A Phase 2b, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of 3 Active Dose Regimens of MORF-057 in Adults With Moderately to Severely Active Ulcerative Colitis (EMERALD-2)
Phase: PHASE2
Conditions: Inflammatory Bowel Diseases, Colitis, Ulcerative
Sponsor: Morphic Therapeutic, Inc. (A Wholly Owned Subsidiary of Eli Lilly and Company)

Protocol: J6E-MC-KWAD 
 
 
A Phase 2b, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and 
Efficacy of 3 Active Dose Regimens of MORF-057 in Adults with Moderately to Severely 
Active Ulcerative Colitis 
 
 
NCT05611671 
 
 
Approval Date: 27-Mar-2025 
 
 
 

CONFIDENTIAL  
 
MORF-057-202 Protocol 
 
Version 3.0 Final 26MAR2025 
1 
 
 
 
Clinical Study Protocol 
Protocol Title:  
A Phase 2b, Randomized, Double-blind, Placebo-controlled 
Study to Evaluate the Safety and Efficacy of 3 Active Dose 
Regimens of MORF-057 in Adults with Moderately to Severely 
Active Ulcerative Colitis (EMERALD-2) 
Protocol Number: 
MORF-057-202 
Compound: 
MORF-057 
Brief Title: 
A Phase 2b Study to Evaluate MORF-057 in Adults with 
Moderately to Severely Active UC 
Indication 
Moderately to severely active ulcerative colitis 
Study Phase: 
2b 
Sponsor:  
Morphic Therapeutic, Inc.  
(A Wholly Owned Subsidiary of Eli Lilly and Company) 
35 Gatehouse Drive, A2 
Waltham, MA 02451, USA 
IND Number: 
147011 
UTN Number: 
U1111-1283-7075 
EU CT Number: 
2022-500953-17-00 
Protocol Version: 
Version 3.0, 26 March 2025 
 
Confidentiality Statement 
The information contained herein is confidential and the proprietary property of Morphic Therapeutic, Inc. (A 
Wholly Owned Subsidiary of Eli Lilly and Company; 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. 

CONFIDENTIAL  
 
MORF-057-202 Protocol 
 
 
Version 3.0 Final 26MAR2025 
 
2 
 
Protocol Version: Version 3.0, 26 March 2025 
 
 
Sponsor Signatory: 
______________ 
 
___________________ 
  
 
 
 
 
 
 
 Date 
Head of Morphic Clinical Development 
Morphic Therapeutic, Inc. (A Wholly Owned Subsidiary of Eli Lilly and Company) 
 
 
 
 
Docusign Envelope ID: B7D522FA-18F9-494D-B7FC-6F18A46743AB
27-Mar-2025 | 8:19 AM PDT
PPDPPD

CONFIDENTIAL  
 
MORF-057-202 Protocol 
 
Version 3.0 Final 26MAR2025 
3 
 
Protocol Amendment Summary of Changes  
 
DOCUMENT HISTORY 
Document 
Date 
Protocol V1.0 
01 June 2022 
Protocol V2.0 
26 April 2023 
Protocol V2.1 (EU) 
26 April 2023 
Protocol V3.0 
26 March 2025 
Version 3.0 dated 26 March 2025 
Overall Rationale for the Amendment 
The overall rationale for this protocol amendment is to add the following major changes: 
• To merge Global Protocol Version 2.0 and European Union Protocol Version 2.1 
• To revise to the most up to date development program information 
• To clarify and revise the name of the extension period 
• To revise the dose for the Long-Term Extension Period 
• To add the Dose Switch Follow-up 1 and 2 
• To revise the definition for the End of Study 
• To add an optional exploratory fecal calprotectin sample 
• To revise the study schema 
• To revise the contraception requirements 

CONFIDENTIAL  
 
MORF-057-202 Protocol 
 
 
Version 3.0 Final 26MAR2025 
 
4 
 
Summary of Changes Table 
This protocol amendment merges the 2 previous protocol versions: Protocol Version 2.0 (applicable globally in countries outside of the 
European Union [EU]) and Version 2.1 (applicable only in the EU). Additional changes have also been incorporated into this 
Version 3.0, which is now applicable globally. 
This protocol amendment is considered Substantial by the Sponsor, according to the criteria specified in the EU Clinical Trials 
Regulation 536/2014. Changes to the protocol as implemented by this amendment 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. 
Section No. and Name 
Description of Change 
Brief Rationale 
Global change 
Add “(A Wholly Owned Subsidiary of Eli Lilly and Company)” after Morphic Therapeutic, Inc. 
To update Sponsor 
name 
Global change 
“Maintenance Extension” and “Extension” was changed to “Long-Term Extension” or “LTE” 
throughout the Protocol. 
To clarify and revise 
the names of the 
extension period 
Global change 
The Long-Term Extension Period End of Treatment Visit was changed to Long-Term Extension 
End of Treatment throughout Protocol. 
To clarify the extension 
period End of 
Treatment Visit 
Global change 
LTE was replaced with LTE Period. 
To be consistent 
Global change 
Changed CYP3A4 to CYP3A throughout document. 
To clarify for 
consistency 
Abbreviations 
CYP3A4 Cytochrome P450 3A4 
DDI 
Drug-drug interaction 
DSFU 
Dose Switch Follow-up 
EU 
European Union 
IB 
Investigator’s Brochure 
LTE 
Long-Term Extension 
To update the 
abbreviations used 
throughout the protocol 
1.1. 
Synopsis-
Rationale: 
Relevant data from all non-clinical and clinical studies in the MORF-057 development program are 
provided in the current Investigator’s Brochure. 
A first in human Phase 1 study of MORF-057 (MORF-057-101) in healthy study participants has been 
completed. The study included 3 parts: a single ascending dose ([SAD] up to 400 mg) part, a multiple 
ascending dose ([MAD] up to 100 mg twice a day [B.I.D.] for 14 days) part, and a food effect ([FE] 
fixed dose of 100 mg B.I.D.) part. MORF 057 was demonstrated to be safe and well tolerated in these 
healthy study participants across all parts of the study. MORF-057 also exhibited favorable 
pharmacokinetics (PK) profiles. The observed exposure in healthy individuals is expected to be similar 
in patients with UC and to provide the receptor occupancy at these exposures that may translate to 
intended efficacy and safety outcomes. The 100 mg B.I.D. regimen in participants with UC is being 
To revise to the most up 
to date development 
program information 

CONFIDENTIAL  
 
MORF-057-202 Protocol 
 
 
Version 3.0 Final 26MAR2025 
 
5 
 
Section No. and Name 
Description of Change 
Brief Rationale 
evaluated in an ongoing open label, single arm, Phase 2 study (MORF-057-201) to provide safety, PK, 
pharmacodynamics (PD), and preliminary efficacy data to inform further development of MORF-057 in 
patients with UC. 
A Phase 1 study (
) was conducted in healthy participants to investigate the safety, 
tolerability, PK, and PD of single and multiple doses of MORF-057 immediate-release (IR) capsules. 
The single (25 mg, 200 mg, and 100 mg [with and without food]) and multiple (200 mg B.I.D. for 14 
days) dosing of MORF-057 IR capsules was demonstrated to be safe and well tolerated. The new 
MORF-057 IR capsule formulation was selected to be used in future studies. Data from this study and 
the MORF-057-101 study were primarily used for selecting the doses and dosing regimens for this 
current Phase 2b study (MORF-057-202). 
1.1. Synopsis – Overall 
Design: 
 
4.1. Overall Design 
During the optional LTE Period, there will be up to 57 scheduled visits: 4 Treatment Visits (Visits 11-
14 at Weeks 65, 78, 91, and 104 [Long-Term Extension (LTE) EOT]), 2 Dose Switch Follow-ups 
(DSFUs; these 2 visits will only occur if participant consents to dose switch), and an SFU Visit (visit to 
occur 4 weeks after the last dose of study drug is received, which will be at Week 108 if the full LTE 
Period is completed or earlier if treatment is discontinued early). 
Due to the changes in Version 3.0 of this protocol, all participants who choose to continue their 
treatment in the LTE Period will be asked to re-consent to the LTE Period dose switch to 200 mg twice 
a day (B.I.D.). The dose switch will occur at Visit 10 or at a scheduled visit in the LTE Period (Visit 11, 
12, or 13). If the participant does not consent to the dose switch, they will be allowed to remain on their 
current LTE Period dose and schedule; they will not need to attend DSFUs 1 or 2. Participants in the 
LTE Period who consent to the dose switch will have a scheduled DSFU 1 at 4 weeks after the dose 
switch, and then DSFU 2 will be 4 weeks after DSFU 1. The participant will then attend the next 
scheduled visit (Visit 11, 12, 13, or 14) per the Schedule of Activities (SoA). A participant cannot switch 
their dose after Visit 13. An SFU Visit will occur 4 weeks after the last dose of study drug is received, 
which will be at Week 108 if the full LTE Period is completed or earlier if treatment is discontinued 
early. 
Participants who do not enroll into the LTE Period mustwill complete the final SFU Period for the main 
part of the study, including the Week 56 Visit (4 weeks after receiving the last dose of MORF-057), for 
the main part of the study (a maximum time on study of 62 weeks). Participants who choose to continue 
in the LTE Period will not complete the SFU PeriodVisit for the main part of the study; instead, they 
will directly enter the LTE Period and complete a separate SFU PeriodVisit, including the Week 108 
Visit (4 weeks after receiving the last dose of MORF-057 in the LTE Period), for a maximum time on 
study of 114 weeks. 
To revise the dose, the 
number of visits, and 
add Dose Switch 
Follow-ups for the 
Long-Term Extension 
Period 
In the Induction Period 
analysis for this study, a 
dose-response was 
observed between the 3 
active doses, and 200 
mg B.I.D. was the 
clinically most active 
dose. Changing the 
dose for the Long-Term 
Extension Period from 
100 mg B.I.D. to 200 
mg B.I.D. will provide 
current study 
participants with an 
opportunity to receive a 
higher dose that may be 
more clinically active. 
Based on all available 
clinical data, this 
change is not expected 
to increase the risk of 
any potential safety 
effects. 
CCI

CONFIDENTIAL  
 
MORF-057-202 Protocol 
 
 
Version 3.0 Final 26MAR2025 
 
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Section No. and Name 
Description of Change 
Brief Rationale 
1.1. Synopsis – Study 
Treatment: 
 
4.1. Overall Design 
All participants who choose to continue in the LTE Period will continue receiving the same MORF-057 
regimen they had during the Maintenance Period for up to an additional 52 weeks. However, at Visit 10 
or at a scheduled visit in the LTE Period (Visit 11, 12, or 13), if the participant consents, the MORF-
057 dose for the LTE Period will be switched to 200 mg B.I.D. If the participant does not consent to the 
dose switch, they will be allowed to remain on their current LTE Period dose and schedule. The dosing 
regimens for the 4 treatment groups during the study are shown below. 
 
Induction Period 
(12 Weeks) 
Maintenance Period (40 
Weeks)/ 
LTE Period (52 Weeks) 
LTE Period (52 Weeks)* 
Group 
1 
MORF-057 (200 mg 
B.I.D.) 
MORF-057 (100 mg B.I.D.) 
MORF-057 (200 mg B.I.D.) 
Group 
2 
MORF-057 (100 mg 
B.I.D.) 
MORF-057 (100 mg B.I.D.) 
MORF-057 (200 mg B.I.D.) 
Group 
3 
MORF-057 (100 mg 
Q.D.-M) 
MORF-057 (100 mg Q.D.-M) 
MORF-057 (200 mg B.I.D.) 
Group 
4  
Placebo 
MORF-057 (200 mg Q.D.-E) 
MORF-057 (200 mg B.I.D.) 
Abbreviations: B.I.D., twice a day; LTE, Long-Term Extension; Q.D. E, once a day (evening); Q.D. M, 
once a day (morning). 
* Relevant for participants who consent to the dose switch in the LTE Period. For those that do not 
consent to the dose switch in the LTE Period, they will remain on their current LTE Period dose. 
In the Induction Period 
analysis for this study, a 
dose-response was 
observed between the 3 
active doses, and 200 
mg B.I.D. was the 
clinically most active 
dose. Changing the 
dose for the Long-Term 
Extension Period from 
100 mg B.I.D. to 200 
mg B.I.D. will provide 
current study 
participants with an 
opportunity to receive a 
higher dose that may be 
more clinically active. 
Based on all available 
clinical data, this 
change is not expected 
to increase the risk of 
any potential safety 
effects. 
1.1. Synopsis – Study 
Treatment: 
The study drug will be supplied as IRimmediate release capsules for oral administration (MORF-057 
100 mg capsule or placebo). Refer to the main protocol for additional treatment details.Participants will 
receive their study drug supplies in “morning bottles” and “evening bottles.” Each participant will 
receive the same number of “morning bottles” and “evening bottles” according to the respective study 
period (Induction or Maintenance/Maintenance Extension). In the morning, participants should take 1 
capsule from EACH “morning bottle.” In the evening, participants should take 1 capsule from EACH 
“evening bottle.” Each participant will be instructed to take 4 capsules per day during the Induction 
Period and 3 capsules per day during the Maintenance Period/Maintenance Extension Period. 
To clarify the number 
of capsules to be taken 
per day during the 
Long-Term Extension 
Period 

CONFIDENTIAL  
 
MORF-057-202 Protocol 
 
 
Version 3.0 Final 26MAR2025 
 
7 
 
Section No. and Name 
Description of Change 
Brief Rationale 
1.1. Synopsis – Study 
Schema: 
 
4.1. Overall Design 
 
Abbreviations: B.I.D., twice a day; DSFU, Dose Switch Follow-up; EOT, End of Treatment; Q.D.-E, 
once a day (evening); Q.D.-M, once a day (morning); SFU, Safety Follow-up; UC, ulcerative colitis; V, 
visit; W, week. 
a* The SFU Visit at Week 56 will not be performed at Week 56 for participants who enter the LTE Period. 
b† The assessments to be performed at each visit and the acceptable time windows for each visit are 
provided in the Schedule of Activities. 
c‡ 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. 
d At Visit 10 or at a scheduled visit in the LTE Period (Visit 11, 12, or 13), all participants will be asked 
to re-consent to switch their dose to 200 mg B.I.D. Participants who do not consent to the dose switch 
will remain on their current LTE Period dose. The DSFU 1 will occur 4 weeks after the dose switch, 
and DSFU 2 will occur 4 weeks after DSFU 1. Participants who do not consent to the dose switch will 
not need to attend DSFUs 1 or 2. 
To revise the dose, the 
number of visits, and 
add Dose Switch 
Follow-ups for the 
Long-Term Extension 
Period 

CONFIDENTIAL  
 
MORF-057-202 Protocol 
 
 
Version 3.0 Final 26MAR2025 
 
8 
 
Section No. and Name 
Description of Change 
Brief Rationale 
1.1. Synopsis –Main 
Inclusion Criteria: 
 
5.1. Inclusion Criteria 
“oral aminosalicylates” was in Version 2.0 but not in Version 2.1, which has been combined in 
Version 3.0. 
Type of Participant and Disease Characteristics #4 
4. Demonstrated an inadequate response, loss of response, or intolerance to at least one of the following 
treatments (including oral aminosalicylates*, corticosteroids, immunosuppressants, and/or advanced 
therapies for UC) in the opinion of the Investigator, as defined below: 
a. Oral aminosalicylates (e.g., mesalamine, sulfasalazine, olsalazine, or balsalazide) 
• 
Signs and symptoms of persistently active disease during a current or prior course of at 
least 4 weeks of treatment with ≥2.0 g/day mesalamine, 4 g/day sulfasalazine, 1 g/day 
olsalazine, or 6.75 g/day balsalazide 
*Note: Inadequate response, loss of response, or intolerance to oral aminosalicylates does not 
apply to this Inclusion Criterion in European Union (EU) countries. 
 
d. Advanced therapies for UC (e.g., biologic agents, Janus kinase [JAK] antagonists, or 
sphingosine 1 phosphate [S1P] receptor agonists) 
Note: Participants who have received a prior advanced therapy agent for up to 1 year and did 
not have a documented non-response may be enrolled; however, the participants must have 
discontinued the advanced therapy agent for reasons other than inadequate response or 
intolerance (e.g., change of insurance, well controlled disease) and must meet the criteria for 
inadequate response, loss of response, or intolerance to aminosalicylates, corticosteroids, 
and/or immunosuppressants, as defined above. 
To combine Protocol 
Amendment Version 
2.0 and Version 2.1 to 
Version 3.0 
1.1. Synopsis –Main 
Inclusion Criteria: 
 
5.1. Inclusion Criteria 
“8-week” was in Version 2.0 and “12-week” was in Version 2.1, which have been combined in 
Version 3.0. 
Type of Participant and Disease Characteristics #4 
b.c. Immunosuppressants (e.g., azathioprine, 6-mercaptopurine, or methotrexate) 
• 
Signs and symptoms of persistently active disease despite a history of at least one 8*-
week regimen of oral azathioprine (≥1.5 mg/kg/day), 6-mercaptopurine (≥1 mg/kg/day or 
a documented 6-thioguanine nucleotide level of 230-450 pmol/8 × 108 red blood cell 
count or higher on the current dosing regimen), injectable methotrexate (≥12.5 mg/week 
subcutaneous [SC] or intramuscular) 
*Note: A history of signs and symptoms of persistently active disease despite a history of at 
least one 12-week regimen of immunosuppressants is required in EU countries. 
To combine Protocol 
Amendment Version 
2.0 and Version 2.1 to 
Version 3.0 

CONFIDENTIAL  
 
MORF-057-202 Protocol 
 
 
Version 3.0 Final 26MAR2025 
 
9 
 
Section No. and Name 
Description of Change 
Brief Rationale 
1.1. Synopsis –Main 
Inclusion Criteria: 
 
5.1. Inclusion Criteria 
“4 weeks” was in Version 2.0 and “12 weeks” was in Version 2.1, which have been combined in 
Version 3.0. 
Type of Participant and Disease Characteristics #6 
a. 
Oral 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/day, budesonide 9 mg/day, 
beclomethasone dipropionate 5 mg/day, methylprednisolone 24 mg/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 
*Note: Participants must be on any stable dose of 6-mercaptopurine, azathioprine, or methotrexate 
for at least 12 weeks prior to study Day 1 in EU countries. 
To combine Protocol 
Amendment Version 
2.0 and Version 2.1 to 
Version 3.0 
1.1. Synopsis –Main 
Inclusion Criteria: 
 
5.1. Inclusion Criteria 
Type of Participant and Disease Characteristics #7 
7. If the participant has had UC for over 7 years, he/she must have had a full colonoscopy in the last 2 
years or must agree to have a full colonoscopy (rather than sigmoidoscopy) with appropriate, per local 
guidelines, colon cancer surveillance biopsies at Screening 
To clarify inclusion 
criteria 
1.1. Synopsis –Main 
Inclusion Criteria: 
 
5.1. Inclusion Criteria 
Sex and Contraceptive/Barrier Requirements #10 
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 MORF-057 
Note: For contraception requirements on or after Protocol Amendment Version 3.0, see Section 10.5.2.2. 
To revise the 
contraception 
requirements for study 
participants who 
receive the increased 
dose of MORF-057 
(200 mg B.I.D.) during 
the Long-Term 
Extension Period 
1.1. Synopsis –Exclusion 
Criteria: 
5.1. Exclusion Criteria 
6. Has positive findings on a Subjective Pprogressive Mmultifocal Lleukoencephalopathy (PML) 
subjective symptom checklist during Screening or prior to the administration of the first dose of study 
drug on study Day 1 
 
6. Has positive findings on a Subjective PML subjective symptom checklist during Screening or prior to 
the administration of the first dose of study drug on study Day 1 
Administrative change 

CONFIDENTIAL  
 
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Version 3.0 Final 26MAR2025 
 
10  
Section No. and Name 
Description of Change 
Brief Rationale 
1.1. Synopsis –Statistical 
Methods: 
9.3. 
Analyses for 
Induction Period, 52-
week Treatment Period, 
and LTE Period 
Analyses for Induction Period, 52-week Treatment Period, and LTE Period 
The details of the analyses will be described in the SAP. The results for the main part of the study will 
be reported in the Clinical Study Report. Additional analysis of the optional 52-week LTE Period for 
the participants enrolled into the LTE Period will also be performed as appropriate. The results for the 
LTE Period will be reported in a Clinical Study Report Addendum. 
To clarify the analyses 
for each period 
1.1. Synopsis –Statistical 
Methods: 
9.3. Analyses for 
Induction Period, 
52-week Treatment 
Period, and LTE Period 
52-week Treatment Period Analysis 
The analysis of the 52-week Treatment Period will be performed after all the participants have 
completed the Week 52 assessments (and Safety Follow-up Period for participants not rolling over into 
the LTE Period) or discontinued from the study beforeduring the 52-Weekweek assessmentsTreatment 
Period. 
52-week LTE Period Analysis 
The analysis of the LTE Period will be performed after all the participants enrolled into the LTE Period 
have completed the 52-week LTE Period and the Safety Follow-up Period or discontinued the study 
beforeduring the Week 104 assessmentLTE Period. The analysis will evaluate the long-term safety of 
MORF-057 and selected efficacy endpoints at Week 104 as appropriate during the LTE Period plus the 
Safety Follow-up Period. 
To clarify the Long-
Term Extension Period 
Analysis 
1.2. Schedule of 
Activities (SoA) 
The SoA for the Treatment Period is provided in Table 1. The SoA for the LTE Period* is provided in 
Table 2. 
To reflect the changes 
in the Long-Term 
Extension Period due to 
changes in the dosing 
regimen 
1.2. Schedule of 
Activities (SoA) 
Table 1. Schedule of Activities for the Treatment Period 
Visit 
1 
5 
7 
10/EOT 
 
Stage 1 
Stage 2 
 
Stage 2 
Future Research (Optional) 
 
 
 
 
Fecal sample for fecal calprotectinhh 
 
 
 
X 
Efficacy Assessments 
 
 
 
 
Fecal sample for fecal calprotectin 
X 
X 
X 
X 
 
hh Participation in future research sample collection is optional. Fecal samples for fecal calprotectin 
will be collected at the same visits as the fecal calprotectin efficacy assessments (Visit 10/EOT). Fecal 
samples may be collected at any time on the day prior to the scheduled visit day.  
To reflect the addition 
of an optional 
exploratory fecal 
calprotectin sample 
1.2. Schedule of 
Activities (SoA) 
Added Footnote ‘hh,’ which reordered the footnotes afterwards. 
Administrative 
1.2. Schedule of 
Activities (SoA) 
Table 1 Footnote 
Abbreviations: AE, adverse event; B.I.D., twice a day; C. diff., Clostridiodes difficile; ECG, 
electrocardiogram; EOT, End of Treatment; HIV, human immunodeficiency virus; hs-CRP, high 
Administrative 

CONFIDENTIAL  
 
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Version 3.0 Final 26MAR2025 
 
11  
Section No. and Name 
Description of Change 
Brief Rationale 
sensitivity C reactive protein; IBDQ, Inflammatory Bowel Disease Questionnaire; ICF, Informed 
Consent Form; IGRA, interferon gamma release assay; LTE, Long-Term Extension; MCS, Mayo Clinic 
Score; MES, Mayo Endoscopic Subscore; NI, Nancy Histopathology Index; PD, pharmacodynamics; 
PK, pharmacokinetics; PML, progressive multifocal leukoencephalopathy; RHI, Robarts 
Histopathology Index; RNA, ribonucleic acid; RO, receptor occupancy; SAE, serious adverse event; 
SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SCR, Screening; SFU, Safety Follow-
up; TB, tuberculosis; UNS, unscheduled. 
1.2. Schedule of 
Activities (SoA) 
Table 1 Footnote 
d Visit 10 is split into Stage 1 and Stage 2 to clarify the timing of the endoscopy procedure. The 
endoscopy procedure at Visit 10 Stage 1 should be performed on or within 7 days before the Visit 10 
Stage 2 in clinic assessments have been completed. 
 
kkll For tThe Visit 10/EOT Stage 1 endoscopy procedure should occur on or within, there is a window 
of +7 days frombefore the actual Stage 2 visit date. 
To clarify the timing of 
endoscopy at Visit 10 
1.2. Schedule of 
Activities (SoA) 
Table 1 Footnote 
n Participant Diaries are to be completed daily by the participant at home and brought to each study 
visit for review by study personnel. Participant Diaries should not be completed after the participant 
has finished their participation in the study at the SFU Visit. See Section 8.5 for the required contents 
of the Participant Diaries. 
To clarify the 
Participant Diary 
should not be 
completed after the 
participant exits the 
study 
1.2. Schedule of 
Activities (SoA) 
Table 1 Footnote 
r Participants will be provided the option to participate in the LTE Period. Participants who want to 
continue in the LTE Period will be required to provide informed consent. Due to the changes in Version 
3.0 of this protocol, all participants who choose to continue their treatment in the LTE Period will be 
asked to re-consent to the LTE Period dose to 200 mg B.I.D. The dose switch will occur at Visit 10 or at 
a scheduled visit in the LTE Period (Visit 11, 12, or 13). 
To reflect the changes 
to the Long-Term 
Extension Period 
1.2. Schedule of 
Activities (SoA) 
Table 1 Footnote 
sstt Site staff will contact the participants, by phone or other formsmeans, on the next business day after 
the Visit 5 clinic visit is complete to confirm the participants are using the new supply of study drugs 
for the Maintenance Period. Record the date and time of the participant’s first Maintenance Period 
dose. 
To clarify language 
1.2. Schedule of 
Activities (SoA) 
Added DSFU 1 and 2 columns to Table 2 along with their respective activities. Only these changes 
are shown here and not the whole table. Addition of ‘a’ and ‘b’ footnotes reordered footnotes 
afterwards. 
Table 2. Schedule of Activities for the LTE Period* 
To reflect the changes 
to the Long-Term 
Extension Period, and 
to clarify that 
participants do not need 
to record study drug 
administration details in 
their Participant Diaries 

CONFIDENTIAL  
 
MORF-057-202 Protocol 
 
 
Version 3.0 Final 26MAR2025 
 
12  
Study Procedure 
Dose 
Switch 
Follow-up 
1 a 
Dose 
Switch 
Follow-up 
2 b 
LTE Period* 
Safety 
Follow-up 
UNS ac 
Visit 
DSFU 1 
DSFU 2 
11 
12 
13 
14/LTE 
EOT bd, ce 
SFU df, eg 
 
Week 
4 weeks 
after the 
dose switch 
4 weeks 
after DSFU 
1 
65 
78 
91 
104 
108 
 
Study Day 
 
 
456±
7 
547±
7 
638±
7 
729±7 
757+7 fh 
 
Informed 
consent 
 
 
X * 
X * 
X * 
 
 
 
Fill out 
Participant 
Diary (daily 
rectal bleeding, 
stool frequency, 
study drug 
administration) 
gi 
X 
X 
 
 
 
 
 
 
Participant 
Diary 
completion and 
compliance 
review 
X 
X 
 
 
 
 
 
 
Pregnancy test hj 
X 
X 
 
 
 
 
 
 
Safety 
Assessments 
 
 
 
 
 
 
 
 
Concomitant 
medications 
X 
X 
 
 
 
 
 
 
Physical exam jl 
X 
X 
 
 
 
 
 
 
Vital signs km 
X 
X 
 
 
 
 
 
 
PML checklist ln 
X 
X 
 
 
 
 
 
 
Hematology and 
coagulation 
X 
X 
 
 
 
 
 
 
during the LTE Period 

CONFIDENTIAL  
 
MORF-057-202 Protocol 
 
 
Version 3.0 Final 26MAR2025 
 
13  
Section No. and Name 
Description of Change 
Brief Rationale 
Serum 
chemistry 
X 
X 
 
 
 
 
 
 
Urinalysis 
X 
X 
 
 
 
 
 
 
AE/SAE 
assessment mo, np 
X 
X 
 
 
 
 
 
 
Study Drug 
 
 
 
 
 
 
 
 
Study drug 
accountability 
X 
X 
 
 
 
 
 
 
Confirm switch 
of study drug t 
X 
 
 
 
 
 
 
 
Abbreviations: AE, adverse event; B.I.D., twice a day; DSFU, Dose Switch Follow-up; ICF, Informed 
Consent Form; LTE, Long-Term Extension; LTE EOT, Long-Term Extension End of Treatment; MES, 
Mayo Endoscopic Subscore; NI, Nancy Histopathology Index; PML, progressive multifocal 
leukoencephalopathy; RHI, Robarts Histopathology Index; SAE, serious adverse event; SFU, Safety 
Follow-up; UNS, unscheduled. 
* Note: Due to the changes in Version 3.0 of this protocol, all participants who choose to continue their 
treatment in the LTE Period will be asked to re-consent to the LTE Period dose switch to 200 mg B.I.D. 
The dose switch will occur at Visit 10 or at a scheduled visit in the LTE Period (Visit 11, 12, or 13). 
For example, a participant who has already completed Visit 11 at the time that Protocol Version 3.0 is 
active will complete the dose switch at Visit 12 (Week 78). Then, the DSFU 1 will be completed 4 weeks 
later (Week 82), and the DSFU 2 will be 4 weeks after DSFU 1 (Week 86). Then, the participant will 
resume regular visits with the next visit at Visit 13 (Week 91) through the end of the study. If the 
participant does not consent to the dose switch, they will remain on their current LTE Period dose and 
schedule and will not need to attend DSFUs 1 or 2. 
a The DSFU 1 will occur 4 weeks after the dose switch. 
b The DSFU 2 will occur 4 weeks after the DSFU 1. 
t Site staff will contact the participants who consented, by phone or other means, on the next business 
day after the dose switch in the LTE Period to confirm the participants have switched to the new dose 
(200 mg B.I.D.) of study drug correctly. Record the date and time of the participant’s first dose of the 
new dose (200 mg B.I.D.) in the source documents. 
1.2. Schedule of 
Activities (SoA) 
Table 2 Footnote 
bd Visit 14 is split into Stage 1 and Stage 2 to clarify the timing of the endoscopy procedure. The 
endoscopy procedure at Visit 14 Stage 1 should be performed on or within 7 days before the Visit 14 
Stage 2 in clinic assessments have been completed. 
 
To clarify the timing of 
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pr Endoscopy is required at Visit 14/LTE EOT Stage 1 unless it was performed within 6 months of the 
LTE EOT Visit. The Visit 14/LTE EOT Stage 1 endoscopy procedure should occur on or within 7 days 
before the actual Stage 2 visit date. There is a window of +7 days for the endoscopy procedure from the 
actual visit date. 
2.1. 
Study Rationale 
It is currently being developed as an oral therapy for UC because vedolizumab, which has the same 
mechanism of action, has demonstrated efficacy in patients with UC who have moderately to severely 
active disease. Relevant data from all non-clinical and clinical studies in the MORF-057 development 
program are provided in the current Investigator’s Brochure (IB). 
A first in human Phase 1 MORF-057 study (MORF-057-101) in healthy study participants has been 
completed. The study included 3 parts: a single ascending dose ([SAD] up to 400 mg) part, a multiple 
ascending dose ([MAD] up to 100 mg twice a day [B.I.D.] for 14 days) part, and a food effect ([FE] 
fixed dose of 100 mg B.I.D.) part. MORF-057 was demonstrated to be safe and well tolerated in these 
healthy study participants across all parts of the study. MORF-057 also exhibited favorable 
pharmacokinetics (PK) profiles. The observed exposure in healthy individuals is expected to be similar 
in patients with UC and to provide the receptor occupancy at these exposures that may translate to 
intended efficacy and safety outcomes. The 100 mg B.I.D. regimen in participants with UC is being 
evaluated in an ongoing open label, single arm, Phase 2 study (MORF-057-201) to provide safety, PK, 
pharmacodynamics (PD), and preliminary efficacy data to inform further development of MORF-057 in 
patients with UC. 
A Phase 1 study (
) was conducted in healthy participants to investigate the safety, 
tolerability, PK, and PD of single and multiple doses of MORF-057 immediate-release (IR) capsules. 
The single (25 mg, 200 mg, and 100 mg [with and without food]) and multiple (200 mg B.I.D. for 14 
days) dosing of MORF-057 IR capsules was demonstrated to be safe and well tolerated. The new 
MORF-057 IR capsule formulation was selected to be used in future studies. Data from this study and 
the MORF-057-101 study were primarily used for selecting the doses and dosing regimens for this 
current Phase 2b study (MORF-057-202). 
To revise to the most up 
to date development 
program information 
2.2.1. 
Non-clinical 
Findings 
MORF 057 has a moderate blood clearance with a terminal half-life of less than 3 hours in mice, rats, 
dogs, and monkeys. Absorption following oral administration was rapid with a Tmax of up to 2 hours. 
Moderate bioavailability was observed in rats and dogs, but low bioavailability was observed in mice 
and cynomolgus monkeys. The binding of MORF 057 to plasma proteins was high across species and 
was not different from the in vitro assessment in human plasma. 
MORF-057 has been characterized in Good Laboratory Practice-compliant toxicity and safety studies. 
MORF-057 had no effect on respiration, neurobehavior, or cardiovascular function, and had no 
genotoxicity or phototoxicity potential. Potential toxicity risks based on non-clinical data include 
effects to the stomach, liver, hematopoietic system, and embryo-fetal development. 
See the current MORF-057 IB for additional details. 
In 3-month oral repeat dose toxicity studies in Sprague Dawley rats and beagle dogs, the no observed 
adverse effect levels (NOAELs) were 450 mg/kg/day in male and female rats, and 300 mg/kg/day in 
male and female dogs. 
To revise to the most up 
to date development 
program information 
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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 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 values were 10-fold higher and area under the concentration-time curve 
(AUC)last values were up to 20-fold higher in dogs compared to rats. 
For a human dose of 200 mg B.I.D. for 3 months, the safety margin for MORF 057 in rats, the most 
sensitive toxicology species, is 47.1 65.8–fold. For a human dose of 100 mg B.I.D., the safety margins 
are 101.5 141.8–fold for 3 months of dosing and 6.5 8.7–fold for chronic dosing. The safety margins 
compared to dogs is 121.4 136.9–fold for a human dose of 200 mg B.I.D. for 3 months and 161 177–
fold for a human dose of 100 mg B.I.D. 
MORF 057 had no effects on fertility in male or female Sprague Dawley rats, no effect on early 
embryonic development in female rats, and no effects on embryo-fetal development in Sprague Dawley 
rats or white New Zealand rabbits. 
For human doses of 100 or 200 mg twice a day (B.I.D.), the calculated safety margin based on the no 
observed adverse effect levels (NOAELs) for the gastric changes identified in the 26-week study (50 
mg/kg/day) is 8.2-fold or 4.1-fold, respectively. Likewise, the exposure multiple based on the NOAEL 
observed in dogs in the 39-week study (300 mg/kg/day) is 190.2-fold or 95.6-fold for the 100 or 200 mg 
B.I.D. doses, respectively. The exposure margin based on a dose (60 mg/kg) that caused non-adverse 
minimal elevations of liver transaminases (alanine transaminase [ALT] 1.24 x) in dogs dosed for 39 
weeks is approximately 20-fold for the 100 mg B.I.D. and 10-fold for the 200 mg B.I.D. doses. The 
safety margin based on the embryo-fetal NOAEL in rabbits (50 mg/kg/day) is 0.8-fold or 1.6-fold for 
the 100 or 200 mg B.I.D. doses, respectively (refer to Section 4 of the current IB for details). 
2.2.2. 
Clinical 
Findings 
MORF 057 has been evaluated in a first in human study (MORF 057 101). This study included SAD, 
FE, and MAD assessments in healthy study participants. Overall, MORF 057 was well tolerated at all 
doses in the SAD, FE, and MAD cohorts with no safety signals identified. All treatment-emergent 
adverse events (TEAEs) reported during the study were mild to moderate in severity and resolved 
within the safety reporting period; none required study drug discontinuation. Following single doses 
between 25 mg and 400 mg and multiple doses between 25 mg B.I.D. and 100 mg B.I.D., MORF 057 
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program information 

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was rapidly absorbed, and systemic exposure increased with an increase in dose in a generally 
proportional manner. No clinically relevant FE was demonstrated, indicating MORF 057 can be dosed 
without regard to timing of food intake. In the SAD and MAD cohorts, mean α4β7 receptor occupancy 
increased with dose and study day, achieving saturation (>99%) in certain individuals in each cohort 
above 25 mg, particularly in all study participants in the 100 mg B.I.D. MAD cohort. The variability of 
α4β7 receptor occupancy following single and multiple doses between 25 mg B.I.D. and 100 mg B.I.D. 
tended to decrease with an increase in dose and decreased after repeated B.I.D. doses from Day 1 to 
Day 14. In contrast, α 4β 1 receptor occupancy was below the lower limit of quantification at all doses in 
the SAD and MAD cohorts. Preliminary analyses of changes in lymphocyte subsets and C C chemokine 
receptor 9 (CCR9) transcripts over time in the MAD cohort were consistent with those reported with 
other integrin pathway inhibitors, including vedolizumab. Overall, the results of this Phase 1 study 
demonstrated favorable PK/PD and safety profiles, supporting further clinical development of MORF 
057. 
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 multiple daily doses at 100 mg B.I.D. for 14 days (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 100 
mg B.I.D. 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 (CIs) 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% CIs 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 of hormonal contraceptives was observed. 
Study 
 was conducted to evaluate the safety, tolerability, PK, PD, and FE of MORF 057 
optimized formulation with IR capsules, which were tested at single doses of 25 mg, 100 mg, and 200 
mg and at multiple doses of 200 mg B.I.D. (100 mg/capsule) in healthy participants. MORF 057 IR 
capsules were demonstrated to be safe and well tolerated, and only mild, non-serious adverse events 
(AEs) were observed, none of which were related to MORF 057. The IR capsules were rapidly 
absorbed, with a median Tmax of approximately 2.5 hours. High levels of target engagement of the 
α4β7 integrin receptor were observed following single and multiple B.I.D. doses of 200 mg MORF 057, 
with 99% mean α4β7 receptor occupancy observed after 14 days of 200 mg B.I.D. dosing. Changes in 
lymphocyte subsets were consistent with those reported for other integrin pathway inhibitors. Overall, 
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the new MORF 057 IR capsule formulation performed well and thus was recommended for use in the 
MORF 057 Phase 2 program. 
Collectively from 7 Phase 1 MORF-057 studies conducted in healthy participants (N=171 who received 
MORF-057 across all 7 studies), MORF-057 was well tolerated. There were no deaths or serious 
adverse events (SAEs). 
Drug-drug interactions (DDI) were also evaluated in the Phase 1 clinical program. At a dose of 100 
mg B.I.D., MORF-057 is a weak inducer of cytochrome P450 3A (CYP3A). Although other doses have 
not been assessed for CYP3A induction, higher doses likely carry the risk of greater induction. MORF-
057 is also a substrate of hepatic transporters organic anion transporting polypeptide (OATP) 1B1/3 
and a sensitive substrate of CYP3A. 
Safety data are also available from the completed 52-week Treatment Period in the open-label Phase 
2a study, MORF-057-201 (N=39) and from the 12-week Induction Period in this ongoing placebo-
controlled Phase 2b study, MORF-057-202 (N=280). Overall, the treatment with MORF-057 was well 
tolerated in participants with moderately to severely active UC. 
• 
No death occurred in any of the completed or ongoing studies. 
• 
In the Phase 2b study, 5 participants who received either MORF-057 or placebo reported at 
least 1 serious treatment-emergent adverse event (TEAE), all in Study MORF-057-202. The 
Investigator considered that none of these serious TEAEs were related to the study drug. 
• 
In the Phase 2 studies, a total of 11 participants discontinued the study treatment due to 
TEAEs, with 6 MORF-057 treated participants in Study MORF-057-201 and 5 participants 
who received either MORF-057 or placebo in Study MORF-057-202. 
• 
The most frequently reported TEAEs in participants receiving MORF-057 at any dose in the 
Phase 2 studies included ulcerative colitis, anemia, nasopharyngitis, and headache. 
• 
No cases of Progressive Multifocal Leukoencephalopathy (PML) were reported in any of the 
completed or ongoing studies. 
The observed safety profile was consistent with the class safety profile for α4β7 integrin inhibitors. 
No safety signals have been identified in any of the MORF-057 clinical studies. 
The clinical efficacy of MORF-057 has been evaluated in UC patients in the open label Study MORF-
057-201. In this study, a statistically significant decrease in Robarts Histopathology Index (RHI) Score 
from baseline to Week 12 was achieved, as well as a reduced modified Mayo Clinic Score (mMCS) 
from baseline. Additionally, a 25.7% remission rate was demonstrated based on mMCS. 
In the 12-week Induction Period analysis for this ongoing placebo-controlled Phase 2b study, MORF-
057-202, the primary and secondary objectives of clinical remission and clinical response, respectively, 
were not achieved. A dose-response was observed between the 3 active doses, and 200 mg B.I.D. was 
the clinically most active dose. 
Refer to the current IB for details on the clinical studies conducted to date. 

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Brief Rationale 
2.3.2.1. Risks of 
MORF-057 
Potential toxicity risks based on MORF-057 non-clinical data include effects to the stomach, liver, 
hematopoietic system, and embryo-fetal development. The gastric, hepatic, and hematopoietic findings 
demonstrated partial or complete reversibility and are generally clinically monitorable. 
Phase 1 DDI studies indicate that MORF-057 is a weak inducer of CYP3A. Sensitive CYP3A substrates 
for which small decreases in exposure can result in an unacceptable decrease in efficacy should be 
used with caution. In particular, systemic hormonal contraception should not be considered reliable 
and should not be used for the purpose of contraception. 
Based on available clinical data from both completed and ongoing studies, there are no anticipated 
risks of particular severity that require monitoring beyond the routine monitoring typically associated 
with integrin receptor antagonists or other immunomodulatory products in human studies. 
In healthy study participants (Study MORF 057 101), MORF 057 was well tolerated at all doses in the 
SAD, MAD, and FE cohorts with no safety signals identified. All TEAEs reported during the study 
were mild to moderate in severity and resolved within the safety reporting period; none required study 
drug discontinuation. 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: 
• 
Progressive multifocal leukoencephalopathy (PML) is a fatal opportunistic infection of the 
central nervous system and has been associated with systemic immunosuppressants, including 
integrin receptor antagonists (e.g., natalizumab and vedolizumab). 
• 
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 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. 
• 
Potential toxicity risks of MORF-057 based on non-clinical data include effects to embryo-
fetal development. There is no clinical experience with MORF-057 in pregnant and 
breastfeeding women and therefore, the potential effects of MORF-057 use during pregnancy 
and lactation are not known. Women who are breastfeeding or pregnant are excluded from 
this study. Women of childbearing potential (WOCBP) and men who participate in this study 
must agree to avoid pregnancy and will be instructed on contraception requirements while 
they are in this study (see Section 10.5). 
• 
Clinical studies have demonstrated that MORF-057 is a weak inducer of CYP3A, a substrate 
of hepatic transporters OATP1B1/3, and a sensitive substrate of CYP3A. Inhibitors of 
OATP1B1/3 or inhibitors/inducers of CYP3A can alter exposures of MORF-057 and their use 
is prohibited in this study (see Section 6.7.3).  
To revise to the most up 
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program information 

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Section No. and Name 
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Brief Rationale 
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 main part of the study and attended the SFU Visit OR has completed the 
Week 52/EOT Visit and has been enrolled into the LTE Period. A participant is considered to have 
completed the study if he/she has completed the Screening Period and 52‑week Treatment Period of the 
main part of the study and attended the SFU Visit OR has been enrolled into the LTE Period, completed 
the Week 104/LTE EOT Visit and attended the SFU Visit. 
The end of the study is defined as the date of the last visit or last scheduled procedure for the last 
participant in the study globally. This may occur during the main part of the study, or in the optional 
LTE Period, depending on that participant’s choice whether or not to continue in the LTE Period. 
To revise the End of 
Study definition 
6.1. Study Treatment 
Description 
A description of each study treatment type is provided in Table 3, and a description of each treatment 
group is provided in Table 4. More detailed information about MORF 057 and placebo can be found in 
the Pharmacy Manual. Refer to Section 8.3 for study drug administration instructions. 
More detailed information about MORF-057 and placebo can be found in the Pharmacy Manual. 
MORF-057 and placebo capsules will be manufactured, quality control tested, and released in 
accordance with Good Manufacturing Practice. 
To clarify text 
6.1. Study Treatment 
Description 
Table 4. Treatment Groups 
Group title 
Group 1 
Group 2 
Group 3 
Group 4 
Type 
• 
Induction: 
Experimental 
Maintenance/LTE 
Period: 
Experimental 
• 
Induction: 
Experimental 
Maintenance/LTE 
Period: 
Experimental 
• 
Induction: 
Experimental 
Maintenance/LTE 
Period: 
Experimental 
• 
Induction: 
Placebo 
Maintenance/LTE 
Period: 
Experimental 
Induction 
Period dosing 
regimen 
(12 Weeks) 
MORF-057 
(200 mg B.I.D.) 
Total dose/day: 
400 mg 
 
 
MORF-057 
(100 mg B.I.D.) 
Total dose/day: 
200 mg 
 
Placebo 
MORF-057 
(100 mg Q.D.-M) 
Total dose/day: 
100 mg 
 
Placebo 
Placebo 
 
To revise the dose for 
the Long-Term 
Extension Period 
 
In the Induction Period 
analysis for this study, a 
dose-response was 
observed between the 3 
active doses, and 200 
mg B.I.D. was the 
clinically most active 
dose. Changing the 
dose for the Long-Term 
Extension Period from 
100 mg B.I.D. to 200 
mg B.I.D. will provide 
current study 
participants with an 
opportunity to receive a 
higher dose that may be 
more clinically active. 
Based on all available 
clinical data, this 
change is not expected 

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Section No. and Name 
Description of Change 
Brief Rationale 
Maintenance 
Period dosing 
regimen 
(40 Weeks)/ 
LTE Period 
dosing 
regimen 
(52 Weeks) 
MORF-057 
(100 mg B.I.D.) 
Total dose/day: 
200 mg 
 
Placebo 
MORF-057 
(100 mg B.I.D.) 
Total dose/day: 
200 mg 
 
Placebo 
MORF-057 
(100 mg Q.D.-M) 
Total dose/day: 
100 mg 
 
Placebo 
MORF-057 
(200 mg Q.D.-E) 
Total dose/day: 
200 mg 
 
Placebo 
Instructions 
for 
administration 
Take 1 capsule 
from EACH bottle 
for the respective 
dosing time 
(morning or 
evening). Each 
bottle contains 30 
capsules of either 
MORF-057 or 
placebo. 
Take 1 capsule 
from EACH 
bottle for the 
respective dosing 
time (morning or 
evening). Each 
bottle contains 30 
capsules of either 
MORF-057 or 
placebo. 
Take 1 capsule 
from EACH bottle 
for the respective 
dosing time 
(morning or 
evening). Each 
bottle contains 30 
capsules of either 
MORF-057 or 
placebo. 
Take 1 capsule 
from EACH bottle 
for the respective 
dosing time 
(morning or 
evening). Each 
bottle contains 30 
capsules of either 
MORF-057 or 
placebo. 
LTE Period 
(52 Weeks)* 
MORF-057 
(200 mg B.I.D.) 
Total dose/day: 
400 mg 
MORF-057 
(200 mg B.I.D.) 
Total dose/day: 
400 mg 
MORF-057 
(200 mg B.I.D.) 
Total dose/day: 
400 mg 
MORF-057 
(200 mg B.I.D.) 
Total dose/day: 
400 mg 
to increase the risk of 
any potential safety 
effects. 

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Section No. and Name 
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Brief Rationale 
Instructions 
for 
administration 
Bottles will 
contain 30 (thirty) 
MORF-057 100 
mg capsules. Take 
2 capsules in the 
morning and 2 
capsules in the 
evening. 
Bottles will 
contain 30 
(thirty) MORF-
057 100 mg 
capsules. Take 2 
capsules in the 
morning and 2 
capsules in the 
evening. 
Bottles will 
contain 30 (thirty) 
MORF-057 100 
mg capsules. Take 
2 capsules in the 
morning and 2 
capsules in the 
evening. 
Bottles will 
contain 30 (thirty) 
MORF-057 100 
mg capsules. Take 
2 capsules in the 
morning and 2 
capsules in the 
evening. 
 
Abbreviations: B.I.D., twice a day; LTE, Long-Term Extension; Q.D.-E, once a day (evening); Q.D.-M, once a day 
(morning). 
* Relevant for participants who consent to the dose switch in the LTE Period. For those that do not consent to the 
dose switch in the LTE Period, they will remain on their current LTE Period dose. 
6.3.1. Randomization 
Participants initially randomized into the placebo group will be switched to an active MORF-057 
regimen (200 mg Q.D.-E) after they complete the Induction Period and the scheduled assessments at 
Week 12 (including endoscopy). All participants who consent will be switched to a new MORF-057 
dose in the LTE Period. 
To clarify treatment 
assignment due to the 
dose switch for the 
Long-Term Extension 
Period 
6.3.2. Blinding 
Each participant will receive the same number of “morning bottles” and “evening bottles” according to 
the respective study period (Induction or Maintenance/LTE Period prior to dose switch). In the 
morning, participants should take 1 capsule from EACH “morning bottle.” In the evening, participants 
should take 1 capsule from EACH “evening bottle.” In the LTE Period after the dose switch, bottles 
will contain 30 (thirty) MORF-057 100 mg capsules. Participants who consent will take 2 capsules in 
the morning and 2 capsules in the evening. Those that do not consent to the dose switch will remain on 
their current LTE Period dose. 
All other Sponsor personnel, the project study team, site Investigator, site staff, and study participants 
will remain blinded to the individual treatment assignments in the Induction and Maintenance/LTE 
Period through the end of the study including the LTE Period. 
To clarify blinding 
procedures relative to 
the study period 
6.3.2. Blinding 
Sponsor safetyPharmacovigilance staff or designee maywill unblind theall SAE reports in the safety 
databasetreatment assignment for any participant in case the SAE meets the requirement for expedited 
reporting (e.g., is a suspected unexpected serious adverse reaction [SUSAR]). 
To reflect the new 
process due to the 
transfer of 
pharmacovigilance 
responsibilities to Eli 
Lilly and Company 

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6.4. Study Treatment 
Compliance 
The site staff will contact participants, by phone or other formsmeans, on the next business day after the 
Visit 5 clinic visit to confirm the participants have switched from the Induction Period study drug to the 
new Maintenance Period study drug bottles. In addition, the site staff will contact the participants who 
consented, by phone or other means, on the next business day after the dose switch in the LTE Period to 
confirm the participants have switched to the new dose (200 mg B.I.D.) of study drug correctly. Record 
the date and time of the participant’s first dose of the new dose (200 mg B.I.D.) in the source 
documents. 
To clarify the process 
to confirm participants' 
treatment compliance 
following the dose 
switch for the Long-
Term Extension Period 
6.4. Study Treatment 
Compliance 
When participants self-administer the study drug at home, compliance with prescribed treatment 
regimen will be assessed at each visit. Participants will be instructed to record all details about the study 
drug administered at home in the Participant Diary during the Induction and Maintenance Periods. 
To clarify that 
participants do not need 
to record study drug 
administration details in 
their Participant Diaries 
during the LTE Period 
6.6. Overdose 
An overdose is defined as any timepoint where the study participant took more pills than directed or 
took pills from a different bottle than directed (if the total daily number of capsules consumed could 
exceed the maximum total daily number of capsules possible per protocol [4 total capsules/day]). 
To clarify overdose 
definition 
7.1.1. Permanent 
Discontinuation 
• 
The participant has confirmed PML 
• 
The participant has abnormal liver function results and re-testing results indicate clinically 
significant abnormalities, as detailed in Table 12 
• 
Repeated or significant Nnon-compliance with study treatment (see Section 6.4) or study 
procedures to the extent that continued participation would pose an unacceptable risk to the 
participant, as determined by the Investigator 
To revise permanent 
discontinuation reasons 
7.1.2. Dose Interruptions 
and Re-challenge 
7.1.2. Dose Interruptions and Re-challenge 
Situations requiring study drug interruption and the potential for re-challenge are presented in Table 7. 
Decisions regarding dose interruptions and re-challenges will be made by the Investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant. 
Table 7. Study Drug Interruption and Re-challenge Guidelines 
Clinical Situation/Event 
Study Drug Interruption 
Re-Challenge 
Possible drug-induced 
liver damage 
Requirements are outlined in 
Table 12 
Requirements are outlined in 
Table 12 
PML Screening 
Requirements for study drug 
interruption after positive 
Subjective PML questionnaire 
are outlined in Section 8.8.5 
Requirements for re-challenge are 
dependent on PML being definitively 
ruled out as outlined in algorithm 
within the PML Reference Guide 
Serious Adverse Event 
Investigator and Sponsor 
Medical Monitor may interrupt 
Re-challenge decision will be made 
in each clinical situation in 
To clarify and 
consolidate dose 
interruptions and re-
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study drug administration if 
deemed necessary 
consultation with Investigator and 
Sponsor Medical Monitor 
Abbreviations: PML, progressive multifocal leukoencephalopathy. 
.Guidance regarding dose interruptions for possible drug-induced liver injury (i.e., Hy’s law cases) can 
be found in Table 11. 
7.1.3. 
Re-challenge 
Re-challenge may be allowed at the discretion of the Investigator and Medical Monitor. 
7.1.2. Dose Interruption 
and Re-challenge 
Addition of Table 7 required reordering of Tables. 
To reflect the addition 
of Table 7 
8.1.1. Prior Medications 
Study sites should make every effort to collectdocument a participant’s prior UC medications. 
To clarify text 
8.3.1. Dosing 
Instructions 
Induction Period 
For the Induction Period, each 30-day study drug supply will consist of 2 cartons (1 for morning and 1 
for evening). Inside each carton, there will be 2 corresponding bottles of study drug. Thus, an Induction 
Period 30-day study drug supply will consist of the following bottles: morning bottle #1, morning bottle 
#2, evening bottle #1, and evening bottle #2. Each participant will be instructed to take 4 capsules per 
day, 1 from each bottle, during the Induction Period. 
Maintenance Period/LTE Period (all participants including those who do not consent to the dose switch 
in the LTE Period) 
For the Maintenance Period/LTE Period, each 30-day study drug supply will consist of 1 carton. Inside 
the single carton, there will be 3 bottles of study drug: morning bottle, evening bottle #1, and evening 
bottle #2. In the morning, participants should take 1 capsule from EACHthe “morning bottle.” In the 
evening, participants should take 1 capsule from EACH “evening bottle.” Each participant will be 
instructed to take 4 capsules per day during the Induction Period and 3 capsules per day during the 
Maintenance Period/LTE Period (no dose switch). It is important to note that the bottles may contain 
capsules with either MORF-057 100 mg or placebo. Thus, the study drug must be taken exactly as 
directed in the Pharmacy Manual. 
LTE Period (for participants who re-consent to the dose switch in the LTE Period) 
All participants will be asked to re-consent to switch their dose to 200 mg B.I.D. The dose switch will 
occur at Visit 10 or at a scheduled visit in the LTE Period (Visit 11, 12, or 13). If a participant does not 
consent to the dose switch, they will be allowed to stay on their current LTE Period dose as described 
above. During the LTE Period, all participants will receive their study drug supplies as bottles 
containing 30 (thirty) MORF-057 100 mg capsules. Participants should take 2 capsules in the morning 
and 2 capsules in the evening. 
Participants will take the assigned study drug (MORF 057 or placebo [see Section 6.1]) with water 
twice daily. The study drug can be taken with or without food. No unplanned dose adjustments will be 
allowed. 
To revise the dose for 
the Long-Term 
Extension Period based 
on the completed 
Induction Period 
analysis where a dose-
response was observed 
between the 3 active 
doses, and 200 mg 
B.I.D. was the most 
clinically active dose 

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8.5. 
Participant 
Diary 
Participant Diaries should not be completed after the participant has finished their participation in the 
study at the SFU Visit. Diary entries will include study drug administration details in the Induction and 
Maintenance Periods, along with daily rectal bleeding, and stool frequency information (the 2 patient 
reported outcome measures of the Full and mMCS, see Section 8.7.3). 
To clarify the 
Participant Diary 
should not be 
completed after the 
participant exits the 
study, and to clarify 
that participants do not 
need to record study 
drug administration 
details in their 
Participant Diaries 
during the LTE Period 
8.6. Stool Collection 
Stool samples will be required for pathogen/parasite testing, to assess fecal calprotectin levels, and for 
future microbiome research (if participant consents; see Section 8.12). 
To reflect the addition 
of an optional 
exploratory fecal 
calprotectin sample 
8.7.1. Endoscopy with 
Biopsy 
Endoscopy will be performed at Screening (Visit 1) and during Stage 1 of Visits 5, 10/EOT, and 
14/LTE EOT. 
To reflect the change in 
the Long-Term 
Extension Period End 
of Treatment name 
8.7.1. Endoscopy with 
Biopsy 
Table 89. Instructions for Endoscopic Biopsies 
 
Visit 14/ 
(Week 104 or LTE EOT) 
Abbreviations: EOT, End of Treatment; LTE EOT, Long-Term Extension End of Treatment. 
To reflect the change in 
the Long-Term 
Extension Period End 
of Treatment name 
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, Visit 10/EOT, and Visit 14/LTE EOT; and a targeted 
exam may be performed at all other required visits. 
To reflect the change in 
the Long-Term 
Extension Period End 
of Treatment name 
8.8.4. Clinical Safety 
Laboratory Tests 
All protocol-required laboratory tests, as defined in Section 10.3, must be conducted in accordance with 
the Laboratory Manual. In case of abnormal liver function test results, Investigators should follow the 
instructions in Table 11 (Hy’s law cases table) Table 12 for re-testing and follow-up procedures. 
Administrative 
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 at study visits according to the schedule in the SoA (Section 1.2). 
If the results of the questionnaire are suggestive of signs and symptoms of PML, thehold any further 
doses of study drug and notify the Medical Monitor. The participant will undergo Objective PML 
Checklist testing (Section 10.2), a full neurological exam by a neurologist, and, if indicated, additional 
testing. Study drug may not be resumed until PML has been definitively ruled out. 
To clarify PML 
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A participant with confirmed PML will be excluded from the study or will permanently discontinue 
study drug and will be withdrawn from the study (see Section 7.1.1). 
8.9. Adverse Events and 
Other Safety Reporting 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant’s legally authorizedacceptable representative). 
To reflect current ICH 
guidelines 
8.9.4. Regulatory 
Reporting Requirements 
for SAEs, SUSARs, and 
Periodic Reports 
Morphic TherapeuticThe Sponsor or a designee is responsible for notifying the relevant regulators 
(including the authorities in the European Economic Area (EEA) via EudraVigilance and the 
IRBs/IECs) and the Investigator sites within the specified timeframes of all SUSARs, as applicable per 
local requirements. Morphic TherapeuticThe Sponsor will make the determination whether the event is 
unexpected. 
The following sentence is in Protocol Amendment Version 2.0 but not in Version 2.1 and is added 
to Version 3.0. 
It is the Principal Investigator’s responsibility to notify the IRB/IEC according to the relevant 
regulatory timelines of all SUSARs of which the Investigator is notified by Morphic Therapeuticthe 
Sponsor that occur at his or her site, if appropriate. 
To clarify reporting 
requirements 
8.12. Future Research 
If consent is provided by the participant, blood, stool, and colonic tissue samples will be collected and 
may be used for furtherfuture PD, pharmacogenomics, microbiome-related research, fecal calprotectin 
assessment, and future research. If consent is provided by the participant, the remaining blood and 
colonic tissue samples from the study-required procedures may also be used for future research, 
including future PK research.  
To reflect the addition 
of an optional 
exploratory fecal 
calprotectin sample and 
clarify sample 
collection for future 
research 
8.13. 
Potential 
Adjustments due to 
COVID-19 or Other 
Global Issues  
8.13. Potential Adjustments due to COVID-19Pandemics or Other Global Issues 
Adjustments to the planned study procedures might be necessary due to the ongoing COVID-19 
pandemic events and/or newly identified global issues.  
To revise for any 
pandemic 
10.1.1. Regulatory and 
Ethical Considerations 
IRB/IEC information was in Protocol Amendment Version 2.0 but not Version 2.1, and “Member 
States Concerned” was in Version 2.1 but not Version 2.0. Both are now in Version 3.0. 
The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., advertisements) must 
be submitted to, an IRB/IEC or to the Member States Concerned and reviewed, and approved by the 
IRB/IEC or Member States Concerned, as applicable, before the study is initiated. 
Any amendments to the protocol will require IRB/IEC or Member States Concerned, as applicable, 
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 Member States Concerned or 
health authority, as applicable, approval prior to initiation, in line with country-specific requirements. 
The Investigator will be responsible for the following: 
To combine Protocol 
Amendment Version 
2.0 and Version 2.1 to 
Version 3.0 

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• 
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, as applicable 
• 
Notifying the IRB/IEC of SAEs or other significant safety findings as required by IRB/IEC 
procedures, as applicable 
• 
Providing oversight of the conduct of the study at the site and adherence to requirements of 21 
CFR, ICH guidelines, the IRB/IEC or Member States Concerned, as applicable, European 
Union Clinical Trials Regulation 536/2014 for clinical studies, and all other applicable local 
regulations 
10.1.4. Informed 
Consent Process 
IRB/IEC information was in Protocol Amendment Version 2.0 but not Version 2.1, and “Member 
States Concerned” was in Version 2.1 but not Version 2.0. Both are now in Version 3.0. 
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 authorizedacceptable representative, if applicable, and 
answer all questions regarding the study. 
Participants must be informed that their participation is voluntary. Each participant or his/her legally 
authorizedacceptable representative, if applicable, 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, Member States Concerned/and the IRB/IEC or study center. 
 
A copy of the ICF(s) must be provided to the participant or his/her legally authorizedacceptable 
representative, if applicable. 
To reflect current ICH 
guidelines and combine 
Protocol Amendment 
Version 2.0 and 
Version 2.1 to Version 
3.0 
10.1.4. Informed 
Consent Process 
Additional Consents 
The main ICF will contain separate sections for the following additional consents: 
• 
Optional collection of blood, colonic tissue, and stool samples for future PD, microbiome-
related analyses, fecal calprotectin assessment, and future research., and If consent is 
provided, use of the remaining blood and colonic tissue samples from the study-required 
procedures may also be used for future research, including future PK research (see Sections 
8.7.1, 8.10, 8.12, and the SoA in Section 1.2). 
To reflect the addition 
of an optional 
exploratory fecal 
calprotectin sample 
10.1.4. Informed 
Consent Process 
Additional ICFs will be provided to participants or their partners for review and signature, as needed: 
• 
Pregnant PartnerPregnancy Follow-up (see Section 8.9.5) 
To revise the name of 
the consent form 
10.1.5. Data Protection 
IRB/IEC information was in Protocol Amendment Version 2.0 but not Version 2.1, and “Member 
States Concerned” was in Version 2.1 but not Version 2.0. Both are now in Version 3.0. 
In particular, 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 or Member States Concerned members, as applicable, and by inspectors 
from regulatory authorities. 
To combine Protocol 
Amendment Version 
2.0 and Version 2.1 to 
Version 3.0 
10.1.9. Data Quality 
Assurance 
IRB/IEC information was in Protocol Amendment Version 2.0 but not Version 2.1 and is now in 
Version 3.0. 
To combine Protocol 
Amendment Version 

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Section No. and Name 
Description of Change 
Brief Rationale 
The Investigator must permit study-related monitoring, audits, IRB/IEC review (if applicable), and 
regulatory agency inspections and provide direct access to source data documents. 
2.0 and Version 2.1 to 
Version 3.0 
10.1.9. Data Quality 
Assurance 
The following paragraph was kept from Protocol Amendment Version 2.1 and not edited as is in 
Version 2.0. 
The contents of the electronic Trial Master File pertaining to the conduct of this study must be retained 
by the Sponsor and the Investigator for at least 25 years after study completion unless local regulations, 
institutional policies, or by an agreement with the Sponsor require a longer retention period. However, 
the medical files of participants shall be archived in accordance with national law. It is the 
responsibility of the Sponsor to inform the Investigator/institution as to when these documents no 
longer need to be retained. 
To combine Protocol 
Amendment Version 
2.0 and Version 2.1 to 
Version 3.0 
10.1.9. Data Quality 
Assurance 
Please reference the current version of ICH E6 (R2) Section 8 for the minimum list of essential 
documents required for the conduct of a clinical trial. 
To reflect current ICH 
guidelines 
10.1.11.2.
 
Study/Site 
Termination  
IRB/IEC information was in Protocol Amendment Version 2.0 but not Version 2.1, and “Member 
States Concerned” was in Version 2.1 but not Version 2.0. Both are now in Version 3.0. 
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 
For site termination: 
• 
Failure of the Investigator to comply with the protocol, the requirements of the Member States 
Concerned or IRB/IEC, as applicable, 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 enrolled earlier than expected 
Reasons for study termination include, but are not limited to: 
• 
Recommendation of the DSMB based on the ongoing review of safety 
• 
If a positive benefit/risk ratio is no longer observed, based on DSMB review of unblinded data 
• 
Discontinuation of further study drug development 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, the Member States Concerned, and/or the IRBs/IECs, as applicable, the regulatory 
authorities, and any CROs used in the study of the reason for termination or suspension, as specified by 
the applicable regulatory requirements. 
To combine Protocol 
Amendment Version 
2.0 and Version 2.1 to 
Version 3.0 and clarify 
study/site termination 
10.2. Appendix 2: 
Progressive Multifocal 
Leukoencephalopathy 
Checklists 
Objective PML Checklist – To be completed for patientsparticipants with positive subjective finding 
Table Footnotes 
× If objective test corroborates the reported symptom, refer the participant for a Neurology consult. 
Otherwise, please follow up with the participant one week after the Oobjective Cchecklist was 
administered to ensure symptoms are not recurring. 
Administrative 

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Brief Rationale 
× Please notify your Clinical Research Associate and Morphic Therapeuticthe Sponsor of any positive 
Oobjective Cchecklist findings. 
10.3. 
Appendix 3: 
Clinical Laboratory 
Tests 
IRB/IEC information was in Protocol Amendment Version 2.0 but not Version 2.1, and “Member 
States Concerned” was in Version 2.1 but not Version 2.0. Both are now in Version 3.0. 
Table 11 Footnotes 
a Local urine testing will be standard for the protocol unless serum testing is required by local 
regulation or Member States Concerned or IRB/IEC, as applicable. 
To combine Protocol 
Amendment Version 
2.0 and Version 2.1 to 
Version 3.0 
10.3. 
Appendix 3: 
Clinical Laboratory 
Tests 
Table 1112. 
Abnormal Liver Function Results: Re-testing and Follow-up Procedures 
Next steps: 
• 
Discuss with Medical Monitor regarding resumption of IMP** 
 
Table 12 Footnotes 
** Resumption of the study drug can be considered only in consultation with the Medical Monitor and 
only if the liver test results returned to near baseline and if a self-limited non-study drug etiology is 
identified. Otherwise, the study drug should be permanently discontinued. 
To clarify follow-up 
procedures for 
abnormal liver function 
results 
10.4.2. Definition of 
SAE 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been admitted to the hospital for inpatient 
care, regardless of the length of stay(usually involving at least an overnight stay) at the hospital or 
emergency ward for observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. 
To clarify the definition 
of SAE 
10.4.4. Reporting of 
SAEs 
• 
SAEs will be reported to Lilly Global Patient Safety by email 
(email address will be defined in a study-specific safety 
reporting plan). 
To update SAE 
reporting email due to 
the transfer of 
pharmacovigilance 
responsibilities to Eli 
Lilly and Company 
10.5.2. Contraception 
Guidance for Female 
Study Participants 
10.5.2. Contraception Guidance for Female Study Participants 
10.5.2.1. Female Study Participants Who Do Not Consent to Dose Switch in LTE Period 
Note: This is relevant for participants who do not consent to the dose switch in the LTE Period. For 
contraception requirements for those who do consent to the dose switch in the LTE Period, see Section 
10.5.2.2. 
10.5.2.2. Female Study Participants Who Do Consent to Dose Switch in LTE Period 
Note: This is relevant for participants who do consent to the dose switch to 200 mg B.I.D. in the LTE 
Period. For contraception requirements for those who do not consent to the dose switch in the LTE 
Period, see Section 10.5.2.1. 
For participants that are currently using systemic (e.g., oral, implantable) hormonal contraception but 
have consented to the MORF-057 dose switch:  
To revise the 
contraception 
requirements for 
participants who 
consent to the increased 
study drug dose in the 
LTE Period 
CCI

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Section No. and Name 
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• 
They must change to new contraception by the time of DSFU 2 (8 weeks after the dose switch) 
or as soon as possible.  
• 
All participants must remain abstinent until new contraception is in place. 
WOCBP and WONCBP may participate in this trial. 
WOCBP who are completely abstinent as their preferred and usual lifestyle, or exclusively engage in 
sexual relations with other individual(s) who are assigned female at birth, as their preferred and usual 
lifestyle must follow the rules in this table. 
Must… 
Must not… 
agree 
to 
either 
remain abstinent or 
exclusively engage in 
sexual relations with 
other 
individual(s) 
who 
are 
assigned 
female at birth, and 
not plan a pregnancy 
during the study 
• 
use periodic abstinence methods 
o 
calendar 
o 
ovulation 
o 
symptothermal, or 
o 
post-ovulation 
• 
declare abstinence just for the duration of a 
trial, or 
• 
use the withdrawal method 
WOCBP who are NOT completely abstinent as their preferred and usual lifestyle, or who do NOT 
exclusively engage in sexual relations with other individual(s) who are assigned female at birth, as 
their preferred and usual lifestyle, must follow the rules in this table. 
Must… 
Agree to use 1 highly effective method of contraception together with a barrier method of 
contraception (see below). Note: During this study, systemic hormonal contraception is not 
considered effective or highly effective and therefore is not permitted as a means of 
contraception. 
Barrier method of contraception includes condoms (male or female) with or without a 
spermicidal agent, diaphragm, or cervical cap with spermicide. 

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Section No. and Name 
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These methods of contraception must be used during the study and for at least 28 days after the 
last dose of the study intervention. 
Examples of different methods of contraception: 
Note: Participants who switch to 200 mg B.I.D. cannot use oral or systemic hormonal contraception as 
an effective method. 
Methods 
Examples 
Highly 
effective 
contraception 
(less 
than 1% failure rate) 
• 
Fallopian tubal sterilization methods other than bilateral 
salpingectomy (laparoscopic bipolar electrocoagulation, plastic 
ring application on the uterine tubes, fallopian tube ligation, 
hysteroscopic sterilization). Note: Bilateral salpingectomy is 
indicative of permanent sterilization. Please see the WONCBP 
definition above. 
• 
Total abstinence 
• 
Sexual relationships exclusively between individuals who are 
assigned the same sex at birth 
• 
Vasectomy – for individuals assigned male at birth in clinical 
trials and for the partner of an individual assigned female at 
birth (if only sexual partner) 
• 
Fallopian tube implants (if confirmed by hysterosalpingogram), 
or 
• 
Intrauterine devices (IUD) with or without hormone-releasing 
system 
Effective contraception 
• 
Penile condom with or without spermicide 
• 
Vaginal condom with or without spermicide 
• 
Diaphragm with spermicide 

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Section No. and Name 
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• 
Cervical sponge with spermicide, or 
• 
Cervical cap with spermicide 
Note: Penile and vaginal condoms should not be used in combination. 
Ineffective methods of 
contraception whether 
used alone or in any 
combination 
• 
Combined (estrogen- and progestogen-containing) hormonal 
contraception associated with inhibition of ovulation (listed 
below) 
− oral 
− intravaginal 
− transdermal 
− injectable 
• 
Progestogen-only hormone contraception associated with 
inhibition of ovulation 
− oral 
− injectable 
− implantable 
• 
Spermicide alone 
• 
Periodic abstinence 
• 
Fertility awareness (calendar method, temperature method, 
cervical mucus, or symptothermal) 
• 
Withdrawal 
• 
Postcoital douche, or 
• 
Lactational amenorrhea 
• 
Ablation (endometrial or uterine) is not considered a form of 
contraception 

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Section No. and Name 
Description of Change 
Brief Rationale 
Abbreviations: IUD, intrauterine device; WONCBP, woman of non-childbearing potential. 
10.5.3. Contraception 
Guidance for Male Study 
Participants 
10.5.3. Contraception Guidance for Male Study Participants 
Participant Population 
Contraception Guidance 
All male study participants… 
should refrain from sperm donation for the duration of 
the study and for at least 14 days after the last dose of 
the study intervention. 
Male study participants with partner(s) 
who are WOCBP a… 
must 
• 
remain abstinent (if this is their preferred and 
usual lifestyle), or 
• 
use condoms and at least 1 additional effective 
method of contraception (see “Examples of 
different methods of contraception” table) for 
the duration of the study and for at least 
28 days after the last dose of the study 
intervention.  
Male study participants with partner(s) 
who are pregnant a… 
must 
• 
remain abstinent (if this is their preferred and 
usual lifestyle), or 
• 
use condoms for the duration of the study and 
for at least 28 days after the last dose of the 
study intervention. 
Male 
study 
participants 
who 
exclusively engage in sexual relations 
with other individual(s) who are 
 
are not required to use contraception. 
To revise the 
contraception 
requirements for 
participants who 
consent to the increased 
study drug dose in the 
LTE Period 

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Section No. and Name 
Description of Change 
Brief Rationale 
assigned male at birth, as their 
preferred and usual lifestyle… 
Abbreviations: WOCBP, woman of childbearing potential. 
a Male study participants who have undergone orchiectomy but not penectomy must use condoms 
during sex, but the partner who is WOCBP is not required to use an additional form of 
contraception. Male study participants who have undergone orchiectomy and penectomy are not 
required to use condoms. 
Examples of different methods of contraception a: 
Methods 
Examples 
Highly effective 
contraception 
(less 
than 
1% 
failure rate) 
• 
Fallopian tubal sterilization methods other than bilateral 
salpingectomy (laparoscopic bipolar electrocoagulation, plastic 
ring application on the uterine tubes, fallopian tube ligation, 
hysteroscopic sterilization). Note: Bilateral salpingectomy is 
indicative of permanent sterilization. Please see the WONCBP 
definition above. 
• 
Combined (estrogen and progestogen-containing) hormonal 
contraception associated with inhibition of ovulation (listed below) 
− oral 
− intravaginal  
− transdermal  
− injectable 
• 
Progestogen-only 
hormonal 
contraception 
associated 
with 
inhibition of ovulation 
− oral 
− injectable 
− implantable 

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Section No. and Name 
Description of Change 
Brief Rationale 
• 
Total abstinence 
• 
Sexual relationships exclusively between individuals who are 
assigned the same sex at birth 
• 
Vasectomy – for individuals assigned male at birth in clinical trials 
and for the partner of an individual assigned female at birth (if only 
sexual partner) 
• 
Fallopian tube implants (if confirmed by hysterosalpingogram), or 
• 
Intrauterine devices (IUD) with or without hormone-releasing 
system 
Effective 
contraception 
• 
Progestogen-only hormonal contraception, where inhibition of 
ovulation is not the primary mode of action 
• 
Penile condom with or without spermicide 
• 
Vaginal condom with or without spermicide 
• 
Diaphragm with spermicide 
• 
Cervical sponge with spermicide 
• 
Cervical cap with spermicide 
Note: Penile and vaginal condoms should not be used in combination. 
Ineffective 
methods 
of 
contraception 
whether 
used 
alone or in any 
combination 
• 
Spermicide alone 
• 
Periodic abstinence 
• 
Fertility awareness (calendar method, temperature method, 
cervical mucus, or symptothermal) 
• 
Withdrawal 
• 
Postcoital douche, or 

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Section No. and Name 
Description of Change 
Brief Rationale 
• 
Lactational amenorrhea 
Abbreviations: IUD, intrauterine device; WONCBP, woman of non-childbearing potential. 
a Ablation (endometrial or uterine) is not considered a form of contraception. 
10.9. 
Appendix 9: 
Genetics 
IRB/IEC information was in Protocol Amendment Version 2.0 but not Version 2.1, and “Member 
States Concerned” was in Version 2.1 but not Version 2.0. Both are now in Version 3.0. 
• 
Genetic variation may impact a participant’s response to the study drug, susceptibility to, and 
severity and progression of disease. Variable response to study treatment may be due to 
genetic determinants that impact treatment absorption, distribution, metabolism, and excretion; 
mechanism of action of the treatment; disease etiology; and/or molecular subtype of the 
disease being treated. Therefore, where local regulations and IRB/IEC or Member States 
Concerned allow, as applicable, blood samples will be collected for DNA analysis from 
consenting participants. 
To combine Protocol 
Amendment Version 
2.0 and Version 2.1 to 
Version 3.0 
10.11. 
Appendix 11: 
Changes to This Protocol 
in Previous Amendments 
Added Appendix 11 showing changes made in previous Protocol Amendment Version 2.0 and 2.1. 
Administrative 
 

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TABLE OF CONTENTS 
 
Clinical Study Protocol ..................................................................................................................1 
Protocol Amendment Summary of Changes ...............................................................................3 
Table of Contents .........................................................................................................................36 
Table of Tables .............................................................................................................................40 
Table of Figures............................................................................................................................41 
Abbreviations ...............................................................................................................................42 
1. 
Protocol Summary ........................................................................................................45 
1.1. 
Synopsis ..........................................................................................................................45 
1.2. 
Schedule of Activities (SoA) ..........................................................................................66 
2. 
Introduction ...................................................................................................................77 
2.1. 
Study Rationale ...............................................................................................................77 
2.2. 
Background .....................................................................................................................78 
2.2.1. 
Non-clinical Findings......................................................................................................78 
2.2.2. 
Clinical Findings .............................................................................................................79 
2.3. 
Benefit/Risk Assessment ................................................................................................80 
2.3.1. 
Benefits ...........................................................................................................................80 
2.3.2. 
Risks ................................................................................................................................80 
2.3.3. 
Overall Benefit Risk Conclusion ....................................................................................82 
3. 
Objectives and Endpoints ............................................................................................82 
4. 
Study Design ..................................................................................................................87 
4.1. 
Overall Design ................................................................................................................87 
4.2. 
Scientific Rationale for Study Design ............................................................................89 
4.3. 
Justification for Dose ......................................................................................................90 
4.4. 
End of Study Definition ..................................................................................................91 
5. 
Study Population ...........................................................................................................91 
5.1. 
Inclusion Criteria ............................................................................................................91 
5.2. 
Exclusion Criteria ...........................................................................................................96 
5.3. 
Lifestyle Considerations .................................................................................................99 
5.4. 
Screen Failures ................................................................................................................99 
6. 
Study Treatment and Concomitant Therapies ........................................................100 
6.1. 
Study Treatment Description ........................................................................................100 
6.2. 
Preparation, Handling, Storage, and Accountability ....................................................103 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ..........................................103 
6.3.1. 
Randomization ..............................................................................................................103 
6.3.2. 
Blinding.........................................................................................................................103 
6.4. 
Study Treatment Compliance .......................................................................................104 
6.5. 
Continued Access to Study Treatment After the End of the Study ..............................105 
6.6. 
Overdose .......................................................................................................................105 
6.7. 
Concomitant Therapy ...................................................................................................105 

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6.7.1. 
Concomitant Medications .............................................................................................105 
6.7.2. 
Allowed Medications for the Treatment of Ulcerative Colitis .....................................106 
6.7.3. 
Prohibited Medications .................................................................................................107 
6.7.4. 
Prohibited Procedures ...................................................................................................109 
7. 
Discontinuation of Study Treatment and Participant 
Discontinuation/Withdrawal......................................................................................110 
7.1. 
Discontinuation of Study Treatment .............................................................................110 
7.1.1. 
Permanent Discontinuation ...........................................................................................110 
7.1.2. 
Dose Interruption and Re-challenge .............................................................................111 
7.2. 
Participant Discontinuation/Withdrawal from the Study ..............................................111 
7.3. 
Lost to Follow-up..........................................................................................................112 
8. 
Study Assessments and Procedures...........................................................................112 
8.1. 
Medical History ............................................................................................................112 
8.1.1. 
Prior Medications ..........................................................................................................113 
8.2. 
Screening-specific Tests ...............................................................................................113 
8.2.1. 
Screening Stages ...........................................................................................................113 
8.2.2. 
Screening for Pathogens and/or Infections ...................................................................113 
8.2.3. 
Drug/Alcohol Screening ...............................................................................................115 
8.3. 
Study Drug Administration ...........................................................................................115 
8.3.1. 
Dosing Instructions .......................................................................................................115 
8.3.2. 
Missed Dose Instructions ..............................................................................................116 
8.4. 
Virtual/Hybrid Visits ....................................................................................................116 
8.5. 
Participant Diary ...........................................................................................................117 
8.6. 
Stool Collection ............................................................................................................117 
8.7. 
Efficacy Assessments ...................................................................................................117 
8.7.1. 
Endoscopy with Biopsy ................................................................................................117 
8.7.2. 
Histologic Scores ..........................................................................................................119 
8.7.3. 
Mayo Clinic Score ........................................................................................................119 
8.7.4. 
Non-endoscopic Biomarkers of Inflammation ..............................................................120 
8.7.5. 
Inflammatory Bowel Disease Questionnaire ................................................................120 
8.8. 
Safety Assessments .......................................................................................................121 
8.8.1. 
Physical Examinations ..................................................................................................121 
8.8.2. 
Vital Signs .....................................................................................................................121 
8.8.3. 
Electrocardiograms .......................................................................................................121 
8.8.4. 
Clinical Safety Laboratory Tests ..................................................................................121 
8.8.5. 
Progressive Multifocal Leukoencephalopathy ..............................................................122 
8.8.6. 
Pregnancy/Menopause Testing .....................................................................................122 
8.8.7. 
Concomitant Therapies .................................................................................................122 
8.9. 
Adverse Events and Other Safety Reporting ................................................................123 
8.9.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ...................................................................................................................123 
8.9.2. 
Method of Detecting AEs and SAEs ............................................................................123 
8.9.3. 
Follow-up of AEs and SAEs .........................................................................................123 
8.9.4. 
Regulatory Reporting Requirements for SAEs, SUSARs, and 
Periodic Reports ............................................................................................................124 
8.9.5. 
Pregnancy ......................................................................................................................124 

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8.9.6. 
Adverse Events of Special Interest ...............................................................................125 
8.10. 
Pharmacokinetics ..........................................................................................................125 
8.10.1. Collection of Blood Samples for MORF-057 Concentration 
Determination in Plasma ...............................................................................................125 
8.10.2. Determination of Drug Concentration and PK Parameters ...........................................126 
8.11. 
Pharmacodynamics .......................................................................................................126 
8.11.1. Receptor Occupancy .....................................................................................................126 
8.11.2. CCR9 mRNA ................................................................................................................126 
8.11.3. Lymphocyte Subsets .....................................................................................................126 
8.12. 
Future Research ............................................................................................................127 
8.13. 
Potential Adjustments due to Pandemics or Other Global Issues .................................127 
9. 
Statistical Considerations ...........................................................................................127 
9.1. 
Analysis Sets .................................................................................................................127 
9.2. 
Statistical Analyses .......................................................................................................128 
9.2.1. 
General Considerations .................................................................................................128 
9.2.2. 
Analysis of Demographics and Baseline Characteristics ..............................................128 
9.2.3. 
Efficacy Analyses .........................................................................................................128 
9.2.4. 
Safety Analyses .............................................................................................................131 
9.2.5. 
Pharmacokinetics Analyses ..........................................................................................132 
9.2.6. 
Pharmacodynamics Analyses........................................................................................132 
9.3. 
Analyses for Induction Period, 52-week Treatment Period, and 
LTE Period ....................................................................................................................132 
9.4. 
Interim Analysis ............................................................................................................133 
9.5. 
Sample Size Determination ..........................................................................................133 
10. 
Appendices: Supporting Documentation and Operational 
Considerations .............................................................................................................134 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ..............................................................................................................134 
10.1.1. Regulatory and Ethical Considerations .........................................................................134 
10.1.2. Financial Disclosure......................................................................................................135 
10.1.3. Insurance .......................................................................................................................135 
10.1.4. Informed Consent Process ............................................................................................135 
10.1.5. Data Protection..............................................................................................................136 
10.1.6. Data and Safety Monitoring Board ...............................................................................137 
10.1.7. PML Adjudication Committee ......................................................................................137 
10.1.8. Dissemination of Clinical Study Data...........................................................................137 
10.1.9. Data Quality Assurance ................................................................................................137 
10.1.10. Source Documents ........................................................................................................138 
10.1.11. Study and Site Start and Closure ..................................................................................138 
10.1.12. Publication Policy .........................................................................................................139 
10.2. 
Appendix 2: Progressive Multifocal Leukoencephalopathy 
Checklists ......................................................................................................................140 
10.3. 
Appendix 3: Clinical Laboratory Tests .........................................................................142 
10.4. 
Appendix 4: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .......................................................145 
10.4.1. Definition of AE ...........................................................................................................145 

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10.4.2. Definition of SAE .........................................................................................................146 
10.4.3. Recording and Follow-up of AE and/or SAE ...............................................................147 
10.4.4. Reporting of SAEs ........................................................................................................149 
10.5. 
Appendix 5: Contraceptive and Barrier Guidance ........................................................151 
10.5.1. Definitions.....................................................................................................................151 
10.5.2. Contraception Guidance for Female Study Participants ...............................................152 
10.5.3. Contraception Guidance for Male Study Participants ..................................................155 
10.6. 
Appendix 6: Histological Scoring Indices ....................................................................158 
10.7. 
Appendix 7: Mayo Clinic Scoring System for Assessment of 
Ulcerative Colitis Activity ............................................................................................159 
10.8. 
Appendix 8: Inflammatory Bowel Disease Questionnaire (IBDQ) ..............................161 
10.9. 
Appendix 9: Genetics....................................................................................................171 
10.10. 
Appendix 10: Investigator’s Agreement .......................................................................172 
10.11. 
Appendix 11: Changes to This Protocol in Previous Amendments..............................173 
11. 
References ....................................................................................................................230 

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Table of Tables 
Table 1. 
Schedule of Activities for the Treatment Period ............................................... 66 
Table 2. 
Schedule of Activities for the LTE Period* ...................................................... 74 
Table 3. 
Study Treatment .............................................................................................. 100 
Table 4. 
Treatment Groups ............................................................................................ 101 
Table 5. 
Corticosteroid Equivalent Doses† .................................................................... 106 
Table 6. 
Examples of Drugs Potentially Altering Exposures to MORF-057# ............... 109 
Table 7. 
Study Drug Interruption and Re-challenge Guidelines ................................... 111 
Table 8. 
Summary of Tuberculosis Screening and Eligibility ...................................... 114 
Table 9. 
Instructions for Endoscopic Biopsies .............................................................. 118 
Table 10. 
Pharmacokinetics Sampling Windows ............................................................ 126 
Table 11. 
Protocol-required Laboratory Tests ................................................................ 142 
Table 12. 
Abnormal Liver Function Results: Re-testing and Follow-up Procedures ..... 144 

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Table of Figures 
Figure 1. 
Study Schema .................................................................................................... 89 
Figure 2. 
Hierarchical Testing Procedure ....................................................................... 131 
 

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Abbreviations 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine transaminase 
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 
B.I.D. 
Twice a day 
BMI 
Body mass index 
C24 
Plasma concentration at 24 hours post-dose 
CCR9 
C-C chemokine receptor 9 
C. difficile 
Clostridiodes difficile 
CI 
Confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
Cmax 
Maximum observed plasma concentration 
CMH 
Cochran-Mantel-Haenszel 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
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 
DDI 
Drug-drug interaction 
DNA 
Deoxyribonucleic acid 
DSFU 
Dose Switch Follow-up 
DSMB 
Data and Safety Monitoring Board 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic data capture 
EEA 
European Economic Area 
EOT 
End of Treatment 
EU 
European Union 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FE 
Food effect 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
hCG 
human chorionic gonadotropin 
HIV 
Human immunodeficiency virus 
HRQoL 
Health-related quality of life 

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HRT 
Hormonal replacement therapy 
hs-CRP 
High-sensitivity C-reactive protein 
IB 
Investigator’s Brochure 
IBD 
Inflammatory bowel disease 
IBDQ 
Inflammatory Bowel Disease Questionnaire 
IC50 
Half maximal inhibitory concentration 
IC90 
90% of maximal inhibitory concentration 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation  
IEC 
Independent Ethics Committee 
IGRA 
Interferon gamma release assay 
IL 
Interleukin 
IR 
Immediate-release 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
JAK 
Janus kinase 
LTE 
Long-Term Extension 
LTE EOT 
Long-Term Extension End of Treatment 
LVEF 
Left ventricular ejection fraction 
MAD 
Multiple ascending dose 
MCS 
Full Mayo Clinic Score 
MedDRA 
Medical Dictionary of Regulatory Activities 
MES 
Mayo Endoscopic Score 
mMCS 
Modified Mayo Clinic Score 
mRNA 
Messenger ribonucleic acid 
NI 
Nancy Histopathology Index 
NOAEL 
No-observed-adverse-effect level 
PD 
Pharmacodynamics 
PGA 
Physician’s Global Assessment 
PK 
Pharmacokinetics 
PML 
Progressive multifocal leukoencephalopathy 
P.O. 
By mouth 
PP 
Per Protocol 
PPD 
Purified protein derivative 
PRO 
Patient-reported outcome 
PT 
Preferred Term 
Q.D. 
Once a day 
Q.D. -E 
Once a day (evening) 
Q.D. -M 
Once a day (morning) 
QTcF 
QT interval corrected through use of Fridericia’s formula 
RAMP 
Risk Assessment and Minimization Program 
RHI  
Robarts Histopathology Index 
S1P 
Sphingosine-1-phosphate 
SAD 
Single ascending dose 

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SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SC 
Subcutaneous 
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 
WOCBP 
Woman of Childbearing Potential 
WONCBP 
Woman of Non-childbearing Potential 

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1. 
Protocol Summary 
1.1. 
Synopsis 
Protocol Title: A Phase 2b, Randomized, Double-blind, Placebo-controlled Study to Evaluate the 
Safety and Efficacy of 3 Active Dose Regimens of MORF-057 in Adults with Moderately to 
Severely Active Ulcerative Colitis (EMERALD-2) 
Brief Title: A Phase 2b Study to Evaluate MORF-057 in Adults with Moderately to Severely 
Active UC 
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 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 abdominal 
pain, bloody stool, diarrhea, urgency to defecate, fatigue, nausea, loss of appetite, weight loss, 
fever, and anemia. Initial therapy for moderately to severely active UC generally includes 
5-aminosalicylates and corticosteroids. However, long-term use of corticosteroids has been 
associated with adverse effects. 
Integrins are a family of receptors known to regulate aspects of mucosal inflammation that underlie 
UC disease progression. UC is associated with activation of immune cells expressing the integrin 
α4β7 and trafficking these cells from the bloodstream into the gut and the surrounding tissue to 
promote chronic inflammation. Specific 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 that is designed to 
selectively inhibit integrin α4β7 and that is administered orally, thus avoiding the need for periodic 
therapeutic infusions and the complications associated with this form of drug administration. 
Relevant data from all non-clinical and clinical studies in the MORF-057 development program 
are provided in the current Investigator’s Brochure. 
The current Phase 2b study (MORF-057-202) aims to evaluate the efficacy and safety of 3 active 
dose regimens of MORF-057 (as capsule, by mouth [P.O.]) versus placebo in study participants 
with moderately to severely active UC. Data from this study will provide further information to 
advance the clinical development program of MORF-057 for the treatment of UC. 
Objectives and Endpoints: 
The following study objectives will be completed by assessing the associated endpoints in 
participants with moderately to severely active UC. 
 
 
Objectives 
Endpoints  
Primary Efficacy 
 
To evaluate the effects of MORF-057 on 
clinical remission at Week 12 
• Proportion of participants in clinical 
remission at Week 12 as determined using 
CCI

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Objectives 
Endpoints  
the Modified Mayo Clinic Score (mMCS). 
The mMCS is a composite of the following 
subscores: 
o Mayo endoscopic subscore (MES) 
o Mayo Clinic Score (MCS) stool 
frequency subscore 
o MCS rectal bleeding subscore 
Secondary Efficacy 
 
To evaluate the effects of MORF-057 on 
clinical response at Week 12 
• Proportion of participants with clinical 
response at Week 12 as determined using 
the mMCS 
Exploratory Efficacy 
 
To evaluate the effects of MORF-057 on 
clinical remission at Week 52 
• Proportion of participants in clinical 
remission at Week 52 as determined using 
the mMCS 
To evaluate the effects of MORF-057 on 
clinical response at Week 52 
• Proportion of participants with clinical 
response at Week 52 as determined using 
the mMCS 
To evaluate the effect of MORF-057 on MCS 
remission at Weeks 12 and 52 
• Proportion of participants in MCS remission 
at Weeks 12 and 52. 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 evaluate the effect of MORF-057 on MCS 
response at Weeks 12 and 52 
• Proportion of participants with MCS 
response at Weeks 12 and 52 
To evaluate the effects of MORF-057 on 
histologic remission at Weeks 12 and 52 
• Proportion of participants in histologic 
remission at Weeks 12 and 52 as determined 
using the Robarts Histopathology Index 
(RHI) Score 
• Proportion of participants in histologic 
remission at Weeks 12 and 52 as determined 
using the Nancy Histopathology Index (NI) 

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Objectives 
Endpoints  
• Proportion of participants in histologic 
remission at Weeks 12 and 52 as determined 
using the Continuous Geboes Score 
To evaluate the effects of MORF-057 on 
histologic improvement at Weeks 12 and 52 
• Proportion of participants with histologic 
improvement at Weeks 12 and 52 as 
determined using the RHI 
To evaluate the effect of MORF-057 on 
endoscopic improvement at Weeks 12 and 52 
• Proportion of participants with endoscopic 
improvement at Weeks 12 and 52 as 
determined using the MES 
To evaluate the effects of MORF-057 on 
endoscopic remission at Weeks 12 and 52 
• Proportion of participants in endoscopic 
remission at Weeks 12 and 52 as determined 
using the MES 
To evaluate the effects of MORF-057 on 
mucosal healing at Weeks 12 and 52 
• Proportion of participants in endoscopic 
remission as determined using the MES and 
histologic remission as determined using the 
RHI at Weeks 12 and 52 
To evaluate the effects of MORF-057 on 
mucosal improvement at Weeks 12 and 52 
• Proportion of participants with endoscopic 
improvement as determined using the MES 
and a histologic improvement as determined 
using the RHI at Weeks 12 and 52 
To evaluate the effects of MORF-057 on 
symptomatic response at Weeks 2 and 6 
• Proportion of participants with symptomatic 
response at Weeks 2 and 6 as determined 
using the Partial mMCS. Partial mMCS is a 
composite of the following subscores: 
o MCS stool frequency subscore 
o MCS rectal bleeding subscore 
To evaluate the effects of MORF-057 on 
Partial MCS response at Week 6 
• Proportion of participants with Partial MCS 
response at Week 6. Partial MCS is a 
composite of the following subscores: 
o MCS stool frequency subscore 
o MCS rectal bleeding subscore 
o MCS PGA 
To determine time to symptomatic response 
by Week 12 
• Time to symptomatic response by Week 12 
as determined using the Partial mMCS 

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Objectives 
Endpoints  
To assess the effect of MORF-057 on 
non-endoscopic biomarkers of inflammation 
at Weeks 12 and 52  
• Change from baseline to Weeks 12 and 52 
in high-sensitivity C-reactive protein 
(hs-CRP) levels 
• Change from baseline to Weeks 12 and 52 
in fecal calprotectin levels 
To evaluate the effect of MORF-057 on 
patient-reported outcomes at 
Weeks 12 and 52 
• Change from baseline to Weeks 12 and 52 
in Inflammatory Bowel Disease 
Questionnaire (IBDQ) Score 
To evaluate the effect of MORF-057 on 
corticosteroid-free remission at Week 52 
• Proportion of participants in 
corticosteroid-free remission at Week 52, as 
determined using the mMCS, among the 
participants who were on a stable dose of 
corticosteroids at baseline 
To characterize the effect of MORF-057 on 
the need for UC-related hospitalizations and 
surgeries 
• Percentage of participants requiring 
UC-related hospitalization or surgery at 
Weeks 12 and 52 

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Objectives 
Endpoints  
To evaluate the long-term histologic and 
endoscopic effects of MORF-057 at 
Week 104 
• Proportion of participants in histologic 
remission at Week 104 as determined using 
the RHI 
• Proportion of participants in histologic 
remission at Week 104 as determined using 
the NI 
• Proportion of participants in histologic 
remission at Week 104 as determined using 
the Continuous Geboes Score 
• Proportion of participants with histologic 
improvement at Week 104 as determined 
using the RHI 
• Proportion of participants with endoscopic 
improvement at Week 104 as determined 
using the MES 
• Proportion of participants in endoscopic 
remission at Week 104 as determined using 
the MES 
• Proportion of participants in endoscopic 
remission as determined using the MES and 
histologic remission as determined using the 
RHI at Week 104 
• Proportion of participants with endoscopic 
improvement as determined using the MES 
and a histologic improvement as determined 
using the RHI at Week 104 
Safety 
 
To assess the safety and tolerability of 
MORF-057 
• Frequencies and proportions for 
treatment-emergent adverse events 
(TEAEs), treatment-emergent serious 
adverse events (TESAEs), and TEAEs 
leading to study drug discontinuation 
Pharmacokinetics (PK) 
 
To characterize the PK of MORF-057  
• MORF-057 concentration in plasma 

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Objectives 
Endpoints  
Exploratory Pharmacodynamics (PD) 
 
To characterize the PD of MORF-057 in 
peripheral blood  
• α4β7 receptor occupancy in blood over time 
• α4β1 receptor occupancy in blood over time 
• Change from baseline over time in blood 
C-C chemokine receptor 9 (CCR9) 
messenger ribonucleic acid (mRNA) 
• Change from baseline over time in blood 
lymphocyte subsets 
 
Efficacy Analysis Definitions 
Clinical remission: Determined using the mMCS. Rectal bleeding subscore of 0; a stool frequency 
subscore of ≤1; and an MES of ≤1 without friability 
Clinical response: Determined using the mMCS. 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 
MCS remission: MCS ≤2 and no subscore higher than 1 
MCS response: Decrease in MCS ≥3 points and ≥30% from baseline, plus a decrease in rectal 
bleeding score ≥1 or an absolute rectal bleeding score ≤1 
Histologic remission by RHI: RHI ≤2 (with 0 for lamina propria neutrophils score and neutrophils 
in the epithelium score and without ulcers or erosions) 
Histologic remission by NI: NI=0 
Histologic remission by Continuous Geboes: Continuous Geboes ≤3 
Histologic improvement: ≥7-point reduction in RHI 
Endoscopic improvement: MES ≤1 
Endoscopic remission: MES=0 
Mucosal healing: MES=0 and RHI ≤3 (with 0 for lamina propria neutrophils score and 
neutrophils in the epithelium score and without ulcers or erosions) 
Mucosal improvement: MES ≤1 and ≥7-point reduction in RHI 
Symptomatic response: Decrease in Partial mMCS ≥1 point and ≥30% from baseline, plus a 
decrease in rectal bleeding subscore ≥1 or an absolute rectal bleeding subscore ≤1 
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 
Time to symptomatic response: Time from randomization date to symptomatic response 
Corticosteroid-free remission: Determined only in participants who were receiving 
corticosteroids on study Day 1. Includes such participants who are both in clinical remission (as 
determined using the mMCS) at Week 52 and off corticosteroids for ≥12 consecutive weeks prior 
to Week 52. 

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Overall Design: 
This study is a randomized, double-blind, placebo-controlled, multicenter, Phase 2b study to 
evaluate the efficacy and safety of 3 active dose regimens of MORF-057 (as capsule, P.O.) versus 
matching placebo in study participants with moderately to severely active UC. 
Approximately 280 participants will be randomized into the 4 treatment groups in a 1:1:1:1 ratio 
(i.e., 70 participants per group). The study will enroll participants who are advanced therapy-naïve 
(i.e., have no previous exposure to an advanced therapy treatment for UC) and advanced 
therapy-experienced (excluding vedolizumab), with at least 30% but no more than 40% of 
advanced therapy-experienced participants. Randomization stratification factors will include 
baseline MES (<3 vs 3) and previous use of advanced therapy treatment (advanced therapy-naïve 
vs advanced therapy-experienced). All participants will be enrolled from approximately 
150 centers worldwide. For this study, moderately to severely active UC will be defined as having 
an mMCS of 5 to 9 (inclusive), with an MES ≥2 (confirmed by central reader). 
The main part of this Phase 2b study will consist of a Screening Period (up to 6 weeks, consisting 
of Stage 1 and Stage 2 testing), a Treatment Period (52 weeks, including a 12-week Induction 
Period and a 40-week Maintenance Period), and a Safety Follow-up (SFU) Period (4 weeks). 
During the main part of this 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, 18, 
24, 32, 42, and 52 [End of Treatment (EOT)]), and an SFU Visit (visit to occur 4 weeks after the 
last dose of study drug is received, which will be at Week 56 if the full Treatment Period 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). 
All participants who complete the 52-week Treatment Period will have the opportunity to continue 
their treatment in a 52-week Long-Term Extension (LTE) Period. 
During the optional LTE Period, there will be up to 7 scheduled visits: 4 Treatment Visits 
(Visits 11-14 at Weeks 65, 78, 91, and 104 [Long-Term Extension (LTE) EOT]), 2 Dose Switch 
Follow-ups (DSFUs; these 2 visits will only occur if participant consents to dose switch), and an 
SFU Visit (visit to occur 4 weeks after the last dose of study drug is received, which will be at 
Week 108 if the full LTE Period is completed or earlier if treatment is discontinued early). 
Due to the changes in Version 3.0 of this protocol, all participants who choose to continue their 
treatment in the LTE Period will be asked to re-consent to the LTE Period dose switch to 200 mg 
twice a day (B.I.D.). The dose switch will occur at Visit 10 or at a scheduled visit in the LTE 
Period (Visit 11, 12, or 13). If the participant does not consent to the dose switch, they will be 
allowed to remain on their current LTE Period dose and schedule; they will not need to attend 
DSFUs 1 or 2. Participants in the LTE Period who consent to the dose switch will have a scheduled 
DSFU 1 at 4 weeks after the dose switch, and then DSFU 2 will be 4 weeks after DSFU 1. The 
participant will then attend the next scheduled visit (Visit 11, 12, 13, or 14) per the Schedule of 
Activities (SoA). A participant cannot switch their dose after Visit 13. An SFU Visit will occur 
4 weeks after the last dose of study drug is received, which will be at Week 108 if the full LTE 
Period is completed or earlier if treatment is discontinued early. 
Participants who do not enroll into the LTE Period will complete the final SFU Visit (4 weeks 
after receiving the last dose of MORF-057) for the main part of the study (a maximum time 

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on-study of 62 weeks). Participants who choose to continue in the LTE Period will not complete 
the SFU Visit for the main part of the study; instead, they will directly enter the LTE Period and 
complete a separate SFU Visit (4 weeks after receiving the last dose of MORF-057 in the LTE 
Period), for a maximum time on-study of 114 weeks. 
An independent Data and Safety Monitoring Board (DSMB) will review participant safety data 
and monitor scientific integrity throughout the study. Details related to the DSMB will be clearly 
delineated in the DSMB Charter. 
Study Treatment: 
Enrolled participants will be randomized to a treatment group to receive active MORF-057 or 
placebo. Participants initially randomized into an active MORF-057 treatment group will receive 
an active treatment (according to study period and group assignment) for the full 52-week 
Treatment Period. Participants initially randomized into the placebo group will be switched to an 
active MORF-057 regimen (200 mg once a day – evening [Q.D.-E]) after they complete the 
Induction Period and the Week 12 assessments. After participants complete the full 52-week 
Treatment Period, they will have the option to enter an additional 52-week LTE Period. All 
participants who choose to continue in the LTE Period will continue receiving the same 
MORF-057 regimen they had during the Maintenance Period for up to an additional 52 weeks. 
However, at Visit 10 or at a scheduled visit in the LTE Period (Visit 11, 12, or 13), if the participant 
consents, the MORF-057 dose for the LTE Period will be switched to 200 mg B.I.D. If the 
participant does not consent to the dose switch, they will be allowed to remain on their current 
LTE Period dose and schedule. The dosing regimens for the 4 treatment groups during the study 
are shown below. 
 
Induction Period 
(12 Weeks) 
Maintenance Period (40 Weeks)/ 
LTE Period (52 Weeks) 
LTE Period (52 Weeks)* 
Group 1 
MORF-057 (200 mg 
B.I.D.) 
MORF-057 (100 mg B.I.D.) 
MORF-057 (200 mg B.I.D.) 
Group 2 
MORF-057 (100 mg 
B.I.D.) 
MORF-057 (100 mg B.I.D.) 
MORF-057 (200 mg B.I.D.) 
Group 3 
MORF-057 (100 mg 
Q.D.-M) 
MORF-057 (100 mg Q.D.-M) 
MORF-057 (200 mg B.I.D.) 
Group 4  
Placebo 
MORF-057 (200 mg Q.D.-E) 
MORF-057 (200 mg B.I.D.) 
Abbreviations: B.I.D., twice a day; LTE, Long-Term Extension; Q.D.-E, once a day (evening); Q.D.-M, once a day (morning). 
* Relevant for participants who consent to the dose switch in the LTE Period. For those that do not consent to the dose switch in 
the LTE Period, they will remain on their current LTE Period dose. 
The study drug will be supplied as immediate-release capsules for oral administration (MORF-057 
100 mg capsule or placebo). Refer to the main protocol for additional treatment details. 
The first dose of the study drug will be administered in the clinic on study Day 1 under the 
supervision of study personnel. All subsequent doses will be self-administered at home, with the 
exception of the morning doses for Visits 2-10, which will be administered during the study visits 

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after pre-dose blood samples have been drawn (see details in the SoA). Participants will be 
instructed to record all details about the doses administered at home in the Participant Diary. 
A study schema is provided below. 
Study Schema: 
 
Abbreviations: B.I.D., twice a day; DSFU, Dose Switch Follow-up; EOT, End of Treatment; Q.D.-E, once a day (evening); Q.D.-M, 
once a day (morning); SFU, Safety Follow-up; UC, ulcerative colitis; V, visit; W, week. 
a The SFU Visit will not be performed at Week 56 for participants who enter the LTE Period. 
b The assessments to be performed at each visit and the acceptable time windows for each visit are provided in the Schedule of 
Activities. 
c 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. 
d At Visit 10 or at a scheduled visit in the LTE Period (Visit 11, 12, or 13), all participants will be asked to re-consent to switch 
their dose to 200 mg B.I.D. Participants who do not consent to the dose switch will remain on their current LTE Period dose. The 
DSFU 1 will occur 4 weeks after the dose switch, and DSFU 2 will occur 4 weeks after DSFU 1. Participants who do not consent 
to the dose switch will not need to attend DSFUs 1 or 2. 
Main Inclusion Criteria: 
Participants are eligible to be included in the study only if all the following criteria apply: 
Age 
1. Male or female, 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 diagnosis of UC supported by signs/symptoms, endoscopy, and histology 
for at least 3 months prior to Screening. Moderately to severely active UC was determined 
during the Screening Period with the following criteria: an mMCS of 5 to 9 (inclusive), with 
an MES ≥2 (confirmed by central reader) 
3. Has evidence of UC extending at least 15 cm from the anal verge 

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4. Demonstrated an inadequate response, loss of response, or intolerance to at least one of the 
following treatments (including oral aminosalicylates*, corticosteroids, immunosuppressants, 
and/or advanced therapies for UC) in the opinion of the Investigator, as defined below: 
a. Oral aminosalicylates (e.g., mesalamine, sulfasalazine, olsalazine, or balsalazide) 
• Signs and symptoms of persistently active disease during a current or prior 
course of at least 4 weeks of treatment with ≥2.0 g/day mesalamine, 4 g/day 
sulfasalazine, 1 g/day olsalazine, or 6.75 g/day balsalazide 
*Note: Inadequate response, loss of response, or intolerance to oral aminosalicylates 
does not apply to this Inclusion Criterion in European Union (EU) countries. 
b. Corticosteroids 
• Signs and symptoms of persistently active disease despite a history of at 
least one induction regimen that included a dose equivalent to prednisone 
≥30 mg/day orally for at least 3 weeks or intravenously for 1 week 
OR 
• Unable to taper corticosteroids to below a dose equivalent to prednisone 
10 mg daily orally without recurrent active disease 
OR 
• Signs and symptoms of persistently active disease during or after a course 
of at least 4 weeks of treatment with 9 mg/day budesonide or 5 mg/day 
beclomethasone 
OR 
• Unable to taper oral budesonide below 6 mg/day without recurrent active 
disease 
OR 
• History of intolerance to corticosteroids (including, but not limited to, 
Cushing's syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, or 
infection) 
c. Immunosuppressants (e.g., azathioprine, 6-mercaptopurine, or methotrexate) 
• Signs and symptoms of persistently active disease despite a history of at 
least one 8*-week regimen of oral azathioprine (≥1.5 mg/kg/day), 
6-mercaptopurine (≥1 mg/kg/day or a documented 6-thioguanine 
nucleotide level of 230-450 pmol/8 × 108 red blood cell count or higher 
on the current dosing regimen), injectable methotrexate (≥12.5 mg/week 
subcutaneous [SC] or intramuscular) 
*Note: A history of signs and symptoms of persistently active disease 
despite a history of at least one 12-week regimen of immunosuppressants 
is required in EU countries. 
OR 

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• History of intolerance to at least one immunosuppressant (including, but not 
limited to, nausea/vomiting, abdominal pain, pancreatitis, liver enzyme 
abnormalities, lymphopenia, or infection) 
Note: Oral methotrexate use is allowed during the study; however, prior or current 
use of oral methotrexate is not sufficient for inclusion into the study unless the 
participant was previously treated with aminosalicylates, corticosteroids, or 
immunosuppressants (azathioprine or 6-mercaptopurine) and had an inadequate 
response, loss of response, or intolerance to the therapy as defined above. 
d. Advanced therapies for UC (e.g., biologic agents, Janus kinase [JAK] antagonists, 
or sphingosine-1-phosphate [S1P] receptor agonists) 
• Primary non-response – Signs and symptoms of persistently active disease 
despite a history of any of the following: 
o At least one 6-week induction regimen of infliximab (5-10 mg/kg 
intravenously at 0, 2, and 6 weeks) 
o At least one 4-week induction regimen of adalimumab (one 160 mg 
SC dose followed by one 80 mg SC dose [or one 80 mg SC dose in 
countries where this dosing regimen is allowed followed by one 
40 mg SC dose] at 2 weeks or earlier) 
o At least one 2-week induction regimen of golimumab (one 200 mg 
SC dose followed by one 100 mg SC dose at least 2 weeks apart) 
o At least one induction regimen of ustekinumab (single intravenous 
weight-based infusion of 260 mg [<55 kg body weight], 390 mg 
[55-85 kg body weight], or 520 mg [>85 kg body weight]) 
o A history of completed Induction regimen according to prescribing 
information for JAK antagonists or S1P receptor agonists 
OR 
• Secondary non-response – Initially responded to Induction therapy and then 
had recurrence of symptoms after receiving at least 2 of the Maintenance 
doses specified below (discontinuation despite clinical benefit does not 
qualify): 
o Infliximab: ≥5 mg/kg 
o Adalimumab: 40 mg every week or every other week 
o Golimumab: 100 mg injection at Week 6 and every 4 weeks 
o Ustekinumab: 90 mg SC dose 8 weeks after the initial intravenous 
dose, then every 8-12 weeks thereafter or more frequently 
OR 
• History of intolerance to at least one advanced therapy agent (including, but 
not limited to, infusion-related reaction, demyelination, congestive heart 
failure, or infection) 
Note: Participants who have received a prior advanced therapy agent for up to 
1 year and did not have a documented non-response may be enrolled; however, the 
participants must have discontinued the advanced therapy agent for reasons other 

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than inadequate response or intolerance (e.g., change of insurance, well-controlled 
disease) and must meet the criteria for inadequate response, loss of response, or 
intolerance to aminosalicylates, corticosteroids, and/or immunosuppressants, as 
defined above. 
Note: Participant cannot have had inadequate response, loss of response, or 
intolerance to more than 3 drugs in 2 classes of the following advanced therapies: 
a. Tumor necrosis factor alpha (TNF-α) antagonists, including infliximab, 
adalimumab, or golimumab 
b. Interleukin (IL)-12/IL-23 antagonists, including ustekinumab 
c. JAK antagonists, including tofacitinib or upadacitinib 
d. S1P receptor agonists, including ozanimod 
e. Any investigational product with the same mechanism as one of those 
outlined above (a through d) or a novel mechanism of action 
Note: Participants who have a history of primary non-response to 2 or more of the 
advanced therapy 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. 
5. 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 or upadacitinib: at least 1 week 
d. S1P receptor agonists, including ozanimod: at least 4 weeks 
Note: Participants who do not meet the full washout period but have the results of a local 
drug concentration level performed during the Screening Window deemed by the Medical 
Monitor to be sub-therapeutic may be eligible for the study earlier than the full washout 
period. 
6. 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 SFU Period, with the exception of tapering oral corticosteroid dose after 12 weeks 
of being in the trial. 
a. Oral 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/day, budesonide 9 mg/day, 
beclomethasone dipropionate 5 mg/day, methylprednisolone 24 mg/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 
*Note: Participants must be on any stable dose of 6-mercaptopurine, azathioprine, or 
methotrexate for at least 12 weeks prior to study Day 1 in EU countries. 

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7. If the participant has had UC for over 7 years, he/she must have had a full colonoscopy in the 
last 2 years or must agree to have a full colonoscopy (rather than sigmoidoscopy) with 
appropriate, per local guidelines, colon cancer surveillance biopsies at Screening 
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) ≥18.0 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 10.5.3) when having sexual 
intercourse with a woman of childbearing potential who is not 
currently pregnant. 
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 MORF-057 
Note: For contraception requirements on or after Protocol Amendment Version 3.0, see 
Section 10.5.2.2. 

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11. For the study Treatment Period and at least 14 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 
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 
Crohn’s disease, or has clinical findings suggestive of Crohn’s disease 
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 
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 
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 Progressive Multifocal Leukoencephalopathy (PML) 
symptom checklist during Screening or prior to the administration of the first dose of study 
drug on study Day 1 
7. Has a potentially active bacterial, viral, or parasitic pathogenic enteric infection, including 
Clostridiodes difficile (C. difficile); has 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 active tuberculosis (TB), as evidenced by any of the following: 
a. A diagnostic test for TB performed within 30 days prior to Screening or during 
the Screening Period that is positive, as defined below: 
• A positive interferon gamma release assay (IGRA) test (e.g., 
 
 TB test) or 2 consecutive indeterminate 
IGRA tests 
OR 
• A purified protein derivative (PPD) skin test ≥5 mm 
CCI

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b. A chest X-ray or imaging per local guidelines within 3 months prior to Screening 
where active or latent pulmonary TB cannot be excluded 
Note: Participants who have tested negative for TB at a certified local lab using an IGRA test 
within 3 months prior to Screening are not required to repeat this test during the Screening 
Period if that participant has no clinical signs or symptoms of TB and no known 
exposures/increased risk factors since the last negative TB test (according to the Investigator’s 
clinical judgement), and the test result is available in the participant’s medical record 
Note: Participants with a history of latent TB may be enrolled if they complete an assessment 
for evidence of active TB versus latent TB. Documentation will include a chest X-ray or 
imaging per local guidelines during the Screening Window and no signs, symptoms, or 
evidence of ongoing active TB. Participants have had treatment per the local standard of care 
for a minimum of 2 weeks before the first dose of study drug OR documentation of completing 
appropriate treatment for latent TB within 2 years before Day 1 of the study. See 
Section 8.2.2.1 for more details. 
9. Has a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result 
during the Screening Period. Testing for SARS-CoV-2 is required only per local regulations. 
Participants who have a positive test result can be randomized after a subsequent negative test 
result during the Screening Period. 
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 

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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 >5.5 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. Participants with an international normalized 
ratio >1.5 due to anticoagulant therapy (e.g., Coumadin) may only be enrolled after 
a consultation with the Medical Monitor. 
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 >2.0 × 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 
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 licensed or investigational integrin 
inhibitors 
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. Participant needs to continue treatment with a moderate-to-strong cytochrome P450 3A 
(CYP3A) inducer or inhibitor and, therefore, will be unable to do a washout period of at least 

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30 days or 5 half-lives (whichever is shorter) prior to study Day 1. See Section 6.7.3 for a list 
of moderate-to-strong P450 inducers and inhibitors. 
25. Participant needs to continue treatment with a moderate-to-strong organic anion transporter 
polypeptide-1B inhibitor and, therefore, will be unable to do a washout period of at least 
14 days or 5 half-lives (whichever is shorter) prior to study Day 1. See Section 6.7.3 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. Known allergies/hypersensitivity to any component of the study drug and/or 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 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 
Statistical Methods: 
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. 
Sample Size Determination 
The sample size was determined based on the primary endpoint of clinical remission at Week 12 
by using the Chi-Squared Test to compare two proportions. A sample size of 70 participants per 
group (giving a total of 280) will provide 80% power to detect a difference of 15% in the clinical 
remission rate between MORF-057 and placebo, based on the use of a two-sided test at the 
alpha=0.10 level of significance. The calculation is based upon an assumed placebo remission rate 
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Analysis Populations 
The Full Analysis Set (FAS) will consist of all randomized participants who received at least 
1 dose of study drug. The FAS Population will be used as the primary analysis population for all 
efficacy endpoints. Participants will be analyzed according to the treatment group they were 
randomized into. 
The Per Protocol (PP) Population is defined as all participants in the FAS Population who did 
not have any major protocol deviations related to the primary or secondary efficacy endpoint 
analyses. All decisions to exclude participants for the PP Population will be made prior to the 
unblinding of the study. The PP Population may be used for sensitivity efficacy analyses of, at a 
minimum, the primary efficacy endpoint. 
The Safety Population will include all participants who received at least 1 dose of the study drug. 
Participants in this set will be analyzed according to the treatment they actually received. This 
population will be used for the safety analyses. 
The Pharmacokinetics (PK) Population is defined as all participants who received at least 1 dose 
of study drug and had at least 1 measurable PK concentration. The PK Population will be used for 
the summarization/analysis of PK data. 
The Pharmacodynamics (PD) Population is defined as all participants who received at least 
1 dose of study drug and had 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. 
Analysis of Demographics and Baseline Characteristics 
Demographic and baseline characteristics will be summarized by treatment group and overall. 
Efficacy Analyses 
All the efficacy analyses will be performed based on the FAS, unless otherwise specified. 
Primary Efficacy Endpoint 
The primary efficacy endpoint for this study is proportion of participants in clinical remission at 
Week 12 as determined using the mMCS, which will be evaluated in the FAS. 
The primary efficacy endpoint will be analyzed using a two-sided Cochran-Mantel-Haenszel 
(CMH) test at the 10% level of significance, stratified by randomization stratification factors 
(baseline MES [<3 vs 3] and previous use of advanced therapy treatment [advanced therapy-naïve 
vs advanced therapy-experienced]), for comparison of each MORF-057 dose group with the 
placebo group. The p-values and point estimates of risk difference, along with 95% confidence 
interval (CIs), will be provided. The study will be considered a success if at least one MORF-057 
dose achieves the statistical significance at the specified significance level after the multiplicity 
adjustment. All participants with missing data for determination of endpoint status will be 
considered as a non-responder in the primary analysis. 
The primary analysis will be repeated on the PP Population as a sensitivity analysis. Other 
sensitivity analyses for the primary efficacy endpoints may also be performed as appropriate. The 
primary efficacy endpoint will be analyzed for the subgroups defined based on selected categorized 

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demographic and baseline variables, e.g., age, gender, race, exposure to an advanced therapy 
treatment for UC (advanced therapy-naïve and advanced therapy-experienced). The details will be 
described in the Statistical Analysis Plan (SAP). 
Secondary Efficacy Endpoint 
The secondary endpoint for this study is the proportion of participants with clinical response at 
Week 12 as determined using the mMCS, which will be evaluated in the FAS. 
The secondary endpoint will be analyzed using CMH tests stratified by randomization 
stratification factors (baseline MES [<3 vs 3] and previous use of advanced therapy treatment 
[advanced therapy-naïve vs advanced therapy-experienced]) for comparison of each MORF-057 
dose group with the placebo group, similar to the primary analysis performed for the primary 
endpoint. The p-values and point estimates of risk difference, along with 95% CIs, will be 
provided. All participants with missing data for determination of endpoint status will be considered 
as a non-responder in the analysis. 
Exploratory Efficacy Endpoints 
All proportion-based exploratory efficacy endpoints at Week 12 as defined in Section 3 (e.g., 
histologic remission or improvement, endoscopic remission or improvement, mucosal healing or 
improvement, MCS remission or response, UC-related hospitalization or surgery) will be analyzed 
in the FAS using CMH tests stratified by randomization stratification factors for comparison of 
each MORF-057 dose group with the placebo group, similar to the primary analysis performed for 
the primary efficacy endpoint. The p-values will be calculated for the exploratory use. The point 
estimates of risk difference, along with 95% CIs, will be provided. All participants with missing 
data for determination of endpoint status will be considered as a non-responder in the analysis. 
All the continuous exploratory efficacy endpoints expressed as change from baseline at Week 12 
as defined in Section 3 (e.g., non-endoscopic biomarkers of inflammation, patient-reported 
outcomes) will be analyzed in the FAS using an analysis of covariance model with treatment and 
randomization stratification factors as factors and baseline values as a covariate. The least-squares 
means and standard errors with 95%◦CIs for both changes from baseline in each treatment group 
and differences between MORF-057 and placebo groups will be provided. P-values will also be 
calculated for the exploratory use. Participants who do not have the baseline value or the value at 
Week 12 will be excluded from the analysis. 
The time-to-event endpoint (time to symptomatic response) will be analyzed using the stratified 
Cox regression model with treatment group as an independent variable. The stratification factors 
include the randomization stratification factors. 
All exploratory efficacy endpoints at Week 52 will be summarized descriptively by dose regimens. 
The participants randomized to the placebo arm at the Induction Period and switched to an active 
MORF-057 dose regimen at the Maintenance Period will be summarized separately for the 
endpoints at Week 52. 
Safety Analyses 
The Safety Population will be used for the summarization of all safety data. 
Adverse events (AEs) will be coded using the current Medical Dictionary of Regulatory Activities 
(MedDRA) by System Organ Class (SOC) and Preferred Term (PT), classified from verbatim 

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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 and 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. 
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 Population. The incidence of laboratory abnormalities will be summarized. Worst 
shift in grade and changes from baseline of the laboratory analytes will be reported. Physical 
examination findings that are recorded as AEs will be included in those data presentations. 
The safety analyses will be performed for the 12-week Induction Period, the 52-week Treatment 
Period, and the 52-week LTE Period plus the Safety Follow-up Period. In the safety analyses for 
the 12-week Induction Period, the participants initially randomized into the placebo group and 
switched to an active MORF-057 regimen after the Week 12 assessments will be analyzed as the 
placebo group. In the safety analyses for the 52-week Treatment Period and 52-week LTE Period, 
the placebo recipients switched to an active MORF-057 regimen will be analyzed according to the 
active MORF-057 regimen they received after Week 12, and their data will be presented separately 
based on only the safety data collected after the start of the MORF-057 dose. 
Pharmacokinetics Analyses 
PK concentration will be summarized. Additional PK and PK/PD analyses will be conducted as 
deemed appropriate and may be reported separately from the Clinical Study Report. 
Pharmacodynamics Analyses 
The exploratory PD endpoints (changes over time in α4β7 and α4β1 receptor occupancies and blood 
CCR9 mRNA level) will be summarized descriptively. Additional analysis of PD endpoints may 
be described 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 PD exploratory endpoints. 
Analyses for Induction Period, 52-week Treatment Period, and LTE Period 
The Treatment Period in the main part of the study includes 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 one for 
the 52-week Treatment Period (i.e., the 12-week Induction Period plus the 40-week Maintenance 
Period and Safety Follow-up Period). The details of the analyses will be described in the SAP. 
Additional analysis of the optional 52-week LTE Period for the participants enrolled into the LTE 
Period will also be performed as appropriate. 
Induction Period Analysis 
The analysis of the 12-week Induction Period will be performed after all the participants have 
completed the Week 12 assessments or discontinued the study before the Week 12 assessments. 
The analysis will formally evaluate the primary and secondary efficacy endpoints, all the 

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exploratory efficacy endpoints defined by Week 12, and safety of MORF-057 vs placebo during 
the 12-week Induction Period. The PK and PD data during the 12-week Induction Period will also 
be summarized. 
52-week Treatment Period Analysis 
The analysis of the 52-week Treatment Period will be performed after all the participants have 
completed the Week 52 assessments (and Safety Follow-up Period for participants not rolling over 
into the LTE Period) or discontinued from the study during the 52-week Treatment Period. The 
analysis will formally evaluate the efficacy (including all the exploratory efficacy endpoints 
defined by Week 52), PK, PD, and safety of MORF-057 during the 52-week Treatment Period 
(and the Safety Follow-up Period for participants not rolling over into the LTE Period). The 
cumulative data, including those from the Induction Period, will be used in this analysis. 
52-week LTE Period Analysis 
The analysis of the LTE Period will be performed after all the participants enrolled into the LTE 
Period have completed the 52-week LTE Period and the Safety Follow-up Period or discontinued 
the study during the LTE Period. The analysis will evaluate the long-term safety of MORF-057 
and selected efficacy endpoints at Week 104 as appropriate during the LTE Period plus the Safety 
Follow-up Period. 
Data and Safety Monitoring: 
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 treatment, 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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1.2. 
Schedule of Activities (SoA) 
The SoA for the Treatment Period is provided in Table 1. The SoA for the LTE Period* is provided in Table 2. 
Table 1. 
Schedule of Activities for the Treatment Period 
Study Procedure 
SCR a 
Treatment Period 
Safety 
Follow-
up 
UNS b 
Induction Period 
Maintenance Period 
Visit 
1 
2 
3 
4 
5 c 
6 
7 
8 
9 
10/EOT d, e 
SFU f, g 
UNS 
Week 
-6 to -1 
0 
2 
6 
12 
18 
24 
32 
42 
52 
56 
 
Study Day 
-42 to -1 
1 
15±3 
43±3 
85+5 
127±7 
169±7 
225±7 
295±7 
365±7 
393+7 h 
 
 
Stage 
1 
Stage 
2 
 
 
 
Stage 
1 
Stage 
2 
 
 
 
 
Stage 
1 
Stage 
2 
 
 
Informed consent i 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical and surgical history 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Assess inclusion/exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirm inclusion/exclusion 
criteria 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization j 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
SARS-CoV-2 screening k 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test for TB l 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fecal sampling and cell culture 
for C. diff. and enteric 
pathogens, including ova and 
parasite testing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Testing for HIV antibody, 
hepatitis B surface antigen, and 
hepatitis C virus antibody 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum alcohol screen  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine drug screen 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review of change in substance 
use m 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
Review Participant Diary 
instructions 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fill out Participant Diary (daily 
rectal bleeding, stool 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
 

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Study Procedure 
SCR a 
Treatment Period 
Safety 
Follow-
up 
UNS b 
Induction Period 
Maintenance Period 
Visit 
1 
2 
3 
4 
5 c 
6 
7 
8 
9 
10/EOT d, e 
SFU f, g 
UNS 
Week 
-6 to -1 
0 
2 
6 
12 
18 
24 
32 
42 
52 
56 
 
Study Day 
-42 to -1 
1 
15±3 
43±3 
85+5 
127±7 
169±7 
225±7 
295±7 
365±7 
393+7 h 
 
 
Stage 
1 
Stage 
2 
 
 
 
Stage 
1 
Stage 
2 
 
 
 
 
Stage 
1 
Stage 
2 
 
 
frequency, study drug 
administration) n 
Participant Diary completion 
and compliance review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Pregnancy test o 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
X b 
Serum test for 
follicle-stimulating hormone p 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dispense stool collection kit q 
X q 
X 
 
X 
 
X 
 
 
X 
 
 
 
Discuss participation in LTE 
Period and informed consent r 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
 
Safety Assessments 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X b 
12-lead ECG s 
X 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Physical exam t 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
X b 
Vital signs u 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
X b 
PML checklist v 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
 
Hematology and coagulation 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
X b 
Serum chemistry 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
X b 
Urinalysis 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
X b 
AE/SAE assessment w, x 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X b 
Pharmacokinetic Assessment 
 
Plasma sample for PK analysis  
 
 
X y 
X y 
X z 
X y 
X z 
X y 
X z 
X z 
X y 
 
 
Pharmacodynamic 
Biomarkers 
 
Whole blood sample for RO aa 
 
 
X 
X 
 
 
X 
 
X 
 
 
 
X 
 
 
Whole blood sample for 
immunophenotyping bb 
(country-specific testing) 
 
 
X 
X 
 
 
X 
 
 
X 
 
 
PAXgene RNA blood sample 
for gene expression cc 
 
 
X 
X 
 
 
X 
 
 
 
 
 
X 
 
 

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Study Procedure 
SCR a 
Treatment Period 
Safety 
Follow-
up 
UNS b 
Induction Period 
Maintenance Period 
Visit 
1 
2 
3 
4 
5 c 
6 
7 
8 
9 
10/EOT d, e 
SFU f, g 
UNS 
Week 
-6 to -1 
0 
2 
6 
12 
18 
24 
32 
42 
52 
56 
 
Study Day 
-42 to -1 
1 
15±3 
43±3 
85+5 
127±7 
169±7 
225±7 
295±7 
365±7 
393+7 h 
 
 
Stage 
1 
Stage 
2 
 
 
 
Stage 
1 
Stage 
2 
 
 
 
 
Stage 
1 
Stage 
2 
 
 
Future Research (Optional) 
 
Blood PD sample collection dd 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Blood pharmacogenomics 
sample collection ee 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sample for 
microbiome-derived metabolite 
analysis ff 
 
 
X 
 
 
X 
 
 
 
X 
 
 
Fecal sample for microbiome 
analyses gg 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Fecal sample for fecal 
calprotectin hh 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Efficacy Assessments 
 
Sigmoidoscopy with biopsy ii 
X jj 
 
 
X kk, 
mm 
 
 
 
 
X ll, 
mm 
 
 
 
MCS Physician’s Global 
Assessment  
 
X 
X 
 
X 
X 
 
X 
 
 
MCS rectal bleeding subscore 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
 
 
MCS stool frequency subscore 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
 
 
Centrally read MES  
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Centrally read RHI Score, 
Continuous Geboes Score, and 
NI 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Serum for hs-CRP test nn 
X 
 
X 
 
X 
X 
 
 
X 
 
 
Fecal sample for fecal 
calprotectin 
X 
 
 
 
X 
X 
 
 
X 
 
 
IBDQ 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
Study Drug 
 
Study drug accountability 
 
 
 
X 
X 
 
X 
X 
X 
X 
X 
 
X oo 
 
 
Dispense study drug 
 
 
X 
X 
X 
 
X pp 
X 
X 
X 
X 
 
X qq 
 
 
Study drug administration 
on-site rr 
 
 
X 
X 
X 
 
X pp 
X 
X 
X 
X 
 
X ss 
 
 

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Study Procedure 
SCR a 
Treatment Period 
Safety 
Follow-
up 
UNS b 
Induction Period 
Maintenance Period 
Visit 
1 
2 
3 
4 
5 c 
6 
7 
8 
9 
10/EOT d, e 
SFU f, g 
UNS 
Week 
-6 to -1 
0 
2 
6 
12 
18 
24 
32 
42 
52 
56 
 
Study Day 
-42 to -1 
1 
15±3 
43±3 
85+5 
127±7 
169±7 
225±7 
295±7 
365±7 
393+7 h 
 
 
Stage 
1 
Stage 
2 
 
 
 
Stage 
1 
Stage 
2 
 
 
 
 
Stage 
1 
Stage 
2 
 
 
Confirm initiation of study 
drug for the Maintenance 
Period tt 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Abbreviations: AE, adverse event; B.I.D., twice a day; C. diff., Clostridiodes difficile; ECG, electrocardiogram; EOT, End of Treatment; HIV, human immunodeficiency virus; 
hs-CRP, high-sensitivity C-reactive protein; IBDQ, Inflammatory Bowel Disease Questionnaire; ICF, Informed Consent Form; IGRA, interferon gamma release assay; LTE, 
Long-Term Extension; MCS, Mayo Clinic Score; MES, Mayo Endoscopic Subscore; NI, Nancy Histopathology Index; PD, pharmacodynamics; PK, pharmacokinetics; PML, 
progressive multifocal leukoencephalopathy; RHI, Robarts Histopathology Index; RNA, ribonucleic acid; RO, receptor occupancy; SAE, serious adverse event; SARS-CoV-2, 
severe acute respiratory syndrome coronavirus 2; SCR, Screening; SFU, Safety Follow-up; TB, tuberculosis; UNS, unscheduled. 
a 
Once informed consent is obtained, the procedures listed for Stage 1 of Screening should be performed. Stage 1 will be 
approximately 2 weeks long and should include the collection of Participant Diary information for 7 days. At the end of Stage 1, 
the Investigator should use the information collected in the Participant Diary to assess the severity of UC. If the participant is 
consistently having 3 or more stools per day than normal, often with visible blood, then he/she should proceed to Stage 2 of 
Screening (including endoscopy). If the participant’s stool frequency and rectal bleeding symptoms are milder than what is 
described, Stage 2 of Screening should not be pursued. 
b 
No specific tests or procedures are required for unscheduled visits. Results of any study procedures performed at an unscheduled 
visit will be recorded and collected for the study. Clinically relevant laboratory testing or re-testing (e.g., hematology, coagulation, 
serum chemistry, or urinalysis) may be performed at unscheduled visits. 
c 
Visit 5 is split into Stage 1 and Stage 2 to clarify the timing of the endoscopy procedure. The endoscopy procedure at Visit 5 Stage 1 
should be performed before the Visit 5 Stage 2 in-clinic assessments have been completed. 
d 
Visit 10 is split into Stage 1 and Stage 2 to clarify the timing of the endoscopy procedure. The endoscopy procedure at Visit 10 
Stage 1 should be performed on or within 7 days before the Visit 10 Stage 2 in-clinic assessments have been completed. 
e 
If the participant discontinues early from the study Treatment Period, perform the EOT procedures and schedule SFU for 28 days 
(+7 days) after the participant takes the last dose of study drug (unless consent is withdrawn). 
f 
Participants not participating in the LTE Period will complete the SFU Visit, which should be performed 28 days (+7 days) after 
the participant takes the last dose of study drug. Eligible participants who choose to participate in the LTE Period after Visit 10 will 
complete a separate SFU Visit at Week 108 (Table 2). 
g 
If the participant discontinues early from the study Treatment Period, perform the SFU procedures 28 days (+7 days) after the 
participant takes the last dose of study drug (unless consent is withdrawn). 

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h 
The SFU Visit is to occur 28 days (+7 days) after the last dose of study drug is received. If the EOT Visit occurs before Day 365, 
the day for the SFU Visit can be adjusted according to the date of last study drug dose. 
i 
Informed consent process can begin prior to the start of the Screening Window. For example, this can be done if washout from 
medications is required. 
j 
Enrollment may occur at any point within a 42-day window of when all Screening procedures have been completed and all results 
required to assess eligibility are available. Enrolled participants will be randomized to a treatment group. Enrollment will usually 
occur the same day as first dosing, but if dosing the same day is not feasible, then enrollment will be considered Day -1 and first 
dose will be considered Day 1. 
k 
Testing for SARS-CoV-2 is required only per local regulations. Participants who have a positive test result will be excluded from 
randomization until a subsequent test result is negative. 
l 
Participants who have tested negative for TB at a certified local lab using an interferon gamma release assay (IGRA) test (e.g., 
 
 TB test) within 3 months prior to Screening are not required to repeat this test during the Screening 
Period if that participant has no clinical signs or symptoms of TB and no known exposures/increased risk factors since the last 
negative TB test (according to the Investigator’s clinical judgement). In cases where the IGRA test is indeterminate, the participant 
may have the test repeated once, and if their second test is negative, they will be eligible. The purified protein derivative skin test 
should be performed when the IGRA test is not possible or if both tests are required by local guidelines. 
m 
Collect information on the participant’s change in substance use (e.g., alcohol, tobacco, and drugs). 
n 
Participant Diaries are to be completed daily by the participant at home and brought to each study visit for review by study 
personnel. Participant Diaries should not be completed after the participant has finished their participation in the study at the SFU 
Visit. See Section 8.5 for the required contents of the Participant Diaries. 
o 
Only required for women of childbearing potential. A serum test should be used at Screening, and a urine test should be used 
throughout rest of study. On Day 1, a urine test must be completed and results reviewed prior to start of the study drug. 
p 
Serum test for follicle-stimulating hormone level to be performed only for female participants of non-childbearing potential. 
q 
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 stored as described in the sample collection 
instructions and brought to the clinic on the day of the site visit. If the participant is unable to produce a stool sample at the Stage 1 
Screening Visit, they can collect a sample at home and return it to the site. Note: Sample is to be collected prior to bowel preparation 
for Visits 5 and 10/EOT. 
r 
Participants will be provided the option to participate in the LTE Period. Participants who want to continue in the LTE Period will 
be required to provide informed consent. Due to the changes in Version 3.0 of this protocol, all participants who choose to continue 
their treatment in the LTE Period will be asked to re-consent to the LTE Period dose to 200 mg B.I.D. The dose switch will occur 
at Visit 10 or at a scheduled visit in the LTE Period (Visit 11, 12, or 13). 
CCI

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s 
ECGs to be performed before the AM dose and 2 hours (±30 minutes) after the AM dose during the Induction and Maintenance 
Periods. ECGs will be obtained after the participant has rested for at least 10 minutes in the supine position. 
t 
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, the type of exam (if necessary to be performed at all) 
will be at the Investigator’s discretion and determined based on the reason for the visit. The Screening exam will include collection 
of height and weight. 
u 
Vital signs to be recorded at most visits. At unscheduled visits, vital signs are not required and are at the discretion of the 
Investigator. These will include blood pressure, heart rate, respiratory rate, and temperature. Vital signs are to be taken before blood 
collection for laboratory tests. Blood pressure and pulse measurements should be preceded by at least 10 minutes of rest for the 
participant. 
v 
If the results of the questionnaire are suggestive of PML, a full neurological exam and, if indicated, additional testing are to be 
performed. 
w 
Record adverse events from the time the ICF is signed. 
x 
Participants are to be contacted by phone as needed to monitor the status of the event. 
y 
PK testing at Visits 2, 3, 5, 7, and 10/EOT: Blood samples will be collected before the AM dose and at 1 (±10 min), 2 (±15 min), 
and 4 (±30 min) hours after the AM dose. For all pre-AM dose sampling, the samples should be obtained before the AM dose is 
administered. If consent is provided by the participant, these samples may also be used for future PK research studies. 
z 
PK testing at Visits 4, 6, 8, and 9: Blood sample will be collected before the AM dose and 1 hour (±10 min) after the AM dose. For 
all pre-AM dose sampling, the samples should be obtained before the AM dose is administered. If consent is provided by the 
participant, these samples may also be used for future PK research studies. 
aa RO testing at Visit 2, 3, 5, 7, and 10/EOT: Blood sampling will be required before the AM dose. RO sampling to occur at the 
corresponding PK sampling time, when applicable. 
bb Blood samples for immunophenotyping (lymphocyte subsets analysis) will be collected from a subset of participants (sampling to 
be country-specific). Samples will be collected before the AM dose on Visits 2, 3, 5, and 10/EOT. Collection time on Visits 3, 5, 
and 10/EOT must be consistent with baseline (Visit 2) collection ±2 hours. 
cc PAXgene RNA blood samples (for CCR9 analysis) will be collected before the AM dose on Visit 2, 3, 5, and 10/EOT. Collection 
time at Visits 3, 5, and 10/EOT must be consistent with baseline (Visit 2) collection ±2 hours. 
dd Participation in future research sample collection is optional. Blood PD samples will be collected before the AM dose on 
Visits 2-10/EOT. 
ee Participation in future research sample collection is optional. Blood pharmacogenomics sample will be collected before the AM 
dose on Visit 2. 
ff 
Participation in future research sample collection is optional. Blood samples for microbiome-derived metabolite analysis will be 
collected before the AM dose on Visits 2, 5, and 10/EOT. 

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gg Participation in future research sample collection is optional. Fecal samples for microbiome analysis will be collected before the 
AM dose on Visits 2, 5, and 10/EOT. Fecal samples may be collected at any time on the day prior to the scheduled visit day. 
hh Participation in future research sample collection is optional. Fecal samples for fecal calprotectin will be collected at the same visits 
as the fecal calprotectin efficacy assessments (Visit 10/EOT). Fecal samples may be collected at any time on the day prior to the 
scheduled visit day. 
ii 
Full colonoscopy is optional at any timepoint if the Investigator deems it necessary. However, if the participant has had UC for 
over 7 years, he/she must undergo a full colonoscopy (rather than sigmoidoscopy) at Screening if a full colonoscopy has not been 
performed in the last 2 years. 
jj 
During the Screening endoscopy, up to 6 colonic mucosa biopsies will be collected. Two biopsies for the required histopathology 
must be collected from the worst inflamed area, 15-25 cm from the anus. Record the extent of disease in centimeters from the anal 
verge. If consent is provided by the participant, 4 additional mucosa biopsies may be collected for the optional future research 
studies (2 biopsies from the worst inflamed area and 2 from a non-inflamed/least inflamed area). If consent is provided by the 
participant, any remaining tissue from the required histopathology biopsies may be used for future research studies. See 
Section 8.7.1 for details on biopsy requirements. 
kk The Visit 5 Stage 1 endoscopy procedure should be performed before the in-clinic assessments at Visit 5 Stage 2 have been 
completed. 
ll 
The Visit 10/EOT Stage 1 endoscopy procedure should occur on or within 7 days before the actual Stage 2 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. Participants who 
complete the EOT Visit within 2 months after the Week 12 endoscopy are not required to repeat the procedure. 
mm Collect up to 6 biopsy samples total (2 for required histopathology and 4 for optional future research studies [if consent is provided 
by the participant]). If consent is provided by the participant, any remaining tissue from the required histopathology biopsies may 
be used for future research studies. All biopsies should be collected from the same distance from the anus as collected at the 
Screening Visit, regardless of the tissue state at the time of the sampling. Record the extent of disease in centimeters from the anal 
verge. Record the number of centimeters from the anus in which biopsies are collected at all follow-up visits into the Requisition 
Form. 
nn Blood samples for hs-CRP analysis will be collected at Stage 1 Screening and before the AM dose on Visits 4, 5, 7, and 10/EOT. 
oo Participants not participating in the LTE Period should return all study drug to the site. No additional dosing should occur after the 
completion of the EOT Visit. 
pp At Visit 5, the Induction Period study drug kits supplied at the previous visit should be used for the AM dose. Please note, a new 
supply of Maintenance Period study drug kits will be provided at the conclusion of Visit 5. Participants should use the Maintenance 
Period study drug kits for all future doses after the completion of Visit 5. 
qq For participants continuing treatment in the LTE Period, additional study drug will be dispensed at Visit 10. 

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rr 
AM dosing required on-site for all visits except the SFU Visit. 
ss 
At Visit 10/EOT, participants not participating in the LTE Period will only receive an AM dose for the day. No PM dose will be 
provided. 
tt 
Site staff will contact the participants, by phone or other means, on the next business day after the Visit 5 clinic visit is complete to 
confirm the participants are using the new supply of study drugs for the Maintenance Period. Record the date and time of the 
participant’s first Maintenance Period dose. 

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Table 2. 
Schedule of Activities for the LTE Period* 
Study Procedure 
Dose Switch 
Follow-up 1 a 
Dose Switch 
Follow-up 2 b 
LTE Period* 
Safety 
Follow-up 
UNS c 
Visit 
DSFU 1 
DSFU 2 
11 
12 
13 
14/LTE EOT d, e 
SFU f, g 
UNS 
Week 
4 weeks after 
the dose 
switch 
4 weeks after 
DSFU 1 
65 
78 
91 
104 
108 
 
Study Day 
 
 
456±7 
547±7 
638±7 
729±7 
757+7 h 
 
 
 
 
 
 
 
Stage 1 
Stage 2 
 
 
Informed consent 
 
 
X * 
X * 
X * 
 
 
 
 
Fill out Participant Diary 
(daily rectal bleeding, 
stool frequency) i 
X 
X 
X 
X 
X 
 
X 
X 
 
Participant Diary 
completion and 
compliance review 
X 
X 
X 
X 
X 
 
X 
X 
 
Pregnancy test j 
X 
X 
X 
X 
X 
 
X 
X 
X c 
Review of change in 
substance use k 
 
 
 
 
 
 
X 
 
 
Safety Assessments 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X c 
Physical exam l 
X 
X 
X 
X 
X 
 
X 
X 
X c 
Vital signs m 
X 
X 
X 
X 
X 
 
X 
X 
X c 
PML checklist n 
X 
X 
X 
X 
X 
 
X 
X 
 
Hematology and 
coagulation 
X 
X 
X 
X 
X 
 
X 
X 
X c 
Serum chemistry 
X 
X 
X 
X 
X 
 
X 
X 
X c 
Urinalysis 
X 
X 
X 
X 
X 
 
X 
X 
X c 
AE/SAE assessment o, p 
X 
X 
X 
X 
X 
X 
X 
X 
X c 
Efficacy Assessments 
 
 
 
 
 
 
 
 
Sigmoidoscopy with 
biopsy q 
 
 
 
 
X r 
 
 
 
Centrally read MES 
 
 
 
 
 
 
X 
 
 
Centrally read RHI Score, 
Continuous Geboes Score, 
and NI 
 
 
 
 
 
 
X 
 
 
Study Drug 
 
 
 
 
 
 
 
 
Study drug accountability 
X 
X 
X 
X 
X 
 
X s 
 
 

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Study Procedure 
Dose Switch 
Follow-up 1 a 
Dose Switch 
Follow-up 2 b 
LTE Period* 
Safety 
Follow-up 
UNS c 
Visit 
DSFU 1 
DSFU 2 
11 
12 
13 
14/LTE EOT d, e 
SFU f, g 
UNS 
Week 
4 weeks after 
the dose 
switch 
4 weeks after 
DSFU 1 
65 
78 
91 
104 
108 
 
Study Day 
 
 
456±7 
547±7 
638±7 
729±7 
757+7 h 
 
 
 
 
 
 
 
Stage 1 
Stage 2 
 
 
Dispense study drug 
 
 
X 
X 
X 
 
 
 
 
Confirm switch of study 
drug t 
X 
 
 
 
 
 
 
 
 
Abbreviations: AE, adverse event; B.I.D., twice a day; DSFU, Dose Switch Follow-up; ICF, Informed Consent Form; LTE, Long-Term Extension; LTE EOT, Long-Term Extension 
End of Treatment; MES, Mayo Endoscopic Subscore; NI, Nancy Histopathology Index; PML, progressive multifocal leukoencephalopathy; RHI, Robarts Histopathology Index; 
SAE, serious adverse event; SFU, Safety Follow-up; UNS, unscheduled. 
* 
Note: Due to the changes in Version 3.0 of this protocol, all participants who choose to continue their treatment in the LTE Period 
will be asked to re-consent to the LTE Period dose switch to 200 mg B.I.D. The dose switch will occur at Visit 10 or at a scheduled 
visit in the LTE Period (Visit 11, 12, or 13). For example, a participant who has already completed Visit 11 at the time that Protocol 
Version 3.0 is active will complete the dose switch at Visit 12 (Week 78). Then, the DSFU 1 will be completed 4 weeks later 
(Week 82), and the DSFU 2 will be 4 weeks after DSFU 1 (Week 86). Then, the participant will resume regular visits with the next 
visit at Visit 13 (Week 91) through the end of the study. If the participant does not consent to the dose switch, they will remain on 
their current LTE Period dose and schedule and will not need to attend DSFUs 1 or 2. 
a 
The DSFU 1 will occur 4 weeks after the dose switch. 
b 
The DSFU 2 will occur 4 weeks after the DSFU 1. 
c 
No specific tests or procedures are required for unscheduled visits. Results of any study procedures performed at an unscheduled 
visit will be recorded and collected for the study. Clinically relevant laboratory testing or re-testing (e.g., hematology, coagulation, 
serum chemistry, or urinalysis) may be performed at unscheduled visits. 
d 
Visit 14 is split into Stage 1 and Stage 2 to clarify the timing of the endoscopy procedure. The endoscopy procedure at Visit 14 
Stage 1 should be performed on or within 7 days before the Visit 14 Stage 2 in-clinic assessments have been completed. 
e 
If the participant discontinues early from the LTE Period, perform the LTE EOT procedures and schedule the SFU for 28 days 
(+7 days) after the participant takes the last dose of study drug (unless consent is withdrawn). 
f 
All participants enrolled in the LTE Period will complete the SFU Visit, which should be performed 28 days (+7 days) after the 
participant takes the last dose of study drug. 
g 
If the participant discontinues early from the LTE Period, perform the SFU procedures 28 days (+7 days) after the participant takes 
the last dose of study drug (unless consent is withdrawn). 

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h 
The SFU Visit is to occur 28 days (+7 days) after the last dose of study drug is received. If the LTE EOT Visit occurs before 
Day 729, the day for the SFU Visit can be adjusted according to the date of last study drug dose. 
i 
Participant Diaries are to be completed daily by the participant at home and brought to each study visit for review by study 
personnel. See Section 8.5 for the required contents of the Participant Diaries. 
j 
Only required for women of childbearing potential. A urine test should be used throughout the LTE Period. 
k 
Collect information on the participant’s change in substance use (e.g., alcohol, tobacco, and drugs). 
l 
A complete physical exam is to be performed at Visit 14/LTE EOT, and a targeted exam may be performed at all other required 
visits (see Section 8.8.1 for descriptions). For unscheduled visits, the type of exam (if necessary to be performed at all) will be at 
the Investigator’s discretion and determined based on the reason for the visit. 
m 
Vital signs to be recorded at most visits. At unscheduled visits, vital signs are not required and are at the discretion of the 
Investigator. These will include blood pressure, heart rate, respiratory rate, and temperature. Vital signs are to be taken before blood 
collection for laboratory tests. Blood pressure and pulse measurements should be preceded by at least 10 minutes of rest for the 
participant. 
n 
If the results of the questionnaire are suggestive of PML, a full neurological exam and, if indicated, additional testing are to be 
performed. 
o 
Record adverse events from the time the ICF for the LTE Period is signed. 
p 
Participants are to be contacted by phone as needed to monitor the status of the event. 
q 
Full colonoscopy is optional at any timepoint if the Investigator deems it necessary. Collect up to 6 biopsy samples total (2 for 
required histopathology and 4 for optional future research studies [if consent is provided by the participant]). If consent is provided 
by the participant, any remaining tissue from the required histopathology biopsies may be used for future research studies. All 
biopsies should be collected from the same distance from the anus as collected at the Screening Visit, regardless of tissue state at 
the time of sampling. Record the extent of disease in centimeters from the anal verge. Record the number of centimeters from the 
anus in which biopsies are collected at all follow-up visits into the Requisition Form. 
r 
Endoscopy is required at Visit 14/LTE EOT Stage 1 unless it was performed within 6 months of the LTE EOT Visit. The 
Visit 14/LTE EOT Stage 1 endoscopy procedure should occur on or within 7 days before the actual Stage 2 visit date. 
s 
At the LTE EOT Visit, participants should return all study drug to the site. No additional dosing should occur after the completion 
of the LTE EOT Visit. 
t 
Site staff will contact the participants who consented, by phone or other means, on the next business day after the dose switch in 
the LTE Period to confirm the participants have switched to the new dose (200 mg B.I.D.) of study drug correctly. Record the date 
and time of the participant’s first dose of the new dose (200 mg B.I.D.) in the source documents. 

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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 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 abdominal 
pain, bloody stool, diarrhea, urgency to defecate, fatigue, nausea, loss of appetite, weight loss, 
fever, and anemia. 
Initial therapy for UC generally includes the anti-inflammatory drugs 5-aminosalicylates and 
corticosteroids. Immunomodulators (e.g., methotrexate, azathioprine, and 6-mercaptopurine) may 
subsequently be used to maintain remission and avoid long-term corticosteroid use. However, 
these treatments often fail to control the disease long-term, particularly in patients with moderately 
to severely active UC, and both the corticosteroids 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 (
). Other therapeutic options recently approved for the treatment of 
UC are Janus kinase (JAK) inhibitors, such as the small molecule tofacitinib (
) or 
upadacitinib (
). 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 demonstrated efficacy in patients with UC who have moderately to severely active 
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disease. Relevant data from all non-clinical and clinical studies in the MORF-057 development 
program are provided in the current Investigator’s Brochure (IB). 
The aim of the current MORF-057-202 study is to evaluate the efficacy and safety of 3 active dose 
regimens of MORF-057 (as capsule, by mouth [P.O.]) versus placebo in study participants with 
moderately to severely active UC. Data from the MORF-057-202 study will provide further 
information to advance the clinical development program of MORF-057 for the treatment of UC. 
2.2. 
Background 
Inhibition of α4β7 integrin is an important therapeutic goal for the treatment of moderately to 
severely active UC that has been clinically validated with the monoclonal antibody vedolizumab 
(
). MORF-057 is an orally administered small molecule designed to selectively inhibit 
integrin α4β7. It prevents MAdCAM-1 from binding to the α4β7 integrin via a competitive 
mechanism (Yu, 2012). 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 advantages include a 
flexible dosing regimen and minimal safety concerns regarding immunogenicity and serious 
infusion reactions, requiring fewer 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. 
A detailed description of the chemistry, pharmacology, and safety of MORF-057 is provided in 
the current IB. Important non-clinical and clinical study results are summarized below. 
2.2.1. 
Non-clinical Findings 
Non-clinical studies have demonstrated that MORF-057 is highly selective for α4β7 over other 
integrins by a range of >100-fold to 143,000-fold. In addition, in a monkey gut homing model, 
MORF-057 blocked gut homing of α4β7-positive T-cells into lymphoid tissue, as measured by 
frequency of lymphocytes in tissue and in circulating blood as biomarkers, suggesting MORF-057 
can inhibit an established and important mechanism involved in the pathogenesis of IBD. 
MORF-057 has been characterized in Good Laboratory Practice-compliant toxicity and safety 
studies. MORF-057 had no effect on respiration, neurobehavior, or cardiovascular function, and 
had no genotoxicity or phototoxicity potential. Potential toxicity risks based on non-clinical data 
include effects to the stomach, liver, hematopoietic system, and embryo-fetal development. 
See the current MORF-057 IB for additional details. 
For human doses of 100 or 200 mg twice a day (B.I.D.), the calculated safety margin based on the 
no observed adverse effect levels (NOAELs) for the gastric changes identified in the 26-week 
study (50 mg/kg/day) is 8.2 -fold or 4.1-fold, respectively. Likewise, the exposure multiple based 
on the NOAEL observed in dogs in the 39-week study (300 mg/kg/day) is 190.2-fold or 95.6-fold 
for the 100 or 200 mg B.I.D. doses, respectively. The exposure margin based on a dose (60 mg/kg) 
that caused non-adverse minimal elevations of liver transaminases (alanine transaminase [ALT] 
1.24 x) in dogs dosed for 39 weeks is approximately 20-fold for the 100 mg B.I.D. and 10-fold for 
the 200 mg B.I.D. doses. The safety margin based on the embryo-fetal NOAEL in rabbits 
(50 mg/kg/day) is 0.8-fold or 1.6-fold for the 100 or 200 mg B.I.D. doses, respectively (refer to 
Section 4 of the current IB for details). 
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2.2.2. 
Clinical Findings 
Collectively from 7 Phase 1 MORF-057 studies conducted in healthy participants (N=171 who 
received MORF-057 across all 7 studies), MORF-057 was well tolerated. There were no deaths or 
serious adverse events (SAEs). 
Drug-drug interactions (DDI) were also evaluated in the Phase 1 clinical program. At a dose of 
100 mg B.I.D., MORF-057 is a weak inducer of cytochrome P450 3A (CYP3A). Although other 
doses have not been assessed for CYP3A induction, higher doses likely carry the risk of greater 
induction. MORF-057 is also a substrate of hepatic transporters organic anion transporting 
polypeptide (OATP) 1B1/3 and a sensitive substrate of CYP3A. 
Safety data are also available from the completed 52-week Treatment Period in the open-label 
Phase 2a study, MORF-057-201 (N=39) and from the 12-week Induction Period in this ongoing 
placebo-controlled Phase 2b study, MORF-057-202 (N=280). Overall, the treatment with 
MORF-057 was well tolerated in participants with moderately to severely active UC. 
• No death occurred in any of the completed or ongoing studies. 
• In the Phase 2b study, 5 participants who received either MORF-057 or placebo reported 
at least 1 serious treatment-emergent adverse event (TEAE), all in Study MORF-057-202. 
The Investigator considered that none of these serious TEAEs were related to the study 
drug. 
• In the Phase 2 studies, a total of 11 participants discontinued the study treatment due to 
TEAEs, with 6 MORF-057 treated participants in Study MORF-057-201 and 5 participants 
who received either MORF-057 or placebo in Study MORF-057-202. 
• The most frequently reported TEAEs in participants receiving MORF-057 at any dose in 
the Phase 2 studies included ulcerative colitis, anemia, nasopharyngitis, and headache. 
• No cases of Progressive Multifocal Leukoencephalopathy (PML) were reported in any of 
the completed or ongoing studies. 
The observed safety profile was consistent with the class safety profile for α4β7 integrin inhibitors. 
No safety signals have been identified in any of the MORF-057 clinical studies. 
The clinical efficacy of MORF-057 has been evaluated in UC patients in the open-label Study 
MORF-057-201. In this study, a statistically significant decrease in Robarts Histopathology Index 
(RHI) Score from baseline to Week 12 was achieved, as well as a reduced modified Mayo Clinic 
Score (mMCS) from baseline. Additionally, a 25.7% remission rate was demonstrated based on 
mMCS. 
In the 12-week Induction Period analysis for this ongoing placebo-controlled Phase 2b study, 
MORF-057-202, the primary and secondary objectives of clinical remission and clinical response, 
respectively, were not achieved. A dose-response was observed between the 3 active doses, and 
200 mg B.I.D. was the clinically most active dose. 
Refer to the current IB for details on the clinical studies conducted to date. 

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2.3. 
Benefit/Risk Assessment 
Detailed information about the known and expected benefits and risks and reasonably expected 
adverse events (AEs) of MORF-057 may be found in the current IB. 
2.3.1. 
Benefits 
MORF-057 inhibits α4β7 integrin binding to MAdCAM-1, which is the same mechanism used by 
the marketed drug vedolizumab. Studies of vedolizumab have shown this to be an effective 
mechanism for treating patients with UC (Feagan, 2013). Therefore, MORF-057 may benefit 
patients with moderately to severely active UC whose disease has progressed or has been 
unresponsive to currently approved standard of care agents. In addition, 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). These include the following: 
• 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. 
• Biologics, such as vedolizumab, can act as antigens and induce anti-drug antibodies, which 
may alter pharmacokinetics (PK)/pharmacodynamics (PD) and impact efficacy. 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). In addition, serious infusion reactions, including anaphylaxis, have been 
reported with vedolizumab. Oral small molecule drugs avoid safety issues related to 
intravenous administration and immunogenicity that are often associated with biologics. 
MORF-057 is an oral small molecule drug that is not immunogenic and does not have 
intravenous administration-related challenges. 
2.3.2. 
Risks 
2.3.2.1. 
Risks of MORF-057 
Overall, based on the available data for MORF-057 to date, the risk to study participants is 
expected to be minimal. 
Potential toxicity risks based on MORF-057 non-clinical data include effects to the stomach, liver, 
hematopoietic system, and embryo-fetal development. The gastric, hepatic, and hematopoietic 
findings demonstrated partial or complete reversibility and are generally clinically monitorable. 
Phase 1 DDI studies indicate that MORF-057 is a weak inducer of CYP3A. Sensitive CYP3A 
substrates for which small decreases in exposure can result in an unacceptable decrease in efficacy 
should be used with caution. In particular, systemic hormonal contraception should not be 
considered reliable and should not be used for the purpose of contraception. 
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Based on available clinical data from both completed and ongoing studies, there are no anticipated 
risks of particular severity that require monitoring beyond the routine monitoring typically 
associated with integrin receptor antagonists or other immunomodulatory products in human 
studies. 
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 electrocardiograms (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. 
• PML is a fatal opportunistic infection of the central nervous system and has been associated 
with systemic immunosuppressants, including integrin receptor antagonists (e.g., 
natalizumab and vedolizumab). Natalizumab, a monoclonal antibody that inhibits both α4β1 
and α4β7 integrins, has been associated with PML, a serious brain infection. One case of 
PML in an 
 (vedolizumab)-treated patient with multiple contributory factors has 
been reported in the post-marketing setting (e.g., human immunodeficiency virus [HIV] 
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). 
• Potential toxicity risks of MORF-057 based on non-clinical data include effects to 
embryo-fetal development. There is no clinical experience with MORF-057 in pregnant 
and breastfeeding women and therefore, the potential effects of MORF-057 use during 
pregnancy and lactation are not known. Women who are breastfeeding or pregnant are 
excluded from this study. Women of childbearing potential (WOCBP) and men who 
participate in this study must agree to avoid pregnancy and will be instructed on 
contraception requirements while they are in this study (see Section 10.5). 
• Clinical studies have demonstrated that MORF-057 is a weak inducer of CYP3A, a 
substrate of hepatic transporters OATP1B1/3, and a sensitive substrate of CYP3A. 
Inhibitors of OATP1B1/3 or inhibitors/inducers of CYP3A can alter exposures of 
MORF-057 and their use is prohibited in this study (see Section 6.7.3). 
Safety criteria for study drug discontinuation are outlined in Section 7. 
The Sponsor will immediately notify the Investigator of any significant safety or toxicology 
information during the study. 
2.3.2.2. 
Risk of MORF-057 in Combination with COVID-19 Vaccine 
Non-live COVID-19 vaccination is considered a simple concomitant medication within the study. 
However, the efficacy and safety of non-live vaccines (including non-live COVID-19 vaccines) in 
subjects receiving MORF-057 is unknown. The individual benefit risk assessment of a vaccine 
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remains with the Investigator. If the assessment of the Investigator suggests the vaccine to be 
beneficial, it must be a non-live, replication incompetent vaccine, and be approved or authorized 
by national health authorities. 
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 UC. 
3. 
Objectives and Endpoints 
The following study objectives will be completed by assessing the associated endpoints in 
participants with moderately to severely active UC. 
Objectives 
Endpoints  
Primary Efficacy 
 
To evaluate the effects of MORF-057 on 
clinical remission at Week 12 
• Proportion of participants in clinical 
remission at Week 12 as determined using 
the Modified Mayo Clinic Score (mMCS). 
The mMCS is a composite of the following 
subscores: 
o Mayo endoscopic subscore (MES) 
o Mayo Clinic Score (MCS) stool 
frequency subscore 
o MCS rectal bleeding subscore 
Secondary Efficacy 
 
To evaluate the effects of MORF-057 on 
clinical response at Week 12 
• Proportion of participants with clinical 
response at Week 12 as determined using 
the mMCS 
Exploratory Efficacy 
 
To evaluate the effects of MORF-057 on 
clinical remission at Week 52 
• Proportion of participants in clinical 
remission at Week 52 as determined using 
the mMCS 
To evaluate the effects of MORF-057 on 
clinical response at Week 52 
• Proportion of participants with clinical 
response at Week 52 as determined using 
the mMCS 

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Objectives 
Endpoints  
To evaluate the effect of MORF-057 on MCS 
remission at Weeks 12 and 52 
• Proportion of participants in MCS remission 
at Weeks 12 and 52. 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 evaluate the effect of MORF-057 on MCS 
response at Weeks 12 and 52 
• Proportion of participants with MCS 
response at Weeks 12 and 52 
To evaluate the effects of MORF-057 on 
histologic remission at Weeks 12 and 52 
• Proportion of participants in histologic 
remission at Weeks 12 and 52 as determined 
using the Robarts Histopathology Index 
(RHI) Score 
• Proportion of participants in histologic 
remission at Weeks 12 and 52 as determined 
using the Nancy Histopathology Index (NI) 
• Proportion of participants in histologic 
remission at Weeks 12 and 52 as determined 
using the Continuous Geboes Score 
To evaluate the effects of MORF-057 on 
histologic improvement at Weeks 12 and 52 
• Proportion of participants with histologic 
improvement at Weeks 12 and 52 as 
determined using the RHI 
To evaluate the effect of MORF-057 on 
endoscopic improvement at Weeks 12 and 52 
• Proportion of participants with endoscopic 
improvement at Weeks 12 and 52 as 
determined using the MES 
To evaluate the effects of MORF-057 on 
endoscopic remission at Weeks 12 and 52 
• Proportion of participants in endoscopic 
remission at Weeks 12 and 52 as determined 
using the MES 
To evaluate the effects of MORF-057 on 
mucosal healing at Weeks 12 and 52 
• Proportion of participants in endoscopic 
remission as determined using the MES and 
histologic remission as determined using the 
RHI at Weeks 12 and 52 

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Objectives 
Endpoints  
To evaluate the effects of MORF-057 on 
mucosal improvement at Weeks 12 and 52 
• Proportion of participants with endoscopic 
improvement as determined using the MES 
and a histologic improvement as determined 
using the RHI at Weeks 12 and 52 
To evaluate the effects of MORF-057 on 
symptomatic response at Weeks 2 and 6 
• Proportion of participants with symptomatic 
response at Weeks 2 and 6 as determined 
using the Partial mMCS. Partial mMCS is a 
composite of the following subscores: 
o MCS stool frequency subscore 
o MCS rectal bleeding subscore 
To evaluate the effects of MORF-057 on 
Partial MCS response at Week 6 
• Proportion of participants with Partial MCS 
response at Week 6. Partial MCS is a 
composite of the following subscores: 
o MCS stool frequency subscore 
o MCS rectal bleeding subscore 
o MCS PGA 
To determine time to symptomatic response 
by Week 12 
• Time to symptomatic response by Week 12 
as determined using the Partial mMCS 
To assess the effect of MORF-057 on 
non-endoscopic biomarkers of inflammation 
at Weeks 12 and 52 
• Change from baseline to Weeks 12 and 52 
in high-sensitivity C-reactive protein 
(hs-CRP) levels 
• Change from baseline to Weeks 12 and 52 
in fecal calprotectin levels 
To evaluate the effect of MORF-057 on 
patient-reported outcomes (PROs) at 
Weeks 12 and 52 
• Change from baseline to Weeks 12 and 52 
in Inflammatory Bowel Disease 
Questionnaire (IBDQ) Score 
To evaluate the effect of MORF-057 on 
corticosteroid-free remission at Week 52 
• Proportion of participants in 
corticosteroid-free remission at Week 52, as 
determined using the mMCS, among the 
participants who were on a stable dose of 
corticosteroids at baseline 
To characterize the effect of MORF-057 on 
the need for UC-related hospitalizations and 
surgeries 
• Percentage of participants requiring 
UC-related hospitalization or surgery at 
Weeks 12 and 52 

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Objectives 
Endpoints  
To evaluate the long-term histologic and 
endoscopic effects of MORF-057 at 
Week 104 
• Proportion of participants in histologic 
remission at Week 104 as determined using 
the RHI 
• Proportion of participants in histologic 
remission at Week 104 as determined using 
the NI 
• Proportion of participants in histologic 
remission at Week 104 as determined using 
the Continuous Geboes Score 
• Proportion of participants with histologic 
improvement at Week 104 as determined 
using the RHI 
• Proportion of participants with endoscopic 
improvement at Week 104 as determined 
using the MES 
• Proportion of participants in endoscopic 
remission at Week 104 as determined using 
the MES 
• Proportion of participants in endoscopic 
remission as determined using the MES and 
histologic remission as determined using the 
RHI at Week 104 
• Proportion of participants with endoscopic 
improvement as determined using the MES 
and a histologic improvement as determined 
using the RHI at Week 104 
Safety 
 
To assess the safety and tolerability of 
MORF-057 
• Frequencies and proportions for TEAEs, 
treatment-emergent serious adverse events 
(TESAEs), and TEAEs leading to study 
drug discontinuation 
Pharmacokinetics (PK) 
 
To characterize the PK of MORF-057 
• MORF-057 concentration in plasma 
Exploratory Pharmacodynamics (PD) 
 
To characterize the PD of MORF-057 in 
peripheral blood 
• α4β7 receptor occupancy in blood over time 

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Objectives 
Endpoints  
• α4β1 receptor occupancy in blood over time 
• Change from baseline over time in blood 
CCR9 messenger ribonucleic acid (mRNA) 
• Change from baseline over time in blood 
lymphocyte subsets 
 
Efficacy Analysis Definitions 
Clinical remission: Determined using the mMCS. Rectal bleeding subscore of 0; a stool frequency 
subscore of ≤1; and an MES of ≤1 without friability 
Clinical response: Determined using the mMCS. 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 
MCS remission: MCS ≤2 and no subscore higher than 1 
MCS response: Decrease in MCS ≥3 points and ≥30% from baseline, plus a decrease in rectal 
bleeding score ≥1 or an absolute rectal bleeding score ≤1 
Histologic remission by RHI: RHI ≤2 (with 0 for lamina propria neutrophils score and neutrophils 
in the epithelium score and without ulcers or erosions) 
Histologic remission by NI: NI=0 
Histologic remission by Continuous Geboes: Continuous Geboes ≤3 
Histologic improvement: ≥7-point reduction in RHI 
Endoscopic improvement: MES ≤1 
Endoscopic remission: MES=0 
Mucosal healing: MES=0 and RHI ≤3 (with 0 for lamina propria neutrophils score and 
neutrophils in the epithelium score and without ulcers or erosions) 
Mucosal improvement: MES ≤1 and ≥7-point reduction in RHI 
Symptomatic response: Decrease in Partial mMCS ≥1 point and ≥30% from baseline, plus a 
decrease in rectal bleeding subscore ≥1 or an absolute rectal bleeding subscore ≤1 
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 
Time to symptomatic response: Time from randomization date to symptomatic response 
Corticosteroid-free remission: Determined only in participants who were receiving 
corticosteroids on study Day 1. Includes such participants who are both in clinical remission (as 
determined using the mMCS) at Week 52 and off corticosteroids for ≥12 consecutive weeks prior 
to Week 52. 
 

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4. 
Study Design 
4.1. 
Overall Design 
This study is a randomized, double-blind, placebo-controlled, multicenter, Phase 2b study to 
evaluate the efficacy and safety of 3 active dose regimens of MORF-057 (as capsule, P.O.) versus 
matching placebo in study participants with moderately to severely active UC. 
Approximately 280 participants will be randomized into the treatment groups in a 1:1:1:1 ratio 
(i.e., 70 participants per group). The study will enroll participants who are advanced therapy-naïve 
(i.e., have no previous exposure to an advanced therapy treatment for UC) and advanced 
therapy-experienced (excluding vedolizumab), with at least 30% but no more than 40% of 
advanced therapy-experienced participants. Randomization stratification factors will include 
baseline MES (<3 vs 3) and previous use of advanced therapy treatment (advanced therapy-naïve 
vs advanced therapy-experienced). All participants will be enrolled from approximately 
150 centers worldwide. For this study, moderately to severely active UC will be defined as having 
an mMCS of 5 to 9 (inclusive), with an MES ≥2 (confirmed by central reader). 
The main part of this Phase 2b study will consist of a Screening Period (up to 6 weeks, consisting 
of Stage 1 and Stage 2 testing), a Treatment Period (52 weeks, including a 12-week Induction 
Period and a 40-week Maintenance Period), and a Safety Follow-up (SFU) Period (4 weeks). 
During the main part of this 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, 18, 
24, 32, 42, and 52 [End of Treatment (EOT)]), and an SFU Visit (visit to occur 4 weeks after the 
last dose of study drug is received, which will be at Week 56 if the full Treatment Period 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). 
All participants who complete the 52-week Treatment Period will have the opportunity to continue 
their treatment in a 52-week Long-Term Extension (LTE) Period. 
During the optional LTE Period, there will be up to 7 scheduled visits: 4 Treatment Visits 
(Visits 11-14 at Weeks 65, 78, 91, and 104 [Long-Term Extension (LTE) EOT]), 2 Dose Switch 
Follow-ups (DSFUs; these 2 visits will only occur if participant consents to dose switch), and an 
SFU Visit (visit to occur 4 weeks after the last dose of study drug is received, which will be at 
Week 108 if the full LTE Period is completed or earlier if treatment is discontinued early). 
Due to the changes in Version 3.0 of this protocol, all participants who choose to continue their 
treatment in the LTE Period will be asked to re-consent to the LTE Period dose switch to 200 mg 
B.I.D. The dose switch will occur at Visit 10 or at a scheduled visit in the LTE Period (Visit 11, 
12, or 13). If the participant does not consent to the dose switch, they will be allowed to remain on 
their current LTE Period dose and schedule; they will not need to attend DSFUs 1 or 2. Participants 
in the LTE Period who consent to the dose switch will have a scheduled DSFU 1 at 4 weeks after 
the dose switch, and then DSFU 2 will be 4 weeks after DSFU 1. The participant will then attend 
the next scheduled visit (Visit 11, 12, 13, or 14) per the Schedule of Activities (SoA). A participant 
cannot switch their dose after Visit 13. An SFU Visit will occur 4 weeks after the last dose of study 
drug is received, which will be at Week 108 if the full LTE Period is completed or earlier if 
treatment is discontinued early. 

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Participants who do not enroll into the LTE Period will complete the final SFU Visit (4 weeks 
after receiving the last dose of MORF-057) for the main part of the study (a maximum time 
on-study of 62 weeks). Participants who choose to continue in the LTE Period will not complete 
the SFU Visit for the main part of the study; instead, they will directly enter the LTE Period and 
complete a separate SFU Visit (4 weeks after receiving the last dose of MORF-057 in the LTE 
Period), for a maximum time on-study of 114 weeks. 
An independent DSMB will review participant safety data and monitor scientific integrity 
throughout the study. Details related to the DSMB will be clearly delineated in the DSMB Charter. 
Enrolled participants will be randomized to a treatment group to receive active MORF-057 or 
placebo. Participants initially randomized into an active MORF-057 treatment group will receive 
an active treatment (according to study period and group assignment) for the full 52-week 
Treatment Period. Participants initially randomized into the placebo group will be switched to an 
active MORF-057 regimen (200 mg once a day – evening [Q.D.-E]) after they complete the 
Induction Period and the Week 12 assessments. After participants complete the full 52-week 
Treatment Period, they will have the option to enter an additional 52-week LTE Period. All 
participants who choose to continue in the LTE Period will continue receiving the same 
MORF-057 regimen they had during the Maintenance Period for up to an additional 52 weeks. 
However, at Visit 10 or at a scheduled visit in the LTE Period (Visit 11, 12, or 13), if the participant 
consents, the MORF-057 dose for the LTE Period will be switched to 200 mg B.I.D. If the 
participant does not consent to the dose switch, they will be allowed to remain on their current 
LTE Period dose and schedule. The dosing regimens for the 4 treatment groups during the study 
are shown below. 
 
Induction Period 
(12 Weeks) 
 
Maintenance Period (40 Weeks)/ 
LTE Period (52 Weeks) 
LTE Period (52 Weeks)* 
 
Group 1 
MORF-057 (200 mg 
B.I.D.) 
MORF-057 (100 mg B.I.D.) 
MORF-057 (200 mg B.I.D.) 
Group 2 
MORF-057 (100 mg 
B.I.D.) 
MORF-057 (100 mg B.I.D.) 
MORF-057 (200 mg B.I.D.) 
Group 3 
MORF-057 (100 mg 
Q.D.-M) 
MORF-057 (100 mg Q.D.-M) 
MORF-057 (200 mg B.I.D.) 
Group 4  
Placebo 
MORF-057 (200 mg Q.D.-E) 
MORF-057 (200 mg B.I.D.) 
Abbreviations: B.I.D., twice a day; LTE, Long-Term Extension; Q.D.-E, once a day (evening); Q.D.-M, once a day (morning). 
* Relevant for participants who consent to the dose switch in the LTE Period. For those that do not consent to the dose switch in 
the LTE Period, they will remain on their current LTE Period dose. 
A study schema is provided in Figure 1. 

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Figure 1. 
Study Schema 
 
Abbreviations: B.I.D. twice a day; DSFU, Dose Switch Follow-up; EOT, End of Treatment; Q.D.-E, once a day (evening); Q.D.-M, 
once a day (morning); SFU, Safety Follow-up; UC, ulcerative colitis; V, visit; W, week. 
a The SFU Visit will not be performed at Week 56 for participants who enter the LTE Period. 
b The assessments to be performed at each visit and the acceptable time windows for each visit are provided in the Schedule of 
Activities. 
c 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. 
d At Visit 10 or at a scheduled visit in the LTE Period (Visit 11, 12, or 13), all participants will be asked to re-consent to switch 
their dose to 200 mg B.I.D. Participants who do not consent to the dose switch will remain on their current LTE Period dose. The 
DSFU 1 will occur 4 weeks after the dose switch, and DSFU 2 will occur 4 weeks after DSFU 1. Participants who do not consent 
to the dose switch will not need to attend DSFUs 1 or 2. 
The objectives and endpoints for the study are provided in Section 3. 
4.2. 
Scientific Rationale for Study Design 
This is a randomized, double-blind, placebo-controlled study. This design will allow for a rigorous 
evaluation of the safety and efficacy of MORF-057 in participants with moderately to severely 
active UC. 
In the study, 3 active dose regimens of MORF-057 will be compared to placebo for a 12-week 
Induction Period in order to determine the best overall dosing regimen for future clinical 
development of MORF-057. This study is the first MORF-057 study with multiple dose arms in 
UC participants. Multiple B.I.D. doses are being evaluated to compare efficacy, safety, PK 
parameters, and α4β7 and α4β1 receptor occupancy of MORF-057 B.I.D. administration in UC. An 
additional Q.D. treatment group is included to compare B.I.D. administration to Q.D. 
administration. A placebo group is included as a control to compare the efficacy and safety data 
observed in the active treatment groups to that in a non-active control group. Dose reductions in 
response to AEs will not be possible due to the double-blind study design; however, study drug 
interruption will be allowed as deemed necessary by the Investigator and Sponsor Medical 
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In total, the 3 active dose regimens of MORF-057 will be administered for 52 weeks (including a 
12-week Induction Period plus a 40-week Maintenance Period). This 52-week design simulates 
assessment of treatment goals for UC in clinical practice, wherein participants are evaluated for 
induction of remission, followed by assessment of maintenance of remission over a longer period 
of time (usually assessed over 52 weeks of continuous treatment in clinical studies). Modern UC 
clinical trials have Induction Periods lasting 6 to 14 weeks. The 52-week treatment will be followed 
by an optional 52-week LTE Period. This extension will provide the participants further access to 
the study drug and collect additional safety and efficacy data up to 104 weeks of exposure. 
Participants who are initially randomized to receive placebo will be switched to an active 
MORF-057 regimen after the 12-week Induction Period. The main purpose for the switch is to 
collect additional safety data about the active treatment. 
The MCS and its derivates are well-established instruments to measure clinical response or 
remission in patients with UC. The mMCS was chosen for the primary endpoint because it 
excludes the PGA, a component that the Food and Drug Administration (FDA) and key opinion 
leaders recommend against using as an endpoint measure to support a marketing application. This 
recommendation was made because signs and symptoms are best assessed using an outcome 
instrument that directly reports measurements by patients as opposed to clinicians. 
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. 
Patients were not involved in the design of this study. 
4.3. 
Justification for Dose 
The dose regimens selected for this study are provided in Section 4.1. 
The selection of dosing regimens was based on the non-clinical and clinical data on mechanism of 
action of MORF-057, the PK and PD properties, and the safety profile in healthy subjects. In 
Studies MORF-057-101 and 
 and based on PK-PD modeling, which included PK 
and PD assessments in healthy adults, separation of exposures was observed/simulated at low 
(100 mg once a day – morning [Q.D.-M]), mid (100 mg B.I.D.), and high (200 mg B.I.D.) doses, 
and maximum saturation of α4β7 receptor occupancy was observed following 100 mg B.I.D. and 
200 mg B.I.D. doses. It is expected that α4β7 receptor occupancy will be approximately 70% at 
trough level following 100 mg Q.D.-M dosing. MORF-057 exhibited favorable and near 
dose-proportional PK across doses with only mild, non-serious AEs reported that did not result in 
study drug discontinuation. The plasma exposure (AUC), peak (Cmax) and trough (Ctrough) 
concentrations across selected dosing regimens would help to study dose-response and 
exposure/concentration response relationships. This exposure was seen in healthy individuals and 
is expected to be similar in patients with UC to provide levels that would achieve the intended 
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 
CCI

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to α4β7 and α4β1 for MORF-057 are 1:610 and 1:700, respectively. The MORF-057 doses 
selected for the current study are 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. 
The International Council for Harmonisation (ICH)E4 guidelines as well as the Guideline on the 
development of new medicinal products for the treatment of UC (CHMP/EWP/18463/2006 Rev.1) 
accept placebo as an acceptable comparator (monotherapy or add-on to established therapy) in 
clinical trials. 
The placebo group serves as a control to evaluate the safety as well as efficacy of MORF-057 in a 
contemporaneous population. 
All participants will be allowed to continue stable background therapy to which either MORF-057 
or placebo will be added for 12 weeks. 
4.4. 
End of Study Definition 
A participant is considered to have completed the study if he/she has completed the Screening 
Period and 52‑week Treatment Period of the main part of the study and attended the SFU Visit OR 
has been enrolled into the LTE Period, completed the Week 104/LTE EOT Visit and attended the 
SFU Visit. 
The end of the study is defined as the date of the last visit or last scheduled procedure for the last 
participant in the study globally. This may occur during the main part of the study, or in the 
optional LTE Period, depending on that participant’s choice whether or not to continue in the LTE 
Period. 
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. Male or female, 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 diagnosis of UC supported by signs/symptoms, endoscopy, and histology 
for at least 3 months prior to Screening. Moderately to severely active UC was determined 
during the Screening Period with the following criteria: an mMCS of 5 to 9 (inclusive), with 
an MES ≥2 (confirmed by central reader) 
3. Has evidence of UC extending at least 15 cm from the anal verge 

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4. Demonstrated an inadequate response, loss of response, or intolerance to at least one of the 
following treatments (including oral aminosalicylates*, corticosteroids, immunosuppressants, 
and/or advanced therapies for UC) in the opinion of the Investigator, as defined below: 
a. Oral aminosalicylates (e.g., mesalamine, sulfasalazine, olsalazine, or balsalazide) 
• Signs and symptoms of persistently active disease during a current or prior 
course of at least 4 weeks of treatment with ≥2.0 g/day mesalamine, 
4 g/day sulfasalazine, 1 g/day olsalazine, or 6.75 g/day balsalazide 
*Note: Inadequate response, loss of response, or intolerance to oral aminosalicylates 
does not apply to this Inclusion Criterion in European Union (EU) countries. 
b. Corticosteroids 
• Signs and symptoms of persistently active disease despite a history of at 
least one induction regimen that included a dose equivalent to prednisone 
≥30 mg/day orally for at least 3 weeks or intravenously for 1 week 
OR 
• Unable to taper corticosteroids to below a dose equivalent to prednisone 
10 mg daily orally without recurrent active disease 
OR 
• Signs and symptoms of persistently active disease during or after a course 
of at least 4 weeks of treatment with 9 mg/day budesonide or 5 mg/day 
beclomethasone 
OR 
• Unable to taper oral budesonide below 6 mg/day without recurrent active 
disease 
OR 
• History of intolerance to corticosteroids (including, but not limited to, 
Cushing's syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, 
or infection) 
c. Immunosuppressants (e.g., azathioprine, 6-mercaptopurine, or methotrexate) 
• Signs and symptoms of persistently active disease despite a history of at 
least one 8*-week regimen of oral azathioprine (≥1.5 mg/kg/day), 
6-mercaptopurine (≥1 mg/kg/day or a documented 6-thioguanine 
nucleotide level of 230-450 pmol/8 × 108 red blood cell count or higher on 
the current dosing regimen), injectable methotrexate (≥12.5 mg/week 
subcutaneous [SC] or intramuscular) 
*Note: A history of signs and symptoms of persistently active disease 
despite a history of at least one 12-week regimen of immunosuppressants 
is required in EU countries. 
OR 

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• History of intolerance to at least one immunosuppressant (including, but not 
limited to, nausea/vomiting, abdominal pain, pancreatitis, liver enzyme 
abnormalities, lymphopenia, or infection) 
Note: Oral methotrexate use is allowed during the study; however, prior or current 
use of oral methotrexate is not sufficient for inclusion into the study unless the 
participant was previously treated with aminosalicylates, corticosteroids, or 
immunosuppressants (azathioprine or 6-mercaptopurine) and had an inadequate 
response, loss of response, or intolerance to the therapy as defined above. 
d. Advanced therapies for UC (e.g., biologic agents, JAK antagonists, or 
sphingosine-1-phosphate [S1P] receptor agonists) 
• Primary non-response – Signs and symptoms of persistently active disease 
despite a history of any of the following: 
o At least one 6-week induction regimen of infliximab (5-10 mg/kg 
intravenously at 0, 2, and 6 weeks) 
o At least one 4-week induction regimen of adalimumab (one 160 mg 
SC dose followed by one 80 mg SC dose [or one 80 mg SC dose in 
countries where this dosing regimen is allowed followed by one 
40 mg SC dose] at 2 weeks or earlier) 
o At least one 2-week induction regimen of golimumab (one 200 mg 
SC dose followed by one 100 mg SC dose at least 2 weeks apart) 
o At least one induction regimen of ustekinumab (single intravenous 
weight-based infusion of 260 mg [<55 kg body weight], 390 mg 
[55-85 kg body weight], or 520 mg [>85 kg body weight]) 
o A history of completed Induction regimen according to prescribing 
information for JAK antagonists or S1P receptor agonists 
OR 
• Secondary non-response – Initially responded to Induction therapy and 
then had recurrence of symptoms after receiving at least 2 of the 
Maintenance doses specified below (discontinuation despite clinical 
benefit does not qualify): 
o Infliximab: ≥5 mg/kg 
o Adalimumab: 40 mg every week or every other week 
o Golimumab: 100 mg injection at Week 6 and every 4 weeks 
o Ustekinumab: 90 mg SC dose 8 weeks after the initial intravenous 
dose, then every 8-12 weeks thereafter or more frequently 
OR 
• History of intolerance to at least one advanced therapy agent (including, but 
not limited to, infusion-related reaction, demyelination, congestive heart 
failure, or infection) 
Note: Participants who have received a prior advanced therapy agent for up to 
1 year and did not have a documented non-response may be enrolled; however, the 
participants must have discontinued the advanced therapy agent for reasons other 
than inadequate response or intolerance (e.g., change of insurance, well-controlled 

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disease) and must meet the criteria for inadequate response, loss of response, or 
intolerance to aminosalicylates, corticosteroids and/or immunosuppressants, as 
defined above. 
Note: Participant cannot have had inadequate response, loss of response, or 
intolerance to more than 3 drugs in 2 classes of the following advanced therapies: 
a. TNF-α antagonists, including infliximab, adalimumab, or golimumab 
b. Interleukin (IL)-12/IL-23 antagonists, including ustekinumab 
c. JAK antagonists, including tofacitinib or upadacitinib 
d. S1P receptor agonists, including ozanimod 
e. Any investigational product with the same mechanism as one of those 
outlined above (a through d) or a novel mechanism of action 
Note: Participants who have a history of primary non-response to 2 or more of the 
advanced therapy 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. 
5. 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 or upadacitinib: at least 1 week 
d. S1P receptor agonists, including ozanimod: at least 4 weeks 
Note: Participants who do not meet the full washout period but have the results of a local 
drug concentration level performed during the Screening Window deemed by the Medical 
Monitor to be sub-therapeutic may be eligible for the study earlier than the full washout 
period. 
6. 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 SFU Period, with the exception of tapering oral corticosteroid dose after 12 weeks 
of being in the trial. 
a. Oral 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/day, budesonide 9 mg/day, 
beclomethasone dipropionate 5 mg/day, methylprednisolone 24 mg/day, or 
equivalent; see Table 5): 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 
*Note: Participants must be on any stable dose of 6-mercaptopurine, azathioprine, or 
methotrexate for at least 12 weeks prior to study Day 1 in EU countries. 
7. If the participant has had UC for over 7 years, he/she must have had a full colonoscopy in the 
last 2 years or must agree to have a full colonoscopy (rather than sigmoidoscopy) with 
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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) ≥18.0 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 10.5.3) when having sexual 
intercourse with a woman of childbearing potential who is not 
currently pregnant. 
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 
MORF-057 
Note: For contraception requirements on or after Protocol Amendment Version 3.0, see 
Section 10.5.2.2. 
11. For the study Treatment Period and at least 14 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). 

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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 
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 
Crohn’s disease, or has clinical findings suggestive of Crohn’s disease 
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 
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 
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 PML symptom checklist during Screening or prior to the 
administration of the first dose of study drug on study Day 1 
7. Has a potentially active bacterial, viral, or parasitic pathogenic enteric infection, including 
Clostridiodes difficile (C. difficile); has hepatitis B or C virus, or 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 active tuberculosis (TB), as evidenced by any of the following: 
a. A diagnostic test for TB performed within 30 days prior to Screening or during 
the Screening Period that is positive, as defined below: 
• A positive interferon gamma release assay (IGRA) test (e.g., 
 
 TB test) or 2 consecutive indeterminate 
IGRA tests 
OR 
• A purified protein derivative (PPD) skin test ≥5 mm 
b. A chest X-ray or imaging per local guidelines within 3 months prior to Screening 
where active or latent pulmonary TB cannot be excluded 
Note: Participants who have tested negative for TB at a certified local lab using an IGRA test 
within 3 months prior to Screening are not required to repeat this test during the Screening 
Period if that participant has no clinical signs or symptoms of TB and no known 
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exposures/increased risk factors since the last negative TB test (according to the Investigator’s 
clinical judgement), and the test result is available in the participant’s medical record 
Note: Participants with a history of latent TB may be enrolled if they complete an assessment 
for evidence of active TB versus latent TB. Documentation will include a chest X-ray or 
imaging per local guidelines during the Screening Window and no signs, symptoms, or 
evidence of ongoing active TB. Participants have had treatment per the local standard of care 
for a minimum of 2 weeks before the first dose of study drug OR documentation of completing 
appropriate treatment for latent TB within 2 years before Day 1 of the study. See 
Section 8.2.2.1 for more details. 
9. Has a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result 
during the Screening Period. Testing for SARS-CoV-2 is required only per local regulations. 
Participants who have a positive test result can be randomized after a subsequent negative test 
result during the Screening Period. 
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 >5.5 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. Participants with an international normalized 
ratio >1.5 due to anticoagulant therapy (e.g., Coumadin) may only be enrolled after 
a consultation with the Medical Monitor. 

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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 >2.0 × 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 
equation (National Kidney Foundation), 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 licensed or investigational integrin 
inhibitors 
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. Participant needs to continue treatment with a moderate-to-strong CYP3A inducer or inhibitor 
and, therefore, will be unable to do a washout period of at least 30 days or 5 half-lives 
(whichever is shorter) prior to study Day 1. See Section 6.7.3 for a list of moderate-to-strong 
P450 inducers and inhibitors. 
25. Participant needs to continue treatment with a moderate-to-strong organic anion transporter 
polypeptide-1B inhibitor and, therefore, will be unable to do a washout period of at least 
14 days or 5 half-lives (whichever is shorter) prior to study Day 1. See Section 6.7.3 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. Known allergies/hypersensitivity to any component of the study drug and/or previous exposure 
to MORF-057 and/or a known hypersensitivity to drugs with a similar mechanism to 
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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 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 
No new non-pharmacological therapies should be started during the study period. Information 
should be collected on the participant’s change in substance use (e.g., alcohol, tobacco, and drugs) 
per the SoA in Section 1.2. 
The following dietary and lifestyle restrictions are recommended throughout the duration of the 
study: 
• Refrain from consuming grapefruit, grapefruit juice, starfruit, limes, and bitter oranges. 
• Refrain from excessive caffeine consumption, defined as 800 mg/day (or >8 cups of 
brewed coffee per 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 morning 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 morning 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 
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. 
Note: Participants who are unable to complete all required procedures or assessments within the 
Screening Window due to technicalities may be eligible to extend their Screening Period up to 

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2 weeks based on an agreement between the Investigator and the Sponsor Medical Monitor. 
Screening activities that require repeating will be determined by the Sponsor Medical Monitor and 
the process outlined in the Monitoring Plan. 
Individuals who did not meet the Screening criteria for the MORF-057-201 study may be eligible 
to be screened for the MORF-057-202 study. The Investigator should discuss such cases with the 
Sponsor before proceeding. 
6. 
Study Treatment and Concomitant Therapies 
6.1. 
Study Treatment Description 
A description of each study treatment type is provided in Table 3, and a description of each 
treatment group is provided in Table 4. Refer to Section 8.3 for study drug administration 
instructions. 
More detailed information about MORF-057 and placebo can be found in the Pharmacy Manual. 
MORF-057 and placebo capsules will be manufactured, quality control tested, and released in 
accordance with Good Manufacturing Practice. 
Table 3. 
Study Treatment 
Treatment name 
MORF-057 
Placebo 
Treatment type 
Small molecule drug  
Placebo 
Dose strength and 
formulation 
100-mg IR capsule (Swedish orange capsule 
size 0) 
0-mg IR capsule (Swedish orange capsule 
size 0) 
Route of 
administration 
Oral 
Oral 
Dosage regimens 
See Table 4 
See Table 4 
Use 
Experimental 
Placebo 
IMP/NIMP 
IMP 
IMP 
Sourcing 
Provided by Sponsor 
Provided by Sponsor 
Packaging and 
labeling 
30 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. 
30 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 
Store according to the country-specific label 
Store according to the country-specific label 
Abbreviations: IMP, investigational medicinal product; NIMP, non-investigational medicinal product; IR, immediate-release. 
 

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Table 4. 
Treatment Groups 
Group title 
Group 1 
Group 2 
Group 3 
Group 4 
Type 
• 
Induction: Experimental 
• 
Maintenance/LTE Period: 
Experimental 
• 
Induction: Experimental 
• 
Maintenance/LTE Period: 
Experimental 
• 
Induction: Experimental 
• 
Maintenance/LTE Period: 
Experimental 
• 
Induction: Placebo 
• 
Maintenance/LTE Period: 
Experimental 
Induction Period 
dosing regimen 
(12 Weeks) 
MORF-057 
(200 mg B.I.D.) 
Total dose/day: 400 mg 
MORF-057 
(100 mg B.I.D.) 
Total dose/day: 200 mg 
MORF-057 
(100 mg Q.D.-M) 
Total dose/day: 100 mg 
Placebo 
 
Maintenance 
Period dosing 
regimen 
(40 Weeks)/ 
LTE Period 
dosing regimen 
(52 Weeks) 
MORF-057 
(100 mg B.I.D.) 
Total dose/day: 200 mg 
MORF-057 
(100 mg B.I.D.) 
Total dose/day: 200 mg 
MORF-057 
(100 mg Q.D.-M) 
Total dose/day: 100 mg 
MORF-057 
(200 mg Q.D.-E) 
Total dose/day: 200 mg 
Instructions for 
administration 
Take 1 capsule from EACH 
bottle for the respective dosing 
time (morning or evening). 
Each bottle contains 30 
capsules of either MORF-057 
or placebo.  
Take 1 capsule from EACH 
bottle for the respective dosing 
time (morning or evening). 
Each bottle contains 30 
capsules of either MORF-057 
or placebo. 
Take 1 capsule from EACH 
bottle for the respective dosing 
time (morning or evening). 
Each bottle contains 30 
capsules of either MORF-057 
or placebo. 
Take 1 capsule from EACH 
bottle for the respective dosing 
time (morning or evening). 
Each bottle contains 30 
capsules of either MORF-057 
or placebo. 

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Group title 
Group 1 
Group 2 
Group 3 
Group 4 
LTE Period (52 
Weeks)* 
MORF-057 
(200 mg B.I.D.) 
Total dose/day: 400 mg 
MORF-057 
(200 mg B.I.D.) 
Total dose/day: 400 mg 
MORF-057 
(200 mg B.I.D.) 
Total dose/day: 400 mg 
MORF-057 
(200 mg B.I.D.) 
Total dose/day: 400 mg 
Instructions for 
administration 
Bottles will contain 30 (thirty) 
MORF-057 100 mg capsules. 
Take 2 capsules in the morning 
and 2 capsules in the evening. 
Bottles will contain 30 (thirty) 
MORF-057 100 mg capsules. 
Take 2 capsules in the morning 
and 2 capsules in the evening. 
Bottles will contain 30 (thirty) 
MORF-057 100 mg capsules. 
Take 2 capsules in the morning 
and 2 capsules in the evening. 
Bottles will contain 30 (thirty) 
MORF-057 100 mg capsules. 
Take 2 capsules in the morning 
and 2 capsules in the evening. 
Abbreviations: B.I.D., twice a day; LTE, Long-Term Extension; Q.D.-E, once a day (evening); Q.D.-M, once a day (morning). 
* Relevant for participants who consent to the dose switch in the LTE Period. For those that do not consent to the dose switch in the LTE Period, they will remain on their current 
LTE Period dose 

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6.2. 
Preparation, Handling, Storage, and Accountability 
The Investigator or designee must confirm appropriate temperature conditions (per 
country-specific label) 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 the study drug, and only authorized site staff 
may supply or administer the study drug. All study drug 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, 
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 study drug capsules remaining at the completion of the study will either be returned to 
the Sponsor-designated depot 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 
6.3.1. 
Randomization 
An interactive response technology (IRT) will be used to centrally randomize all participants into 
1 of the 4 treatment groups (see Sections 4.1 and 6.1 for dosing regimens). The randomization 
code will be maintained by the IRT provider. Randomization will be stratified by baseline MES 
(<3 vs 3) and previous use of advanced therapy treatment (advanced therapy-naïve vs advanced 
therapy-experienced). Participants initially randomized into the placebo group will be switched to 
an active MORF-057 regimen (200 mg Q.D.-E) after they complete the Induction Period and the 
scheduled assessments at Week 12 (including endoscopy). All participants who consent will be 
switched to a new MORF-057 dose in the LTE Period. 
Study treatment will be dispensed at the study visits as summarized in the SoA (Section 1.2). 
6.3.2. 
Blinding 
This is a double-blind study in which the Sponsor, participants, site staff, site pharmacy, 
Investigators, and outcome assessors will be blinded to the study treatment through Week 12. The 
double-blind will be maintained by using identical study drug bottles and labels for MORF-057 
and placebo. The placebo will have identical appearance to that of the MORF-057 capsules. 
Participants will receive their study drug supplies in “morning bottles” and “evening bottles.” Each 
participant will receive the same number of “morning bottles” and “evening bottles” according to 
the respective study period (Induction or Maintenance/LTE Period prior to dose switch). In the 
morning, participants should take 1 capsule from EACH “morning bottle.” In the evening, 
participants should take 1 capsule from EACH “evening bottle.” In the LTE Period after the dose 
switch, bottles will contain 30 (thirty) MORF-057 100 mg capsules. Participants who consent will 

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take 2 capsules in the morning and 2 capsules in the evening. Those that do not consent to the dose 
switch will remain on their current LTE Period dose. After all participants have completed the 
Induction Period and scheduled assessments at the Week 12 Visit, the Induction Period analyses 
will be performed. After the database lock for the Induction Period analyses, the analysis results 
will be unblinded at the population level. However, the access to treatment assignment for 
individual participants will be limited to only the necessary persons from the Sponsor and the 
external vendors that will generate the unblinded analysis results and perform the validation. All 
other Sponsor personnel, the project study team, site Investigator, site staff, and study participants 
will remain blinded to the individual treatment assignments in the Induction and Maintenance/LTE 
Period through the end of the study including the LTE Period. 
The IRT will be programmed with blind-breaking instructions. In case of an emergency, the 
Investigator has the sole responsibility for determining if unblinding a participant’s treatment 
assignment is warranted. Participant safety must always be the first consideration in making such 
a determination. If the Investigator decides that unblinding is warranted, the Investigator should 
make every effort to contact the Sponsor prior to unblinding a participant’s treatment assignment, 
unless this could delay emergency treatment for the participant. If a participant’s treatment 
assignment is unblinded, the Sponsor must be notified within 24 hours of this occurrence. The date 
and reason for the unblinding must be recorded in the participant’s medical records and IRT. If a 
participant’s treatment is unblinded, the participant will be withdrawn from the study. 
Sponsor Pharmacovigilance staff will unblind all SAE reports in the safety database. If the report 
requires expedited reporting to one or more regulatory agency, a copy of the report, identifying the 
participant’s treatment assignment, will be sent to the regulatory agency in accordance with local 
regulations and/or Sponsor policy. All other Sponsor staff, as well as the Investigators and study 
participants, will remain blinded to study assignments until database lock. 
6.4. 
Study Treatment Compliance 
When participants are dosed at the site, they will receive the study drug under medical supervision. 
The date and time of each dose administered in the clinic will be recorded in the source documents. 
The IRT assignment 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 treatment. 
When participants self-administer the study drug at home, compliance with prescribed treatment 
regimen will be assessed at each visit. Participants will be instructed to record all details about the 
study drug administered at home in the Participant Diary during the Induction and Maintenance 
Periods. 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 treatment regimen should be recorded. 
The site staff will contact participants, by phone or other means, on the next business day after the 
Visit 5 clinic visit to confirm the participants have switched from the Induction Period study drug 
to the new Maintenance Period study drug bottles. In addition, the site staff will contact the 
participants who consented, by phone or other means, on the next business day after the dose 
switch in the LTE Period to confirm the participants have switched to the new dose (200 mg B.I.D.) 
of study drug correctly. Record the date and time of the participant’s first dose of the new dose 
(200 mg B.I.D.) in the source documents. 

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A record of the quantity of study drug dispensed to and administered by each participant must be 
maintained and reconciled with study treatment and compliance records. Treatment start and stop 
dates, including dates for treatment delays and/or dose reductions, will also be recorded. 
6.5. 
Continued Access to Study Treatment After the End of the Study 
Participants will no longer have access to the study drug after they complete the study. 
6.6. 
Overdose 
An overdose is defined as any timepoint where the study participant took more pills than directed 
or took pills from a different bottle than directed (if the total daily number of capsules consumed 
could exceed the maximum total daily number of capsules possible per protocol [4 total 
capsules/day]). 
No specific information is available on the treatment of acute or chronic overdosage of 
MORF-057. In the event of overdose: 
• The Investigator will notify the Medical Monitor immediately. 
• Evaluate the participant, to determine in collaboration with the Medical Monitor, whether 
the study drug should be interrupted or discontinued. 
• The participant should be observed closely. Appropriate supportive treatment should be 
provided if clinically indicated. 
• Overdose with or without clinical symptoms or abnormal laboratory results should be 
recorded on the overdose electronic Case Report Form (eCRF) within 24 hours of 
becoming aware. 
• AEs and SAEs associated with overdose will be recorded on the AE eCRF, and SAEs 
associated with overdose will be reported via the SAE reporting procedure outlined in 
Section 8.9. 
6.7. 
Concomitant Therapy 
6.7.1. 
Concomitant Medications 
Any medications (including over-the-counter or prescription medicines, recreational drugs [e.g., 
psychoactive drugs like marijuana], vitamins, and/or herbal supplements) or vaccines that the 
participant receives from the time of ICF signing through the SFU Visit must be recorded in the 
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 an AE should be recorded as such from the time of informed consent. 

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6.7.2. 
Allowed Medications for the Treatment of Ulcerative Colitis 
The following list of concomitant medications for UC will be allowed during the study: 
• Oral 5-aminosalicylates (not exceeding 4.8 g per day) 
• Oral corticosteroids (not exceeding prednisone 30 mg per day, budesonide 9 mg per day, 
beclomethasone dipropionate 5 mg per day, methylprednisolone 24 mg per day, or 
equivalent; see Table 5) 
• 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 all 
UC-related concomitant medications throughout the study until the end of the SFU Period, with 
the exception of tapering oral corticosteroid dose after 12 weeks of being in the trial. See Inclusion 
Criterion 6 (Section 5.1) for Screening-related requirements for these medications, including how 
long a stable dose must be maintained before study Day 1. 
If any other medications need to be started due to worsening of UC symptoms, the Medical 
Monitor should be contacted. 
Table 5. 
Corticosteroid Equivalent Doses† 
 
Equivalent 
Glucocorticoid Dose 
(mg)* 
Maximum Dose per day 
for Study 
(mg) 
Short acting 
 
 
Hydrocortisone (cortisol) 
20 
120 
Cortisone acetate 
25 
150 
Intermediate acting 
 
 
Prednisone 
5 
30 
Prednisolone 
5 
30 
Triamcinolone 
4 
25 
Methylprednisolone 
4 
24 
Long acting 
 
 
Dexamethasone 
0.75 
5 
Betamethasone 
0.6 
5 
* Source: Parente 2017 
† Other corticosteroids may be used per the medical judgement of the Investigator. Consult the Medical Monitor as needed. 

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6.7.2.1. 
Tapering of Oral Corticosteroids 
The following corticosteroid tapering schedules should be used, unless medically contraindicated 
after discussion with the Medical Monitor. 
Participants receiving oral corticosteroids at the time of enrollment should maintain their current 
dose regimen during the Induction Period (first 12 weeks). Upon entering the Maintenance Period, 
it is strongly recommended that all the participants responding to treatment, as assessed by the 
Investigator, start tapering their corticosteroid dose OR, in cases where corticosteroids were used 
as rescue medications (Section 6.7.2.2), tapering must start within 4 weeks after the increase in the 
corticosteroid therapy, as outlined below: 
• Prednisolone (or equivalent) dose should be tapered by 5 mg/day every week until the daily 
dose reaches 10 mg/day (or prednisone equivalent); then, it should be tapered by 
2.5 mg/day every week (or prednisone equivalent) until completely tapered off. 
• Budesonide dose should be tapered by 3 mg/day for every 2 weeks until completely tapered 
off. 
• If the participant is on methylprednisolone or beclomethasone, then taper the dose 
according to the local medical practice. 
• If the participant is on corticosteroids as a rescue medication during the Maintenance 
Period, then taper as suggested above or more quickly if clinically appropriate. 
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 4 weeks. 
6.7.2.2. 
Rescue Therapies 
If during the study a participant’s UC condition worsens and requires rescue therapies of changing 
any UC background medications or initiating a new UC therapy (with the exception of returning 
the background corticosteroid therapy dose to baseline level), the participant should be withdrawn 
from the study and appropriate treatment should be given at the discretion of the Investigator. 
Anti-diarrheals for control of chronic diarrhea and antibiotics for control of infection are not 
considered rescue medication. 
6.7.3. 
Prohibited Medications 
The following concomitant medications/therapies are prohibited for the entire duration of the study, 
including SFU: 
• Treatments for UC other than those listed in Section 6.7.2 (including TNF-α antagonists, 
integrin antagonists [e.g., vedolizumab], IL-12/IL-23 antagonists, JAK antagonists, and 
S1P receptor agonists) 
• Biologics including, but not limited to, the following list: 
o Etanercept 
o Abatacept 
o Anakinra 
o Rituximab 

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o Natalizumab 
o Tocilizumab 
o Efalizumab 
o Ustekinumab 
o Belimumab 
o Golimumab 
o Vedolizumab 
o Infliximab 
o Adalimumab 
o Certolizumab pegol 
o Secukinumab 
• Receipt of a live virus vaccine from 3 weeks prior to study Day 1 until 28 days after the 
last dose of study drug. Live vaccines include but are not limited to the following list: 
o Monovalent live influenza A (H1N1) (intranasal) 
o Seasonal trivalent live influenza (intranasal) 
o Zostavax (herpes zoster, live attenuated) 
o Rotavirus 
o Varicella (chicken pox) 
o Measles-mumps-rubella or measles-mumps-rubella-varicella 
o Oral polio vaccine 
o Smallpox 
o Yellow fever 
o Bacille Calmette-Guérin (BCG) 
o Typhoid (oral) 
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 5.2). 
• Moderate-to-strong CYP3A inhibitor or inducer (see Table 6) 
• Moderate-to-strong organic anion transporter polypeptide-1B inhibitor (see Table 6) 
• Cyclosporine, mycophenolate, tacrolimus, thalidomide, or sirolimus 
• Nonsteroidal anti-inflammatory drugs including but not limited to ibuprofen, naproxen, 
indomethacin, and celecoxib. (However, participants may take aspirin for cardio-protection 
at a dose as per local guidelines but not exceeding 325 mg per day.) 
• Intravenous corticosteroids 
• Rectal 5-aminosalicylates 
• Rectal corticosteroids 
• Total parenteral nutrition 

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• Traditional Chinese/Eastern medicines 
• Any investigational therapy 
Table 6. 
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 of CYP3A inhibitors/inducers or OATP1B1 inhibitors. 
* Time-dependent inhibitors 
† Glucocorticoids permitted at the doses indicated in Section 6.7.2 
Sources: (Flockhart, 2021) (US FDA, 2020) 
6.7.4. 
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 
• Donation of sperm or oocytes during the study and for 14 days after the last dose of study 
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7. 
Discontinuation of Study Treatment 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 SFU Visit. See the SoA (Section 1.2) for the assessments to be performed 
at the time of study drug discontinuation (EOT 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 6.7.3 and 6.7.4 
• Severe uncontrolled infection 
• Changes in ECG considered clinically significant and with reasonable possibility of 
relationship to study drug 
• 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 with the exception of 
returning the background corticosteroid therapy dose to baseline level). 
Anti-diarrheals for control of chronic diarrhea and antibiotics for control of 
infection are not considered rescue medication. 
o Requirement for abdominal surgery due to complications from UC 
• Pregnancy or planned pregnancy of the female participant or female partner of a male 
participant as the participant will be unblinded (see Section 8.9.5) 
• The participant has confirmed PML 
• The participant has abnormal liver function results and re-testing results indicate clinically 
significant abnormalities, as detailed in Table 12 
• Repeated or significant non-compliance with study treatment (see Section 6.4) or study 
procedures to the extent that continued participation would pose an unacceptable risk to 
the participant, as determined by the Investigator 
• Sponsor or the Investigator deems it is necessary for the participant 
• The participant wishes to voluntarily withdraw from the study (see Section 7.2) 
• The participant does not return to the clinic, and attempts to contact the participant are 
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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. 
In rare circumstances, consideration may be given to the participant when there is a compelling 
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. 
Dose Interruption and Re-challenge 
Situations requiring study drug interruption and the potential for re-challenge are presented in 
Table 7. Decisions regarding dose interruptions and re-challenges will be made by the Investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the participant. 
Table 7. 
Study Drug Interruption and Re-challenge Guidelines 
Clinical Situation/Event 
Study Drug Interruption 
Re-Challenge 
Possible drug-induced liver 
damage 
Requirements are outlined in 
Table 12 
Requirements are outlined in Table 12 
PML screening 
Requirements for study drug 
interruption after positive Subjective 
PML questionnaire are outlined in 
Section 8.8.5 
Requirements for re-challenge are 
dependent on PML being definitively 
ruled out as outlined in algorithm within 
the PML Reference Guide 
Serious Adverse Event 
Investigator and Sponsor Medical 
Monitor may interrupt study drug 
administration if deemed necessary 
Re-challenge decision will be made in 
each clinical situation in consultation 
with Investigator and Sponsor Medical 
Monitor 
Abbreviations: PML, progressive multifocal leukoencephalopathy. 
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 EOT Visit at the time of study drug 
discontinuation and the SFU Visit at 28 days (+7 days) after the last dose of study drug. See the 
SoA (Section 1.2) for details regarding the data to be collected at the EOT and SFU 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. 

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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. 
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 complete medical and surgical history, including initial UC 
diagnosis date and history of UC medication use, will be collected during Screening and recorded 
in the participant’s eCRF. 
Study sites should make every effort to collect UC-related medical and surgical history after initial 
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8.1.1. 
Prior Medications 
Study sites should make every effort to document a participant’s prior UC medications. All prior 
treatments for UC, including advanced therapies (e.g., antagonists to TNF-α, JAK, or IL-12/IL-23; 
S1P receptor agonists; or other new investigational treatments), should be collected and recorded 
in the eCRF, including dates of start, stop, and dosing regimen changes, along with the reason for 
discontinuation, where possible. 
Information about non-UC therapies and medications received within 1 month prior to Screening 
will be recorded in the eCRF, including dates of start, stop, and dosing regimen changes. 
Non-prohibited UC medications (see Section 6.7.2) started prior to Day 1 that will be continued 
as concomitant medications during the study must be on a stable regimen, consistent with the 
requirements in Inclusion Criterion 6 (see Section 5.1). 
8.2. 
Screening-specific Tests 
8.2.1. 
Screening Stages 
Once informed consent is obtained, the procedures listed for Stage 1 of Screening should be 
performed. Stage 1 will be approximately 2 weeks long and should include the collection of 
Participant Diary information for 7 days. At the end of Stage 1, the Investigator should use the 
information collected in the Participant Diary to assess the severity of UC. If the participant is 
consistently having 3 or more stools per day than normal, often with visible blood, then he/she 
should proceed to Stage 2 of Screening (including endoscopy). If the participant's stool frequency 
and rectal bleeding symptoms are milder than what is described, Stage 2 of Screening should not 
be pursued. If the participant has had UC for over 7 years and a full colonoscopy has not been 
performed in the past 2 years, he/she must undergo a full colonoscopy at Screening (rather than 
sigmoidoscopy). 
8.2.2. 
Screening for Pathogens and/or Infections 
8.2.2.1. 
Tuberculosis 
All participants will complete TB Screening to determine eligibility. Participants with a negative 
TB test and chest X-ray (or imaging per local guidelines) not suggestive of active TB may be 
enrolled. Participants with a history of active TB may be enrolled if it has been adequately treated 
with no evidence of current active TB. Participants with a positive TB test must be assessed for 
evidence of active TB versus latent TB. Please refer to Table 8 for TB Screening and eligibility 
details. Exclusion criteria includes those participants with a positive TB diagnostic test performed 
within 30 days prior to Screening or during the Screening Period (e.g., a positive IGRA test such 
as a 
 
 TB test, 2 consecutive indeterminate IGRA tests, or a PPD skin 
test ≥5 mm), and those who had a chest X-ray within 3 months prior to Screening where active or 
latent pulmonary TB could not be excluded. 
The TB Screening tests are diagnostic, and the results should be interpreted with the participant’s 
medical history and exam findings. 
The IGRA test should be performed at Screening on all participants, except for those who have 
had a confirmed negative IGRA test within 3 months prior to Screening. The PPD skin test 
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should be performed when the IGRA test is not possible or if both tests are required by local 
guidelines. Test results should be interpreted as shown below: 
• For regions that require both IGRA and PPD tests, if either test is positive, the TB test is 
considered positive. 
If the IGRA test is indeterminate, then the Investigator should perform a second IGRA test to rule 
out a positive test result. If testing remains indeterminate or is positive, then the participant is 
considered TB positive. 
The PPD skin test should be read by a licensed healthcare professional between 48 and 72 hours 
after administration. A reaction of induration ≥5 mm is considered a positive reaction. 
Participants who have tested negative for TB at a certified local lab using an IGRA test within 
3 months prior to Screening are not required to repeat this test during the Screening Period if that 
participant has no clinical signs or symptoms of TB, no known exposures/increased risk factors 
since the last negative TB test (according to the Investigator’s clinical judgement), and the test 
result is available and adequately documented in the participant’s medical record. 
Table 8. 
Summary of Tuberculosis Screening and Eligibility 
Test Performed Within 30 Days Prior to Screening or During the Screening Period 
Inclusion 
Exclusion 
A positive interferon gamma release assay (IGRA) test (e.g., 
 
 
 TB test) 
  
X 
2 consecutive indeterminate IGRA tests  
  
X 
A purified protein derivative (PPD) skin test ≥5 mm 
  
X 
Test Performed Within 3 Months Prior to Screening 
Inclusion 
Exclusion 
A chest X-ray within 3 months prior to Screening where active or latent pulmonary TB 
cannot be excluded 
 
X 
A negative test for TB at a certified local lab using an IGRA test (e.g., 
 
 TB test) within 3 months prior to Screening AND 
• 
Has no clinical signs or symptoms of TB 
• 
No known exposures/increased risk factors since the last negative TB test 
(according to the Investigator’s clinical judgement) 
• 
The test result is available and adequately documented in the participant’s 
medical record 
Note: Re-testing is not required at Screening if all the above criteria are met  
X 
  
History of Latent TB 
Inclusion 
Exclusion 
Study participants with a positive TB test must be assessed for evidence of active TB 
versus latent TB. Documentation will include: 
X 
 
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• 
Chest X-ray or imaging per local guidelines during the Screening Window 
• 
No signs and symptoms (no evidence of ongoing active TB) 
• 
Study participant is being treated per local standard of care for a minimum of 
2 weeks before the first dose of study drug OR 
• 
Study participant has documentation of completing appropriate treatment for 
latent TB within 2 years before Day 1 of the study 
Abbreviations: IGRA, interferon gamma release assay; PPD, purified protein derivative; TB, tuberculosis. 
See Exclusion Criterion 8 (Section 5.2) and the SoA (Section 1.2) for additional details regarding 
testing requirements. 
8.2.2.2. 
SARS-CoV-2 
Testing for SARS-CoV-2 is required only per local regulations. Participants who have a positive 
test result will be excluded from randomization until a subsequent test result is negative. See 
Exclusion Criterion 9 (Section 5.2) and the SoA (Section 1.2) for details regarding testing 
requirements. 
8.2.2.3. 
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. 
8.2.2.4. 
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. 
8.2.3. 
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. 
8.3. 
Study Drug Administration 
8.3.1. 
Dosing Instructions 
The first dose of the study drug will be administered in the clinic on study Day 1 under the 
supervision of study personnel. All subsequent doses will be self-administered at home, with the 
exception of the morning doses for Visits 2-10, which will be administered during the study visits 
after pre-dose blood samples have been drawn (see details in the SoA, Section 1.2). Participants 
will be instructed to record all details about the doses administered at home in the Participant Diary. 
Participants will receive their study drug supplies in “morning bottles” and “evening bottles.” Each 
participant will receive the same number of “morning bottles” and “evening bottles” according to 
the respective study period (Induction or Maintenance/LTE Period). 

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Induction Period 
For the Induction Period, each 30-day study drug supply will consist of 2 cartons (1 for morning 
and 1 for evening). Inside each carton, there will be 2 corresponding bottles of study drug. Thus, 
an Induction Period 30-day study drug supply will consist of the following bottles: morning 
bottle #1, morning bottle #2, evening bottle #1, and evening bottle #2. Each participant will be 
instructed to take 4 capsules per day, 1 from each bottle, during the Induction Period. 
Maintenance Period/LTE Period (all participants including those who do not consent to the dose 
switch in the LTE Period) 
For the Maintenance Period/LTE Period, each 30-day study drug supply will consist of 1 carton. 
Inside the single carton, there will be 3 bottles of study drug: morning bottle, evening bottle #1, 
and evening bottle #2. In the morning, participants should take 1 capsule from the “morning bottle.” 
In the evening, participants should take 1 capsule from EACH “evening bottle.” Each participant 
will be instructed to take 3 capsules per day during the Maintenance Period/LTE Period (no dose 
switch). It is important to note that the bottles may contain capsules with either MORF-057 100 mg 
or placebo. Thus, the study drug must be taken exactly as directed in the Pharmacy Manual. 
LTE Period (for participants who re-consent to the dose switch in the LTE Period) 
All participants will be asked to re-consent to switch their dose to 200 mg B.I.D. The dose switch 
will occur at Visit 10 or at a scheduled visit in the LTE Period (Visit 11, 12, or 13). If a participant 
does not consent to the dose switch, they will be allowed to stay on their current LTE Period dose 
as described above. During the LTE Period, all participants will receive their study drug supplies 
as bottles containing 30 (thirty) MORF-057 100 mg capsules. Participants should take 2 capsules 
in the morning and 2 capsules in the evening. 
Participants will take the assigned study drug with water twice daily. The study drug can be taken 
with or without food. No unplanned dose adjustments will be allowed. The study drug capsules 
should be taken at approximately the same time every day in the morning and in the evening. The 
interval between doses should be as close to 12 hours as possible. 
8.3.2. 
Missed Dose Instructions 
Participants should be instructed that if they forget to take a dose, they can take the dose 
within 6 hours of the normal dosing time; otherwise, they should take their next dose at the regular 
time. 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 should be 
reminded to complete their Participant Diary accordingly. Participants should be instructed to 
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 and 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 
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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 SFU Visit.  
Participant Diaries should not be completed after the participant has finished their participation in 
the study at the SFU Visit. Diary entries will include study drug administration details in the 
Induction and Maintenance Periods, along with daily rectal bleeding, and stool frequency 
information (the 2 patient-reported outcome measures of the Full and mMCS, 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 the electronic data 
capture (EDC) database and during each study visit at the times noted in the SoA (Section 1.2). 
Participants who remain chronically non-compliant with diary entries despite intervention and 
follow-up by the Investigator and site team may be subject to discontinuation as per Section 7.1. 
Detailed descriptions regarding Participant Diary recordings can be found in the corresponding 
Patient Guide. 
8.6. 
Stool Collection 
Stool samples will be required for pathogen/parasite testing, to assess fecal calprotectin levels, and 
for future research (if participant consents; see Section 8.12). 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 stored as described in the sample collection instructions and 
brought to the clinic on the day of the site visit. If the participant is unable to produce a stool 
sample at the Stage 1 Screening Visit, they can collect a sample at home and return it to the site. 
Note: Sample is to be collected prior to bowel preparation for Visits 5 and 10/EOT. 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. 
8.7. 
Efficacy Assessments 
8.7.1. 
Endoscopy with Biopsy 
Endoscopy will be performed at Screening (Visit 1) and during Stage 1 of Visits 5, 10/EOT, and 
14/LTE EOT. Flexible sigmoidoscopy with colonoscopy scope is the suggested procedure, but full 
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During these procedures, colonic mucosa biopsies will be collected for histopathology and optional 
future research studies. Up to 6 biopsies will be collected during each endoscopy procedure 
(2 biopsies for the required histopathology and 4 biopsies for the optional future research). The 
biopsies for future studies will only be collected from the participants who consent to the optional 
future research. The remaining tissue from the histopathology biopsies may also be used for future 
research from participants who consent to the optional future research. 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. 
Biopsy specimen transfer, processing, slide preparation, and digitization of slides for 
histopathologic scoring procedures will be detailed within the applicable Laboratory Manual or 
Histopathology Reference Guide. Histopathology results will not be made available to study sites 
but will be located within the histopathology laboratory database and added to the electronic Trial 
Master File after the completion of the trial. 
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 by a central reader. However, treatment decisions post-randomization will 
be made by the treating Investigator. 
For all biopsies in Table 9: 
• Record the extent of disease in centimeters from the anal verge 
• Record the distance in centimeters from the anus where biopsies are taken into the 
Requisition Form 
• Always review the Laboratory Manual for full instructions related to biopsy sample 
collection containers, labeling, and storage 
• Biopsies for histopathology are the required part of the study 
• Optional biopsies are only to be taken in participants who have consented for future 
research 
Table 9. 
Instructions for Endoscopic Biopsies 
Visit 1 
(Screening) 
Worst inflamed area 
Take biopsies of the worst inflamed area within 15-25 cm from the anus. 
• 
2 required biopsies for histopathology 
• 
2 optional biopsies for future research 
 
Non-inflamed/least inflamed area 
Take biopsies from a non-inflamed or least inflamed area of the colon. 
• 
2 optional biopsies for future research 

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Visit 5 
(Week 12) 
 
Visit 10 
(Week 52 or EOT) 
 
Visit 14 
(Week 104 or LTE 
EOT) 
Take all biopsies at the same distance (cm) from the anus as collected at Visit 1, 
regardless of tissue state at the time of the sampling. 
• 
2 required biopsies for histopathology 
• 
4 optional biopsies for future research 
Abbreviations: EOT, End of Treatment; LTE EOT, Long-Term Extension End of Treatment. 
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 10.5.3. 
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 
score. 
Nancy Histopathology 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 MCS, mMCS, Partial mMCS, and Partial MCS will be used to assess clinical changes. The 
MCS is a composite of the following subscores: MES, MCS stool frequency subscore, MCS rectal 
bleeding subscore, and the PGA. The mMCS is a composite of the following subscores: MES, 
MCS stool frequency subscore, and MCS rectal bleeding subscore. The Partial mMCS is a 
composite of the following subscores: MCS stool frequency subscore and MCS rectal bleeding 
subscore. The Partial MCS is a composite of the following subscores: MCS stool frequency 
subscore, MCS rectal bleeding subscore, and the PGA. Each subscore of the MCS, mMCS, Partial 
mMCS, and Partial 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. 

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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 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 source documents and eCRF at the 
specified study visits. 
8.7.4. 
Non-endoscopic Biomarkers of Inflammation 
8.7.4.1. 
High-sensitivity C-reactive Protein 
Blood will be collected for measurement of C-reactive protein 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. 
8.7.5. 
Inflammatory Bowel Disease Questionnaire 
The IBDQ questionnaire is a psychometrically validated patient-reported outcome instrument to 
assess health-related quality of life (HRQoL) in patients with IBD, including UC (Irvine, 1994). 
The IBDQ consists of 32 items, grouped into 4 dimensions: bowel function, emotional status, 
systemic symptoms, and social function. Response to each of the questions is graded from 1 to 7, 
with the overall score ranging from 32 (very poor HRQoL) to 224 (perfect HRQoL). For the total 
score and each domain, a higher score indicates better quality of life. A score of ≥170 corresponds 
to clinical remission, and an increase of ≥16 points indicates a clinically meaningful improvement. 
The IBDQ (Section 10.8) will be completed by the participant and checked for completeness at 
the study site as indicated in the SoA (Section 1.2) and will be used in support of the efficacy 
outcomes. Participants should complete the IBDQ at the clinic before they undergo any procedures 
or are administered the study drug. 

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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, Visit 10/EOT, and Visit 14/LTE EOT; and a 
targeted exam may be performed at all other required visits. For unscheduled visits, the choice of 
whether to perform a complete or targeted physical exam (if necessary to be performed at all) 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 most visits as summarized in the SoA (Section 1.2). At unscheduled 
visits, vital signs are not required and are at the discretion of the Investigator. 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. 
Vital signs are to be taken before blood collection for laboratory tests. 
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). See Section 10.3 

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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. In case of abnormal liver function test results, Investigators should 
follow the instructions in Table 12 for re-testing and follow-up procedures. 
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), then the results must be recorded in the EDC database. 
8.8.5. 
Progressive Multifocal Leukoencephalopathy 
The Subjective PML Checklist will be administered to participants during Screening. The 
Subjective PML Checklist (Section 10.2) will also be completed at study visits according to the 
schedule in the SoA (Section 1.2). If the results of the questionnaire are suggestive of signs and 
symptoms of PML, hold any further doses of study drug and notify the Medical Monitor. The 
participant will undergo Objective PML Checklist testing (Section 10.2), a full neurological exam 
by a neurologist, and, if indicated, additional testing. Study drug may not be resumed until PML 
has been definitively ruled out. 
A participant with confirmed PML will be excluded from the study or will permanently 
discontinue study drug and will be withdrawn from the study (see Section 7.1.1). 
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. 
A serum test for follicle-stimulating hormone (FSH) level will be performed at Screening only for 
female participants of non-childbearing potential. 
Refer to Section 8.9.5 for details regarding pregnancy reporting. 
8.8.7. 
Concomitant Therapies 
Any medications and vaccines that participants receive from Screening through the last visit (SoA 
in Section 1.2) must be recorded in the eCRF (Section 6.7). Refer to Section 6.7.2 for allowed 
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8.9. 
Adverse Events and Other Safety Reporting 
The definitions of AEs and SAEs can be found in Section 10.4. 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant’s legally acceptable 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), resolution (date), 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 SFU 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 
Screening, 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, SUSARs, and Periodic Reports 
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 
treatment under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. The Sponsor 
will comply with country-specific regulatory requirements relating to safety reporting to the 
Member States Concerned, the applicable 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 IB and will notify the IRB/IEC, if appropriate, according to local requirements. 
Investigator Safety Reports must be prepared for 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 IB 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. 
The Sponsor or a designee is responsible for notifying the relevant regulators (including the 
authorities in the European Economic Area (EEA) via EudraVigilance and the IRBs/IECs) and the 
Investigator sites within the specified timeframes of all SUSARs, as applicable per local 
requirements. The Sponsor will make the determination whether the event is unexpected. It is the 
Principal Investigator’s responsibility to notify the IRB/IEC according to the relevant regulatory 
timelines of SUSARs of which the Investigator is notified by the Sponsor that occur at his or her 
site, if appropriate. 
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. 
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 EOT and SFU 
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 
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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. Pregnancy 
in a male participant’s partner will require unblinding. The male study participant will be 
withdrawn from the study and the participant should complete the EOT and SFU Visits. 
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. 
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 AEs 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 and 
metabolites (if needed) according to the schedule specified in the SoA (Section 1.2). If consent is 
provided by the participant, these samples may also be used for future PK research studies. 
Additional detailed instructions for the blood collection, processing, storage, and shipment to the 
bioanalytical laboratory will be detailed in the Laboratory Manual. The actual date and time 
(24-hour clock time) of each sample will be recorded, along with the date and time of study drug 
administration. 
The sampling windows for the PK assessment are provided in Table 10. 

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Table 10. 
Pharmacokinetics Sampling Windows 
Visit 
Collection Timepoints and Associated Windows 
2, 3, 5, 7, and 10/EOT 
Before AM dose and at 1hr (±10 min), 2hr (±15 min), and 4hr (±30 min) 
after AM dose 
4, 6, 8, and 9 
Before AM dose and 1 hr (±10 min) after the AM dose 
Abbreviations: EOT, End of Treatment; hr, hour; min, minute. 
For all pre-AM dose sampling, the samples should be obtained before the AM dose is 
administered. Participants will be instructed to record all details about the study drug administered 
at home in the Participant Diary (Section 6.4), especially date/time of previous day morning and 
evening dosing details and on PK visit days. 
8.10.2. Determination of Drug Concentration and PK Parameters 
Samples for determining the concentration of MORF-057 and potential metabolites in plasma will 
be analyzed using appropriate validated bioanalytical methods and may be used in MORF-057 
concentration determination investigations. A summary of the bioanalytical methods will be 
provided in the Laboratory Manual. 
This data may be included to perform Population PK analyses. 
8.11. 
Pharmacodynamics 
Details on the handling and processing of blood samples for PD analysis 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). 
A physiologically relevant receptor occupancy assay will be performed that assesses drug 
inhibition of α4β7 integrin binding to its natural ligand MAdCAM-1. 
To evaluate inhibition of binding to the off-target α4β1 integrin, a receptor occupancy assay using 
its ligand, LDV peptide fragment of fibronectin, will also be performed. 
8.11.2. 
CCR9 mRNA 
Blood samples will be collected in PAXgene ribonucleic acid tubes to assess changes of transcript 
levels of CCR9. 
8.11.3. 
Lymphocyte Subsets 
Blood samples for immunophenotyping will be collected from a subset of participants (sampling 
to be country-specific) 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. 

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8.12. 
Future Research 
If consent is provided by the participant, blood, stool, and colonic tissue samples will be collected 
and may be used for future PD, pharmacogenomics, microbiome-related research, fecal 
calprotectin assessment, and future research. If consent is provided by the participant, the 
remaining blood and colonic tissue samples from the study-required procedures may also be used 
for future research, including future PK research. The purpose of future research is 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 the collection of samples for future 
research is optional (see Section 10.1.4 for additional consents). Details on the handling and 
processing of samples for this future research are outlined in the Laboratory Manual. 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 Pandemics or Other Global Issues 
Adjustments to the planned study procedures might be necessary due to pandemic events and/or 
newly identified global issues. Any such specific measures will be detailed in the respective 
ancillary documents, such as site-facing and patient-facing documents. Examples are provided 
below. 
• A virtual or hybrid visit may be considered for participants who are not able to participate 
in an on-site visit (see Section 8.4 for details). If a home study support visit is performed 
by a study nurse, a courier company will pick up the collected samples (blood/feces) from 
the participant’s home. The nurse will take care of the communications with the courier 
company and will hand over the samples to the courier. 
• Clinical supplies related to the study, including study drug, may be shipped directly to the 
participant’s home in the event the participant cannot visit the study doctor at the clinic to 
collect the needed study supplies. The courier company used to deliver the supplies will be 
contracted by the study Sponsor’s sub-contractor. 
9. 
Statistical Considerations 
The Statistical Analysis Plan (SAP) will be finalized prior to the primary endpoint analysis, and 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: 
The Full Analysis Set (FAS) will consist of all randomized participants who received at least 
1 dose of study drug. The FAS Population will be used as the primary analysis population for all 
efficacy endpoints. Participants will be analyzed according to the treatment group they were 
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The Per Protocol (PP) Population is defined as all participants in the FAS Population who did 
not have any major protocol deviations related to the primary or secondary efficacy endpoint 
analyses. All decisions to exclude participants for the PP Population will be made prior to the 
unblinding of the study. The PP Population may be used for sensitivity efficacy analyses of, at a 
minimum, the primary efficacy endpoint. 
The Safety Population will include all participants who received at least 1 dose of the study drug. 
Participants in this set will be analyzed according to the treatment they actually received. This 
population will be used for the safety analyses. 
The PK Population is defined as all participants who received at least 1 dose of study drug and 
had at least 1 measurable PK concentration. The PK Population will be used for the 
summarization/analysis of PK data. 
The PD Population is defined as all participants who received at least 1 dose of study drug and 
had 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. 
9.2.2. 
Analysis of Demographics and Baseline Characteristics 
Demographic and baseline characteristics will be summarized by treatment group and overall. 
9.2.3. 
Efficacy Analyses 
All the efficacy analyses will be performed based on the FAS, unless otherwise specified. 
9.2.3.1. 
Primary Efficacy Endpoint 
The primary efficacy endpoint for this study is proportion of participants in clinical remission at 
Week 12 as determined using the mMCS, which will be evaluated in the FAS. 
The primary efficacy endpoint will be analyzed using a two-sided Cochran-Mantel-Haenszel 
(CMH) test at the 10% level of significance, stratified by randomization stratification factors 
(baseline MES [<3 vs 3] and previous use of advanced therapy treatment [advanced therapy-naïve 
vs advanced therapy-experienced]), for comparison of each MORF-057 dose group with the 
placebo group. The p-values and point estimates of risk difference, along with 95% CIs, will be 
provided. The study will be considered a success if at least one MORF-057 dose achieves the 
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specified in Section 9.2.3.4. All participants with missing data for determination of endpoint status 
will be considered as a non-responder in the primary analysis. 
The primary analysis will be repeated on the PP Population as a sensitivity analysis. Other 
sensitivity analyses for the primary efficacy endpoints may also be performed as appropriate. The 
primary efficacy endpoint will be analyzed for the subgroups defined based on selected categorized 
demographic and baseline variables, e.g., age, gender, race, exposure to an advanced therapy 
treatment for UC (advanced therapy-naïve and advanced therapy-experienced). The details will be 
described in the SAP. 
9.2.3.2. 
Secondary Efficacy Endpoints 
The secondary endpoint for this study is the proportion of participants with clinical response at 
Week 12 as determined using the mMCS, which will be evaluated in the FAS. 
The secondary endpoint will be analyzed using CMH tests stratified by randomization 
stratification factors (baseline MES [<3 vs 3] and previous use of advanced therapy treatment 
[advanced therapy-naïve vs advanced therapy-experienced]) for comparison of each MORF-057 
dose group with the placebo group, similar to the primary analysis performed for the primary 
endpoint. The p-values and point estimates of risk difference, along with 95% CIs, will be 
provided. All participants with missing data for determination of endpoint status will be considered 
as a non-responder in the analysis. 
9.2.3.3. 
Exploratory Efficacy Endpoints 
All proportion-based exploratory efficacy endpoints at Week 12 as defined in Section 3 (e.g., 
histologic remission or improvement, endoscopic remission or improvement, mucosal healing or 
improvement, MCS remission or response, UC-related hospitalization or surgery) will be analyzed 
in the FAS using CMH tests stratified by randomization stratification factors for comparison of 
each MORF-057 dose group with the placebo group, similar to the primary analysis performed for 
the primary efficacy endpoint. The p-values will be calculated for the exploratory use. The point 
estimates of risk difference, along with 95% CIs, will be provided. All participants with missing 
data for determination of endpoint status will be considered as a non-responder in the analysis. 
All the continuous exploratory efficacy endpoints expressed as change from baseline at Week 12 
as defined in Section 3 (e.g., non-endoscopic biomarkers of inflammation, PROs) will be analyzed 
in the FAS using an analysis of covariance model with treatment and randomization stratification 
factors as factors and baseline values as a covariate. The least-squares means and standard errors 
with 95%◦CIs for both changes from baseline in each treatment group and differences between 
MORF-057 and placebo groups will be provided. P-values will also be calculated for the 
exploratory use. Participants who do not have the baseline value or the value at Week 12 will be 
excluded from the analysis. 
The time-to-event endpoint (time to symptomatic response) will be analyzed using the stratified 
Cox regression model with treatment group as an independent variable. The stratification factors 
include the randomization stratification factors. 
All exploratory efficacy endpoints at Week 52 will be summarized descriptively by dose regimens. 
The participants randomized to the placebo arm at the Induction Period and switched to an active 

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MORF-057 dose regimen at the Maintenance Period will be summarized separately for the 
endpoints at Week 52. 
9.2.3.4. 
Multiplicity Adjustments 
All statistical inference will be 2-sided at a 0.1 level of significance. To control the overall Type I 
error rate, a hierarchical testing approach as illustrated in Figure 2 will be applied to the statistical 
testing of the primary and secondary endpoints for comparisons of each MORF-057 dose group 
with the placebo group. 
First, for the primary efficacy endpoint of clinical remission at Week 12, the Hochberg method 
will be applied to the comparisons of 200 mg B.I.D. with placebo and 100 mg B.I.D. with placebo. 
If both p-values are <0.1, both doses will be declared significant. If one of the p-values is ≥0.1, the 
other p-value will be tested at a 0.05 significance level and the corresponding dose will be declared 
significant only if the p-value is <0.05. If both p-values are ≥0.1, no dose will be declared 
significant, and no further formal testing will be performed. 
If both 200 mg B.I.D. and 100 mg B.I.D. achieved the statistical significance for the primary 
efficacy endpoint, the fixed-sequence method will be used to test the comparison of 100 mg Q.D. 
with placebo for the primary efficacy endpoint and the comparison of each dose with placebo for 
the secondary efficacy endpoint of clinical response at Week 12 in a predefined order as specified 
in Figure 2 below. All tests will be performed at the same significance level alpha=0.1, with the 
moving to a second test only after a success, i.e., p-value <0.1, on the previous test. Further testing 
stops as soon as one test in the sequence fails to meet significance, i.e., p-value ≥0.1. 
The testing of the exploratory efficacy endpoints not included in the hierarchical procedure will 
be used for exploratory purposes only. The details will be specified in the SAP. 

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Figure 2. 
Hierarchical Testing Procedure 
9.2.4. 
Safety Analyses 
The Safety Population will be used for the summarization of all safety data. 
AEs will be coded using the current Medical Dictionary of Regulatory Activities (MedDRA) 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 and 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. 
200 mg B.I.D. vs Placebo, 
Clinical Remission  
100 mg B.I.D. vs Placebo, 
Clinical Remission 
Hochberg testing procedure (2-sided α = 0.1) 
p-values < 0.1 
for both tests  
Yes  
No  
Any p-value 
< 0.05 
Claim significance for the dose with 
p-value <0.05, and end formal testing  
Yes  
No  
End formal 
testing 
100 mg Q.D. vs Placebo, 
Clinical Remission 
200 mg B.I.D. vs placebo,  
Clinical Response 
100 mg B.I.D. vs Placebo,  
Clinical Response 
100 mg Q.D. vs Placebo, 
Clinical Response 
p-value < 0.1  
p-value < 0.1  
p-value < 0.1  

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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 Population. The incidence of laboratory abnormalities will be summarized. Worst 
shift in grade and changes from baseline of the laboratory analytes will be reported. Physical 
examination findings that are recorded as AEs will be included in those data presentations. 
The safety analyses will be performed for the 12-week Induction Period, the 52-week Treatment 
Period, and the 52-week LTE Period plus the Safety Follow-up Period. In the safety analyses for 
the 12-week Induction Period, the participants initially randomized into the placebo group and 
switched to an active MORF-057 regimen after the Week 12 assessments will be analyzed as the 
placebo group. In the safety analyses for the 52-week Treatment Period and 52-week LTE Period, 
the placebo recipients switched to an active MORF-057 regimen will be analyzed according to the 
active MORF-057 regimen they received after Week 12, and their data will be presented separately 
based on only the safety data collected after the start of the MORF-057 dose. 
9.2.5. 
Pharmacokinetics Analyses 
PK concentration will be summarized. Additional PK and PK/PD analyses will be conducted as 
deemed appropriate and may be reported separately from the Clinical Study Report. 
9.2.6. 
Pharmacodynamics Analyses 
The exploratory PD endpoints (changes over time in α4β7 and α4β1 receptor occupancies and blood 
CCR9 mRNA level) will be summarized descriptively. Additional analysis of PD endpoints may 
be described 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 PD exploratory endpoints. 
9.3. 
Analyses for Induction Period, 52-week Treatment Period, and LTE 
Period 
The Treatment Period in the main part of the study includes 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 one for 
the 52-week Treatment Period (i.e., the 12-week Induction Period plus the 40-week Maintenance 
Period and Safety Follow-up Period). The details of the analyses will be described in the SAP. 
Additional analysis of the optional 52-week LTE Period for the participants enrolled into the LTE 
Period will also be performed as appropriate. 
Induction Period Analysis 
The analysis of the 12-week Induction Period will be performed after all the participants have 
completed the Week 12 assessments or discontinued the study before the Week 12 assessments. 
The analysis will formally evaluate the primary and secondary efficacy endpoints, all the 
exploratory efficacy endpoints defined by Week 12, and safety of MORF-057 vs placebo during 

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the 12-week Induction Period. The PK and PD data during the 12-week Induction Period will also 
be summarized. 
52-week Treatment Period Analysis 
The analysis of the 52-week Treatment Period will be performed after all the participants have 
completed the Week 52 assessments (and Safety Follow-up Period for participants not rolling over 
into the LTE Period) or discontinued from the study during the 52-week Treatment Period. The 
analysis will formally evaluate the efficacy (including all the exploratory efficacy endpoints 
defined by Week 52), PK, PD, and safety of MORF-057 during the 52-week Treatment Period 
(and the Safety Follow-up Period for participants not rolling over into the LTE Period). The 
cumulative data, including those from the Induction Period, will be used in this analysis. 
52-week LTE Period Analysis 
The analysis of the LTE Period will be performed after all the participants enrolled into the LTE 
Period have completed the 52-week LTE Period and the Safety Follow-up Period or discontinued 
the study during the LTE Period. The analysis will evaluate the long-term safety of MORF-057 
and selected efficacy endpoints at Week 104 as appropriate during the LTE Period plus the Safety 
Follow-up Period. 
9.4. 
Interim Analysis 
The analysis of the 12-week Induction Period (Induction Period Analysis) will be performed after 
all the participants have completed the Week 12 assessments or discontinued the study before the 
Week 12 assessment, as described in Section 9.3. 
An independent DSMB will review participant safety data and monitor scientific integrity 
throughout the study. Details related to the DSMB will be clearly delineated in the DSMB Charter. 
9.5. 
Sample Size Determination 
The sample size was determined based on the primary endpoint of clinical remission at Week 12 
by using the Chi-Squared Test to compare two proportions. A sample size of 70 participants per 
group (giving a total of 280) will provide 80% power to detect a difference of 15% in the clinical 
remission rate between MORF-057 and placebo, based on the use of a two-sided test at the 
alpha=0.10 level of significance. The calculation is based upon an assumed placebo remission rate 
of 7%. 

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10. 
Appendices: 
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, including European Union Clinical Trials 
Regulation 536/2014 
The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., advertisements) 
must be submitted to an IRB/IEC or to the Member States Concerned and reviewed and approved 
by the IRB/IEC or Member States Concerned, as applicable, before the study is initiated. 
Any amendments to the protocol will require IRB/IEC or Member States Concerned, as applicable, 
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 Member States Concerned 
or health authority, as applicable, approval prior to initiation, in line with country-specific 
requirements. 
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, as applicable 
• Notifying the IRB/IEC of SAEs or other significant safety findings as required by IRB/IEC 
procedures, as applicable 
• Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 CFR, ICH guidelines, the IRB/IEC or Member States Concerned, as applicable, 
European Union Clinical Trials Regulation 536/2014 for clinical studies, and all other 
applicable local regulations 
After reading the protocol, each Investigator will sign the Investigator’s Agreement page 
(Section 10.10). The study will not start at any study center at which the Investigator has not signed 
the protocol. 
The Sponsor will notify the authorities as applicable (in line with country/region requirements) 
about a serious breach of the regulations or of the version of the protocol applicable at the time of 
the breach. A ‘serious breach’ means a breach likely to affect to a significant degree the safety and 
rights of a participant or the reliability and robustness of the data generated in the clinical trial. 

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If the Investigator identifies a potential instance of a serious breach, the Sponsor and Contract 
Research Organization (CRO) should be notified immediately at 
 
Include any available information at the time of the incident and copies of all documentation, if 
any, supporting the suspicion. 
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 
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 acceptable representative, if applicable, and 
answer all questions regarding the study. 
Participants must be informed that their participation is voluntary. Each participant or his/her 
legally acceptable representative, if applicable, 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, Member States Concerned/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. 
If a participant or legal representative is unable to read and/or write, an impartial witness should 
be present during the entire informed consent discussion. 
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 acceptable 
representative, if applicable. 
Additional Consents 
The main ICF will contain separate sections for the following additional consents: 
• Optional collection of blood, colonic tissue, and stool samples for future PD, 
microbiome-related analyses, fecal calprotectin assessment, and future research. If consent 
is provided, use of the remaining blood and colonic tissue samples from the study-required 
procedures may also be used for future research, including future PK research (see 
Sections 8.7.1, 8.10, 8.12, and the SoA in Section 1.2). 
CCI

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• Optional blood sampling for future pharmacogenomics analysis, which will involve 
genetic testing (see Section 8.12, Section 10.9, and the SoA in Section 1.2). 
Additional ICFs will be provided to participants or their partners for review and signature, as 
needed: 
• Optional LTE Period (see Section 4.1 and the SoA in Section 1.2) 
• Consent to courier deliveries/pick-ups (see Section 8.13) 
• Pregnancy Follow-up (see Section 8.9.5) 
The Investigator or authorized designee will explain to each participant the objectives of the 
optional sampling. 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). Signatures will be required to document a 
participant’s agreement to allow the optional samplings. Participants who decline to participate in 
optional samplings will not be asked to provide signatures. 
10.1.5. 
Data Protection 
• Measures must be described that will be implemented to ensure confidentiality of records 
containing personal data of participants. In particular, the personnel of the site, Sponsor, 
and vendors (CRO) involved in data processing are bound by obligations of confidentiality 
and the 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. In particular, 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 or 
Member States Concerned members, as applicable, and by inspectors from regulatory 
authorities. 
• The contract between Sponsor and study sites specifies the responsibilities of the parties 
regarding data protection, including handling of data security breaches and respective 
communication and cooperation of the parties. The process to handle data security 
breaches, in order to mitigate the possible adverse effects of such breaches to the privacy 
of study participants, must be described. 
• Organizational and technical arrangements that will be implemented to avoid unauthorized 
access, disclosure, dissemination, alteration, or loss of personal data must be described. In 
particular, the information technology systems used to collect, process, and store 
study-related data are secured by technical and organizational security measures designed 
to protect such data against accidental or unlawful loss, alteration, or unauthorized 
disclosure or access. 

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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 treatment, 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 schedules of the DSMB will be described in a separate 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 (including clinicaltrials.gov and the public domain of the Clinical Trials Information 
System database at https://euclinicaltrials.eu/home) 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 paper-based Case Report Forms 
(CRFs) or eCRFs unless transmitted to the Sponsor or designee electronically (e.g., laboratory 
data). The Investigator is responsible for having quality system processes and procedures in place 
verifying that CRF data entries against source data are accurate and correct. The Investigator is 
responsible for ensuring source records are maintained in real-time, eCRFs are completed per 
eCRF Completion Guidelines, and physically or electronically signing the CRF. 
Guidance on completion of CRFs and eCRFs will be provided in the corresponding guidelines. 
The Investigator must permit study-related monitoring, audits, IRB/IEC review (if applicable), 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 scheduled 
data audits and verification against original source data/documentation. 
The Sponsor assumes accountability for actions delegated to other individuals (e.g., CROs). 
The contents of the electronic Trial Master File pertaining to the conduct of this study must be 
retained by the Sponsor and the Investigator for at least 25 years after study completion unless 
local regulations, institutional policies, or by an agreement with the Sponsor require a longer 
retention period. However, the medical files of participants shall be archived in accordance with 
national law. It is the responsibility of the Sponsor to inform the Investigator/institution as to when 
these documents no longer need to be retained. 

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Please reference the current version of ICH E6 for the minimum list of essential documents 
required for the conduct of a clinical trial. Additional documentation may be required by the 
Sponsor or CRO before, during, and after completion of the trial. 
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 and digitized 
copies are maintained in the site section of the electronic Trial Master File. 
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 by the Investigator 
and documented in the CRF. The Investigator may need to request previous and current medical 
records or transfer records as source documents for participants involvement (or enrollment) in 
this study. 
The Investigator must maintain accurate documentation (source data) that supports the information 
entered in the CRF and eCRF. 
Sponsor-designated study monitors will perform ongoing source data verification to confirm that 
data entered into the CRF/eCRF 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, all quality compliance activities have been completed, 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. 

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Reasons for the early closure of a study site by the Sponsor or Investigator may include but are not 
limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the Member 
States Concerned or IRB/IEC, as applicable, 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 enrolled earlier than expected 
Reasons for study termination include, but are not limited to: 
• Recommendation of the DSMB based on the ongoing review of safety 
• If a positive benefit/risk ratio is no longer observed, based on DSMB review of unblinded 
data 
• Discontinuation of further study drug development 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, the Member States Concerned and/or the IRBs/IECs, as applicable, the regulatory 
authorities, and any CROs 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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10.2. 
Appendix 2: Progressive Multifocal Leukoencephalopathy Checklists 
Subjective PML Checklist 
Symptoms 
“Compared to 
how you usually 
feel, have you 
had a significant 
change in any of 
the following?” 
If the answer is “Yes,” 
obtain a description of 
the symptom(s) with 
examples. 
Applicable Objective 
Test(s): Document results on 
PML Objective Checklist 
 
Yes 
No 
 
 
1. Have you been experiencing 
any persistent difficulty with your 
vision, such as loss of vision or 
double vision? Have you been 
having trouble with reading? 
 
 
 
Test visual fields and ocular 
motility. 
2. Have you been experiencing 
any persistent difficulty speaking 
or having your speech understood 
by others? 
 
 
 
Casual observation of 
speech output for dysarthria 
or aphasia. Ask patient to 
name a few objects and 
repeat a multipart phrase. 
3. Have you been experiencing 
any persistent weakness in an arm 
or a leg? 
 
 
 
Test for pronator drift (Barré 
maneuver) and/or fixation 
on arm roll. Assess the 
ability to hop on either foot; 
foot and finger tapping. Test 
symmetric muscle strength. 
4. Have you noticed yourself 
regularly bumping into things or 
having difficulty writing? 
 
 
 
Ask for spontaneous writing 
sample and observe finger to 
nose, heel to shin, and 
tandem gait. 
5. Have you regularly been 
experiencing difficulty 
understanding others? 
 
 
 
Ability to follow serial 
commands (close your eyes, 
stick out your tongue, and 
touch your left finger to your 
left ear). 
6. Have you had persistent 
problems with your memory or 
thinking? 
 
 
 
Recall of 3 objects over 
1 minute with distraction; 
ability to follow commands. 
7. Have you been experiencing 
any persistent numbness or other 
loss of sensation? 
 
 
 
Test sensation side to side 
with pinprick. 
PML, progressive multifocal leukoencephalopathy. 
 

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Objective PML Checklist – To be completed for participants with positive subjective 
finding 
Perform the objective test(s) that correspond to the subjective checklist finding 
Positive 
Symptom(s) 
Applicable Objective Test(s) 
Test Result(s) 
If test result is abnormal,  
briefly describe result 
 
 
Normal 
Abnormal 
 
1. Difficulty 
with vision or 
reading 
Test 
visual 
field 
and 
ocular 
motility. 
 
 
 
2. Difficulty 
with speaking 
Casual 
observation 
of 
speech 
output for dysarthria or aphasia. 
Ask patient to name a few objects 
and repeat a multipart phrase. 
 
 
 
3. Weakness 
in an arm or a 
leg 
Test for pronator drift and/or 
fixation on arm roll. Assess the 
ability to hop on either foot; foot 
and finger tapping. Test muscle 
strength. 
 
 
 
4. Bumping 
into things or 
difficulty 
writing 
Ask 
for 
spontaneous 
written 
sample and observe finger to nose, 
heel to shin, and tandem gait. 
 
 
 
5. Difficulty 
understanding 
others 
Ability to follow serial commands 
(Close your eyes, stick out your 
tongue, and touch your left finger to 
your left ear). 
 
 
 
6. Problems 
with memory 
or thinking 
Recall of 3 objects over 1 minute 
with distraction; ability to follow 
commands. 
 
 
 
7. Problems 
with 
numbness 
Test sensation side to side with 
pinprick. 
 
 
 
Source: Parikh 2018 
× If objective test corroborates the reported symptom, refer the participant for a Neurology consult. Otherwise, please follow up 
with the participant one week after the Objective Checklist was administered to ensure symptoms are not recurring. 
× Please notify your Clinical Research Associate and the Sponsor of any positive Objective Checklist findings. 
 
 

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10.3. 
Appendix 3: Clinical Laboratory Tests 
The tests detailed in Table 11 will be performed by the central laboratory. 
Local laboratory results are only required in the event that the central laboratory results are not 
available in time for either study 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. 
In case of abnormal liver function test results, Investigators should follow the instructions in 
Table 12 (Hy’s law cases table) for re-testing and follow-up procedures. 
Investigators must document their review of each laboratory safety report. 
Table 11. 
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 
• 
aPTT 
• 
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 all subsequent visits for women of childbearing potential only) a 
Other Screening 
tests 
• 
SARS-CoV-2 test (test to be determined by the site) 
• 
Tuberculosis test (test to be determined by the site) 

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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) 
Efficacy 
• 
Serum hs-CRP 
• 
Fecal calprotectin 
Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; aPTT, activated partial thromboplastin time; 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; 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 Member States 
Concerned or IRB/IEC, as applicable. 
 

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Table 12. 
Abnormal Liver Function Results: Re-testing and Follow-up Procedures 
Initial Lab Alert 
Initial results: 
ALT or AST >3 × ULN, BUT <8 × ULN 
OR 
ALT or AST >3 × ULN, AND bilirubin >2 × ULN 
 
BUT without signs/symptoms of acute liver failure* 
 
Next steps (first approximately 48-72 hours): 
• Withhold IMP 
• Elicit history 
• Physical exam 
• Repeat LFT in 48-72 hours, or as soon as practical (central laboratory) 
• Check INR 
Initial results: 
ALT or AST >3 × ULN, with signs/symptoms of acute 
liver failure* 
OR 
AST or ALT >8 × ULN, with or without bilirubin increase 
 
Next steps (first approximately 48-72 hours): 
• Withhold IMP 
• Elicit history 
• Physical exam 
• Repeat LFT in 48-72 hours, or as soon as practical  
(central laboratory) 
• Check INR 
Re-test Review 
Re-test Review 
Re-test results  
(after approximately 
48-72 hours): 
ALT or AST  
>3 × ULN 
AND 
bilirubin  
>2 × ULN  
and/or 
INR >1.5 
 
Next steps: 
• Discontinue IMP 
• Investigate abnormal 
LFT further 
• Early Termination Visit 
Re-test results  
(after approximately 
48-72 hours): 
AST or ALT  
>5 × ULN 
 
Next steps: 
• Continue to withhold 
IMP 
• Repeat in 1-2 weeks. 
If still >5 × ULN, 
• Discontinue IMP 
• Investigate abnormal 
LFT further 
• Early Termination Visit 
Re-test results  
(after approximately 48-72 
hours): 
AST or ALT  
>8 × ULN 
OR 
ALT or AST  
>3 × ULN 
with signs/symptoms of 
acute liver failure* 
 
Next steps: 
• Discontinue IMP 
• Investigate abnormal LFT 
further 
• Early Termination Visit 
Re-test results  
(after approximately 
48-72 hours): 
Improvement 
 
Next steps: 
• Discuss with Medical 
Monitor regarding 
resumption of IMP** 
Re-test results  
(after approximately 
48-72 hours): 
Similar findings as above or 
with worsening such as 
bilirubin >2 × ULN or  
INR >1.5 
 
Next steps: 
• Discontinue IMP 
• Investigate abnormal LFT 
further 
• Early Termination Visit 
Re-test results  
(after approximately 
48-72 hours): 
Improvement 
 
Next steps: 
• Discuss with Medical 
Monitor regarding 
resumption of IMP** 
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; IMP, investigational medicinal product (MORF-057 or placebo); INR, international 
normalized ratio; LFT, liver function tests; ULN, upper limit of normal. 
*Signs/symptoms of liver failure: fatigue, nausea, right upper quadrant pain and/or tenderness, fever, rash, and eosinophilia. 
** Resumption of the study drug can be considered only in consultation with the Medical Monitor and only if the liver test results returned to near baseline and if a self-limited 
non-study drug etiology is identified. Otherwise, the study drug should be permanently discontinued. 

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10.4. 
Appendix 4: AEs and SAEs: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting 
10.4.1. 
Definition of AE 
AE Definition 
• An AE is any untoward medical occurrence in a clinical study participant, temporally 
associated with use of the study drug, whether or not considered related to the study 
drug. 
• NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with use of the study drug. 
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECG, vital signs measurements), including those that 
worsen from baseline, considered clinically significant in the medical and scientific 
judgement of the Investigator (i.e., not related to progression of underlying disease) 
• Exacerbation of a chronic or intermittent pre-existing condition, including an increase in 
frequency and/or intensity of the condition 
• New condition detected or diagnosed after study drug administration even though it may 
have been present before the start of the study 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study drug 
or a concomitant medication. Overdose per se will not be reported as an AE/SAE unless 
it is an intentional overdose taken with possible suicidal/self-harming intent. Such 
overdoses should be reported regardless of sequelae. 
• Lack of efficacy or failure of expected pharmacological action per se will not be reported 
as an AE or SAE. Such instances will be captured in the efficacy assessments. However, 
the signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be 
reported as AE or SAE if they fulfill the definition of an AE or SAE. 
Events NOT Meeting the AE Definition 
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
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• The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the 
participant’s condition 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that leads 
to the procedure is the AE 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital) 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen 
10.4.2. 
Definition of SAE 
An SAE is Defined as any Untoward Medical Occurrence That, at any Dose, Meets one 
or More of the Criteria Listed Below: 
a. Results in death 
b. Is life-threatening 
The term life-threatening in the definition of serious refers to an event in which the participant 
was at risk of death at the time of the event. It does not refer to an event, which hypothetically 
might have caused death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been admitted to the hospital for 
inpatient care, regardless of the length of stay. Complications that occur during hospitalization 
are AEs. If a complication prolongs hospitalization or fulfills any other serious criteria, the event 
is serious. When in doubt as to whether hospitalization occurred or was necessary, the AE should 
be considered serious. 
Note: The following are not considered an SAE: 
• Scheduled hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline 
• Hospitalization for social/convenience considerations 
• Scheduled therapy for the target disease of the study, including admissions for 
colonoscopy or convenience 
d. Results in persistent or significant disability/incapacity 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
This definition is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle) that may interfere with or prevent everyday life functions but do not 
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e. 
Is a congenital anomaly/birth defect 
f. 
Other serious and important medical events: 
Medical or scientific judgement should be exercised by the Investigator in deciding whether 
SAE reporting is appropriate in other situations such as significant medical events that may 
jeopardize the participant or may require medical or surgical intervention to prevent one of the 
other outcomes listed in the above definition. These events should usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive treatment for allergic 
bronchospasm, blood dyscrasias, convulsions or development of intervention dependency or 
intervention abuse. 
10.4.3. 
Recording and Follow-up of AE and/or SAE 
AE and SAE Recording 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all documentation 
(e.g., hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
The Investigator will then record all relevant AE/SAE information in the eCRF. Each event must 
be recorded separately. 
It is not acceptable for the Investigator to send photocopies of the participant’s medical records 
to the Sponsor in lieu of completion of the AE/SAE eCRF page. 
There may be instances when copies of medical records for certain cases are requested by the 
Sponsor. In this case, all participant identifiers, with the exception of the participant number, 
will be redacted on the copies of the medical records before submission to the Sponsor. 
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The severity of an AE will be graded according to the scale below using the Common 
Terminology Criteria for Adverse Events (CTCAE) Version 5.0. The severity of the AE is 
determined by the Investigator. The Investigator is encouraged to consult with the Medical 
Monitor if he/she would like to discuss the case. 
Severity will be assessed according to the following scale: 
• Grade 1 (Mild): Asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 
• Grade 2 (Moderate): Minimal, local, or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living. 
• Grade 3 (Severe): Medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
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• Grade 4 (Life-Threatening): Life-threatening consequences; urgent intervention 
indicated. 
• Grade 5 (Death): Death related to AE. 
It is important to distinguish between serious and severe AEs. Severity is a measure of intensity, 
whereas seriousness is defined by the criteria under Section 10.4.2. An AE of severe intensity 
may not be considered serious. 
Assessment of Causality 
The Investigator is obligated to assess the relationship between the study drug and the 
occurrence of each AE/SAE. The Investigator will use clinical judgement to determine the 
relationship. A reasonable possibility of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship. Alternative causes, such as underlying 
disease(s), concomitant therapy, and other risk factors, as well as the temporal relationship of 
the event to study drug administration, will be considered and investigated. The Investigator will 
also consult the Investigator’s Brochure and consider known actions or toxicity of the study drug 
in his/her assessment. 
For each AE/SAE, the Investigator must document in the medical notes that he/she has reviewed 
the AE/SAE and has provided an assessment of causality. 
There may be situations in which an SAE has occurred and the Investigator has minimal 
information to include in the initial report to the Sponsor. However, it is very important that the 
Investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to the Sponsor. The Investigator may change his/her opinion of 
causality in light of follow-up information and send an SAE follow-up report with the updated 
causality assessment. The causality assessment is one of the criteria used when determining 
regulatory reporting requirements. 
The causal relationship between the study medication and the AE will be assessed using one of 
the following categories: 
Not Related: An AE is not associated with study medication if: 
• Temporal relationship is lacking (e.g., the event did not occur within a reasonable time 
frame following administration of the study medication). 
• Other causative factors more likely explain the event (e.g., a pre-existing condition, other 
concomitant treatments). 
• De-challenge was either not clinically indicated or did not result in clinical improvement. 
• AE did not re-occur upon re-challenge (if applicable). 
Related: An AE is attributed to the study medication if: 
• There is a positive temporal relationship (i.e., the event occurred within a reasonable 
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• The AE is more likely explained by the study drug than by another cause (i.e. the AE 
shows a pattern consistent with previous knowledge of the study drug or the class of the 
study drug). 
• The event improved on de-challenge and/or re-occurred upon re-challenge (if 
applicable). 
The Sponsor will make the final determination of relatedness of the AE to the study drug, taking 
into consideration the Investigator’s assessment of suspected relatedness. If the relationship 
between the AE/SAE and the study drug is determined to be “suspected to be related”, the event 
will be considered to be related to the study drug for the purposes of expedited regulatory 
reporting or determination of stopping rules. 
Follow-up of AEs and SAEs 
• 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). 
• The Investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the Sponsor 
to elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals. 
• If a participant dies during participation in the study or during a recognized follow-up 
period, the Investigator will provide the Sponsor with a copy of any postmortem findings 
including histopathology. 
• The Investigator will submit any updated SAE data to the Sponsor within 24 hours of 
receipt of the information. 
10.4.4. 
Reporting of SAEs 
SAE Reporting to the Sponsor or Designee via an Electronic Data Collection Tool 
• The primary mechanism for reporting an SAE to the Sponsor will be the electronic data 
collection tool. The SAE must be reported within 24 hours of the study staff becoming 
aware. 
• If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section). The SAE must be reported within 24 hours of the study 
staff becoming aware. 
• The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• After the study is completed at a given site, the electronic data collection tool will be 
taken offline to prevent the entry of new data or changes to existing data. 

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• If a site receives a report of a new SAE from a study participant or receives updated data 
on a previously reported SAE after the electronic data collection tool has been taken 
offline, then the site can report this information on a paper SAE form (see next section) 
or to the Sponsor or designee by telephone. 
• SAEs will be reported to Lilly Global Patient Safety by email (email address will be 
defined in a study-specific safety reporting plan). 
SAE Reporting to the Sponsor or Designee via Paper Data Collection Tool  
(Back-up Option) 
• E-mail transmission of the SAE paper data collection tool is the preferred method to 
transmit this information to the Sponsor or designee. 
• Initial notification via telephone does not replace the need for the Investigator to 
complete and sign the SAE data collection tool within the designated reporting 
timeframes. 
• SAEs will be reported to Lilly Global Patient Safety by email (email address will be 
defined in a study-specific safety reporting plan). 
 

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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 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 treatment, 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: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 

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• 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 postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
o 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. 
o 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 for Female Study Participants 
10.5.2.1. Female Study Participants Who Do Not Consent to Dose Switch in LTE Period 
Note: This is relevant for participants who do not consent to the dose switch in the LTE Period. 
For contraception requirements for those who do consent to the dose switch in the LTE Period, 
see Section 10.5.2.2. 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb 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/ligation 
• 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. 
• 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 treatment. 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 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, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhea method are not acceptable methods of contraception. Male 
condom and female condom should not be used together (due to risk of failure from friction). 
10.5.2.2. Female Study Participants Who Do Consent to Dose Switch in LTE Period  
Note: This is relevant for participants who do consent to the dose switch to 200 mg B.I.D. in the 
LTE Period. For contraception requirements for those who do not consent to the dose switch in 
the LTE Period, see Section 10.5.2.1. 
For participants that are currently using systemic (e.g., oral, implantable) hormonal contraception 
but have consented to the MORF-057 dose switch:  
• They must change to new contraception by the time of DSFU 2 (8 weeks after the dose 
switch) or as soon as possible.  
• All participants must remain abstinent until new contraception is in place. 
WOCBP and WONCBP may participate in this trial. 
WOCBP who are completely abstinent as their preferred and usual lifestyle, or exclusively engage 
in sexual relations with other individual(s) who are assigned female at birth, as their preferred and 
usual lifestyle must follow the rules in this table. 
Must… 
Must not… 
agree to either remain abstinent 
or exclusively engage in sexual 
relations with other individual(s) 
who are assigned female at birth, 
and not plan a pregnancy during 
the study 
• 
use periodic abstinence methods 
o 
calendar 
o 
ovulation 
o 
symptothermal, or 
o 
post-ovulation 
• 
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Must… 
Must not… 
• 
use the withdrawal method 
WOCBP who are NOT completely abstinent as their preferred and usual lifestyle, or who do NOT 
exclusively engage in sexual relations with other individual(s) who are assigned female at birth, 
as their preferred and usual lifestyle, must follow the rules in this table. 
Must… 
Agree to use 1 highly effective method of contraception together with a barrier method of contraception (see 
below). Note: During this study, systemic hormonal contraception is not considered effective or highly effective 
and therefore is not permitted as a means of contraception. 
Barrier method of contraception includes condoms (male or female) with or without a spermicidal agent, 
diaphragm, or cervical cap with spermicide. 
These methods of contraception must be used during the study and for at least 28 days after the last dose of the 
study intervention. 
Examples of different methods of contraception: 
Note: Participants who switch to 200 mg B.I.D. cannot use oral or systemic hormonal 
contraception as an effective method. 
Methods 
Examples 
Highly 
effective 
contraception 
(less 
than 1% failure rate) 
• 
Fallopian tubal sterilization methods other than bilateral salpingectomy 
(laparoscopic bipolar electrocoagulation, plastic ring application on the uterine 
tubes, fallopian tube ligation, hysteroscopic sterilization). Note: Bilateral 
salpingectomy is indicative of permanent sterilization. Please see the WONCBP 
definition above. 
• 
Total abstinence 
• 
Sexual relationships exclusively between individuals who are assigned the same sex 
at birth 
• 
Vasectomy – for individuals assigned male at birth in clinical trials and for the 
partner of an individual assigned female at birth (if only sexual partner) 
• 
Fallopian tube implants (if confirmed by hysterosalpingogram), or 
• 
Intrauterine devices (IUD) with or without hormone-releasing system 
Effective 
contraception 
• 
Penile condom with or without spermicide 
• 
Vaginal condom with or without spermicide 
• 
Diaphragm with spermicide 
• 
Cervical sponge with spermicide, or 

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Methods 
Examples 
• 
Cervical cap with spermicide 
Note: Penile and vaginal condoms should not be used in combination. 
Ineffective methods of 
contraception whether 
used alone or in any 
combination 
• 
Combined (estrogen- and progestogen-containing) hormonal contraception 
associated with inhibition of ovulation (listed below) 
− oral 
− intravaginal 
− transdermal 
− injectable 
• 
Progestogen-only hormone contraception associated with inhibition of ovulation 
− oral 
− injectable 
− implantable 
• 
Spermicide alone 
• 
Periodic abstinence 
• 
Fertility awareness (calendar method, temperature method, cervical mucus, or 
symptothermal) 
• 
Withdrawal 
• 
Postcoital douche, or 
• 
Lactational amenorrhea 
• 
Ablation (endometrial or uterine) is not considered a form of contraception 
Abbreviations: IUD, intrauterine device; WONCBP, woman of non-childbearing potential. 
10.5.3. 
Contraception Guidance for Male Study Participants 
Participant Population 
Contraception Guidance 
All male study participants… 
should refrain from sperm donation for the duration of the study 
and for at least 14 days after the last dose of the study intervention. 
Male study participants with partner(s) who 
are WOCBP a… 
must 
• 
remain abstinent (if this is their preferred and usual 
lifestyle), or 
• 
use condoms and at least 1 additional effective method of 
contraception (see “Examples of different methods of 
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Participant Population 
Contraception Guidance 
at least 28 days after the last dose of the study 
intervention.  
Male study participants with partner(s) who 
are pregnant a… 
must 
• 
remain abstinent (if this is their preferred and usual 
lifestyle), or 
• 
use condoms for the duration of the study and for at least 
28 days after the last dose of the study intervention. 
Male study participants who exclusively 
engage in sexual relations with other 
individual(s) who are assigned male at birth, 
as their preferred and usual lifestyle… 
 
are not required to use contraception. 
Abbreviations: WOCBP, woman of childbearing potential. 
a Male study participants who have undergone orchiectomy but not penectomy must use condoms during sex, but the partner 
who is WOCBP is not required to use an additional form of contraception. Male study participants who have undergone 
orchiectomy and penectomy are not required to use condoms. 
Examples of different methods of contraception a: 
Methods 
Examples 
Highly 
effective 
contraception 
(less 
than 1% failure rate) 
• 
Fallopian tubal sterilization methods other than bilateral salpingectomy 
(laparoscopic bipolar electrocoagulation, plastic ring application on the uterine 
tubes, fallopian tube ligation, hysteroscopic sterilization). Note: Bilateral 
salpingectomy is indicative of permanent sterilization. Please see the WONCBP 
definition above. 
• 
Combined (estrogen and progestogen-containing) hormonal contraception 
associated with inhibition of ovulation (listed below) 
− oral 
− intravaginal  
− transdermal  
− injectable 
• 
Progestogen-only hormonal contraception associated with inhibition of ovulation 
− oral 
− injectable 
− implantable 
• 
Total abstinence 
• 
Sexual relationships exclusively between individuals who are assigned the same 
sex at birth 

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Methods 
Examples 
• 
Vasectomy – for individuals assigned male at birth in clinical trials and for the 
partner of an individual assigned female at birth (if only sexual partner) 
• 
Fallopian tube implants (if confirmed by hysterosalpingogram), or 
• 
Intrauterine devices (IUD) with or without hormone-releasing system 
Effective 
contraception 
• 
Progestogen-only hormonal contraception, where inhibition of ovulation is not the 
primary mode of action 
• 
Penile condom with or without spermicide 
• 
Vaginal condom with or without spermicide 
• 
Diaphragm with spermicide 
• 
Cervical sponge with spermicide 
• 
Cervical cap with spermicide 
Note: Penile and vaginal condoms should not be used in combination. 
Ineffective methods 
of 
contraception 
whether used alone 
or 
in 
any 
combination 
• 
Spermicide alone 
• 
Periodic abstinence 
• 
Fertility awareness (calendar method, temperature method, cervical mucus, or 
symptothermal) 
• 
Withdrawal 
• 
Postcoital douche, or 
• 
Lactational amenorrhea 
Abbreviations: IUD, intrauterine device; WONCBP, woman of non-childbearing potential. 
a Ablation (endometrial or uterine) is not considered a form of contraception. 

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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 Histopathology 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 MCS, mMCS, and Partial mMCS will be used to assess clinical changes. The MCS is a 
composite of the following subscores: MES, MCS stool frequency subscore, MCS rectal bleeding 
subscore, and the PGA. The mMCS is a composite of the following subscores: MES, MCS stool 
frequency subscore, and MCS rectal bleeding subscore. The Partial mMCS is a composite of the 
following subscores: MCS stool frequency subscore and MCS rectal bleeding subscore. 
The MCS ranges from 0 to 12, the mMCS ranges from 0 to 9, and the Partial mMCS ranges from 
0 to 6. For all 3 of these composite scores, higher scores indicate 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 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 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 

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

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10.8. 
Appendix 8: Inflammatory Bowel Disease Questionnaire (IBDQ) 
CCI

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10.9. 
Appendix 9: Genetics 
Use/analysis of DNA for optional future pharmacogenomics research (see Section 8.12 and 
SoA in Section 1.2) 
• Genetic variation may impact a participant’s response to the study drug, susceptibility to, 
and severity and progression of disease. Variable response to study treatment may be due 
to genetic determinants that impact treatment absorption, distribution, metabolism, and 
excretion; mechanism of action of the treatment; disease etiology; and/or molecular 
subtype of the disease being treated. Therefore, where local regulations and IRB/IEC or 
Member States Concerned allow, as applicable, 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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10.10. 
Appendix 10: Investigator’s Agreement 
 
By signing below, I agree that: 
 
I have read Protocol MORF-057-202 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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10.11. 
Appendix 11: Changes to This Protocol in Previous Amendments 
Version 2.0 dated 26 April 2023 
Overall Rationale for the Amendment 
The overall rationale for this protocol amendment is to add the following major changes: 
• Add a 52-week Maintenance Extension following the 52-week Treatment Period, add 
corresponding endpoints, and update the study design/schema and statistical analyses 
• Clarify the enrollment plan for prior advanced therapy-experienced participants 
• Extend the Screening Period to ensure sufficient time for screening activities 
• Revise the Inclusion/Exclusion criteria regarding inadequate response, washout criteria of 
prior UC therapy, tuberculosis screening, and testing of SARS-CoV-2 
• Update the Schedule of Activities for clarity and add study activities for the Maintenance 
Extension Period 
• Remove the Week 24 clinical improvement assessment timepoint 
• Revise the sequence of events for Week 12, Week 52/EOT, and Week 104/LTE EOT 
wherein the endoscopy occurs during Stage 1, followed by the clinic visit at Stage 2 
• Add a follow-up contact on the day after the Week 12 clinic visit to ensure participants 
begin using the study drugs for the Maintenance Period 
• Update risks of MORF-057 
• Clarify the re-screening process and the blinding process after Week 12 
• Specify the process of reporting and capturing the overdose information 
• Clarify the acceptable use of aspirin 
• Clarify the discontinuation/withdrawal criteria regarding lack of efficacy, ineligible 
participants, and male participant whose partner becomes pregnant 
• Specify the number of biopsies for histopathology and the optional future research 
• Clarify the additional informed consents 
• Update the exclusion criteria regarding participant allergies/hypersensitivities 
• Add a justification for use of placebo 
• Explain the adjustment for multiple testing 
• Identify the calculation for determining sample size 
This protocol amendment is considered Substantial by the Sponsor, according to the criteria 
specified in the European Union Clinical Trials Regulation 536/2014.

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Summary of Changes Table 
This protocol amendment is considered Substantial by the Sponsor, according to the criteria specified in the European Union Clinical 
Trials Regulation 536/2014. Changes to the protocol as implemented by this amendment 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. 
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 
Abbreviations 
5-ASA 
5-aminosalicylates 
AST 
Aspartate transaminase 
AUC0-12 
Area under the concentration-time curve from time 0 to 12 hours post-dose 
AUCtau 
Area under the concentration-time curve across the dosing interval 
C12 
Plasma concentration at 12 hours post-dose 
C. difficile Clostridiodes difficile 
CI 
Confidence interval 
CMH 
Cochran-Mantel-Haenszel 
CRA 
Clinical Research Associate 
CRO 
Contract Research Organization 
EDC 
Electronic data capture database 
EEA 
European Economic Area 
ESR 
Erythrocyte sedimentation rate 
FSH 
Follicle-stimulating hormone 
HRT 
Hormonal Replacement Therapy 
IBDQ 
Inflammatory Bowel Disease Questionnaire 
IC90 
90% of maximal inhibitory concentration 
ICH 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use 
IGRA 
Interferon gamma release assay 
MDRD 
Modification of Diet in Renal Disease 
MmMCS Modified Mayo Clinic Score 
mRNA 
Messenger ribonucleic acid 
PI 
Principal Investigator 
PP 
Per Protocol 
PRO 
Patient-reported outcome 
Q.D. – E 
Once a day (evening) 
Q.D. – M Once a day (morning) 
To update the 
abbreviations used 
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RO 
Receptor occupancy 
SC 
Subcutaneous 
TNF-α 
Tumor necrosis factor alpha 
WOCBP 
Woman of Childbearing Potential 
WONCBP Woman of Non-childbearing Potential 
1.1. Synopsis – 
Objectives and 
Endpoints 
3. Objectives and 
Endpoints 
To determine time to symptomatic 
response by Week 12 
• Time to symptomatic response by Week 12 as determined 
using the Partial mMCS 
To clarify the endpoint 
1.1. Synopsis – 
Objectives and 
Endpoints 
3. Objectives and 
Endpoints 
To evaluate the long-term histologic 
and endoscopic effects of MORF-057 at 
Week 104 
• Proportion of participants in histologic remission at 
Week 104 as determined using the RHI 
• Proportion of participants in histologic remission at 
Week 104 as determined using the NI 
• Proportion of participants in histologic remission at 
Week 104 as determined using the Continuous Geboes Score 
• Proportion of participants with histologic improvement at 
Week 104 as determined using the RHI 
• Proportion of participants with endoscopic improvement at 
Week 104 as determined using the MES 
• Proportion of participants in endoscopic remission at 
Week 104 as determined using the MES 
• Proportion of participants in endoscopic remission as 
determined using the MES and histologic remission as 
determined using the RHI at Week 104 
• Proportion of participants with endoscopic improvement 
as determined using the MES and a histologic improvement 
as determined using the RHI at Week 104 
To include endpoints 
corresponding to the 
Maintenance Extension 
1.1. Synopsis – Efficacy 
Analysis Definitions 
3. Objectives and 
Endpoints  
Histologic remission by RHI: RHI ≤32 (with 0 for lamina propria neutrophils score and neutrophils in 
the epithelium score and without ulcers or erosions) 
To clarify efficacy 
analysis definitions 
1.1. Synopsis – Efficacy 
Analysis 
Definitions 
3. Objectives and 
Endpoints 
Corticosteroid-free remission: Determined only in participants who were receiving corticosteroids on 
study Day 1. Includes such participants who are both in clinical remission (as determined using the 
mMCS) at Week 52 and off corticosteroids for ≥812 consecutive weeks prior to Week 52. 
To clarify efficacy 
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Section No. and Name 
Description of Change 
Brief Rationale 
1.1. Synopsis – Overall 
Design 
4.1. Overall Design 
The overall design section was reorganized for clarity and updated to reflect study changes. Text 
revisions are summarized below. 
To reorganize 
paragraphs for clarity  
1.1. Synopsis – Overall 
Design 
4.1. Overall Design 
For each treatment group, theThe study will enroll at least 30% of the participants from each of 
theparticipants who are advanced therapy-naïve (i.e., have no previous exposure to an advanced therapy 
treatment for UC) and advanced therapy-experienced (excluding vedolizumab) strata, with at least 30% 
but no more than 40% of the advanced therapy-experienced patientsparticipants. 
To clarify the 
enrollment plan for 
prior advanced 
therapy-experienced 
participants 
1.1. Synopsis – Overall 
Design 
4.1. Overall Design 
ThisThe main part of this Phase 2b study will consist of 3 study periods: a Screening Period (up to 
4 6 weeks, consisting of Stage 1 and Stage 2 testing), a Treatment Period (52 weeks, including a 
12-week Induction Period and a 40-week Maintenance Period), and a Safety Follow-up (SFU) Period 
(4 weeks). 
During the main part of this study, there will be approximately 11 scheduled study visits: Screening 
Visit(s) (Visit 1 at Weeks -4 6 to -1), multiple Treatment Visits (Visits 2-10 at Weeks 0, 2, 6, 12, 18, 
24, 3632, 42, and 52 [End of Treatment (EOT)]), and an SFU 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 Treatment Periodstudy is 
completed or earlier if treatment is discontinued early). 
To reflect the expanded 
Screening Period  
1.1. Synopsis – Overall 
Design 
4.1. Overall Design 
All participants who complete the 52-week Treatment Period will have the opportunity to continue their 
treatment in a 52-week Maintenance Extension Period. 
During the optional Maintenance Extension, there will be 5 scheduled visits: 4 Treatment Visits 
(Visits 11-14 at Weeks 65, 78, 91, and 104 [EOT]) and an SFU Visit (visit to occur 4 weeks after the 
last dose of study drug is received, which will be at Week 108 if the full Maintenance Extension is 
completed or earlier if treatment is discontinued early). 
Participants who do not enroll into the Maintenance Extension must complete the final SFU 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 
Maintenance Extension will not complete the SFU Period for the main part of the study; instead, they 
will directly enter the Maintenance Extension and complete a separate SFU Period, including the 
Week 108 Visit (4 weeks after receiving the last dose of MORF-057), for a maximum time on-study of 
114 weeks. 
To reflect the addition 
of the 52-week 
Maintenance Extension 
Period 
1.1. Synopsis – Overall 
Design 
4.1. Overall Design 
Any participant who has not shown clinical improvement (as determined by the Investigator) by Week 
24 will be discontinued from the study following an End of Treatment (EOT) Visit and a SFU Visit. 
To remove the Week 24 
clinical improvement 
assessment timepoint 
1.1. Synopsis  
4.1. Overall Design 
6.1. Study Treatment 
Description 
Descriptions of study treatment in the synopsis section were consolidated and updated to reflect 
study changes. Maintenance Extension Period (52 Weeks) was added to the dosing regimens for 
the 4 treatment groups and Table 4 in Section 6.1. 
After completion of the 12-week Induction Period, all participants randomized into the placebo group 
(Group 4) will be switched to receive an active MORF-057 regimen during the Maintenance Period. 
To reflect the addition 
of the 52-week 
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Section No. and Name 
Description of Change 
Brief Rationale 
The dosing regimens for the 4 treatment groups during the Induction and Maintenance Periods are 
shown below. 
Study Treatment: 
Enrolled participants will be randomized to a treatment group to receive active MORF-057 or placebo. 
Participants initially randomized into an active MORF-057 treatment group will receive an active 
treatment (according to study periodtreatment phase and group assignment) for the full 52-week 
Treatment Period. Participants initially randomized into the placebo group will be switched to an active 
MORF-057 regimen (200 mg once a day - evening [Q.D.-E]) after they complete the Induction Period 
and the Week 12 assessments. After participants complete the full 52-week Treatment Period, they will 
have the option to enter an additional 52-week Maintenance Extension Period. Participants All 
participants who completechoose to continue in the final SFU Period, including the Week 56 Visit 
(4 weeks afterMaintenance Extension will continue receiving the last dose ofsame MORF-057), will 
have a maximum time on study of 60 regimen they had during the Maintenance Period for up to an 
additional 52 weeks. The dosing regimens for the 4 treatment groups during the study are shown below. 
 
Induction Period (12 Weeks) 
Maintenance Period (40 Weeks)/ 
Maintenance Extension Period 
(52 Weeks) 
Group 1 
MORF-057 (200 mg B.I.D.) 
MORF-057 (100 mg B.I.D.) 
Group 2 
MORF-057 (100 mg B.I.D.) 
MORF-057 (100 mg B.I.D.) 
Group 3 
MORF-057 (100 mg Q.D.-M) 
MORF-057 (100 mg Q.D.-M) 
Group 4  
Placebo  
MORF-057 (200 mg Q.D.-E) 
The Sponsor may decide to allow participants to continue receiving MORF-057 by adding a 
Maintenance Extension Period via a subsequent regulatory submission. In this case, participants who 
complete the 52-week Treatment Period and associated assessments will continue receiving MORF-057 
through the Maintenance Extension Period before completing the SFU Period. 
1.1. Synopsis – Study 
Treatment 
The study drug will be supplied as IR capsules for oral administration (MORF-057 100 mg capsule or 
placebo). Participants will receive their study drug supplies in “morning bottles” and “evening bottles.” 
Each participant will receive the same number of “morning bottles” and “evening bottles” according to 
the respective study period (Induction or Maintenance/Maintenance Extension). In the morning, 
participants should take 1 capsule from EACH “morning bottle.” In the evening, participants should 
take 1 capsule from EACH “evening bottle.” Each participant maywill be instructed to take up to 
4 capsules per day during the Induction Period and 3 capsules per day during the Maintenance 
Period/Maintenance Extension Perioddepending on the number of bottles dispensed to the participant. 
To clarify treatment 
description and add the 
Maintenance Extension 
Period 

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Section No. and Name 
Description of Change 
Brief Rationale 
1.1. Synopsis – Study 
Schema 
4.1. Overall Design 
The study schema and corresponding footnotes were updated to include the 52-week 
Maintenance Extension Period. The new schema also shows the expanded Screening Period. 
To reflect the addition 
of the 52-week 
Maintenance Extension 
Period and the 
expanded Screening 
Period 
1.1. Synopsis – Study 
Schema 
4.1. Overall Design 
Study Schema: 
Abbreviations: 
D, day; 
P.O., by mouth 
V, visit; 
§ Sponsor may decide to allow participants to continue receiving MORF-057 by adding a Maintenance 
Extension Period via a subsequent regulatory submission. 
To reflect updated 
study schema 
1.1. Synopsis – Main 
Inclusion Criteria 
5.1. Inclusion Criteria 
Type of Participant and Disease Characteristics 
4. Demonstrated an inadequate response, loss of response, or intolerance to at least one of the following 
treatments (including oral aminosalicylates, corticosteroids, immunosuppressants, and/or advanced 
therapies for UC) in the opinion of the Investigator, as defined below: 
 a. Oral aminosalicylates (e.g., mesalamine, sulfasalazine, olsalazine, or balsalazide) 
• 
Signs and symptoms of persistently active disease during a current or prior course of at least 
4 weeks of treatment with ≥2.40 g/day mesalamine, 4 g/day sulfasalazine, 1 g/day 
olsalazine, or 6.75 g/day balsalazide 
Note: PatientParticipant cannot have had inadequate response, loss of response, or intolerance to more 
than 3 drugs in 2 classes of the following advanced therapies: 
c. JAK antagonists, including tofacitinib or upadacitinib 
e. Any investigational product with the same mechanism as one of those outlined above (a through d) 
or a novel mechanism of action 
Note: PatientParticipant who have a history of primary non-response to 2 or more of the advanced 
therapy classes above will not be eligible. PatientParticipant who have received treatment with these 
agents at sub-therapeutic doses or durations should be discussed with the Medical Monitor to assess 
eligibility. 
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5. Meets the following washout criteria of prior UC therapy relative to study Day 1: 
c. JAK antagonists, including tofacitinib or upadacitinib: at least 3 days1 week 
d. S1P receptor agonists, including ozanimod: at least 8 4 weeks 
Note: Participants who do not meet the full washout period but have the results of a local drug 
concentration level performed during the Screening window deemed by the Medical Monitor to be 
sub-therapeutic may be eligible for the study earlier than the full washout period. 
6. If the patientparticipant 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 SFU Period, with the exception of tapering oral corticosteroid dose after 12 weeks of being in the 
trial. 
a. Oral 5-Aminosalicylates (not exceeding 4.8 g per day): at least 2 weeks prior to study Day 1 
1.1. Synopsis – 
Exclusion Criteria 
5.2. Exclusion Criteria 
Medical Conditions 
7. Has ana potentially active bacterial, viral, or parasitic pathogenic enteric infection, including 
ClostridiumClostridiodes difficile (C. difficile); has 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 an active or latent tuberculosis (TB), as evidenced by any of the following: 
a. 
A diagnostic test for TB performed within 30 days ofprior to Screening or during the Screening 
Period that is positive, as defined as below: 
• 
A positive interferon gamma release assay (IGRA) test (e.g., Positive 
 
 
 TB test) or 2 consecutive indeterminate 
 IGRA tests 
OR 
• 
A purified protein derivative (PPD) skin test ≥5 mm 
b. ChestA chest X-ray or imaging per local guidelines within 3 months ofprior to Screening where 
active or latent pulmonary TB cannot be excluded 
Note: Participants who have tested negative for TB at a certified local lab using an IGRA test within 3 
months prior to Screening are not required to repeat this test during the Screening Period if that 
participant has no clinical signs or symptoms of TB and no known exposures/increased risk factors 
since the last negative TB test (according to the Investigator’s clinical judgement), and the test result is 
available in the participant’s medical record 
Note: PatientsParticipants with a history of latent TB may be enrolled if it is being treated per localthey 
complete an assessment for evidence of active TB versus latent TB. Documentation will include a chest 
X-ray or imaging per local guidelines during the Screening Window and no signs, symptoms, or 
evidence of ongoing active TB. Participants have had treatment per the local standard of care for a 
minimum of 2 weeks before the first dose of study drug with no evidence of ongoing active TB or who 
haveOR documentation of completing appropriate treatment for latent TB within 2 years before Day 1 
To revise exclusion 
criteria 
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Brief Rationale 
Participants with inadequate documentation of treatment should be cleared by a TB specialist before 
enrollmentof the study. See Section 8.2.2.1 for more details. 
9. Tests positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the 
Screening Period. Testing to be performed according to site specific testing procedures and 
country-specific requirements.Has a positive severe acute respiratory syndrome coronavirus 2 
(SARS-CoV-2) test result during the Screening Period. Testing for SARS-CoV-2 is required only per 
local regulations. Participants who have a positive test result can be randomized after a subsequent 
negative test result during the Screening Period. 
16. g. International normalized ratio >1.5. Participants with an international normalized ratio >1.5 due 
to anticoagulant therapy (e.g., Coumadin) may only be enrolled after a consultation with the Medical 
Monitor. 
1.1. Synopsis – 
Exclusion Criteria 
5.2. Exclusion Criteria 
Prior/Concurrent Clinical Study Experience 
28. PreviousKnown allergies/hypersensitivity to any component of the study drug and/or previous 
exposure to MORF-057 and/or a known hypersensitivity to drugs with a similar mechanism to 
MORF-057 
To update exclusion 
criteria regarding 
participant 
allergies/hypersensitivit
ies 
1.1. Synopsis – Study 
Treatment 
Study Treatment: 
MORF-057 is a small molecule therapy that selectively inhibits the α4β7 integrin. The study drug will 
be supplied as immediate-release capsules for oral administration (MORF-057 100 mg capsule or 
placebo). The dose regimens for the 4 treatment groups are provided below: 
To update for clarity 
1.1. Synopsis – 
Statistical Methods: 
Sample Size 
Determination 
9.5. Sample Size 
Determination 
The sample size was determined based on the primary endpoint of clinical remission at Week 12 by 
using the Chi-Squared Test to compare two proportions. A sample size of 70 participants per group 
(giving a total of 280) will provide 80% power to detect a difference of 15% in the clinical remission 
rate between MORF-057 and placebo, based on the use of a two-sided test at the alpha=0.10 level of 
significance. The calculation is based upon an assumed placebo remission rate of 7%. 
To identify the 
calculation for 
determining sample 
size 
1.1. Synopsis – 
Statistical Methods: 
Primary Efficacy 
Endpoint 
9.2.3.1. Primary Efficacy 
Endpoint 
The primary analysis will be repeated on the PP Population as a sensitivity analysis. Other sensitivity 
analyses for the primary efficacy endpoints may also be performed as appropriate. The primary efficacy 
endpoint will be analyzed for the subgroups defined based on someselected categorized demographic 
and baseline variables, e.g., age, gender, race, exposure to an advanced therapy treatment for UC 
(advanced therapy-naïve and advanced therapy-experienced). The details will be described in the 
Statistical Analysis Plan (SAP). 
To clarify the primary 
efficacy endpoint 
1.1. Synopsis – 
Statistical Methods: 
Exploratory Efficacy 
Endpoints 
9.2.3.3. Exploratory 
Efficacy Endpoints 
All the continuous exploratory efficacy endpoints expressed as change from baseline at Week 12 as 
defined in Section 3 (e.g., non-endoscopic biomarkers of inflammation, PROs) will be analyzed in the 
FAS using an analysis of covariance (ANCOVA) model with treatment and randomization stratification 
factors as factors and baseline values as a covariate. 
To identify the type of 
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Description of Change 
Brief Rationale 
1.1. Synopsis – 
Statistical Methods: 
Safety Analyses 
9.2.4. Safety Analyses 
The safety analyses will be performed for the 12-week Induction Period and, the overall 52-week 
Treatment Period, and the 52-week Maintenance Extension Period plus the Safety Follow-up Period. In 
the safety analyses for the 12-week Induction Period, the participants initially randomized into the 
placebo group and switched to an active MORF-057 regimen after the Week 12 assessments will be 
analyzed as the placebo group. In the safety analyses for the overall 52-week Treatment Period and 
52-week Maintenance Extension Period, the placebo recipients switched to an active MORF-057 
regimen will be analyzed according to the active MORF-057 regimen they received after Week 12, and 
their data will be presented separately based on only the safety data collected after the start of the 
MORF-057 dose. Week 12 assessments, i.e., during the 40-week Maintenance Period and Safety 
Follow-up Period. 
To add safety analyses 
of the Maintenance 
Extension 
1.1. Synopsis – 
Statistical Methods: 
Pharmacodynamics 
Analyses 
9.2.6. 
Pharmacodynamics 
Analyses 
The exploratory PD endpoints (changes over time in α4β7 and α4β1 receptor occupancy,occupancies and 
blood CCR9 mRNA level, and blood lymphocyte subsets) will be summarized descriptively. Additional 
analysis of PD endpoints may be described 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 PD 
exploratory endpoints. 
Section 9.2.6. 
The exploratory PD endpoints (changes over time in α4β7 receptor occupancy, changes over time in 
and α4β1 receptor occupancy,occupancies and blood CCR9 mRNA level, and blood lymphocyte 
subsets) will be summarized descriptively. 
To clarify how the 
exploratory PD 
endpoints will be 
reported 
1.1. Synopsis – 
Statistical Methods: 
Analyses for Induction 
Period, 52-week 
Treatment Period, and 
Maintenance Extension 
Period 
9.3. Analyses for 
Induction Period, 
52-week Treatment 
Period, and Maintenance 
Extension Period 
Analyses for Induction Period and Total, 52-week Treatment Period, and Maintenance Extension 
Period 
The Treatment Period in the main part of the study includes 2 treatment periods: 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 
one for the 52-week Total Treatment Period (i.e., the 12-week Induction Period plus the 40-week 
Maintenance Period and Safety Follow-up Period). The details of the analyses will be described in the 
SAP. The results for the main part of the study will be reported in the Clinical Study Report. 
Additional analysis of the optional 52-week Maintenance Extension Period for the participants enrolled 
into the Maintenance Extension will also be performed as appropriate. The results for the Maintenance 
Extension will be reported in a Clinical Study Report Addendum. 
Induction Period Analysis 
The analysis of the 12-week Induction Period will be performed after all the participants have 
completed the Induction Period (i.e., completed the Week 12 visitassessments or discontinued the study 
before the Week 12 assessments). The analysis will formally evaluate the efficacy (including the 
primary and secondary efficacy endpoints, and all the exploratory efficacy endpoints defined by Week 
12), and safety of MORF-057 vs. placebo during the 12-week Induction Period. The PK and PD data 
during the 12-week Induction Period will also be summarized. 
To add statistical 
analyses of the 
Maintenance Extension 
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Total 52-week Treatment Period Analysis 
The analysis of the 52-week Total Treatment Period will be performed after all the participants have 
completed the Week 52 assessments (and Safety Follow-up Period for participants not rolling over into 
the Maintenance Extension Period) or discontinued from the study before the Week 52 assessments. 
The analysis will formally evaluate the efficacy (including all the exploratory efficacy endpoints 
defined by Week 52), PK, PD, and safety of MORF-057 during the 52-week Total Treatment Period 
(and the Safety Follow-up Period for participants not rolling over into the Maintenance Extension 
Period). The cumulative data, including those from the Induction Period, will be used in this analysis. 
Maintenance Extension Analysis 
The analysis of the Maintenance Extension will be performed after all the participants enrolled into the 
Maintenance Extension have completed the 52-week Maintenance Extension Period and the Safety 
Follow-up Period or discontinued the study before the Week 104 assessment. The analysis will evaluate 
the safety of MORF-057 and selected efficacy endpoints as appropriate during the Maintenance 
Extension plus the Safety Follow-up Period. 
1.2. Schedule of 
Activities (SoA)  
Section 1.2. was updated to reflect the changes in study procedures. Table 1 Schedule of Activities 
for the Treatment Period was added. A new SoA table (Table 2) identifies the timepoints and 
assessments of the Maintenance Extension Period. Addition of these 2 tables required 
renumbering tables. 
The SoA for the Treatment Period is provided in Table 1. The SoA for the Maintenance Extension 
Period is provided in Table 2. 
Abbreviations: 
ClostridiumClostridiodes 
ICF, Informed Consent Form; 
IGRA, interferon gamma release assay; 
To reflect changes to 
the Induction Period 
and include activities 
during the Maintenance 
Extension Period  
1.2. Schedule of 
Activities (SoA) 
The SoA Table 1 was updated to clarify the Induction and Maintenance Periods, reflect the 
expanded Screening Period, add Stage 1 and 2 at Visits 5 and 10 with testing updated per 
respective stage, collect information on participant’s change in substance use at Stage 2 of Visits 5 
and 10/EOT, remove Visit 11 from the SFU label, add /EOT to the corresponding mentions of 
Visit 10, clarify SARS-CoV-2 and TB testing, clarify back-up stool collection at Screening Stage 1 
and optional stool collection for future research, clarify PK time windows, clarify endoscopy 
biopsies, include informed consent for the Maintenance Extension, remove the Week 24 clinical 
improvement review, and add confirm initiation of study drug for the Maintenance Period at 
Visit 5 Stage 2. 
To update study 
activities during the 
52-week Treatment 
Period 
1.2. Schedule of 
Activities (SoA) 
Dispense study drug was added to Visit 10. 
To update study 
activities 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “b”: 
No specific tests or procedures are required for unscheduled visits. Results of any study procedures 
performed at an unscheduled visit will be recorded and collected for the study. b  Clinically relevant 
To clarify study 
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laboratory testing or re-testing (e.g., hematology, coagulation, serum chemistry, or urinalysis) may be 
performed at unscheduled visits. 
1.2. Schedule of 
Activities (SoA) 
Addition of definition of Visit 5 Stage 1 and Stage 2 to Table 1, footnote “c” required 
reorganization of footnotes. 
To include definitions 
of Visit 5 Stage 1 and 
Stage 2 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “c”: 
If participant discontinues early from the study Treatment Period, perform the Visit 10/EOT procedures 
and schedule Visit 11/SFU for 28 days (+7 days) after the participant takes the last dose of study drug 
(unless consent is withdrawn). 
Visit 5 is split into Stage 1 and Stage 2 to clarify the timing of the endoscopy procedure. The endoscopy 
procedure at Visit 5 Stage 1 should be performed before the Visit 5 Stage 2 in-clinic assessments have 
been completed. 
To include timing of 
the endoscopy 
procedure 
1.2. Schedule of 
Activities (SoA) 
Addition of definition of Visit 10 Stage 1 and Stage 2 to Table 1, footnote “d” required 
reorganization of footnotes. 
To include definitions 
of Visit 10 Stage 1 and 
Stage 2 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “d”: 
Participants not participating in Maintenance Extension Period will complete the SFU Visit, which 
should be performed 28 days (+7 days) after the participant takes the last dose of study drug. Eligible 
participants who choose to participate in the Maintenance Extension Period after Visit 10/EOT will not 
attend the SFU Visit. 
Visit 10 is split into Stage 1 and Stage 2 to clarify the timing of the endoscopy procedure. The 
endoscopy procedure at Visit 10 Stage 1 should be performed before the Visit 10 Stage 2 in clinic 
assessments have been completed. 
To include timing of 
the endoscopy 
procedure 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “ce”: 
If the participant discontinues early from the study Treatment Period, perform the Visit 10/EOT 
procedures and schedule Visit 11/SFU for 28 days (+7 days) after the participant takes the last dose of 
study drug (unless consent is withdrawn). 
To clarify the visits 
after early 
discontinuation 
1.2. Schedule of 
Activities (SoA)  
Table 1, Footnote “df”: 
Participants not participating in the Maintenance Extension Period will complete the SFU Visit, which 
should be performed 28 days (+7 days) after the participant takes the last dose of study drug. Eligible 
participants who choose to participate in the Maintenance Extension Period after Visit 10/EOT will not 
attend the SFU Visit complete a separate SFU Visit at Week 108 (Table 2). 
To clarify study 
procedures 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “eg”: 
If the participant discontinues early from the study Treatment Period, perform the Visit 11/SFU 
procedures 28 days (+7 days) after the participant takes the last dose of study drug (unless consent is 
withdrawn). 
To reflect the removal 
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Table 1, Footnote “fh”: 
The SFU Visit is to occur 28 days (+7 days) after the last dose of study drug is received. If the EOT 
Visit occurs before Day 365, the day for the SFU Visit can be adjusted according to the date of last 
study drug dose. 
To clarify the timing of 
the study procedure 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “hj”: 
Enrollment may occur at any point within a 2842-day window of when all screening procedures have 
been completed and all results required to assess eligibility are available. Enrolled participants will be 
randomized to a treatment group. Enrollment will usually occur the same day as first dosing, but if 
dosing the same day is not feasible, then enrollment will be considered Day -1 and first dose will be 
considered Day 1. 
To reflect the expanded 
Screening Period and 
clarify study procedures  
1.2. Schedule of 
Activities (SoA) 
8.2.2.2. SARS-CoV-2 
Table 1, Footnote “ik”: 
SARS-CoV-2 test will be performed during the Screening Period according to site-specific procedures 
and country-specific requirements.Testing for SARS-CoV-2 is required only per local regulations. 
Participants who have a positive test result will be excluded from randomization until a subsequent test 
result is negative. 
Section 8.2.2.2.: 
All participants will complete SARS-CoV-2 screening to determine eligibility.Testing for SARS-CoV-2 
is required only per local regulations. Participants who have a positive test result will be excluded from 
randomization until a subsequent test result is negative. 
To allow re-testing of 
participants who tested 
positive for 
SARS-CoV-2 during the 
Screening Period 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “jl”: 
TB test. Participants who have tested negative for TB at a certified local lab using an 
interferon gamma release assay (IGRA) test (e.g., 
 
 TB test) within 3 
months prior to Screening are not required to repeat this test during the Screening Period if that 
participant has no clinical signs or symptoms of TB and no known exposures/increased risk factors 
since the last negative TB test (according to site specific procedures and country-specific requirements 
the Investigator’s clinical judgement). In cases where the 
 IGRA test is indeterminate, 
the participant may have the test repeated once, and if their second test is negative, they will be eligible. 
In the event 
 is unavailable, the Investigator has the option to perform aThe purified 
protein derivative skin test should be performed when the IGRA test is not possible or if both tests are 
required by local guidelines. 
To clarify TB screening 
requirements 
1.2. Schedule of 
Activities (SoA) 
Addition of review of change in substance use to Table 1, footnote “m” required reorganization of 
footnotes. 
To include review of 
change in substance use 
1.2. Schedule of 
Activities (SoA) 
5.3. Lifestyle 
Considerations 
Table 1, Footnote “m”: 
Collect information on the participant’s change in substance use (e.g., alcohol, tobacco, and drugs). 
Section 5.3.: 
No new non-pharmacological therapies should be started during the study period. Information should 
be collected on the participant’s change in substance use (e.g., alcohol, tobacco, and drugs) per the 
SoA in Section 1.2. 
To include review of 
change in substance use 
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8.8.6. 
Pregnancy/Menopause 
Testing 
Table 1, Footnote “mp”: 
Serum test for follicle-stimulating hormone level to be performed only for female participants of 
non-childbearing potential who are not surgically sterile. 
Section 8.8.6.: 
A serum test for follicle-stimulating hormone (FSH) level will be performed at Screening only for 
female participants of non-childbearing potential who are not surgically sterile. 
To align with central 
lab processes and 
Appendix 3 
1.2. Schedule of 
Activities (SoA) 
8.6. Stool Collection 
Table 1, Footnote “nq”: 
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 
stored as described in the sample collection instructions and brought to the clinic on the day of the site 
visit. If the participant is unable to produce a stool sample at the Stage 1 Screening Visit, they can 
collect a sample at home and return it to the site. Note: Sample is to be collected prior to bowel 
preparation for Visits 5 and 10/EOT. 
Section 8.6.: 
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 stored as described in the sample collection instructions and brought to the 
clinic on the day of the site visit. If the participant is unable to produce a stool sample at the Stage 1 
Screening Visit, they can collect a sample at home and return it to the site. 
To clarify back-up stool 
sample collection at 
Screening Stage 1 Visit 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “or”: 
Participants will be provided the option to participate in the Maintenance Extension Period. 
Participants who want to continue in the Maintenance Extension will be required to provide informed 
consent. If the Sponsor decides to add a Maintenance Extension Period, willing participants should sign 
the relevant revised ICF, as required. 
To identify when the 
separate ICF for the 
Maintenance Extension 
Period must be signed  
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “ps”: 
ECGs to be performed before the AM dose and 2 hours (±30 minutes) after the AM dose during the 
Induction and Maintenance Periods. ECGs will be obtained after the participant has rested for at least 
10 minutes in the supine position. 
To clarify the ECG 
procedure 
1.2. Schedule of 
Activities (SoA) 
8.8.1. Physical 
Examinations 
Table 1, Footnote “qt”: 
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, the 
type of exam (if necessary to be performed at all) will be at the Investigator’s discretion and 
determined based on the reason for the visit. The Screening exam will include collection of height and 
weight. 
Section 8.8.1.: 
A complete physical exam is required at Screening and, Visit 10/EOT, and Visit 14/EOT; and a targeted 
exam may be performed at all other required visits. For unscheduled visits, the choice of whether to 
perform a complete or targeted physical exam (if necessary to be performed at all) is at the discretion of 
the Investigator and will depend on the reason for the unscheduled visit. 
To clarify type of 
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8.8.2. Vital Signs 
Table 1, Footnote “ru”: 
Vital signs to be recorded at allmost visits. At unscheduled visits, vital signs are not required and are at 
the discretion of the Investigator. These will include blood pressure, heart rate, respiratory rate, and 
temperature. Vital signs are to be taken before blood collection for laboratory tests. Blood pressure and 
pulse measurements should be preceded by at least 10 minutes of rest for the participant. 
Section 8.8.2.: 
Vital signs to be recorded at allmost visits as summarized in the SoA (Section 1.2). At unscheduled 
visits, vital signs are not required and are at the discretion of the Investigator. These will include blood 
pressure, heart rate, respiratory rate, and temperature. 
To clarify the vital 
signs recording times 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “vy”: 
PK testing at Visits 2, 3, 5, 7, and 10/EOT: Blood samples will be collected before the AM dose and at 
1, (±10 min), 2, (±15 min), and 4 (±30 min) hours after the AM dose. Time windows for PK sampling 
can be found in Section 8.10.1. For all pre-AM dose sampling, the samples should be obtained before 
the AM dose is administered. If consent is provided by the participant, these samples may also be used 
for future PK research studies. 
Table 1, Footnote “wz”: 
PK testing at Visits 4, 6, 8, and 9: Blood sample will be collected before the AM dose and 1 hour (±10 
min) after the AM dose. For all pre-AM dose sampling, the samples should be obtained before the AM 
dose is administered. If consent is provided by the participant, these samples may also be used for 
future PK research studies. 
To clarify the PK 
samples from 
participants who 
consent may also be 
used for future PK 
research studies  
1.2. Schedule of 
Activities (SoA) 
Addition of optional stool sample to Table 1, footnote “gg” required reorganization of footnotes. 
To clarify optional stool 
sample for future 
research 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “gg”: 
Participation in future research sample collection is optional. Fecal samples for microbiome analysis 
will be collected before the AM dose on Visits 2, 5, and 10/EOT. Fecal samples may be collected at any 
time on the day prior to the scheduled visit day. 
To clarify optional stool 
sample for future 
research 
1.2. Schedule of 
Activities (SoA) 
Removal of footnote “hh” Table 1 required reorganization of footnotes. 
Any patient who has not shown clinical improvement (as determined by the Investigator) by Week 24 
will be discontinued from the study following an EOT Visit and a SFU Visit. 
To remove the Week 24 
clinical improvement 
assessment timepoint 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “ddhh”: 
Full colonoscopy is optional at any timepoint if the Investigator deems it necessary. However, if the 
patientparticipant has had UC for over 7 years, he/she must undergo a full colonoscopy (rather than 
sigmoidoscopy) at Screening if a full colonoscopy has not been performed in the last 2 years. Colonic 
mucosa biopsies will be collected for histopathology and optional future research studies. 
To identify the number 
of biopsies for 
histopathology and the 
optional future research 
(for participants who 
consent) and clarify the 
procedures 
1.2. Schedule of 
Activities (SoA) 
Addition of a separate footnote on the specifics of the Screening endoscopy biopsies to Table 1, 
footnote “ii” required reorganization of footnotes. 
To clarify the Screening 
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Table 1, Footnote “ii”: 
During the Screening endoscopy, up to 6 colonic mucosa biopsies will be collected. Two biopsies for 
the required histopathology must be collected from the worst inflamed area, 15-25 cm from the anus. 
Record the extent of disease in centimeters from the anal verge. If consent is provided by the 
participant, 4 additional mucosa biopsies may be collected for the optional future research studies (2 
biopsies from the worst inflamed area and 2 from a non-inflamed/least inflamed area). If consent is 
provided by the participant, any remaining tissue from the required histopathology biopsies may be 
used for future research studies. See Section 8.7.1 for details on biopsy requirements. 
To clarify the Screening 
endoscopy biopsies 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “eejj”: 
The Visit 5 Stage 1 endoscopy procedure should be performed afterbefore the in-clinic assessments at 
Visit 5 Stage 2 have been completed. 
To clarify the timing of 
the Visit 5 endoscopy 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “ffkk”: 
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. Participants who complete the EOT Visit within 2 
months after the Week 12 endoscopy are not required to repeat the procedure. 
To clarify the 
endoscopy 
requirements 
1.2. Schedule of 
Activities (SoA) 
Addition of a separate footnote on the endoscopy biopsy specifics of the Visit 5 Stage 1 and 
Visit 10/EOT Stage 1 to Table 1, footnote “ll” required reorganization of footnotes. 
To clarify the 
Visits 5 and 10/EOT 
endoscopy biopsies 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “ll”: 
Collect up to 6 biopsy samples total (2 for required histopathology and 4 for optional future research 
studies [if consent is provided by the participant]). If consent is provided by the participant, any 
remaining tissue from the required histopathology biopsies may be used for future research studies. All 
biopsies should be collected from the same distance from the anus as collected at the Screening Visit, 
regardless of the tissue state at the time of the sampling. Record the extent of disease in centimeters 
from the anal verge. Record the number of centimeters from the anus in which biopsies are collected at 
all follow-up visits into the Requisition Form. 
To clarify the 
Visits 5 and 10/EOT 
endoscopy biopsies 
1.2. Schedule of 
Activities (SoA) 
Addition of a footnote on clarifying study treatment handling for participants not participating in 
the Maintenance Extension Period to Table 1, footnote “nn” required reorganization of footnotes. 
To clarify study 
treatment handling for 
participants not 
participating in the 
Maintenance Extension 
Period 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “nn”: 
Participants not participating in the Maintenance Extension Period should return all study drug to the 
site. No additional dosing should occur after the completion of the EOT Visit. 
To clarify study 
treatment handling for 
participants not 
participating in the 

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Maintenance Extension 
Period 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “iioo”: 
At Visit 5, the Induction Period study drugs kits supplied at the previous visit should be used for the 
AM and PM dose. Please note, a new supply of Maintenance Period study drugs kits will be provided 
at the conclusion of Visit 5, but the new supply should be started the day AFTER the required 
sigmoidoscopy is performed. This is to ensure that participants moving onto the Maintenance Period 
are on the appropriate MORF-057 treatment and dose. Participants should use the Maintenance Period 
study drug kits for all future doses after the completion of Visit 5. 
To clarify study drug 
dispensing at Visit 5 
1.2. Schedule of 
Activities (SoA) 
Addition of a footnote on clarifying study drug dispensing at Visit 10/EOT to Table 1, footnote 
“pp” required reorganization of footnotes. 
To clarify study drug 
dispensing at 
Visit 10/EOT 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “pp”: 
For participants continuing treatment in the Maintenance Extension, additional study drug will be 
dispensed at Visit 10. 
To clarify study drug 
dispensing at 
Visit 10/EOT 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “jjqq”: 
AM dosing required on-site for all visits except the SFU Visit. 
To align with document 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “kkrr”: 
At Visit 10/EOT, participants not participating in the Maintenance Extension Period will only receive 
an AM dose for the day. No PM dose will be provided. 
To clarify dosing 
instructions for 
participants not 
participating in the 
Maintenance Extension 
Period  
1.2. Schedule of 
Activities (SoA) 
Addition of a footnote to add a follow-up contact to Table 1, footnote “ss” 
To add a follow-up 
contact to ensure 
participants begin using 
the study drugs for the 
Maintenance Period 
1.2. Schedule of 
Activities (SoA) 
6.4. Study Treatment 
Compliance 
Table 1, Footnote “ss”: 
Site staff will contact the participants, by phone or other forms, on the next business day after the 
Visit 5 clinic visit is complete to confirm the participants are using the new supply of study drugs for 
the Maintenance Period. Record the date and time of the participant's first Maintenance Period dose. 
Section 6.4.: 
The site staff will contact participants, by phone or other forms, on the next business day after the 
Visit 5 clinic visit to confirm the participants have switched from the Induction Period study drug to the 
new Maintenance Period study drug bottles. 
To add a follow-up 
contact to ensure 
participants begin using 
the study drugs for the 
Maintenance Period 
2.1. Study Rationale 
AnotherOther therapeutic options recently approved for the treatment of UC isare Janus kinase (JAK) 
inhibitors, such as the small molecule tofacitinib (
) or upadacitinib (
). 
Upadacitinib was added 
to reflect currently 
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approved JAK 
inhibitors 
2.3.2.1. Risks of 
MORF-057 
• Progressive multifocal leukoencephalopathy (PML) is a fatal opportunistic infection of the central 
nervous system and has been associated with systemic immunosuppressants, including integrin receptor 
antagonists (e.g., natalizumab and vedolizumab). Natalizumab, a monoclonal antibody that inhibits both 
α4β1 and α4β7 integrins, has been associated with PML, a serious brain infection. One case of PML was 
reported in a patient treated with vedolizumab (α4β7 integrin antagonist) during post-marketing setting 
in an 
 (vedolizumab)-treated patient with multiple contributory factors has been reported in 
the post-marketing setting (e.g., human immunodeficiency virus [HIV] 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 pProgram (RAMP). 
To update risks of 
MORF-057 
4.2. Scientific Rationale 
for Study Design 
The 52-week treatment will be followed by an optional 52-week Maintenance Extension Period. This 
extension will provide the participants further access to the study drug and collect additional safety and 
efficacy data up to 104 weeks of exposure. 
To add rationale for 
adding the Maintenance 
Extension 
4.3. Justification for 
Dose 
The ICH E4 guidelines as well as the Guideline on the development of new medicinal products for the 
treatment of UC (CHMP/EWP/18463/2006 Rev.1) accept placebo as an acceptable comparator 
(monotherapy or add-on to established therapy) in clinical trials. 
The placebo group serves as a control to evaluate the safety as well as efficacy of MORF-057 in a 
contemporaneous population. 
All participants will be allowed to continue stable background therapy to which either MORF-057 or 
placebo will be added for 12 weeks. 
To add a justification 
for use of placebo 
4.4. End of Study 
Definition 
A participant is considered to have completed the study if he/she has completed all periodsthe 
Screening and 52-week Treatment Periods of the main part of the study and attended the SFU Visit OR 
has completed the Week 52/EOT Visit and has been enrolled into the Maintenance Extension Period. 
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 sSchedule of aActivities (SoA) for the last participant in 
the main part of the study globally. 
To define participant 
study completion 
5.1. Inclusion Criteria 
Weight 
9. Has a body mass index (BMI) ≥1718.0 at Screening 
To align with synopsis 
5.4. Screen Failures 
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. For 
example, participants who test positive for SARS-CoV-2 during screening can be re-screened once they 
have a negative PCR test and are symptom-free. Re-screened participants should be assigned a new 
participant number for every sScreening/re-screening event. 
To allow re-testing of 
participants who test 
positive for 
SARS-CoV-2 during 
Screening 
5.4. Screen Failures 
Note: Participants who are unable to complete all required procedures or assessments within the 
Screening Window due to technicalities may be eligible to extend their Screening Period up to 2 weeks 
based on an agreement between the Investigator and the Sponsor Medical Monitor. Screening activities 
To clarify the 
re-screening process 
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that require repeating will be determined by the Sponsor Medical Monitor and the process outlined in 
the Monitoring Plan. 
6.1. Study Treatment 
Description – Table 3. 
Table 3. Study Treatment was renumbered from Table 1 due to addition of tables. 
To update table 
numbering 
6.1. Study Treatment 
Description – Table 3. 
Packaging and 
Llabeling 
30 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. 
30 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. 
To clarify the number 
of capsules per bottle 
6.1. Study Treatment 
Description – Table 3. 
Abbreviations: 
B.I.D., twice a day; 
IR, immediate-release. 
To update abbreviations 
for the table 
6.1. Study Treatment 
Description – Table 4. 
Table 4. Treatment Groups was renumbered from Table 2 due to addition of tables. 
To update table 
numbering 
6.1. Study Treatment 
Description – Table 4. 
Group title 
Group 1 
Group 2 
Group 3 
Group 4 
To include the 
Experimental 
Maintenance Period 
Type 
• Induction: 
Experimental 
• Maintenance 
/Maintenance 
Extension: 
Experimental 
• Induction: 
Experimental 
• Maintenance 
/Maintenance 
Extension: 
Experimental 
• Induction: 
Experimental 
• Maintenance 
/Maintenance 
Extension: 
Experimental 
• Induction: 
Experimental 
• Maintenance 
/Maintenance 
Extension: 
Experimental 
Maintenance 
Period dosing 
regimen 
(40 Weeks)/ 
Maintenance 
Extension 
Period dosing 
regimen (52 
Weeks) 
 
 
 
 
6.3.2. Blinding 
This is a double-blind study in which the Sponsor, participants, site staff, site pharmacy, Investigators, 
and outcomes assessors will be blinded to the study treatment through Week 12. …. Each participant 
will receive the same number of “morning bottles” and “evening bottles” according to the respective 
study period (Induction or Maintenance)./Maintenance Extension). …. TheAfter the database lock for 
the Induction Period analyses, the analysis results will be unblinded at the population level. However, 
To clarify the blinding 
process  

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the access to treatment assignment for individual participants will be limited within a very small 
subgroup, includingto only the necessary persons from the Sponsor and the external vendors that will 
generate the unblinded analysis results and perform the validation. All other Sponsor personnel, the 
project study team, site Investigator, site staff, and study participants will remain blinded to the 
individual treatment assignments through the end of the study. 
If the report requires expedited reporting to one or more regulatory agenciesagency, a copy of the 
report, identifying the participant’s treatment assignment, maywill be sent to the Rregulatory Aagency 
in accordance with local regulations and/or Sponsor policy. 
6.6. Overdose 
• Overdose with or without clinical symptoms or abnormal laboratory results should be recorded on the 
overdose electronic Case Report Form (eCRF) within 24 hours of becoming aware. 
• AEs and SAEs associated with overdose will be recorded on the AE CRFeCRF, and SAEs associated 
with overdose will be reported via the SAE reporting procedure outlined in Section 8.9. 
To specify the process 
of capturing overdose 
information  
6.7.2. Allowed 
Medications for the 
Treatment of Ulcerative 
Colitis – Table 5. 
Table 5. Corticosteroid Equivalent Doses† was renumbered from Table 3 due to addition of 
tables. 
To update table 
numbering 
6.7.2.2. Rescue 
Therapies 
Anti-diarrheals for control of chronic diarrhea and antibiotics for control of infection are not 
considered rescue medication. 
To align with 
Section 7.1.1. 
6.7.3. 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 at a dose as 
per local guidelines but not exceeding 81325 mg per day.) 
To clarify the 
acceptable use of 
aspirin 
6.7.3. Prohibited 
Medications – Table 6. 
Table 6. Examples of Drugs Potentially Altering Exposures to MORF-057# was renumbered from 
Table 4 due to addition of tables. 
To update table 
numbering 
7.1.1. Permanent 
Discontinuation 
• Lack of efficacy, defined as: 
o Administration of a rescue medication (a new medication or increase in dose of a baseline medication 
to treat new or unresolved UC symptoms with the exception of returning the background corticosteroid 
therapy dose to baseline level). Anti-diarrheals for control of chronic diarrhea and antibiotics for 
control of infection are not considered rescue medication. 
• Pregnancy or planned pregnancy of the female participant or female partner of a male participant as 
the participant will be unblinded (see Section 8.9.5) 
• Non-compliance with study treatment (see Section 6.4) or study procedures 
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. In rare 
circumstances, consideration may be given to the participant when there is a compelling 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. 
To clarify permanent 
discontinuation criteria 
7.2. Participant 
Discontinuation/Withdra
wal from the Study 
The participant should be encouraged to complete the EOT Visit (Visit 10) at the time of study drug 
discontinuation and the SFU Visit (Visit 11) at 28 days (+7 days) after the last dose of study drug. 
To clarify 
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8.1. Medical History 
The participant’s demographics and complete medical and surgical history, including initial UC 
diagnosis date, UC onset date, and history of UC medication use, will be collected during Screening 
and recorded in the participant’s eCRF. 
To clarify medical 
history details 
8.2.2.1. Tuberculosis 
All participants will complete TB screening to determine eligibility. Participants with a negative TB test 
and chest X-ray (or imaging per local guidelines) not suggestive of active or TB may be enrolled. 
Participants with a history of active TB may be enrolled if it has been adequately treated with no evidence 
of current active TB. Participants with a positive TB test must be assessed for evidence of active TB 
versus latent TB will be excluded, including. Please refer to Table 7 for TB Screening and eligibility 
details. Exclusion criteria includes those participants with a positive TB diagnostic test performed within 
30 days ofprior to Screening or during the Screening Period (e.g., a positive IGRA test such as a 
 
 TB test, 2 consecutive indeterminate IGRA tests, or a PPD skin test ≥5 mm), 
and those who had a chest X-ray within 3 months ofprior to Screening where active or latent pulmonary 
TB could not be ruled outexcluded. 
The 
GRA test should be performed at Screening on all participants., except for those 
who have had a confirmed negative IGRA test within 3 months prior to Screening. The PPD skin test 
should be performed when the 
IGRA test is not possible or if both tests are required by 
local guidelines. Test results should be interpreted as shown below: 
• 
For regions that require both 
IGRA and PPD tests, if either test is positive, the 
TB test is considered positive. 
If the 
IGRA test is indeterminate, then the Investigator should perform a second 
IGRA test to rule out a positive test result. If testing remains indeterminate or is 
positive, then the participant is considered TB positive. 
The PPD skin test should be performed when 
 test is not possible. PPD should be read 
by a licensed healthcare professional between 48 and 72 hours after administration. A reaction of 
induration ≥5 mm is considered a positive reaction. 
Participants who have tested negative for TB at a certified local lab using an IGRA test within 3 months 
prior to Screening are not required to repeat this test during the Screening Period if that participant 
has no clinical signs or symptoms of TB, no known exposures/increased risk factors since the last 
negative TB test (according to the Investigator’s clinical judgement), and the test result is available and 
adequately documented in the participant’s medical record. 
To update the TB test 
methods 
8.2.2.1. Tuberculosis – 
Table 7. 
Table 7. Summary of Tuberculosis Screening and Eligibility was added. The table depicts 
inclusion/exclusion criteria based on IGRA, 
 TB test results. 
Addition of the table required renumbering tables. 
To clarify TB testing 
inclusion/exclusion 
criteria 
8.2.2.1. Tuberculosis – 
Table 7. 
Test Performed Within 30 Days Prior to Screening or 
During the Screening Period 
Inclusion 
Exclusion 
A positive interferon gamma release assay (IGRA) test 
(e.g., 
 or T-SPOT® TB test) 
  
X 
2 consecutive indeterminate IGRA tests  
  
X 
To clarify TB testing 
inclusion/exclusion 
criteria 
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A purified protein derivative (PPD) skin test ≥5 mm 
  
X 
Test Performed Within 3 Months Prior to Screening 
Inclusion 
Exclusion 
A chest X-ray within 3 months prior to Screening where 
active or latent pulmonary TB cannot be excluded 
 
X 
A negative test for TB at a certified local lab using an IGRA 
test (e.g., 
 
 TB test) within 
3 months prior to Screening AND 
• 
Has no clinical signs or symptoms of TB 
• 
No known exposures/increased risk factors since 
the last negative TB test (according to the 
Investigator’s clinical judgement) 
• 
The test result is available and adequately 
documented in the participant’s medical record 
Note: Re-testing is not required at Screening if all the 
above criteria are met  
X 
  
History of Latent TB 
Inclusion 
Exclusion 
Study participants with a positive TB test must be assessed 
for evidence of active TB versus latent TB. Documentation 
will include: 
• 
Chest X-ray or imaging per local guidelines 
during the Screening Window 
• 
No signs and symptoms (no evidence of ongoing 
active TB 
• 
Study participant is being treated per local 
standard of care for a minimum of 2 weeks before 
the first dose of study drug OR 
• 
Study 
participant 
has 
documentation 
of 
completing appropriate treatment for latent TB 
within 2 years before Day 1 of the study 
X 
 
Abbreviations: IGRA, interferon gamma release assay; PPD, purified protein 
derivative; TB, tuberculosis. 
8.3.1. Dosing 
Instructions 
The first dose of the study drug will be administered in the clinic on study Day 1 under the supervision 
of study personnel. All subsequent doses will be self-administered at home, with the exception of the 
morning doses for Visits 2-10, which will be administered during the study visits after pre-dose blood 
samples have been drawn (see details in the SoA, Section 1.2). Participants will be instructed to record 
all details about the doses administered at home in the Participant Diary. 
To clarify dosing 
instructions 
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Participants will receive their study drug supplies in “morning bottles” and “evening bottles.” Each 
participant will receive the same number of “morning bottles” and “evening bottles” according to the 
respective study period (Induction or Maintenance/Maintenance Extension). 
For the Induction Period, each 30-day study drug supply will consist of 2 cartons (1 for morning and 1 
for evening). Inside each carton, there will be 2 corresponding bottles of study drug. Thus, an Induction 
Period 30-day study drug supply will consist of the following bottles: morning bottle #1, morning bottle 
#2, evening bottle #1, and evening bottle #2. For the Maintenance Period/Maintenance Extension 
Period, each 30-day study drug supply will consist of 1 carton. Inside the single carton, there will be 3 
bottles of study drug: morning bottle, evening bottle #1, and evening bottle #2. 
In the morning, participants should take 1 capsule from EACH “morning bottle.” In the evening, 
participants should take 1 capsule from EACH “evening bottle.” Each participant maywill be instructed 
to take up to 4 capsules per day depending on the number of bottles dispensed to the participantduring 
the Induction Period and 3 capsules per day during the Maintenance Period/Maintenance Extension 
Period. 
8.5. Participant Diary 
Participants who remain chronically non-compliant with diary entries despite intervention and 
follow-up by the Investigator and site team may be subject to discontinuation as per Section 7.1. 
Detailed descriptions regarding Participant Diary recordings can be found in the corresponding Study 
ManualPatient Guide. 
To align with 
Section 7.1. and update 
the source for 
Participant Diary 
instructions 
8.7.1. Endoscopy with 
Biopsy 
Endoscopy will be performed at Stage 2 of Screening (Visit 1) and during Stage 1 of Visits 5 and, 
10/EOT, and 14/EOT. Flexible 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 histopathology and optional 
future research studies. Up to 6 biopsies will be collected during each endoscopy procedure (2 biopsies 
for the required histopathology and 4 biopsies for the optional future research). The biopsies for future 
studies will only be collected from the participants who consent to the optional future research. The 
remaining tissue from the histopathology biopsies may also be used for future research from 
participants who consent to the optional future research. 
Detailed instructions for endoscopic biopsies (e.g., anatomic site, normal or inflamed mucosa) can be 
found in the Laboratory Manual. A brief description is provided below: 
• 
At Screening (Visit 1), collect 6 biopsy samples total: 4 from the most inflamed/affected 
area and 2 from a non-inflamed area. 
o 
Record the number of centimeters from the anus the biopsy is collected for from inflamed 
and the non-inflamed area into the Requisition Form Label. 
o 
Inflamed biopsies should be collected from the worst affected area, 15-25 cm from the 
anus. 
o 
Non-inflamed biopsies can be collected from anywhere in the colon and are not limited to 
15-25 cm from the anus. If there are no non-inflamed areas, biopsies are to be collected 
from the least inflamed areas. 
To identify the number 
of biopsies for 
histopathology and the 
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• For follow-up at Visits 5 (Week 12) and Visit 10/EOT biopsies from both the inflamed and 
non-inflamed areas should be collected from the same distance (cm) from the anus as collected at the 
Screening Visit. Record the number of centimeters from the anus in which biopsies are collected at all 
follow-up visits into the Requisition Form. 
Biopsy specimen transfer, processing, slide preparation, and digitization of slides for histopathologic 
scoring procedures will be detailed in a within the applicable Laboratory Manual or Histopathology 
Manual Reference Guide. Histopathology results will not be made available to study sites but will be 
located within the histopathology laboratory database and added to the electronic Trial Master File 
after the completion of the trial. 
The MES will be scored by a central reader. However, treatment decisions post-randomization will be 
made by the treating Investigator. 
For all biopsies in Table 8: 
• 
Record the extent of disease in centimeters from the anal verge 
• 
Record the distance in centimeters from the anus where biopsies are taken into the Requisition 
Form 
• 
Always review the Laboratory Manual for full instructions related to biopsy sample collection 
containers, labeling, and storage 
• 
Biopsies for histopathology are the required part of the study 
• 
Optional biopsies are only to be taken in participants who have consented for future research 
8.7.1. Endoscopy with 
Biopsy – Table 8. 
Table 8. Instructions for Endoscopic Biopsies was added to clarify biopsy procedures. Addition of 
the table required renumbering tables. 
To clarify biopsy 
procedures 
8.7.1. Endoscopy with 
Biopsy – Table 8. 
Visit 1 
(Screening) 
Worst inflamed area 
Take biopsies of the worst inflamed area within 15-25 
cm from the anus. 
• 
2 required biopsies for histopathology 
• 
2 optional biopsies for future research 
 
Non-inflamed/least inflamed area 
Take biopsies from a non-inflamed or least inflamed 
area of the colon. 
• 
2 optional biopsies for future research 
Visit 5 
(Week 12) 
 
Visit 10 
(Week 52 or EOT) 
 
Take all biopsies at the same distance (cm) from the 
anus as collected at Visit 1, regardless of tissue state 
at the time of the sampling. 
• 
2 required biopsies for histopathology 
• 
4 optional biopsies for future research 
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Visit 14 
(Week 104 or EOT) 
Abbreviations: EOT, End of Treatment. 
8.7.3. Mayo Clinic Score 
The Investigator will record the PGA in the site tablet or other relevant device or systemsource 
documents and eCRF at the specified study visits. 
To clarify the PGA 
recording procedure 
8.8.4. Clinical Safety 
Laboratory Tests 
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), then the results must be recorded in the EDC database. 
To align with the 
protocol 
8.9.4. Regulatory 
Reporting Requirements 
for SAEs, SUSARs, and 
Periodic Reports 
The Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the Member States Concerned, the applicable regulatory authority, Institutional Review Boards 
(IRBs)/Independent Ethics Committees (IECs), and Investigators. 
To clarify regulatory 
reporting requirements 
8.9.5. Pregnancy 
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. Pregnancy in a male participant’s 
partner will require unblinding. The male study participant will be withdrawn from the study and the 
participant should complete the EOT and SFU Visits. 
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. 
To clarify the criteria 
and procedures for 
discontinuing a male 
study participant with a 
partner who becomes 
pregnant during the 
study 
8.10.1. Collection of 
Blood Samples for 
MORF-057 
Concentration 
Determination in Plasma 
– Table 9. 
Table 9. Pharmacokinetics Sampling Windows was renumbered from Table 5 due to addition of 
tables. 
To update table 
numbering 
8.10.1. Collection of 
Blood Samples for 
MORF-057 
Concentration 
Determination in Plasma 
– Table 9. 
Section 8.10.1.: 
TheseIf consent is provided by the participant, these samples may also be used for future PK research 
studies. 
Table 9. Pharmacokinetics Sampling Windows 
Visit 
Collection Ttimepoints and Aassociated Wwindows 
To clarify the PK 
samples from 
participants who 
consent may also be 
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2, 3, 5, 7, and 10/EOT 
Before AM dose (-60 min) and at 1hr (±10 min), 2hr (±15 min), 
and 4hr (±30 min) after AM dose 
4, 6, 8, and 9 
Before AM dose (-60 min) and 1 hr (±10 min) after the AM dose 
Abbreviations: EOT, End of Treatment; hr, hour; min, minute. 
For all pre-AM dose sampling, the samples should be obtained within approximately 60 minutes before 
the AM dose is administered. Furthermore, the samples should be obtained at 12 hours (60 min) after 
the previous evening’s PM dose. 
8.12. Future Research 
Blood, If consent is provided by the participant, blood, stool, and colonic tissue samples will be 
collected and may be used for further PD, pharmacogenomics, and microbiome-related research, and 
future researchby Morphic Therapeutics. If consent is provided by the participant, the remaining blood 
and colonic tissue samples from the study-required procedures may also be used for future research, 
including future PK research. The purpose of future research is 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 thisthe collection of samples for future research is optional (see 
Section 10.1.4 for additional consents). 
To clarify sampling and 
analyses for future 
research 
9. Statistical 
Considerations 
Any deviationchange from the planned statistical analyses specified in the protocol will be fully 
described in the SAP and Clinical Study Report. 
To clarify terminology 
9.2.3.4. Multiplicity 
Adjustments 
All statistical inference will be 2-sided at a 0.1 level of significance. To control the overall Type I error 
rate, a hierarchical testing approach as illustrated in Figure 2 will be applied to the statistical testing of 
the primary and secondary endpoints for comparisons of each MORF-057 dose group with the placebo 
group. 
First, for the primary efficacy endpoint of clinical remission at Week 12, the Hochberg method will be 
applied to the comparisons of 200 mg B.I.D. with placebo and 100 mg B.I.D. with placebo. If both 
p-values are <0.1, both doses will be declared significant. If one of the p-values is ≥0.1, the other 
p-value will be tested at a 0.05 significance level and the corresponding dose will be declared 
significant only if the p-value is <0.05. If both p-values are ≥0.1, no dose will be declared significant, 
and no further formal testing will be performed. 
If both 200 mg B.I.D and 100 mg B.I.D. achieved the statistical significance for the primary efficacy 
endpoint, the fixed-sequence method will be used to test the comparison of 100 mg Q.D. with placebo 
for the primary efficacy endpoint and the comparison of each dose with placebo for the secondary 
efficacy endpoint of clinical response at Week 12 in a predefined order as specified in Figure 2 below. 
All tests will be performed at the same significance level alpha=0.1, with the moving to a second test 
only after a success, i.e., p-value <0.1, on the previous test. Further testing stops as soon as one test in 
the sequence fails to meet significance, i.e., p-value ≥0.1. 
The testing of the exploratory efficacy endpoints not included in the hierarchical procedure will be used 
for exploratory purposes only. The details will be specified in the SAP. 
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9.2.3.4. Multiplicity 
Adjustments 
Figure 2. Hierarchical Testing Procedure 
To illustrate the 
adjustment for multiple 
testing 
9.4. Interim Analysis 
The analysis of the 12-week Induction Period (Induction Period Analysis) will be performed after all the 
participants have completed the Week 12 assessments or discontinued the study before the Week 12 
assessment, as described in Section 9.3. 
An independent DSMB will review participant safety data and monitor scientific integrity throughout the 
study. Details related to the DSMB will be clearly delineated in the DSMB Charter. 
To clarify there is no 
interim analysis 
planned for this study 
10.1.1. Regulatory and 
Ethical Considerations 
• Providing oversight of the conduct of the study at the site and adherence to requirements of 21 CFR, 
ICH guidelines, the IRB/IEC, European Union Clinical Trials Directive 2001/20/EC or European 
regulationTrials Regulation 536/2014 for clinical studies (as applicable), and all other applicable local 
regulations 
To clarify the 
Investigator 
responsibilities 
10.1.1. Regulatory and 
Ethical Considerations 
If the Investigator identifies a potential instance of a serious breach, the Sponsor and Contract 
Research Organization (CRO) should be notified immediately at 
 
Include any available information at the time of the incident and copies of all documentation, if any, 
supporting the suspicion. 
To identify a contact 
email for serious 
breaches 
10.1.4. Informed 
Consent Process 
“if applicable” was added after legally authorized representative. 
Additional Consents 
The main ICF will contain separate sections for the following additional consents: 
To clarify additional 
informed consent forms 
200 mg B.I.D. vs Placebo, 
Clinical Remission  
100 mg B.I.D. vs Placebo, 
Clinical Remission 
Hochberg testing procedure (2-sided α = 0.1) 
p-values < 0.1 
for both tests  
Yes  
No  
Any p-value 
< 0.05 
Claim significance for the dose with 
p-value <0.05, and end formal testing  
Yes  
No  
End formal 
testing 
100 mg Q.D. vs Placebo, 
Clinical Remission 
200 mg B.I.D. vs placebo,  
Clinical Response 
100 mg B.I.D. vs Placebo,  
Clinical Response 
100 mg Q.D. vs Placebo, 
Clinical Response 
p-value < 0.1  
p-value < 0.1  
p-value < 0.1  
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• Optional sampling for additional receptor occupancy testing (see Section 8.11.1 and the SoA in 
Section 1.2). 
• Optional sampling collection of blood, colonic tissue, and stool samples for future PD, and 
microbiome-related analyses and future research, and use of the remaining blood and colonic tissue 
samples from the study-required procedures for future research, including future PK research (see 
Sections 8.7.1, 8.10, 8.12, and the SoA in Section 1.2). 
• Optional blood sampling for future pharmacogenomics analysis, which will involve genetic testing 
(see Section 8.12, Section 10.9, and the SoA in Section 1.2). 
Additional ICFs will be provided to participants or their partners for review and signature, as needed: 
• Optional Maintenance Extension (see Section 4.1 and the SoA in Section 1.2) 
• Consent to courier deliveries/pick-ups (see Section 8.13) 
• Pregnant Partner (see Section 8.9.5) 
10.1.5. Data Protection 
• Organizational and technical arrangements that will be implemented to avoid unauthorized access, 
disclosure, dissemination, alteration, or loss of personal data processed must be described. 
To clarify data 
protection 
10.1.9. Data Quality 
Assurance 
All participant data relating to the study will be recorded on paper-based Case Report Forms (CRFs) or 
eCRFs unless transmitted to the Sponsor or designee electronically (e.g., laboratory data). The 
Investigator is responsible for having quality system processes and procedures in place verifying that 
CRF data entries against source data are accurate and correct by. The Investigator is responsible for 
ensuring source records are maintained in real-time, eCRFs are completed per eCRF Completion 
Guidelines, and physically or electronically signing the CRF. 
Guidance on completion of CRFs and eCRFs will be provided in the corresponding guidelines. 
The Sponsor or designee is responsible for the data management of this study, including quality 
checking of the datascheduled data audits and verification against original source data/documentation. 
Essential source 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. 
Please reference ICH E6 (R2) Section 8 for the minimum list of essential documents required for the 
conduct of a clinical trial. Additional documentation may be required by the Sponsor or CRO before, 
during, and after completion of the trial. 
To clarify the 
responsibilities of the 
Investigator and data 
quality assurance 
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 and digitized copies are 
maintained in the site section of the electronic Trial Master File. 
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. by the Investigator and 
documented in the CRF. The Investigator may need to request previous medical records or transfer 
records, depending on the study. Also,and current medical records must be availableor transfer records 
as source documents for participants involvement (or enrollment) in this study. 
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The Investigator must maintain accurate documentation (source data) that supports the information 
entered in the CRF and eCRF. 
Sponsor-designated study monitors will perform ongoing source data verification to confirm that data 
entered into the CRF/eCRF 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. 
10.1.11.2. Study/Site 
Termination 
A study site is considered closed when all required documents and study supplies have been collected, 
all quality compliance activities have been completed, and a study site closure visit has been performed. 
•Total number of participants includedenrolled earlier than expected 
To clarify study/site 
termination 
10.3. Appendix 3: 
Clinical Laboratory 
Tests- Table 10. 
Table 10. Protocol-required Laboratory Tests. Addition of other tables required renumbering the 
table from Table 6 to Table 10. 
Renumber of tables due 
to addition of tables 
10.3. Appendix 3: 
Clinical Laboratory 
Tests – Table 10. 
Table 10. Protocol-required Laboratory Tests 
Coagulation 
• aPTT 
To update coagulation 
parameters 
10.3. Appendix 3: 
Clinical Laboratory 
Tests – Table 10. 
Table 10. Protocol-required Laboratory Tests 
Pregnancy testing 
• Urine hCG test (at Visits 2-11all subsequent visits for women of childbearing potential only) a 
To align with 
Section 8.8.6. 
10.3. Appendix 3: 
Clinical Laboratory 
Tests – Table 10. 
Table 10. Protocol-required Laboratory Tests 
• 
SARS-CoV-2 test (test to be determined by the site) 
• 
Tuberculosis test (
 test, with to be determined by the site) 
To align with other 
sections of the protocol 
10.3. Appendix 3: 
Clinical Laboratory 
Tests – Table 10. 
Table 10. Protocol-required Laboratory Tests 
Abbreviations: 
aPTT, activated partial thromboplastin time 
ESR, erythrocyte sedimentation rate 
PTT, partial thromboplastin time 
To update abbreviations 
10.3. Appendix 3: 
Clinical Laboratory 
Tests – Table 11. 
Table 11. Abnormal Liver Function Results: Re-testing and Follow-up Procedures. Addition of 
other tables required renumbering the table from Table 7 to Table 11. 
Renumber of tables due 
to addition of tables 
10.3. Appendix 3: 
Clinical Laboratory 
Tests – Table 11. 
Table 11. Abnormal Liver Function Results: Re-testing and Follow-up Procedures 
Re-test Review 
To clarify, a cell was 
added 
10.4.4. Reporting of 
SAEs 
“Event” was replaced by “The SAE”. 
To align with the 
section 
10.5.2. Contraception 
Guidance 
• Bilateral tubal occlusion/ligation 
To clarify contraception 
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10.7. Appendix 7: Mayo 
Clinic Scoring System 
for Assessment of 
Ulcerative Colitis 
Activity 
Endoscopy: The endoscopy subscore will be determined both locally and centrally by qualified 
personnel. 
To align with 
Section 8.7.1. 
11. References 
. Package insert. Takeda Pharmaceuticals America, Inc., 20202022. 
To update protocol 
references 
 
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Version 2.1 dated 26 April 2023 
Overall Rationale for the Amendment 
The overall rationale for this protocol amendment is to add the following major changes: 
• Add a 52-week Maintenance Extension following the 52-week Treatment Period, add 
corresponding endpoints, and update the study design/schema and statistical analyses 
• Clarify the enrollment plan for prior advanced therapy-experienced participants 
• Extend the Screening Period to ensure sufficient time for screening activities 
• Revise the Inclusion/Exclusion criteria regarding inadequate response, washout criteria of 
prior UC therapy, tuberculosis screening, and testing of SARS-CoV-2 
• Update the Schedule of Activities for clarity and add study activities for the Maintenance 
Extension Period 
• Remove the Week 24 clinical improvement assessment timepoint 
• Revise the sequence of events for Week 12, Week 52/EOT, and Week 104/LTE EOT 
wherein the endoscopy occurs during Stage 1, followed by the clinic visit at Stage 2 
• Add a follow-up contact on the day after the Week 12 clinic visit to ensure participants 
begin using the study drugs for the Maintenance Period 
• Update risks of MORF-057 
• Clarify the re-screening process and the blinding process after Week 12 
• Specify the process of reporting and capturing the overdose information 
• Clarify the acceptable use of aspirin 
• Clarify the discontinuation/withdrawal criteria regarding lack of efficacy, ineligible 
participants, and male participant whose partner becomes pregnant 
• Specify the number of biopsies for histopathology and the optional future research 
• Clarify the additional informed consents 
This protocol amendment is considered Substantial by the Sponsor, according to the criteria 
specified in the European Union Clinical Trials Regulation 536/2014. 

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Protocol Summary of Changes Table 
This protocol amendment is considered Substantial by the Sponsor, according to the criteria specified in the European Union Clinical 
Trials Regulation 536/2014. Changes to the protocol as implemented by this amendment 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. 
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 
Abbreviations 
5-ASA 
5-aminosalicylates 
AST 
Aspartate transaminase 
AUC0-12 
Area under the concentration-time curve from time 0 to 12 hours post-dose 
AUCtau 
Area under the concentration-time curve across the dosing interval 
C12 
Plasma concentration at 12 hours post-dose 
C. difficile Clostridiodes difficile 
CI 
Confidence interval 
CMH 
Cochran-Mantel-Haenszel 
CRA 
Clinical Research Associate 
CRO 
Contract Research Organization 
EDC 
Electronic data capture database 
EEA 
European Economic Area 
ESR 
Erythrocyte sedimentation rate 
FSH 
Follicle-stimulating hormone 
HRT 
Hormonal Replacement Therapy 
IBDQ 
Inflammatory Bowel Disease Questionnaire 
IC90 
90% of maximal inhibitory concentration 
ICH 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use 
IGRA 
Interferon gamma release assay 
MDRD 
Modification of Diet in Renal Disease 
MmMCS Modified Mayo Clinic Score 
mRNA 
Messenger ribonucleic acid 
PI 
Principal Investigator 
PP 
Per Protocol 
PRO 
Patient-reported outcome 
Q.D. – E 
Once a day (evening) 
Q.D. – M Once a day (morning) 
To update the 
abbreviations used 
throughout the 
protocol 

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RO 
Receptor occupancy 
SC 
Subcutaneous 
TNF-α 
Tumor necrosis factor alpha 
WOCBP 
Woman of Childbearing Potential 
WONCBP Woman of Non-childbearing Potential 
1.1. Synopsis – 
Objectives and 
Endpoints 
3. Objectives and 
Endpoints 
To determine time to symptomatic 
response by Week 12 
• Time to symptomatic response by Week 12 as determined using 
the Partial mMCS 
To clarify the endpoint 
1.1. Synopsis – 
Objectives and 
Endpoints 
3. Objectives and 
Endpoints 
To evaluate the long-term histologic 
and endoscopic effects of MORF-057 
at Week 104 
• Proportion of participants in histologic remission at Week 104 
as determined using the RHI 
• Proportion of participants in histologic remission at Week 104 
as determined using the NI 
• Proportion of participants in histologic remission at Week 104 
as determined using the Continuous Geboes Score 
• Proportion of participants with histologic improvement at 
Week 104 as determined using the RHI 
• Proportion of participants with endoscopic improvement at 
Week 104 as determined using the MES 
• Proportion of participants in endoscopic remission at Week 104 
as determined using the MES 
• Proportion of participants in endoscopic remission as 
determined using the MES and histologic remission as determined 
using the RHI at Week 104 
• Proportion of participants with endoscopic improvement as 
determined using the MES and a histologic improvement as 
determined using the RHI at Week 104 
To include endpoints 
corresponding to the 
Maintenance 
Extension 
1.2. Synopsis – 
Efficacy Analysis 
Definitions 
3. Objectives and 
Endpoints 
Histologic remission by RHI: RHI ≤32 (with 0 for lamina propria neutrophils score and neutrophils in the 
epithelium score and without ulcers or erosions) 
To clarify efficacy 
analysis definitions 
1.2. Synopsis – 
Efficacy Analysis 
Definitions 
3. Objectives and 
Endpoints 
Corticosteroid-free remission: Determined only in participants who were receiving corticosteroids on study 
Day 1. Includes such participants who are both in clinical remission (as determined using the mMCS) at 
Week 52 and off corticosteroids for ≥812 consecutive weeks prior to Week 52. 
To clarify efficacy 
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Brief Rationale 
1.1. Synopsis – Overall 
Design 
4.1. Overall Design 
The overall design section was reorganized for clarity and updated to reflect study changes. Text 
revisions are summarized below. 
To reorganize 
paragraphs for clarity  
1.1. Synopsis – Overall 
Design 
4.1. Overall Design 
For each treatment group, theThe study will enroll at least 30% of the participants from each of 
theparticipants who are advanced therapy-naïve (i.e., have no previous exposure to an advanced therapy 
treatment for UC) and advanced therapy-experienced (excluding vedolizumab) strata, with at least 30% but 
no more than 40% of the advanced therapy-experienced patientsparticipants. 
To clarify the 
enrollment plan for 
prior advanced 
therapy-experienced 
participants 
1.1. Synopsis – Overall 
Design 
4.1. Overall Design 
ThisThe main part of this Phase 2b study will consist of 3 study periods: a Screening Period (up to 
4 6 weeks, consisting of Stage 1 and Stage 2 testing), a Treatment Period (52 weeks, including a 12-week 
Induction Period and a 40-week Maintenance Period), and a Safety Follow-up (SFU) Period (4 weeks). 
During the main part of this study, there will be approximately 11 scheduled study visits: Screening 
Visit(s) (Visit 1 at Weeks -4 6 to -1), multiple Treatment Visits (Visits 2-10 at Weeks 0, 2, 6, 12, 18, 24, 
3632, 42, and 52 [End of Treatment (EOT)]), and an SFU 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 Treatment Periodstudy is completed or 
earlier if treatment is discontinued early). 
To reflect the 
expanded Screening 
Period 
1.1. Synopsis – Overall 
Design 
4.1. Overall Design 
All participants who complete the 52-week Treatment Period will have the opportunity to continue their 
treatment in a 52-week Maintenance Extension Period. 
During the optional Maintenance Extension, there will be 5 scheduled visits: 4 Treatment Visits 
(Visits 11-14 at Weeks 65, 78, 91, and 104 [EOT]) and an SFU Visit (visit to occur 4 weeks after the last 
dose of study drug is received, which will be at Week 108 if the full Maintenance Extension is completed or 
earlier if treatment is discontinued early). 
Participants who do not enroll into the Maintenance Extension must complete the final SFU 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 Maintenance 
Extension will not complete the SFU Period for the main part of the study; instead, they will directly enter 
the Maintenance Extension and complete a separate SFU Period, including the Week 108 Visit (4 weeks 
after receiving the last dose of MORF-057), for a maximum time on study of 114 weeks. 
To reflect the addition 
of the 52-week 
Maintenance 
Extension Period 
1.1. Synopsis – Overall 
Design 
4.1. Overall Design 
Any participant who has not shown clinical improvement (as determined by the Investigator) by Week 24 
will be discontinued from the study following an End of Treatment (EOT) Visit and a SFU Visit. 
To remove the 
Week 24 clinical 
improvement 
assessment timepoint 
1.1. Synopsis  
4.1. Overall Design 
6.1. Study Treatment 
Description 
Descriptions of study treatment in the synopsis section were consolidated and updated to reflect 
study changes. Maintenance Extension Period (52 Weeks) was added to the dosing regimens for the 
4 treatment groups and Table 4 in Section 6.1. 
After completion of the 12-week Induction Period, all participants randomized into the placebo group 
(Group 4) will be switched to receive an active MORF-057 regimen during the Maintenance Period. The 
dosing regimens for the 4 treatment groups during the Induction and Maintenance Periods are shown 
below. 
To reflect the addition 
of the 52-week 
Maintenance 
Extension Period 

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Study Treatment: 
Enrolled participants will be randomized to a treatment group to receive active MORF-057 or placebo. 
Participants initially randomized into an active MORF-057 treatment group will receive an active treatment 
(according to study periodtreatment phase and group assignment) for the full 52-week Treatment Period. 
Participants initially randomized into the placebo group will be switched to an active MORF-057 regimen 
(200 mg once a day - evening [Q.D.-E]) after they complete the Induction Period and the Week 12 
assessments. After participants complete the full 52-week Treatment Period, they will have the option to 
enter an additional 52-week Maintenance Extension Period. Participants All participants who 
completechoose to continue in the final SFU Period, including the Week 56 Visit (4 weeks 
afterMaintenance Extension will continue receiving the last dose ofsame MORF-057), will have a 
maximum time on study of 60 regimen they had during the Maintenance Period for up to an additional 
52 weeks. The dosing regimens for the 4 treatment groups during the study are shown below. 
 
Induction Period (12 Weeks) 
Maintenance Period (40 Weeks)/ 
Maintenance Extension Period 
(52 Weeks) 
Group 1 
MORF-057 (200 mg B.I.D.) 
MORF-057 (100 mg B.I.D.) 
Group 2 
MORF-057 (100 mg B.I.D.) 
MORF-057 (100 mg B.I.D.) 
Group 3 
MORF-057 (100 mg Q.D.-M) 
MORF-057 (100 mg Q.D.-M) 
Group 4  
Placebo  
MORF-057 (200 mg Q.D.-E) 
The Sponsor may decide to allow participants to continue receiving MORF-057 by adding a Maintenance 
Extension Period via a subsequent regulatory submission. In this case, participants who complete the 
52-week Treatment Period and associated assessments will continue receiving MORF-057 through the 
Maintenance Extension Period before completing the SFU Period. 
1.1. Synopsis – Study 
Treatment 
The study drug will be supplied as IR capsules for oral administration (MORF-057 100 mg capsule or 
placebo). Participants will receive their study drug supplies in “morning bottles” and “evening bottles.” 
Each participant will receive the same number of “morning bottles” and “evening bottles” according to the 
respective study period (Induction or Maintenance/Maintenance Extension). In the morning, participants 
should take 1 capsule from EACH “morning bottle.” In the evening, participants should take 1 capsule 
from EACH “evening bottle.” Each participant maywill be instructed to take up to 4 capsules per day 
during the Induction Period and 3 capsules per day during the Maintenance Period/Maintenance 
Extension Perioddepending on the number of bottles dispensed to the participant. 
To clarify treatment 
description and add 
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Brief Rationale 
1.1. Synopsis – Study 
Schema 
4.1. Overall Design 
The study schema and corresponding footnotes were updated to include the 52-week Maintenance 
Extension Period. The new schema also shows the expanded Screening Period. 
To reflect the addition 
of the 52-week 
Maintenance 
Extension Period and 
the expanded 
Screening Period 
1.1. Synopsis – Study 
Schema 
4.1. Overall Design 
Study Schema: 
Abbreviations: 
D, day; 
P.O., by mouth 
V, visit; 
§ Sponsor may decide to allow participants to continue receiving MORF-057 by adding a Maintenance 
Extension Period via a subsequent regulatory submission. 
To reflect updated 
study schema 
1.1. Synopsis – Main 
Inclusion Criteria 
5.1. Inclusion Criteria 
Type of Participant and Disease Characteristics 
Note: PatientParticipant cannot have had inadequate response, loss of response, or intolerance to more 
than 3 drugs in 2 classes of the following advanced therapies: 
c. JAK antagonists, including tofacitinib or upadacitinib 
e. Any investigational product with the same mechanism as one of those outlined above (a through d) or a 
novel mechanism of action 
Note: PatientParticipant who have a history of primary non-response to 2 or more of the advanced therapy 
classes above will not be eligible. PatientParticipant who have received treatment with these agents at 
sub-therapeutic doses or durations should be discussed with the Medical Monitor to assess eligibility. 
5. Meets the following washout criteria of prior UC therapy relative to study Day 1: 
c. JAK antagonists, including tofacitinib or upadacitinib: at least 3 days1 week 
d. S1P receptor agonists, including ozanimod: at least 8 4 weeks 
Note: Participants who do not meet the full washout period but have the results of a local drug 
concentration level performed during the Screening window deemed by the Medical Monitor to be 
sub-therapeutic may be eligible for the study earlier than the full washout period. 
6. If the patientparticipant 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 
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of these concomitant medications starting from the time specified below until the end of the SFU Period, 
with the exception of tapering oral corticosteroid dose after 12 weeks of being in the trial. 
a. Oral 5-Aminosalicylates (not exceeding 4.8 g per day): at least 2 weeks prior to study Day 1 
1.1. Synopsis – 
Exclusion Criteria 
5.2. Exclusion Criteria 
Medical Conditions 
7. Has ana potentially active bacterial, viral, or parasitic pathogenic enteric infection, including 
ClostridiumClostridiodes difficile (C. difficile); has 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 an active or latent tuberculosis (TB), as evidenced by any of the following: 
a. 
A diagnostic test for TB performed within 30 days ofprior to Screening or during the Screening 
Period that is positive, as defined as below: 
• 
A positive interferon gamma release assay (IGRA) test (e.g., Positive 
 
 TB test) or 2 consecutive indeterminate 
IGRA tests 
OR 
• 
A purified protein derivative (PPD) skin test ≥5 mm 
b. ChestA chest X-ray or imaging per local guidelines within 3 months ofprior to Screening where 
active or latent pulmonary TB cannot be excluded 
Note: Participants who have tested negative for TB at a certified local lab using an IGRA test within 
3 months prior to Screening are not required to repeat this test during the Screening Period if that 
participant has no clinical signs or symptoms of TB and no known exposures/increased risk factors since 
the last negative TB test (according to the Investigator’s clinical judgement), and the test result is 
available in the participant’s medical record 
Note: PatientsParticipants with a history of latent TB may be enrolled if it is being treated per localthey 
complete an assessment for evidence of active TB versus latent TB. Documentation will include a chest 
X-ray or imaging per local guidelines during the Screening Window and no signs, symptoms, or evidence 
of ongoing active TB. Participants have had treatment per the local standard of care for a minimum of 
2 weeks before the first dose of study drug with no evidence of ongoing active TB or who haveOR 
documentation of completing appropriate treatment for latent TB within 2 years before Day 1 Participants 
with inadequate documentation of treatment should be cleared by a TB specialist before enrollmentof the 
study. See Section 8.2.2.1 for more details. 
9. Tests positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the Screening 
Period. Testing to be performed according to site specific testing procedures and country-specific 
requirements.Has a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result 
during the Screening Period. Testing for SARS-CoV-2 is required only per local regulations. Participants 
who have a positive test result can be randomized after a subsequent negative test result during the 
Screening Period. 
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criteria 
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16. g. International normalized ratio >1.5. Participants with an international normalized ratio >1.5 due to 
anticoagulant therapy (e.g., Coumadin) may only be enrolled after a consultation with the Medical 
Monitor. 
1.1. Synopsis – Study 
Treatment 
Study Treatment: 
MORF-057 is a small molecule therapy that selectively inhibits the α4β7 integrin. The study drug will be 
supplied as immediate-release capsules for oral administration (MORF-057 100 mg capsule or placebo). 
The dose regimens for the 4 treatment groups are provided below: 
To update for clarity 
1.1. Synopsis – 
Statistical Methods: 
Primary Efficacy 
Endpoint 
9.2.3.1. Primary 
Efficacy Endpoint 
The primary analysis will be repeated on the PP Population as a sensitivity analysis. Other sensitivity 
analyses for the primary efficacy endpoints may also be performed as appropriate. The primary efficacy 
endpoint will be analyzed for the subgroups defined based on someselected categorized demographic and 
baseline variables, e.g., age, gender, race, exposure to an advanced therapy treatment for UC (advanced 
therapy-naïve and advanced therapy-experienced). The details will be described in the Statistical Analysis 
Plan (SAP). 
To clarify the primary 
efficacy endpoint 
1.1. Synopsis – 
Statistical Methods: 
Exploratory Efficacy 
Endpoints 
9.2.3.3. Exploratory 
Efficacy Endpoints 
All the continuous exploratory efficacy endpoints expressed as change from baseline at Week 12 as 
defined in Section 3 (e.g., non-endoscopic biomarkers of inflammation, PROs) will be analyzed in the FAS 
using an analysis of covariance (ANCOVA) model with treatment and randomization stratification factors 
as factors and baseline values as a covariate. 
To identify the type of 
biomarkers 
1.1. Synopsis – 
Statistical Methods: 
Safety Analyses 
9.2.4. Safety Analyses 
The safety analyses will be performed for the 12-week Induction Period and, the overall 52-week 
Treatment Period, and the 52-week Maintenance Extension Period plus the Safety Follow-up Period. In the 
safety analyses for the 12-week Induction Period, the participants initially randomized into the placebo 
group and switched to an active MORF-057 regimen after the Week 12 assessments will be analyzed as the 
placebo group. In the safety analyses for the overall 52-week Treatment Period and 52-week Maintenance 
Extension Period, the placebo recipients switched to an active MORF-057 regimen will be analyzed 
according to the active MORF-057 regimen they received after Week 12, and their data will be presented 
separately based on only the safety data collected after the start of the MORF-057 dose. Week 12 
assessments, i.e., during the 40-week Maintenance Period and Safety Follow-up Period. 
To add safety analyses 
of the Maintenance 
Extension 
1.1. Synopsis – 
Statistical Methods: 
Pharmacodynamics 
Analyses 
9.2.6. 
Pharmacodynamics 
Analyses 
The exploratory PD endpoints (changes over time in α4β7 and α4β1 receptor occupancy,occupancies and 
blood CCR9 mRNA level, and blood lymphocyte subsets) will be summarized descriptively. Additional 
analysis of PD endpoints may be described 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 PD exploratory 
endpoints. 
Section 9.2.6. 
The exploratory PD endpoints (changes over time in α4β7 receptor occupancy, changes over time in and 
α4β1 receptor occupancy,occupancies and blood CCR9 mRNA level, and blood lymphocyte subsets) will 
be summarized descriptively. 
To clarify how the 
exploratory PD 
endpoints will be 
reported 
1.1. Synopsis – 
Statistical Methods: 
Analyses for Induction Period and Total, 52-week Treatment Period, and Maintenance Extension Period 
To add statistical 
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Analyses for Induction 
Period, 52-week 
Treatment Period, and 
Maintenance Extension 
Period 
9.3. Analyses for 
Induction Period, 
52-week Treatment 
Period, and 
Maintenance Extension 
Period 
The Treatment Period in the main part of the study includes 2 treatment periods: 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 one for the 
52-week Total Treatment Period (i.e., the 12-week Induction Period plus the 40-week Maintenance Period 
and Safety Follow-up Period). The details of the analyses will be described in the SAP. The results for the 
main part of the study will be reported in the Clinical Study Report. 
Additional analysis of the optional 52-week Maintenance Extension Period for the participants enrolled 
into the Maintenance Extension will also be performed as appropriate. The results for the Maintenance 
Extension will be reported in a Clinical Study Report Addendum. 
Induction Period Analysis 
The analysis of the 12-week Induction Period will be performed after all the participants have completed 
the Induction Period (i.e., completed the Week 12 visitassessments or discontinued the study before the 
Week 12 assessments). The analysis will formally evaluate the efficacy (including the primary and 
secondary efficacy endpoints, and all the exploratory efficacy endpoints defined by Week 12), and safety of 
MORF-057 vs. placebo during the 12-week Induction Period. The PK and PD data during the 12-week 
Induction Period will also be summarized. 
Total 52-week Treatment Period Analysis 
The analysis of the 52-week Total Treatment Period will be performed after all the participants have 
completed the Week 52 assessments (and Safety Follow-up Period for participants not rolling over into the 
Maintenance Extension Period) or discontinued from the study before the Week 52 assessments. The 
analysis will formally evaluate the efficacy (including all the exploratory efficacy endpoints defined by 
Week 52), PK, PD, and safety of MORF-057 during the 52-week Total Treatment Period (and the Safety 
Follow-up Period for participants not rolling over into the Maintenance Extension Period). The 
cumulative data, including those from the Induction Period, will be used in this analysis. 
Maintenance Extension Analysis 
The analysis of the Maintenance Extension will be performed after all the participants enrolled into the 
Maintenance Extension have completed the 52-week Maintenance Extension Period and the Safety 
Follow-up Period or discontinued the study before the Week 104 assessment. The analysis will evaluate the 
safety of MORF-057 and selected efficacy endpoints as appropriate during the Maintenance Extension plus 
the Safety Follow-up Period. 
Maintenance 
Extension and clarify 
each analysis period 
1.2. Schedule of 
Activities (SoA)  
Section 1.2. was updated to reflect the changes in study procedures. Table 1 Schedule of Activities 
for the Treatment Period was added. A new SoA table (Table 2) identifies the timepoints and 
assessments of the Maintenance Extension Period. Addition of these 2 tables required renumbering 
tables. 
The SoA for the Treatment Period is provided in Table 1. The SoA for the Maintenance Extension Period is 
provided in Table 2. 
Abbreviations: 
ClostridiumClostridiodes 
To reflect changes to 
the Induction Period 
and include activities 
during the 
Maintenance 
Extension Period  

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ICF, Informed Consent Form; 
IGRA, interferon gamma release assay; 
1.2. Schedule of 
Activities (SoA) 
The SoA Table 1 was updated to clarify the Induction and Maintenance Periods, reflect the 
expanded Screening Period, add Stage 1 and 2 at Visits 5 and 10 with testing updated per respective 
stage, collect information on participant’s change in substance use at Stage 2 of Visits 5 and 10/EOT, 
remove Visit 11 from the SFU label, add /EOT to the corresponding mentions of Visit 10, clarify 
SARS-CoV-2 and TB testing, clarify back-up stool collection at Screening Stage 1 and optional stool 
collection for future research, clarify PK time windows, clarify endoscopy biopsies, include informed 
consent for the Maintenance Extension, remove the Week 24 clinical improvement review, and add 
confirm initiation of study drug for the Maintenance Period at Visit 5 Stage 2. 
To update study 
activities during the 
52-week Treatment 
Period 
1.2. Schedule of 
Activities (SoA) 
Dispense study drug was added to Visit 10. 
To update study 
activities 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “b”: 
No specific tests or procedures are required for unscheduled visits. Results of any study procedures 
performed at an unscheduled visit will be recorded and collected for the study. b  Clinically relevant 
laboratory testing or re-testing (e.g., hematology, coagulation, serum chemistry, or urinalysis) may be 
performed at unscheduled visits. 
To clarify study 
procedures for 
unscheduled visits 
1.2. Schedule of 
Activities (SoA) 
Addition of definition of Visit 5 Stage 1 and Stage 2 to Table 1, footnote “c” required reorganization 
of footnotes. 
To include definitions 
of Visit 5 Stage 1 and 
Stage 2 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “c”: 
If participant discontinues early from the study Treatment Period, perform the Visit 10/EOT procedures 
and schedule Visit 11/SFU for 28 days (+7 days) after the participant takes the last dose of study drug 
(unless consent is withdrawn). 
Visit 5 is split into Stage 1 and Stage 2 to clarify the timing of the endoscopy procedure. The endoscopy 
procedure at Visit 5 Stage 1 should be performed before the Visit 5 Stage 2 in-clinic assessments have been 
completed. 
To include timing of 
the endoscopy 
procedure 
1.2. Schedule of 
Activities (SoA) 
Addition of definition of Visit 10 Stage 1 and Stage 2 to Table 1, footnote “d” required 
reorganization of footnotes. 
To include definitions 
of Visit 10 Stage 1 and 
Stage 2 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “d”: 
Participants not participating in Maintenance Extension Period will complete the SFU Visit, which should 
be performed 28 days (+7 days) after the participant takes the last dose of study drug. Eligible participants 
who choose to participate in the Maintenance Extension Period after Visit 10/EOT will not attend the SFU 
Visit. 
Visit 10 is split into Stage 1 and Stage 2 to clarify the timing of the endoscopy procedure. The endoscopy 
procedure at Visit 10 Stage 1 should be performed before the Visit 10 Stage 2 in clinic assessments have 
been completed. 
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1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “ce”: 
If the participant discontinues early from the study Treatment Period, perform the Visit 10/EOT procedures 
and schedule Visit 11/SFU for 28 days (+7 days) after the participant takes the last dose of study drug 
(unless consent is withdrawn). 
To clarify the visits 
after early 
discontinuation 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “df”: 
Participants not participating in the Maintenance Extension Period will complete the SFU Visit, which 
should be performed 28 days (+7 days) after the participant takes the last dose of study drug. Eligible 
participants who choose to participate in the Maintenance Extension Period after Visit 10/EOT will not 
attend the SFU Visit complete a separate SFU Visit at Week 108 (Table 2). 
To clarify study 
procedures 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “eg”: 
If the participant discontinues early from the study Treatment Period, perform the Visit 11/SFU procedures 
28 days (+7 days) after the participant takes the last dose of study drug (unless consent is withdrawn). 
To reflect the removal 
of Visit 11 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “fh”: 
The SFU Visit is to occur 28 days (+7 days) after the last dose of study drug is received. If the EOT Visit 
occurs before Day 365, the day for the SFU Visit can be adjusted according to the date of last study drug 
dose. 
To clarify the timing 
of the study procedure 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “hj”: 
Enrollment may occur at any point within a 2842-day window of when all screening procedures have been 
completed and all results required to assess eligibility are available. Enrolled participants will be 
randomized to a treatment group. Enrollment will usually occur the same day as first dosing, but if dosing 
the same day is not feasible, then enrollment will be considered Day -1 and first dose will be considered 
Day 1. 
To reflect the 
expanded Screening 
Period and clarify 
study procedures  
1.2. Schedule of 
Activities (SoA) 
8.2.2.2. SARS-CoV-2 
Table 1, Footnote “ik”: 
SARS-CoV-2 test will be performed during the Screening Period according to site-specific procedures and 
country-specific requirements.Testing for SARS-CoV-2 is required only per local regulations. Participants 
who have a positive test result will be excluded from randomization until a subsequent test result is 
negative. 
Section 8.2.2.2.: 
All participants will complete SARS-CoV-2 screening to determine eligibility.Testing for SARS-CoV-2 is 
required only per local regulations. Participants who have a positive test result will be excluded from 
randomization until a subsequent test result is negative. 
To allow re-testing of 
participants who tested 
positive for 
SARS-CoV-2 during 
the Screening Period 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “jl”: 
 Participants who have tested negative for TB at a certified local lab using an 
interferon gamma release assay (IGRA) test (e.g., 
 TB test) within 3 months 
prior to Screening are not required to repeat this test during the Screening Period if that participant has no 
clinical signs or symptoms of TB and no known exposures/increased risk factors since the last negative TB 
test (according to site specific procedures and country-specific requirements the Investigator’s clinical 
judgement). In cases where the 
 IGRA test is indeterminate, the participant may have the 
To clarify TB 
screening 
requirements 
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test repeated once, and if their second test is negative, they will be eligible. In the event 
 is 
unavailable, the Investigator has the option to perform aThe purified protein derivative skin test should be 
performed when the IGRA test is not possible or if both tests are required by local guidelines. 
1.2. Schedule of 
Activities (SoA) 
Addition of review of change in substance use to Table 1, footnote “m” required reorganization of 
footnotes. 
To include review of 
change in substance 
use 
1.2. Schedule of 
Activities (SoA) 
5.3. Lifestyle 
Considerations 
Table 1, Footnote “m”: 
Collect information on the participant’s change in substance use (e.g., alcohol, tobacco, and drugs). 
Section 5.3.: 
No new non-pharmacological therapies should be started during the study period. Information should be 
collected on the participant’s change in substance use (e.g., alcohol, tobacco, and drugs) per the SoA in 
Section 1.2. 
To include review of 
change in substance 
use 
1.2. Schedule of 
Activities (SoA) 
8.8.6. 
Pregnancy/Menopause 
Testing 
Table 1, Footnote “mp”: 
Serum test for follicle-stimulating hormone level to be performed only for female participants of 
non-childbearing potential who are not surgically sterile. 
Section 8.8.6.: 
A serum test for follicle-stimulating hormone (FSH) level will be performed at Screening only for female 
participants of non-childbearing potential who are not surgically sterile. 
To align with central 
lab processes and 
Appendix 3 
1.2. Schedule of 
Activities (SoA) 
8.6. Stool Collection 
Table 1, Footnote “nq”: 
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 
stored as described in the sample collection instructions and brought to the clinic on the day of the site 
visit. If the participant is unable to produce a stool sample at the Stage 1 Screening Visit, they can collect 
a sample at home and return it to the site. Note: Sample is to be collected prior to bowel preparation for 
Visits 5 and 10/EOT. 
Section 8.6.: 
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 stored as described in the sample collection instructions and brought to the clinic on the 
day of the site visit. If the participant is unable to produce a stool sample at the Stage 1 Screening Visit, 
they can collect a sample at home and return it to the site. 
To clarify back-up 
stool sample collection 
at Screening Stage 1 
Visit 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “or”: 
Participants will be provided the option to participate in the Maintenance Extension Period. Participants 
who want to continue in the Maintenance Extension will be required to provide informed consent. If the 
Sponsor decides to add a Maintenance Extension Period, willing participants should sign the relevant 
revised ICF, as required. 
To identify when the 
separate ICF for the 
Maintenance 
Extension Period must 
be signed  
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Table 1, Footnote “ps”: 
ECGs to be performed before the AM dose and 2 hours (±30 minutes) after the AM dose during the 
Induction and Maintenance Periods. ECGs will be obtained after the participant has rested for at least 
10 minutes in the supine position. 
To clarify the ECG 
procedure 
1.2. Schedule of 
Activities (SoA) 
8.8.1. Physical 
Examinations 
Table 1, Footnote “qt”: 
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, the type 
of exam (if necessary to be performed at all) will be at the Investigator’s discretion and determined based 
on the reason for the visit. The Screening exam will include collection of height and weight. 
Section 8.8.1.: 
A complete physical exam is required at Screening and, Visit 10/EOT, and Visit 14/EOT; and a targeted 
exam may be performed at all other required visits. For unscheduled visits, the choice of whether to 
perform a complete or targeted physical exam (if necessary to be performed at all) is at the discretion of 
the Investigator and will depend on the reason for the unscheduled visit. 
To clarify type of 
physical exam at 
which timepoints 
1.2. Schedule of 
Activities (SoA) 
8.8.2. Vital Signs 
Table 1, Footnote “ru”: 
Vital signs to be recorded at allmost visits. At unscheduled visits, vital signs are not required and are at the 
discretion of the Investigator. These will include blood pressure, heart rate, respiratory rate, and 
temperature. Vital signs are to be taken before blood collection for laboratory tests. Blood pressure and 
pulse measurements should be preceded by at least 10 minutes of rest for the participant. 
Section 8.8.2.: 
Vital signs to be recorded at allmost visits as summarized in the SoA (Section 1.2). At unscheduled visits, 
vital signs are not required and are at the discretion of the Investigator. These will include blood pressure, 
heart rate, respiratory rate, and temperature. 
To clarify the vital 
signs recording times 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “vy”: 
PK testing at Visits 2, 3, 5, 7, and 10/EOT: Blood samples will be collected before the AM dose and at 1, 
(±10 min), 2, (±15 min), and 4 (±30 min) hours after the AM dose. Time windows for PK sampling can be 
found in Section 8.10.1. For all pre-AM dose sampling, the samples should be obtained before the AM 
dose is administered. If consent is provided by the participant, these samples may also be used for future 
PK research studies. 
Table 1, Footnote “wz”: 
PK testing at Visits 4, 6, 8, and 9: Blood sample will be collected before the AM dose and 1 hour 
(±10 min) after the AM dose. For all pre-AM dose sampling, the samples should be obtained before the 
AM dose is administered. If consent is provided by the participant, these samples may also be used for 
future PK research studies. 
To clarify the PK 
samples from 
participants who 
consent may also be 
used for future PK 
research studies  
1.2. Schedule of 
Activities (SoA) 
Addition of optional stool sample to Table 1, footnote “gg” required reorganization of footnotes. 
To clarify optional 
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Table 1, Footnote “gg”: 
Participation in future research sample collection is optional. Fecal samples for microbiome analysis will 
be collected before the AM dose on Visits 2, 5, and 10/EOT. Fecal samples may be collected at any time on 
the day prior to the scheduled visit day. 
To clarify optional 
stool sample for future 
research 
1.2. Schedule of 
Activities (SoA) 
Removal of footnote “hh” Table 1 required reorganization of footnotes. 
Any patient who has not shown clinical improvement (as determined by the Investigator) by Week 24 will 
be discontinued from the study following an EOT Visit and a SFU Visit. 
To remove the 
Week 24 clinical 
improvement 
assessment timepoint 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “ddhh”: 
Full colonoscopy is optional at any timepoint if the Investigator deems it necessary. However, if the 
patientparticipant has had UC for over 7 years, he/she must undergo a full colonoscopy (rather than 
sigmoidoscopy) at Screening if a full colonoscopy has not been performed in the last 2 years. Colonic 
mucosa biopsies will be collected for histopathology and optional future research studies. 
To identify the 
number of biopsies for 
histopathology and the 
optional future 
research (for 
participants who 
consent) and clarify 
the procedures 
1.2. Schedule of 
Activities (SoA) 
Addition of a separate footnote on the specifics of the Screening endoscopy biopsies to Table 1, 
footnote “ii” required reorganization of footnotes. 
To clarify the 
Screening endoscopy 
biopsies 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “ii”: 
During the Screening endoscopy, up to 6 colonic mucosa biopsies will be collected. Two biopsies for the 
required histopathology must be collected from the worst inflamed area, 15-25 cm from the anus. Record 
the extent of disease in centimeters from the anal verge. If consent is provided by the participant, 
4 additional mucosa biopsies may be collected for the optional future research studies (2 biopsies from the 
worst inflamed area and 2 from a non-inflamed/least inflamed area). If consent is provided by the 
participant, any remaining tissue from the required histopathology biopsies may be used for future 
research studies. See Section 8.7.1 for details on biopsy requirements. 
To clarify the 
Screening endoscopy 
biopsies 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “eejj”: 
The Visit 5 Stage 1 endoscopy procedure should be performed afterbefore the in-clinic assessments at 
Visit 5 Stage 2 have been completed. 
To clarify the timing 
of the Visit 5 
endoscopy 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “ffkk”: 
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. Participants who complete the EOT Visit within 2 months after 
the Week 12 endoscopy are not required to repeat the procedure. 
To clarify the 
endoscopy 
requirements 
1.2. Schedule of 
Activities (SoA) 
Addition of a separate footnote on the endoscopy biopsy specifics of the Visit 5 Stage 1 and 
Visit 10/EOT Stage 1 to Table 1, footnote “ll” required reorganization of footnotes. 
To clarify the 
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Table 1, Footnote “ll”: 
Collect up to 6 biopsy samples total (2 for required histopathology and 4 for optional future research 
studies [if consent is provided by the participant]). If consent is provided by the participant, any remaining 
tissue from the required histopathology biopsies may be used for future research studies. All biopsies 
should be collected from the same distance from the anus as collected at the Screening Visit, regardless of 
the tissue state at the time of the sampling. Record the extent of disease in centimeters from the anal verge. 
Record the number of centimeters from the anus in which biopsies are collected at all follow-up visits into 
the Requisition Form. 
To clarify the 
Visits 5 and 10/EOT 
endoscopy biopsies 
1.2. Schedule of 
Activities (SoA) 
Addition of a footnote on clarifying study treatment handling for participants not participating in 
the Maintenance Extension Period to Table 1, footnote “nn” required reorganization of footnotes. 
To clarify study 
treatment handling for 
participants not 
participating in the 
Maintenance 
Extension Period 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “nn”: 
Participants not participating in the Maintenance Extension Period should return all study drug to the site. 
No additional dosing should occur after the completion of the EOT Visit. 
To clarify study 
treatment handling for 
participants not 
participating in the 
Maintenance 
Extension Period 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “iioo”: 
At Visit 5, the Induction Period study drugs kits supplied at the previous visit should be used for the AM 
and PM dose. Please note, a new supply of Maintenance Period study drugs kits will be provided at the 
conclusion of Visit 5, but the new supply should be started the day AFTER the required sigmoidoscopy is 
performed. This is to ensure that participants moving onto the Maintenance Period are on the appropriate 
MORF-057 treatment and dose. Participants should use the Maintenance Period study drug kits for all 
future doses after the completion of Visit 5. 
To clarify study drug 
dispensing at Visit 5 
1.2. Schedule of 
Activities (SoA) 
Addition of a footnote on clarifying study drug dispensing at Visit 10/EOT to Table 1, footnote “pp” 
required reorganization of footnotes. 
To clarify study drug 
dispensing at 
Visit 10/EOT 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “pp”: 
For participants continuing treatment in the Maintenance Extension, additional study drug will be 
dispensed at Visit 10. 
To clarify study drug 
dispensing at 
Visit 10/EOT 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “jjqq”: 
AM dosing required on-site for all visits except the SFU Visit. 
To align with 
document 
1.2. Schedule of 
Activities (SoA) 
Table 1, Footnote “kkrr”: 
At Visit 10/EOT, participants not participating in the Maintenance Extension Period will only receive an 
AM dose for the day. No PM dose will be provided. 
To clarify dosing 
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participating in the 
Maintenance 
Extension Period 
1.2. Schedule of 
Activities (SoA) 
Addition of a footnote to add a follow-up contact to Table 1, footnote “ss” 
To add a follow-up 
contact to ensure 
participants begin 
using the study drugs 
for the Maintenance 
Period 
1.2. Schedule of 
Activities (SoA) 
6.4. Study Treatment 
Compliance 
Table 1, Footnote “ss”: 
Site staff will contact the participants, by phone or other forms, on the next business day after the Visit 5 
clinic visit is complete to confirm the participants are using the new supply of study drugs for the 
Maintenance Period. Record the date and time of the participant's first Maintenance Period dose. 
Section 6.4.: 
The site staff will contact participants, by phone or other forms, on the next business day after the Visit 5 
clinic visit to confirm the participants have switched from the Induction Period study drug to the new 
Maintenance Period study drug bottles. 
To add a follow-up 
contact to ensure 
participants begin 
using the study drugs 
for the Maintenance 
Period 
2.1. Study Rationale 
AnotherOther therapeutic options recently approved for the treatment of UC isare Janus kinase (JAK) 
inhibitors, such as the small molecule tofacitinib (
) or upadacitinib (
). 
Upadacitinib was 
added to reflect 
currently approved 
JAK inhibitors 
2.3.2.1. Risks of 
MORF-057 
• Progressive multifocal leukoencephalopathy (PML) is a fatal opportunistic infection of the central 
nervous system and has been associated with systemic immunosuppressants, including integrin receptor 
antagonists (e.g., natalizumab and vedolizumab). Natalizumab, a monoclonal antibody that inhibits both 
α4β1 and α4β7 integrins, has been associated with PML, a serious brain infection. One case of PML was 
reported in a patient treated with vedolizumab (α4β7 integrin antagonist) during post-marketing setting in 
an 
 (vedolizumab)-treated patient with multiple contributory factors has been reported in the 
post-marketing setting (e.g., human immunodeficiency virus [HIV] 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 pProgram 
(RAMP). 
To update risks of 
MORF-057 
4.2. Scientific Rationale 
for Study Design 
The 52-week treatment will be followed by an optional 52-week Maintenance Extension Period. This 
extension will provide the participants further access to the study drug and collect additional safety and 
efficacy data up to 104 weeks of exposure. 
To add rationale for 
adding the 
Maintenance 
Extension 
4.4. End of Study 
Definition 
A participant is considered to have completed the study if he/she has completed all periodsthe Screening 
and 52-week Treatment Periods of the main part of the study and attended the SFU Visit OR has 
completed the Week 52/EOT Visit and has been enrolled into the Maintenance Extension Period. 
To define participant 
study completion 
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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 sSchedule of aActivities (SoA) for the last participant in the 
main part of the study globally. 
5.1. Inclusion Criteria 
Weight 
9. Has a body mass index (BMI) ≥1718.0 at Screening 
To align with synopsis 
5.4. Screen Failures 
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. For example, 
participants who test positive for SARS-CoV-2 during screening can be re-screened once they have a 
negative PCR test and are symptom-free. Re-screened participants should be assigned a new participant 
number for every sScreening/re-screening event. 
To allow re-testing of 
participants who test 
positive for 
SARS-CoV-2 during 
Screening 
5.4. Screen Failures 
Note: Participants who are unable to complete all required procedures or assessments within the Screening 
Window due to technicalities may be eligible to extend their Screening Period up to 2 weeks based on an 
agreement between the Investigator and the Sponsor Medical Monitor. Screening activities that require 
repeating will be determined by the Sponsor Medical Monitor and the process outlined in the Monitoring 
Plan. 
To clarify the 
re-screening process 
6.1. Study Treatment 
Description – Table 3. 
Table 3. Study Treatment was renumbered from Table 1 due to addition of tables. 
To update table 
numbering 
6.1. Study Treatment 
Description – Table 3. 
Packaging and 
Llabeling 
30 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. 
30 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. 
To clarify the number 
of capsules per bottle 
6.1. Study Treatment 
Description – Table 3. 
Abbreviations: 
B.I.D., twice a day; 
IR, immediate-release. 
To update 
abbreviations for the 
table 
6.1. Study Treatment 
Description – Table 4. 
Table 4. Treatment Groups was renumbered from Table 2 due to addition of tables. 
To update table 
numbering 
6.1. Study Treatment 
Description – Table 4. 
Group title 
Group 1 
Group 2 
Group 3 
Group 4 
To include the 
Experimental 
Maintenance Period 
Type 
• Induction: 
Experimental 
• Maintenance 
/Maintenance 
Extension: 
Experimental 
• Induction: 
Experimental 
• Maintenance 
/Maintenance 
Extension: 
Experimental 
• Induction: 
Experimental 
• Maintenance 
/Maintenance 
Extension: 
Experimental 
• Induction: 
Experimental 
• Maintenance 
/Maintenance 
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Experimental 

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Maintenance 
Period dosing 
regimen 
(40 Weeks)/ 
Maintenance 
Extension 
Period dosing 
regimen (52 
Weeks) 
 
 
 
 
6.3.2. Blinding 
This is a double-blind study in which the Sponsor, participants, site staff, site pharmacy, Investigators, and 
outcomes assessors will be blinded to the study treatment through Week 12. …. Each participant will 
receive the same number of “morning bottles” and “evening bottles” according to the respective study 
period (Induction or Maintenance)./Maintenance Extension). …. TheAfter the database lock for the 
Induction Period analyses, the analysis results will be unblinded at the population level. However, the 
access to treatment assignment for individual participants will be limited within a very small subgroup, 
includingto only the necessary persons from the Sponsor and the external vendors that will generate the 
unblinded analysis results and perform the validation. All other Sponsor personnel, the project study team, 
site Investigator, site staff, and study participants will remain blinded to the individual treatment 
assignments through the end of the study. 
If the report requires expedited reporting to one or more regulatory agenciesagency, a copy of the report, 
identifying the participant’s treatment assignment, maywill be sent to the Rregulatory Aagency in 
accordance with local regulations and/or Sponsor policy. 
To clarify the blinding 
process 
6.6. Overdose 
• Overdose with or without clinical symptoms or abnormal laboratory results should be recorded on the 
overdose electronic Case Report Form (eCRF) within 24 hours of becoming aware. 
• AEs and SAEs associated with overdose will be recorded on the AE CRFeCRF, and SAEs associated 
with overdose will be reported via the SAE reporting procedure outlined in Section 8.9. 
To specify the process 
of capturing overdose 
information  
6.7.2. Allowed 
Medications for the 
Treatment of Ulcerative 
Colitis – Table 5. 
Table 5. Corticosteroid Equivalent Doses† was renumbered from Table 3 due to addition of tables. 
To update table 
numbering 
6.7.2.2. Rescue 
Therapies 
Anti-diarrheals for control of chronic diarrhea and antibiotics for control of infection are not considered 
rescue medication. 
To align with 
Section 7.1.1. 
6.7.3. 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 at a dose as per 
local guidelines but not exceeding 81325 mg per day.) 
To clarify the 
acceptable use of 
aspirin 
6.7.3. Prohibited 
Medications – Table 6. 
Table 6. Examples of Drugs Potentially Altering Exposures to MORF-057# was renumbered from 
Table 4 due to addition of tables. 
To update table 
numbering 

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7.1.1. Permanent 
Discontinuation 
• Lack of efficacy, defined as: 
o Administration of a rescue medication (a new medication or increase in dose of a baseline medication to 
treat new or unresolved UC symptoms with the exception of returning the background corticosteroid 
therapy dose to baseline level). Anti-diarrheals for control of chronic diarrhea and antibiotics for control of 
infection are not considered rescue medication. 
• Pregnancy or planned pregnancy of the female participant or female partner of a male participant as the 
participant will be unblinded (see Section 8.9.5) 
• Non-compliance with study treatment (see Section 6.4) or study procedures 
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. In rare 
circumstances, consideration may be given to the participant when there is a compelling 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. 
To clarify permanent 
discontinuation 
criteria 
7.2. Participant 
Discontinuation/Withdr
awal from the Study 
The participant should be encouraged to complete the EOT Visit (Visit 10) at the time of study drug 
discontinuation and the SFU Visit (Visit 11) at 28 days (+7 days) after the last dose of study drug. 
To clarify 
discontinuation 
procedures  
8.1. Medical History 
The participant’s demographics and complete medical and surgical history, including initial UC diagnosis 
date, UC onset date, and history of UC medication use, will be collected during Screening and recorded in 
the participant’s eCRF. 
To clarify medical 
history details 
8.2.2.1. Tuberculosis 
All participants will complete TB screening to determine eligibility. Participants with a negative TB test and 
chest X-ray (or imaging per local guidelines) not suggestive of active or TB may be enrolled. Participants 
with a history of active TB may be enrolled if it has been adequately treated with no evidence of current 
active TB. Participants with a positive TB test must be assessed for evidence of active TB versus latent TB 
will be excluded, including. Please refer to Table 7 for TB Screening and eligibility details. Exclusion 
criteria includes those participants with a positive TB diagnostic test performed within 30 days ofprior to 
Screening or during the Screening Period (e.g., a positive IGRA test such as a 
 
 
TB test, 2 consecutive indeterminate IGRA tests, or a PPD skin test ≥5 mm), and those who had a chest X-ray 
within 3 months ofprior to Screening where active or latent pulmonary TB could not be ruled outexcluded. 
The 
IGRA test should be performed at Screening on all participants., except for those who 
have had a confirmed negative IGRA test within 3 months prior to Screening. The PPD skin test should be 
To update the TB test 
methods 
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performed when the 
IGRA test is not possible or if both tests are required by local 
guidelines. Test results should be interpreted as shown below: 
• 
For regions that require both 
IGRA and PPD tests, if either test is positive, the TB 
test is considered positive. 
If the 
IGRA test is indeterminate, then the Investigator should perform a second 
IGRA test to rule out a positive test result. If testing remains indeterminate or is positive, 
then the participant is considered TB positive. 
The PPD skin test should be performed when 
 test is not possible. PPD should be read by a 
licensed healthcare professional between 48 and 72 hours after administration. A reaction of induration 
≥5 mm is considered a positive reaction. 
Participants who have tested negative for TB at a certified local lab using an IGRA test within 3 months 
prior to Screening are not required to repeat this test during the Screening Period if that participant has 
no clinical signs or symptoms of TB, no known exposures/increased risk factors since the last negative TB 
test (according to the Investigator’s clinical judgement), and the test result is available and adequately 
documented in the participant’s medical record. 
8.2.2.1. Tuberculosis – 
Table 7. 
Table 7. Summary of Tuberculosis Screening and Eligibility was added. The table depicts 
inclusion/exclusion criteria based on IGRA, 
 
 TB test results. Addition 
of the table required renumbering tables. 
To clarify TB testing 
inclusion/exclusion 
criteria 
8.2.2.1. Tuberculosis – 
Table 7. 
Test Performed Within 30 Days Prior to Screening or 
During the Screening Period 
Inclusion 
Exclusion 
A positive interferon gamma release assay (IGRA) test 
(e.g., 
 
 TB test) 
  
X 
2 consecutive indeterminate IGRA tests  
  
X 
A purified protein derivative (PPD) skin test ≥5 mm 
  
X 
Test Performed Within 3 Months Prior to Screening 
Inclusion 
Exclusion 
A chest X-ray within 3 months prior to Screening where 
active or latent pulmonary TB cannot be excluded 
 
X 
A negative test for TB at a certified local lab using an IGRA 
test (e.g., 
 
 TB test) within 
3 months prior to Screening AND 
• 
Has no clinical signs or symptoms of TB 
• 
No known exposures/increased risk factors since 
the last negative TB test (according to the 
Investigator’s clinical judgement) 
• 
The test result is available and adequately 
documented in the participant’s medical record 
Note: Re-testing is not required at Screening if all the 
above criteria are met  
X 
  
To clarify TB testing 
inclusion/exclusion 
criteria 
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History of Latent TB 
Inclusion 
Exclusion 
Study participants with a positive TB test must be assessed 
for evidence of active TB versus latent TB. Documentation 
will include: 
• 
Chest X-ray or imaging per local guidelines 
during the Screening Window 
• 
No signs and symptoms (no evidence of ongoing 
active TB 
• 
Study participant is being treated per local 
standard of care for a minimum of 2 weeks before 
the first dose of study drug OR 
• 
Study 
participant 
has 
documentation 
of 
completing appropriate treatment for latent TB 
within 2 years before Day 1 of the study 
X 
 
Abbreviations: IGRA, interferon gamma release assay; PPD, purified protein 
derivative; TB, tuberculosis. 
8.3.1. Dosing 
Instructions 
The first dose of the study drug will be administered in the clinic on study Day 1 under the supervision of 
study personnel. All subsequent doses will be self-administered at home, with the exception of the morning 
doses for Visits 2-10, which will be administered during the study visits after pre-dose blood samples have 
been drawn (see details in the SoA, Section 1.2). Participants will be instructed to record all details about 
the doses administered at home in the Participant Diary. 
Participants will receive their study drug supplies in “morning bottles” and “evening bottles.” Each 
participant will receive the same number of “morning bottles” and “evening bottles” according to the 
respective study period (Induction or Maintenance/Maintenance Extension). 
For the Induction Period, each 30-day study drug supply will consist of 2 cartons (1 for morning and 1 for 
evening). Inside each carton, there will be 2 corresponding bottles of study drug. Thus, an Induction 
Period 30-day study drug supply will consist of the following bottles: morning bottle #1, morning bottle #2, 
evening bottle #1, and evening bottle #2. For the Maintenance Period/Maintenance Extension Period, each 
30-day study drug supply will consist of 1 carton. Inside the single carton, there will be 3 bottles of study 
drug: morning bottle, evening bottle #1, and evening bottle #2. 
In the morning, participants should take 1 capsule from EACH “morning bottle.” In the evening, 
participants should take 1 capsule from EACH “evening bottle.” Each participant maywill be instructed to 
take up to 4 capsules per day depending on the number of bottles dispensed to the participantduring the 
Induction Period and 3 capsules per day during the Maintenance Period/Maintenance Extension Period. 
To clarify dosing 
instructions 
8.5. Participant Diary 
Participants who remain chronically non-compliant with diary entries despite intervention and follow-up 
by the Investigator and site team may be subject to discontinuation as per Section 7.1. 
Detailed descriptions regarding Participant Diary recordings can be found in the corresponding Study 
ManualPatient Guide. 
To align with 
Section 7.1. and 
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Participant Diary 
instructions 
8.7.1. Endoscopy with 
Biopsy 
Endoscopy will be performed at Stage 2 of Screening (Visit 1) and during Stage 1 of Visits 5 and, 10/EOT, 
and 14/EOT. Flexible 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 histopathology and optional future 
research studies. Up to 6 biopsies will be collected during each endoscopy procedure (2 biopsies for the 
required histopathology and 4 biopsies for the optional future research). The biopsies for future studies 
will only be collected from the participants who consent to the optional future research. The remaining 
tissue from the histopathology biopsies may also be used for future research from participants who consent 
to the optional future research. 
Detailed instructions for endoscopic biopsies (e.g., anatomic site, normal or inflamed mucosa) can be 
found in the Laboratory Manual. A brief description is provided below: 
• 
At Screening (Visit 1), collect 6 biopsy samples total: 4 from the most inflamed/affected area and 
2 from a non-inflamed area. 
o 
Record the number of centimeters from the anus the biopsy is collected for from inflamed 
and the non-inflamed area into the Requisition Form Label. 
o 
Inflamed biopsies should be collected from the worst affected area, 15-25 cm from the anus. 
o 
Non-inflamed biopsies can be collected from anywhere in the colon and are not limited to 15-
25 cm from the anus. If there are no non-inflamed areas, biopsies are to be collected from the 
least inflamed areas. 
• For follow-up at Visits 5 (Week 12) and Visit 10/EOT biopsies from both the inflamed and non-inflamed 
areas should be collected from the same distance (cm) from the anus as collected at the Screening Visit. 
Record the number of centimeters from the anus in which biopsies are collected at all follow-up visits into 
the Requisition Form. 
Biopsy specimen transfer, processing, slide preparation, and digitization of slides for histopathologic 
scoring procedures will be detailed in a within the applicable Laboratory Manual or Histopathology 
Manual Reference Guide. Histopathology results will not be made available to study sites but will be 
located within the histopathology laboratory database and added to the electronic Trial Master File after 
the completion of the trial. 
The MES will be scored by a central reader. However, treatment decisions post-randomization will be 
made by the treating Investigator. 
For all biopsies in Table 8: 
• 
Record the extent of disease in centimeters from the anal verge 
• 
Record the distance in centimeters from the anus where biopsies are taken into the Requisition 
Form 
• 
Always review the Laboratory Manual for full instructions related to biopsy sample collection 
containers, labeling, and storage 
To identify the 
number of biopsies for 
histopathology and the 
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• 
Biopsies for histopathology are the required part of the study 
• 
Optional biopsies are only to be taken in participants who have consented for future research 
8.7.1. Endoscopy with 
Biopsy – Table 8. 
Table 8. Instructions for Endoscopic Biopsies was added to clarify biopsy procedures. Addition of 
the table required renumbering tables. 
To clarify biopsy 
procedures 
8.7.1. Endoscopy with 
Biopsy – Table 8. 
Visit 1 
(Screening) 
Worst inflamed area 
Take biopsies of the worst inflamed area within 15-25 
cm from the anus. 
• 
2 required biopsies for histopathology 
• 
2 optional biopsies for future research 
 
Non-inflamed/least inflamed area 
Take biopsies from a non-inflamed or least inflamed 
area of the colon. 
• 
2 optional biopsies for future research 
Visit 5 
(Week 12) 
 
Visit 10 
(Week 52 or EOT) 
 
Visit 14 
(Week 104 or EOT) 
Take all biopsies at the same distance (cm) from the 
anus as collected at Visit 1, regardless of tissue state at 
the time of the sampling. 
• 
2 required biopsies for histopathology 
• 
4 optional biopsies for future research 
Abbreviations: EOT, End of Treatment. 
To clarify biopsy 
procedures 
8.7.3. Mayo Clinic 
Score 
The Investigator will record the PGA in the site tablet or other relevant device or systemsource documents 
and eCRF at the specified study visits. 
To clarify the PGA 
recording procedure 
8.8.4. Clinical Safety 
Laboratory Tests 
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), then the results must be recorded in the EDC database. 
To align with the 
protocol 
8.9.4. Regulatory 
Reporting 
Requirements for 
SAEs, SUSARs, and 
Periodic Reports 
The Sponsor will comply with country-specific regulatory requirements relating to safety reporting to the 
Member States Concerned, the applicable 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. 
Morphic Therapeutic will make the determination whether the event is unexpected. It is the Principal 
Investigator’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. 
To clarify regulatory 
reporting requirements 
for Europe 

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8.9.5. Pregnancy 
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. Pregnancy in a male participant’s 
partner will require unblinding. The male study participant will be withdrawn from the study and the 
participant should complete the EOT and SFU Visits. 
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. 
To clarify the criteria 
and procedures for 
discontinuing a male 
study participant with 
a partner who 
becomes pregnant 
during the study 
8.10.1. Collection of 
Blood Samples for 
MORF-057 
Concentration 
Determination in 
Plasma – Table 9. 
Table 9. Pharmacokinetics Sampling Windows was renumbered from Table 5 due to addition of tables. 
To update table 
numbering 
8.10.1. Collection of 
Blood Samples for 
MORF-057 
Concentration 
Determination in 
Plasma – Table 9. 
Section 8.10.1.: 
TheseIf consent is provided by the participant, these samples may also be used for future PK research studies. 
Table 9. Pharmacokinetics Sampling Windows 
Visit 
Collection Ttimepoints and Aassociated Wwindows 
2, 3, 5, 7, and 10/EOT 
Before AM dose (-60 min) and at 1hr (±10 min), 2hr (±15 min), and 
4hr (±30 min) after AM dose 
4, 6, 8, and 9 
Before AM dose (-60 min) and 1 hr (±10 min) after the AM dose 
Abbreviations: EOT, End of Treatment; hr, hour; min, minute. 
For all pre-AM dose sampling, the samples should be obtained within approximately 60 minutes before the 
AM dose is administered. Furthermore, the samples should be obtained at 12 hours (60 min) after the 
previous evening’s PM dose. 
To clarify the PK 
samples from 
participants who 
consent may also be 
used for future PK 
research studies 
8.12. Future Research 
Blood, If consent is provided by the participant, blood, stool, and colonic tissue samples will be collected 
and may be used for further PD, pharmacogenomics, and microbiome-related research, and future 
researchby Morphic Therapeutics. If consent is provided by the participant, the remaining blood and 
colonic tissue samples from the study-required procedures may also be used for future research, including 
To clarify sampling 
and analyses for future 
research 

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future PK research. The purpose of future research is 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 thisthe collection of samples for future research is optional (see Section 10.1.4 for 
additional consents). 
9. Statistical 
Considerations 
Any deviationchange from the planned statistical analyses specified in the protocol will be fully 
described in the SAP and Clinical Study Report. 
To clarify terminology 
9.4. Interim Analysis 
The analysis of the 12-week Induction Period (Induction Period Analysis) will be performed after all the 
participants have completed the Week 12 assessments or discontinued the study before the Week 12 
assessment, as described in Section 9.3. 
An independent DSMB will review participant safety data and monitor scientific integrity throughout the 
study. Details related to the DSMB will be clearly delineated in the DSMB Charter. 
To clarify there is no 
interim analysis 
planned for this study 
10.1.1. Regulatory and 
Ethical Considerations 
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/IECMember States Concerned before the study is initiated. 
Any amendments to the protocol will require IRB/IECMember States Concerned 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 authorityMember States 
Concerned approval prior to initiation, in line with country-specific requirements. 
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/IECMember States Concerned, European Union Clinical Trials Directive 2001/20/EC 
or European regulationTrials Regulation 536/2014 for clinical studies (as applicable), and all other 
applicable local regulations 
To clarify regulatory 
responsibilities for 
Europe 
10.1.1. Regulatory and 
Ethical Considerations 
If the Investigator identifies a potential instance of a serious breach, the Sponsor and Contract Research 
Organization (CRO) should be notified immediately at 
 Include any 
available information at the time of the incident and copies of all documentation, if any, supporting the 
suspicion. 
To identify a contact 
email for serious 
breaches 
10.1.4. Informed 
Consent Process 
“if applicable” was added after legally authorized representative. 
Each participant or his/her legally authorized representative, if applicable, 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, Member States Concerned, and the 
IRB/IEC or study center. 
Additional Consents 
The main ICF will contain separate sections for the following additional consents: 
To clarify additional 
informed consent 
forms 
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• Optional sampling for additional receptor occupancy testing (see Section 8.11.1 and the SoA in Section 
1.2). 
• Optional sampling collection of blood, colonic tissue, and stool samples for future PD, and microbiome-
related analyses and future research, and use of the remaining blood and colonic tissue samples from the 
study-required procedures for future research, including future PK research (see Sections 8.7.1, 8.10, 
8.12, and the SoA in Section 1.2). 
• Optional blood sampling for future pharmacogenomics analysis, which will involve genetic testing (see 
Section 8.12, Section 10.9, and the SoA in Section 1.2). 
Additional ICFs will be provided to participants or their partners for review and signature, as needed: 
• Optional Maintenance Extension (see Section 4.1 and the SoA in Section 1.2) 
• Consent to courier deliveries/pick-ups (see Section 8.13) 
• Pregnant Partner (see Section 8.9.5) 
10.1.5. Data Protection 
• …. In particular, 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/IECMember States Concerned members, and by inspectors from regulatory authorities. 
• Organizational and technical arrangements that will be implemented to avoid unauthorized access, 
disclosure, dissemination, alteration, or loss of personal data processed must be described. 
To clarify data 
protection for Europe 
10.1.9. Data Quality 
Assurance 
All participant data relating to the study will be recorded on paper-based Case Report Forms (CRFs) or 
eCRFs unless transmitted to the Sponsor or designee electronically (e.g., laboratory data). The Investigator 
is responsible for having quality system processes and procedures in place verifying that CRF data entries 
against source data are accurate and correct by. The Investigator is responsible for ensuring source 
records are maintained in real-time, eCRFs are completed per eCRF Completion Guidelines, and 
physically or electronically signing the CRF. 
Guidance on completion of CRFs and eCRFs 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. 
The Sponsor or designee is responsible for the data management of this study, including quality checking 
of the datascheduled data audits and verification against original source data/documentation. 
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 documents should be retained 
for a longer period, however, if required by the applicable regulatory requirements or by an agreement with 
the Sponsor. The contents of the electronic Trial Master File pertaining to the conduct of this study must 
be retained by the Sponsor and the Investigator for at least 25 years after study completion unless local 
regulations, institutional policies, or by an agreement with the Sponsor require a longer retention period. 
However, the medical files of participants shall be archived in accordance with national law. It is the 
responsibility of the Sponsor to inform the Investigator/institution as to when these documents no longer 
need to be retained. 
To clarify the 
responsibilities of the 
Investigator and data 
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Please reference ICH E6 (R2) Section 8 for the minimum list of essential documents required for the 
conduct of a clinical trial. Additional documentation may be required by the Sponsor or CRO before, 
during, and after completion of the trial. 
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 and digitized copies are maintained in 
the site section of the electronic Trial Master File. 
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. by the Investigator and 
documented in the CRF. The Investigator may need to request previous medical records or transfer records, 
depending on the study. Also,and current medical records must be availableor transfer records as source 
documents for participants involvement (or enrollment) in this study. 
The Investigator must maintain accurate documentation (source data) that supports the information entered 
in the CRF and eCRF. 
Sponsor-designated study monitors will perform ongoing source data verification to confirm that data 
entered into the CRF/eCRF 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. 
To clarify the 
management of 
documents 
10.1.11.2. Study/Site 
Termination 
A study site is considered closed when all required documents and study supplies have been collected, all 
quality compliance activities have been completed, and a study site closure visit has been performed. 
• Failure of the Investigator to comply with the protocol, the requirements of the Member States 
Concerned, IRB/IEC or local health authorities, the Sponsor’s procedures, or GCP guidelines 
•Total number of participants includedenrolled earlier than expected 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the Investigators, 
the Member States Concerned, the IRBs/IECs, the regulatory authorities, and any contract research 
organization(s)CROs used in the study of the reason for termination or suspension, as specified by the 
applicable regulatory requirements. 
To clarify study/site 
termination for Europe 
10.3. Appendix 3: 
Clinical Laboratory 
Tests- Table 10. 
Table 10. Protocol-required Laboratory Tests. Addition of other tables required renumbering the 
table from Table 6 to Table 10. 
Renumber of tables 
due to addition of 
tables 
10.3. Appendix 3: 
Clinical Laboratory 
Tests – Table 10. 
Table 10. Protocol-required Laboratory Tests 
Coagulation 
• aPTT 
To update coagulation 
parameters 
10.3. Appendix 3: 
Clinical Laboratory 
Tests – Table 10. 
Table 10. Protocol-required Laboratory Tests 
Pregnancy testing 
• Urine hCG test (at Visits 2-11all subsequent visits for women of childbearing potential only) a 
To align with 
Section 8.8.6. 
10.3. Appendix 3: 
Clinical Laboratory 
Tests – Table 10. 
Table 10. Protocol-required Laboratory Tests 
• 
SARS-CoV-2 test (test to be determined by the site) 
To align with other 
sections of the 
protocol 

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• 
Tuberculosis test (
 test, with to be determined by the site) 
10.3. Appendix 3: 
Clinical Laboratory 
Tests – Table 10. 
Table 10. Protocol-required Laboratory Tests 
Abbreviations: 
aPTT, activated partial thromboplastin time 
ESR, erythrocyte sedimentation rate 
PTT, partial thromboplastin time 
a Local urine testing will be standard for the protocol unless serum testing is required by local regulation or 
IRB/IECMember States Concerned. 
To update 
abbreviations and 
footnote for Europe 
10.3. Appendix 3: 
Clinical Laboratory 
Tests – Table 11. 
Table 11. Abnormal Liver Function Results: Re-testing and Follow-up Procedures. Addition of other 
tables required renumbering the table from Table 7 to Table 11. 
Renumber of tables 
due to addition of 
tables 
10.3. Appendix 3: 
Clinical Laboratory 
Tests – Table 11. 
Table 11. Abnormal Liver Function Results: Re-testing and Follow-up Procedures 
Re-test Review 
To clarify, a cell was 
added 
10.4.4. Reporting of 
SAEs 
“Event” was replaced by “The SAE”. 
To align with the 
section 
10.5.2. Contraception 
Guidance 
• Bilateral tubal occlusion/ligation 
To clarify 
contraception 
10.7. Appendix 7: 
Mayo Clinic Scoring 
System for Assessment 
of Ulcerative Colitis 
Activity 
Endoscopy: The endoscopy subscore will be determined both locally and centrally by qualified personnel. 
To align with 
Section 8.7.1. 
10.9. Appendix 9: 
Genetics 
• …. Therefore, where local regulations and IRB/IECMember States Concerned allow, blood samples will 
be collected for DNA analysis from consenting participants. 
To clarify genetic 
regulations for Europe 
11. References 
. Package insert. Takeda Pharmaceuticals America, Inc., 20202022. 
To update protocol 
references 
 
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11. 
References 
. Package insert. Takeda Pharmaceuticals America, Inc., 2022. 
Feagan BG, Rutgeerts P, Sands BE, et al. GEMINI 1 Study Group. Vedolizumab as induction and 
maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369(8):699-710. 
Fedyk ER, Wyant T, Yang LL, et al. Exclusive antagonism of the α4β7 integrin by vedolizumab 
confirms the gut-selectivity of this pathway in primates. Inflamm Bowel Dis. 2012;18(11):2107-19. 
Flockhart DA, Thacker, D, McDonald, C, et al. The Flockhart Cytochrome P450 Drug-Drug 
Interaction Table. Division of Clinical Pharmacology, Indiana University School of Medicine 
(Updated 2021). https://drug-interactions.medicine.iu.edu/. Accessed 20 August 2021. 
Geboes K, Riddell R, Öst A, et al. A reproducible grading scale for histological assessment of 
inflammation in ulcerative colitis. Gut. 2000;47(3):404-9. 
. Package insert. AbbVie, Inc., 2020. 
Irvine EJ, Feagan B, Rochon J, et al. Quality of life: a valid and reliable measure of therapeutic 
efficacy in the treatment of inflammatory bowel disease. Canadian Crohn’s Relapse Prevention 
Trial Study Group. Gastroenterology. 1994;106(2):287-96. 
Marchal-Bressenot A, Salleron J, Boulagnon-Rombi C, et al. Development and validation of the 
Nancy histological index for UC. Gut. 2017;66(1):43-9. 
Marchal-Bressenot A, Scherl A, Salleron J, et al. A practical guide to assess the Nancy histological 
index for UC. Gut. 2016;65(11):1919-20. 
Mosli MH, Feagan BG, Zou G, et al. Development and validation of a histological index for UC. 
Gut. 2017;66(1):50-8. 
National 
Kidney 
Foundation. 
MDRD 
Study 
Equation. 
https://www.kidney.org/content/mdrd-study-equation. Accessed 15 Mar. 2022. 
Parente L. Deflazacort: therapeutic index, relative potency and equivalent doses versus other 
corticosteroids. BMC Pharmacol Toxicol. 2017;18(1):1. 
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. 
US FDA. Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. 
(Updated 
10 
Mar. 
2020). 
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-ta
ble-substrates-inhibitors-and-inducers. Accessed 20 August 2021. 
von Andrian UH, MacKay CR. T-cell function and migration: Two sides of the Same Coin. N Engl 
J Med. 2000;343(14):1020-34. 
Yu Y, Zhu J, Mi L, et al. Structural specializations of α4β7, an integrin that mediates rolling 
adhesion. J Cell Biol. 2012;196:131-46. 
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