion date: 2025-02-19
Enrollment: 39 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is an open-label, single arm, multicenter, Phase 2a study evaluating the efficacy, safety, and tolerability of MORF-057 in adult patients with Moderately to Severely Active Ulcerative Colitis (UC)

Detailed description:
The main part of this Phase 2a study will consist of 3 study periods: a Screening Period, a Treatment Period and a Safety Follow-up Period. All participants who complete the open-label Treatment Period will have the opportunity to continue their treatment in an optional 26-week Long-term Extension study after completing the Week 52 assessments.

Arms: arm 1: None
Interventions: intervention 1: MORF-057
Intervention descriptions: intervention 1: MORF-057 is a small molecule that is designed to selectively inhibit integrin α4β7 and is administered orally.

Protocol documents:
Prot_000.pdf: 
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CLINICAL STUDY PROTOCOL 
 
Protocol Title:  
A Phase 2a, Open-label, Single-arm Study to Evaluate the 
Efficacy, Safety, and Tolerability of MORF-057 in Adults with 
Moderately to Severely Active Ulcerative Colitis 
(EMERALD-1) 
Protocol Number: 
MORF-057-201 
Compound: 
MORF-057 
Brief Title: 
A Phase 2a Study to Evaluate the Efficacy and Safety of 
MORF-057 in Adults with UC 
Indication 
Moderately to severely active ulcerative colitis 
Study Phase: 
2a 
Sponsor:  
Morphic Therapeutic, Inc. 
35 Gatehouse Drive, A2 
Waltham, MA 02451, USA 
IND Number: 
147011 
Date of Protocol: 
Version 4, 27 July 2023 
 
 
 
 
 
 
 
 
 
Confidentiality Statement 
The information contained herein is confidential and the proprietary property of Morphic Therapeutic, Inc. 
(hereinafter, Morphic Therapeutic) and any unauthorized use or disclosure of such information without the prior 
written authorization of Morphic Therapeutic is expressly prohibited. This study will be conducted according to the 
protocol and in compliance with Good Clinical Practice, the ethical principles stated in the Declaration of Helsinki, 
and other applicable regulatory requirements. 
 


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PROTOCOL AMENDMENT SUMMARY OF CHANGES 
DOCUMENT HISTORY 
Document 
Date 
Protocol V1 
16 December 2021 
Protocol V2 
09 February 2022 
Protocol V3 
01 September 2022 
Protocol V4 
27 July 2023 
 
Version 4 dated 27 July 2023 
Overall Rationale for the Amendment 
The overall rationale for the protocol amendment Version 4.0 is to introduce planned analyses of 
the 52-week Treatment Period for the Main Cohort, and the 12-week Treatment Period for the 
Exploratory Cohort.  
The protocol amendment Version 4.0 is considered Substantial by the Sponsor, in accordance with 
international regulations.  
 
Version 3 dated 01 September 2022 
Overall Rationale for the Amendment  
The overall rationale for the protocol amendment Version 3.0 is to add the following major 
changes: 
• 
Change Open-label Extension to Long-term Extension and add details to Schedule of 
Assessments, add corresponding objective and endpoints, and update study 
design/schema 
• 
Clarify and expand the enrollment goal 
• 
Update the indication name 
• 
Add Safety Analysis Population and PK Evaluable Population 
• 
Remove the planned interim analysis for sample size reassessment and accordingly 
adjust the statistical significance level to be used in the analysis of the primary 
efficacy endpoint  
• 
Clarify the planned analyses for Induction Period, 52-week Treatment Period, and 
Long-term Extension 
• 
Revise Inclusion/Exclusion criteria regarding rectal bleeding subscore, body mass 
index, surgical procedures, tuberculosis testing, exploratory cohort (vedolizumab 
failures) and vedolizumab levels testing 
• 
Specify timing of blood draws for safety-related laboratory tests 
• 
Add the progressive multifocal leukoencephalopathy (PML) objective list 
• 
Add guidance on overdose reporting  


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• 
Add guidance on budesonide tapering 
• 
Remove erythrocyte sedimentation rate test 
• 
Add PML Adjudication Committee responsibilities 
The protocol amendment Version 3.0 is considered Substantial by the Sponsor, in accordance with 
international regulations.  
 
Version 2 dated 09 February 2022 
Overall Rationale for the Amendment  
The overall rationale for the protocol amendment Version 2.0 is to extend the study treatment 
period from 12 weeks to 52 weeks (resulting in the addition of 5 new study site visits), to add 
European study sites, and to add the option of participating in an Open-label Extension study at 
the end of the current study.  
The protocol amendment Version 2.0 is considered Substantial by the Sponsor, in accordance with 
international regulations.  
The changes of the protocol amendment Version 2.0 in comparison to Version 1.0 are summarized 
in Section 10.10. 


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Summary of Changes Table 
Changes to the protocol as implemented by the protocol amendment Version 4.0 in comparison to Version 3.0 are summarized in the 
Summary of Changes table below. New text is shown in italics, deleted text is shown in strikeout, and bold text is informational. In 
addition to the changes provided in the Summary of Changes table, minor editorial changes have been made throughout the protocol. 
Version 4.0 vs Version 3.0 
Section No. and Name 
Description of Change 
Brief Rationale 
Synopsis - Overall Design 
Section 4.1. Overall Design 
 
Thus, there will be a total of 30 to 40 participants in the study. because wWhen the Main Cohort recruits 
30 participants, the entire study will be closed to new enrollees for any new screening in the Main Cohort, 
and the remaining participants already in screening will be allowed to complete the process and enroll, if 
eligible. 
To clarify that the 
remaining participants 
already in screening, when 
the maximum number of 
participants have enrolled 
into the main cohort, will 
be allowed to complete the 
process and enroll, if 
eligible 
Synopsis - Statistical Methods; 
General Considerations 
Section 9.2.1. General 
Considerations 
The Main Cohort and Exploratory Cohort will be analyzed separately, unless specified otherwise. Data 
from participants in the Exploratory Cohort will be analyzed only for exploratory purposes. 
To clarify that the Main 
Cohort and Exploratory 
Cohorts will be analyzed 
separately 
Synopsis - Statistical Methods; 
Analyses for Induction Period, 52-
week Treatment Period, and Long-
term Extension 
Section 9.3. Analyses for Induction 
Period, 52-week Treatment Period, 
and Long-term Extension 
There will be 24 analyses planned: twoone for the 12-week Induction Periods of the Main and Exploratory 
Cohorts respectively (i.e., the period for the primary efficacy endpoint) and the other two for the 52-week 
Treatment Periods of the Main and Exploratory cohorts respectively (i.e., the 12-week Induction Period 
plus the 40-week Maintenance Period and the Safety Follow-up). 
Introduction of the Main 
Cohort 52-week analysis 
and Exploratory Cohort 
12-week analysis 
Synopsis - Statistical Methods; 
Induction Period Analysis 
Section 9.3. Analyses for Induction 
Period, 52-week Treatment Period, 
and Long-term Extension, Induction 
Period Analysis 
The analysis of the Induction Period will be performed after all the participants in the Main Cohort have 
completed the 12-week Induction Period (i.e., completed the Week 12 visit) or discontinued the study 
before the Week 12 assessment). The analysis will formally evaluate the primary and secondary efficacy 
endpoints, all the exploratory endpoints defined by Week 12, PK concentrations and parameters, and 
safety of MORF-057 for the Main Cohort during the 12-week Induction Period.  
The analysis of the Induction Period for the Exploratory Cohort will be performed after all the participants 
in the Exploratory Cohort have completed the 12-week Induction Period (i.e., completed the Week 12 visit) 
or discontinued the study before the Week 12 assessment. The analysis will evaluate all the efficacy and 
To clarify the Main 
Cohort induction analyses 


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Section No. and Name 
Description of Change 
Brief Rationale 
exploratory endpoints, PK concentrations and parameters, and safety of MORF-057 for the Exploratory 
Cohort during the 12-week Induction Period. In the event that the timing of the Induction Period analysis 
for the Exploratory Cohort aligns closely with the timing of the 52-week Treatment Period analysis for the 
Main Cohort described below, both analyses will be combined into one analysis. 
Only Induction Period data will be used in thise Induction Period analysies. 
Synopsis - Statistical Methods; 52-
week Treatment Period Analysis 
Section 9.3. Analyses for Induction 
Period, 52-week Treatment Period, 
and Long-term Extension, 52-week 
Treatment Period Analysis 
 
For the Main Cohort, tThe analysis of the 52-week Treatment Period will be performed after all the 
participants have completed the 52-week open-label Treatment Period (and the Safety Follow-up Period for 
participants not enrolling into the optional Long-term Extension Period) or discontinued the study before 
the Week 52 assessment and the Safety Follow-up Period. In the event that the timing of the 52-week 
Treatment Period analysis for the Main Cohort aligns closely with the timing of the Induction Period 
analysis for the Exploratory Cohort, both analyses will be combined into one analysis. 
For the Exploratory Cohort, the analysis of the 52-week Treatment Period will be performed after all the 
participants have completed the 52-week open-label Treatment Period (and the Safety Follow-up Period for 
participants not enrolling into the optional Long-term Extension Period) or discontinued the study before 
the Week 52 assessment and the Safety Follow-up Period. 
 The 52-week Treatment Period analyseis will formally evaluate all the exploratory endpoints defined by 
Week 52, PK concentration and parameters, and safety of MORF-057 during the 52-week open-label 
Treatment Period plus the Safety Follow-up Period. The cumulative data, including those from the Induction 
Period, will be used in thisese analysies. The data from the Main and Exploratory Cohorts may be pooled 
together in the safety analyses as appropriate 
For the Main Cohort participants, tThe analysis of the 52-week Treatment Period will be performed after 
all the participants have completed the 52-week open-label Treatment Period (and the Safety Follow-up 
Period for participants not enrolling into the optional Long-term Extension Period) or discontinued the 
study before the Week 52 assessment and the Safety Follow-up Period. In the event that the timing of the 
52-week Treatment Period analysis for the Main Cohort aligns closely with the timing of the Induction 
Period analysis for the Exploratory Cohort, both analyses will be combined into one analysis. 
For the Exploratory Cohort participants, the analysis of the 52-week Treatment Period will be performed 
after all participants have completed the 52-week open-label Treatment Period (and the Safety Follow-up 
Period for participants not enrolling into the optional Long-term Extension Period) or discontinued the 
study before the Week 52 assessment and the Safety Follow-up Period. 
The 52-week Treatment Period analysies for the Main and Exploratory Cohorts will formally evaluate all 
the exploratory endpoints defined by Week 52, PK concentration and parameters, and safety of MORF-
057 during the 52-week open-label Treatment Period plus the Safety Follow-up Period. The cumulative 
data, including those from the Induction Period, will be used in theseis analyseis.  
Introduction of Main 
Cohort 52-week analysis 
and Exploratory Cohort 
12-week analysis 


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Section No. and Name 
Description of Change 
Brief Rationale 
The data from the Main and Exploratory Cohorts may be pooled together in the safety analyses as 
appropriate. 
Section 1.2 Schedule of 
Assessments (SoA); Tables 1 and 2. 
Schedule of Activities for the 
Treatment Period and for the Long-
term Extension 
 
 
 
Section 8.8.1 Physical Examinations 
 
Schedule of Activities, Table 1, Footnote “r” and Table 2, Footnote “h”:  
Footnote “r”: A complete physical exam is to be performed at Screening and Visit 10/EOT, and a targeted 
exam may be performed at all other required visits (see Section 8.8.1 for descriptions). For unscheduled 
visits, that involve the Investigator or clinical assessment and not the visits that would be for dispensing 
study drug or for laboratory draws only, the type of exam will be at the Investigator’s discretion and 
determined based on the reason for the visit. 
Footnote “h”: A targeted physical exam is to be performed at all visits (see Section 8.8.1 for descriptions). 
For unscheduled visits, that involve the Investigator or clinical assessment and not the visits that would be 
for dispensing study drug or for laboratory draws only, the type of exam will be at the Investigator’s 
discretion and determined based on the reason for the visit. 
Physical examinations will be performed at the timepoints specified in the SoA (Section 1.2). A complete 
physical exam is required at Screening and Visit 10/EOT, and a targeted exam may be performed at all 
other required visits. For unscheduled visits, that involve the Instigator or clinical assessment and not the 
visits that would be for dispensing study drug or for laboratory draws only, the choice of whether to 
perform a complete or targeted physical exam is at the discretion of the Investigator and will depend on 
the reason for the unscheduled visit. Physical examinations must be performed by an Investigator or a 
medically qualified designee.   
To clarify that a 
completed or targeted 
physical exam only needs 
to be performed for visits 
that involve the 
Investigator or clinical 
assessment visits 
Section 1.2. Schedule of 
Assessments (SoA); Tables 1 and 2. 
Schedule of Activities for the 
Treatment Period and for the Long-
term Extension 
Section 8.8.2. Vital Signs 
Schedule of Activities, Table 1, Footnote “s” and Table 2, Footnote “i”: 
Vital signs to be recorded at all visits that involve the Investigator or clinical assessment visits, and not the 
visits that would be for dispensing study drug or for laboratory draws only. These will include blood 
pressure, heart rate, respiratory rate, and temperature. 
To clarify that vital signs 
only need to be performed 
during clinical 
assessments 
Section 1.2. Schedule of 
Assessments (SoA); Table 1. 
Schedule of Activities for the 
Treatment Period 
Section 8.10.1. Collection of Blood 
Samples for MORF-057 
Concentration Determination in 
Plasma 
Schedule of Activities, Table 1, Footnote “w”: 
PK testing at Visits 2, 3, and 5: Blood sampling will be required before the 
 and at 1, 2, 3, 4, and 
6 hours after the 
. Blood sampling will be optional at 8, 10, and 12 hours after the 
. The 
12-hour 
 sample will be collected prior to the second daily dose. Time windows for PK 
sampling can be found in Section 8.10.1. Each 
 sample should be obtained within 
approximately 30 minutes before the 
 is administered and at 12 hours (±1 hour)
 
 
To clarify that all 
 
 sampling should be 
collected approximately 
30 minutes before
 
 is administered. 
Samples do not need to be 
collected 12 hours after 
the previous dose. 




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TABLE OF CONTENTS 
Clinical Study Protocol ..................................................................................................................1 
Protocol Amendment Summary of Changes ...............................................................................2 
Table of Contents ...........................................................................................................................8 
Table Of Tables ............................................................................................................................12 
Table Of Figures ..........................................................................................................................13 
Abbreviations ...............................................................................................................................14 
1. 
Protocol Summary ........................................................................................................17 
1.1. 
Synopsis ..........................................................................................................................17 
1.2. 
Schedule of Activities (SoA) ..........................................................................................32 
2. 
Introduction ...................................................................................................................39 
2.1. 
Study Rationale ...............................................................................................................39 
2.2. 
Background .....................................................................................................................40 
2.2.1. 
Non-clinical Findings......................................................................................................40 
2.2.2. 
Clinical Findings .............................................................................................................41 
2.3. 
Benefit/Risk Assessment ................................................................................................42 
2.3.1. 
Benefits ...........................................................................................................................42 
2.3.2. 
Risks ................................................................................................................................43 
2.3.3. 
Overall Benefit Risk Conclusion ....................................................................................44 
3. 
Objectives and Endpoints ............................................................................................45 
4. 
Study Design ..................................................................................................................47 
4.1. 
Overall Design ................................................................................................................47 
4.2. 
Scientific Rationale for Study Design ............................................................................48 
4.3. 
Justification for Dose ......................................................................................................49 
4.4. 
End of Study Definition ..................................................................................................49 
5. 
Study Population ...........................................................................................................50 
5.1. 
Inclusion Criteria ............................................................................................................50 
5.2. 
Exclusion Criteria ...........................................................................................................53 
5.3. 
Lifestyle Considerations .................................................................................................56 
5.4. 
Screen Failures ................................................................................................................56 
6. 
Study Treatment ...........................................................................................................57 
6.1. 
Study Treatment Description ..........................................................................................57 
6.2. 
Preparation, Handling, Storage, and Accountability ......................................................57 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ............................................58 
6.4. 
Study Treatment Compliance .........................................................................................58 
6.5. 
Continued Access to Study Intervention after the End of the Study
 ........................................................................................................................................58 
6.6. 
Treatment of Overdose ...................................................................................................58 
6.7. 
Concomitant Therapy .....................................................................................................59 
6.7.1. 
Allowed Medications for the Treatment of Ulcerative Colitis .......................................59 
6.7.2. 
Prohibited Medications ...................................................................................................60 


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6.7.3. 
Prohibited Procedures .....................................................................................................62 
7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal........................................................................................63 
7.1. 
Discontinuation of Study Treatment ...............................................................................63 
7.1.1. 
Permanent Discontinuation .............................................................................................63 
7.1.2. 
Temporary Discontinuation ............................................................................................63 
7.1.3. 
Re-challenge ...................................................................................................................63 
7.2. 
Participant Discontinuation/Withdrawal from the Study ................................................64 
7.3. 
Lost to Follow-up............................................................................................................64 
8. 
Study Assessments and Procedures.............................................................................65 
8.1. 
Medical History ..............................................................................................................65 
8.2. 
Screening-specific Tests .................................................................................................65 
8.2.1. 
Pathogen Screening .........................................................................................................65 
8.2.2. 
Drug/Alcohol Screening .................................................................................................66 
8.2.3. 
Exploratory Cohort Screening Tests ...............................................................................66 
8.3. 
Study Drug Administration .............................................................................................66 
8.3.1. 
Dosing Instructions .........................................................................................................66 
8.3.2. 
Missed Dose Instructions ................................................................................................66 
8.4. 
Virtual/Hybrid Visits ......................................................................................................67 
8.5. 
Participant Diary .............................................................................................................67 
8.6. 
Stool Collection ..............................................................................................................67 
8.7. 
Efficacy Assessments .....................................................................................................68 
8.7.1. 
Endoscopy with Biopsy ..................................................................................................68 
8.7.2. 
Histologic Scores ............................................................................................................68 
8.7.3. 
Mayo Clinic Score ..........................................................................................................69 
8.7.4. 
Non-endoscopic Biomarkers of Inflammation ................................................................70 
8.8. 
Safety Assessments .........................................................................................................70 
8.8.1. 
Physical Examinations ....................................................................................................70 
8.8.2. 
Vital Signs .......................................................................................................................70 
8.8.3. 
Electrocardiograms .........................................................................................................71 
8.8.4. 
Clinical Safety Laboratory Tests ....................................................................................71 
8.8.5. 
Progressive Multifocal Leukoencephalopathy ................................................................71 
8.8.6. 
Pregnancy/Menopause Testing .......................................................................................71 
8.9. 
Adverse Events and Other Safety Reporting ..................................................................72 
8.9.1. 
Time Period and Frequency for Collecting AE and SAE 
Information .....................................................................................................................72 
8.9.2. 
Method of Detecting AEs and SAEs ..............................................................................72 
8.9.3. 
Follow-up of AEs and SAEs ...........................................................................................72 
8.9.4. 
Regulatory Reporting Requirements for SAEs ...............................................................73 
8.9.5. 
Pregnancy ........................................................................................................................73 
8.9.6. 
Adverse Events of Special Interest .................................................................................74 
8.10. 
Pharmacokinetics ............................................................................................................74 
8.10.1. Collection of Blood Samples for MORF-057 Concentration 
Determination in Plasma .................................................................................................74 
8.10.2. Determination of Drug Concentration and PK Parameters .............................................75 
8.11. 
Pharmacodynamics .........................................................................................................76 


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8.11.1. Receptor Occupancy .......................................................................................................76 
8.11.2. CCR9 mRNA ..................................................................................................................76 
8.11.3. Lymphocyte Subsets .......................................................................................................76 
8.11.4. Gene and/or Protein Expression ......................................................................................76 
8.11.5. Microbiome Analyses .....................................................................................................76 
8.11.6. Physiological Intermolecular Modulation Spectroscopy ................................................77 
8.12. 
Future Pharmacodynamics and Pharmacogenomics Research .......................................77 
8.13. 
Potential Adjustments Due to COVID-19 ......................................................................77 
9. 
Statistical Considerations .............................................................................................78 
9.1. 
Analysis Sets ...................................................................................................................78 
9.2. 
Statistical Analyses .........................................................................................................78 
9.2.1. 
General Considerations ...................................................................................................78 
9.2.2. 
Primary Endpoint ............................................................................................................79 
9.2.3. 
Secondary Endpoints ......................................................................................................79 
9.2.4. 
Exploratory Endpoints ....................................................................................................79 
9.2.5. 
Other Safety Analyses.....................................................................................................80 
9.3. 
Analyses for Induction Period, 52-week Treatment Period, and 
Long-term Extension ......................................................................................................80 
9.4. 
Sample Size Determination ............................................................................................81 
10. 
Supporting Documentation and Operational Considerations ..................................82 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ................................................................................................................82 
10.1.1. Regulatory and Ethical Considerations ...........................................................................82 
10.1.2. Financial Disclosure........................................................................................................82 
10.1.3. Insurance .........................................................................................................................83 
10.1.4. Informed Consent Process ..............................................................................................83 
10.1.5. Data Protection................................................................................................................83 
10.1.6. Data and Safety Monitoring Board .................................................................................84 
10.1.7. PML Adjudication Committee ........................................................................................84 
10.1.8. Dissemination of Clinical Study Data.............................................................................84 
10.1.9. Data Quality Assurance ..................................................................................................84 
10.1.10. Source Documents ..........................................................................................................85 
10.1.11. Study and Site Start and Closure ....................................................................................85 
10.1.12. Publication Policy ...........................................................................................................86 
10.2. 
Appendix 2: Progressive Multifocal Leukoencephalopathy 
Checklists ........................................................................................................................87 
10.3. 
Appendix 3: Clinical Laboratory Tests ...........................................................................90 
10.4. 
Appendix 4: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .........................................................92 
10.4.1. Definition of AE .............................................................................................................92 
10.4.2. Definition of SAE ...........................................................................................................93 
10.4.3. Recording and Follow-Up of AE and/or SAE ................................................................94 
10.4.4. Reporting of SAEs ..........................................................................................................96 
10.5. 
Appendix 5: Contraceptive and Barrier Guidance ..........................................................97 
10.5.1. Definitions.......................................................................................................................97 
10.5.2. Contraception Guidance..................................................................................................98 


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10.6. 
Appendix 6: Histological Scoring Indices ....................................................................100 
10.7. 
Appendix 7: Mayo Clinic Scoring System for Assessment of 
Ulcerative Colitis Activity ............................................................................................101 
10.8. 
Appendix 8: Genetics....................................................................................................102 
10.9. 
Appendix 9: Investigator’s Agreement .........................................................................103 
10.10. 
Appendix 10: Summary of Changes Table – Protocol Amendment 
Version 2.0 ....................................................................................................................104 
11. 
References ....................................................................................................................131 


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Table Of Tables 
Table 1. 
Schedule of Activities for the Treatment Period ............................................... 32 
Table 2. 
Schedule of Activities for the Long-term Extension ......................................... 37 
Table 3. 
Study Intervention ............................................................................................. 57 
Table 4. 
Examples of Drugs Potentially Altering Exposures to MORF-057# ................. 61 
Table 5. 
Pharmacokinetics Sampling Windows .............................................................. 75 
Table 6. 
Protocol-required Laboratory Tests .................................................................. 90 
 


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Table Of Figures 
Figure 1. 
Study Schema .................................................................................................... 48 
 
 


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ABBREVIATIONS 
5-ASA 
5-aminosalicylates 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine transaminase 
AST 
Aspartate transaminase 
AT 
Advanced therapy 
AUC 
Area under the concentration-time curve 
AUC0-12 
Area under the concentration-time curve from time 0 to 12 hours post-dose 
AUC0-24 
Area under the concentration-time curve from time 0 to 24 hours post-dose 
AUC0-inf 
Area under the concentration-time curve from time 0 to infinity 
AUC0-t 
Area under the concentration-time curve from time 0 to last measurable 
concentration 
AUCtau 
Area under the concentration-time curve across the dosing interval 
AUClast 
Area under the concentration-time curve from time 0 to last data point 
 
 
BMI 
Body mass index 
C12 
Plasma concentration at 12 hours post-dose 
C24 
Plasma concentration at 24 hours post-dose 
CCR9 
C-C chemokine receptor 9 
CD 
Crohn’s disease 
CIMS 
Central Image Management Solutions 
CIOMS 
Council for International Organizations of Medical Sciences 
Cmax 
Maximum observed plasma concentration 
CRF 
Case report form 
Ctrough 
Trough plasma concentration (measured concentration at the end of a dosing 
interval, taken before the next dose) 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
Cytochrome P450 
CYP3A 
Cytochrome P450 3A 
CYP3A4 
Cytochrome P450 3A4 
DNA 
Deoxyribonucleic acid 
DSMB 
Data and Safety Monitoring Board 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture database 
ELISA 
Enzyme-linked immunosorbent assay 
EOT 
End of Treatment 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FE 
Food effect 


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GCP 
Good Clinical Practice 
hCG 
human chorionic gonadotropin 
HIV 
Human immunodeficiency virus 
hs-CRP 
High-sensitivity C-reactive protein 
IBD 
Inflammatory bowel disease 
IC50 
Half maximal inhibitory concentration 
IC90 
90% inhibitory concentration 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IL 
Interleukin 
IRB 
Institutional Review Board 
JAK 
Janus kinase 
LVEF 
Left ventricular ejection fraction 
MAD 
Multiple ascending dose 
MCS 
Mayo Clinic Score 
MDRD 
Modification of Diet in Renal Disease 
MES 
Mayo Endoscopic Score 
NI 
Nancy Index 
NOAEL 
No-observed-adverse-effect level 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamics 
PGA 
Physician’s Global Assessment 
PI 
Principal Investigator 
PIMS 
Physiological intermolecular modulation spectroscopy 
PK 
Pharmacokinetics 
PML 
Progressive multifocal leukoencephalopathy 
P.O. 
By mouth 
PP 
Per Protocol (Population) 
PPD 
Purified protein derivative 
PT 
Preferred Term 
QTcF 
QT interval corrected through use of Fridericia’s formula 
RAMP 
Risk Assessment and Minimization Program 
RHI  
Robarts Histopathology Index 
RO 
Receptor occupancy 
S1P 
Sphingosine-1-phosphate 
SAD 
Single ascending dose 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 


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SFU 
Safety Follow-up 
SoA 
Schedule of activities 
SOC 
System Organ Class 
SUSAR 
Suspected unexpected serious adverse event 
TB 
Tuberculosis 
TEAE 
Treatment-emergent adverse event 
TESAE 
Treatment-emergent serious adverse event 
tmax 
Time to reach Cmax. Defined as the first point if multiple maximum values occur 
TNF-α 
Tumor necrosis factor alpha 
UC 
Ulcerative colitis 
ULN 
Upper limit of normal 
WBC 
White blood cell 
 






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Objectives 
Endpoints  
To assess the effect of 
MORF-057 on non-endoscopic 
biomarkers of inflammation  
• 
Change from baseline to Weeks 2, 6, 12, 20, 28, 36, and 52 in 
high-sensitivity C-reactive protein (hs-CRP) levels  
• 
Change from baseline to Weeks 2, 6, 12, 20, 28, 36, and 52 in 
fecal calprotectin levels  
To characterize the 
pharmacodynamics (PD) of 
MORF-057 in peripheral blood 
and mucosal tissue 
• 
α4β7 and α4β1 receptor occupancies in blood over time 
• 
Change from baseline over time in blood C-C chemokine 
receptor 9 (CCR9) mRNA  
• 
Change from baseline over time in blood lymphocyte subsets  
• 
Blood and mucosal tissue gene and/or protein expression over 
time 
To characterize the effect of 
MORF-057 on microbiome 
parameters in stool, blood, and 
mucosal tissue  
• 
Microbiome composition in stool and mucosal tissue over time 
• 
Changes in microbiome-derived metabolites in stool and blood 
over time  
• 
Metatranscriptomic changes in the stool and mucosal tissue 
microbiome over time 
To assess the long-term safety 
of MORF-057 and effects of 
MORF-057 on hs-CRP and 
fecal calprotectin levels  
• 
Frequencies and proportions for TEAEs, TESAEs, and TEAEs 
leading to study drug discontinuation through Week 82 
• 
Change from baseline to Week 65 and Week 78 in hs-CRP 
levels  
• 
Change from baseline to Week 65 and Week 78 in fecal 
calprotectin levels 
Overall Design: 
This study is an open-label, single-arm, multicenter Phase 2a study to evaluate the efficacy, PK, 
PD, safety, and tolerability of MORF-057 in participants with moderately to severely active UC. 
The Main Cohort of the study will include 
 participants with moderately to 
severely active UC who have or have not been exposed to biologics therapies and have not 
previously been treated with vedolizumab. In addition, an Exploratory Cohort will be comprised 
of a 
 participants with moderately to severely active UC who are 
intolerant to or secondary non-responders (as defined in Section 5.1) to vedolizumab. Thus, there 
will be a total of 
 participants in the study. When the Main Cohort recruits 
 participants, 
the study will be closed for any new screening in the Main Cohort, and the remaining participants 
already in screening will be allowed to complete the process and enroll, if eligible. All participants 
will be enrolled from up to 30 centers located in North America and Europe. For this study, 
moderately to severely active UC will be defined as having a Modified MCS of 5 to 9 (inclusive) 
with an MES ≥2 (confirmed by central reader). In the Main Cohort, the enrollment goal is for 
approximately 55% to 75% of the participants to be advanced therapy (AT)-naïve (i.e., to have no 
previous exposure to a biologic treatment, Janus kinase [JAK] antagonists, or sphingosine-1-
phosphate [S1P] receptor agonists for UC).  
Participant safety data will be reviewed by an independent Data and Safety Monitoring Board 
(DSMB). Details related to the DSMB will be clearly delineated in the DSMB Charter.  




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‡ In cases where the participant withdraws early from the study treatment, the EOT and SFU Visit assessments may 
be performed earlier than the timepoints shown here. 
Main Inclusion Criteria: 
Participants are eligible to be included in the study only if all the following criteria apply: 
Age 
1. 18 to 85 years of age, inclusive, at the time of signing the Informed Consent Form 
(ICF) 
Type of Participant and Disease Characteristics 
2. Participant has had signs/symptoms of moderately to severely active UC for at least 
3 months prior to Screening, and the diagnosis was confirmed during the Screening 
Period with the following criteria: a Modified MCS of 5 to 9 (inclusive) with an MES 
≥2 (confirmed by central reader) 
3. Has an RHI Score of 10 or greater 
4. Has evidence of UC extending at least 15 cm from the anal verge 
5. Is an AT-naïve participant or a participant who had an inadequate response, loss of 
response, or intolerance to no more than 3 drugs in 2 classes of the following:   
a. Tumor necrosis factor (TNF-α) antagonists, including infliximab, adalimumab, or 
golimumab 
b. Interleukin (IL)-12/IL-23 antagonists, including ustekinumab 
c. JAK antagonists, including tofacitinib and upadacitinib 
d. S1P receptor agonists, including ozanimod  
e. Any investigational product with the same mechanism as one of those outlined 
above (5a through 5d) 
f. Integrin inhibitors, including vedolizumab (participants in the Exploratory Cohort 
only) 
Note: Participants who have a history of primary non-response to 2 of the classes above 
will not be eligible. Participants who have received treatment with these agents at 
sub-therapeutic doses, or durations, should be discussed with the Medical Monitor to 
assess eligibility. 
6. Meets the following washout criteria of prior UC therapy relative to study Day 1:  
a. TNF-α antagonists: at least 8 weeks 
b. IL-12/IL-23 antagonists, including ustekinumab: at least 8 weeks 
c. JAK antagonists, including tofacitinib and upadacitinib: at least 2 weeks 
d. S1P receptor agonists, including ozanimod: at least 4 weeks 
7. If the participant has been receiving any of the non-prohibited medications for UC 
listed below, he/she must discontinue use at least 5 half-lives before study Day 1 or 
must agree to maintain stable doses of these concomitant medications starting from 
the time specified below until the end of the Safety Follow-up Period, with the 
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a. 5-Aminosalicylates (not exceeding 4.8 g per day): at least 2 weeks prior to study 
Day 1 
b. Oral corticosteroids (not exceeding prednisone 30 mg per day, budesonide 9 mg 
per day, or equivalent): at least 2 weeks prior to study Day 1 
c. 6-Mercaptopurine (any stable dose): at least 4 weeks prior to study Day 1 
d. Azathioprine (any stable dose): at least 4 weeks prior to study Day 1 
e. Methotrexate (any stable dose): for at least 4 weeks prior to study Day 1 
8. In the opinion of the Investigator, the participant can fully participate in all aspects 
of this clinical study 
Weight 
9. Has a body mass index (BMI) within the range of 18.0 and 40.0 kg/m2 (inclusive) at 
Screening 
Sex and Contraceptive/Barrier Requirements  
10. A participant is eligible to participate if he/she agrees to abide by the guidelines set 
forth in this protocol regarding contraception requirements (see full contraception 
guidelines in Section 10.5): 
a. A male participant is eligible to participate if he agrees to the following during the 
study Treatment Period and for at least 28 days after receiving the last dose of 
MORF-057: 
• 
Abstains from heterosexual intercourse as his preferred and usual lifestyle 
(abstinent on a long-term and persistent basis) and agrees to remain abstinent 
OR 
• 
Agrees to use contraception/barrier methods as detailed below: 
o Agrees to use a male condom, with female partner use of an additional 
highly effective contraceptive method with a failure rate of <1% per 
year (as described in Section 10.5.2) when having sexual intercourse 
with a woman of childbearing potential who is not currently pregnant 
o Agrees to use a male condom when engaging in any activity that allows 
for passage of ejaculate to another person 
b. A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and one of the following conditions applies: 
• 
Is a woman of non-childbearing potential (as defined in Section 10.5.1)  
OR 
• 
Is a woman of childbearing potential (as defined in Section 10.5.1) and 
agrees to use a contraceptive method that is highly effective with a failure 
rate of <1% per year (as described in Section 10.5.2) during the study 
Treatment Period and for at least 28 days after receiving the last dose of 
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Note: Women who use any oral hormonal contraception must use an additional 
physical barrier method (Section 10.5.2). 
11. For the study Treatment Period and at least 28 days after receiving the last dose of 
MORF-057, male participants must agree not to donate sperm and female participants 
must agree not to donate eggs (ova, oocytes). 
Informed Consent 
12. Capable of giving signed informed consent, as described in Section 10.1.4, which 
includes compliance with the requirements and restrictions listed in the ICF and in 
this protocol 
 
Exploratory Cohort Inclusion Criteria: 
In addition to meeting Inclusion Criteria 1 through 12, the following criteria must be met for 
participants to be included in the Exploratory Cohort: 
13. Those intolerant to (e.g. infusion-related skin reaction, allergy, or side effects 
unrelated to α4β7 inhibition) or secondary non-responders* to vedolizumab who have 
been dosed within the past 5 years with the drug. Up to 5 of the 10 Exploratory Cohort 
participants may be included based on clinical criteria only. The remaining 
participants must also meet at least 1 of the following criteria:  
a. Documented vedolizumab levels in blood of ≤10 µg/mL 6 to 8 weeks after their 
most recent dose or at what is considered clinical trough. If the participant has 
had vedolizumab levels in blood tested and documented in their medical chart 
prior to Screening, the test does not need to be repeated. 
b. Non-saturating receptor occupancy of vedolizumab in blood 6 to 8 weeks after 
their most recent dose 
c. Documented presence of anti-drug antibodies against vedolizumab. If the 
participant has had a positive anti-drug antibody test that has been documented 
prior to Screening, the test does not need to be repeated. 
*Note: Secondary non-response is defined as having initially responded to Induction 
therapy and then had recurrence of symptoms after receiving at least 2 of the 
Maintenance doses, 300 mg every 8 weeks (discontinuation despite clinical benefit 
does not qualify). 
14. The participants should also have received their last dose of vedolizumab at least 
6 weeks prior to study Day 1 to allow sufficient washout 
 
Exclusion Criteria: 
Participants will be excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. Diagnosed with indeterminate colitis, microscopic colitis, ischemic colitis, radiation 
colitis, or CD or has clinical findings suggestive of CD 


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2. Has current evidence of un-resected colonic dysplasia or un-resected adenomatous 
colonic polyps or evidence of toxic megacolon, abdominal abscess, symptomatic 
colonic stricture, fistula, stoma, ileostomy, or colostomy at Screening  
3. Currently requires or is anticipated to require surgical intervention for UC during the 
study or is planning to undergo major surgery during the study period 
4. Has had a surgical procedure requiring general anesthesia within 30 days prior to 
Screening  
5. Has a history of any major neurological disorders, including stroke, multiple 
sclerosis, brain tumor, demyelinating, or neurodegenerative disease. For questions 
about whether this applies to a specific case, consult with the Medical Monitor. 
6. Has positive findings on a subjective neurological screening questionnaire or 
progressive multifocal leukoencephalopathy (PML) subjective symptom checklist 
during Screening or prior to the administration of the first dose of study drug on study 
Day 1 
7. Has an active bacterial, viral, or parasitic pathogenic enteric infection, including 
Clostridium difficile; has cytomegalovirus, hepatitis B or C virus, or human 
immunodeficiency virus (HIV); had an infection requiring hospitalization or 
intravenous antimicrobial therapy, or an opportunistic infection within 3 months prior 
to Screening; had any infection requiring oral antimicrobial therapy within 2 weeks 
prior to Screening; or has a history of more than 1 episode of herpes zoster or any 
episode of disseminated herpes zoster infection  
8. Has a positive diagnostic tuberculosis (TB) test at Screening (defined as a positive 
test). If the participant has had a confirmed negative 
 
or other Interferon Gamma Release Assay test within 90 days prior to Screening, the 
test does not need to be repeated. In cases where the 
 test result is 
indeterminate, the participant may have the test repeated once, and if the second test 
is negative, the participant will be eligible. In the event the second test also has an 
indeterminate result or 
 is unavailable, the Investigator has the option 
to perform a purified protein derivative (PPD) skin test. If the PPD reaction is <5 mm, 
then the participant is eligible. If the reaction is ≥5 mm or PPD testing is not done, 
the participant is not eligible. An exception can be made for participants with a 
history of latent TB who are currently receiving treatment for latent TB per local 
standard care, who will initiate treatment for latent TB before the first dose of study 
drug, or who have documentation of completing appropriate treatment for latent TB 
within 2 years prior to study Day 1. 
9. Tests positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 
during the Screening Period. Participants who test positive for SARS-CoV-2 can 
undergo retesting throughout the Screening Period. Testing to be performed 
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10. Had any vaccination (including live virus vaccinations) within 3 weeks prior to study 
Day 1. Note: For vaccinations requiring a series of doses, the last in the series should 
be completed by 3 weeks prior to study Day 1 (e.g., SARS-CoV-2 two-shot 
vaccination series). 
11. Has a concurrent, clinically significant, serious, unstable comorbidity (such as 
uncontrolled 
cardiovascular, 
pulmonary, 
hepatic, 
renal, 
gastrointestinal, 
genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or 
other medical disorder) that, in the judgement of the Investigator, would compromise 
compliance with the protocol, interfere with interpretation of the study results, or 
pre-dispose participants to safety risks 
12. Has a known primary or secondary immunodeficiency 
13. Has a history of myocardial infarction, unstable angina, transient ischemic attack, 
decompensated heart failure requiring hospitalization, congestive heart failure (New 
York Heart Association Class 3 or 4), uncontrolled arrhythmias, cardiac 
revascularization, uncontrolled hypertension, or uncontrolled diabetes within 
6 months of Screening 
14. Has a history of left ventricular ejection fraction (LVEF) <50%  
15. Has a clinically significant abnormal electrocardiogram (ECG) at Screening, 
including a QT interval corrected through use of Fridericia’s formula (QTcF) 
≥450 ms for males and ≥470 ms for females 
16. Abnormal hematology (hemoglobin level, white blood cell [WBC] count, or platelet 
count) or coagulation results at Screening, as evidenced by the ranges provided 
below:*  
a. Hemoglobin level <8.0 g/dL  
b. Absolute WBC count <3.0 × 109/L 
c. Absolute lymphocyte count <0.5 × 109/L  
d. Absolute lymphocyte count >5.0 x 109/L 
e. Absolute neutrophil count <1.2 × 109/L  
f. Platelet count <100 × 109/L or >1000 × 109/L    
g. International normalized ratio >1.5  
17. Clinically significant abnormal urinalysis results, as deemed by the Investigator or 
designee 
18. Abnormal organ function at Screening, as evidenced by the following:* 
a. Alanine aminotransferase or aspartate aminotransferase >2.5 × upper limit of 
normal (ULN) 
b. Chronic kidney disease stages 4 and 5, defined as having a glomerular filtration rate 
<30 mL/min/1.73m2 as calculated using the Modification of Diet in Renal Disease 
(MDRD) equation, receiving dialysis, or being listed for or has received a renal 
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c. Total bilirubin ≥1.5 × ULN 
*Note: Repeat testing should be done at the discretion of the Investigator. Consult with the 
Medical Monitor as needed. 
19. History of active malignancy in the 5 years preceding study Day 1, except in cases of 
basal cell skin cancer, squamous cell skin cancer, or other in-situ malignancies that 
have been excised and resolved and the participant was deemed clear of cancer after 
appropriate follow-up. Participants with a history of malignancy or those at high risk 
for malignancy may only be enrolled after a consultation with the Medical Monitor. 
Prior/Concomitant Therapy 
20. Treatment with cyclosporine, mycophenolate, tacrolimus, or sirolimus within 30 days 
or 5 half-lives (whichever is shorter) prior to study Day 1  
21. Any previous treatment with vedolizumab or other integrin inhibitors (except 
participants for the Exploratory Cohort) 
22. Experiencing toxicities from prior therapy with Grade >1 within 1 week prior to first 
dose of study drug 
23. Fecal microbiota transplantation within 3 months prior to Screening 
24. If treatment with a moderate-to-strong cytochrome P450 3A4 (CYP3A4) inducer or 
inhibitor was received, a washout period of at least 30 days or 5 half-lives (whichever 
is shorter) is required prior to study Day 1. See Section 6.7.2 for a list of moderate-
to-strong P450 inducers and inhibitors. 
25. If treatment with a moderate-to-strong organic anion transporter polypeptide-1B 
inhibitor was received, a washout period of at least 14 days or 5 half-lives (whichever 
is shorter) is required prior to study Day 1. See Section 6.7.2 for a list of moderate-
to-strong organic anion transporter polypeptide-1B inhibitors. 
Prior/Concurrent Clinical Study Experience 
26. Concurrent participation in any other interventional study  
27. Received any investigational therapy within 30 days or 5 half-lives (whichever is 
longer) prior to study Day 1 
28. Previous exposure to MORF-057 and/or a known hypersensitivity to drugs with a 
similar mechanism to MORF-057 
Other Exclusions 
29. Females who are pregnant or lactating or who are planning on becoming pregnant 
during the course of the study 
30. Current or recent history of alcohol dependence or illicit drug use that, in the opinion 
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Analyses for Induction Period, 52-week Treatment Period, and Long-term Extension  
The study open-label treatment period includes 2 parts: the 12-week Induction Period and the 
40-week Maintenance Period. For the purpose of statistical analyses, the Induction Period and the 
Maintenance Period will be treated as 2 independent parts. There will be 4 analyses planned: two  
for the 12-week Induction Periods of the Main and Exploratory Cohorts respectively (i.e., the 
period for the primary efficacy endpoint) and the other two for the 52-week Treatment Periods of 
the Main and Exploratory cohorts respectively (i.e., the 12-week Induction Period plus the 
40-week Maintenance Period and the Safety Follow-up). Additional analysis of the optional Long-
term Extension Period for the participants enrolled into the Long-term Extension will be performed 
as appropriate. 
Induction Period Analysis  
The analysis of the Induction Period will be performed after all the participants in the Main Cohort 
have completed the 12-week Induction Period (i.e., completed the Week 12 visit) or discontinued 
the study before the Week 12 assessment. The analysis will formally evaluate the primary and 
secondary efficacy endpoints, all the exploratory endpoints defined by Week 12, PK 
concentrations and parameters, and safety of MORF-057 for the Main Cohort during the 12-week 
Induction Period.  
The analysis of the Induction Period for the Exploratory Cohort will be performed after all the 
participants in the Exploratory Cohort have completed the 12-week Induction Period (i.e., 
completed the Week 12 visit) or discontinued the study before the Week 12 assessment. The 
analysis will evaluate all the efficacy and exploratory endpoints, PK concentrations and 
parameters, and safety of MORF-057 for the Exploratory Cohort during the 12-week Induction 
Period. In the event that the timing of the Induction Period analysis for the Exploratory Cohort 
aligns closely with the timing of the 52-week Treatment Period analysis for the Main Cohort 
described below, both analyses will be combined into one analysis. 
Only Induction Period data will be used in the Induction Period analyses.   
52-week Treatment Period Analysis  
For the Main Cohort, the analysis of the 52-week Treatment Period will be performed after all the 
participants have completed the 52-week open-label Treatment Period (and the Safety Follow-up 
Period for participants not enrolling into the optional Long-term Extension Period) or discontinued 
the study before the Week 52 assessment and the Safety Follow-up Period. In the event that the 
timing of the 52-week Treatment Period analysis for the Main Cohort aligns closely with the timing 
of the Induction Period analysis for the Exploratory Cohort, both analyses will be combined into 
one analysis. 
 
For the Exploratory Cohort, the analysis of the 52-week Treatment Period will be performed after 
all the participants have completed the 52-week open-label Treatment Period (and the Safety 
Follow-up Period for participants not enrolling into the optional Long-term Extension Period) or 
discontinued the study before the Week 52 assessment and the Safety Follow-up Period.  
The 52-week Treatment Period analyses will formally evaluate all the exploratory endpoints 
defined by Week 52, PK concentration and parameters, and safety of MORF-057 during the 
52-week open-label Treatment Period plus the Safety Follow-up Period. The cumulative data, 


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including those from the Induction Period, will be used in these analyses. The data from the Main 
and Exploratory Cohorts may be pooled together in the safety analyses as appropriate. 
Long-term Extension Analysis  
The analysis of the Long-term Extension will be performed after all the participants enrolled into 
the Long-term Extension have completed the 26-week extended Treatment Period and the Safety 
Follow-up Period or discontinued the study before the Week 78 assessment. The analysis will 
formally evaluate the safety of MORF-057 and selected efficacy endpoints as appropriate during 
the Long-term Extension plus the Safety Follow-up Period.  
Analysis Populations 
The Full Analysis Set (FAS) is defined as all enrolled participants in the Main Cohort and 
Exploratory Cohort who took at least one dose of study medication. The FAS will be used for 
efficacy analyses. 
The Per Protocol (PP) Population is defined as all participants in the FAS who do not have any 
major protocol deviations relevant to the primary and secondary efficacy endpoint analysis. All 
decisions to exclude participants from the PP set will be made prior to the database lock of the 
study. The PP Population will be used for sensitivity analysis of the primary efficacy endpoint and 
maybe other selected efficacy endpoints as appropriate.  
The Safety Analysis Population is defined as all participants in both the Main Cohort and 
Exploratory Cohort who received at least 1 dose of study medication. The Safety Analysis 
Population will be used for safety analysis. 
The PK Population is defined as all participants in the FAS who have adequate measurable 
concentrations to define Cmax or AUC. The PK Population will be used in the individual plasma 
concentration, PK parameter estimation listings, and individual figures. 
The PK Evaluable Population (a subset of the PK Population) will be used to determine the 
inclusion of a participant in the overall PK summaries. Participants included in this subset must 
not violate the protocol in a way that may invalidate or bias the results, and must have the reliable 
data for the overall PK summaries. The criteria that the data must meet for the inclusion of a 
participant in this population will be specified in the study SAP. 
The PD Population is defined as all participants in the FAS who have at least 1 measurable 
post-dose PD measurement and its corresponding pre-dose PD measurement for, at minimum, 1 
of the PD biomarkers. This population will be used for the summarization of PD (exploratory) 
endpoints. 
Primary Endpoint 
The primary efficacy endpoint for this study is change from baseline to Week 12 in RHI Score, 
which will be tested using the FAS. The data for the primary efficacy endpoint will be assessed 
for normality. If the data are normally distributed, then a one-sample t-test will be used for the 
analysis. If the data are not normally distributed, then a signed rank test will be used. If there are 
a large number of participants excluded from the Per Protocol Population due to major protocol 
deviations, then a sensitivity analysis of the primary efficacy endpoint will be performed using the 
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baseline to Week 12 that is at least -7 (that is, a reduction ≥7) and the proportion of participants 
with at least a 50% reduction in RHI score from baseline to Week 12 will be provided.   
Secondary Endpoints 
The continuous secondary efficacy endpoint (change from baseline to Week 12 in Modified MCS) 
will be analyzed similarly to the primary efficacy endpoint using the FAS. No hypothesis testing 
will be performed for the secondary efficacy endpoint.  
The Safety Analysis Population will be used for the summarization of all safety data. Adverse 
events will be coded using the current Medical Dictionary of Regulatory Activities by System 
Organ Class (SOC) and Preferred Term (PT), classified from verbatim terms. A TEAE is defined 
as an AE that occurs between administration of the first dose of study drug and 7 days after the 
last dose of study drug. TEAEs and TESAEs will be summarized using frequencies and 
proportions; summaries will be provided for overall and according to SOC and PT. TEAEs leading 
to study drug discontinuation will be summarized or listed, as appropriate. Summaries of TEAEs 
will also be presented by severity and relationship (see Section 10.4.3). The duration of TEAEs 
will be determined and included in listings, along with the action taken and outcome.  
The plasma PK parameters AUC0-12, AUCtau, Cmax, Ctrough, tmax, and C12 will be estimated by 
non-compartmental analysis using the PK Population. PK/PD analyses will be conducted as 
deemed appropriate and may be reported separately from the Clinical Study Report. 
Exploratory Endpoints 
The continuous exploratory efficacy endpoints (change from baseline to Weeks 6 and 52 in RHI 
Score and Modified MCS; change from baseline to Weeks 6, 12, and 52 in NI, Continuous Geboes 
Score, and Full MCS; and change from baseline to Weeks 2, 6, 12, 20, 28, 36, and 52 in hs-CRP 
and fecal calprotectin levels) will be analyzed similarly to the primary efficacy endpoint using the 
FAS. No hypothesis testing will be performed for the exploratory efficacy endpoints. In addition, 
the proportion of participants with NI score ≤1 at Week 12 will be provided. 
The exploratory PD endpoints (α4β7 and α4β1 receptor occupancies over time and change from 
baseline over time in blood CCR9 mRNA) will be summarized descriptively. Additional analysis 
of blood and mucosal tissue gene and/or protein expression over time, microbiome composition in 
stool and mucosal tissue over time, changes in microbiome-derived metabolites in stool and blood 
over time, and metatranscriptomic changes in the stool and mucosal tissue microbiome over time 
will be provided in a biomarker analysis plan separate from the study SAP and reported separately. 
The PD Population will be used for the summarization and analysis of these exploratory endpoints. 
Other Safety Assessments 
Other safety data will include safety laboratory parameters, vital signs, and ECG findings. These 
data will be summarized with descriptive statistics by absolute values and change from baseline 
using the Safety Analysis Population. The incidence of laboratory abnormalities will be 
summarized. Worst shift in grade and changes from baseline to Weeks 6, 12, and 52 of the 
laboratory analytes will be reported. Physical examination findings that are recorded as AEs will 
be included in those data presentations.   
Data and Safety Monitoring: 


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A DSMB has been appointed to this study. The DSMB is a group of independent 
clinicians/scientists who are appointed to monitor the safety and scientific integrity of a human 
research intervention, and to make recommendations to the Sponsor regarding the modification, 
continuance, or stopping of a study based on assessments of safety. Additionally, a separate PML 
Adjudication Committee will oversee a PML Risk Assessment and Minimization Program 
(RAMP) to monitor all participants for PML. The composition, responsibilities, and meeting 
schedules of the DSMB and the PML Adjudication Committee will be described in separate 
charters. 










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ff Participation in future biomarker research sample collection is optional. Blood PD samples will be collected before the 
 on Visits 2-10. Blood pharmacogenomics 
sample will be collected before the 
 on Visit 2. PD and pharmacogenomics sampling to occur at the corresponding PK sampling time. 
gg Full colonoscopy is optional at any timepoint if the Investigator deems it necessary. The screening endoscopy procedure should be scheduled at least 16 days prior to the planned 
start of the study drug (Day 1) to allow for central reading. Colonic mucosa biopsies will be collected for cytomegalovirus testing (Screening only), histopathology, microbiome, 
spatial transcriptomics/proteomics, and gene expression analyses. 
hh The Visit 4 endoscopy is optional. 
ii For the Visit 10/EOT endoscopy procedure, there is a window of ±7 days from the actual visit date. For participants who discontinue treatment before Week 6, a repeat 
sigmoidoscopy will be performed any time after MORF-057 dosing Day 14. For participants who discontinue treatment after Week 6, a repeat sigmoidoscopy will be performed 
any time if the optional Week 6 sigmoidoscopy was not exercised. If the Week 6 optional sigmoidoscopy was exercised, a repeat sigmoidoscopy will be performed after the 28th 
day post Week 6 sigmoidoscopy. Participants who complete a sigmoidoscopy/colonoscopy within 12 weeks of the EOT visit are not required to repeat the procedure. If the 
procedure was performed further than 12 weeks, please consult the Sponsor Medical Monitor. 
jj Blood samples for hs-CRP analysis will be collected 
 on Visits 2-8 and Visit 10. 
kk At Visit 10/EOT, the study drug will be dispensed only for participants continuing treatment in the Long-term Extension.  
ll 
 required on site for all visits. For Visits 2, 3, and 5, if optional PK/RO sampling will be performed at 8-12 hours 
, the 
 must not be taken 
until PK/RO sampling is complete for that day. 
mm At Visit 10/EOT, participants will only receive an 
 will be provided. 
 
 
 




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g Stool collection kits are to be dispensed to participants at the visits indicated. The participant should use this kit to collect one sample at home within 24 hours before the next 
site visit. The sample should be frozen immediately and brought to the clinic on the day of the site visit.  
h A targeted physical exam is to be performed at all visits (see Section 8.8.1 for descriptions). For unscheduled visits, that involve the Investigator or clinical assessment and not 
the visits that would be for dispensing study drug or for laboratory draws only, the type of exam will be at the Investigator’s discretion and determined based on the reason for 
the visit.  
i Vital signs to be recorded at all visits that involve the Investigator or clinical assessment visits, and not the visits that would be for dispensing study drug or for laboratory draws 
only. These will include blood pressure, heart rate, respiratory rate, and temperature. 
j If the results of the questionnaire are suggestive of PML, a full neurological exam and, if indicated, additional testing are to be performed. 
k Blood samples for hematology, coagulation, and serum chemistry assessments will be collected before the 
 on Visits 11-12. 
l Record adverse events from the time the ICF for the Long-term Extension is signed.  
m Participants are to be contacted by phone as needed to monitor the status of the event. 
n Blood samples for hs-CRP analysis will be collected before the 
 on Visits 11-12. 


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2. 
INTRODUCTION 
2.1. 
Study Rationale 
Inflammatory bowel disease (IBD) is a term used to describe 2 idiopathic conditions characterized 
by chronic inflammation of the gastrointestinal tract: Crohn’s disease (CD) and ulcerative colitis 
(UC). In patients with UC, mucosal inflammation and ulceration occurs in the rectum and can 
extend proximally to a portion of or to the full colon, resulting in symptoms and signs such as 
urgency to defecate, fatigue, bloody stool, diarrhea, nausea or loss of appetite, weight loss, fever, 
and anemia.  
Initial therapy for UC generally includes the anti-inflammatory drugs 5-aminosalicylates (5-ASA) 
and steroids. Immunomodulators (e.g., methotrexate, azathioprine, and 6-mercaptopurine) may 
subsequently be used to maintain remission and avoid long-term steroid use. However, these 
treatments often fail to control the disease long-term, particularly in patients with moderately to 
severely active UC, and both the steroids and the immunomodulators can produce significant side 
effects. 
The introduction of biologic agents has improved the therapeutic options for patients with 
moderately to severely active UC. Approved biologics include tumor necrosis factor alpha 
(TNF-α) antagonists (infliximab, adalimumab, certolizumab, and golimumab), the anti-α4β7 
integrin monoclonal antibody vedolizumab (
), and the anti-interleukin 12/23 monoclonal 
antibody ustekinumab (Stelara®). Another therapeutic option recently approved for the treatment 
of UC is Janus kinase (JAK) inhibitors, such as the small molecule tofacitinib (Xeljanz®). Despite 
this increase in therapeutic options for the treatment of UC, the percentage of patients with 
moderately to severely active UC who do not respond to induction therapy is still substantial, and 
the durability of response is low. For example, in Phase 3 studies in patients with moderately to 
severely active UC, adalimumab treatment achieved clinical remission at 8 weeks in 18.5% of 
patients and maintained remission in 8.5% at 52 weeks (
 package insert). Thus, there 
remains an unmet need for more effective therapies for UC. 
The pathogenesis of IBD is associated with activation of immune cells and their trafficking into 
the gut and the surrounding tissue to promote chronic inflammation. The integrin α4β7 is required 
by immune cells to facilitate trafficking from the bloodstream to mucosal tissues, including the 
gut. This is achieved through binding of the α4β7 integrin on immune cells to its cognate ligand, 
MAdCAM-1, expressed on the endothelial vessels within close proximity to mucosal tissues. 
Importantly, the α4β7 integrin is employed by immune cells in the pathogenesis of IBD; therefore, 
inhibiting α4β7 blocks the entry of immune cells into mucosal tissue, thereby alleviating the 
inflammation associated with IBD in many patients. Thus, the α4β7 integrin is an ideal therapeutic 
target for selectively blocking inflammation of the gastrointestinal tract while minimizing effects 
in other organs (Fedyk, 2012). Inhibition of α4β7 is a validated mechanism for the treatment of 
IBD, as demonstrated by vedolizumab (
), a monoclonal antibody administered via 
intravenous infusion.  
MORF-057 is a small molecule designed to selectively inhibit integrin α4β7. It is currently being 
developed as an oral therapy for UC because vedolizumab, which has the same mechanism of 
action, has shown more favorable responses in UC patients with moderately to severely active 








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• 
Oral drugs are preferred by patients and healthcare providers over injectables. Beyond the 
fear of needles, the requirement for frequent infusion center visits is a substantial burden, 
particularly for younger patients with UC who have active professional and family lives.  
• 
Oral formulation allows for flexible dosing regimen. An oral drug that is rapidly cleared 
upon cessation of dosing may be desirable for treating physicians in clinical situations such 
as pregnancy, during serious infections, and in the peri-operative period. Additionally, an 
oral drug is more easily titrated to clinical effect and may be used in fixed-dose 
combinations with other oral agents. The long half-life of vedolizumab means that it cannot 
be removed rapidly.  
• 
As with all therapeutic proteins, there is the potential for immunogenicity with 
vedolizumab. During the Phase 3 trials, 4% of patients developed anti-vedolizumab 
antibodies, 59% of which were neutralizing antibodies that reduced plasma levels of the 
treatment antibody 
 package insert). 
• 
Serious infusion reactions, including anaphylaxis, have been reported with vedolizumab.  
2.3.2. 
Risks 
Overall, based on the available data for MORF-057, the risk to study participants is expected to be 
minimal. 
 
Collectively from 4 completed MORF-057 studies conducted in 
, MORF-057 
was well tolerated with or without food or in combination with midazolam. There were no deaths 
or SAEs. 
 
 In a 6-month toxicology study in Sprague Dawley rats and a 9-month toxicology study in beagle 
dogs, the NOAEL values were 50 mg/kg/day for rats and 300 mg/kg/day for dogs (Section 2.2.1). 
Safety precautions that will be taken during the study are listed below: 
• 
Safety assessments and monitoring will be performed throughout the study, including 
evaluating the incidence of TEAEs, as well as abnormalities in clinical laboratory 
values, vital signs, and 12-lead ECGs. 
• 
A Data and Safety Monitoring Board (DSMB) has been appointed to this study. The 
DSMB will monitor the safety of the participants and the scientific integrity of the 
study.  
• 
Natalizumab, a monoclonal antibody that inhibits both α4β1 and α4β7 integrins, has been 
associated with PML, a serious brain infection. Data from human whole blood ex vivo 
assay suggests that MORF-057 has significant selectivity (~700 fold at IC90) for 
binding integrin α4β7 over integrin α4β1. However, out of an abundance of caution, all 
participants enrolled in this study will be monitored for PML through the use of a PML 
Risk Assessment and Minimization program (RAMP). 
• 
Non-clinical Good Laboratory Practice studies in rats and rabbits showed that 
MORF-057 has no effects on fertility, early embryonic development, or embryo-fetal 


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development. The available non-clinical data suggest that exposure to clinical-strength 
doses of MORF-057 does not present a risk to the mother or fetus. Additional studies 
evaluating the effects of MORF-057 on pre- and post-natal development have not been 
conducted and the safety profile of MORF-057 in women who are pregnant or lactating 
is not available; therefore, inclusion/exclusion criteria (see Section 5) and safety 
monitoring regarding contraception and pregnancy have been included to mitigate the 
potential relevant risks. 
Safety criteria for study drug discontinuation are outlined in Section 7. 
The Sponsor will immediately notify the Investigator if any additional safety or toxicology 
information becomes available during the study.  
2.3.3. 
Overall Benefit Risk Conclusion 
Considering the measures taken to minimize risk to the participants in this study and given that the 
potential risks identified in association with MORF-057 can be readily monitored during the study, 
the participants are not being exposed to undue risk, and the potential risks are justified by the 
anticipated benefits that may eventually be afforded to patients with moderately to severely active 
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Objectives 
Endpoints  
To evaluate the effect of MORF-057 on 
clinical improvement at Weeks 6, 12, and 52  
• 
Change from baseline to Weeks 6 and 52 in 
the Modified MCS. Modified MCS is a 
composite of the following subscores:  
o MES 
o MCS stool frequency subscore  
o MCS rectal bleeding subscore  
• 
Change from baseline to Weeks 6, 12, and 
52 in the Full MCS. Full MCS is a 
composite of the following subscores: 
o MES 
o MCS stool frequency subscore  
o MCS rectal bleeding subscore 
o MCS Physician’s Global Assessment 
(PGA) 
To assess the effect of MORF-057 on 
non-endoscopic biomarkers of inflammation  
• 
Change from baseline to Weeks 2, 6, 12, 20, 
28, 36, and 52 in high-sensitivity C-reactive 
protein (hs-CRP) levels  
• 
Change from baseline to Weeks 2, 6, 12, 20, 
28, 36, and 52 in fecal calprotectin levels  
To characterize the PD of MORF-057 in 
peripheral blood and mucosal tissue 
• 
α4β7 and α4β1 receptor occupancies in blood 
over time 
• 
Change from baseline over time in blood 
CCR9 mRNA  
• 
Change from baseline over time in blood 
lymphocyte subsets  
• 
Blood and mucosal tissue gene and/or 
protein expression over time 
To characterize the effect of MORF-057 on 
microbiome parameters in stool, blood, and 
mucosal tissue  
• 
Microbiome composition in stool and 
mucosal tissue over time 
• 
Changes in microbiome-derived metabolites 
in stool and blood over time  
• 
Metatranscriptomic changes in the stool and 
mucosal tissue microbiome over time 
To assess the long-term safety of MORF-057 
and effects of MORF-057 on hs-CRP and 
fecal calprotectin levels  
• 
Frequencies and proportions for TEAEs, 
TESAEs, and TEAEs leading to study drug 
discontinuation through Week 82 
• 
Change from baseline to Week 65 and 
Week 78 in hs-CRP levels  
• 
Change from baseline to Week 65 and 
Week 78 in fecal calprotectin levels 
 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This study is an open-label, single-arm, multicenter Phase 2a study to evaluate the efficacy, PK, 
PD, safety, and tolerability of MORF-057 in participants with moderately to severely active UC. 
The Main Cohort of the study will include approximately 
 with moderately to 
severely active UC who have or have not been exposed to biologics therapies and have not 
previously been treated with vedolizumab. In addition, an Exploratory Cohort will be comprised 
of a maximum of 10 additional participants with moderately to severely active UC who are 
intolerant to or secondary non-responders (as defined in Section 5.1) to vedolizumab. Thus, there 
will be a total of 
 in the study. When the Main Cohort recruits 
, 
the  study will be closed  for any new screening in the main cohort and the remaining participants 
already in screening will be allowed to complete the process and enroll, if eligible. All participants 
will be enrolled from up to 30 centers located in North America and Europe. For this study, 
moderately to severely active UC will be defined as having a Modified MCS of 5 to 9 (inclusive) 
with an MES ≥2 (confirmed by central reader). In the Main Cohort, the enrollment goal is for 
approximately 55% to 75% of the participants to be advanced therapy (AT)naïve (i.e., to have no 
previous- exposure to a biologic treatment, JAK antagonists, or sphingosine-1-phosphate [S1P] 
receptor agonists for UC).   
Participant safety data will be reviewed by an independent DSMB. Details related to the DSMB 
will be clearly delineated in the DSMB Charter.  
The main part of this Phase 2a study will consist of 3 study periods: a Screening Period (up to 6 
weeks), a Treatment Period (52 weeks, including a 12-week Induction Period and a 40-week 
Maintenance Period), and a Safety Follow-up Period (4 weeks). During the study, there will be 
approximately 11 scheduled study visits: Screening Visit(s) (Visit 1 at Weeks -6 to -1), multiple 
Treatment Visits (Visits 2-10 at Weeks 0, 2, 6, 12, 20, 28, 36, 44, and 52), and a Safety Follow-up 
Visit (visit to occur 4 weeks after the last dose of study drug is received, which will be Visit 11 at 
Week 56 if the full study is completed or earlier if treatment is discontinued early). Study Day 1 
represents the first day of the Treatment Period (i.e., when the participant will receive the first dose 
of study drug). Participants will receive the same MORF-057 dosage (
 mg 
. by mouth 
[P.O.]) for the full 52-week Treatment Period.  
All participants who complete the open-label Treatment Period will have the opportunity to 
continue their treatment in an optional 26-week Long-term Extension after completing the Week 
52 assessments. Participants who do not enroll into the Long-term Extension must complete the 
final Safety Follow-up Period for the main part of the study, including the Week 56 Visit (4 weeks 
after receiving the last dose of MORF-057), for a maximum time on-study of 62 weeks. 
Participants who choose to continue in the Long-term Extension will not complete the Safety 
Follow-up Period for the main part of the study; instead, they will directly enter the Long-term 
Extension and complete a separate Safety Follow-up Period, including the Week 82 Visit (4 weeks 
after receiving the last dose of MORF-057). 
During the optional Long-term Extension, there will be 3 scheduled study visits: 2 Treatment Visits 
(Visits 11-12 at Weeks 65 and 78), and a Safety Follow-up Visit (4 weeks after the last dose of 
study drug is received, which will be Visit 13 at Week 82 if the full Long-term Extension is 




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Histology plays a critical role in diagnosing UC and monitoring disease progression. Robarts 
Histopathology Index is a validated and reliable tool that is commonly used to evaluate the 
histological response of a treatment in patients with UC. Therefore, the RHI was selected as the 
primary efficacy endpoint of this study.  
Study entry criteria were carefully selected to reflect an adult population consistent with the 
moderately to severely active UC population likely to be treated with MORF-057 in clinical 
practice. 
4.3. 
Justification for Dose 
A dosing regimen of 
 mg 
 has been selected for the current study. In study 
MORF-057-101, which included SAD and MAD assessments in healthy adults, maximum 
saturation of α4β7 receptor occupancy was observed following 
mg 
 dosing in the 
 
part of the study. MORF-057 exhibited favorable PK profiles with only mild, non-serious AEs 
reported that did not result in study drug discontinuation. The mean plasma trough concentration 
obtained with 
 mg 
 was 22 ng/mL. This exposure seen in healthy individuals is expected 
to be similar in UC patients and will provide levels to achieve adequate efficacy and safety.  
MORF-057 is designed specifically to inhibit α4β7, which is involved in the trafficking of immune 
cells to sites of inflammation in the intestinal mucosa but exhibits low inhibition of all other 
integrins, including α4β1. Integrin α4β1 regulates immune cell trafficking to many non-mucosal 
tissue sites including skin, lung, and the central nervous system (von Andrian, 2000). In human 
whole blood ex vivo studies, the selectivity ratio of IC50 and IC90 values with respect to α4β7 and 
α4β1 for MORF-057 are 
 and 
, respectively. The MORF-057 dose selected for the 
current study is anticipated to cause minimal to no α4β1 inhibition in humans, and α4β7 and α4β1 
receptor occupancies in blood will be assessed as an exploratory endpoint. 
4.4. 
End of Study Definition 
A participant is considered to have completed the study if he/she has completed the Screening and 
52-week Treatment Periods of the study and attended the Safety Follow-up Visit OR has 
completed the Week 52/EOT Visit and has been enrolled into the Long-term Extension.  
The end of the study is defined as the date of the last visit of the last participant in the main part 
of the study or last scheduled procedure shown in the schedule of activities (SoA) for the last 
participant in the main part of the study globally.  
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5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
Main Inclusion Criteria: 
Participants are eligible to be included in the study only if all the following criteria apply: 
Age 
1. 18 to 85 years of age, inclusive, at the time of signing the Informed Consent Form 
(ICF) 
Type of Participant and Disease Characteristics 
2. Participant has had signs/symptoms of moderately to severely active UC for at least 
3 months prior to Screening, and the diagnosis was confirmed during the Screening 
Period with the following criteria: a Modified MCS of 5 to 9 (inclusive) with an MES 
≥2 (confirmed by central reader)  
3. Has an RHI Score of 10 or greater 
4. Has evidence of UC extending at least 15 cm from the anal verge 
5. Is an AT-naïve participant or a participant who had an inadequate response, loss of 
response, or intolerance to no more than 3 drugs in 2 classes of the following: 
a. TNF-α antagonists, including infliximab, adalimumab, or golimumab 
b. Interleukin (IL)-12/IL-23 antagonists, including ustekinumab 
c. JAK antagonists, including tofacitinib and upadacitinib 
d. S1P receptor agonists, including ozanimod  
e. Any investigational product with the same mechanism as one of those outlined 
above (5a through 5d) 
f. Integrin inhibitors, including vedolizumab (participants in the Exploratory Cohort 
only) 
Note: Participants who have a history of primary non-response to 2 of the classes above 
will not be eligible. Participants who have received treatment with these agents at 
sub-therapeutic doses, or durations, should be discussed with the Medical Monitor to 
assess eligibility. 
6. Meets the following washout criteria of prior UC therapy relative to study Day 1:  
a. TNF-α antagonists: at least 8 weeks 
b. IL-12/IL-23 antagonists, including ustekinumab: at least 8 weeks 
c. JAK antagonists, including tofacitinib and upadacitinib: at least 2 weeks 
d. S1P receptor agonists, including ozanimod: at least 4 weeks 
7. If the participant has been receiving any of the non-prohibited medications for UC 
listed below, he/she must discontinue use at least 5 half-lives before study Day 1 or 
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the time specified below until the end of the Safety Follow-up Period, with the 
exception of tapering oral corticosteroid dose after 12 weeks of being in the trial. 
a. 5-Aminosalicylates (not exceeding 4.8 g per day): at least 2 weeks prior to study 
Day 1 
b. Oral corticosteroids (not exceeding prednisone 30 mg per day, budesonide 9 mg 
per day, or equivalent): at least 2 weeks prior to study Day 1 
c. 6-Mercaptopurine (any stable dose): at least 4 weeks prior to study Day 1 
d. Azathioprine (any stable dose): at least 4 weeks prior to study Day 1 
e. Methotrexate (any stable dose): for at least 4 weeks prior to study Day 1 
8. In the opinion of the Investigator, the participant can fully participate in all aspects 
of this clinical study 
Weight 
9. Has a body mass index (BMI) within the range of 18.0 and 40.0 kg/m2 (inclusive) at 
Screening 
Sex and Contraceptive/Barrier Requirements  
10. A participant is eligible to participate if he/she agrees to abide by the guidelines set 
forth in this protocol regarding contraception requirements (see full contraception 
guidelines in Section 10.5): 
a. A male participant is eligible to participate if he agrees to the following during the 
study Treatment Period and for at least 28 days after receiving the last dose of 
MORF-057: 
• 
Abstains from heterosexual intercourse as his preferred and usual lifestyle 
(abstinent on a long-term and persistent basis) and agrees to remain 
abstinent 
OR 
• 
Agrees to use contraception/barrier methods as detailed below: 
o Agrees to use a male condom, with female partner use of an additional 
highly effective contraceptive method with a failure rate of <1% per 
year (as described in Section 10.5.2) when having sexual intercourse 
with a woman of childbearing potential who is not currently pregnant 
o Agrees to use a male condom when engaging in any activity that 
allows for passage of ejaculate to another person 
b. A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and one of the following conditions applies: 
• 
Is a woman of non-childbearing potential (as defined in Section 10.5.1)  
OR 
• 
Is a woman of childbearing potential (as defined in Section 10.5.1) and 
agrees to use a contraceptive method that is highly effective with a failure 
rate of <1% per year (as described in Section 10.5.2) during the study 


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Treatment Period and for at least 28 days after receiving the last dose of 
MORF-057 
Note: Women who use any oral hormonal contraception must use an 
additional physical barrier method (Section 10.5.2). 
11. For the study Treatment Period and at least 28 days after receiving the last dose of 
MORF-057, male participants must agree not to donate sperm and female participants 
must agree not to donate eggs (ova, oocytes). 
Informed Consent 
12. Capable of giving signed informed consent, as described in Section 10.1.4, which 
includes compliance with the requirements and restrictions listed in the ICF and in 
this protocol 
Exploratory Cohort Inclusion Criteria: 
In addition to meeting Inclusion Criteria 1 through 12, the following criteria must be met for 
participants to be included in the Exploratory Cohort: 
13. Those intolerant to (e.g. infusion-related skin reaction, allergy, or side effects 
unrelated to α4β7 inhibition) or secondary non-responders* to vedolizumab who have 
been dosed within the past 5 years with the drug. Up to 5 of the 10 Exploratory Cohort 
participants may be included based on clinical criteria only. The remaining 
participants must also meet at least 1 of the following criteria:  
a. Documented vedolizumab levels in blood of ≤10 µg/mL 6 to 8 weeks after their 
most recent dose or at what is considered clinical trough. If the participant has 
had vedolizumab levels in blood tested and documented in their medical chart 
prior to Screening, the test does not need to be repeated. 
b. Non-saturating receptor occupancy of vedolizumab in blood 6 to 8 weeks after 
their most recent dose 
c. Documented presence of anti-drug antibodies against vedolizumab. If the 
participant has had a positive anti-drug antibody test that has been documented 
prior to Screening, the test does not need to be repeated. 
*Note: Secondary non-response is defined as having initially responded to 
Induction therapy and then had recurrence of symptoms after receiving at least 2 
of the Maintenance doses, 300 mg every 8 weeks (discontinuation despite clinical 
benefit does not qualify). 
14. The participants should also have received their last dose of vedolizumab at least 6 
weeks prior to study Day 1 to allow sufficient washout 
 


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5.2. 
Exclusion Criteria 
Participants will be excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. Diagnosed with indeterminate colitis, microscopic colitis, ischemic colitis, radiation 
colitis, or CD or has clinical findings suggestive of CD 
2. Has current evidence of un-resected colonic dysplasia or un-resected adenomatous 
colonic polyps or evidence of toxic megacolon, abdominal abscess, symptomatic 
colonic stricture, fistula, stoma, ileostomy, or colostomy at Screening  
3. Currently requires or is anticipated to require surgical intervention for UC during the 
study or is planning to undergo major surgery during the study period 
4. Has had a surgical procedure requiring general anesthesia within 30 days prior to 
Screening  
5. Has a history of any major neurological disorders, including stroke, multiple 
sclerosis, brain tumor, demyelinating, or neurodegenerative disease. For questions 
about whether this applies to a specific case, consult with the Medical Monitor. 
6. Has positive findings on a subjective neurological screening questionnaire or PML 
subjective symptom checklist during Screening or prior to the administration of the 
first dose of study drug on study Day 1 
7. Has an active bacterial, viral, or parasitic pathogenic enteric infection, including 
Clostridium difficile; has cytomegalovirus, hepatitis B or C virus, or human 
immunodeficiency virus (HIV); had an infection requiring hospitalization or 
intravenous antimicrobial therapy, or an opportunistic infection within 3 months prior 
to Screening; had any infection requiring oral antimicrobial therapy within 2 weeks 
prior to Screening; or has a history of more than 1 episode of herpes zoster or any 
episode of disseminated herpes zoster infection 
8. Has a positive diagnostic tuberculosis (TB) test at Screening (defined as a positive 
 test). If the participant has had a confirmed negative 
 
or other Interferon Gamma Release Assay test within 90 days prior to Screening, the 
test does not need to be repeated. In cases where the 
 test result is 
indeterminate, the participant may have the test repeated once, and if the second test 
is negative, the participant will be eligible. In the event the second test also has an 
indeterminate result or 
 is unavailable, the Investigator has the option 
to perform a purified protein derivative (PPD) skin test. If the PPD reaction is <5 
mm, then the participant is eligible. If the reaction is ≥5 mm or PPD testing is not 
done, the participant is not eligible. An exception can be made for participants with 
a history of latent TB who are currently receiving treatment for latent TB per local 
standard care, who will initiate treatment for latent TB before the first dose of study 
drug, or who have documentation of completing appropriate treatment for latent TB 
within 2 years prior to study Day 1. 


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9. Tests positive for Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 
during the Screening Period. Participants who test positive for SARS-CoV-2 can 
undergo retesting throughout the Screening Period. Testing to be performed 
according to site-specific testing procedures and country-specific requirements. 
10. Had any vaccination (including live virus vaccinations) within 3 weeks prior to study 
Day 1. Note: For vaccinations requiring a series of doses, the last in the series should 
be completed by 3 weeks prior to study Day 1 (e.g., SARS-CoV-2 two-shot 
vaccination series). 
11. Has a concurrent, clinically significant, serious, unstable comorbidity (such as 
uncontrolled 
cardiovascular, 
pulmonary, 
hepatic, 
renal, 
gastrointestinal, 
genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or 
other medical disorder) that, in the judgement of the Investigator, would compromise 
compliance with the protocol, interfere with interpretation of the study results, or pre-
dispose participants to safety risks 
12. Has a known primary or secondary immunodeficiency 
13. Has a history of myocardial infarction, unstable angina, transient ischemic attack, 
decompensated heart failure requiring hospitalization, congestive heart failure (New 
York Heart Association Class 3 or 4), uncontrolled arrhythmias, cardiac 
revascularization, uncontrolled hypertension, or uncontrolled diabetes within 
6 months of Screening 
14. Has a history of left ventricular ejection fraction (LVEF) <50%  
15. Has a clinically significant abnormal ECG at Screening, including a QT interval 
corrected through use of Fridericia’s formula (QTcF) ≥450 ms for males and ≥470 ms 
for females 
16. Abnormal hematology (hemoglobin level, WBC count, or platelet count) or 
coagulation results at Screening, as evidenced by the ranges provided below:*  
a. Hemoglobin level <8.0 g/dL  
b. Absolute WBC count <3.0 × 109/L 
c. Absolute lymphocyte count <0.5 × 109/L  
d. Absolute lymphocyte count >5.0 x 109/L 
e. Absolute neutrophil count <1.2 × 109/L  
f. Platelet count <100 × 109/L or >1000 × 109/L    
g. International normalized ratio >1.5  
17. Clinically significant abnormal urinalysis results, as deemed by the Investigator or 
designee 
18. Abnormal organ function at Screening, as evidenced by the following:* 
a. Alanine aminotransferase or aspartate aminotransferase >2.5 × upper limit of 
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b. Chronic kidney disease stages 4 and 5, defined as having a glomerular filtration 
rate <30 mL/min/1.73m2 as calculated using the Modification of Diet in Renal 
Disease (MDRD) equation, receiving dialysis, or being listed for or has received a 
renal transplant 
c. Total bilirubin ≥1.5 × ULN 
*Note: Repeat testing should be done at the discretion of the Investigator. Consult with the 
Medical Monitor as needed. 
19. History of active malignancy in the 5 years preceding study Day 1, except in cases of 
basal cell skin cancer, squamous cell skin cancer, or other in-situ malignancies that 
have been excised and resolved and the participant was deemed clear of cancer after 
appropriate follow-up. Participants with a history of malignancy or those at high risk 
for malignancy may only be enrolled after a consultation with the Medical Monitor. 
Prior/Concomitant Therapy 
20. Treatment with cyclosporine, mycophenolate, tacrolimus, or sirolimus within 30 days 
or 5 half-lives (whichever is shorter) prior to study Day 1  
21. Any previous treatment with vedolizumab or other integrin inhibitors (except 
participants for the Exploratory Cohort) 
22. Experiencing toxicities from prior therapy with Grade >1 within 1 week prior to first 
dose of study drug 
23. Fecal microbiota transplantation within 3 months prior to Screening 
24. If treatment with a moderate-to-strong CYP3A4 inducer or inhibitor was received, a 
washout period of at least 30 days or 5 half-lives (whichever is shorter) is required 
prior to study Day 1. See Section 6.7.2 for a list of moderate-to-strong P450 inducers 
and inhibitors. 
25. If treatment with a moderate-to-strong organic anion transporter polypeptide-1B 
inhibitor was received, a washout period of at least 14 days or 5 half-lives (whichever 
is shorter) is required prior to study Day 1. See Section 6.7.2 for a list of moderate-
to-strong organic anion transporter polypeptide-1B inhibitors. 
Prior/Concurrent Clinical Study Experience 
26. Concurrent participation in any other interventional study  
27. Received any investigational therapy within 30 days or 5 half-lives (whichever is 
longer) prior to study Day 1 
28. Previous exposure to MORF-057 and/or a known hypersensitivity to drugs with a 
similar mechanism to MORF-057 
Other Exclusions 
29. Females who are pregnant or lactating or who are planning on becoming pregnant 
during the course of the study 


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30. Current or recent history of alcohol dependence or illicit drug use that, in the opinion 
of the Investigator, may interfere with the participant’s ability to comply with the 
study procedures 
31. Mental or legal incapacitation or a history of clinically significant psychiatric 
disorders at the time of the Screening Visit that would impact the ability to participate 
in the trial according to the Investigator 
32. Unable to attend study visits or comply with procedures 
5.3. 
Lifestyle Considerations 
The following dietary and lifestyle restrictions are recommended:  
• 
Refrain from consuming grapefruit, grapefruit juice, starfruit, limes, and bitter oranges. 
• 
Refrain from excessive caffeine consumption, defined as ≥800 mg/day. For each 
scheduled study visit, participants should refrain from ingesting caffeine- or xanthine-
containing products (e.g., coffee, tea, cola drinks, and chocolate) before the 
 
dose until after all study assessments and blood collections have been completed for 
that visit. 
• 
For each scheduled study visit, participants should refrain from consuming alcohol 
before the 
 dose until after all study assessments and blood collections have 
been completed for that visit. 
• 
Refrain from the use of cannabidiol and tetrahydrocannabinol. 
5.4. 
Screen Failures 
A screen failure occurs when a participant who consents to participate in the clinical study is not 
subsequently enrolled in the study. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials publishing requirements and to respond to queries from regulatory authorities. 
Minimal information includes demography, screen failure details, eligibility criteria, and any 
serious adverse events (SAEs). 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
re-screened based on discussion and agreement between the Investigator and the Sponsor Medical 
Monitor. Re-screened participants should be assigned a new participant number for every 
screening/re-screening event. 


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6. 
STUDY TREATMENT 
6.1. 
Study Treatment Description 
A description of the study drug is provided in Table 3. More detailed information about the study 
drug can be found in the Pharmacy Manual.  
Refer to Section 8.3 for study drug administration instructions. 
MORF-057 capsules will be manufactured, quality control tested, and released in accordance with 
Good Manufacturing Practice. 
Table 3. 
Study Intervention  
Study drug 
MORF-057 
Type  
Small molecule drug  
Dose formulation 
 capsule (Swedish orange capsule size 4) 
Unit dose strength 
 mg/capsule 
Route of Administration 
Oral 
Dosage 
 mg 
  
Use 
Experimental 
IMP/NIMP 
IMP 
Sourcing 
Provided by Sponsor 
Packaging and Labeling 
Capsules are packaged in a high-density polyethylene bottle 
containing an oxygen absorber canister and coil and closed with a 
child-resistant cap equipped with a heat-sealed foil liner. Each 
bottle will be labeled as per country requirements. 
Storage 
Capsules must be stored at 20°C to 25°C (68°F to 77°F). 
Excursions are permitted from 15°C to 30°C (59°F to 86°F). 
Abbreviations: 
., 
 IMP, investigational medicinal product; NIMP, non-investigational medicinal 
product. 
6.2. 
Preparation, Handling, Storage, and Accountability 
The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study drug received, and any discrepancies are reported and 
resolved before use of the study drug. 
Only participants enrolled in the study may receive MORF-057, and only authorized site staff may 
supply or administer MORF-057. All MORF-057 supplies must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
labeled storage conditions with access limited to the Investigator and authorized site staff. 
The Investigator, institution, or the head of the medical institution (where applicable) is responsible 
for study drug accountability, reconciliation, and record maintenance (i.e., receipt, reconciliation, 


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and final disposition records). All unused study drug for all participants should be maintained until 
review by a study monitor during site visits and at the time of database lock. 
All unused MORF-057 capsules remaining at the completion of the study will either be returned 
to the Sponsor or destroyed at the investigational site per Sponsor instruction. It is the 
responsibility of the Investigator to ensure that the Sponsor has provided written authorization 
prior to return or destruction of study drug. Study drug return/destruction will be documented in 
the site files. No unused study drug may be disposed until fully accounted for by the study monitor.  
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
This is an open-label, single-arm study; therefore, randomization and blinding will not be used.  
Enrollment will be conducted using interactive response technology. 
6.4. 
Study Treatment Compliance 
When participants are dosed at the site, they will receive the study drug directly from the 
Investigator or designee, under medical supervision. The date and time of each dose administered 
in the clinic will be recorded in the source documents. The dose of study drug and study participant 
identification will be confirmed at the time of dosing by a member of the study site staff other than 
the person administering the study intervention.  
When participants self-administer the study drug at home, compliance with prescribed dosage will 
be assessed at each visit. Participants will be instructed to record all details about the doses 
administered at home in the Participant Diary. Participants will also be advised to bring any 
remaining study drug supply to each site visit. Compliance will be assessed by reviewing the 
Participant Diary entries and counting returned capsules during the site visits; the findings will be 
documented in the source documents and relevant form. Deviation(s) from the prescribed dosage 
regimen should be recorded. 
A record of the quantity of MORF-057 dispensed to and administered by each participant must be 
maintained and reconciled with study intervention and compliance records. Intervention start and 
stop dates, including dates for intervention delays and/or dose reductions, will also be recorded. 
6.5. 
Continued Access to Study Intervention after the End of the Study 
All participants will have the opportunity to enroll into a separate Long-term Extension after 
completing the Week 52 assessments. Participants who are willing to enroll into the Long-term 
Extension will skip the Safety Follow-up Visit at Week 56 and directly enter the Long-term 
Extension. Participants enrolled into the Long-term Extension will complete the Safety Follow-up 
Visit at Week 82. 
Participants who do not enroll in the Long-term Extension will no longer have access to the study 
drug after they complete the 52-week Treatment Period. Participants who continue in the 
Long-term Extension will no longer have access to the study drug after they complete the 26-week 
extended Treatment Period. 
6.6. 
Treatment of Overdose 
There are no data available on the effects of acute or chronic overdosage with MORF-057. 


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For this study, any total daily dose of MORF-057 greater than 200 mg will be considered an 
overdose. 
In the event of an overdose, the Investigator/treating physician should: 
• 
Contact the Medical Monitor within 24 hours 
• 
Evaluate the participant to determine, in consultation with the Medical Monitor, 
whether study drug should be interrupted or discontinued 
• 
Closely monitor the participant for any AEs/SAEs and/or laboratory abnormalities  
• 
Document the quantity of the excess dose as well as the duration of the overdose 
• 
Enter the overdose information into the electronic data capture database (EDC) within 
24 hours of notification 
6.7. 
Concomitant Therapy 
Any medications (including over-the-counter or prescription medicines, recreational drugs, 
vitamins, and/or herbal supplements) or vaccines that the participant receives from the time of 
Screening through the Safety Follow-up Visit must be recorded in the electronic case report form 
(eCRF) along with: 
• 
Reason for use 
• 
Dates of administration including start and end dates 
• 
Dosage information including dose, frequency, and route of administration 
Any medication given for a study-related AE should be recorded from the time of informed 
consent.  
6.7.1. 
Allowed Medications for the Treatment of Ulcerative Colitis 
The following list of concomitant medications for UC will be allowed during the study: 
• 
5-Aminosalicylates (not exceeding 4.8 g per day) 
• 
Oral corticosteroids (not exceeding prednisone 30 mg per day, budesonide 9 mg per 
day, or equivalent) 
• 
6-Mercaptopurine (any stable dose) 
• 
Azathioprine (any stable dose) 
• 
Methotrexate (any stable dose) 
Although these medications are allowed, participants should not start or stop any of these 
medications during the study. Furthermore, participants must maintain stable doses of these 
concomitant medications throughout the study until the end of the Safety Followup- Period, with 
the exception of tapering oral corticosteroid dose after 12 weeks of being in the trial. See Inclusion 
Criterion 3 (Section 5.1) for screening r-elated requirements for these medications.  
If any other medications need to be started due to worsening of UC symptoms, the Medical 
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6.7.1.1. 
Tapering of Oral Corticosteroids 
If medically appropriate to initiate a taper of oral corticosteroids (e.g., at least 1 month of stable 
clinical improvement approximating baseline status), the following steroid tapering schedules 
should be used, unless medically contraindicated after discussion with the Medical Monitor. 
Participants receiving prednisone at the time of enrollment should maintain their current dose 
regimen during the Induction Period. After completion of the Week 12 visit, participants are 
allowed to completely taper off prednisone by reducing dose at 5 mg per week until daily dose 
reaches 10 mg per day, then further reducing dose at 2.5 mg per week until prednisone is 
completely tapered off.  
Participants receiving budesonide at the time of enrollment should maintain their current dose 
regimen during the Induction Period. After completion of the Week 12 visit, participants are 
allowed to completely taper off budesonide by reducing dose at 3 mg per day for every 2 weeks 
until budesonide is completely tapered off. Participants receiving budesonide MMX (1 tablet, 
9 mg) can reduce dosage by taking 6 mg budesonide (2 tablets, 3 mg each) daily for two weeks, 
followed by 3 mg budesonide (1 tablet, 3 mg) daily for two weeks to complete the tapering process.  
However, during the taper, if participants experience clinical worsening of UC, increasing the dose 
back up to the dose used at trial entry (but not higher) is permitted. Participants are advised to 
resume the taper within 2 to 4 weeks. 
6.7.2. 
Prohibited Medications 
The following concomitant medications/therapies are prohibited for the entire duration of the study, 
including Safety Follow-up: 
• 
Treatments for UC other than those listed in Section 6.7.1 (including TNF-α 
antagonists, integrin antagonists, IL-12/IL-23 antagonists, JAK antagonists, and S1P 
receptor agonists) 
• 
Receipt of a live virus vaccine from 3 weeks prior to study Day 1 until 28 days after 
the last dose of study drug 
• 
Note: Non-live vaccines, including those for SARS-CoV-2, should not be 
administered between 3 weeks prior to study Day 1 and the Week 12 assessments. 
After the Week 12 assessments, such vaccines can be administered according to local 
vaccination standards. Per Exclusion Criterion 10, if the participant has started a 
vaccination series before Day 1, the last in the series should be completed by 3 weeks 
prior to Day 1 (Section 5.1).  
• 
Moderate-to-strong CYP3A inhibitor or inducer (see Table 4) 
• 
Moderate-to-strong organic anion transporter polypeptide-1B inhibitor (see Table 4) 
• 
Cyclosporine, mycophenolate, tacrolimus, or sirolimus 
• 
Nonsteroidal anti-inflammatory drugs (NSAIDs) including but not limited to 
ibuprofen, naproxen, indomethacin, and celecoxib. However, participants may take 
aspirin for secondary prevention of cardiovascular event at a dose not exceeding 
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• 
Any investigational therapy 
 
Table 4. 
Examples of Drugs Potentially Altering Exposures to MORF-057# 
CYP3A Inhibitors (Moderate to Strong) 
Aprepitant 
Indinavir 
Telithromycin 
Mifepristone* 
Ceritinib 
Itraconazole 
Tucatinib 
Norfloxacin* 
Clarithromycin 
Ketoconazole 
Verapamil 
Norfluoxetine* 
Crizotinib 
Mibefradil 
Voriconazole 
Regorafenib* 
Diltiazem 
Nefazodone 
Amiodarone* 
Telaprevir* 
Erythromycin 
Nelfinavir 
Boceprevir* 
 
Fluconazole 
Ribociclib 
Ciprofloxacin* 
 
Grapefruit juice 
Ritonavir 
Delavirdine* 
 
Idelalisib 
Saquinavir 
Fluvoxamine* 
 
CYP3A Inducers 
Barbiturates 
Elagolix 
Modafinil 
Pioglitazone 
Brigatinib 
Enzalutamide 
Nevirapine 
Rifabutin 
Carbamazepine 
Eslicarbazepine 
Oritavancin 
Rifampin 
Clobazam 
Glucocorticoids 
Oxcarbazepine 
St. John’s wort 
Dabrafenib 
Letermovir 
Phenobarbital 
Telotristat 
Efavirenz 
Lorlatinib 
Phenytoin 
Troglitazone 
OATP1B1/3 Inhibitors 
Atazanavir and 
ritonavir 
Cyclosporine 
Gemfibrozil 
Rifampin (single dose) 
Clarithromycin 
Erythromycin 
Lopinavir and ritonavir 
Simeprevir 
# This is not an exhaustive list CYP3A inhibitors/inducers or OATP1B1 inhibitors.   
* Time-dependent inhibitors 
Sources: (Flockhart, 2021) (US FDA, 2020) 
 


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6.7.3. 
Prohibited Procedures 
The following concomitant procedures are prohibited during the study: 
• 
Major elective surgery 
• 
Immunoadsorption columns 
• 
Intravenous immunoglobulin or plasmapheresis 
• 
Blood donations during the study and for 28 days after the last dose of study drug 


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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Treatment 
7.1.1. 
Permanent Discontinuation 
In rare instances, it may be necessary for a participant to permanently discontinue the study drug. 
If the study drug is permanently discontinued, the participant should remain in the study to be 
evaluated for the 4-week Safety Follow-up Visit. See the SoA (Section 1.2) for the assessments to 
be performed at the time of study drug discontinuation (End of Treatment Visit) and follow-up for 
any further evaluations that need to be completed. 
A participant’s study treatment may be discontinued if any of the following occur during the study: 
• 
Use of disallowed medications and/or procedures as defined in Sections 6.7.2 and 
6.7.3 
• 
Severe uncontrolled infection 
• 
Lack of efficacy defined as:  
o Determined by the Investigator that the participant is not benefiting from the 
investigational treatment and/or continued participation would pose an 
unacceptable risk to the participant 
o Administration of a rescue medication (a new medication or increase in dose of a 
baseline medication to treat new or unresolved UC symptoms). Anti-diarrheals for 
control of chronic diarrhea are not considered rescue medication.  
o Requirement for abdominal surgery due to complications from UC 
• 
Pregnancy or planned pregnancy (see Section 8.9.5) 
• 
Non-compliance with study treatment (see Section 6.4) 
• 
Sponsor or the Investigator deems it is necessary for the participant 
If a participant who does not meet the enrollment criteria is inadvertently enrolled, that participant 
must be discontinued from the study drug, and the Sponsor or Sponsor designee must be contacted. 
An exception may be granted in rare circumstances for which there is a compelling safety reason 
to allow the participant to continue. In these rare cases, the Investigator must obtain documented 
approval from the Sponsor or Sponsor’s designee to allow the participant to continue in the study. 
The reason for discontinuation of the study drug will be recorded in the clinical records and the 
participant’s eCRF. 
7.1.2. 
Temporary Discontinuation 
Decisions regarding dose interruptions will be made by the Investigator in consultation with the 
Medical Monitor based on the clinical evaluation of the participant. 
7.1.3. 
Re-challenge 
Re-challenge may be allowed at the discretion of the Investigator and Medical Monitor. 


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7.2. 
Participant Discontinuation/Withdrawal from the Study 
A participant may withdraw from the study at any time at his/her own request or may be withdrawn 
at any time at the discretion of the Investigator for safety, behavioral, or compliance reasons. This 
is expected to be uncommon. 
The participant should be encouraged to complete the End of Treatment Visit (Visit 10 in the main 
part of the study, or Visit 12 in the Long-term Extension) at the time of study drug discontinuation 
and the Safety Follow-up Visit (Visit 11 in the main part of the study, or Visit 13 in the Long-term 
Extension) at 28 days (+7) after the last dose of study drug. See the SoA (Section 1.2) for details 
regarding the data to be collected at the End of Treatment and Safety Follow-up Visits. 
If the participant withdraws consent for disclosure of future information, the Sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the Investigator must document this in the site study records. 
Participants who withdraw or are withdrawn from the study will not be replaced. 
Closure/termination of specific study centers or of the study as a whole are handled as described 
in Section 10.1.11.2. 
7.3. 
Lost to Follow-up 
A participant will be considered lost to follow-up if he/she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required study 
visit: 
• 
The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible, counsel the participant on the importance of maintaining the 
assigned visit schedule, and ascertain whether the participant wishes to and/or should 
continue in the study. 
• 
Before a participant is deemed lost to follow-up, the Investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls, and if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s clinical record. 
• 
Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study.  


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8. 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the SoA (Section 1.2). Protocol waivers or 
exemptions are not allowed. 
Immediate safety concerns should be discussed with the Sponsor immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue study drug. 
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 participants 
meet all eligibility criteria. The Investigator will maintain a Screening Log to record details of all 
participants screened and to confirm eligibility or record reasons for screening failure, as 
applicable. 
Repeat or unscheduled blood samples may be taken for safety reasons or for technical issues with 
the samples. 
Maximum volume of blood to be obtained over the duration of the study will not exceed local 
regulation requirements. 
8.1. 
Medical History 
The participant’s demographics and medical and surgical history are to be recorded at Screening. 
In addition, the participant’s medication history should be collected for at least 12 months prior to 
Day 1.  
All prior advanced therapies for the treatment of UC (e.g., antagonists to TNF-α, JAK, or 
IL-12/IL-23; S1P receptor agonists; integrin inhibitors [Exploratory Cohort only]; or other new 
investigational treatments) with the reason for discontinuation are to be collected for participants 
where possible.  
8.2. 
Screening-specific Tests 
8.2.1. 
Pathogen Screening 
8.2.1.1. 
Tuberculosis 
All participants will complete TB screening to determine eligibility. See Exclusion Criterion 8 
(Section 5.2) and the SoA (Section 1.2) for details regarding testing requirements. 
8.2.1.2. 
SARS-CoV-2 
All participants will complete SARS-CoV-2 screening to determine eligibility. See Exclusion 
Criterion 9 (Section 5.2) and the SoA (Section 1.2) for details regarding testing requirements. 
8.2.1.3. 
C. difficile and Enteric Pathogens 
All participants will complete C. difficile and enteric pathogen screening (including ova and 
parasite testing) to determine eligibility. See Exclusion Criterion 7 (Section 5.2) and the SoA 
(Section 1.2) for details regarding testing requirements. 


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8.2.1.4. 
Cytomegalovirus 
All participants will complete cytomegalovirus screening to determine eligibility. See Exclusion 
Criterion 7 (Section 5.2) and the SoA (Section 1.2) for details regarding testing requirements. 
8.2.1.5. 
HIV, Hepatitis B, and Hepatitis C 
All participants will complete the following screening tests to determine eligibility: HIV antibody, 
hepatitis B surface antigen, and hepatitis C virus antibody. See Exclusion Criterion 7 (Section 5.2) 
and the SoA (Section 1.2) for details regarding testing requirements. 
8.2.2. 
Drug/Alcohol Screening 
All participants will complete a serum alcohol screen and a urine drug screen to determine 
eligibility. See Exclusion Criterion 30 (Section 5.2) and the SoA (Section 1.2) for details regarding 
testing requirements. 
8.2.3. 
Exploratory Cohort Screening Tests 
All participants being considered for the Exploratory Cohort must undergo a specific panel of 
blood tests to determine eligibility (see Inclusion Criteria 13 and 14 [Section 5.1] and the SoA 
[Section 1.2]). The specific tests are described below: 
• 
Vedolizumab blood levels 6 to 8 weeks after their most recent dose or at what is 
considered clinical trough. (If the participant has had vedolizumab levels in blood 
tested and documented in their medical chart prior to Screening, the test does not 
need to be repeated.) 
• 
Receptor occupancy of vedolizumab in blood 6 to 8 weeks after their most recent 
dose 
• 
Anti-vedolizumab antibody testing (If the participant has had a positive anti-drug 
antibody test that has been documented prior to Screening, the test does not need to 
be repeated.) 
8.3. 
Study Drug Administration 
8.3.1. 
Dosing Instructions 
Participants will swallow 
mg capsules of MORF-057 with water 
. MORF-057 
can be taken with or without food. No dose adjustments will be allowed. 
8.3.2. 
Missed Dose Instructions 
MORF-057 capsules should be taken at approximately the same time every day in the 
 
and in the 
. The interval between doses should be as close to 12 hours as possible. 
Participants should be instructed that if they forget to take a dose, they can take the dose within 
 of the 
; otherwise, they should take their next dose at the regular time 
on the following day. Participants who vomit a capsule should be instructed not to take another 
capsule at that dosing time, but to take the next scheduled dose at the regular time. Participants 
will record their daily dose in the Participant Diary. Missed doses that occur at any time during a 
week prior to PK sampling should be recorded in the eCRF. Participants should be instructed to 


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contact the Investigator if they miss more than 2 consecutive doses; in such cases, the Investigator 
should consult with the Medical Monitor regarding any actions required.  
8.4. 
Virtual/Hybrid Visits 
To allow participants to remain in the study to continue to be evaluated, a virtual or hybrid visit 
may be considered only for participants who are not able to participate in an on-site visit. Some 
visit assessments and procedures may be performed virtually or off-site with the permission of the 
Investigator and Sponsor in accordance with all national, state, and local laws or regulations of the 
pertinent regulatory authorities. Examples of assessments or procedures that may be conducted 
virtually, if allowed by local law and regulation, include safety assessments as applicable (e.g., 
AE/SAE assessments), review of Participant Diary compliance, and collection of samples for 
pregnancy testing and/or central laboratory assessments.  
Regardless of how a study visit and its associated procedures are conducted, all study procedures 
should be performed by qualified study site staff or qualified individuals as delegated by the 
Investigator.  
8.5. 
Participant Diary 
Participants will be asked to capture study data in their Participant Diary. Entries will begin on the 
first day of Screening after diary training is completed and will continue through the Safety 
Follow-up Visit. Diary entries will include study drug administration details and daily rectal 
bleeding and stool frequency information (the 2 patient-reported outcome measures of the Full and 
Modified MCS, see Section 8.7.3). Diaries are to be completed daily by the participant. The 
Participant’s Diary will be reviewed by study site staff to ensure the participant is compliant with 
diary entries through EDC and during each study visit at the times noted in the SoA (Section 1.2).  
Detailed descriptions regarding Participant Diary recordings can be found in the Patient Guide. 
8.6. 
Stool Collection 
Stool samples will be required to assess fecal calprotectin levels, microbiome composition in stool, 
microbiome-derived metabolites in stool, and meta-transcriptomic changes in stool microbiome. 
Samples for these tests should be collected on site, if possible, according to the respective 
schedules shown in the SoA (Section 1.2). 
In addition, stool collection kits are to be dispensed to participants at the visits indicated in the 
SoA. The participant should use this kit to collect one sample at home within 24 hours before the 
next site visit. The sample should be frozen immediately and brought to the clinic on the day of 
the site visit. Note: Sample is to be collected prior to bowel preparation for Visits 4, 5, and 10/EOT 
of the main Treatment Period. These samples will be used as back-ups if the participant is unable 
to provide a fresh sample during the respective site visit. 
See the Laboratory Manual for additional details about stool collection procedures. 


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8.7. 
Efficacy Assessments 
8.7.1. 
Endoscopy with Biopsy 
Endoscopy will be performed at Screening (Visit 1) and Visits 4 (optional), 5, and 10/EOTFlexible 
sigmoidoscopy with colonoscopy scope is the suggested procedure, but full colonoscopy is 
optional at any timepoint if the Investigator deems it necessary. During these procedures, colonic 
mucosa biopsies will be collected for cytomegalovirus testing (Screening only), histopathology, 
spatial transcriptomics/proteomics, microbiome, and gene expression analyses. A total of 12 
biopsies will be collected during each endoscopy procedure. To ensure quality data and 
standardization, the same endoscopist should be used throughout the study wherever possible. A 
detailed image review charter from the central reading laboratory will outline the endoscopic 
procedures, video recordings, and equipment.  
For each participant, a video recording of the entire endoscopic procedure will be performed using 
an acceptable storage medium.  
The original location (colonic segment) of biopsy specimens acquired at Screening must be clearly 
indicated. Detailed instructions for endoscopic biopsies (e.g., anatomic site, normal or inflamed 
mucosa) can be found in the Central Image Management Solutions (CIMS) Biopsy Quick 
Reference Card. 
Biopsy specimen transfer, processing, slide preparation, and digitization of slides for 
histopathologic scoring procedures will be detailed in the Image Review Charter. Histopathology 
results will not be made available to study sites, except for the RHI Score at Screening, which will 
be required for determining study eligibility. 
Biopsy samples will be processed by a central laboratory. The histologic endpoints (i.e., RHI 
Score, Continuous Geboes Score, and NI) will be scored centrally.  
The MES will be scored both locally and centrally. If there is a disagreement between the local 
and central scoring, a second central reader (adjudicator), who will be blinded to knowing if the 
score is local or central, will select either the local reader or first central reader score to be used as 
the final score (forced adjudication). However, treatment decisions will be made by the treating 
Investigator. 
Processing, transfer, and storage of biopsy specimens for PD biomarker analysis will be described 
in the Laboratory Manual. 
8.7.2. 
Histologic Scores 
Histological improvement will be assessed with the RHI Score, NI, and Continuous Geboes Score. 
These are each described in detail in Section 10.6. 
RHI Score 
The RHI Score is determined by evaluating 4 histologic items: chronic inflammatory infiltrate 
score, lamina propria neutrophils score, neutrophils in epithelium score, and erosion or ulceration 
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Nancy Index 
The NI is determined by evaluating 3 histological items: ulceration, acute inflammatory cells 
infiltrate, and chronic inflammatory infiltrate. 
Geboes Score  
For the Geboes Score, the microscopic appearance of the mucosa is categorized into 6 grades: 
structural change only (Grade 0), chronic inflammation (Grade 1), lamina propria neutrophils 
(Grade 2), neutrophils in epithelium (Grade 3), crypt destruction (Grade 4), and erosions or ulcers 
(Grade 5). 
8.7.3. 
Mayo Clinic Score 
The Full MCS and Modified MCS will be used to assess clinical improvement. The Full MCS is 
a composite of the following subscores: MES, MCS stool frequency subscore, MCS rectal bleeding 
subscore, and the Physician’s Global Assessment. The Modified MCS is a composite of the 
following subscores: MES, MCS stool frequency subscore, and MCS rectal bleeding subscore. 
Each subscore of the Full MCS and Modified MCS is described below; the subscores will be 
calculated at the timepoints shown in the SoA (Section 1.2).  
Mayo endoscopic subscore: Endoscopy will be used to visualize the mucosa to enable calculation 
of the MES. The MES reports the worst appearance of the mucosa as visualized by flexible 
sigmoidoscopy or colonoscopy on a 4-point scale (see Section 10.7).  
Rectal bleeding subscore: The rectal bleeding subscore is a patient-reported measure. This item 
reports the most severe amount of blood passed per rectum for a given day on a 4-point scale (see 
Section 10.7). The participant will record this in their Participant Diary daily. 
Stool frequency subscore: The stool frequency subscore is a patient-reported measure. This item 
reports the number of stools in a 24-hour period, relative to the normal number of stools for that 
participant in the same period on a 4-point scale (see Section 10.7). A stool is defined as a trip to 
the toilet when the participant has either a bowel movement, passage of blood alone, passage of 
blood and mucus, or passage of mucus only. The total number of stools passed in a 24-hour period 
will be recorded by the participant in their Participant Diary daily. The reference “normal” stool 
frequency for that participant will be recorded on the first day of the Screening visit and is the 
number of stools in a 24-hour period when the participant is in remission. If the participant has 
never achieved remission, the reported stool frequency before initial onset of signs and symptoms 
of UC will be used as the reference stool frequency. 
Physician’s Global Assessment: The PGA is a physician-reported measure that summarizes the 
Investigator’s assessment of the participant’s UC disease activity on a 4-point scale (see 
Section 10.7). The Investigator will record the PGA in the site tablet or other relevant device or 
system at the specified study visits.  


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8.7.4. 
Non-endoscopic Biomarkers of Inflammation 
8.7.4.1. 
High-sensitivity C-reactive Protein 
Blood will be collected for measurement of CRP according to the schedule specified in the SoA 
(Section 1.2). C-reactive protein is an acute-phase protein that is expressed in response to 
inflammation. It will be assessed using an hs-CRP test. 
8.7.4.2. 
Fecal Calprotectin 
Stool samples will be collected for measurement of fecal calprotectin according to the schedule 
specified in the SoA (Section 1.2). Fecal calprotectin levels correlate with the number of 
neutrophils in the gut and thus are used as a biomarker of intestinal inflammation. 
8.8. 
Safety Assessments 
8.8.1. 
Physical Examinations 
Physical examinations will be performed at the timepoints specified in the SoA (Section 1.2). A 
complete physical exam is required at Screening and Visit 10/EOT, and a targeted exam may be 
performed at all other required visits. For unscheduled visits, that involve the Investigator or 
clinical assessment and not the visits that would be for dispensing study drug or for laboratory 
draws only, the choice of whether to perform a complete or targeted physical exam is at the 
discretion of the Investigator and will depend on the reason for the unscheduled visit. Physical 
examinations must be performed by an Investigator or a medically qualified designee.  
Complete physical examinations include the following body systems: general appearance, skin, 
head, ears, eyes, nose, throat, neck, lungs, heart, abdomen, musculoskeletal, extremities, and 
neurological. At Screening, this exam will also include height and weight to calculate BMI. 
Targeted physical examinations include the following: abdominal examination, assessment of any 
new symptoms or observations, and follow-up of any previously identified clinically abnormalities 
and examination of related body systems. 
8.8.2. 
Vital Signs 
Vital signs to be recorded at all visits that involve the Investigator or clinical assessment visits, 
and not the visits that would be for dispensing study drug or for laboratory draws only. These will 
include blood pressure, heart rate, respiratory rate, and temperature. 
The following guidelines should be followed during the measurement of blood pressure: 
• 
The participant’s arm should be bare and supported at heart level. 
• 
An appropriately sized cuff (cuff bladder encircling at least 80% of the arm) should 
be used. 
• 
The participant’s legs should not be crossed during the evaluation. 
Blood pressure and pulse measurements should be preceded by at least 10 minutes of rest for the 
participant in a quiet setting without distractions. 
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8.8.3. 
Electrocardiograms 
Single 12-lead ECGs will be performed at the timepoints specified in the SoA (Section 1.2). 
Measurements will include PR, QRS, QT, and QTcF.  
Single 12-lead ECGs will be obtained after the participant has rested for at least 10 minutes in the 
supine position; this rest period can be combined with the required vital signs rest period. 
Repeat ECGs will be permitted as necessary due to poor quality and/or by Investigator discretion.  
8.8.4. 
Clinical Safety Laboratory Tests 
Blood/urine samples will be collected for safety laboratory testing (serum chemistry, hematology, 
coagulation, and urinalysis) at the timepoints specified in the SoA (Section 1.2). Blood samples 
will be collected before the 
 on Visits 2-10 of the main Treatment Period and before the 
 on Visits 11-12 of the Long-term Extension. See Section 10.3 for a listing of laboratory 
analytes to be collected. Repeat/unscheduled samples may be collected at the Investigator’s 
discretion. 
The Investigator must review the laboratory report, document this review, and record any clinically 
significant changes occurring during the study as an AE. The laboratory reports must be filed with 
the source documents.  
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within 28 days after the last dose of study drug should be repeated until the values 
return to normal or baseline or are no longer considered clinically significant by the Investigator 
or Medical Monitor. 
If clinically significant 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 notified. 
All protocol-required laboratory tests, as defined in Section 10.3, must be conducted in accordance 
with the Laboratory Manual. 
If laboratory values from non-protocol-specified laboratory tests performed at the institution’s 
local laboratory require a change in participant management or are considered clinically significant 
by the Investigator (e.g., SAE or AE or dose modification), then the results must be recorded. 
8.8.5. 
Progressive Multifocal Leukoencephalopathy 
The Subjective PML Checklist will be administered to participants during Screening to exclude 
individuals with a positive response from enrolling into the study. The Subjective PML Checklist 
(Section 10.2) will also be completed according to the schedule in the SoA (Section 1.2). If the 
results of the questionnaire are suggestive of PML, the participant will undergo Objective PML 
Checklist testing (Section 10.2), a full neurological exam by a neurologist, and, if indicated, 
additional testing. 
8.8.6. 
Pregnancy/Menopause Testing 
Pregnancy testing will be required for women of childbearing potential. A serum β human 
chorionic gonadotropin (hCG) pregnancy test will be performed at Screening. A urine hCG 
pregnancy test will be performed at all subsequent visits. On Day 1, a urine test must be completed 
and results reviewed prior to start of the study drug.  


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A serum test for follicle-stimulating hormone level will be performed at Screening only for female 
participants of non-childbearing potential who are not surgically sterile.  
8.9. 
Adverse Events and Other Safety Reporting 
The definitions of AEs and SAEs can be found in Section 10.4. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant’s legally authorized representative). 
The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious and considered related to the study drug or study procedures. For each AE, 
the Investigator will evaluate and report the onset (date and time), resolution (date and time), 
severity, causality, action taken, serious outcomes (if applicable), and whether or not it caused the 
participant to discontinue the study. 
The method of recording, evaluating, and assessing causality and study drug relationship of AEs 
and SAEs and the procedures for completing and transmitting SAE reports are provided in 
Section 10.4. 
8.9.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs and SAEs will be collected from the signing of the ICF until the Safety Follow-up Visit 
at the timepoints specified in the SoA (Section 1.2).  
All SAEs will be recorded and reported to the Sponsor or designee immediately and under no 
circumstance should this exceed 24 hours, as indicated in Section 10.4.4. 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 information on 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 participant has been discharged from the study, and he/she considers the event to be 
reasonably related to the study drug or study participation, the Investigator must promptly notify 
the Sponsor. 
8.9.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Participants should be 
instructed to report any AEs that they experience to the Investigator. Beginning at the time of first 
dose, Investigators should make an assessment for AEs at each visit and record the event on the 
appropriate AE eCRF. Open-ended and non-leading verbal questioning of the participant is the 
preferred method to inquire about AE occurrences.  
8.9.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the event is 
otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). Further 
information on follow-up procedures is provided in Section 10.4.3. 


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8.9.4. 
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 participants and the safety of a study 
intervention under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Institutional Review Boards (IRBs)/Independent Ethics Committees 
(IECs), and Investigators. 
An Investigator who receives an Investigator Safety Report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the Sponsor will review and then file 
it along with the Investigator’s Brochure and will notify the IRB/IEC, if appropriate, according to 
local requirements. 
Investigator Safety Reports must be prepared for suspected unexpected serious adverse reactions 
(SUSARs) according to local regulatory requirements and Sponsor policy and forwarded to 
Investigators as necessary. The term SUSAR refers to an AE that occurs in a participant and which 
is assessed by the Sponsor and/or Investigator as being unexpected (i.e., not listed in the 
Investigator’s Brochure or not listed at the specificity or severity that has been observed), serious, 
and as having a reasonable possibility of a causal relationship with the study drug (i.e., related to 
the study drug per causality assessment in Section 10.4.3). Reports of these reactions are subject 
to expedited submission to regulatory authorities. 
Morphic Therapeutic or designee is responsible for notifying the relevant regulatory authorities 
and Investigator sites within the specified timeframes of all SUSARs. Morphic Therapeutic will 
make the determination whether the event is unexpected. It is the PI’s responsibility to notify the 
IRB/IEC according to the relevant regulatory timelines of all SUSARs of which the Investigator 
is notified by Morphic Therapeutic that occur at his or her site. 
Morphic Therapeutic or designee will report all relevant information about SUSARs that are fatal 
or life-threatening as soon as possible to the US Food and Drug Administration (FDA), and, in any 
case, no later than 7 days after knowledge by the Sponsor of such a case. Relevant follow-up 
information will subsequently be communicated within an additional 8 days. 
Morphic Therapeutic or designee will report all other SUSARs to the FDA as soon as possible but 
within 15 days of Morphic Therapeutics’ first knowledge of the event. 
The Sponsor will also report any additional expedited safety reports required in accordance with 
the timelines outlined in country-specific legislation. 
Morphic Therapeutic will also inform all Investigators as required per local regulation. 
The requirements above refer to the requirements relating to investigational medicinal product. 
8.9.5. 
Pregnancy 
Details of all pregnancies in female participants and female partners of male participants will be 
collected from the start of the study Treatment Period until 28 days after the last dose of study drug 
is received. 


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If a pregnancy is reported in a female participant or female partner of a male participant, the 
Investigator should follow the procedures outlined below:  
Female participant who becomes pregnant 
If a pregnancy is reported in a female study participant, the study drug should be 
discontinued immediately and the participant should then complete the End of Treatment 
and Safety Follow-up Visits. Pregnancy information will be recorded on the appropriate 
form and submitted to the Sponsor within 24 hours of learning of the participant’s 
pregnancy. The participant will then undergo pregnancy follow-up to determine the 
outcome of the pregnancy. The Investigator will collect follow-up information on the study 
participant and the neonate, and the information will be forwarded to the Sponsor. 
Generally, follow-up will not be required for longer than 6 to 8 weeks beyond the estimated 
delivery date. Any termination of pregnancy will be reported, regardless of fetal status 
(presence or absence of anomalies) or indication for the procedure. 
Male participant with a partner who becomes pregnant 
The Investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while the male participant is in this study. After 
obtaining the necessary signed informed consent from the pregnant female partner directly, 
the Investigator will record pregnancy information on the appropriate form and submit it 
to the Sponsor within 24 hours. The female partner will then undergo pregnancy follow-up 
to determine the outcome of the pregnancy. The Investigator will collect follow-up 
information on the mother and the neonate, and the information will be forwarded to the 
Sponsor. Generally, the follow-up will be no longer than 6 to 8 weeks following the 
estimated delivery date. Any termination of the pregnancy will be reported regardless of 
fetal status (presence or absence of anomalies) or indication for the procedure. The male 
study participant may continue taking the study drug. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) will also be considered SAEs and will be reported as such. 
Any post-study pregnancy-related SAE considered reasonably related to the study drug by the 
Investigator will be reported to the Sponsor as described in Section 8.9.4. While the Investigator 
is not obligated to actively seek this information in former study participants/pregnant female 
partners, he or she may learn of an SAE through spontaneous reporting. 
8.9.6. 
Adverse Events of Special Interest 
There are no adverse events of special interest for this study.  
8.10. 
Pharmacokinetics 
8.10.1. 
Collection of Blood Samples for MORF-057 Concentration Determination in 
Plasma 
Blood samples will be collected for measurement of plasma concentrations of MORF-057 
according to the schedule specified in the SoA (Section 1.2).  




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8.11. 
Pharmacodynamics 
Details on the handling and processing of PD samples (blood, stool, and mucosal tissue) are 
outlined in the Laboratory Manual. 
8.11.1. 
Receptor Occupancy 
Whole blood samples for receptor occupancy assays will be collected according to the schedule 
specified in the SoA (Section 1.2). The following receptor occupancy assays will be performed: 
• 
A pharmacologically relevant receptor occupancy assay that assesses drug inhibition 
of α4β7 integrin binding to its natural ligand MAdCAM-1 
• 
Receptor occupancy assay that evaluates drug inhibition of the off-target integrin 
α4β1. To evaluate inhibition of α4β1 integrin binding, an exploratory receptor 
occupancy assay using its ligand, LDV peptide fragment of fibronectin, will be used. 
8.11.2. 
CCR9 mRNA 
Blood samples will be collected in PAXgene RNA tubes to assess changes of transcript levels of 
CCR9. 
8.11.3. 
Lymphocyte Subsets 
Blood samples for immunophenotyping will be collected according to the schedule specified in 
the SoA (Section 1.2). Lymphocyte subsets assessed may include α4β7-high effector memory and 
central memory T-cells and B-cells. Additional subsets may be analyzed, as well. 
8.11.4. 
Gene and/or Protein Expression 
Gene and/or protein expression will be assessed in blood and mucosal tissues. 
Mucosal tissues for this analysis will be collected at the time of endoscopy. 
Blood samples for protein biomarkers will be collected according to the schedule specified in the 
SoA (Section 1.2). 
8.11.5. 
Microbiome Analyses 
Microbiome composition will be assessed in stool and mucosal tissue samples. 
Microbiome-derived metabolites will be measured in stool and blood samples. Metatranscriptomic 
changes over time in the stool and mucosal tissue microbiome will also be examined. 
Mucosal tissues for metatranscriptomic and microbiome composition analyses will be collected at 
the time of endoscopy. 
Stool samples for microbiome composition, metabolite, and metatranscriptomic analyses will be 
collected according to the schedule specified in the SoA (Section 1.2). 
Blood samples for microbiome-derived metabolite analysis will be collected according to the 
schedule specified in the SoA (Section 1.2). 


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8.11.6. 
Physiological Intermolecular Modulation Spectroscopy 
Blood samples for physiological intermolecular modulation spectroscopy (PIMS) will be collected 
according to the schedule specified in the SoA (Section 1.2). 
8.12. 
Future Pharmacodynamics and Pharmacogenomics Research 
With participants’ consent, blood samples will be collected and used for further PD and 
pharmacogenomics research by Morphic Therapeutics to contribute to the understanding of UC or 
related diseases, to the development of related or new treatments, or to the development of new 
research methods. Participation in this collection of samples for future research is optional. 
Samples for future research will be collected according to the schedule specified in the SoA 
(Section 1.2). Samples may be stored for a maximum of 15 years (or according to local regulations) 
following the last participant’s last visit for the study at a facility selected by the Sponsor. 
8.13. 
Potential Adjustments Due to COVID-19  
Adjustments to the planned study procedures might be necessary due to the ongoing COVID-19 
pandemic. Any such specific measures will be detailed in the respective ancillary documents, such 
as site-facing and patient-facing documents.  


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9. 
STATISTICAL CONSIDERATIONS 
The Statistical Analysis Plan (SAP) will be finalized prior to the first participant dosed and may 
be amended as needed due to a protocol amendment. It will include a more technical and detailed 
description of the data summarization and analysis described in this section. Any change from the 
planned statistical analyses specified in the protocol will be fully described in the SAP and Clinical 
Study Report.  
9.1. 
Analysis Sets 
The following analysis sets will be used for the study analyses: 
Full Analysis Set (FAS) is defined as all enrolled participants in the Main Cohort and Exploratory 
Cohort who took at least 1 dose of study medication. The FAS will be used for efficacy analyses.  
Per Protocol (PP) Population is defined as all participants in the FAS who do not have any major 
protocol deviations relevant to the primary and secondary efficacy endpoint analysis. All decisions 
to exclude participants from the PP set will be made prior to the database lock of the study. The 
PP Population will be used for sensitivity analysis of the primary efficacy endpoint and maybe 
other selected efficacy endpoints as appropriate.  
Safety Analysis Population is defined as all participants in both the Main Cohort and Exploratory 
Cohort who received at least 1 dose of study medication. The Safety Analysis Population will be 
used for safety analysis. 
PK Population is defined as all participants in the FAS who have adequate measurable 
concentrations to define Cmax or AUC. The PK Population will be used in the individual plasma 
concentration, PK parameter estimation listings, and individual figures.  
PK Evaluable Population (a subset of the PK Population) will be used to determine the inclusion 
of a participant in the overall PK summaries. Participants included in this subset must not violate 
the protocol in a way that may invalidate or bias the results, and must have the reliable data for the 
overall PK summaries. The criteria that the data must meet for the inclusion of a participant in this 
population will be specified in the study SAP. 
PD Population is defined as all participants in the FAS who have at least 1 measurable post-dose 
PD measurement and its corresponding pre-dose PD measurement for, at minimum, 1 of the PD 
biomarkers. This population will be used for the summarization of PD (exploratory) endpoints.   
9.2. 
Statistical Analyses 
9.2.1. 
General Considerations 
Descriptive statistics will be reported for all primary, secondary, and exploratory data. Categorical 
parameters will be reported using frequency and proportions, whereas continuous parameters will 
be reported using mean, standard deviation, median, minimum, and maximum. Data will be 
summarized/analyzed at scheduled visits unless stated otherwise. A significance level of 0.025 
one-sided (0.05 two-sided) will be used for the primary efficacy endpoint. No hypothesis testing 
will be performed for the secondary and exploratory efficacy endpoints. No hypothesis testing will 
be performed on safety data. The Main Cohort and Exploratory Cohort will be analyzed separately, 


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unless specified otherwise. Data from participants in the Exploratory Cohort will be analyzed only 
for exploratory purposes. 
9.2.2. 
Primary Endpoint 
The primary efficacy endpoint for this study is change from baseline to Week 12 in RHI Score, 
which will be tested using the FAS. The data for the primary efficacy endpoint will be assessed 
for normality. If the data are normally distributed, then a one-sample t-test will be used for the 
analysis. If the data are not normally distributed, then a signed rank test will be used. If there are 
a large number of participants excluded from the Per Protocol Population due to major protocol 
deviations, then a sensitivity analysis of the primary efficacy endpoint will be performed using the 
Per Protocol Population. In addition, the proportion of participants in the FAS with a change from 
baseline to Week 12 that is at least -7 (that is, a reduction ≥7) and the proportion of participants 
with at least a 50% reduction in RHI score from baseline to Week 12 will be provided.   
9.2.3. 
Secondary Endpoints 
The continuous secondary efficacy endpoint (change from baseline to Week 12 in Modified MCS) 
will be analyzed similarly to the primary efficacy endpoint using the FAS. No hypothesis testing 
will be performed for the secondary efficacy endpoint.  
The Safety Analysis Population will be used for the summarization of all safety data. Adverse 
events will be coded using the current Medical Dictionary of Regulatory Activities by System 
Organ Class (SOC) and Preferred Term (PT), classified from verbatim terms. A TEAE is defined 
as an AE that occurs between administration of the first dose of study drug and 7 days after the 
last dose of study drug. TEAEs and TESAEs will be summarized using frequencies and 
proportions; summaries will be provided for overall and according to SOC and PT. TEAEs leading 
to study drug discontinuation will be summarized or listed, as appropriate. Summaries of TEAEs 
will also be presented by severity and relationship (see Section 10.4.3). The duration of TEAEs 
will be determined and included in listings, along with the action taken and outcome.  
The plasma PK parameters AUC0-12, AUCtau, Cmax, Ctrough, tmax, and C12 will be estimated by 
non-compartmental analysis using the PK Population. PK/PD analyses will be conducted as 
deemed appropriate and may be reported separately from the Clinical Study Report. 
9.2.4. 
Exploratory Endpoints 
The continuous exploratory efficacy endpoints (change from baseline to Weeks 6 and 52 in RHI 
Score and Modified MCS; change from baseline to Weeks 6, 12, and 52 in NI, Continuous Geboes 
Score, and Full MCS; and change from baseline to Weeks 2, 6, 12, 20, 28, 36, and 52 in hs-CRP 
and fecal calprotectin levels) will be analyzed similarly to the primary efficacy endpoint using the 
FAS. No hypothesis testing will be performed for the exploratory efficacy endpoints. In addition, 
the proportion of participants with NI score ≤1 at Week 12 will be provided. 
The exploratory PD endpoints (α4β7 and α4β1 receptor occupancies over time and change from 
baseline over time in blood CCR9 mRNA) will be summarized descriptively. Additional analysis 
of blood and mucosal tissue gene and/or protein expression over time, microbiome composition in 
stool and mucosal tissue over time, changes in microbiome-derived metabolites in stool and blood 
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will be provided in a biomarker analysis plan separate from the study SAP and reported separately. 
The PD Population will be used for the summarization and analysis of these exploratory endpoints. 
9.2.5. 
Other Safety Analyses 
Other safety data will include safety laboratory parameters, vital signs, and ECG findings. These 
data will be summarized with descriptive statistics by absolute values and change from baseline 
using the Safety Analysis Population. The incidence of laboratory abnormalities will be 
summarized. Worst shift in grade and changes from baseline to Weeks 6, 12, and 52 of the 
laboratory analytes will be reported. Physical examination findings that are recorded as AEs will 
be included in those data presentations.   
Participant safety data will be reviewed by an independent DSMB. Additional details related to 
the DSMB are included in Section 10.1.6 and will be clearly delineated in the DSMB Charter. 
9.3. 
Analyses for Induction Period, 52-week Treatment Period, and 
Long-term Extension 
The study open-label treatment period includes 2 parts: the 12-week Induction Period and the 
40-week Maintenance Period. For the purpose of statistical analyses, the Induction Period and the 
Maintenance Period will be treated as 2 independent parts. There will be 4 analyses planned:  two 
for the 12-week Induction Periods of the Main and Exploratory Cohorts respectively (i.e., the 
period for the primary efficacy endpoint) and the other two for the 52-week Treatment Periods of 
the Main and Exploratory Cohorts respectively (i.e., the 12-week Induction Period plus the 40-
week Maintenance Period and the Safety Follow-up). Additional analysis of the optional Long-
term Extension Period for the participants enrolled into the Long-term Extension will be performed 
as appropriate. 
Induction Period Analysis  
The analysis of the Induction Period for the Main Cohort will be performed after all the participants 
in the Main Cohort have completed the 12-week Induction Period (i.e., completed the Week 12 
visit) or discontinued the study before the Week 12 assessment. The analysis will formally evaluate 
the primary and secondary efficacy endpoints, all the exploratory endpoints defined by Week 12, 
PK concentrations and parameters, and safety of MORF-057 for the Main Cohort during the 12-
week Induction Period.  
The analysis of the Induction Period for the Exploratory Cohort will be performed after all the 
participants in the Exploratory Cohort have completed the 12-week Induction Period (i.e., 
completed the Week 12 visit) or discontinued the study before the Week 12 assessment. The 
analysis will evaluate all the efficacy and exploratory endpoints, PK concentrations and 
parameters, and safety of MORF-057 for the Exploratory Cohort during the 12-week Induction 
Period. In the event that the timing of the Induction Period analysis for the Exploratory Cohort 
aligns closely with the timing of the 52-week Treatment Period analysis for the Main Cohort 
described below, both analyses will be combined into one analysis.  
Only Induction Period data will be used in the Induction Period  analyses.   
 
 


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52-week Treatment Period Analysis  
For the Main Cohort participants, the analysis of the 52-week Treatment Period will be performed 
after all participants have completed the 52-week open-label Treatment Period (and the Safety 
Follow-up Period for participants not enrolling into the optional Long-term Extension Period) or 
discontinued the study before the Week 52 assessment and the Safety Follow-up Period. In the 
event that the timing of the 52-week Treatment Period analysis for the Main Cohort aligns closely 
with the timing of the Induction Period analysis for the Exploratory Cohort, both analyses will be 
combined into one analysis. 
 
For the Exploratory Cohort participants, the analysis of the 52-week Treatment Period will be 
performed after all participants have completed the 52-week open-label Treatment Period (and the 
Safety Follow-up Period for participants not enrolling into the optional Long-term Extension 
Period) or discontinued the study before the Week 52 assessment and the Safety Follow-up Period.  
 
The 52-week Treatment Period analyses for the Main and Exploratory Cohorts will formally 
evaluate all the exploratory endpoints defined by Week 52, PK concentration and parameters, and 
safety of MORF-057 during the 52-week open-label Treatment Period plus the Safety Follow-up 
Period. The cumulative data, including those from the Induction Period, will be used in these 
analyses.  
 
The data from the Main and Exploratory Cohorts may be pooled together in the safety analyses, 
as appropriate. 
 
Long-term Extension Analysis  
The analysis of the Long-term Extension will be performed after all the participants enrolled into 
the Long-term Extension have completed the 26-week extended Treatment Period and the Safety 
Follow-up Period or discontinued the study before the Week 78 assessment. The analysis will 
formally evaluate the safety of MORF-057 and selected efficacy endpoints as appropriate during 
the Long-term Extension plus the Safety Follow-up Period. 
9.4. 
Sample Size Determination 
The sample size for this study is based on the number of participants needed for the Main Cohort. 
Assuming a one-sided alpha at 0.025 for the final analysis, a standard deviation of 12, and a 
one-sample t-test, a mean treatment effect of ≥7-point reduction in RHI can be detected using 
28 participants with >80% power. A dropout rate of 5% would lead to a total of 30 participants 
being enrolled in the Main Cohort. -A maximum of 10 additional participants may be enrolled in 
the Exploratory Cohort, giving a total of 30 to 40 enrolled participants in the study. 
 


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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
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 International Council for Harmonisation (ICH) Good Clinical Practice 
(GCP) guidelines 
• 
Applicable laws and regulations 
The protocol, protocol amendments, ICF, Investigator’s Brochure, and other relevant documents 
(e.g., 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 
participants.  
Protocols and any substantial amendments to the protocol will require health authority approval 
prior to initiation except for changes necessary to eliminate an immediate hazard to study 
participants. 
The Investigator will be responsible for the following: 
• 
Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC 
• 
Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
• 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European Clinical Trials 
Directive 2001/20/EC or European regulation 536/2014 for clinical studies (as 
applicable), and all other applicable local regulations 
After reading the protocol, each Investigator will sign the Investigator’s Agreement page 
(Section 10.9). The study will not start at any study center at which the Investigator has not signed 
the protocol. 
10.1.2. 
Financial Disclosure 
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 


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certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
10.1.3. 
Insurance 
The Sponsor has obtained liability insurance, which covers this study as required by local law 
and/or national regulations and/or ICH guidelines, whichever is applicable. The terms of the 
insurance will be kept in the study files. 
10.1.4. 
Informed Consent Process 
The Investigator or his/her representative will explain the nature of the study, including the risks 
and benefits, to each participant or his/her legally authorized representative and answer all 
questions regarding the study. 
Participants must be informed that their participation is voluntary. Each participant or his/her 
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, privacy and data 
protection requirements, where applicable, and the IRB/IEC or study center. 
The medical record must include a statement that written informed consent was obtained before 
the participant was 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 participant or his/her legally authorized 
representative. 
The ICF will contain a separate section that addresses the use of samples for optional exploratory 
research. The Investigator or authorized designee will explain to each participant the objectives of 
the exploratory research. Participants will be told that they are free to refuse to participate and may 
withdraw their consent at any time and for any reason during the sample storage period 
(determined based on local country regulations). A separate signature will be required to document 
a participant’s agreement to allow samples to be used for exploratory research. Participants who 
decline to participate in this optional research will not provide this separate signature. 
10.1.5. 
Data Protection 
Participants will be assigned a unique identifier by the Sponsor. Any participant records or datasets 
that are transferred to the Sponsor will contain the identifier only; participant names or any 
information which would make the participant identifiable will not be transferred. 
The participant must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant who will be required to give consent for their data to be used as 
described in the ICF.  


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The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by appropriate 
IRB/IEC members, and by inspectors from regulatory authorities. 
10.1.6. 
Data and Safety Monitoring Board  
A DSMB has been appointed to this study. The DSMB is a group of independent 
clinicians/scientists who are appointed to monitor the safety and scientific integrity of a human 
research intervention, and to make recommendations to the Sponsor regarding the modification, 
continuance, or stopping of a study based on assessments of safety. The composition, 
responsibilities, and meeting schedule of the DSMB will be described in a separate DSMB Charter.  
10.1.7. 
PML Adjudication Committee 
A PML Adjudication Committee will oversee a PML RAMP to monitor all participants for PML. 
The composition, responsibilities, and meeting schedules of the PML Adjudication Committee 
will be described in a separate charter.  
10.1.8. 
Dissemination of Clinical Study Data 
The Sponsor will submit a summary of the results of the clinical study to the relevant clinical study 
databases in a timely manner. As appropriate, this will be accompanied by a summary written in a 
manner that is understandable to laypersons. 
10.1.9. 
Data Quality Assurance 
All participant data relating to the study will be recorded on printed or eCRFs unless transmitted 
to the Sponsor or designee electronically (e.g., laboratory data). The Investigator is responsible for 
verifying that data entries are accurate and correct by physically or electronically signing the case 
report form (CRF). 
Guidance on completion of CRFs will be provided in the corresponding guidelines. 
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, including definition of study critical data items and 
processes (e.g., 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 non-compliance 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 (e.g., contract 
research organizations). 
Essential documents for this study should be retained by the Investigator/institution until at least 
2 years after the last approval of a marketing application in an ICH region and until there are no 
pending or contemplated marketing applications in an ICH region or at least 2 years have elapsed 
since the formal discontinuation of clinical development of the investigational product. These 


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documents should be retained for a longer period, however, if required by the applicable regulatory 
requirements or by an agreement with the sponsor. It is the responsibility of the Sponsor to inform 
the Investigator/institution as to when these documents no longer need to be retained. 
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. 
10.1.10. 
Source Documents 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the Investigator’s site. 
Data reported on the CRF or 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. 
The Investigator must maintain accurate documentation (source data) that supports the information 
entered in the CRF. 
Study monitors will perform ongoing source data verification to confirm that data entered into the 
CRF by authorized site personnel are accurate, complete, and verifiable from source documents; 
that the safety and rights of participants are being protected; and that the study is being conducted 
in accordance with the currently approved protocol and any other study agreements, ICH GCP, 
and all applicable regulatory requirements. 
10.1.11. 
Study and Site Start and Closure 
10.1.11.1. First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants (i.e., when the first site is open). 
10.1.11.2. Study/Site Termination 
The Sponsor or 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: 
For study termination: 
• 
Discontinuation of further study drug development 


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For site termination: 
• 
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 or no recruitment (evaluated after a reasonable amount of time) of 
participants by the Investigator 
• 
Total number of participants included earlier than expected 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, the IRBs/IECs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The Investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up. 
10.1.12. 
Publication Policy 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the Investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. 
This allows the Sponsor to protect proprietary information and to provide comments. 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a coordinating 
Investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 
 
 








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10.3. 
Appendix 3: Clinical Laboratory Tests 
The tests detailed in Table 6 will be performed by the central laboratory. 
Local laboratory results are only required in the event that the central laboratory results are not 
available in time for either study treatment administration and/or response evaluation. If a local 
sample is required, it is important that the sample for central analysis is obtained at the same time. 
Additionally, if the local laboratory results are used to make either a study treatment decision or 
response evaluation, the results must be recorded. 
Protocol-specific requirements for inclusion or exclusion of participants are detailed in Section 5 
of the protocol. 
Additional tests may be performed at any time during the study as determined necessary by the 
Investigator or required by local regulations.  
Investigators must document their review of each laboratory safety report. 
Table 6. 
Protocol-required Laboratory Tests 
Laboratory Tests 
Parameters 
Hematology 
• 
Platelet count  
• 
RBC count 
• 
Hemoglobin 
• 
Hematocrit 
 
RBC Indices: 
• 
MCV 
• 
MCH 
• 
% Reticulocytes 
WBC count with 
differential: 
• 
Neutrophils 
• 
Lymphocytes 
• 
Monocytes 
• 
Eosinophils 
• 
Basophils 
Coagulation 
 
• 
Prothrombin time 
• 
PTT 
• 
INR 
Clinical chemistry 
• 
Blood urea 
nitrogen  
• 
Creatinine 
• 
Glucose 
(fasting) 
• 
Albumin 
• 
Potassium 
• 
Sodium 
• 
Calcium 
• 
Phosphate 
• 
AST/SGOT 
• 
ALT/SGPT 
• 
ALP  
• 
Total and 
direct bilirubin 
• 
Total protein 
Routine urinalysis 
• 
Specific gravity 
• 
pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase 
by dipstick 
• 
Microscopic examination (if blood or protein is abnormal) 
Pregnancy testing 
• 
Highly sensitive serum hCG pregnancy test (at Screening and as needed for women of 
childbearing potential only)  
• 
Urine hCG test (at Visits 2-11 in the main Treatment Period and Visits 11-13 of the 
Long-term Extension for women of childbearing potential only) a 
Other screening 
tests 
• 
SARS-CoV-2 test (test to be determined by site) 
• 
Tuberculosis test (
 test, with PPD test as needed) 
• 
Biopsy for cytomegalovirus test 


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Laboratory Tests 
Parameters 
• 
Fecal sampling and cell culture for C. difficile and enteric pathogens, including ova and 
parasite testing 
• 
Serology: HIV antibody, hepatitis B surface antigen, and hepatitis C virus antibody  
• 
Follicle-stimulating hormone (at Screening and as needed for women of 
non-childbearing potential only) 
• 
Serum alcohol screen  
• 
Urine drug screen (to include at minimum: amphetamines, barbiturates, cocaine, 
opiates, cannabinoids, and benzodiazepines) 
• 
For exploratory Cohort only: vedolizumab blood levels, receptor occupancy of 
vedolizumab, and anti-drug antibodies against vedolizumab 
Efficacy 
• 
Serum hs-CRP 
• 
Fecal calprotectin 
Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; hCG, 
human chorionic gonadotropin; HIV, human immunodeficiency virus; hs-CRP, high-sensitivity C-reactive protein; 
INR, international normalized ratio; MCH, mean corpuscular hemoglobin; MCV, mean corpuscular volume; PPD, 
purified protein derivative; PTT, partial thromboplastin time; RBC, red blood cell; SGOT, serum glutamic-
oxaloacetic transaminase; SGPT, serum glutamic-pyruvic transaminase; WBC, white blood cell; 
a Local urine testing will be standard for the protocol unless serum testing is required by local regulation or 
IRB/IEC. 
 
 












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10.5. 
Appendix 5: Contraceptive and Barrier Guidance 
10.5.1. 
Definitions 
Woman of Childbearing Potential (WOCBP) 
Women in the following categories are considered WOCBP (fertile): 
1. Following menarche 
2. From the time of menarche until becoming postmenopausal unless permanently sterile (see 
below) 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
o A high follicle-stimulating hormone (FSH) level in the postmenopausal range 
(≥30 IU/L) 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 may be required.  
o Females 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 at least 
6 weeks before study Day 1 to allow confirmation of postmenopausal status before 
study enrollment. 
• Permanent sterilization methods (for the purpose of this study) include: 
o Documented hysterectomy 
o Documented bilateral salpingectomy 
o Documented bilateral oophorectomy 
o For individuals with permanent infertility due to an alternate medical cause other than 
the above, (e.g., Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), 
Investigator discretion should be applied to determining study entry. 
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
• If fertility is unclear (e.g., amenorrhea in athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be 
considered. 
Woman of Non-childbearing Potential (WONCBP) 
Women in the following categories are considered WONCBP: 
1. Premenopausal female with permanent infertility due to one of the following: 
a. Documented hysterectomy 
b. Documented bilateral salpingectomy 
c. Documented bilateral oophorectomy 


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d. For individuals with permanent infertility due to an alternate medical cause other than 
the above, (e.g., Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), 
Investigator discretion should be applied to determining study entry. 
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
2. Postmenopausal female 
a. A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
i. A high FSH level in the postmenopausal range (≥30 IU/L) may be used to confirm a 
postmenopausal state in women not using hormonal contraception or HRT. 
However, in the absence of 12 months of amenorrhea, confirmation with more than 
one FSH measurement may be required. 
ii. Females on HRT and whose menopausal status is in doubt must discontinue HRT for 
at least 6 weeks before study Day 1 to allow confirmation of postmenopausal status 
before study enrollment. 
10.5.2. 
Contraception Guidance 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb That Have Low User Dependency Failure rate of < 1% per year when 
used consistently and correctly. 
• 
Implantable progestogen-only hormone contraception associated with inhibition of ovulationc + 1 
physical barrier methodd 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS)c + 1 physical barrier methodd 
• 
Bilateral tubal occlusion 
• 
Azoospermic partner (vasectomized or due to a medical cause) 
Azoospermia 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. 
Note: documentation of azoospermia for a male participant can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history interview. 
Highly Effective Methodsb That Are User Dependent Failure rate of < 1% per year when used 
consistently and correctly. 
• 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc (listed below) + 1 physical barrier methodd 
­ oral 
­ intravaginal 
­ transdermal 
­ injectable 


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• 
Progestogen-only hormone contraception associated with inhibition of ovulationc + 1 physical 
barrier methodd 
­ 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 study intervention. 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 participant.) 
a. Contraceptive use by men or women should be consistent with local regulations regarding the use 
of contraceptive methods for those participating in clinical studies. 
b. Failure rate of < 1% per year when used consistently and correctly. Typical use failure rates differ 
from those when used consistently and correctly. 
c. If locally required, in accordance with Clinical Trial Facilitation Group (CTFG) guidelines, 
acceptable contraceptive methods are limited to those which inhibit ovulation as the primary mode 
of action. 
d. Barrier method of contraception: condoms (male or female) with or without a spermicidal agent, 
diaphragm or cervical cap with spermicide   
Note: Periodic abstinence (calendar, symptothermal, postovulation methods), withdrawal (coitus 
interruptus), spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods 
of contraception. Male condom and female condom should not be used together (due to risk of failure 
from friction). 
 
 
 


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10.6. 
Appendix 6: 
Histological Scoring Indices 
Robarts Histopathology Index 
The RHI is an evaluative index derived from the Geboes Score that was designed to be 
reproducible and responsive to clinically meaningful change in disease activity in UC over time. 
It is calculated by evaluating 4 histologic items, each on a scale from 0 to 3. Each item is 
individually weighted in the RHI formula. The formula is as follows: RHI = (1 × chronic 
inflammatory infiltrate score) + (2 × lamina propria neutrophils score) + (3 × neutrophils in 
epithelium score) + (5 × erosion or ulceration score). Thus, the total RHI Score ranges from 0 (no 
disease activity) to 33 (severe disease activity) (Mosli, 2017). 
Nancy Index 
The NI is a validated index for assessing histological disease activity in UC. It is determined by 
evaluating 3 histological items: ulceration, acute inflammatory cells infiltrate, and chronic 
inflammatory infiltrate. These items are used to define 5 grades of disease activity (Grades 0 to 4). 
The presence of ulceration on the biopsy specimen corresponds to severely active disease 
(Grade 4). If there is no ulceration, acute inflammatory cells infiltrate (presence of neutrophils) is 
assessed. Moderate or severe acute inflammatory cells infiltrate corresponds to moderately active 
disease (Grade 3), whereas mild acute inflammatory cells infiltrate correspond to mildly active 
disease (Grade 2). If there is no acute inflammatory cells infiltrate, an assessment of chronic 
inflammatory infiltrate (presence of lymphocytes and/or plasmacytes and/or eosinophils) is made. 
A biopsy specimen showing moderate or marked chronic inflammatory infiltrate corresponds to 
moderate or marked chronic acute inflammatory infiltrate (Grade 1). A biopsy specimen showing 
mild or no chronic inflammatory infiltrate corresponds to absence of significant histological 
disease (Grade 0) (Marchal-Bressenot, 2017; Marchal-Bressenot, 2016). 
Continuous Geboes Score 
The Geboes Score is a stepwise grading system used for the evaluation of microscopic 
inflammation and histopathologic disease activity in UC. The microscopic appearance of the 
mucosa is categorized into 6 grades: structural change only (Grade 0); chronic inflammation 
(Grade 1); lamina propria neutrophils (Grade 2); neutrophils in epithelium (Grade 3); crypt 
destruction (Grade 4); and erosions or ulcers (Grade 5) (Geboes, 2000). Each of these grades has 
4 to 5 sub-grades. This scoring system has been converted into a continuous scale that is calculated 
by adding up the numerical values of the different subscores, yielding a final value between 
0 and 22. 
 
 


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10.7. 
Appendix 7: Mayo Clinic Scoring System for Assessment of 
Ulcerative Colitis Activity  
The Mayo Clinic Score ranges from 0 to 12, with higher scores indicating more severe disease. 
Each subscore is described below. 
Stool frequency: Each participant serves as his or her own control to establish the degree of 
abnormality of the stool frequency. 
0=Normal number of stools for this participant 
1=1 to 2 stools more than normal 
2=3 to 4 stools more than normal 
3=5 or more stools more than normal 
Subscore: 0 to 3 
Rectal bleeding: The daily bleeding score represents the most severe bleeding of the day. 
0=No blood seen 
1=Streaks of blood with stool less than half the time 
2=Obvious blood (more than just streaks) or streaks of blood with stool most of the time 
3=Blood alone passed 
Subscore: 0 to 3 
Endoscopy: The endoscopy subscore will be determined both locally and centrally by qualified 
personnel.  
0=Normal or inactive disease 
1=Mild disease (erythema, decreased vascular pattern, no friability) 
2=Moderate disease (marked erythema, lack of vascular pattern, friability, erosions) 
3=Severe disease (spontaneous bleeding, ulceration) 
Subscore: 0 to 3 
Physician’s Global Assessment: The Physician’s Global Assessment acknowledges the 3 other 
criteria, the participant’s daily recollection of abdominal discomfort and general sense of 
well-being, and other observations, such as physical findings and the participant’s performance 
status. 
0=Normal 
1=Mild disease 
2=Moderate disease 
3=Severe disease 
Subscore: 0 to 3 
 


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10.8. 
Appendix 8: Genetics 
Use/Analysis of DNA 
• 
Genetic variation may impact a participant’s response to the study drug, susceptibility 
to, and severity and progression of disease. Variable response to study intervention 
may be due to genetic determinants that impact intervention absorption, distribution, 
metabolism, and excretion; mechanism of action of the intervention; disease etiology; 
and/or molecular subtype of the disease being treated. Therefore, where local 
regulations and IRB/IEC allow, blood samples will be collected for DNA analysis 
from consenting participants. 
• 
DNA samples will be used for research related to MORF-057 or UC and related 
diseases. They may also be used to develop tests/assays, including diagnostic tests 
related to MORF-057 and/or interventions of this drug class and UC. Genetic 
research may consist of the analysis of one or more candidate genes or the analysis of 
genetic markers throughout the genome or analysis of the entire genome. 
• 
The samples may be analyzed as part of a multi-study assessment of genetic factors 
involved in the response to MORF-057 or study interventions of this class to 
understand the study disease or related conditions. 
• 
The results of genetic analyses may be reported in the Clinical Study Report or 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 MORF-057 or study interventions of 
this class or indication continues but no longer than 15 years or other period as per 
local requirements. 
 
 


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10.9. 
Appendix 9: Investigator’s Agreement 
 
By signing below, I agree that: 
 
I have read Protocol MORF-057-201 and agree to conduct the study as outlined. Furthermore, I 
agree to maintain the confidentiality of all information received or developed in connection with 
this protocol. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
 
 
 
Date 
 
 
 


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10.10. 
Appendix 10: Summary of Changes Table – Protocol Amendment Version 2.0 
Summary of Changes Table 
Changes to the protocol as implemented by the protocol amendment Version 2.0 in comparison to Version 1.0 are summarized in the 
Summary of Changes table below. New text is shown in italics, deleted text is shown in strikeout, and bold text is informational. In 
addition to the changes provided in the Summary of Changes table, minor editorial changes have been made throughout the protocol. 
Version 2.0 vs Version 1.0 
Section No. and Name 
Description of Change 
Brief Rationale 
Title 
A Phase 2a, Open-label, Single-arm Study to Evaluate the Efficacy, 
Safety, and Tolerability of MORF-057 in Adults with Moderate to Severe 
Ulcerative Colitis (EMERALD-1) 
To add trial brand name 
 
“IRB” was changed to “IRB/IEC” throughout the protocol. 
To add IECs to the protocol 
because sites in Europe have been 
added to the study plan 
Abbreviations 
AUC  Area under the concentration-time curve 
AUC0-24  Area under the concentration-time curve from time 0 to 24 hours 
post-dose 
AUC0-inf  Area under the concentration-time curve from time 0 to infinity 
AUC0-t  Area under the concentration-time curve from time 0 to last 
measurable concentration 
AUClast  Area under the concentration-time curve from time 0 to last data 
point 
C24  Plasma concentration at 24 hours post-dose 
CYP  Cytochrome P450 
CYP3A  Cytochrome P450 3A 
CYP3A4  Cytochrome P450 3A4 
DNA  Deoxyribonucleic acid 
DSMB  Data and Safety and Monitoring Board 
IEC  Independent Ethics Committee  
ESR  Erythrocyte sedimentation rate 
To clarify abbreviations 
Synopsis - Objectives and Endpoints table, 
Section 3: Objectives and Endpoints 
To evaluate the effects of MORF-057 on histologic improvement at 
Weeks 6, and 12, and 52 
• 
Change from baseline to Weeks 6 and 52 in RHI Score 
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Section No. and Name 
Description of Change 
Brief Rationale 
• 
Change from baseline to Weeks 6, and 12, and 52 in the 
Nancy Index (NI)  
• 
Change from baseline to Weeks 6, and 12, and 52 in the 
Continuous Geboes Score 
Synopsis - Objectives and Endpoints table, 
Section 3: Objectives and Endpoints 
To evaluate the effect of MORF-057 on clinical improvement at Weeks 6, 
and 12, and 52 
• 
Change from baseline to Weeks 6 and 52 in the Modified Mayo Clinic 
Score (MCS). Modified MCS is a composite of the following 
subscores:  
o 
Mayo endoscopic subscore (MES) 
o 
MCS stool frequency subscore  
o 
MCS rectal bleeding subscore  
• 
Change from baseline to Weeks 6, and 12, and 52 in the Full MCS. 
Full MCS is a composite of the following subscores: 
o 
MES 
o 
MCS stool frequency subscore  
o 
MCS rectal bleeding subscore 
o 
MCS Physician’s Global Assessment (PGA) 
To add Week 52 endpoints.  
Synopsis - Objectives and Endpoints table, 
Section 3: Objectives and Endpoints 
To assess the effect of MORF-057 on non-endoscopic biomarkers of 
inflammation 
• 
Change from baseline to Weeks 2, 6, and 12, 20, 28, 36, and 
52 in high-sensitivity C-reactive protein (hs-CRP) levels  
• 
Change from baseline to Weeks 2, 6, and 12, 20, 28, 36, and 
52 in fecal calprotectin levels  
To add endpoints between 
Week 12 and Week 52 
Synopsis – Overall Design 
Section 4.1: Overall Design 
The Main Cohort of the study will include approximately 30 participants 
with moderate to severe UC who have or have not been exposed to 
biologics therapies and have not previously been treated with 
vedolizumab. In addition, an Exploratory Cohort will be comprised of a 
maximum of 5 additional participants with moderate to severe UC who are 
secondary non-responders (as defined in Section 5.1) to vedolizumab. 
Thus, there will be a total of 30 to 35 participants in the study. All 
participants will be enrolled across approximately 7from up to 30 centers 
located in the United StatesNorth America and Europe. For this study, 
moderate to severe UC will be defined as having a FullModified MCS 
between 6 and 12of 5 to 9 (inclusive), with an MES ≥2, (confirmed by 
central reader) and a rectal bleeding subscore ≥1, and a stool frequency 
subscore ≥1. In the Main Cohort, the enrollment goal is for 45% to 55% of 
To clarify/update participation 
criteria and to extend the study to 
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the participants to be bio-naïve (i.e., to have no previous exposure to a 
biologic treatment for UC).   
Synopsis – Overall Design 
Section 4.1: Overall Design 
Participant safety data will be reviewed by an independent Data and Safety 
Monitoring Board (DSMB).  and a Steering Committee periodically 
throughout the study. The Steering Committee will be comprised of select 
Sponsor personnel who will periodically review data. The data review will 
be performed in a controlled manner. In additionDetails related to the 
DSMB will be clearly delineated in the DSMB Charter. Separately, an 
efficacy-based interim analysis will be performed by an internal Sponsor 
Steering Committee using the initial 5 bio-experienced and initial 5 
bio-naïve subjects in the Main Cohort who have evaluable baseline and 
Week 12 primary endpoint data. The purpose of the interim analysis is to 
assess whether the study remains appropriately powered or if the sample 
size needs to be revised. An independent statistician (not part of the study 
team) will be responsible for providing the relevant information for the 
sample size assessment to the Steering Committee. Note that data from 
participants in the Exploratory Cohort will not be included in the sample 
size assessment that is performed at the interim analysis. Details related to 
the DSMB, the Steering Committee, and the interim analysis will be 
clearly delineatedoutlined in the DSMB Charter. Statistical Analysis Plan 
(SAP). 
To clarify details regarding the use 
of a DSMB and a Steering 
Committee 
Synopsis – Overall Design 
Section 4.1: Overall Design 
This Phase 2a study will consist of 3 study periods: a Screening Period (up 
to 6 weeks), a Treatment Period (52 weeks, including a 12-week Induction 
Period and a 40-week Maintenance Period), and a Safety Follow-up 
Period (4 weeks). During the study, there will be approximately 611 
scheduled study visits: Screening Visit(s) (Visit 1 at Weeks -6 to -1), 
multiple Treatment Visits (Visits 2-510 at Weeks 0, 2, 6, and 12, 20, 28, 
36, 44, and 52), and a Safety Follow-up Visit (visit to occur 4 weeks after 
the last dose of study drug is received, which will be Visit 611 at 
Week 1656 if the full study is completed or earlier if treatment is 
discontinued early). Study Day 1 represents the first day of the Treatment 
Period (i.e., when the participant will receive the first dose of study drug). 
Participants will receive the same MORF-057 dosage 
mg 
. by 
mouth [P.O.]) for the full 1252-week Treatment Period.  
To revise the visit schedule to 
accommodate the extended 
treatment period (now 52 weeks 
instead of 12 weeks) 
Synopsis – Overall Design 
Section 4.1: Overall Design 
Non clinical chronic toxicology studies in animals are currently ongoing. 
Depending on the results of those studies, the Sponsor may amend the 
protocol to extend the treatment duration from 12 weeks to 52 weeks. 
Participants may be given the option to continue receiving study treatment 
for the current study (MORF 057 201) after Week 12 until Week 52. 
To explain the new option to join 
an Open-label Extension study at 
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Participants who choose this option will not complete the Safety Follow
up Period until the end of the full 52 week Treatment Period. A revised 
Informed Consent Form (ICF) will be provided to participants to explain 
the additional procedures necessary for those who want to continue in the 
study beyond the initial 12 week Treatment Period. Maximum time on 
study for participants who choose to complete only the initial 12 week 
Treatment Period will be 22 weeks, whereas that for participants who 
choose to complete the full 52 week Treatment Period (if option is later 
provided) will be 62 weeks.  
Eligible participants will have the opportunity to enroll in a separate 
Open-label Extension study after completing the Week 52 assessments. 
Participants who are eligible and willing to enroll into the Open-label 
Extension study will not complete the Safety Follow-up Period for the 
current study; instead, they will directly enter the Open-label Extension 
study. Participants who do not enroll into the separate Open-label 
Extension study must complete the final Safety Follow-up Period for the 
current study, including the Week 56 Visit (4 weeks after receiving the last 
dose of MORF-057), for a maximum time on-study of 62 weeks. 
Synopsis – Overall Design 
Section 4.1: Overall Design 
A new study schema was provided. The new schema shows that the 
treatment period has been extended from 12 weeks to 52 weeks and 
when the associated new visits will occur. The schema also shows the 
new option to join an Open-label Extension study at the end of the 
current study. 
To reflect changes in the study 
design 
Synopsis – Inclusion Criteria 
Section 5.1: Inclusion Criteria 
2. Patient has had signs/symptoms of moderate to severe UC for at least 3 
months prior to Screening, and the diagnosis was confirmed during the 
Screening Period with the following criteria: a FullModified MCS of 65 to 
129 (inclusive), with an MES ≥2 (confirmed by central reader), and a 
rectal bleeding subscore ≥1, and a stool frequency subscore ≥1 
 
5. Is an advanced therapya bio-naïve patient or a patient who had an 
inadequate response, loss of response, or intolerance to no more than 3 
drugs in 2 classes of the following 
To clarify the inclusion criteria 
Synopsis – Exclusion Criteria 
Section 5.2: Exclusion Criteria 
10. Had any vaccination (including live virus vaccinations) within 3 weeks 
prior to study Day 1. Note: For vaccinations requiring a series of doses, the 
last in the series should be completed by 3 weeks prior to study Day 1 
(e.g., SARS-CoV-2 two-shot vaccination series). 
 
18b. Chronic kidney disease stages 4 and 5, defined as having a glomerular 
filtration rate <30 mL/min/1.73m2 as calculated using the Modification of 
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Diet in Renal Disease (MDRD) equation, receiving dialysis, or being listed 
for or has received a renal transplant 
Synopsis – Study Intervention 
The study drug dosage will be 
 mg 
P.O. for the full 1252-week 
Treatment Period. Each MORF-057 dose will be administered as 
 
-mg capsules with or without food. 
… 
All subsequent doses will be self-administered at home, with the exception 
of the 
 doses for Visits 2-610, which will be administered during 
the study visits after pre-dose blood samples have been drawn (see details 
in the Schedule of Activities). 
To indicate that the treatment 
period has been extended from 
12 weeks to 52 weeks and that 
additional visits will be required 
Synopsis – Statistical Methods – Sample 
Size Determination 
 
An interim analysis will be performed using the initial 5 bio-experienced 
and initial 5 bio-naïve subjects in the Main Cohort who have evaluable 
baseline and Week 12 primary endpoint data. At that time, the assumptions 
regarding the sample size calculation for the primary endpoint (change 
from baseline to Week 12 in RHI Score) and drop-out rate will be 
re-assessed. 
To clarify details regarding the 
interim analysis 
Synopsis – Statistical Methods – 
Exploratory Endpoints 
Section 9.2.4: Exploratory Endpoints 
The continuous exploratory efficacy endpoints (change from baseline to 
Weeks 6 and 52 in RHI Score and Modified MCS; change from baseline 
to Weeks 6, and 12, and 52 in NI, Continuous Geboes Score, and Full 
MCS; and change from baseline to Weeks 2, 6, and 12, 20, 28, 36, and 52 
in hs-CRP and fecal calprotectin levels) will be analyzed similarly to the 
primary efficacy endpoint using the FAS.  
To indicate the additional 
exploratory analyses associated 
with the extended treatment period 
Synopsis – Statistical Methods – Other 
Safety Assessments 
Section 9.2.5: Other Safety Analyses 
Worst shift in grade and changes from baseline to Weeks 6, 12, and 1252 
of the laboratory analytes will be reported 
 
To indicate the additional safety 
analyses associated with the 
extended treatment period  
Synopsis – Data and Safety Monitoring 
Section 10.1.6: Data and Safety 
Monitoring Board 
Section 10.1.6 Section heading: Data and Safety and Monitoring Board 
and Steering Committee 
 
A DSMB has been appointed to this study. The DSMB is a group of 
independent clinicians/scientists who are appointed to monitor the safety 
and scientific integrity of a human research intervention, and to make 
recommendations to the Sponsor regarding the modification, continuance, 
or stopping of a study based on assessments of safetyor for efficacy based 
futility. The DSMB and a Steering Committee will review safety data 
periodically throughout the study. The Steering Committee will be 
comprised of select Sponsor personnel who will periodically review data. 
The data review will be performed in a controlled manner. The 
composition, responsibilities, and meeting schedule of the DSMB and the 
To clarify details regarding the use 
of a DSMB and a Steering 
Committee 




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• 
Footnote regarding Exploratory Cohort eligibility testing 
updated to indicate all 3 tests required (text changed 
from “and/or” to “and”) 
Section 2.2: Background 
There are several potential clinical advantages of using MORF-057 (an 
orally administered drug) for the treatment of UC over vedolizumab (a 
drug administered via intravenous infusion), which uses the same 
mechanism of action. These include the following:These advantages 
include a flexible dosing regimen and minimal safety concerns regarding 
immunogenicity and serious infusion reactions, requiring less clinical 
visits and therefore reducing patient and healthcare provider burden. 
MORF-057 has the potential to be an effective and safe oral α4β7 integrin 
inhibitor that would be an important addition to the therapeutic 
armamentarium for UC. 
• 
Oral drugs are preferred by patients and healthcare providers 
over injectables. Beyond the fear of needles, the requirement 
for frequent infusion center visits is a substantial burden, 
particularly for younger patients with UC who have active 
professional and family lives.  
• 
Oral formulation allows for flexible dosing regimen. An oral 
drug that is rapidly cleared upon cessation of dosing may be 
desirable for treating physicians in clinical situations such as 
pregnancy, during serious infections, and in the peri-
operative period. Additionally, an oral drug is more easily 
titrated to clinical effect and may be used in fixed dose 
combinations with other oral agents. The long half life of 
vedolizumab means that it cannot be removed rapidly.  
• 
As with all therapeutic proteins, there is the potential for 
immunogenicity with vedolizumab. During the Phase 3 trials, 
4% of patients developed anti-vedolizumab antibodies, 59% 
of which were neutralizing antibodies that reduced plasma 
levels of the treatment antibody (
 package insert). 
• 
Serious infusion reactions, including anaphylaxis, have been 
reported with vedolizumab.  
If shown to be safe and effective in patients, MORF 057 could be an 
important oral therapeutic option for the treatment of moderate to severe 
UC.  
To reduce redundancy between 
Section 2.2 and Section 2.3.1 


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Section 2.2.1: Non-clinical Findings 
In 3 month oral repeat dose toxicity studies in Sprague Dawley rats and 
beagle dogs, the no observed adverse effect level (NOAEL) values were 
450 mg/kg/day for rats and 300 mg/kg/day for dogs, the highest doses 
tested in these studies. At the NOAEL dose of 450 mg/kg/day in rats, 
partially reversible, non adverse microscopic findings were observed in 
the liver (mononuclear cell infiltration, periductular), spleen (increased 
lymphoid cellularity of the periarteriolar lymphoid sheaths, correlating 
with increased spleen weights), stomach (degeneration/atrophy of chief 
cells and hyperplasia/hypertrophy of mucous cells), and mesenteric lymph 
node (increased infiltration of mast cells). These histopathological changes 
were associated with a spectrum of non adverse, reversible clinical 
pathology findings (minimal increases in primarily circulating 
lymphocytes and eosinophils) at ≥150 mg/kg/day. At the NOAEL dose of 
300 mg/kg/day in dogs, minimal, reversible increases in circulating 
lymphocytes were observed. A 6 month oral repeat dose toxicity study in 
male and female Sprague Dawley rats and a 9 month oral repeat dose 
toxicity study in male and female beagle dogs are ongoing. 
In a 6-month oral repeat-dose study of MORF-057 in Sprague Dawley 
rats, significant, reversible increases in circulating white blood cells 
(WBCs), lymphocytes, eosinophils, and large unstained cells were seen at 
the high dose of 450 mg/kg/day due to the pharmacological action of 
MORF-057. Non-adverse changes in cellularity in the spleen were 
observed at the high dose of 450 mg/kg/day, which were attributed to the 
pharmacological activity of MORF-057. The no-observed-adverse-effect 
level (NOAEL) in this study was 50 mg/kg/day in male and female rats. 
The adverse changes in rats after 6 months of dosing were 
degeneration/regeneration of chief cells in the glandular stomach at 125 
or 450 mg/kg/day, which appeared to be partially reversible by 4 weeks 
post-dose. 
In a 9-month oral repeat-dose study in beagle dogs, the NOAEL was 
300 mg/kg/day, the highest dose tested. Non-adverse hepatobiliary 
changes were observed in several dogs that received 300 mg/kg/day of 
MORF-057; these changes correlated with increases in alanine 
transaminase (ALT) and alkaline phosphatase (ALP) measured in the 
same dogs. There were no adverse histopathological changes in dogs after 
9 months of dosing. The degeneration/regeneration of chief cells in the 
glandular stomach observed in rats after 6 months of dosing was not noted 
in the beagle dogs at any dose up to 300 mg/kg/day, even though Cmax 
To provide the most current 
non-clinical findings for 
MORF-057 


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values were 10-fold higher and AUClast values were up to 20-fold higher in 
dogs compared to rats.  
For a human dose of 
mg 
., the safety margin for MORF-057 in 
rats, the most sensitive toxicology species, is 6.5-8.7. The safety margins 
compared to dogs is 161 to 177 fold.  
Section 2.2.2 Clinical Findings 
Clinical drug-drug interaction studies (Studies MORF‑057‑102 and 
MORF‑057‑103) evaluating the inhibitory and inductive potential of 
MORF‑057 on cytochrome P450 3A (CYP3A) in healthy participants have 
been completed. MORF‑057 did not have an effect on midazolam PK 
following a single dose, whereas it was identified as a weak inducer of 
cytochrome P450 3A4 (CYP3A4) with a 33% decrease of midazolam AUC 
(a weak inducer is defined as ≥20% and <50% decrease in AUC of a 
sensitive substrate) following 
 at 
 mg 
 (Study 
MORF‑057‑102). The midazolam drug-drug interaction results were 
consistent with the in vitro cytochrome P450 (CYP) inhibition and 
induction data indicating that, at the clinical exposure of 
mg 
 
dose, MORF‑057 has the potential to be a weak CYP3A4 inducer with 
minimal inhibition of major CYPs. Co-administration of ethinyl 
estradiol/levonorgestrel with MORF-057 (Study MORF-057-103), 
compared with administration of ethinyl estradiol/levonorgestrel alone, 
did not substantially alter ethinyl estradiol or levonorgestrel exposure 
(AUCs and Cmax). The 90% confidence intervals of the geometric mean 
ratios for ethinyl estradiol AUC0-24, Cmax, and C24 were contained within 
the 80.00% to 125.00% no-effect range with the exception of the lower 
limits of AUC0-t and AUC0-inf. The 90% confidence intervals of the 
geometric mean ratios for levonorgestrel AUCs and C24 were contained 
within the 80.00% to 125.00% no-effect range with the exception of the 
lower limit of Cmax. An overall marginal decrease in PK parameters was 
observed. 
To add drug-drug interactions data 
for MORF-057 
Section 2.3.2: Risks 
In 3a 6-month toxicology studiesstudy in Sprague Dawley rats and a 
9-month toxicology study in beagle dogs, the NOAEL values were 
45050 mg/kg/day for rats and 300 mg/kg/day for dogs, the highest dose 
tested in those studies (Section 2.2.1). 
To provide the most current 
non-clinical findings for 
MORF-057 
Section 4.2: Scientific Rationale for Study 
Design 
This open-label, single-arm, multicenter Phase 2a study was designed to 
assess the efficacy of MORF-057 (
 mg 
P.O.) in participants with 
moderate to severe UC when administered for at least 12 weeks, but the 
protocol may be amended to extend the treatment duration to 52 weeks if 
ongoing non clinical toxicology studies support this plan.(including a 
12-week Induction Period plus a 40-week Maintenance Period). 
To indicate that the treatment 
period has been extended from 
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Section 4.4: End of Study Definition 
A participant is considered to have completed the study if he/she has 
completed all periods of the study and attended the Safety Follow-up Visit 
OR has completed the Week 52/EOT Visit and has been enrolled into the 
Open-label Extension study. 
To indicate participants now have 
the option to enroll in an 
Open-label Extension study 
Section 6.5: Continues Access to Study 
Intervention after the End of the Study 
Non clinical chronic toxicology studies in animals are currently ongoing. 
Depending on the results of those studies, the Treatment Period for the 
current study (MORF 057 201) may be extended to 52 weeks. Thus, 
although the Treatment Period for this study is currently 12 weeks, 
participants may have the option later to extend the treatment to 52 weeks. 
Once a participant completes the study, he/she Eligible participants will 
have the opportunity to enroll into a separate Open-label Extension study 
after Week 52. Participants who have completed the Week 52 assessments 
and are eligible and willing to enroll into the Open-label Extension study 
will skip the Safety Follow-up Visit and directly enter the Open-label 
Extension study. 
Participants who do not enroll in the Open-label Extension study will no 
longer have access to the study drug after they complete the 52-week 
Treatment Period. 
To specify that the only option to 
continue receiving MORF-057 
after the study is to join the 
Open-label Extension study 
Section 6.7: Concomitant Therapy 
Paracetamol/Acetaminophen at doses of ≤2 grams/day is permitted for 
analgesia during the study. Other concomitant medications may be 
considered on a case by case basis by the Investigator in consultation with 
the Medical Monitor. 
To clarify which concomitant 
therapies will be accepted or not 
Section 6.7.2: Prohibited Medications 
The following concomitant medications/therapies are prohibited for the 
entire duration of the study, including Safety Follow-up: 
• 
Treatments for UC other than those listed in Section 6.7.1 
(including TNF antagonists, integrin antagonists, IL-12/IL-23 
antagonists, JAK antagonists, and S1P receptor agonists) 
• 
Receipt of a live virus vaccine from 3 weeks prior to study Day 1 
until 28 days after the last dose of study drug.  
Note: Non-live vaccines, including those for SARS-CoV-2, 
should not be administered between 3 weeks prior to study Day 1 
and the Week 12 assessments. After the Week 12 assessments, 
such vaccines can be administered according to local vaccination 
standards. Per Exclusion Criterion 10, if the participant has 
started a vaccination series before Day 1, the last in the series 
should be completed by 3 weeks prior to Day 1 (Section 5.1). 
After Day 1, the participant can start a vaccination series with a 
non-live vaccine at any time. 
To clarify which concomitant 
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• 
Moderate-to-strong CYP3A inhibitor or inducer (see Table 4) 
• 
Moderate-to-strong organic anion transporter polypeptide-1B 
inhibitor (see Table 4) 
• 
Cyclosporine, mycophenolate, tacrolimus, or sirolimus 
• 
Nonsteroidal anti-inflammatory drugs (NSAIDs) including but not 
limited to ibuprofen, naproxen, indomethacin, and celecoxib. 
However, participants may take aspirin for cardio-protection at a 
dose not exceeding 325 mg per day. 
• 
Any investigational therapy 
Section 7.2: Participant 
Discontinuation/Withdrawal from the 
Study 
The participant should be encouraged to complete the End of Treatment 
Visit (Visit 510) at the time of study drug discontinuation and the Safety 
Follow-up Visit (Visit 611) at 28 days (+7) after the last dose of study 
drug. 
To indicate the new visit numbers 
for the End of Treatment and 
Safety follow-up visits due to the 
extended treatment period 
Section 8: Study Assessments and 
Procedures 
Local endoscopy may be used for baseline assessments in this study if 
performed within 42 days of study Day 1, consent was obtained from the 
participant for use in a clinical study, video quality and format is 
considered adequate for evaluation by centralized reading facility, and 
biopsy samples are available for central laboratory assessment. 
To remove the possibility of using 
local endoscopy performed before 
study Day 1 for the baseline 
assessments 
Section 8.5: Participant Diary 
Diaries are to be completed at the end of each day daily by the participant 
at home and brought to each study visit for review by study personnel. 
To account for the fact that diary 
entries may occur multiple times a 
day 
Section 8.6: Stool Collection 
Note: Sample is to be collected prior to bowel preparation for Visits 4, 5, 
and 510/EOT. 
To indicate the new visit number 
for the End of Treatment visit due 
to the extended treatment period 
Section 8.7.1: Endoscopy with Biopsy 
Endoscopy will be performed at Screening (Visit 1) and Visits 4 
(optional), 5, and 510/EOT 
To indicate that the Visit 4 
endoscopy is now optional and to 
show the new visit number for the 
End of Treatment visit due to the 
extended treatment period 
Section 8.8.1: Physical Examinations 
A complete physical exam is required at Screening and Visit 510/EOT, 
and a targeted exam may be performed at all other required visits. 
To indicate the new visit number 
for the End of Treatment visit due 
to the extended treatment period 
Section 8.10.1 Collection of Blood 
Samples for MORF-057 Concentration 
Determination in Plasma 
For all 
 sampling, the samples should be obtained within 
approximately 30 minutes before the 
 is administered. 
Furthermore, the samples should be obtained at 12 hours (±1 hour) after 
. 
To clarify pharmacokinetics 
sampling window 
Section 8.10.2 Determination of Drug 
Concentration and PK Parameters 
The following plasma PK parameters will be calculated for MORF-057 (as 
deemed appropriate): 
To account for possible changes in 
PK analyses resulting from the 


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change to optional testing at 
certain timepoints  
Table 3: Pharmacokinetics Sampling 
Windows 
Table 3 was updated to reflect the following changes:  
• 
The pharmacokinetics sampling schedule and associated 
sampling windows were revised due to the extended treatment 
period 
• 
For pharmacokinetics testing at Visits 2, 3, and 5, sampling at 
8, 10, and 12 hours after the 
 was changed to optional 
To indicate changes in 
pharmacokinetics sampling 
Section 8.11.2: CCR9 mRNA 
PAXgene RNA bloodBlood samples will be collected in PAXgene RNA 
tubes to assess changes of transcript levels of CCR9. 
To clarify the wording regarding 
CCR9 mRNA sample collection 
Section 8.13: Potential Adjustments Due 
to COVID-19 
Adjustments to the planned study procedures might be necessary due to the 
ongoing COVID-19 pandemic. Any such specific measures will be detailed 
in the respective ancillary documents, such as site-facing and 
patient-facing documents. 
To explain how the potential 
effects of the COVID-19 
pandemic on the study will be 
addressed 
Section 9.3: Interim Analysis 
An interim analysis will be performed using the initial 5 bio-experienced 
and initial 5 bio-naïve subjects in the Main Cohort who have evaluable 
baseline and Week 12 primary endpoint data. At that time, the assumptions 
regarding the sample size calculation for the primary endpoint (change 
from baseline to Week 12 in RHI Score) and drop-out rate will be 
re-assessed. An independent statistician (not part of the study team) will be 
responsible for providing the relevant information for the sample size 
assessment to the Steering Committee. The Steering Committee will be 
comprised of select Sponsor personnel who will periodically review data. 
The data review will be performed in a controlled manner. Note that no 
data from the participants in the Exploratory Cohort will be included in the 
re-assessment of the sample size assumptions 
In addition, participant safety data will be reviewed by an independent 
DSMB and the Steering Committee periodically throughout the study. 
Details related to the DSMB, the Steering Committee, and the interim 
analysis will be clearly delineated in the DSMB Charter.Further details 
regarding the interim analysis will be outlined in the SAP.  
To clarify details regarding the 
interim analysis 
Section 10.1.4: Informed Consent Process 
The ICF will contain a separate section that addresses the use of samples 
for optional exploratory research. The Investigator or authorized designee 
will explain to each participant the objectives of the exploratory research. 
Participants will be told that they are free to refuse to participate and may 
withdraw their consent at any time and for any reason during the sample 
storage period (determined based on local country regulations). 
To clarify that the sample storage 
period for exploratory research is 
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Section No. and Name 
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Section 10.4.4: Reporting of SAEs 
Contacts for SAE reporting :drugsafety@morphictx.comcan be found in 
the Study Manual 
To update information regarding 
how to report serious adverse 
events 
Table 4. Protocol-required Laboratory 
Tests 
“ESR” moved from Coagulation row to Hematology row 
To correctly classify the ESR test 
Section 10.7: Appendix 7: Mayo Clinic 
Scoring System for Assessment of 
Ulcerative Colitis Activity 
Rectal bleeding: The daily bleeding score represents the most severe 
bleeding of the day. 
… 
2=Obvious blood (more than just streaks) or streaks of blood with stool 
most of the time 
3=Blood alone passespassed 
Endoscopy: The endoscopy subscore will be determined both locally and 
centrally by qualified personnel.  
… 
1=Mild disease (erythema, decreased vascular pattern, no friability) 
To clarify the Mayo Clinic 
Scoring System 
10.11. 
Appendix 10: Summary of Changes Table – Protocol Amendment Version 3.0 
Summary of Changes Table 
Changes to the protocol as implemented by the protocol amendment Version 3.0 in comparison to Version 2.0 are summarized in the 
Summary of Changes table below. New text is shown in italics, deleted text is shown in strikeout, and bold text is informational. In 
addition to the changes provided in the Summary of Changes table, minor editorial changes have been made throughout the protocol. 
Version 3.0 vs Version 2.0 
Section No. and Name 
Description of Change 
Brief Rationale 
Global change 
‘Patients’ was changed to ‘participants’ throughout the Protocol when referring to a study 
participant. 
Administrative change  
Global change 
TNF TNF-α 
To correct protein name 
Title, Indication, and 
throughout 
‘Moderate to severe ulcerative colitis’ was changed to ‘moderately to severely active 
ulcerative colitis’ throughout the Protocol. 
To reflect changes in the 
study indication 
Abbreviations 
AT 
Advanced therapy 
CD 
Crohn’s disease 
CIMS 
Central Image Management Solutions 
ELISA    Enzyme-linked immunosorbent assay 
ESR 
Erythrocyte sedimentation rate 
PCR 
Polymerase chain reaction 
To update the 
abbreviations used 
throughout the protocol 


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PP 
Per Protocol (Population) 
TNF-α Tumor necrosis factor alpha 
Synopsis - Objectives and 
Endpoints 
Section 3. Objectives and 
Endpoints  
To assess the long-term safety of MORF-057 
and effects of MORF-057 on hs-CRP and fecal 
calprotectin levels 
• Frequencies and proportions for TEAEs, 
TESAEs, and TEAEs leading to study drug 
discontinuation through Week 82 
• Change from baseline to Week 65 and Week 
78 in hs-CRP levels  
• Change from baseline to Week 65 and Week 
78 in fecal calprotectin levels 
To add endpoints 
corresponding to Long-
term Extension 
Synopsis - Overall Design 
Section 4.1: Overall Design 
In addition, an Exploratory Cohort will be comprised of a maximum of 510 additional participants 
with moderatemoderately to severeseverely active UC who are intolerant to or secondary non-
responders (as defined in Section 5.1) to vedolizumab. Thus, there will be a total of 30 to 3540 
participants in the study because when the Main Cohort recruits 30 participants, the entire study 
will be closed to new enrollees. 
To expand the enrollment 
goal of the Exploratory 
Cohort: in addition to the 
enrolling vedolizumab 
failures using 
biochemical/lab criteria, 
another cohort of 5 
participants are added 
whose secondary loss of 
response to vedolizumab 
will be defined by 
clinical criteria only 
Synopsis - Overall Design 
Section 4.1: Overall Design 
For this study, moderatemoderately to severeseverely active UC will be defined as having a 
Modified MCS of 5 to 9 (inclusive) with an MES ≥2 (confirmed by central reader) and a rectal 
bleeding subscore ≥1.). In the Main Cohort, the enrollment goal is for 45approximately 55% to 
5575% of the participants to be bio advanced therapy (AT) naïve (i.e., to have no previous 
exposure to a biologic treatment, Janus kinase [JAK] antagonists, or sphingosine-1-phosphate 
[S1P] receptor agonists for UC). 
 
To clarify inclusion 
criterion  
Synopsis - Overall Design 
Section 4.1: Overall Design 
Separately, an efficacy based interim analysis will be performed by an internal Sponsor Steering 
Committee using the initial 5 bio experienced and initial 5 bio naïve subjects in the Main Cohort 
who have evaluable baseline and Week 12 primary endpoint data. The purpose of the interim analysis 
is to assess whether the study remains appropriately powered or if the sample size needs to be 
revised. Note that data from participants in the Exploratory Cohort will not be included in the sample 
size assessment that is performed at the interim analysis. Details related to the interim analysis will 
be outlined in the Statistical Analysis Plan (SAP). 
 
To remove the planned 
interim analysis for 
sample size reassessment 
Synopsis - Overall Design 
Section 4.1: Overall Design 
The main part of this This Phase 2a study will consist of 3 study periods: a Screening Period (up to 
6 weeks), a Treatment Period (52 weeks, including a 12-week Induction Period and a 40-week 
Maintenance Period), and a Safety Follow-up Period (4 weeks). 
To clarify the study 
design 




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Criteria 
Period with the following criteria: a Modified MCS of 5 to 9 (inclusive, with an MES ≥2 
(confirmed by central reader) and a rectal bleeding subscore ≥1 
5. Is an bio AT-naïve participant or a participant who had an inadequate response, loss of response, 
or intolerance to no more than 3 drugs in 2 classes of the following:   
5c. Janus kinase JAK antagonists, including tofacitinib and upadacitinib 
5f. Integrin inhibitors, including vedolizumab (participants in the Exploratory Cohort only) 
6c. JAK antagonists, including tofacitinib and upadacitinib: at least 2 weeks 
Synopsis – Main Inclusion 
Criteria 
Section 5.1. Inclusion 
Criteria – Main Inclusion 
Criteria 
Weight 
9. Has a body mass index (BMI) within the range of 18.0 and 3340.0 kg/m2 (inclusive) at Screening 
 
To change the upper limit 
on BMI in the inclusion 
criteria 
Synopsis –  
Exploratory Cohort 
Inclusion Criteria 
Section 5.1. Inclusion 
Criteria 
13. Secondary Those intolerant to (e.g. infusion-related skin reaction, allergy, or side effects 
unrelated to α4β7 inhibition) or secondary non-responders* to vedolizumab currently being treated 
who have been dosed within the past 5 years with the drug. Up to 5 of the 10 Exploratory Cohort 
participants may be included based on clinical criteria only. The remaining participants must also 
display meet at least 1 of the following criteria: 
a. 
Documented vedolizumab levels in blood of ≤10 µg/mL 6 to 8 weeks after their most 
recent dose or what is considered clinical trough. If the participant has had 
vedolizumab levels in blood tested and documented in their medical chart prior to 
Screening, the test does not need to be repeated. 
b. Non-saturating receptor occupancy of vedolizumab in blood 6 to 8 weeks after their 
most recent dose 
c. 
Presence Documented presence of anti-drug antibodies against vedolizumab. If the 
participant has had a positive anti-drug antibody test that has been documented prior 
to Screening, the test does not need to be repeated. 
*Note: Secondary non-response is defined as having initially responded to Induction 
therapy and then had recurrence of symptoms after receiving at least 2 of the 
Maintenance doses, 300 mg every 8 weeks (discontinuation despite clinical benefit does 
not qualify). 
 
To clarify inclusion 
criteria regarding 
exploratory cohort 
(vedolizumab failures) 
and vedolizumab levels 
testing 
Section 1.2. Schedule of 
Assessments (SoA)  
 
Schedule of Activities, Table 1, Footnote “l”: 
If the participant has had vedolizumab levels in blood or presence of anti-drug antibodies against 
vedolizumab tested and documented in their medical chart prior to Screening, the test does not 
need to be repeated. 
 


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Section 8.2.3. Exploratory 
Cohort Screening Tests 
 
• Vedolizumab blood levels 6 to 8 weeks after their most recent dose or at what is considered 
clinical trough. (If the participant has had vedolizumab levels in blood tested and documented in 
their medical chart prior to Screening, the test does not need to be repeated.) 
• Receptor occupancy of vedolizumab in blood 6 to 8 weeks after their most recent dose 
• Anti-vedolizumab antibody testing (If the participant has had a positive anti-drug antibody test 
that has been documented prior to Screening, the test does not need to be repeated.) 
 
Synopsis - Exclusion 
Criteria 
Section 5.2. Exclusion 
Criteria 
 
Medical Conditions 
3. Currently requires or is anticipated to require surgical intervention for UC during the study or is 
planning to undergo major surgery during the study period 
4. Has had a surgical procedure requiring general anesthesia within 30 days prior to Screening or is 
planning to undergo major surgery during the study period 
7. Has an active bacterial, viral, or parasitic pathogenic enteric infection, including Clostridium 
difficile; has cytomegalovirus, hepatitis B or C virus, or human immunodeficiency virus (HIV); 
had an infection requiring hospitalization or intravenous antimicrobial therapy, or an opportunistic 
infection within 3 months prior to Screening; had any infection requiring oral antimicrobial 
therapy within 2 weeks prior to Screening; or has a history of more than 1 episode of herpes zoster 
or any episode of disseminated herpes zoster infection 
 
To clarify exclusion 
criteria 
 
Synopsis - Exclusion 
Criteria 
Section 5.2. Exclusion 
Criteria 
 
 
Medical Conditions 
8. Has a positive diagnostic tuberculosis (TB) test at Screening (defined as a positive 
 test). If the participant has had a confirmed negative 
 or other 
Interferon Gamma Release Assay test within 90 days prior to Screening, the test does not need to 
be repeated.  
 
To clarify exclusion 
criteria regarding 
tuberculosis testing 
Section 1.2. Schedule of 
Assessments (SoA)  
 
Schedule of Activities, Table 1, Footnote “j”: 
 TB test. If the participant has had a confirmed negative 
or other 
Interferon Gamma Release Assay test within 90 days prior to Screening, the test does not need to 
be repeated. 
Synopsis - Exclusion 
Criteria 
Section 5.2. Exclusion 
Criteria 
 
 
Medical Conditions 
9. Tests positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the 
Screening Period. Participants who test positive for SARS-CoV-2 can undergo retesting throughout 
the Screening Period. Testing to be performed according to site-specific testing procedures and 
country-specific requirements. 
 
To clarify exclusion 
criteria regarding SARS-
CoV-2 testing 
Section 1.2. Schedule of 
Assessments (SoA) 
Schedule of Activities, Table 1, Footnote “i”: 
SARS-CoV-2 test will be performed during the Screening Period according to site-specific 
procedures and country-specific requirements. Participants who test positive for SARS-CoV-2 can 
undergo retesting throughout the Screening Period. 


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Synopsis – 
Study Intervention 
Participants who enroll into the Long-term Extension will continue the study drug dosage (
 mg 
 P.O.) for the 26-week extended Treatment Period. Each MORF-057 dose will be 
administered as four 25-mg capsules with or without food. Through the Long-term Extension, 
MORF-057 will continue to be self-administered at home, with the exception of the 
 doses 
for Visits 11-12, which will be administered during the study visits after pre-dose blood samples 
have been drawn (see details in the Schedule of Activities). Participants will be instructed to 
record all details about the doses administered at home in the Participant Diary. 
To identify details in the 
study design of the Long-
term Extension 
Synopsis – Statistical 
Methods 
Section 9.2: Statistical 
Analysis 
General Considerations 
A significance level of 0.0245 025 one-sided (0.049 05 two-sided) will be used for the primary 
efficacy endpoint. 
 
To update statistical 
methods 
Synopsis – Statistical 
Methods 
Section 9.4: Sample Size 
Determination 
Sample Size Determination 
The sample size for this study is based on the number of participants needed for the Main Cohort. 
Assuming a one-sided alpha at 0.0245 025 for the final analysis, a standard deviation of 12, and a 
one-sample t-test, a mean treatment effect of ≥7-point reduction in RHI can be detected using 28 
participants with >80% power. A drop out rate of 5% would lead to a total of 30 participants being 
enrolled in the Main Cohort. A maximum of 5 10 additional participants may be enrolled in the 
Exploratory Cohort, giving a total of 30 to 35 40 enrolled participants in the study. 
 
To update statistical 
methods and to expand 
the enrollment goal of the 
Exploratory Cohort: in 
addition to the enrolling 
vedolizumab failures 
using biochemical/lab 
criteria, another cohort of 
5 participants are added 
whose secondary loss of 
response to vedolizumab 
will be defined by 
clinical criteria only 
Synopsis – Statistical 
Methods 
Section 9.3. Analyses for 
Induction Period, 52-Week 
Treatment Period, and 
Long-term Extension 
 
Analyses for Induction Period, 52-week Treatment Period, and Long-term Extension 
 
The study open-label treatment period includes 2 parts: the 12-week Induction Period and the 40 
week Maintenance Period. For the purpose of statistical analyses, the Induction Period and the 
Maintenance Period will be treated as 2 independent parts. There will be 2 analyses planned: one 
for the 12-week Induction Period (i.e., the period for the primary efficacy endpoint) and the other 
for the 52-week Treatment Period (i.e., the 12-week Induction Period plus the 40-week 
Maintenance Period and the Safety Follow-up). Additional analysis of the optional Long-term 
Extension Period for the participants enrolled into the Long-term Extension will be performed as 
appropriate. 
 
Induction Period Analysis  
The analysis of the Induction Period will be performed after all the participants have completed 
the 12-week Induction Period (i.e., completed the Week 12 visit or discontinued the study before 
the Week 12 assessment). The analysis will formally evaluate the primary and secondary efficacy 
To clarify the planned 
analyses 


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endpoints, all the exploratory endpoints defined by Week 12, PK concentrations and parameters, 
and safety of MORF-057 during the 12-week Induction Period. Only Induction Period data will be 
used in this analysis.   
 
52-Week Treatment Period Analysis  
The analysis of the 52-week Treatment Period will be performed after all the participants have 
completed the 52-week open-label Treatment Period (and the Safety Follow-up Period for 
participants not enrolling into the optional Long-term Extension Period) or discontinued the study 
before the Week 52 assessment. The analysis will formally evaluate all the exploratory endpoints 
defined by Week 52, PK concentration and parameters, and safety of MORF-057 during the 52-
week open-label Treatment Period plus the Safety Follow-up Period. The cumulative data, 
including those from the Induction Period, will be used in this analysis. 
 
Long-term Extension Analysis  
The analysis of the Long-term Extension will be performed after all the participants enrolled into 
the Long-term Extension have completed the 26-week extended Treatment Period and the Safety 
Follow-up Period or discontinued the study before the Week 78 assessment. The analysis will 
formally evaluate the safety of MORF-057 and selected efficacy endpoints as appropriate during 
the Long-term Extension plus the Safety Follow-up Period. 
Synopsis – Statistical 
Methods 
 
An interim analysis will be performed using the initial 5 bio experienced and initial 5 bio naïve 
subjects in the Main Cohort who have evaluable baseline and Week 12 primary endpoint data. At 
that time, the assumptions regarding the sample size calculation for the primary endpoint (change 
from baseline to Week 12 in RHI Score) and drop out rate will be re assessed. Note that no data 
from the participants in the Exploratory Cohort will be included in the re assessment of the sample 
size assumptions. As there are no formal defined procedures for adjusting the final analysis 
significance level in instances of sample size re assessment, a small adjustment will be made in 
this study, with alpha = 0.001 two sided spent at the interim analysis and the final significance 
level adjusted to alpha = 0.049 two sided / alpha = 0.0245 one sided. 
 
To remove the planned 
interim analysis for 
sample size reassessment 
and clarify the planned 
analyses 
Section 9.2.5. Other Safety 
Analyses 
 
9.2.5 Other Safety Analyses 
Other safety data will include safety laboratory parameters, vital signs, and ECG findings. These 
data will be summarized with descriptive statistics by absolute values and change from baseline 
using the FASSafety Analysis Population. The incidence of laboratory abnormalities will be 
summarized. Worst shift in grade and changes from baseline to Weeks 6, 12, and 52 of the 
laboratory analytes will be reported. Physical examination findings that are recorded as AEs will 
be included in those data presentations.   
 
Participant safety data will be reviewed by an independent DSMB. Additional details related to the 
DSMB are included in Section 10.1.6 and will be clearly delineated in the DSMB Charter. 


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Section 9.3. Interim 
Analysis  
9.3. Interim Analysis 
An interim analysis will be performed using the initial 5 bio experienced and initial 5 bio naïve 
subjects in the Main Cohort who have evaluable baseline and Week 12 primary endpoint data. At 
that time, the assumptions regarding the sample size calculation for the primary endpoint (change 
from baseline to Week 12 in RHI Score) and drop out rate will be re assessed. Further details 
regarding the interim analysis will be outlined in the SAP. 


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Synopsis– Statistical 
Methods: Analysis 
Populations 
Section 9.1 Analysis Sets 
 
The Full Analysis Set (FAS) is defined as all enrolled participants in the Main Cohort and 
Exploratory Cohort who took at least one dose of study medication. The FAS will be used for all 
efficacy, safety, and biomarker summarizations/ analyses. This definition of the FAS is sometimes 
also known as the Safety Population (note that, as indicated above, the FAS will be used for safety 
endpoints).  
 
The Per Protocol (PP) Population is defined as all participants in the FAS who do not have any 
major protocol deviations relevant to the primary and secondary efficacy endpoint analysis. All 
decisions to exclude participants from the PP set will be made prior to the database lock of the 
study. The Per ProtocolPP Population maywill be used for sensitivity efficacy analyses of, at a 
minimum,analysis of the primary efficacy endpoint. and maybe other selected efficacy endpoints 
as appropriate.  
 
The Safety Analysis Population is defined as all participants in both the Main Cohort and 
Exploratory Cohort who received at least 1 dose of study medication. The Safety Analysis 
Population will be used for safety analysis. 
 
The PK Population is defined as all participants in the FAS who have adequate measurable 
concentrations to define Cmax or AUC. The PK Population will be used in the individual plasma 
concentration, PK parameter estimation listings, and individual figures. 
 
The PK Evaluable Population (a subset of the PK Population) will be used to determine the 
inclusion of a participant in the overall PK summaries. Participants included in this subset must 
not violate the protocol in a way that may invalidate or bias the results, and must have the reliable 
data for the overall PK summaries. The criteria that the data must meet for the inclusion of a 
participant in this population will be specified in the study SAP. 
 
As appropriate, participants in the Exploratory Cohort will also have their data included in 
summarization and/or analysis of study endpoints. 
To define the analysis 
sets of the study 
Synopsis– Statistical 
Methods: Secondary 
Endpoints 
Synopsis– Statistical 
Methods: Other Safety 
Assessments 
Section 9.2.3. Secondary 
Endpoints 
Section 9.2.5. Other Safety 
Analyses 
FAS Safety Analysis Population  
To add a Safety Analysis 
Population 


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Brief Rationale 
Synopsis– Statistical 
Methods: Exploratory 
Endpoints 
Section 9.2.4. Exploratory 
Endpoints 
Details related to the summarization and analysis of the otherThe exploratory PD endpoints (α4β7 
and α4β1 receptor occupancies over time, and change from baseline over time in blood CCR9 
mRNA, change from baseline over time in blood lymphocyte subsets,) will be summarized 
descriptively. Additional analysis of blood and mucosal tissue gene and/or protein expression over 
time, microbiome composition in stool and mucosal tissue over time, changes in microbiome-
derived metabolites in stool and blood over time, and metatranscriptomic changes in the stool and 
mucosal tissue microbiome over time) will be provided in a biomarker analysis plan separate from 
the study SAP and reported separately. 
To identify how the 
exploratory PD endpoints 
will be reported 
Synopsis – 
Data and Safety Monitoring 
 
Additionally, a separate PML Adjudication Committee will oversee a PML Risk Assessment and 
Minimization Program (RAMP) to monitor all participants for PML. The composition, 
responsibilities, and meeting schedules of the DSMB and the PML Adjudication Committee will be 
described in a separate charter charters. All participants enrolled in this study will be monitored 
for PML through the use of a PML Risk Assessment and Minimization Program (RAMP), which 
will be overseen by the DSMB. 
 
To describe the 
progressive multifocal 
leukoencephalopathy 
(PML) Adjudication 
Committee 
responsibilities as they 
relate to the study 
Section 2.3.2 Risks 
However, out of an abundance of caution, all participants enrolled in this study will be monitored 
for PML through the use of a PML Risk Assessment and Minimization program (RAMP), which 
will be overseen by the DSMB.). 
 
Section 10.1.7 PML 
Adjudication Committee 
Section 10.1.7. PML Adjudication Committee 
All participants enrolled in this study will be monitored for PML through the use of a PML Risk 
Assessment and Minimization Program (RAMP), which will be overseen by the DSMB. 
 
A PML Adjudication Committee will oversee a PML RAMP to monitor all participants for PML. 
The composition, responsibilities, and meeting schedules of the PML Adjudication Committee will 
be described in a separate charter. 
 
Section 1.2. Schedule of 
Activities (SoA) 
The Schedule of Activities table was updated to change Open-label Extension Study to Long-
term Extension, add dispensation of study drug at Visit 10 for participants who want to 
continue in the Long-term Extension, and add that participants who want to continue in the 
Long-term Extension will sign a separate ICF.  
 
Schedule of Activities, Table 1, Footnote “d”: 
Participants who will not enroll into the Open labelLong-term Extension Study will complete the 
Safety Follow-up Visit, which should be performed 28 days (+7 days) after the participant takes 
the last dose of study drug. Eligible pParticipants who choose to enroll into the Open labelLong-
term Extension Study after Visit 10/EOT will not attend thecomplete a Safety Follow-up Visit at 
Week 82. 
 
To identify the timeline 
and describe the details 
of the Long-term 
Extension 




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Section No. and Name 
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Brief Rationale 
Section 4.4. End of Study 
Definition 
A participant is considered to have completed the study if he/she has completed all periods of the 
study the Screening and 52-week Treatment Periods of the study and attended the Safety Follow-
up Visit OR has completed the Week 52/EOT Visit and has been enrolled into the Long-term 
Extension Open label Extension study.  
The end of the study is defined as the date of the last visit of the last participant in the main part of 
the study or last scheduled procedure shown in the schedule of activities for the last participant in 
the main part of the study globally.  
The results for the Long-term Extension may be reported in a Clinical Study Report Addendum. 
To define participant 
study completion  
Section 6.5. Continued 
Access to Study 
Intervention after the End of 
the Study 
EligibleAll participants will have the opportunity to enroll into a separate Open label Long-term 
Extension study after Week 52. Participants who have completed completing the Week  52 
assessments and Participants who are eligible and willing to enroll into the Open label Long-term 
Extension study will skip the Safety Follow-up Visit at Week 56 and directly enter the Open label 
Long-term Extension study. Participants enrolled into the Long-term Extension will complete the 
Safety Follow-up Visit at Week 82. 
 
Participants who do not enroll in the Open label Long-term Extension study will no longer have 
access to the study drug after they complete the 52-week Treatment Period. Participants who 
continue in the Long-term Extension will no longer have access to the study drug after they 
complete the 26-week extended Treatment Period. 
To add information on 
continued access to study 
intervention in the Long-
term Extension 
Section 6.6. Treatment of 
Overdose 
• Contact the Medical Monitor immediatelywithin 24 hours 
• Enter the overdose information into the electronic data capture database (EDC) within 24 hours 
of notification 
To provide guidance on 
overdose reporting 
Section 6.7.1.1. Tapering of 
Oral Corticosteroids 
Participants receiving budesonide MMX (1 tablet, 9 mg) can reduce dosage by taking 6 mg 
budesonide (2 tablets, 3 mg each) daily for two weeks, followed by 3 mg budesonide (1 tablet, 3 
mg) daily for two weeks to complete the tapering process. 
To add guidance on 
budesonide tapering 
Section 6.7.2 Prohibited 
Medications 
• Nonsteroidal anti-inflammatory drugs (NSAIDs) including but not limited to ibuprofen, 
naproxen, indomethacin, and celecoxib. However, participants may take aspirin for cardio 
protection secondary prevention of cardiovascular event at a dose not exceeding 325 100 mg per 
day. 
To lower the allowed 
dose of aspirin during the 
study 
Section 7.2. Participant 
Discontinuation/Withdrawal 
from the Study 
The participant should be encouraged to complete the End of Treatment Visit (Visit 10 in the main 
part of the study, or Visit 12 in the Long-term Extension) at the time of study drug discontinuation 
and the Safety Follow-up Visit (Visit 11 in the main part of the study, or Visit 13 in the Long-term 
Extension) at 28 days (+7) after the last dose of study drug. 
To identify the different 
End of Treatment Visits 
in the Main Study and 
Long-term Extension if a 
participant discontinues 
from the study. 
Section 8.1. Medical 
History 
All prior advanced therapies for the treatment of UC (e.g., antagonists to TNF-α, JAK, or 
IL-12/IL-23; S1P receptor agonists; integrin inhibitors [Exploratory Cohort only]; or other new 
investigational treatments) with the reason for discontinuation are to be collected for participants 
where possible. 
To update documentation 
of medical history 


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Section 8.5 Participant 
Diary 
Detailed descriptions regarding Participant Diary recordings can be found in the Study 
ManualPatient Guide. 
To update the source for 
Participant Diary 
instructions 
Section 8.7.1. Endoscopy 
with Biopsy 
Detailed instructions for endoscopic biopsies (e.g., anatomic site, normal or inflamed mucosa) can 
be found in the Study Manual Central Image Management Solutions (CIMS) Biopsy Quick 
Reference Card. 
 
Biopsy specimen transfer, processing, slide preparation, and digitization of slides for 
histopathologic scoring procedures will be detailed in a Histopathology Manualthe Image Review 
Charter. 
To add the Biopsy Quick 
Reference Card and 
Image Review Charter 
Section 8.7.1. Endoscopy 
with Biopsy 
The MES will be scored both locally and centrally. If there is a disagreement between the local and 
central scoring, a second central reader (adjudicator), who will be blinded to knowing if the score is 
local or central, will select either the local reader or first central reader score to be used as the final 
score (forced adjudication). However, treatment decisions will be made by the treating 
Investigator. 
To specify that the 
adjudicator will be 
blinded to local vs. 
central score 
Section 8.8.5 Progressive 
Multifocal 
Leukoencephalopathy 
 
 
 
 
 
The PML checklist willThe Subjective PML Checklist will be administered to participants during 
Screening to exclude individuals with a positive response from enrolling into the study. The 
Subjective PML Checklist (Section 10.2) will also be completed according to the schedule in the 
SoA (Section 1.2). The checklist is provided in Section 10.2. If the results of the questionnaire are 
suggestive of PML, the participant will undergo Objective PML Checklist testing (Section 10.2), a 
full neurological exam by a neurologist, and, if indicated, additional testing are to be performed. 
 
To include the complete 
PML checklist in the 
protocol 
Section 10.2 Appendix 2: 
Progressive Multifocal 
Leukoencephalopathy 
Checklists 
The Objective PML Checklist was added to Appendix 2. 
Section 9. Statistical 
Considerations 
The Statistical Analysis Plan (SAP) will be finalized prior to the interim analysis first participant 
dosed, and may be amended as needed due to a protocol amendment. It will include a more 
technical and detailed description of the data summarization and analysis described in this section. 
Any deviation change from the planned statistical analyses specified in the protocol will be fully 
described in the SAP and Clinical Study Report. 
To add details about the 
SAP 
Section 9.2.1. General 
Considerations 
A significance level of 0.0245025 one-sided (0.04905 two-sided) will be used for the primary 
efficacy endpoint. 
To adjust the statistical 
significance level to be 
used in the analysis of 
the primary efficacy 
endpoint 


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Section No. and Name 
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Brief Rationale 
Section 9.4. Sample Size 
Determination 
As there are no formal defined procedures for adjusting the final analysis significance level in 
instances of sample size re assessment, a small adjustment will be made in this study, with 
alpha=0.001 two sided spent at the interim analysis and the final significance level adjusted to 
alpha=0.049 two sided / alpha = 0.0245 one sided. 
To revise the sample 
sizes needed for this 
study  
Section 10.3. Appendix 3: 
Clinical Laboratory Tests 
Laboratory 
Tests 
Parameters 
Hematology 
• 
Platelet count  
• 
RBC count 
• 
Hemoglobin 
• 
Hematocrit 
• 
ESR 
RBC Indices: 
• 
MCV 
• 
MCH 
• 
% Reticulocytes 
WBC count with 
differential: 
• 
Neutrophils 
• 
Lymphocytes 
• 
Monocytes 
• 
Eosinophils 
• 
Basophils 
Pregnancy 
testing 
• 
Highly sensitive serum hCG pregnancy test (at Screening and as needed 
for women of childbearing potential only)  
• 
Urine hCG test (at Visits 2-11 in the main Treatment Period and Visits 
11-13 of the Long-term Extension for women of childbearing potential 
only) a 
To remove erythrocyte 
sedimentation rate test 
and clarify the schedule 
for pregnancy testing 
Section 10.4.4. Appendix 4: 
Reporting of SAEs 
SAE Reporting to the Sponsor or designee via an Electronic Data Collection Tool 
• Contacts for SAE reporting can be found in the Study Manual 
 
SAE Reporting to the Sponsor or Designee via Paper Data Collection Tool  
(Back-up Option) 
• Contacts for SAE reporting can be found in the Study Manual. If the electronic system is not 
available, the SAE paper data collection tool should be signed by the Investigator and emailed to: 
 
To add details for the 
reporting of SAEs 
Section 10.10. Appendix 
10: Summary of Changes 
Table – Protocol 
Amendment Version 2.0  
The summary of changes between Protocol Version 1.0 and Version 2.0 was moved to an 
appendix.  
Administrative change 


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Brief Rationale 
Section 11. References 
Parikh A, Stephens K, Major E, et al. A Programme for Risk Assessment and Minimisation of 
Progressive Multifocal Leukoencephalopathy Developed for Vedolizumab Clinical Trials. Drug 
Saf. 2018;41(8):807-16. 
To add a reference  
 
 



SAP_001.pdf: 


Morphic Therapeutic                     
Study MORF-057-201  
 
Statistical Analysis Plan, V3.0                        
CONFIDENTIAL 
Page 2 of 61
 
Approval of Statistical Analysis Plan for Study MORF-057-201 
 
 
 
 
 
 
 
 
 
 
 
 
Michael Choi, MD 
Senior Director, Clinical Development 
Morphic Therapeutic, Inc. 
35 Gatehouse Drive, A2 
Waltham, MA 02451 
United States 
 
Date 
 
 
 
 
 
 
 
 
Brihad Abhyankar, MS, FRCS, FFPM 
Senior Vice President, Clinical Development 
Morphic Therapeutic, Inc. 
35 Gatehouse Drive, A2 
Waltham, MA 02451 
United States 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
Cuyue Tang, PhD 
Vice President, DMPK & Clinical Pharmacology 
Morphic Therapeutic, Inc. 
35 Gatehouse Drive, A2 
Waltham, MA 02451 
United States 
 
Date 
 
 
 
 
 
 
 
 
Yujun Wu, PhD 
Executive Director, Biostatistics 
Morphic Therapeutic, Inc. 
35 Gatehouse Drive, A2 
Waltham, MA 02451 
United States 
 
Date 


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Mark Jaros, PhD 
Biostatistician 
Summit Analytical, LLC 
8354 Northfield Blvd. 
Bldg. G Suite 3700 
Denver, CO 80238 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lynle Go, PhD 
Associate Director, Clinical Pharmacology and Drug Development 
Everest Clinical Research Corporation 
675 Cochrane Drive 
East Tower, 4th Floor 
Markham, ON 
Canada L3R0B8 
 
Date 
 


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1. 
TABLE OF CONTENTS 
1. 
TABLE OF CONTENTS .............................................................................................4 
2. 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS .................................8 
3. 
INTRODUCTION ......................................................................................................11 
3.1. 
Preface ........................................................................................................................11 
3.2. 
Scope of Analyses .......................................................................................................11 
3.3. 
Summary of Statistical Analysis Changes to the Protocol .........................................11 
3.4. 
Summary of Changes to the Statistical Analysis Plan ................................................12 
4. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................14 
4.1. 
Study Objectives .........................................................................................................14 
4.1.1. 
Primary Objective .......................................................................................................14 
4.1.2. 
Secondary Objectives .................................................................................................14 
4.1.3. 
Exploratory Objectives ...............................................................................................14 
4.2. 
Study Endpoints ..........................................................................................................14 
4.2.1. 
Primary Endpoint ........................................................................................................14 
4.2.2. 
Secondary Endpoints ..................................................................................................14 
4.2.3. 
Exploratory Endpoints ................................................................................................15 
5. 
STUDY METHODS ...................................................................................................17 
5.1. 
General Study Design and Plan ..................................................................................17 
5.2. 
Randomization and Blinding ......................................................................................26 
6. 
SAMPLE SIZE ...........................................................................................................27 
7. 
GENERAL CONSIDERATIONS ..............................................................................28 
7.1. 
Analysis Populations ..................................................................................................28 
7.1.1. 
Full Analysis Set (FAS) ..............................................................................................28 
7.1.2. 
Per Protocol (PP) Set ..................................................................................................28 
7.1.3. 
Safety Analysis Population .........................................................................................28 
7.1.4. 
PK Population .............................................................................................................28 
7.1.5. 
PK Evaluable Population ............................................................................................29 
7.1.6. 
PD Population .............................................................................................................29 
7.2. 
Covariates and Subgroups ..........................................................................................29 
7.2.1. 
Planned Covariates .....................................................................................................29 
7.2.2. 
Planned Subgroups .....................................................................................................30 


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7.3. 
Management of Analysis Data ....................................................................................30 
7.3.1. 
Unscheduled Visits .....................................................................................................30 
7.3.2. 
Missing Data ...............................................................................................................30 
7.3.2.1. 
Handling of Missing Date Values ...............................................................................30 
7.3.2.2. 
Imputation Methods ....................................................................................................31 
7.3.3. 
Handling Rule for PK .................................................................................................31 
7.3.3.1. 
PK Concentrations ......................................................................................................31 
7.3.3.2. 
PK Data Below the Limit of Quantification (BLQ) ...................................................32 
7.3.4. 
PD Data .......................................................................................................................32 
7.3.5. 
Definition of Baseline .................................................................................................32 
7.3.6. 
Analysis Day ...............................................................................................................33 
7.3.7. 
Analysis Visits ............................................................................................................33 
7.3.8. 
Handling of Early Termination Visit Information ......................................................33 
7.3.9. 
Pooling of Study Centers ............................................................................................33 
7.3.10. 
Coding Conventions for Events and Medications ......................................................34 
7.3.11. 
Analysis Software .......................................................................................................34 
7.3.12. 
Study Data ..................................................................................................................34 
7.4. 
Planned Study Analyses .............................................................................................35 
7.4.1. 
Statistical Summaries: Descriptive and Inferential .....................................................35 
7.4.2. 
Data Safety Monitoring Board (DSMB) .....................................................................36 
7.5. 
Analyses for Induction Period, 52-week Treatment Period, and Long-term 
Extension ....................................................................................................................36 
7.6. 
Multiple Testing Procedures .......................................................................................37 
8. 
BASELINE AND EXPOSURE SUMMARIES .........................................................38 
8.1. 
Subject Disposition .....................................................................................................38 
8.2. 
Protocol Deviations ....................................................................................................38 
8.3. 
Demographics and Baseline Disease Characteristics .................................................39 
8.4. 
Medical History ..........................................................................................................40 
8.5. 
Prior and Concomitant Medications ...........................................................................40 
8.6. 
Treatment Exposure and Compliance .........................................................................40 
8.6.1. 
Extent of Treatment Exposure ....................................................................................40 
8.6.2. 
Compliance .................................................................................................................41 
9. 
EFFICACY ANALYSIS ............................................................................................42 


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9.1. 
Efficacy Variable Overview .......................................................................................42 
9.1.1. 
Histologic Scores ........................................................................................................42 
9.1.1.1. 
Robarts Histopathology Index (RHI) Score ...............................................................42 
9.1.1.2. 
Nancy Index (NI) ........................................................................................................42 
9.1.1.3. 
Geboes Score ..............................................................................................................43 
9.1.2. 
Mayo Clinic Score (MCS) and Mayo Endoscopic Subscore (MES) ..........................43 
9.2. 
Primary Efficacy Endpoint Analysis ..........................................................................44 
9.2.1. 
Primary Analysis ........................................................................................................44 
9.2.2. 
Sensitivity Analysis ....................................................................................................45 
9.2.3. 
Subgroup Analysis ......................................................................................................45 
9.2.4. 
Other Analysis ............................................................................................................45 
9.3. 
Secondary Efficacy Endpoint Analyses ......................................................................46 
9.4. 
Exploratory Efficacy Endpoint Analyses ...................................................................46 
9.4.1. 
Clinical Endpoints ......................................................................................................46 
9.4.2. 
Other Exploratory Endpoints ......................................................................................48 
10. 
PHARMACOKINETIC ANALYSES ........................................................................49 
10.1. 
Collection of Blood Samples for MORF-057 Concentration Determination in 
Plasma .........................................................................................................................49 
10.2. 
General Considerations ...............................................................................................49 
10.3. 
Pharmacokinetic Analysis ..........................................................................................51 
11. 
PHARMACODYNAMIC ANALYSES .....................................................................54 
12. 
SAFETY ANALYSES ...............................................................................................55 
12.1. 
Adverse Events ...........................................................................................................55 
12.2. 
Clinical Laboratory Evaluations .................................................................................56 
12.3. 
Vital Signs ..................................................................................................................56 
12.4. 
ECG ............................................................................................................................57 
12.5. 
Physical Examinations ................................................................................................57 
12.6. 
Endoscopy ...................................................................................................................57 
12.7. 
Other Safety Measures ................................................................................................57 
13. 
REPORTING CONVENTIONS ................................................................................58 
13.1. 
General Reporting Conventions .................................................................................58 
13.2. 
Population Summary Conventions .............................................................................59 
APPENDIX 1 MAYO CLINIC SCORE (MCS) CALCULATION ..............................................60 


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LIST OF TABLES 
Table 1: Schedule of Activity (SOA) for the Treatment Period ....................................................19 
Table 2: Schedule of Activities for the Long-term Extension .......................................................24 
Table 3: Sampling Windows ..........................................................................................................49 
Table 4: Pharmacokinetic Parameters by Visit ..............................................................................51 
 
LIST OF FIGURES 
Figure 1 Study Schema ..................................................................................................................18 
Figure 2: SDTM, ADaM, and TFL Development and Validation .................................................35 
 
 
 




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Abbreviation or specialist term 
Explanation 
Cmax 
maximum observed plasma concentration post-dose 
Cmax,ss 
maximum observed plasma concentration post-dose at steady state 
CRF 
case report form 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
Ctrough 
trough plasma concentrations obtained at the end of the dosing 
interval (12 hours post-dose) 
CV 
coefficient of variation 
DSMB 
Data Safety Monitoring Board 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EOT 
 end of treatment 
FAS 
Full Analysis Set 
hs-CRP 
high sensitivity C reactive protein 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonization 
IRT 
Inventory and Resupply Technology 
Lambdaz (λz) 
apparent first-order terminal elimination phase rate constant 
LOCF 
last observation carried forward 
λz,f 
apparent functional first-order elimination phase rate constant 
LLOQ 
lower limit of quantification 
LS 
lymphocyte subsets 
MCS 
Mayo Clinic Score 
MedDRA 
Medical Dictionary for Regulatory Activities 
MES 
Mayo Endoscopic Subscore 
mRNA 
messenger ribonucleic acid 
NCA 
non-compartmental analysis 
NI 
Nancy Index 
PD 
pharmacodynamics 
PGA 
Physician’s Global Assessment 
PIMS 
physiological intermolecular modulation spectroscopy 
PK 
pharmacokinetics 


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Abbreviation or specialist term 
Explanation 
PML 
progressive multifocal leukoencephalopathy 
PO 
by mouth 
PP 
Per Protocol 
PT 
Preferred Term  
QTcF 
QT interval corrected using Fridericia’s formula 
RHI 
Robarts Histopathology Index 
RNA 
ribonucleic acid 
RO 
receptor occupancy 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 
SCR 
screening 
SD 
standard deviation 
SDTM 
Study Data Tabulation Model 
SFU 
safety follow-up 
SoA 
schedule of activity 
SOC 
system organ class  
t1/2 
apparent first-order terminal elimination half-life 
t1/2,f 
apparent functional first-order elimination half-life 
TB 
tuberculosis 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
TFL 
tables, figures, and listings 
tlast 
time of last measured concentration post-dose 
tmax 
time of maximum observed plasma concentration post-dose 
tmax,ss 
time of maximum observed plasma concentration post-dose at 
steady state 
UC 
ulcerative colitis 
ULN 
upper limit of normal 
UNS 
unscheduled 
Vz/F 
apparent volume of distribution during terminal phase after single 
dose oral administration or at steady state after oral administration 
WHODRUG 
World Health Organization Drug Dictionary 


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3. 
INTRODUCTION 
3.1. 
Preface 
This document presents a statistical analysis plan (SAP) for Morphic Therapeutic’s Study 
MORF-057-201 (A phase 2a, open-label, single arm, multicenter study to evaluate the efficacy, 
pharmacokinetics [PK], pharmacodynamics [PD], safety and tolerability of MORF-057 in adults 
with moderate or severe Ulcerative Colitis [UC] [EMERALD-1]). 
Reference materials for SAP version 1.0 (dated 17MAY2022)  includes the protocol amendment 
version 2 (dated 09FEB2022) and eCRF dated 25MAR2022. Reference materials for SAP 
version 2.0 (dated 20DEC2022) includes the protocol amendment version 3 (dated 01SEP2022). 
Reference material for this SAP amendment (SAP version 3.0) includes the protocol version 4 
(dated 27JUL2023). 
3.2. 
Scope of Analyses 
This SAP is to describe the statistical analysis methods and data presentation for all planned 
analyses. Results from the analyses specified in this SAP will be included in the final clinical 
study report (CSR) for Study MORF-057-201, and may also be utilized for regulatory 
submissions, manuscripts, or other clinical development activities. 
Ad-hoc, post-hoc exploratory analyses not identified in this SAP may be performed to further 
examine the study data. These analyses will be clearly described, in the final CSR if relevant. 
Additional analyses not prospectively identified in this SAP may also be completed for 
publications, regulatory or other inquiries. These analyses, if performed, may not be reported in 
the CSR, and will be reported in a separate document appropriately. 
3.3. 
Summary of Statistical Analysis Changes to the Protocol 
The following changes to the protocol amendment version 2 (dated 09FEB2022) have been made 
in the SAP version 1.0 (dated 17MAY2022): 
• Definition of analysis populations (Full Analysis Set [FAS], Per Protocol [PP] set, PK 
population, PK evaluable population, PD population) are modified by including the 
participants from both Main Cohort and Exploratory Cohort in Section 7.1. 
• It is further clarified in Section 7.1 that Safety Analysis Population will be used for 
the safety analysis, instead of using the FAS, even though they are the same. 
• It is clarified in Section 7.1 that the PP Set includes all participants in the FAS who 
do not have a major protocol deviation relevant to the primary and secondary efficacy 
endpoints analysis. 
• Additional exploratory analyses are added in Section 9.4.1 for the following 
variables: 
− Proportion of participants in clinical remission and clinical response at Weeks 12 
and 52 as determined using the Modified Mayo Clinic Score (MCS), 


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− Proportion of participants in MCS remission and MCS response at Weeks 12 and 
52 
− Proportion of participants with endoscopic improvement and endoscopic 
remission at Weeks 12 and 52 
− Proportion of participants with histologic remission at Weeks 12 and 52 as 
determined using the Robarts Histopathology Index (RHI) score. 
3.4. 
Summary of Changes to the Statistical Analysis Plan 
The following major changes to the SAP version 1.0 (dated 17MAY2022) have been made in the 
SAP version 2.0 (dated 20DEC2022): 
• Following the protocol amendment version 3 (dated 01SEP2022) 
− The planned interim analysis for sample size reassessment is removed. 
Accordingly, the statistical significance level to be used in the final analysis of the 
primary efficacy endpoint is adjusted to 0.05 (two-sided). 
− The analysis for Long-term Extension is added. 
• Corticosteroid use at baseline (yes/no) is added in the summary of baseline UC 
disease history. 
• Proportion of participants with NI score ≤1 at Week 12 is added in the exploratory 
analysis for the consistency with the protocol. 
• It is clarified that the summary of safety results will be based on the safety data 
during the on-Treatment Period, unless specified otherwise. 
• The definition of treatment-emergent adverse events is further clarified. 
• It is clarified that, for post baseline calculations of stool frequency and rectal bleeding 
subscores, the visit date or the date of Endoscopy procedure, whichever comes first, 
will be used as the reference date. 
The following major changes to the SAP version 2.0 (dated 20DEC2022) have been made in this 
SAP version 3.0: 
• Following the protocol amendment version 4 (dated 27JUL2023) 
− The analysis of the Induction Period for the Exploratory Cohort will be performed 
after all the participants in the Exploratory Cohort have completed the 12-week 
Induction Period (i.e., completed the Week 12 visit) or discontinued the study 
before the Week 12 assessment. The analysis of the 52-week Treatment Period for 
the Main Cohort will be performed after all the participants in the Main Cohort 
have completed the 52-week Treatment Period (and the Safety Follow-up Period 
for participants who did not enroll into the optional Long-term Extension) or 
discontinued from the study before the Week 52 assessment and the Safety 
Follow-up Period. In the event that the timing of the Induction Period analysis for 
the Exploratory Cohort aligns closely with the timing of the 52-week Treatment 
Period analysis for the Main Cohort, both analyses will be combined into one 
analysis. 


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• The below baseline summaries were added: 
− The number of advanced therapies received for UC 
− Categorized extent of disease 
• The following subgroup factor was added in the subgroup analysis: 
− Baseline MES score (2 vs 3).  
• Additional exploratory analyses are added in Section 9.4.1 for the following 
variables: 
− Proportion of participants with symptomatic remission, proportion of 
participants with partial MCS response, and  proportion of participants with 
partial MCS remission. 
− Proportion of participants in clinical remission at both Weeks 12 and 52, in 
clinical remission at Week 12 but not at Week 52, and in clinical remission at 
Week 52 but not at Week 12, as determined using the Modified MCS based 
on the central Endoscopy subscore 
• The re-allocation rules of early termination visit in Section 7.3.8 were further 
clarified.  
• The calculation of stool frequency subscore and rectal bleeding subscore at study 
visits with no Endoscopy procedure performed was further clarified in Appendix 1 
 
 
 
 
 
 
 


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4. 
STUDY OBJECTIVES AND ENDPOINTS 
4.1. 
Study Objectives 
4.1.1. 
Primary Objective 
• To evaluate the effects of MORF-057 on histologic improvement at Week 12. 
4.1.2. 
Secondary Objectives 
• To assess the safety and tolerability of MORF-057. 
• To evaluate the effect of MORF-057 on clinical improvement at Week 12. 
• To characterize the PK of MORF-057. 
4.1.3. 
Exploratory Objectives 
• To evaluate the effect of MORF-057 on histologic improvement at Weeks 6, 12, and 
52. 
• To evaluate the effect of MORF-057 on clinical improvement at Weeks 6, 12, and 52. 
• To assess the effect of MORF-057 on non-endoscopic biomarkers of inflammation. 
• To characterize the pharmacodynamics (PD) of MORF-057 in peripheral blood and 
mucosal tissue. 
• To characterize the effect of MORF-057 on microbiome parameters in stool, blood, 
and mucosal tissue. 
• To assess the long-term safety of MORF-057 and effects of MORF-057 on hs-CRP 
and fecal calprotectin levels 
4.2. 
Study Endpoints 
4.2.1. 
Primary Endpoint 
• Change from baseline to Week 12 in the RHI Score. 
4.2.2. 
Secondary Endpoints 
• Frequencies and proportions for treatment-emergent adverse events (TEAEs), 
treatment-emergent serious adverse events (TESAEs), and TEAEs leading to study 
drug discontinuation. 
• Change from baseline to Week 12 in the Modified MCS. Modified MCS is a 
composite of the following subscores: 
− Mayo endoscopic subscore (MES). 
− MCS stool frequency subscore. 
− MCS rectal bleeding subscore. 


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• MORF-057 concentration in plasma 
• Plasma PK parameters (AUC0-12, AUCtau, Cmax, Ctrough, tmax, C12). 
4.2.3. 
Exploratory Endpoints 
• Change from baseline to Weeks 6 and 52 in RHI Score. 
• Change from baseline to Weeks 6, 12, and 52 in the Nancy Index (NI). 
• Change from baseline to Weeks 6, 12, and 52 in the Continuous Geboes Score. 
• Change from baseline to Weeks 6 and 52 in the Modified MCS. Modified MCS is a 
composite of the following subscores: 
− MES. 
− MCS stool frequency subscore. 
− MCS rectal bleeding subscore. 
• Change from baseline to Weeks 6, 12, and 52 in the Full MCS. Full MCS is a 
composite of the following subscores: 
− MES. 
− MCS stool frequency subscore. 
− MCS rectal bleeding subscore. 
− MCS Physician’s Global Assessment (PGA). 
• Change from baseline to Weeks 2, 6, 12, 20, 28, 36, and 52 in high sensitivity C 
reactive protein (hs-CRP) levels. 
• Change from baseline to Weeks 2, 6, 12, 20, 28, 36, and 52 in fecal calprotectin 
levels. 
• PD of MORF-057 in peripheral blood and mucosal tissue. 
− α4β7 and α4β1 receptor occupancies (RO) in blood over time. 
− Change from baseline over time in blood C-C chemokine receptor 9 (CCR9) 
mRNA. 
− Change from baseline over time in blood lymphocyte subsets. 
− Blood and mucosal tissue gene and/or protein expression over time. 
• Microbiome parameters in stool, blood, and mucosal tissue 
− Microbiome composition in stool and mucosal tissue over time. 
− Changes in microbiome-derived metabolites in stool and blood over time. 
− Metatranscriptomic changes in the stool and mucosal tissue microbiome over 
time. 
 


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• Long-term Extension 
− Frequencies and proportions for TEAEs, TESAEs, and TEAEs leading to study 
drug discontinuation through Week 82 
− Change from baseline to Week 65 and Week 78 in hs-CRP levels 
− Change from baseline to Week 65 and Week 78 in fecal calprotectin levels 


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5. 
STUDY METHODS 
5.1. 
General Study Design and Plan 
The main part of this Phase 2a study will consist of three study periods: a Screening Period (up 
to 6 weeks), a Treatment Period (52 weeks, including a 12-week Induction Period and a 40-week 
Maintenance Period), and a Safety Follow-up Period (4 weeks). 
During the study, there will be approximately 11 scheduled study visits: Screening Visit(s) (Visit 
1 at Weeks -6 to -1), multiple Treatment Visits (Visits 2 to 10 at Weeks 0, 2, 6, 12, 20, 28, 36, 
44, and 52), and a Safety Follow-up Visit (visit to occur 4 weeks after the last dose of study drug 
is received, which will be Visit 11 at Week 56 if the full study is completed or earlier if treatment 
is discontinued early). 
Study Day 1 represents the first day of the Treatment Period (i.e., when the participant will 
receive the first dose of study drug). Participants will receive the same MORF-057 dosage 
(
 mg 
by mouth [PO]) for the full 52-week Treatment Period. 
All participants who complete the open-label Treatment Period will have the opportunity to 
continue their treatment in an optional 26-week Long-term Extension after completing the Week 
52 assessments. Participants who do not enroll into the Long-term Extension must complete the 
final Safety Follow-up Period for the main part of the study, including the Week 56 Visit (4 
weeks after receiving the last dose of MORF-057), for a maximum time on study of 62 weeks.  
Participants who choose to continue in the Long-term Extension will not complete the Safety 
Follow-up Period for the main part of the study; instead, they will directly enter the Long-term 
Extension.  
During the optional Long-term Extension, there will be 3 scheduled study visits: 2 Treatment 
Visits (Visits 10 to 11 at Weeks 52 and 65), and an End of Treatment Visit (Visit 12 at Week 
78). A Safety Follow-up Visit (4 weeks after the last dose of study drug is received), will be Visit 
13 (Week 82) if the full Long-term Extension is completed or earlier if treatment is discontinued 
before completing the study. Participants will continue to receive the same MORF-057 dosage 
(
 mg 
 PO) for the full 26-week extended Treatment Period. 
A study schema is provided below. 
 
 
 
 
 
 












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any time if the optional Week 6 sigmoidoscopy was not exercised. If the Week 6 optional sigmoidoscopy was exercised, a repeat sigmoidoscopy will be performed after the 28th 
day post Week 6 sigmoidoscopy. Participants who complete a sigmoidoscopy/colonoscopy within 12 weeks of the EOT visit are not required to repeat the procedure. If the 
procedure was performed further than 12 weeks, please consult the Sponsor Medical Monitor. 
jj Blood samples for hs-CRP analysis will be collected 
 on Visits 2-8 and Visit 10. 
kk 
 required on site for all visits. For Visits 2, 3, and 5, if optional PK/RO sampling will be performed at 
 must not be taken 
until PK/RO sampling is complete for that day. 
ll At Visit 10/EOT, participants will only receive an 
 will be provided. 
 
 




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g Stool collection kits are to be dispensed to participants at the visits indicated. The participant should use this kit to collect one sample at home within 24 hours before the next 
site visit. The sample should be frozen immediately and brought to the clinic on the day of the site visit. 
h A targeted physical exam is to be performed at all visits (see Protocol Section 8.8.1 for descriptions). For unscheduled visits, the type of exam will be at the Investigator’s 
discretion and determined based on the reason for the visit. 
i Vital signs to be recorded at all visits. These will include blood pressure, heart rate, respiratory rate, and temperature. 
j If the results of the questionnaire are suggestive of PML, a full neurological exam and, if indicated, additional testing are to be performed. 
k Blood samples for hematology, coagulation, and serum chemistry assessments will be collected 
 on Visits 11-12. 
l Record adverse events from the time the ICF for the Long-term Extension is signed. 
m Participants are to be contacted by phone as needed to monitor the status of the event. 
n Blood samples for hs-CRP analysis will be collected 
 on Visits 11-12. 
 
 


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5.2. 
Randomization and Blinding 
Not applicable. 




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7. 
GENERAL CONSIDERATIONS 
Descriptive statistics will be reported for all primary, secondary, and exploratory data. 
Categorical parameters will be reported using frequency and proportions, whereas continuous 
parameters will be reported using mean, standard deviation, median, minimum, and maximum 
unless otherwise specified. Data will be summarized/analyzed separately for the Main Cohort 
and Exploratory Cohort at scheduled visits unless stated otherwise. Data from participants in the 
Exploratory Cohort will be analyzed only for exploratory purposes. 
No hypothesis testing will be performed for the secondary and exploratory efficacy endpoints. 
No hypothesis testing will be performed on safety data. 
7.1. 
Analysis Populations 
There will be six (6) analysis populations defined for this study. 
7.1.1. 
Full Analysis Set (FAS) 
The FAS includes all enrolled participants in both the Main Cohort and Exploratory Cohort who 
received at least one dose of study drug. The FAS will be used for efficacy analyses. 
7.1.2. 
Per Protocol (PP) Set 
The PP Set includes all participants in the FAS who do not have a major protocol deviation 
relevant to the primary and secondary efficacy endpoints analysis. All decisions to exclude 
participants from the PP set will be made prior to the database lock of the study. 
The PP Set will be used for sensitivity analysis of the primary efficacy endpoint and maybe also 
for some other efficacy endpoints as appropriate. 
7.1.3. 
Safety Analysis Population 
Includes all participants in both the Main Cohort and Exploratory Cohort who received at least 
one dose of study drug. 
The Safety Analysis Population will be used for safety analysis. 
7.1.4. 
PK Population 
The PK Population includes all participants in the FAS and has adequate measurable 
concentrations to define Cmax or AUC. 
The PK Population will be used in the individual plasma concentration, PK parameter estimation 
listings, and individual figures. Plasma concentration-time data and PK parameters that are not 
summarized will be included in the listings and flagged. 


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7.1.5. 
PK Evaluable Population 
A PK Evaluable Population (a subset of the PK Population) will be used to determine the 
inclusion of a participant in the overall PK summaries. Participants included in this subset must 
have data that meet the following criteria: 
• Do not have any occurrence of emesis occurring within two times the median tmax of 
MORF-057 on Visits 2, 3, and 5 where non-compartmental analysis (NCA) are to be 
performed and are deemed to have an impact on the corresponding PK profile. 
Participants who experience emesis within two times the median tmax of MORF-057 
on the other visits where sparse PK sampling occurs will be evaluated on a case-by-
case basis. All emesis occurrences will be discussed with the Sponsor prior to any 
decisions for participant exclusions. 
• Do not use a concomitant medication which renders the concentration profile 
unreliable. 
• Do not have a quantifiable pre-dose concentration that is greater than 5% of the 
corresponding Cmax of Visit 2 Study Day 1; Participants with quantifiable pre-dose 
concentrations greater than 5% of their corresponding Cmax at Visit 2 Study Day 1 
will be evaluated on a case-by-case basis and discussed with the Sponsor to determine 
PK data inclusion in summaries. 
• Do not violate the protocol (major protocol violation) in a way that may invalidate or 
bias the results. 
• Do not have ≥ 2 consecutive missing plasma concentration values at Visit 2, 3, and 5. 
This will be evaluated on a case-by-case basis and discussed with the Sponsor to 
determine the impact of the missing data to the overall PK profile and PK parameter 
estimation. For all other visits where sparse sampling occurs, all available data will be 
included in the relevant summaries if all the other above criteria are met. 
The PK Evaluable Population will be included in the summaries of plasma concentration-time 
data (for all visits where PK samples are available), NCA PK parameter estimation (for Visits 2, 
3, and 5), and mean concentration-time figures (for all visits where PK samples are available). 
7.1.6. 
PD Population 
The PD population is defined as all participants in the FAS who have at least one measurable 
post-dose PD measurement and its corresponding pre-dose PD measurement for, at minimum, 1 
of the PD biomarkers. This population will be used for the summarization of PD (exploratory) 
endpoints. 
7.2. 
Covariates and Subgroups 
7.2.1. 
Planned Covariates 
No covariates are planned to be used in any analyses. 


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7.2.2. 
Planned Subgroups 
The subgroup analyses for the primary efficacy endpoints will be performed as specified in 
Section 9.2.3. 
7.3. 
Management of Analysis Data 
7.3.1. 
Unscheduled Visits 
Unscheduled visit measurements will not be included in the by visit summaries but will be 
included in the shift tables (mapped to the nearest post baseline scheduled visit) for safety 
parameters where the worst/most conservative result will be used. 
The determination of baseline values will be based on all measurements from both scheduled and 
unscheduled visits. 
In the sensitivity analysis of the primary efficacy endpoint, the last observation carried forward 
(LOCF) method will be used. All measurements from both scheduled and unscheduled visits will 
be used to determine the endpoint value at Week 12. 
All visits, scheduled or otherwise, will be provided in data listings. 
7.3.2. 
Missing Data 
Unless otherwise specified, there will be no substitutions made to accommodate missing data 
points. All data recorded on the CRF will be included in data listings that will accompany the 
CSR. 
7.3.2.1. 
Handling of Missing Date Values 
Partial or Missing Dates 
For partial UC diagnosis dates, the following imputation methods will be applied: 
• If month and year are present but day is missing, then the day will be set to the first 
day of the month 
• If year is present but not month and day, month and day will be set to January 1st 
The following conventions will be used to impute missing portions of dates for adverse events 
(AEs) and concomitant medications, if warranted. Note that the imputed values outlined here 
may not always provide the most conservative date. In those circumstances, the imputed value 
may be replaced by a date that will lead to a more conservative analysis. 
 
A. Start Dates 
1) If the year is unknown, then the date will not be imputed and will be assigned a 
missing value. 


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2) If the month is unknown, then: 
i) If the year matches the first dose date year, then impute the month and day of the 
first dose date. 
ii) Otherwise, assign ‘January.’ 
3)  If the day is unknown, then: 
i) If the month and year match the first dose date month and year, then impute the 
day of the first dose date. 
ii) Otherwise, assign the first day of the month. 
B. Stop Dates 
1) If the year is unknown, then the date will not be imputed and will be assigned a 
missing value. 
2) If the month is unknown, then assign ‘December.’ 
3) If the day is unknown, then assign the last day of the month. 
4) If imputed date is after end of study date, then end of study date will be used. 
7.3.2.2. 
Imputation Methods 
Unless otherwise specified, observed cases, without imputation, will be used for the analyses. 
The LOCF method will be used to impute the missing endpoint data at Week 12 for the 
sensitivity analysis of the primary efficacy endpoint. 
7.3.2.2.1. Adverse Events 
If the relationship of an AE is missing, it will be summarized as treatment-related. 
7.3.3. 
Handling Rule for PK 
7.3.3.1. 
PK Concentrations 
For Visits 2 (Day 1), 3 (Week 2), and 5 (Week 12) only: 
Actual sampling time points relative to dosing will be used for the estimation of NCA PK 
parameters from plasma data. If the actual sampling time is missing, but a valid concentration 
value has been measured, the concentration value will be flagged, and the nominal time point 
will be used for the calculation of PK parameters. 
In cases of missing pre-dose concentrations for the first dose at Visit 2 (Day 1), the missing 
concentration will be assumed as zero for the calculation of AUC. In cases of missing pre-dose 
concentrations at Visit 3 and Visit 5, the Ctrough or the minimum observed concentration during 
the dosing interval (if the Ctrough is missing) will be used as pre-dose concentration values for the 
calculation of AUC. For all other visits, the missing data will not be imputed. 


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For all visits with PK samples available: 
Actual sampling time points relative to dosing will be reported along with the nominal time 
point. 
7.3.3.2. 
PK Data Below the Limit of Quantification (BLQ) 
The following rules will be used to handle BLQ for the NCA PK parameter calculation (Visits 2, 
3, and 5) and individual concentration data (for all visits with PK samples collected): 
Plasma concentration values collected at Visits 2, 3, and 5 that are BLQ will be imputed as 
follows for PK parameter calculation via NCA: 
• BLQ values at time points prior to any measurable plasma concentration for the first 
dose or at time points immediately prior to dosing for multiple doses are imputed as 0 
concentration. 
• Any other BLQ values are set to missing. 
• If two BLQ values occur in succession after tmax, the profile is deemed to have 
terminated at the first BLQ value and any subsequent concentrations are omitted 
(until the next dosing event occurs) from PK calculations and individual plots. 
The following general rules will be applied for the concentration data summaries for all visits 
(including tabulation and plotting): 
• Mean concentrations at any individual time point will only be calculated if at least 
half of the participants have valid values (i.e., quantifiable, and not missing) at this 
time point. 
• In cases where a mean value is not calculated, due to the above criterion not being 
met, the mean value will be set to missing for mean plotting purposes. 
BLQ will be set to zero for the calculation of these mean values for Visit 1 (Day 1 only). BLQs 
at pre-dose for all other subsequent dosing days or before the last quantifiable measurement will 
be imputed as lower limit of quantification (LLOQ). 
7.3.4. 
PD Data 
Missing PD data will not be imputed. 
7.3.5. 
Definition of Baseline 
Baseline for non-PK measures is defined as the last non-missing measurement before the first 
dose. 


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7.3.6. 
Analysis Day 
Analysis day will be calculated from the date of the first dose of study drug. The day of the first 
dose of study drug will be Day 1, and the day immediately before Day 1 will be Day -1. There 
will be no Day 0 in this study. 
The following conventions will be used to calculate Study Day for reporting purposes: 
• Study Day = date of measurement – first dose date +1 if date of measurement is on or 
after the first dose date. 
• Study Day = date of measurement – first dose date if date of measurement is prior to 
the first dose date. 
7.3.7. 
Analysis Visits 
No analysis visit windows will be defined unless otherwise specified, i.e., the nominal visits/time 
points will be used for all statistical summaries/analyses, except for those defined in Section 
7.3.1. 
7.3.8. 
Handling of Early Termination Visit Information 
If a participant is terminated early from this study, he/she will be encouraged to complete the 
EOT Visit at the time of study drug discontinuation and the Safety Follow-up Visit. In summary 
tables and statistical tests, all efficacy and safety parameters measured at the EOT Visit will be 
re-allocated according to the following rules: 
• If the assessment date for a given parameter at the EOT Visit is closer to the previous 
scheduled study visit date and this parameter is scheduled to be measured at that visit 
but there is no measurement, the EOT Visit for this parameter will be re-allocated to 
the previous scheduled study visit. 
• If the assessment date for a given parameter at the EOT Visit is closer to the next 
scheduled study visit date and this parameter is scheduled to be measured at that visit 
but there is no measurement, the EOT Visit for this parameter will be re-allocated to 
the next scheduled study visit. 
• Otherwise, the EOT Visit will remain unassigned to a nominal visit. 
The above re-allocation of the EOT Visit will be performed for each efficacy and safety 
parameter based on its individual scheduled visits in the protocol. Please see Table 1 and Table 2 
for the scheduled visits for each parameter to be measured. 
7.3.9. 
Pooling of Study Centers 
Study centers will be pooled for all analyses, unless otherwise specified. 


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7.3.10. 
Coding Conventions for Events and Medications 
All adverse events, and medical history will be mapped to the Medical Dictionary for Regulatory 
Activities (MedDRA) using the version in effect at the time of database lock and Common 
Terminology Criteria for Adverse Events (CTCAE Version 5.0 or later) systems for reporting 
(preferred term and body system). 
Prior and concomitant medications will be coded using World Health Organization – Drug 
Dictionary (WHO-DD) based on the version in effect at the time of database lock. 
7.3.11. 
Analysis Software 
Data manipulation, tabulation of descriptive statistics, calculation of inferential statistics, and 
graphical representations will be performed primarily using SAS (release 9.4 or higher) for 
Windows. If the use of other software is warranted, the final CSR will detail what software was 
used and for what purposes. 
All NCA parameterization will be performed using a validated software, Phoenix® WinNonlin® 
Version 8.3 (Certara, USA). 
7.3.12. 
Study Data 
All study data will be formulated into regulatory compliant data sets to provide transparency, 
traceability, and integrity of trial analysis results from the collection source. Observed study data 
will be mapped to the Clinical Data Interchange Standards Consortium (CDISC) Study Data 
Tabulation Model (SDTM) and serve as the source data from the trial. All study analyses will be 
completed using analysis data sets that are derived from the SDTM and follow the CDISC 
Analysis Data Model (ADaM) architecture. All planned analyses will be performed using the 
ADaM data sets developed for this study. 
The methods for programming the CDISC SDTM and ADaM data sets are described in Figure 2. 




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Expansion of descriptive table categories within each treatment may occur if such elaborations 
are thought to be useful. 
For the summary statistics of all numerical variables unless otherwise specified, minimum and 
maximum will be displayed to the same level of precision as reported. Data not subject to 
analysis according to this plan will not appear in any tables or figures but will be included in the 
data listings as appropriate. 
7.4.2. 
Data Safety Monitoring Board (DSMB) 
A DSMB will be monitoring the safety throughout the study. Details about the frequency and 
content of the reporting will be specified in the DSMB Charter. 
7.5. 
Analyses for Induction Period, 52-week Treatment Period, and 
Long-term Extension 
The study open-label Treatment Period includes 2 parts: the 12-week Induction Period and the 
40-week Maintenance Period. For statistical analyses, the Induction Period and the Maintenance 
Period will be treated as 2 independent parts. There will be 4 analyses planned: two for the 12-
week Induction Period of the Main Cohort and Exploratory Cohort respectively (i.e., the period 
for the primary efficacy endpoint) and the other two for the 52-week Treatment Period of the 
Main Cohort and Exploratory Cohort respectively (the 12-week Induction Period plus the 40-
week Maintenance Period and the Safety Follow-up Period). Additional analysis of the optional 
Long-term Extension Treatment Period for the participants enrolled into the Long-term 
Extension will be performed as appropriate. 
The analysis of the Induction Period is to evaluate the efficacy and safety during the 12-week 
Induction Period. The analysis of the 52-week Treatment Period is to use the cumulative 
combining data from both Induction and Maintenance Periods plus the Safety Follow-up Period. 
Induction Period Analysis 
The analysis of the Induction Period for the Main Cohort will be performed after all the 
participants in the Main Cohort have completed the 12-week Induction Period (i.e., completed 
the Week 12 visit or discontinued the study before the Week 12 assessment). The analysis will 
formally evaluate the primary and secondary efficacy endpoints, all the exploratory endpoints 
defined by Week 12, PK concentration and parameters, PD parameters (α4β7 and α4β1 RO, and 
safety of MORF-057 for the Main Cohort during the 12-week Induction Period.  
The analysis of the Induction Period for the Exploratory Cohort will be performed after all the 
participants in the Exploratory Cohort have completed the 12-week Induction Period (i.e., 
completed the Week 12 visit) or discontinued the study before the Week 12 assessment. The 
analysis will evaluate all the efficacy and exploratory endpoints, PK concentrations and 
parameters, and safety of MORF-057 for the Exploratory Cohort during the 12-week Induction 
Period. In the event that the timing of the Induction Period analysis for the Exploratory Cohort 


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aligns closely with the timing of the 52-week Treatment Period analysis for the Main Cohort 
described below, both analyses will be combined into one analysis. 
Only Induction Period data will be used in this analysis. The disposition, demographics and 
baseline disease characteristics, concomitant medication, and treatment exposure during the 
Induction Period, will also be presented. 
52-week Treatment Period Analysis 
For the Main Cohort, the analysis of the 52-week Treatment Period will be performed after all 
the participants have completed the 52-week open-label Treatment Period (and the Safety 
Follow-up Period for participants who did not enroll into the optional Long-term Extension) or 
discontinued from the study before the Week 52 assessment and the Safety Follow-up Period. In 
the event that the timing of the 52-week Treatment Period analysis for the Main Cohort aligns 
closely with the timing of the Induction Period analysis for the Exploratory Cohort, both 
analyses will be combined into one analysis. 
For the Exploratory Cohort, the analysis of the 52-week Treatment Period will be performed 
after all the participants have completed the 52-week open-label Treatment Period (and the 
Safety Follow-up Period for participants not enrolling into the optional Long-term Extension 
Period) or discontinued the study before the Week 52 assessment and the Safety Follow-up 
Period. 
The 52-Week Treatment Period analyses will formally evaluate all the exploratory efficacy 
endpoints defined by Week 52, PK concentration and parameters, PD parameters, and safety of 
MORF-057 during the 52-week Treatment Period and the Safety Follow-up Period. The 
cumulative data including those from the Induction Period will be used in these analyses. The 
analysis will include all the results to report in the CSR.  
The data from the Main and Exploratory Cohorts may be pooled together in the safety analyses 
as appropriate.  
Long-term Extension Analysis 
The analysis of the Long-term Extension will be performed after all the participants enrolled into 
the Long-term Extension have completed the 26-week extended Treatment Period and the Safety 
Follow-up Period or discontinued the study before the Week 78 assessment. The analysis will 
formally evaluate the safety of MORF-057 and selected efficacy endpoints as appropriate during 
the Long-term Extension plus the Safety Follow-up Period. The results for the Long-term 
Extension may be reported in a CSR Addendum. 
7.6. 
Multiple Testing Procedures 
There will be no multiplicity adjustment. 


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8. 
BASELINE AND EXPOSURE SUMMARIES 
Unless otherwise specified, all study data from enrolled participants will be listed. Exploratory 
Cohort data will be listed in the same listings as the Main Cohort. In the summary tables, the 
Main Cohort, Exploratory Cohort, and total (Main + Exploratory) will be presented in separate 
columns of the same tables, unless otherwise specified.  
8.1. 
Subject Disposition 
The number and percentage of participants will be summarized for the following categories: 
• Participants screened 
• Participants screen failed 
• Participants enrolled 
• Participants completed the 12-week Induction Period 
• Participants discontinued the treatment during the 12-week Induction Period and 
reasons for treatment discontinuation 
• Participants completed the 52-week total Treatment Period 
• Participants discontinued the treatment during the 52-week total Treatment Period 
and reasons for treatment discontinuation 
• Participants discontinued the study and reasons for study discontinuation 
• Participants enrolled into the Long-term Extension 
− Participants completed the Long-term Extension. 
− Participants discontinued the treatment during the Long-term Extension and 
reasons for treatment discontinuation. 
For the screened, and screen failure, percentages will be calculated using the number of screened 
participants as the denominator. Percentages for all other categories of participants will be 
calculated using the number of participants enrolled as the denominator. Disposition data will 
also be presented in a listing. 
Additionally, the analysis populations for FAS, PP, PK, PK evaluable, PD, and safety defined in 
Section 7.1 will be summarized in a table by number of participants on the enrolled population. 
Reasons for screen failure will also be summarized. 
8.2. 
Protocol Deviations 
Deviations from the protocol will be recorded appropriately. Classification of deviations as 
major protocol deviations, and decisions regarding exclusion of participants and/or participant 
data from the statistical analyses, will be decided by the study team before the database lock. All 


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major protocol deviations will be presented in a summary table by deviation category for FAS as 
appropriate and is provided in a data listing. 
8.3. 
Demographics and Baseline Disease Characteristics 
Demographic data and baseline characteristics (including age (years), age category [< 65, ≥ 65], 
sex, childbearing potential, ethnicity, race, height (cm), weight (kg) and body mass index (BMI) 
(kg/m2), country, substance use) will be summarized descriptively for the FAS and PP 
populations. 
The following baseline UC disease history parameters will be summarized using descriptive 
statistics based on the FAS and PP populations: 
• Age at UC diagnosis (years), calculated as (year of UC diagnosis – year of birthday) 
• Years since UC diagnosis, calculated as integer of (informed consent date – UC initial 
diagnosis date)/365.25 
• Previous use of advanced therapy for UC (naïve vs experienced) 
• Number of advanced therapies received for UC (1,  2,  and ≥3) 
• Corticosteroid use at baseline (yes/no) 
• Modified MCS at baseline (using the central Endoscopy subscore) 
• Modified Mayo Clinic Score at baseline (using the Investigator Endoscopy subscore) 
• Full Mayo Clinic Score at baseline (using the central Endoscopy subscore) 
• Full Mayo Clinic Score at baseline (using the Investigator Endoscopy subscore) 
• Mayo component scores at baseline (stool frequency, rectal bleeding, PGA, 
Investigator Endoscopy subscore, central Endoscopy subscore) 
• Robarts Histopathology Index (RHI) Score at baseline 
• Family history of UC (yes/no) 
• Family history of Chron’s Disease (CD) (yes/no) 
• Has participant previously been in remission from UC (yes/no) 
• Extent of disease by Endoscopy assessment (cm) 
• Categorized extent of disease by Endoscopy assessment (cm)  
− Proctosigmoiditis (0 ≤ extent of disease ≤ 30) 
− Left sided colitis (30 < extent of disease ≤ 50) 
− Extensive colitis (extent of disease > 50) 


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8.4. 
Medical History 
Medical and surgical history will be coded using the MedDRA Version effective at the time of 
database lock. Medical history will be summarized by SOC and PT for the Safety Analysis 
Population. 
8.5. 
Prior and Concomitant Medications 
The number and percentages of participants with at least one prior medication will be 
summarized by Anatomical Therapeutic Chemical (ATC) level 4 and PT using the Safety 
Analysis Population. Number and percentage of participants with at least one concomitant 
medication will also be summarized by ATC level 4 and PT. 
A concomitant medication is defined as any medication taken between the first dose date and the 
last dose date (inclusive). A prior medication is defined as any medication that starts prior to the 
first dose of study drug. Medications still ongoing at first dose date or missing stopping date will 
be considered as both prior and concomitant medications. 
Prior UC medications will be summarized separately in the same manner as other prior and 
concomitant medications. 
8.6. 
Treatment Exposure and Compliance 
For exposure and compliance, Main and Exploratory Cohorts are presented in the same listing 
and summary tables. In the summary table, total (Main + Exploratory) will also be presented as a 
column. Study drug (
 mg capsules) will be tracked in the IRT system by pill count of 
dispensation and return, as well as using a patient diary. The pill count results from IRT will be 
the primary source of calculating treatment exposure and compliance. 
Treatment exposure and compliance will be calculated and summarized for the Safety Analysis 
Set for the following time periods: 
• 12-week Induction Period: Day 1 to Week 12 visit. 
• 52-week Treatment Period: the 52-week Open-label Treatment Period (the 12-week 
Induction Period + the 40-week Maintenance Period). 
• 52-week Treatment Period plus Long-term Extension. 
8.6.1. 
Extent of Treatment Exposure 
The extent of treatment exposure will be assessed by the duration of treatment exposure, which 
will be defined as the total number of days a participant is exposed to any study drug, regardless 
of unplanned intermittent discontinuations. For the time Period defined in Section 8.6, the 
duration of treatment exposure will be calculated as the total number of days from the first dose 
date (Study Day 1) to the last dose date in the given time period. 


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• For the 12-week Induction Period, the last dose date will be Week 12 visit date if the 
participant has completed Week 12 visit, or to the last dose date as recorded on the 
EOT eCRF if the participant has discontinued the treatment prematurely before Week 
12 visit.  
• For the 52-week Treatment Period, the last dose date will be the last dose date as 
recorded on the EOT eCRF, or to Week 52 visit date if the participants have enrolled 
into the Long-term Extension.  
• For the 52-week Treatment Period plus Long-term Extension, the last dose date will 
be the last dose date as recorded on the EOT eCRF. 
Duration of treatment exposure (days) will be summarized using continuous descriptive 
statistics, and summarized categorically by counts and percentage of participants for each of the 
following categories and cumulatively according to these categories: 
• 1 to 42 days 
• 43 to 84 days 
• 85 to 182 days 
• 183 to 252 days 
• 253 to 364 days 
• 365 to 546 days 
• >546 days 
8.6.2. 
Compliance 
Compliance is calculated using the formula below. 
Compliance rate (%) = 
𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇 𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛 𝑜𝑜𝑜𝑜 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 
𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇 𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛 𝑜𝑜𝑜𝑜 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑥𝑥100% 
Total number of capsules expected = 
 
The compliance rate will be summarized using continuous descriptive statistics. The number and 
percentage of participants in the following compliance rate categories will be reported: < 50%, 
50-59%, 60-69%, 70- 79%, 80-100%, > 100%,  and < 80%, >120%. 
Amount of study drug taken according to pill count based on the IRT and number of days 
between visits will be listed for reference. 


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9. 
EFFICACY ANALYSIS 
Unless otherwise specified, all results for enrolled participants in the main and Exploratory 
Cohort will be listed. 
Efficacy will be summarized for the Main Cohort. If the Exploratory Cohort has enough number 
of participants, data from Exploratory Cohort will also be summarized. 
Descriptive statistics will be reported for all primary, secondary, and exploratory data if 
applicable. No hypothesis testing will be performed for the secondary and exploratory efficacy 
endpoints. 
9.1. 
Efficacy Variable Overview 
Endoscopy will be performed at Screening (Visit 1) and Week 6 (optional), Week 12, Week 52 
or EOT visit. 
Biopsy samples will be processed by a central laboratory. The histologic endpoints RHI Score, 
Continuous Geboes Score, and NI will be scored centrally. 
The MES will be scored both locally and centrally. If there is a disagreement between the local 
and central scoring, a second central reader (adjudicator), who will be blinded to knowing if the 
score is local or central, will select either the local reader or first central reader score to be used 
as the final score (forced adjudication). 
9.1.1. 
Histologic Scores 
Histological improvement will be assessed with the RHI Score, NI, and Continuous Geboes 
Score 
9.1.1.1. 
Robarts Histopathology Index (RHI) Score 
The RHI Score is a weighted sum of 4 histologic items: chronic inflammatory infiltrate score (0-
3), lamina propria neutrophils score (0-3), neutrophils in epithelium score (0-3), and erosion or 
ulceration score (0-3). 
Total score will be calculated by an adjudicator. The score ranges from 0 to 33. 
9.1.1.2. 
Nancy Index (NI) 
The NI is determined by evaluating 3 histological items: ulceration (0 or 2), acute inflammatory 
cells infiltrate (0-3), and chronic inflammatory infiltrate (0-4). An overall grade is 0-4, 
adjudicated based on the subscores. 


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9.1.1.3. 
Geboes Score 
For the Geboes Score, the microscopic appearance of the mucosa is categorized into 6 grades: 
structural change only (Grade 0), chronic inflammation (Grade 1), lamina propria neutrophils 
(Grade 2), neutrophils in epithelium (Grade 3), crypt destruction (Grade 4), and erosions or 
ulcers (Grade 5). 
Each of these grades has 4 to 5 sub-grades. The continuous Geboes Score is calculated by adding 
up the numerical values of the different subscores, yielding a final value between 0 and 22. 
9.1.2. 
Mayo Clinic Score (MCS) and Mayo Endoscopic Subscore (MES) 
The Full MCS (0 to 12) and Modified MCS (0 to 9) will be used to assess clinical improvement. 
With higher scores indicating more severe disease. The Full MCS is a composite of the following 
subscores: MES, MCS stool frequency subscore, MCS rectal bleeding subscore, and the PGA. 
The Modified MCS is a composite of the following subscores: MES, MCS stool frequency 
subscore, and MCS rectal bleeding subscore. Each subscore of the Full MCS and Modified MCS 
is described below; the subscores will be calculated at the timepoints shown in Table 1. Method 
of calculation is described in Appendix 1. 
Stool frequency: Each participant serves as his or her own control to establish the degree of 
abnormality of the stool frequency. 
• 0=Normal number of stools for this participant 
• 1=1 to 2 stools more than normal 
• 2=3 to 4 stools more than normal 
• 3=5 or more stools more than normal 
Subscore: 0 to 3 
Rectal bleeding: The daily bleeding score represents the most severe bleeding of the day. 
• 0=No blood seen 
• 1=Streaks of blood with stool less than half the time 
• 2=Obvious blood (more than just streaks) or streaks of blood with stool most of the 
time 
• 3=Blood alone passed 
Subscore: 0 to 3 
Endoscopy: The Endoscopy subscore will be determined both locally and centrally by qualified 
personnel. 
• 0=Normal or inactive disease 


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• 1=Mild disease (erythema, decreased vascular pattern, no friability) 
• 2=Moderate disease (marked erythema, lack of vascular pattern, friability, erosions) 
• 3=Severe disease (spontaneous bleeding, ulceration) 
Subscore: 0 to 3 
Physician’s Global Assessment: The PGA acknowledges the 3 other criteria, the participant’s 
daily recollection of abdominal discomfort and general sense of well-being, and other 
observations, such as physical findings and the participant’s performance status. 
• 0=Normal 
• 1=Mild disease 
• 2=Moderate disease 
• 3=Severe disease 
Subscore: 0 to 3 
9.2. 
Primary Efficacy Endpoint Analysis 
The primary efficacy endpoint for this study is change from baseline to Week 12 in RHI Score, 
which will be tested using the FAS. 
The statistical hypotheses for the primary efficacy endpoint are: 
• Null hypothesis (H0): there is no reduction from baseline to Week 12 in RHI Score 
• Alternative hypothesis (Ha): the reduction from baseline to Week 12 in RHI Score is 
larger than zero 
9.2.1. 
Primary Analysis 
The data for the primary efficacy endpoint will be assessed for normality using Shapiro-Wilk 
test. If the data are normally distributed (p ≥ 0.05), then a two-sided one sample t-test at the 
alpha = 0.05 will be used for the analysis of the change from baseline in RHI Score (week 12 – 
baseline). A histogram with a normal bell curve will be produced. If the data are not normally 
distributed, then a two-sided Wilcoxon signed rank test at the alpha = 0.05 will be used for the 
analysis. The Wilcoxon signed rank test is to test whether the median of change from baseline 
deviates from 0 significantly. The p-values will be calculated. 
The procedure will be based on the following SAS code sample. 
proc univariate data=rhi normaltest alpha=0.05; 
var rhi_change_from_baseline; 
run; 


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Summary statistics (including n, mean, SD, median, 25th and 75th percentiles, minimum and 
maximum) will be provided for RHI Score at baseline, Week 12, and change from baseline to 
Week 12. The 95% CI will be provided for the mean change from baseline assuming that the 
data are normally distributed. 
In the primary analysis, the participants who do not have the RHI Score at the baseline or at 
Week 12 will be excluded. 
9.2.2. 
Sensitivity Analysis 
A sensitivity analysis will be performed to include the participants who have the missing RHI 
Score at Week 12 by imputing the missing endpoint data at Week 12 using the last available post 
baseline observation carried forward (LOCF) method. If participants do not have any non-
missing post baseline measurement, the missing RHI Score at Week 12 will be imputed using the 
baseline values. 
Sensitivity analysis of the primary efficacy endpoint will also be performed using the PP 
Population. 
9.2.3. 
Subgroup Analysis 
Descriptive analyses will be performed on the primary endpoint across subgroups defined by the 
following baseline or Screening factors: 
• Age group (< 65, ≥ 65) 
• Sex (male, female) 
• Race (white, non-white) 
• Previous use of advanced treatment for UC (naïve vs experienced) 
• Corticosteroid use at baseline (yes/no) 
• Baseline MES score (2 or 3) 
Summary statistics (n, mean, SD, minimum, median, and maximum) using observe cases will be 
provided for RHI Score at baseline, Week 12, and change from baseline to Week 12 across the 
subgroups defined by each of the factors above. The 95% CI will be provided for the mean 
change from baseline assuming that the data are normally distributed  
9.2.4. 
Other Analysis 
In addition, the proportion of participants in the FAS with a change from baseline to Week 12 in 
RHI Score that is at least -7 (that is, a reduction ≥7) and the proportion of participants with at 
least a 50% reduction in RHI Score from baseline to Week 12 will be provided. The 95% CI will 
also be provided using the normal approximation method.  


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9.3. 
Secondary Efficacy Endpoint Analyses 
Change from baseline to Week 12 in the Modified MCS (defined in Section 9.1.2) will be 
analyzed similarly to the primary efficacy endpoint using the FAS. The analysis will be 
performed for the Modified MCS using the central Endoscopy subscore. Descriptive summary 
statistics (n, mean, SD, median, 25th and 75th percentiles, minimum, and maximum) will be 
provided for the Modified MCS at baseline, Week 12, and change from baseline to Week 12. 
The 95% CI will be provided for the mean change from baseline assuming that the data are 
normally distributed. Participants who do not have the Modified MCS values at the baseline or at 
Week 12 will be excluded. No hypothesis testing will be performed for the secondary efficacy 
endpoint. 
Similarly, sensitivity analysis will also be performed for the Modified MCS using the 
Investigator Endoscopy subscore for FAS. 
9.4. 
Exploratory Efficacy Endpoint Analyses 
9.4.1. 
Clinical Endpoints 
The following exploratory efficacy endpoints will be summarized descriptively: 
• Change from baseline to Weeks 6 and 52 in RHI Score. 
• Change from baseline to Weeks 6, 12, and 52 in the Nancy Index (NI). 
• Change from baseline to Weeks 6, 12, and 52 in the Continuous Geboes Score. 
• Change from baseline to Weeks 6 and 52 in the Modified MCS. 
• Change from baseline to Weeks 6, 12, and 52 in the Full MCS. 
The summary will include the number of participants (n), mean, SD, median, 25th and 75th 
percentiles, minimum, and maximum for baseline values, observed values and observed changes 
from baseline at scheduled visits (Weeks 6, 12, and 52). The 95% CI will be provided for the 
mean change from baseline assuming that the data are normally distributed. 
Line plots showing mean values (± SD) at each of the scheduled visits of each clinical efficacy 
endpoints will be presented. 
Similarly, the Modified/Full MCS, both the scores using the central Endoscopy subscore and 
using the Investigator Endoscopy subscore will be summarized. 
Additional exploratory summaries will be provided for the following variables, with 95% CI 
provided using the normal approximation method: 
• Proportion of participants in clinical remission and clinical response at Weeks 12 and 
52 as determined using the Modified MCS based on the central Endoscopy subscore. 
− Clinical remission is defined as: rectal bleeding subscore of 0; a stool frequency 
subscore of ≤1; and an MES of ≤1 without friability. 


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− Clinical response is defined as: decrease from baseline in the mMCS ≥2 points 
and ≥30% from baseline, plus a decrease in rectal bleeding subscore ≥1 or an 
absolute rectal bleeding subscore ≤1. 
• Proportion of participants in MCS remission and MCS response at Weeks 12 and 52 
based on the central Endoscopy subscore. 
− MCS remission is defined as MCS ≤ 2 and no subscore higher than 1. 
− MCS response is defined as decrease in MCS by ≥3 points and ≥ 30% from 
baseline, plus a decrease in rectal bleeding score ≥ 1 or an absolute rectal bleeding 
score ≤ 1. 
• Proportion of participants with endoscopic improvement and endoscopic remission at 
Weeks 12 and 52 as determined using the MES by central reading. 
− Endoscopic improvement is defined as MES ≤ 1. 
− Endoscopic remission is defined as MES = 0. 
• Proportion of participants with histologic remission at Weeks 12 and 52 as 
determined using the RHI Score. 
− Histologic remission by RHI is defined as: RHI ≤ 3 (with 0 for lamina propria 
neutrophils score and neutrophils in the epithelium score and without ulcers or 
erosions). 
• Proportion of participants with NI score ≤1 at Week 12. 
• Proportion of participants in clinical remission at both Weeks 12 and 52, in clinical 
remission at Week 12 but not at Week 52, and in clinical remission at Week 52 but 
not at Week 12, as determined using the Modified MCS based on the central 
Endoscopy subscore. 
In the above additional exploratory summaries, participants with missing data at Week 12 or 52 
will be considered as non-responders in the corresponding summaries. All the summaries will be 
provided for the overall group, by previous use of advanced treatment for UC (naïve vs 
experienced), and by baseline MES score (2 vs 3). 
In addition, the proportion of participants with symptomatic remission, the proportion of 
participants with partial MCS response, the proportion of participants with partial MCS 
remission will be summarized at each scheduled visit up to Week 52, including the 95% CI. 
Partial MCS is the sum of stool frequency subscore, rectal bleeding subscore, and PGA. The 
definitions of symptomatic remission, partial MCS response, and partial MCS remission are:  
• Symptomatic remission: stool frequency subscore = 0 (or = 1 with ≥ 1 point decrease 
from baseline) and rectal bleeding subscore = 0  
• Partial MCS response: Decrease in partial MCS ≥2 points and ≥ 30% from baseline, 
plus a decrease in rectal bleeding subscore ≥1 or an absolute rectal bleeding subscore 
≤1. 


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• Partial MCS remission: partial MCS ≤ 2 points and no individual subscore >1 point. 
The calculations of stool frequency subscore and rectal bleeding subscore at each study visit will 
follow the approach described in Appendix 1 . The proportions of symptomatic remission, partial 
MCS response and partial MCS remission will be summarized using the following two 
approaches: 
• All enrolled: at each visit, the proportions will be calculated using the number of all 
participants in the FAS as the denominator, and participants with missing data will be 
considered as non-responders. 
• As observed: at each visit, the proportions will be calculated using the number of 
participants with data available at that visit. 
In both approaches above, the stool frequency subscore, rectal bleeding subscore, and PGA at the 
EOT visit will be re-allocated to the closest study visits following the approaches described in 
section 7.3.8. The summaries will be provided for the overall group, by previous use of advanced 
treatment for UC (naïve vs experienced), and by baseline MES score (2 vs 3). Line plots showing 
the proportion (± 95% CI) at each of the scheduled visits will be provided.  
Line plots showing mean values (± SD) at each of the scheduled visits will also be provided for 
1) stool frequency subscore, 2) rectal bleeding subscore, 3) sum of stool frequency and rectal 
bleeding subscores. 
9.4.2. 
Other Exploratory Endpoints 
Change from baseline to Weeks 2, 6, 12, 20, 28, 36, and 52 in high sensitivity C reactive protein 
(hs-CRP) levels will be summarized descriptively using mean, SD, median, 25th and 75th 
percentiles, minimum and maximum. Similarly, fecal calprotectin levels will be summarized in 
the same manner for the same visits. 
Line plots showing mean values (± SD) at each of the scheduled visits will be presented. 
Change from baseline to Week 65 and Week 78 in hs-CRP levels and fecal calprotectin levels 
during Long-term Extension will also be summarized descriptively for the participants who have 
enrolled into the Long-term Extension. 
The exploratory analysis of blood and mucosal tissue gene and/or protein expression over time, 
microbiome composition in stool and mucosal tissue over time, changes in microbiome-derived 
metabolites in stool and blood over time, and metatranscriptomic changes in the stool and 
mucosal tissue microbiome over time will be provided in a biomarker analysis plan separate 
from the study SAP and reported separately. 




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Nominal sampling time points relative to dosing will be used for plasma concentration-time 
summaries and mean figures of plasma concentration-time data. Actual sampling times will be 
used for individual concentration-time figures, including all recorded concentrations regardless 
of timing. 
All plasma concentration-time data will be reported to the same number of significant figures as 
displayed in the bioanalytical data. 
PK parameters for MORF-057 will be estimated by NCA using the software Phoenix® 
WinNonlin® Version 8.3 or higher (Certara, USA). 
Plasma concentrations at the optional 12 hr post-dose (C12 and Ctrough), Cmax/Cmax,ss, tmax/tmax,ss, 
Clast, and tlast will be obtained directly from experimental observations. If multiple maxima occur 
at equal concentrations, the first temporal value will be taken as the Cmax/Cmax,ss and tmax/tmax,ss. 
Average plasma concentrations based on BID dosing (Cave) will be calculated as AUCtau/tau, 
where feasible. If no 12 hr post-dose sample was obtained, C12 or Ctrough will be calculated using 
one of two methods to allow for the calculation of AUC0-12 or AUCtau: 
• C12 or Ctrough will be calculated using an extrapolation method via Phoenix 
WinNonlin standard calculations. If no lambda z is estimated, then 
• C12 or Ctrough will be imputed using the available pre-dose concentration for that visit 
day. Of note, MORF-057 exhibits diurnal variation and trough concentrations from an 
 vs a 
 do vary. A footnote will be included to indicate that the trough 
concentrations obtained from a 
 will not reflect a true Ctrough of an 
 
. 
All AUCs including AUC0-t, AUCtau, and AUC0-12 will be calculated by the linear-up/log-down 
trapezoidal method, using actual elapsed time values. If the 
or tau time points are not 
collected, then the AUC0-12 and AUCtau will be calculated using an extrapolated concentration 
via standard WinNonlin calculation methods to report a partial AUC or AUCtau.  
In addition, AUC0-inf will be calculated as outlined below following single dose administration 
(Visit 2; Study Day 1): 
AUC0-inf = AUC0-t + (Clast/λZ), 
where Clast is the last temporal measured plasma concentration post-dose corresponding to tlast. 
Regression parameters for estimation of λZ, including the number of time points used, time point 
range used for the regression (minimum time, maximum time) and adjusted coefficient of 
determination (adj R2) will be listed. 
The apparent first-order terminal phase elimination half-life, t1/2, where determinable, will be 
calculated as the natural log of 2 divided by the apparent first-order terminal phase elimination 
rate constant, lambdaz (λz). The λz will be determined by plotting the concentration-time data on 
a semi-logarithmic scale and estimated by linear least square regression analysis. The number of 


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data points included in the regression will be determined by best fit. Visual inspection of the λz 
will also be performed to ensure that a minimum of 3 data points in the terminal phase, excluding 
Cmax, is included. The upper and the lower time points, as well as the number of time points used 
for the λz estimation will be reported. For λz derived parameters (t1/2, AUC0-inf, CL/F, and Vz/F) 
to be summarized, the adj R2 value reported in Phoenix®WinNonlin® must be ≥ 0.8.  
For time-related PK parameters (tmax, tmax.ss, t1/2, and tlast) descriptive statistics will include N, 
arithmetic mean, SD, CV, geometric mean, geometric CV, median, minimum, and maximum. 
The AUC%extrap parameter will be listed and not summarized. This parameter will be reported to 
one decimal place. The adj-R2 parameter will be listed and not summarized and will be reported 
to at least five significant figures. 
PK parameters for clearance and volume of distribution following single dose administration will 
be calculated as follows: CL/F = Dose/AUC0-inf and Vz/F = Dose/λz*AUC0-inf 
PK parameters for clearance and volume of distribution at steady state following multiple-dose 
BID administration will be calculated as follows: CLss/F = Dose/AUCtau and Vz/F = 
Dose/λz*AUCtau, where tau = 12 hours. 
For all other PK parameters, descriptive statistics will include n, arithmetic mean, SD, CV, 
geometric mean, geometric CV, median, minimum, and maximum. These PK parameters will be 
reported to the same significant figures as displayed in the bioanalytical data, apart from λz, 
which will be reported to at least five significant figures. 
For the accumulation indices (AICmax and AIAUC), descriptive statistics will include N, arithmetic 
mean, SD, CV, geometric mean, geometric CV, median, minimum, and maximum. These 
parameters will be reported to one decimal place. 
Figures will be generated to display mean and individual MORF-057 plasma concentration 
versus time curves on linear and semilogarithmic scales. 
Other PK evaluations may be performed for exploratory reasons as needed. 
10.3. 
Pharmacokinetic Analysis 
The following plasma PK parameters in Table 4 will be calculated for MORF-057 (as deemed 
appropriate): 
Table 4: Pharmacokinetic Parameters by Visit 
PK Parameter 
Description 
Visit 2 (Study Day 1) 
AUC0-12  
Area under the concentration-time curve from time zero (0) to 12 hours post-
dose. 
AUC0-t 
Area under the concentration-time curve from time 0 to the last measured 
concentration post-dose. 




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In addition to the parameters above, MORF-057-derived metabolite measurements may be 
performed as deemed appropriate as an exploratory assessment. 
Plasma concentrations of MORF-057 will be listed by visit, participant ID, and timepoint and 
will be summarized by visit and timepoint using descriptive statistics (n, arithmetic means, 
standard deviation (SD), CV, median, minimum, maximum, geometric mean, and geometric 
CV). 
PK parameters for MORF-057 (for Visits 2, 3, and 5 only) will be listed by visit and by 
participant ID and summarized by visit. The arithmetic means (± SD) of plasma concentrations 
of MORF-057 will be presented graphically on both linear and semilogarithmic scales for each 
visit. For individual profiles, figures will be presented for each participant with concentration-
time profiles on both linear and semi-logarithmic scales for each visit. Concentration values of 
zero will not be plotted in the semi-logarithmic plots. 
PK analyses will be conducted as deemed appropriate and may be reported separately from the 
CSR. 


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11. 
PHARMACODYNAMIC ANALYSES 
PD results will be listed and summarized descriptively for the observed values based on the PD 
population. For summary tables, Main and Exploratory Cohorts will be presented together. 
Only RO will be plotted. A line plot will be presented for the mean and SD over nominal time 
points (Day 1 to Week 52). A box plot will be presented for RO by nominal timepoint (Day 1 to 
Week 52). Results from RO measurements made from optional blood samples collected at 12h 
after the AM dose will be analyzed separately from those that are determined from blood 
samples collected before the AM dose. 
Besides PD biomarkers received directly from the lab, expression of CCR9 mRNA in blood 
(relative to the pre-dose baseline) will also be calculated at each timepoint and listed. This value 
is calculated using the lab-reported parameter CCR9_IPO8_DeltaCt, where the expression of 
CCR9 mRNA in blood at a given timepoint relative to baseline is calculated using the following 
formula, where baseline is defined separately by period. 
Relative expression at timepoint x = 2-(CCR9_IPO8_DeltaCt at timepoint x - CCR9_IPO8_DeltaCt at baseline). 
Immunophenotyping results will be listed but analyzed and reported separately from the CSR. 
Additional analyses of PD parameters may be specified in a biomarker analysis plan separate 
from the study SAP and will be reported in a separate document. 
 
 
 
 
 
 
 


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12. 
SAFETY ANALYSES 
All safety analyses will be conducted using the Safety Analysis Population, unless specified 
otherwise. For summary tables, Main and Exploratory Cohorts, as well as total (the pooled Main 
and Exploratory Cohorts), will be presented as separate columns in the same table if applicable. 
The summary of safety results (i.e., adverse events, clinical laboratory, vital signs, and ECG) will 
be presented based on the safety data during the on-Treatment Period, which is defined as the 
period from the administration of the first dose of study drug up to 7 days after the last dose of 
study drug, unless specified otherwise. The listings will include all data. No hypothesis testing 
will be performed on safety data. 
12.1. 
Adverse Events 
The Medical Dictionary for Regulatory Activities (MedDRA) dictionary (effective version at the 
time of database lock) will be used for coding AEs. A treatment-emergent AE (TEAE) is defined 
as an AE that occurs during the period from the administration of the first dose of study drug up 
to 7 days after the last dose of study drug. 
AEs will be classified as related or not related to the study drug by Investigator. If the 
relationship of an AE is missing/unknown, the AE will be considered study drug related. 
The following summary tables will be presented: 
• Overall Summary of TEAEs. 
− TEAE 
− Serious TEAE 
− TEAE with grade 3 or worse 
− Treatment-related TEAE 
− Treatment-related serious TEAE 
− TEAE leading to death 
− TEAE leading to permanent treatment discontinuation 
• TEAEs by system organ class (SOC) and preferred term (PT). 
• TEAEs by SOC, PT, and maximum Severity. 
• TEAEs by SOC, PT, and Relationship to Study Drug. 
• Serious TEAE by SOC and PT 
• Serious TEAEs by SOC, PT, and maximum Severity 
• Serious TEAEs by SOC, PT, and Relationship to Study Drug 
• Non-serious TEAEs (PTs with an incidence >5%) by SOC and PT 


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If more than one event occurred with the same PT or SOC for the same participant, the 
participant will be counted only once for that term. 
The following line listings will be provided: 
• Listing of serious TEAE including duration. 
• Listing of all AEs with a flag for treatment-emergence and variable for duration. 
• Listing of TEAEs Leading to Withdrawal of Study Treatment. 
• Listing of all deaths. 
• Listing of TEAE associated with Overdose 
12.2. 
Clinical Laboratory Evaluations 
Observed and changes from baseline for central clinical laboratory results (hematology, 
coagulation, chemistry, urinalysis) will be summarized descriptively for the on-Treatment Period 
at all scheduled visits (Baseline, Weeks 2, 6, 12, 20, 28, 36, 44, 52, 65, and 78) for each analysis 
specified in Section 7.5 as appropriate. 
Line plots for the mean (SD) and mean change from the baseline (SD) over nominal time will 
also be provided for hematology. Peak alanine transaminase (ALT) or aspartate transaminase 
(AST) vs. peak total bilirubin post baseline will be plotted. 
The number of participants ever experienced abnormalities (scheduled and unscheduled) for each 
lab parameter during on-Treatment Period will be summarized using the shift table for the 12-
week Induction Period, 52-week on-Treatment Period, and Long-term Extension. 
A listing will be provided for altered liver function test (i.e., patients with any elevated ALT or 
AST >3 x ULN and associated with an increase in total bilirubin >2 x ULN), including ALT, 
AST, ALP, and total bilirubin. 
A list of abnormal laboratory values will be created separately. 
Local laboratory results will be listed separately from central as appropriate, but they will not be 
summarized with central lab results due to calibration differences. 
12.3. 
Vital Signs 
The observed vital sign results (systolic blood pressure, diastolic blood pressure, heart rate, 
temperature, respiratory rate, weight, and BMI) and change from baseline will be summarized 
descriptively for the on-Treatment Period at each scheduled visits (Baseline, Weeks 2, 6, 12, 20, 
28, 36, 44, 52, 65, and 78) for each analysis specified in Section 7.5 as appropriate 
A shift table from baseline of each parameter will also be presented. All vital sign data by 
participant ID will be presented in a listing. 


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12.4. 
ECG 
Safety ECG results (PR interval, QRS duration, QT interval, and QTcF interval) will be 
summarized descriptively for the on-Treatment Period at each scheduled visit (Baseline, Weeks 
6, 12 and 52) for the observed value and change from baseline. Overall interpretation along with 
clinical significance will be summarized. 
A shift table of QTcF will be presented for the on-Treatment Period. QTcF > 450 ms among 
male participants and QTcF > 470 ms among female participants will be considered above 
normal ranges. 
12.5. 
Physical Examinations 
Abnormality in physical exams will be reflected in the medical history and adverse event 
summaries. 
12.6. 
Endoscopy 
Extent of disease, distance from anus where sample of the worst inflammation and non-
inflammation are taken in cm, will be listed. 
12.7. 
Other Safety Measures 
The PML checklist, COVID-19 test, overdose reports and pregnancy results will be presented in 
listings only. 
No other safety analyses have been prospectively defined. If, however, after study results are 
reviewed, or Sponsor recommend additional safety parameters or analyses be completed, they 
will be fully described and documented in the final CSR. The SAP does not need to be amended 
to complete any other safety measures identified as post-hoc. 


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13. 
REPORTING CONVENTIONS 
The following reporting conventions will be adopted for the presentation of study data. These 
conventions will enhance the review process and help to standardize presentation with common 
notations. 
13.1. 
General Reporting Conventions 
• All tables and data listings will be developed in Landscape Orientation in PDF 
format, unless presented as part of the text in a CSR. 
• Figures will be presented in Landscape Orientation, unless presented as part of the 
text in a CSR. 
• Legends will be used for all figures with more than one variable or item displayed. 
• Figures will be in presented in color with treatment groups distinguished by different 
symbols and colors. Lines in figures should be wide enough to view the line after 
being photocopied. 
• Specialized text styles, such as bolding, italics, borders, shading, superscripted and 
subscripted text will not be used in tables, figures, and data listings unless they add 
significant value to the table, figure, or data listing. 
• Only standard keyboard characters should be used in tables and data listings. Special 
characters, such as non-printable control characters, printer specific, or font specific 
characters, will not be used on a table, figure, or data listing. Hexadecimal character 
representations are allowed (e.g.,µ,α,β). 
• All titles will be centered on a page. The ICH numbering convention is to be used for 
all tables, figures, and data listings. 
• All footnotes will be left justified and the bottom of a page. Footnotes must be present 
on the page where they are first referenced. Footnotes should be used sparingly and 
must add value to the table, figure, or data listing. If more than four footnote lines are 
planned, then a cover page may be used to display footnotes. 
• Missing values for both numeric and character variables will be presented as blanks 
in a table or data listing. A zero (0) may be used if appropriate to identify when the 
frequency of a variable is not observed. 
• All date values will be presented as YYYY-MM-DD (e.g., 2013-05-17) ISO 8601 
format. 
• All observed time values will be presented using a 24-hour clock HH:MM:SS format 
(e.g., 01:35:45 or 11:26). Seconds should only be reported if they were measured as 
part of the study, also in ISO 8601 format. 
• Time durations will be reported in mixed HHh MMm SSs notation (e.g., 5h 32m, or 
27h 52m 31s). The use of decimal notation to present (display) time durations should 
be avoided (e.g., 0.083h = 5m) unless it is necessary to show the computation of time 


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differences in a table, figure, or data listing, in which case both notations may be used 
to display the time duration. 
• All tables, figures, and data listings will have the Table, Listing, or Graph status 
(DRAFT, FINAL), and a date/time stamp on the bottom of each output. 
• All analysis programs developed for a table, figure, or data listing display will be self-
contained to facilitate transfer of programs to multiple computing environments and 
transfer to a regulatory agency (if requested). 
13.2. 
Population Summary Conventions 
• Population(s) represented on the tables or data listings will be clearly identified in the 
last title of the Table as “<name of population>” and will be identical in name to that 
identified in the protocol or SAP. 
• Consistent terminology will be used to define and identify a population. 
• Sub-population(s) or special population(s) descriptions will provide sufficient detail 
to ensure comprehension of the population used for analysis in a table or figure. 
• Population sizes may be presented for each treatment or dosing category as totals in 
the column header as (N=xxxx), where appropriate. 
• Population sizes shown with summary statistics are the samples sizes (n) of 
participants with non-missing values. 
• All population summaries for categorical variables will include all categories that 
were planned and for which the participants may have had a response. Percentages 
corresponding to null categories (cells) will be suppressed. 
• All population summaries for continuous variables will include N, mean, SD, 
minimum, and maximum. Other summaries (e.g., number missing, median, quartiles, 
5%, 95% intervals, CV or %CV) may be used as appropriate. 
• All percentages are rounded and reported to xx.x%. A percentage of 100% will be 
reported as 100%. No value of 0% will be reported. Any computation of percent that 
results in 0% is to be presented as a blank. 
• Population summaries that include p-values will report the p-value to four decimal 
places with a leading zero (0.0001). All p-values reported on default output from 
statistical software (i.e., SAS® Software version) may be reported at the default level 
of precision. P-values <0.0001 should be reported as <0.0001 not 0.0000. 
 
 


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APPENDIX 1 MAYO CLINIC SCORE (MCS) CALCULATION 
The Full MCS is a composite of four subscores, each ranging from 0-3: MES, stool frequency, 
rectal bleeding, and the PGA. The Modified MCS is a composite of three subscores: MES, stool 
frequency, and rectal bleeding. 
• The Full MCS is calculated as the sum of the four subscores for MES, stool 
frequency, rectal bleeding, and the PGA. 
• The Modified MCS is calculated as the sum of the three subscores for MES, stool 
frequency, and rectal bleeding. 
MES will be derived based on the answer option for ‘Mucosal appearance at Endoscopy’ in the 
MES (Central) eCRF form entered at the scheduled visits. The PGA will be recorded in 
Physician Global Assessment eCRF form at visits. Participants will complete the stool frequency 
and rectal bleeding components into their Participant Diary daily. The derivation of stool 
frequency and rectal bleeding subscores from the diary entries are described below. 
Calculation of the stool frequency and rectal bleeding subscores 
• For baseline calculation, use ‘Visit Date’ entered on the visit Date eCRF form for 
Visit 2 (Week 0) as the reference date. For post baseline calculations at any visits 
with Endoscopy procedure performed, use ‘Visit Date’ entered on the visit Date 
eCRF form or the date of Endoscopy procedure, whichever comes first, as the 
reference date. For post baseline calculations at any visits with no Endoscopy 
procedure performed, use ‘Visit Date’ entered on the visit Date eCRF form as the 
reference date. 
• Take the average of the three most recent consecutive stool frequency/rectal bleeding 
diary submissions within the past 7 days from the reference date. If three consecutive 
diary submissions are not available, then use the three most recent diaries within the 
past 7 days. If there are fewer than three submissions or if the reference date is not 
available, then the subscores will be set to missing. A diary submission can be 
considered in the calculation if both stool frequency and rectal bleeding data are 
available. 
• Exclude the following days if Endoscopy procedure is performed: Bowel preparation 
period, and Endoscopy Start Date to End Date + 3 days. Bowel preparation might not 
be done always and in that case, do not exclude any days for bowel preparation. 
Bowel preparation and Endoscopy dates are recorded in the Endoscopy eCRF form. 
• Round the average to the nearest integer (Decimal 0.5 and above will be rounded to 
the next highest integer. Decimal less than.5 will be rounded to the current integer. 
Example: 1.5 will be rounded to 2 and 1.4 will be rounded to 1). 
• For rectal bleeding subscore, take the rounded average number. Calculate the stool 
frequency subscore as below: 
− 0 if (rounded average number) – normal number of stools ≤ 0 


Morphic Therapeutic                           
Study MORF-057-201  
 
 
 
 
Statistical Analysis Plan, V2.0 
CONFIDENTIAL 
Page 61 of 61 
 
− 1 if (rounded average number) – normal number of stools = 1 or 2 
− 2 if (rounded average number) – normal number of stools = 3 or 4 
− 3 if (rounded average number) – normal number of stools > 4 
Where the normal number of stools are the values recorded in the UC History eCRF 
form, i.e., 
• The value entered for the question ‘On average, when in remission from UC, what 
was the normal number of stools the subject had in 24 hours?’, when ‘Has subject 
previously been in remission from UC?’ = ‘Yes’, 
• The value entered for the question ‘On average, prior to developing Ulcerative 
Colitis symptoms or Ulcerative Colitis diagnosis, what was the normal number of 
stools the subject had in 24 hours?’, when ‘Has subject previously been in 
remission from UC?’ = ‘No’.