Conditions: Ulcerative Colitis
Allocation: RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 57
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of MK-6194 in participants with active UC.

Detailed description:

Arms:
arm 1: Participants received low dose of MK-6194 at specified less frequent intervals arm 2: Participants received medium dose of MK-6194 at specified more frequent intervals arm 3: Participants received high dose of MK-6194 at specified more frequent intervals arm 4: Participants received high dose MK-6194 at specified less frequent intervals arm 5: Participants received MK- 6194-matching placebo via subcutaneous injection, administered either at interval 1 or interval 2

Interventions: intervention 1: MK-6194 intervention 2: MK-6194-matching placebo
Intervention descriptions: intervention 1: Subcutaneous injection intervention 2: Subcutaneous injection

Protocol document:
Prot_000.pdf: 
Official Protocol Title: 
NCT number: 
NCT04924114 
Document Date: 
13-May-2022
A Phase 1b, Randomized, Adaptive, Double-Blind, Placebo-
Controlled, Multicenter Study to Investigate the Safety,
Tolerability, Pharmacokinetics, and Pharmacodynamics of
Multiple Doses of PT101 in Subjects with Active Ulcerative
Colitis


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MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 2 of 157
PROTOCOL SYNOPSIS
Protocol Number
PT101-201
Version
Amendment 8; 13-May-2022
Phase
Phase 1b
Product Name
PT101
Sponsor
Pandion Therapeutics, Inc., a wholly-owned 
subsidiary of Merck & Co., Inc., Rahway, NJ, USA 
(known as MSD outside the United States and 
Canada)
134 Coolidge Ave
Watertown, MA 02472
USA
Protocol Title
A Phase 1b, Randomized, Adaptive, Double-Blind, Placebo-Controlled, Multicenter Study to 
Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple 
Doses of PT101 in Subjects with Active Ulcerative Colitis
Study Objectives
Primary
●To evaluate the safety and tolerability of PT101 in subjects with active ulcerative colitis 
(UC) following multiple subcutaneous (SC) doses
Secondary
●To assess the pharmacokinetics (PK) of PT101 in subjects with UC following multiple SC 
doses
●To assess the pharmacodynamics (PD) of PT101 in subjects with UC following multiple 
SC doses
●To assess the immunogenicity of PT101 in subjects with UC following multiple SC doses
●To assess the PK/PD relationship of PT101 in subjects with UC following multiple SC 
doses
08NYPB


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 3 of 157
Exploratory
●To assess improvement in disease activity in subjects with UC following multiple SC doses 
of PT101
●To evaluate changes in PT101- and UC-associated biomarkers following multiple SC doses
of PT101
Study Endpoints
Primary
●Safety and tolerability as assessed by incidence of treatment-emergent adverse events 
(TEAEs), treatment-emergent serious adverse events (TESAEs), and changes in laboratory 
values, electrocardiograms (ECGs), physical exam findings, and vital signs through Week 
12
Secondary
●PK parameters of PT101 through Week 12
●PD parameters of PT101 through Week 12
●Anti-drug antibodies (ADA) to PT101 through Week 12
●The relationship between the PT101 PK and PD response
Exploratory
●Mean change from baseline in modified Mayo Score at Week 12
●Mean change from baseline in total Mayo Score at Week 12
●Mean change from baseline in partial Mayo Score at Weeks 2, 4, 6, 8, 10, and 12
●Mean change from baseline in Robarts Histopathology Index (RHI) score at Week 12
●Mean change from baseline in UC-100 score at Week 12
●Mean change from baseline in fecal calprotectin (FC) at Weeks 4 and 12
●Mean change from baseline in high sensitivity C-reactive protein (hs-CRP) levels at Weeks 
2, 4, 8, and 12 
08NYPB


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 4 of 157
●Mean change from baseline in patient-reported outcome (PRO) measures at Week 12:
o
Inflammatory Bowel Disease Questionnaire (IBDQ)
o
Short Form-36 (SF-36)
●Proportion of subjects achieving clinical remission at Week 12
●Proportion of subjects achieving endoscopic improvement at Week 12
●Proportion of subjects achieving clinical response at Week 12
●Proportion of subjects achieving symptomatic remission at Weeks 2, 4, 6, 8, 10, and 12
●Proportion of subjects achieving symptomatic response at Weeks 2, 4, 6, 8, 10, and 12
●Proportion of subjects achieving endoscopic remission at Week 12
●Proportion of subjects achieving histologic remission at Week 12
●Proportion of subjects achieving histologic response at Week 12
●Proportion of subjects achieving mucosal healing at Week 12
●Change from baseline in partial Mayo Score beyond Week 12
●Incidence and characterization of TEAEs and laboratory abnormalities beyond Week 12
●Changes in PT101- and UC-associated biomarkers
Study Population
Inclusion Criteria
1. Male or female, 18 to 80 years of age, inclusive.
2. Diagnosis of UC at least 3 months prior to screening; diagnosis must be confirmed by 
endoscopy during the screening period. Source documentation of biopsy results (e.g., 
histopathology report) and endoscopic evidence consistent with the diagnosis of UC in the 
assessment of the Investigator is required.
3. Active UC as follows: subjects with mildly to severely active UC (i.e., 3-component 
modified Mayo Score of 4 to 9, with a rectal bleeding (RB) subscore of ≥ 1, stool frequency 
(SF) subscore of ≥ 1, and endoscopic subscore ≥1 excluding physician global assessment 
[PGA] subscore); and PGA score ≥ 1.
08NYPB


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 5 of 157
Note: The SF and RB Mayo subscores must be calculated based on the subject’s Mayo 
Score diary data recorded over the 3 consecutive days prior to the endoscopy (excluding 
the bowel preparation day; see Section 7.2.1 and Appendix 3).
4. Inadequate response, loss of response, or intolerance to at least 1 prior conventional 
therapy, and no more than 2 prior advanced therapies. 
●
Conventional Therapies
o
Oral 5-aminosalicylates
o
Rectal corticosteroids
o
Oral and/or intravenous (IV) corticosteroids
o
Oral thiopurines 
●
Advanced therapies:
o
Biologic therapy (e.g., anti-tumor necrosis factor-alpha (TNF-α), anti-integrin, anti-
interleukin therapies)
o
Janus kinase (JAK) inhibitors
o
Sphingosine-1-phosphate receptor 1 (S1P1) inhibitors 
5. Subjects at risk for colorectal cancer must have a colonoscopy prior to or at screening as 
follows: 
●
Subjects > 50 years of age must have documentation of a colonoscopy within 3 years 
of the screening visit to exclude adenomatous polyps. Subjects whose adenomas have 
been completely excised at screening are eligible.
●
Subjects with extensive colitis for ≥ 8 years, or disease limited to the left side of the 
colon for ≥10 years, must either have had a full colonoscopy to assess for the presence 
of dysplasia within 1 year before first administration of study drug or a full 
colonoscopy to assess for the presence of malignancy at the screening visit.
6. Meets the following tuberculosis (TB) screening criteria:
●
No evidence of active TB, latent TB, or inadequately treated TB as evidenced by 1 of 
the following:
o
Negative QuantiFERON test or equivalent assay reported by the central lab at 
screening or within 90 days prior to randomization date OR
o
History of fully treated active or latent TB according to local standard of care. 
Investigator must verify adequate previous anti-TB treatment and provide 
08NYPB


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 6 of 157
documentation; these subjects do not require QuantiFERON testing and eligibility 
must be approved by the Sponsor or Medical Monitor prior to enrollment in the 
study.
7. Women of childbearing potential (WOCBP) and males with female partners of 
childbearing potential must utilize highly effective contraceptive methods beginning 4 
weeks prior to first dose of study drug and continue for 30 days after the last dose of study 
drug. 
8. Body mass index (BMI) 18 to 35 kg/m2 inclusive and weight ≥50 kg.
9. Willing and able to comply with this protocol and be available for the entire duration of 
the study.
Exclusion Criteria
1. Prior treatment with recombinant IL-2 or modified IL-2 therapy, including PT101.
2. Known sensitivity to PT101 or its excipients.
3. Known history of hypersensitivity to IL-2.
4. Disease limited to the rectum (i.e., within 15 cm of the anal verge).
5. Diagnosis of toxic megacolon.
6. Suspected or known colon stricture or stenosis.
7. Diagnosis of Crohn's disease, or indeterminant colitis.
8. Has severe colitis as evidenced by: 
●
Current hospitalization for the treatment of UC
●
Likely to require a colectomy within 12 weeks of Day 1 visit, according to the 
Investigator
●
Symptom complex at screening or Day 1 visit that includes at least 4 of the following:
o
Diarrhea with ≥ 6 bowel movements/day with macroscopic blood in stool
o
Focal severe or rebound abdominal tenderness
o
Persistent fever (≥ 37.5°C) for at least 3 consecutive days within 28 days prior to 
Day 1 dosing
o
Tachycardia (> 90 beats/minute)
08NYPB


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+' -///R
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#$$$("$,3%4#/"$,3(#)"$
4(4""#("$$$'
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! $  * "( /$ 94""/ $ " )$: $ ) " /$)
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!' $)($$$$""5'
!'  $$"%"#("&/$)%4#$$2$,3
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!!' D$G/N 
*$$)#?<%"$"$($2
($($$$9')'%"(B#"("$()
G$:%"$"#2%$2)$"
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5# ##C  $,3$

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"$$"$,%#/%.%,,%#,%# $)
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"$4# ##C $,3$4"$/ /5#
"$($ $,3$"9.
=J=#,K:0$)'
"4,! #"$9"$!:#! #"$9"$
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,3.4,$(,#/"#$9$:'?
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 /"#$9$$$$$,"&/$):4,##T($,3$#
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//4"("$4$$$$$(%%0#/
$$$B$))
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74(%"4$/,4""
)#4$/#4#$"#%
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%04""($" 9$ '! !'':%:
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H$(% ),""$##)$ ""#)$$'
;2 %$,3$,),/$,$H#, 9FO:
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:(C(#	"$' E$,3$4""
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#/$#"$9"$!: 9:$$$$$/$( "
B 9,:##/$$$/B$)
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CCI
CCI
1<3%


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"4,$2"$$(9?:/$##C
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CCI
CCI
CCI
1<3%


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 14 of 157
Study drug interruption must occur in the following circumstances:

Intercurrent illness that would, in the judgment of the investigator, affect assessments 
of clinical status to a significant degree.

A nonserious infection (e.g., acute upper respiratory tract infection, simple urinary tract 
infection)

Positive urine pregnancy test (pending confirmation of pregnancy)

Subject is scheduled for elective or emergency surgery (excluding minor skin 
procedures under local or no anesthesia)
Study drug administration may be resumed only after resolution of the condition causing 
interruption and requires consultation with and approval by the medical monitor.
During the time of study drug interruption for any of the above, the subject may continue to 
have study visits and to take part in procedures and assessments if deemed medically 
appropriate by the investigator. Subjects with SARS-CoV 2 infection (or suspected infection) 
must follow local site-specific regulations and the PT101-201 COVID-19 Risk Management 
Plan regarding study visits and procedures.
Individual Stopping Rules
Dosing of study drug will be permanently discontinued in a subject if any of the following 
occurs:

Subject withdraws consent 

Severe worsening of UC disease activity defined as:
o
Requirement for hospitalization due to UC worsening; or
o
Partial Mayo Score increase of ≥ 3 points from baseline value to at least 5 points 
on 2 consecutive visits; or
o
An increase in partial Mayo Score to 9 points on 2 consecutive visits if the baseline
partial Mayo Score is > 6 
Disease worsening visits may include unscheduled visits.

Elevated absolute eosinophil count (AEC):
o
Severe eosinophilia defined as AEC > 5.0 giga/L confirmed on repeat measurement 
after at least 24 hours 
08NYPB


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 15 of 157
o
Persistent moderate eosinophilia defined as AEC > 1.5 to < 5.0 giga/L confirmed 
on repeat measurement after at least 24 hours; recurring after 2 consecutive 
administrations of study drug
o
Any new elevation of AEC > upper limit of normal (ULN) confirmed on repeat 
measurement after at least 24 hours and associated with new onset of suspected 
eosinophil-related end organ injury (see below)
Eosinophil-Related Organ Injury
Manifestations of eosinophil-related organ injury may include but are not limited to the 
following:
o
Gastrointestinal: new onset eosinophilic esophagitis/gastritis
o
Hepatic: significant elevation in liver aminotransferases, liver fibrosis, hepatic 
impairment
o
Pulmonary: eosinophilic pneumonia or new onset or worsening of asthma
o
Cardiac: heart failure, dysrhythmia, intraluminal thrombus
o
Neurologic: peripheral neuropathy or cranial neuropathy
o
Cutaneous: cutaneous fibrosis
o
Renal: interstitial nephritis, eosinophiluria, impaired renal function

Potential drug-induced liver injury (DILI) defined by new onset of an elevated aspartate 
aminotransferase (AST) or alanine aminotransferase (ALT) laboratory value that is ≥ 
3X the ULN and an elevated total bilirubin laboratory value that is ≥ 2X the ULN and, 
at the same time, an alkaline phosphatase laboratory value < 2X the ULN, as 
determined by way of protocol-specified laboratory testing or unscheduled laboratory 
testing
o
Subjects with potential DILI should stop further study drug administration and the 
Investigator should follow directions provided in the DILI Guidance Document 
(Appendix 7). 

Subjects with a marked prolongation of the QTc interval identified on ECG during the 
study (e.g., increase in QTc to > 500 ms, or > 60 ms over baseline, Appendix 8)

New onset of clinically significant cardiovascular disease such as myocardial 
infarction, unstable ischemic heart disease, stroke, heart failure, or clinically significant 
changes in ECG
08NYPB


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CCI
CCI
CCI
1<3%


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CCI
1<3%


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 19 of 157
TABLE OF CONTENTS
PROTOCOL SYNOPSIS.............................................................................................................2
TABLE OF CONTENTS ...........................................................................................................19
LIST OF TABLES .....................................................................................................................23
LIST OF FIGURES....................................................................................................................23
LIST OF APPENDICES ............................................................................................................24
ABBREVIATIONS....................................................................................................................25
1
INTRODUCTION ........................................................................................................28
1.1
Ulcerative Colitis ..........................................................................................................28
1.2
Current Treatment Options for Patients with Ulcerative Colitis...................................28
1.3
PT101............................................................................................................................29
1.4
Rationale for Current Study ..........................................................................................30
2
OBJECTIVES AND ENDPOINTS ..............................................................................30
2.1
Objectives......................................................................................................................31
2.1.1
Primary Objective............................................................................................31
2.1.2
Secondary Objectives ......................................................................................31
2.1.3
Exploratory Objectives....................................................................................31
2.2
Endpoints ......................................................................................................................31
2.2.1
Primary Endpoint.............................................................................................31
2.2.2
Secondary Endpoints.......................................................................................31
2.2.3
Exploratory Endpoints.....................................................................................32
3
INVESTIGATIONAL PLAN.......................................................................................33
3.1
Summary of Study Design ............................................................................................33
3.1.1
Initial Blinded Treatment Phase ......................................................................34
3.1.1.1
Planned Cohorts (Cohorts 1–3) ................................................................34
3.1.1.2
Optional Cohorts (Cohorts 4–6) ...............................................................35
3.1.1.3
Dose-Limiting Toxicity............................................................................35
3.1.1.4
Cohort Progression Criteria......................................................................35
3.1.1.5
In-Cohort Stopping Rules.........................................................................35
3.1.2
Continued Blinded Treatment and Open-Label Phases...................................36
3.1.3
Study Periods...................................................................................................36
3.1.4
Early Termination or Unscheduled Visit.........................................................37
3.1.5
Dose Modification and Dose Schedule Deviation...........................................37
3.1.6
Study Drug Interruption Considerations..........................................................37
3.1.7
Individual Stopping Rules ...............................................................................38
3.2
Discussion and Rationale for Study Design..................................................................40
3.2.1
Method of Assigning Patients to Treatment Groups .......................................40
3.2.2
Rationale for Selection of Doses .....................................................................40
3.2.3
Randomization and Blinding...........................................................................42
3.2.4
Risk-Benefit Profile.........................................................................................43
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MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 20 of 157
4
STUDY POPULATION ...............................................................................................43
4.1
Inclusion Criteria...........................................................................................................43
4.2
Exclusion Criteria .........................................................................................................45
4.3
Lifestyle Considerations................................................................................................48
4.3.1
Activity Restrictions........................................................................................48
4.4
Childbearing Potential...................................................................................................48
4.5
Removal of Patients from Therapy or Assessment.......................................................48
4.5.1
Discontinuation of Study Treatment................................................................48
4.5.2
Subject Withdrawal From Study .....................................................................49
4.6
Subject Replacement Strategy.......................................................................................49
5
TREATMENTS ............................................................................................................49
5.1
Investigational Study Drug ...........................................................................................49
5.1.1
Description ......................................................................................................49
5.1.2
Dose and Administration.................................................................................50
5.1.3
Storage and Handling ......................................................................................50
5.1.4
Packaging and Labeling...................................................................................50
5.1.5
Preparation.......................................................................................................50
5.2
Concomitant Therapy....................................................................................................51
5.2.1
Vaccine Guidelines..........................................................................................51
5.2.2
Prohibited Concomitant Therapy.....................................................................51
5.2.3
Allowed Concomitant Therapy .......................................................................53
5.2.3.1
Corticosteroid Tapering............................................................................53
5.3
Rescue Medications and Supportive Care.....................................................................53
5.4
Treatment Compliance..................................................................................................53
6
STUDY ACTIVITIES ..................................................................................................54
6.1
Schedule of Events........................................................................................................54
6.2
Screening Visit..............................................................................................................54
6.2.1
Screen Failure..................................................................................................54
6.2.2
Rescreening of Subjects...................................................................................54
6.3
Initial Blinded Treatment Phase....................................................................................55
6.3.1
Treatment Administration Visits .....................................................................55
6.3.2
Post-Dose Assessment Visits...........................................................................55
6.3.3
Early Termination Visit...................................................................................55
6.3.4
End of Study Visit ...........................................................................................55
6.4
Continued Blinded Treatment and Open Label Phases.................................................56
6.4.1
Continued Blinded Treatment Phase...............................................................56
6.4.2
Open-Label Phase............................................................................................56
6.5
Study Design/Dosing/Procedures Modifications Permitted Within Protocol Parameters
................................................................................................................................56
7
STUDY ASSESSMENTS.............................................................................................57
7.1
Screening/Baseline Assessments ..................................................................................57
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MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 21 of 157
7.2
Response/Efficacy Assessments ...................................................................................57
7.2.1
Mayo Score......................................................................................................57
7.2.1.1
eDiary Instructions and Review ...............................................................58
7.2.1.2
Endoscopy ................................................................................................58
7.2.2
Modified Mayo Score and Partial Mayo Score ...............................................59
7.2.3
Geboes Score and Robarts Histopathology Index ...........................................60
7.2.3.1
Geboes Score............................................................................................60
7.2.3.2
Robarts Histopathology Index..................................................................60
7.3
Patient-Reported Outcomes and Quality of Life Measures...........................................61
7.3.1
Inflammatory Bowel Disease Questionnaire...................................................61
7.3.2
Short Form-36 .................................................................................................62
7.4
Pharmacokinetic and Immunogenicity Assessments ....................................................62
7.5
Pharmacodynamics and Biomarker Assessments .........................................................62
7.5.1
Pharmacodynamic Assessments......................................................................62
7.5.2
Biomarker Assessments...................................................................................62
7.5.2.1
Future Research........................................................................................63
7.5.2.2
Genetic Analysis.......................................................................................63
7.6
Safety Assessments.......................................................................................................63
7.6.1
Adverse Events................................................................................................63
7.6.1.1
Definitions................................................................................................63
7.6.1.2
Procedures for Eliciting and Recording Adverse Events .........................67
7.6.1.3
Reporting Periods for Adverse Events and Serious Adverse Events........69
7.6.1.4
Serious Adverse Events Require Immediate Reporting ...........................69
7.6.1.5
Sponsor Safety Reporting to Regulatory Authorities...............................70
7.6.1.6
Events of Clinical  Interest .......................................................................70
7.6.1.7
Definition and Treatment of Overdose.....................................................71
7.6.2
Clinical Laboratory Tests ................................................................................71
7.6.3
Stool Sample for Enteric Pathogens Detection................................................72
7.6.4
HBV, HCV, HIV and TB Testing ...................................................................72
7.6.5
12-lead Electrocardiogram ..............................................................................72
7.6.6
Vital Signs .......................................................................................................73
7.6.7
Physical Examination......................................................................................74
7.6.8
Pregnancy Testing ...........................................................................................74
7.7
Appropriateness of Measurements................................................................................74
8
DATA QUALITY CONTROL AND QUALITY ASSURANCE................................75
8.1
Site Training and Monitoring Procedures.....................................................................75
8.2
Data Management Procedures.......................................................................................76
8.3
Access to Source Data...................................................................................................76
8.4
Accuracy and Reliability of Data..................................................................................76
8.5
Quality Assurance Procedures ......................................................................................76
08NYPB


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 22 of 157
8.6
Data Handling and Record Keeping .............................................................................77
8.6.1
Data Handling..................................................................................................77
8.6.2
Investigator Record Retention.........................................................................77
9
DATA ANALYSIS METHODS...................................................................................77
9.1
Determination of Sample Size ......................................................................................77
9.2
Study Endpoint Definitions...........................................................................................78
9.3
Statistical and Analytical Plans.....................................................................................78
9.3.1
General Considerations....................................................................................78
9.3.1.1
Subject Disposition...................................................................................78
9.3.1.2
Subject Characteristics .............................................................................78
9.3.1.3
Protocol Deviations ..................................................................................78
9.3.1.4
Prior and Concomitant Therapy ...............................................................78
9.3.1.5
Randomization and Blinding....................................................................79
9.3.1.6
Adjustments for Covariates ......................................................................79
9.3.1.7
Handling of Dropouts and Missing Data..................................................79
9.3.1.8
Multiple Comparisons and Multiplicity ...................................................79
9.3.1.9
Data Transformations and Derivations.....................................................79
9.3.2
Analysis Sets ...................................................................................................79
9.3.2.1
Intent-to-Treat Analysis Set......................................................................79
9.3.2.2
Full Analysis Set.......................................................................................79
9.3.2.3
Per Protocol Analysis Set.........................................................................80
9.3.2.4
Safety Analysis Set...................................................................................80
9.3.3
Examination of Subgroups ..............................................................................80
9.3.4
Safety and Efficacy Analyses..........................................................................80
9.3.5
Exploratory Efficacy Analyses........................................................................82
9.3.6
Pharmacokinetic and Immunogenicity Analyses.............................................82
9.3.6.1
Pharmacokinetic Analyses........................................................................82
9.3.6.2
Biomarker Analyses .................................................................................82
9.3.7
Safety Analyses ...............................................................................................82
9.3.7.1
Extent of Exposure ...................................................................................82
9.3.7.2
Adverse Events.........................................................................................82
9.3.7.3
Deaths and Serious Adverse Events.........................................................83
9.3.7.4
Clinical Laboratory Results......................................................................83
9.3.7.5
Other Safety Analyses..............................................................................83
10
INFORMED 
CONSENT, 
ETHICAL 
REVIEW, 
AND 
REGULATORY 
CONSIDERATIONS..............................................................................................83
10.1
Informed Consent..........................................................................................................83
10.2
Ethical Review..............................................................................................................84
10.3
Regulatory Considerations............................................................................................84
10.3.1
Investigator Information..................................................................................85
10.3.2
Protocol Amendments and Study Termination................................................85
08NYPB


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CCI
1<3%


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 24 of 157
LIST OF APPENDICES
Appendix 1:
Schedule of Events ..........................................................................................89
Appendix 2:
Guidance on Contraception ...........................................................................100
Appendix 3:
Mayo Scoring System....................................................................................101
Appendix 4:
Original Geboes Scoring System...................................................................103
Appendix 5:
Robarts Histopathology Index.......................................................................105
Appendix 6:
Composite UC-100........................................................................................106
Appendix 7:
Drug-Induced Liver Injury Guidance Document ..........................................107
Appendix 8: 
12-Lead Electrocardiogram Abnormality Criteria.........................................116
Appendix 9: 
Sponsor Signature Page.................................................................................119
Appendix 10:
Investigator Signature Page...........................................................................120
Appendix 11:
Document History .........................................................................................121
Appendix 12: 
SUMMARY OF CHANGES.........................................................................122
08NYPB


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 25 of 157
ABBREVIATIONS
Abbreviation
Definition
6-MP
6-mercaptopurine
ADA
anti-drug antibody
ADL
activities of daily living
AE
adverse event
AEC
absolute eosinophil count
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
AST
aspartate aminotransferase
AUC
area under the curve
AUC0-inf
area under the curve from time 0 to infinity
AUC0-t
area under the curve from time 0 to time t
AZA
azathioprine
BCG
bacille Calmette-Guerin
β-hCG
beta human chorionic gonadotropin 
BLRM
Bayesian Logistic Regression Model
BMI
body mass index
BP
blood pressure
Cmax
maximum concentration
Cmin
minimum concentration (trough)
CBC
complete blood count
CBT
continued blinded treatment
CL/F
apparent clearance
CMH
Cochran–Mantel–Haenszel test
CNS
central nervous system
CRF
case report form
CRO
contract research organization
CRP
C-reactive protein
DILI
drug-induced liver injury
DLT
dose-limiting toxicity
DRC
data review committee
ECI
events of clinical interest
ECG
electrocardiogram
eCRF
electronic case report form
EDC
electronic data capture
eGFR
estimated glomerular filtration rate
EOS
end of study
ET
early termination
EWOC
Escalation With Overdose Control
FAS
full analysis set
Fc
fragment crystallizable
FC
fecal calprotectin
GDPR
General Data Protection Regulation
GLP
Good Laboratory Practice
HBV
hepatitis B virus
08NYPB


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 26 of 157
Abbreviation
Definition
HBVcAb
HBV core antibody
HBVsAg
HBV surface antigen
HCV
hepatitis C virus
HCP
health care professional
HIV
human immunodeficiency virus
hs-CRP
high sensitivity C-reactive protein
HR
heart rate
HV
Healthy volunteer 
IB
Investigator’s Brochure
IBD
inflammatory bowel disease
IBT
initial blinded treatment
IBDQ
Inflammatory Bowel Disease Questionnaire
ICF
informed consent form
ICH
International Council for Harmonisation 
IEC
independent ethics committee
IgG1
immunoglobulin G1
IL-2
interleukin-2
IL-2M
interleukin-2 mutein
IL-2R
interleukin-2 receptor
IL-2Rα
interleukin-2 receptor alpha (also known as CD25)
IL-2Rβ
interleukin-2 receptor beta (also known as CD122)
IL-2Rγ
interleukin-2 receptor gamma (also known as CD132)
IND
investigational new drug
INR
International Normalized Ratio
IPT
immunophenotyping
IRB
institutional review board
ITT
intent-to-treat
IWRS
interactive web response system
JAK
Janus kinase
LAIV
live attenuated influenza vaccine
LDH
lactate dehydrogenase
LLOQ
lower limit of quantification
MedDRA
Medical Dictionary for Regulatory Activities
MMR
measles, mumps, and rubella
MMRM
mixed-model-repeated measure
MMRV
measles, mumps, and rubella plus varicella
MTD
maximum tolerated dose 
NCI CTCAE
National Cancer Institute Common Terminology Criteria for Adverse Events
NK
natural killer
NOAEL
no observed adverse effect level 
OL
open-label
PBMC
peripheral blood mononuclear cell
PCR
polymerase chain reaction
PD
pharmacodynamics
PGA
physician global assessment
PK
pharmacokinetics
08NYPB


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MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 28 of 157
1
INTRODUCTION
1.1
Ulcerative Colitis
Ulcerative colitis (UC) is a chronic inflammatory disease of the rectal and colonic mucosa that 
is characterized by periods of remission and relapse. UC often first appears during young 
adulthood, and typically presents with blood in the stool and diarrhea. Additional symptoms 
vary depending on the severity of inflammation and extent of disease and can include
incontinence, increased frequency of bowel movements, mucus discharge, and abdominal 
discomfort. Up to 15% of patients initially present with severe disease, which is often
associated with systemic symptoms, including fever, weight loss, and malaise. Furthermore, 
UC is associated with an increased risk of colorectal cancer (Ungaro, 2017). With poorly 
controlled disease, the risk of developing colorectal cancer increases with time (Jess, 2012).
The pathogenesis of UC is multifactorial, involving genetic predisposition, epithelial barrier 
defects, dysregulated immune responses, and environmental factors (Chang, 2020). Although 
the precise cause of UC is unknown, genetically susceptible individuals appear to have a 
dysregulated mucosal immune response to commensal gut flora and studies show that the 
homeostatic balance between regulatory T cells (Tregs) and effector T cells is disturbed in the 
colonic mucosa of patients with UC (Ordás, 2012; Ungaro, 2017). 
The incidence and prevalence of UC have been increasing worldwide. In a systematic review 
of population-based studies, the highest reported prevalence values were reported in Europe 
and North America. In Europe, the incidence and prevalence ranged from approximately 
1-58 per 100,000 person years and 2.4–505 per 100,000 person years, respectively and in North 
America, the incidence and prevalence ranged from 8.8–23.1 per 100,000 person years and 
139.8–286.3 per 100,000 person years, respectively. Since the end of the 20th century, the 
incidence of both Crohn’s disease and UC have also been increasing in newly industrialized 
countries in Africa, Asia, and South America (Ng, 2018). 
1.2
Current Treatment Options for Patients with Ulcerative Colitis
While several treatment options are available and in development for the treatment of UC, 
there are currently no curative therapies. Goals of treatment include improved quality of life, 
reduction in long-term corticosteroid use, and minimization of cancer risk. Treatment of UC is 
dependent on the severity and the location of disease. Mild to moderate UC treatment may be 
treated with oral aminosalicylates, topical mesalamine, or topical steroids. For moderately 
active disease, oral corticosteroids and immunomodulators such as azathioprine (AZA) and 
6-mercaptopurine (6-MP) may be utilized (Danese and Fiocchi, 2011). For more severe 
disease, tumor necrosis factor-alpha (TNF-α) antagonists such as infliximab (Remicade®), 
adalimumab (Humira®), and golimumab (Simponi®), or an α4β7 integrin antagonist such as 
vedolizumab (Entyvio®) are often employed. Tofacitinib (Xeljanz®), an oral Janus kinase 
(JAK) inhibitor is also approved for the treatment of adult patients with moderately to severely 
active disease (Harbord, 2017). Although these agents may be effective in inducing disease 
remission, many are associated with toxicities. The use of 6-MP and AZA can result in 
neutropenia, pancytopenia, pancreatitis, nephrotoxicity, hepatotoxicity, and in rare cases, 
hepatosplenic T-cell lymphoma (Bousvaros, 2010; Carter, 2004; Chaparro, 2009; Turner and 
08NYPB


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MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 31 of 157
2.1
Objectives
2.1.1
Primary Objective
●
To evaluate the safety and tolerability of PT101 in subjects with active UC following 
multiple SC doses
2.1.2
Secondary Objectives
●
To assess the PK of PT101 in subjects with UC following multiple SC doses 
●
To assess the PD of PT101 in subjects with UC following multiple SC doses 
●
To assess the immunogenicity of PT101 in subjects with UC following multiple SC 
doses 
●
To assess the PK/PD relationship of PT101 in subjects with UC following multiple SC 
doses
2.1.3
Exploratory Objectives
●
To assess improvement in disease activity in subjects with UC following multiple SC 
doses of PT101
●
To evaluate changes in PT101- and UC-associated biomarkers following multiple SC 
doses of PT101
2.2
Endpoints
2.2.1
Primary Endpoint
●
Safety and tolerability as assessed by incidence of treatment-emergent adverse events 
(TEAEs), treatment-emergent serious adverse events (TESAEs), and changes in 
laboratory values, electrocardiograms (ECGs), physical exam findings, and vital signs
through Week 12
2.2.2
Secondary Endpoints
●
PK parameters of PT101 through Week 12
●
PD parameters of PT101 through Week 12
●
Anti-drug antibodies (ADA) to PT101 through Week 12
●
The relationship between the PT101 PK and PD response 
08NYPB


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 32 of 157
2.2.3
Exploratory Endpoints
●
Mean change from baseline in modified Mayo Score at Week 12
●
Mean change from baseline in total Mayo Score at Week 12
●
Mean change from baseline in partial Mayo Score at Weeks 2, 4, 6, 8, 10, and 12
●
Mean change from baseline in Robarts Histopathology Index (RHI) score at Week 12
●
Mean change from baseline in UC-100 score at Week 12
●
Mean change from baseline in fecal calprotectin (FC) at Weeks 4 and 12
●
Mean change from baseline in high sensitivity C-reactive protein (hs-CRP) levels at 
Weeks 2, 4, 8, and 12 
●
Mean change from baseline in patient-reported outcome (PRO) measures at Week 12
o
Inflammatory Bowel Disease Questionnaire (IBDQ)
o
Short Form-36 (SF-36)
●
Proportion of subjects achieving clinical remission at Week 12 
●
Proportion of subjects achieving endoscopic improvement at Week 12 
●
Proportion of subjects achieving clinical response at Week 12
●
Proportion of subjects achieving symptomatic remission at Weeks 2, 4, 6, 8, 10, and 12
●
Proportion of subjects achieving symptomatic response at Weeks 2, 4, 6, 8, 10, and 12
●
Proportion of subjects achieving endoscopic remission at Week 12 
●
Proportion of subjects achieving histologic remission at Week 12 
●
Proportion of subjects achieving histologic response at Week 12
●
Proportion of subjects achieving mucosal healing at Week 12
●
Change from baseline in partial Mayo Score beyond Week 12
●
Incidence and characterization of TEAEs and laboratory abnormalities beyond 
Week 12
●
Changes in PT101- and UC-associated biomarkers 
08NYPB


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MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 36 of 157
termination of dosing within the cohort; DRC may also recommend de-escalation to lower 
doses/reduced frequency dosing regimen. If dosing within a cohort is terminated, the next-
lower dose may be declared the maximum tolerated dose (MTD). Alternatively, an additional 
cohort at an intermediate dose may be added to better define the MTD.
The study may be stopped at the discretion of the Sponsor based on recommendations of the 
DRC. In all cases, necessary measures will be taken to ensure appropriate safety follow-up for 
all subjects in the trial.
3.1.2
Continued Blinded Treatment and Open-Label Phases
Subjects who have achieved clinical response (based on the modified Mayo Score using the 
endoscopic score derived by the Investigator) at Week 12 will be eligible to enter the continued 
blinded treatment (CBT) phase of the study. Subjects in the CBT phase will receive the same 
treatment allocation (PT101 or placebo) as received during the IBT phase; subjects who
received PT101 will continue receiving PT101 at the same dose/regimen. Corticosteroid 
tapering will be initiated at Week 12 of the IBT phase for subjects entering the CBT phase.
Subjects who do not achieve clinical response at Week 12 will have the option to enter an
open-label (OL) phase of the study. Subjects in the OL phase will receive PT101 at the same 
dose/regimen as received by subjects in their cohort during the IBT phase. Subjects 
participating in the OL phase who achieve a clinical response using the partial Mayo Score at 
Week 24 of the OL phase will also undergo corticosteroid tapering. Subjects who do not 
achieve a clinical response using the partial Mayo Score at Week 24 of the OL phase may 
continue on open-label treatment if it is considered in the best interest of the subject at the 
discretion of the Investigator.
Subjects with insufficient data to assess clinical response at Week 12 of IBT will not be eligible 
to enter the CBT or OL phases and will be discontinued from the study.
For subjects not entering the CBT or OL phases, the site will conduct a follow-up phone call 
approximately 48 hours after the Day 85 visit to confirm no adverse events related to study 
procedures had occurred.
Participation in the CBT and OL is for a maximum of 9 months. 
The clinic will perform a follow-up call approximately 90 days after the last dose of study drug 
for all subjects in the trial (those who complete IBT only or enter the CBT or OL phase) to 
assess any changes in UC disease status.
3.1.3
Study Periods
The study will be conducted as follows:

Screening Period: will begin when the informed consent form (ICF) is signed. During 
this period, a subject will undergo baseline assessments to determine eligibility for 
study participation. Endoscopy (flexible sigmoidoscopy or colonoscopy as indicated) 
08NYPB


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MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 38 of 157

Subject is scheduled for elective or emergency surgery (excluding minor skin 
procedures under local or no anesthesia)
Study drug administration may be resumed only after resolution of the condition causing 
interruption, and requires consultation with and approval by the medical monitor.
During the time of study drug interruption for any of the above, the subject may continue to 
have study visits and to take part in procedures and assessments if deemed medically 
appropriate by the investigator. Subjects with SARS-CoV 2 infection (or suspected infection) 
must follow local site specific regulations and the PT101-201 COVID-19 Risk Management 
Plan regarding study visits and procedures.
3.1.7
Individual Stopping Rules
Dosing of study drug will be permanently discontinued in a subject if any of the following 
occurs:

Subject withdraws consent 

Severe worsening of UC disease activity defined as:
o
Requirement for hospitalization due to UC worsening; or
o
Partial Mayo Score increase of ≥ 3 points from baseline value to at least 5 points 
on 2 consecutive visits; or
o
An increase in partial Mayo Score to 9 points on 2 consecutive visits if the baseline
partial Mayo Score is > 6 
Disease worsening visits may include unscheduled visits.

Elevated absolute eosinophil count (AEC):
o
Severe eosinophilia defined as AEC > 5.0 giga/L confirmed on repeat measurement 
after at least 24 hours 
o
Persistent moderate eosinophilia defined as AEC > 1.5 to < 5.0 giga/L confirmed 
on repeat measurement after at least 24 hours; recurring after 2 consecutive 
administrations of study drug
o
Any new elevation of AEC > upper limit of normal (ULN) confirmed on repeat 
measurement after at least 24 hours and associated with new onset of suspected 
eosinophil-related end organ injury (see below) 
08NYPB


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 39 of 157
Eosinophil-Related Organ Injury
Manifestations of eosinophil-related organ injury may include but are not limited to the 
following:
o
Gastrointestinal: new onset eosinophilic esophagitis/gastritis
o
Hepatic: significant elevation in liver aminotransferases, liver fibrosis, hepatic 
impairment
o
Pulmonary: eosinophilic pneumonia or new onset or worsening of asthma
o
Cardiac: heart failure, dysrhythmia, intraluminal thrombus
o
Neurologic: peripheral neuropathy or cranial neuropathy
o
Cutaneous: cutaneous fibrosis
o
Renal: interstitial nephritis, eosinophiluria, impaired renal function

Potential drug-induced liver injury (DILI) defined by new onset of an elevated aspartate 
aminotransferase (AST) or alanine aminotransferase (ALT) laboratory value that is ≥ 
3X the ULN and an elevated total bilirubin laboratory value that is ≥ 2X the ULN and, 
at the same time, an alkaline phosphatase laboratory value < 2X the ULN, as 
determined by way of protocol-specified laboratory testing or unscheduled laboratory 
testing
o
Subjects with potential DILI should stop further study drug administration and the 
Investigator should follow directions provided in the DILI Guidance Document 
(Appendix 7). 

New onset of clinically significant cardiovascular disease such as myocardial 
infarction, unstable ischemic heart disease, stroke, heart failure, or clinically significant 
changes in ECG

Subjects with a marked prolongation of the QTc interval identified on ECG during the 
study (e.g., increase in QTc to > 500 ms, or > 60 ms over baseline, Appendix 8)

New onset of pulmonary edema, interstitial lung disease, or clinically significant 
dyspnea

New onset of clinically significant peripheral edema or reduced blood pressure (semi 
recumbent [supine or seated also acceptable, per site standard procedures]) SBP < 90 
mmHg associated with symptoms such as lightheadedness, sustained over at least the 
next 90 minutes):
08NYPB


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 40 of 157
o
SBP (supine or seated also acceptable) will be obtained as triplicate 
measurements every 30 minutes over the following 90 minutes (i.e. at 30, 60-
and 90 minutes). If a subject’s SBP remains < 90 mmHg for the median of all 
3 measurements over the 90 minute period, this is defined as a sustained finding, 
and dosing will end for that particular subject.

Reduction of estimated glomerular filtration rate (eGFR) < 60 mL/min confirmed on 
repeat measurement after at least 24 hours

Serious infection requiring hospitalization or intravenous antibiotics

Investigator or Sponsor determines that the subject will not benefit from further study 
drug

Adverse event or laboratory or physical examination finding that in the opinion of the 
Investigator or Sponsor presents excessive risk to the subject

Adverse event of Grade 3 or higher in severity that is attributable to study drug, or any 
unexplained ≥Grade 3 AE that is not reasonably related to the underlying disease 
process

Subject becomes pregnant or plans a pregnancy within the study conduct

Subject is unable to comply with the protocol requirements

Sponsor or Regulatory Agency terminates the study
3.2
Discussion and Rationale for Study Design
This study is a double-blind, randomized, placebo-controlled trial. 
The efficacy endpoints utilize subject-reported and physician-reported components of the 
Mayo Score; therefore, the use of a double-blind, randomized design will minimize bias that 
could be introduced by subject or Investigator knowledge of the treatment assignment. As UC 
has a relapsing and remitting course, the use of a placebo comparator will ensure that a true 
treatment effect is being assessed.
3.2.1
Method of Assigning Patients to Treatment Groups
Centralized registration and treatment assignment for eligible subjects will be completed using 
an interactive web response system (IWRS).
3.2.2
Rationale for Selection of Doses
Study PT101-201 will represent the initial multiple-dose regimen of PT101 in patients with 
UC to determine an improved benefit-risk profile for the proposed study duration of 12 weeks
08NYPB


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1<3%


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 43 of 157
to facilitate planning for subsequent dosing cohorts. All unblinded personnel will be fire-
walled from the operational study team at the Sponsor and CRO to prevent inadvertent 
unblinding of treatment assignment and to minimize the risk of introducing bias into the study 
results. Designation of unblinded study personnel will be authorized by the Sponsor’s Chief 
Medical Officer and the lead study biostatistician. A roster of unblinded personnel will be 
maintained in the TMF. All unblinded personnel will be trained in steps necessary to maintain 
an adequate firewall. 
3.2.4
Risk-Benefit Profile
Although a number of therapeutic options are available for patients with UC, existing agents 
are limited by low efficacy and/or toxicities. Moderately to severely active UC remains a 
serious, life-threatening disease for which new therapies are needed. PT101 is an IL-2M that 
selectively activates Tregs over other cell types and may therefore represent a unique 
opportunity to rebalance the immune system in patients with UC.
Adverse events associated with PT101 in cynomolgus monkey studies and the Phase 1a SAD 
study are detailed in the Investigator Brochure. Overall, on the basis of the available 
nonclinical and clinical data the risk-benefit profile of PT101 is judged acceptable for the 
proposed clinical study. The information obtained in this study will be used for the further 
clinical development of PT101.
Sites will adhere to COVID-19 rules and regulations as mandated by local authorities. Trial 
subject safety and data validity will be prioritized. In case of conflict, safety will be given 
priority. Further information can be found in the PT101-201 COVID-19 Risk Management 
Plan.
4
STUDY POPULATION
Subjects must meet all of the inclusion and none of the exclusion criteria to be eligible for this 
study. Eligibility criteria may not be waived by the investigator.
4.1
Inclusion Criteria
1. Male or female, 18 to 80 years of age, inclusive.
2. Diagnosis of UC at least 3 months prior to screening; diagnosis must be confirmed by 
endoscopy during the screening period. Source documentation of biopsy results (e.g., 
histopathology report) and endoscopic evidence consistent with the diagnosis of UC in the 
assessment of the Investigator is required.
3. Active UC as follows: subjects with mildly to severely active UC (i.e., 3-component 
modified Mayo Score of 4 to 9, with a rectal bleeding subscore of ≥ 1, stool frequency 
subscore of ≥ 1, and endoscopic subscore ≥ 1 excluding physician global assessment [PGA]
subscore) and PGA score ≥ 1.
08NYPB


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 44 of 157
Note: The stool frequency (SF) and rectal bleeding (RB) Mayo subscores must be 
calculated based on the subject’s Mayo Score diary data recorded over the 3 consecutive 
days prior to the endoscopy (excluding the bowel preparation day; see Section 7.2.1 and 
Appendix 3).
4. Inadequate response, loss of response, or intolerance to at least 1 prior conventional 
therapy, and no more than 2 prior advanced therapies.
●Conventional Therapies
o
Oral 5-aminosalicylates
o
Rectal corticosteroids
o
Oral and/or intravenous (IV) corticosteroids
o
Oral thiopurines
●Advanced therapies:
o
Biologic therapy (e.g., anti- tumor necrosis factor-alpha (TNF-α), anti-integrin, 
anti-interleukin therapies)
o
Janus kinase (JAK) inhibitors
o
Sphingosine-1-phosphate receptor 1 (S1P1) inhibitors 
5. Subjects at risk for colorectal cancer must have a colonoscopy prior to or at screening as 
follows: 
●Subjects > 50 years of age must have documentation of a colonoscopy within 3 years 
of the screening visit to exclude adenomatous polyps. Subjects whose adenomas have 
been completely excised at screening are eligible.
●Subjects with extensive colitis for ≥ 8 years, or disease limited to the left side of the 
colon for ≥10 years, must either have had a full colonoscopy to assess for the presence 
of dysplasia within 1 year before first administration of study drug or a full 
colonoscopy to assess for the presence of malignancy at the screening visit. 
6. Meets the following tuberculosis (TB) screening criteria:
●No evidence of active TB, latent TB, or inadequately treated TB as evidenced by 1 of 
the following:
o
Negative QuantiFERON test or equivalent assay reported by the central lab at 
screening or within 90 days prior to randomization date, OR
08NYPB


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 45 of 157
o
History of fully treated active or latent TB according to local standard of care. 
Investigator must verify adequate previous anti-TB treatment and provide 
documentation; these subjects do not require QuantiFERON testing, and 
eligibility must be approved by the Sponsor or Medical Monitor prior to 
enrollment in the study.
7. Women of childbearing potential (WOCBP) and males with female partners of 
childbearing potential must utilize highly effective contraceptive methods beginning 
4 weeks prior to first dose of study drug and continue for 30 days after the last dose of 
study drug (see Appendix 2 for details). 
8. Body mass index (BMI) 18 to 35 kg/m2 inclusive and weight ≥50 kg.
9. Willing and able to comply with this protocol and be available for the entire duration of 
the study.
4.2
Exclusion Criteria
1. Prior treatment with recombinant IL-2 or modified IL-2 therapy, including PT101.
2. Known sensitivity to PT101 or its excipients.
3. Known history of hypersensitivity to IL-2.
4. Disease limited to the rectum (i.e., within 15 cm of the anal verge).
5. Diagnosis of toxic megacolon.
6. Suspected or known colon stricture or stenosis.
7. Diagnosis of Crohn’s disease, or indeterminant colitis.
8. Has severe colitis as evidenced by: 
●Current hospitalization for the treatment of UC
●Likely to require a colectomy within 12 weeks of Day 1 visit, in the opinion of the 
Investigator
●Symptom complex at screening or Day 1 visit that includes at least 4 of the following:
o
Diarrhea with ≥ 6 bowel movements/day with macroscopic blood in stool
o
Focal severe or rebound abdominal tenderness
o
Persistent fever (≥ 37.5°C) for at least 3 consecutive days within 28 days prior 
to Day 1 dosing
08NYPB


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! $  * "(/$ 94""/ $ " )$: $ ) " /$)
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!' &$#)$)$#),#))"$'
!' $)($$$$""5'
!' $$"%"#("&/$)%4#$$2$,3
$((4"$/%#$#'
!!' D$G/N
*$$)#?<%"$"$($2
($($$$9')'%"(B#"("$()
G$:%"$"#2%$2)$"
#)"GBG/'
:6-
#(%	
:6-6+
'%!
,3$ 4/$$$ #"$/ ("$)/$
$("$($)#( ",
#"$
:6:
		
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$.9')'%"$%,$#)%,#":"$
# #$' #$ $ (  $  "$ ( "  
4 / ) 
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$$'
:6>
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"#$ "$)$,(($,3 $4"4($
("$'"$9$:(4"4$,"$,3Y$-E'
:6>6+
(%
$,3Y$$,$(("$$ $ !''+'
CCI
1<3%


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 !
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:6>67
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" H$ ,) / , " #$ 4  , $ $ # ( " /
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$#$ "/ , # .% " 4  ) ,  2 ,4 "
$,3Y$#$("$#$'&"$$%"H$($#
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$,3 4 ) / " $ $ ) $ " $,3 ,) #' "
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>
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>6+6+

$,(("&O($$$((
(,"&)<E'
,$ $#$$,)$,4
/)$',4,$$*TC$*T0)$
CCI
CCI
1<3%


	


 !

"#$%&' (
)* (*+
$,"/$)/$'$)9#,:$$#$)
$4",'
>6+67
'
$,3'$/$ 
)$ (,/"# "$4,,"0-
(4)//4(/,$(%%0%$$(5$$/%
,2'
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  ,  ,( $ ( $ )% $$ "4$ $#(
>6+6-
B	
5# #%  $" , /$ $#  " $ # $) $
4",$$$,".$$(('
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)  $, , ( /$' " (  " ,C$  /$ 4 , 
4"##/$,$$$'
>6+6>
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"$(""/
$4$#' ,4, *TC$*T0)$%4""4,#/,"
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##$($)'
" &/$)%   H( $)% 4 $ $ ) )  "
$$""'
CCI
CCI
CCI
CCI
1<3%


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 51 of 157
5.2
Concomitant Therapy
All concomitant medications administered will be recorded from randomization through the 
safety reporting period. Any concomitant medication given for AEs that are the result of a 
study protocol-specified intervention should be recorded from the time of informed consent.
5.2.1
Vaccine Guidelines
Prior to study participation, it is recommended that the subject’s vaccinations be brought up to 
date according to local vaccination standards.
Inactivated vaccines (such as inactivated influenza vaccines) should be administered according 
to local vaccination standards whenever medically appropriate; however, there are no available 
data on the concurrent use of PT101 and its impact on immune responses following 
vaccination.
Live or attenuated vaccines (including, but not limited to varicella, measles, mumps, and 
rubella [MMR], MMR plus varicella [MMRV], live attenuated influenza vaccine [LAIV], 
yellow fever, Ty21a oral typhoid, bacille Calmette-Guerin [BCG], smallpox, and rotavirus) are 
prohibited within 4 weeks of screening, throughout the study, and for 12 weeks after the last 
dose of study drug.
Regarding precautions related to the vaccination of household or close contacts, subjects 
participating in this study are recommended to follow country-specific guidelines or those of 
the 
US 
Centers 
for 
Disease 
Control 
regarding 
contacts 
as 
appropriate 
(https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.html).
In 
general, household contacts and other close contacts of subjects in this trial may receive all 
age- and exposure-appropriate vaccines.
5.2.2
Prohibited Concomitant Therapy
Some medications and treatments may have an impact on the safety of the subjects and/or 
efficacy assessments of this study. Prohibited concomitant medications that may impact 
efficacy assessments or impact subject safety are presented in Table 1. Subjects who initiate 
any of these concomitant medications at any time during the IBT phase of the study must be
discontinued from study drug and will not be eligible for the OL or CBT phase of the study. 
Subjects who initiate any of these concomitant medications at any time during the OL or CBT 
phase of the study must be discontinued from study drug.
Medications or vaccinations specifically prohibited in the exclusion criteria and in Table 1 are 
not allowed during the ongoing study. If there is a clinical indication for any medications or 
vaccinations specifically prohibited (i.e., as supportive care or to treat AEs as deemed 
necessary by the investigator or the subject’s physician), discontinuation from study drug may 
be required. The investigator should discuss any questions regarding this with the Medical 
Monitor. The final decision on any supportive therapy or vaccination rests with the investigator 
and/or the subject’s primary physician. However, the decision to continue the subject on study 
drug requires the mutual agreement of the investigator, the Sponsor, and the subject.
08NYPB


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 52 of 157
Table 1:
Prohibited Concomitant Medications that May Impact Efficacy 
Assessments or Impact Subject Safety
Drug Class
Agents Disallowed
Prohibited Period
TNFα antagonist
Infliximab (t½: 9.5 days) 
Adalimumab (t½: 10-20 days)
Golimumab (t½: 12-14 days)
Certolizumab (t½: 14 days)
5 half-lives prior to Day 1* through the end 
of treatment
Integrin antagonist
Vedolizumab (t½: 25 days)
Natalizumab (t½: 11 days)
5 half-lives prior to Day 1* through the end 
of treatment
Interleukin antagonist
Ustekinumab (t½: 19 days)
5 half-lives prior to Day 1* through the end 
of treatment
JAK inhibitor
Baricitinib (t½: 12 hours)
Tofacitinib (t½: 3 hours)
Tofacitinib XR (t½: 6-8 hours)
Upadacitinib (t½: 8-14 hours)
5 half-lives prior to Day 1* through the end 
of treatment
S1P1 inhibitor
Fingolimod (t½: 6-9 days)
Ozanimod (t½: 11 days)
Siponimod (t½: 30 hours)
5 half-lives prior to Day 1* through the end 
of treatment
Rectal compounds
Rectal 
mesalamine, 
rectal 
corticosteroids
2 weeks prior to screening endoscopy
through the end of treatment
Antidiarrheal agents**
Loperamide, 
diphenoxylate/atropine
2 weeks prior to screening endoscopy
through the end of treatment
Other (non-biologic)
Cyclosporine (oral), thalidomide, 
tacrolimus, leflunomide, and any
investigational agent
2 weeks prior to Day 1 through the end of 
treatment
Investigational biologics
Any investigational biologic agent
30 days prior to Day 1 (or at least 5 half-
lives) through the end of treatment 
*If subject has taken the concomitant medication within 5 half-lives prior to Day 1, but has an undetectable serum level on a 
commercially available assay assessed at screening, this is also acceptable for inclusion.
** Subjects who mistakenly use an antidiarrheal for a limited period of time (1 – 2 days) may be allowed to continue 
participation in the study following discussion and approval by the Medical Monitor and the Investigator.
If other prohibited concomitant medications, as shown in Table 2 are taken by a subject prior 
to study participation or during the study, the Investigator must contact the Medical Monitor.
Table 2:
Other Prohibited Concomitant Medications
Drug Class
Agents Disallowed
Prohibited Period
Other biologics
Fecal 
Microbiota 
Transplant 
(FMT), antibody based or other 
systemic 
biologics, 
eg, 
denosumab, trastuzumab
Requires 
Medical 
Monitor 
consultation
08NYPB


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,$V	)#'
O4$$#(#B#$(7&0($
9""($$"$,3Y$) 5: ,$4"#
$4""'
"$(#$"$#$4'F#$$-7$",
$$$$,"/$)$,$,$$# $4""
'
>676-6+

$#$",($#$;2 ("&1#"$($,3$
)"1#"$' E$#$ ;2("&1#"$%"$#
$",;2
 ("FO#"$( $,3$4""/"/ 
$#$(, "#'"$$",$)
'* )#42#*)#42(#$9H/#(#$:
"$,3$)$$'1$$",#,! )/U!
42$"$,3$)2),$'E$,3$))$#%
$$,$$$$#)"$) $(
($#$$##',3$4",$#4, 4
"$',3$4"$"$$ ,"C$(
4"#$$ "$$/"$)
$$,$ ("$'
>6-
! 
$ 4,$((4"#$4"###$$($/
"$#$(#$(/'
##C+ ($#(0&O&) $,$/
#DY$O4$$'
>6:
	
 ) $ 4 , #( , H(  $) $ $(( 
$$"-E'
CCI
CCI
1<3%


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 54 of 157
6
STUDY ACTIVITIES
6.1
Schedule of Events
Adverse events and concomitant medications will be recorded from randomization through the 
safety reporting period (see Section 7.6.1.3). Adverse events that are the result of study 
protocol-specified intervention (defined in Section 7.6.1.1) as well as any concomitant 
medications given for treatment of these adverse events, should be recorded from the time of 
informed consent. Schedules of events (SOEs) are provided in Appendix 1. Descriptions of all 
study assessments are presented in Section 7.
On applicable visits, all PRO and quality of life-related assessments must be completed prior
to other study procedures. 
6.2
Screening Visit
Documented, signed, and dated informed consent must be obtained by the Investigator or 
his/her designee prior to the performance of any study related procedures, including washout 
of prohibited medications. In regions where the legal age of consent is older than 18 years, 
informed consent must be obtained from and signed by both the subject and his or her legally 
acceptable representative, as applicable. A copy of the signed ICF must be given to the subject 
for their records.
After informed consent has been obtained, the subject has approximately 4 weeks (± 1 week)
to complete all screening procedures. The subject’s eligibility for the study will be evaluated 
during this period based on medical history, physical examination, laboratory values, Mayo 
Score diary data (SF and RB), and additional assessments, including screening endoscopy. 
Subjects who meet all of the inclusion and none of the exclusion criteria can be enrolled in the 
treatment period. For subjects eligible for this study, the ramdomization number is the same as 
the screening number. 
Refer to Appendix 1 for all the procedures to be performed during the Screening Period. 
6.2.1
Screen Failure
A screen failure is defined as a subject who has provided informed consent and fails to meet 
the inclusion and/or exclusion criteria. Subjects who fail screening will not be randomized into 
the study nor receive study drug. 
6.2.2
Rescreening of Subjects
Subjects may be rescreened once after consultation with the Medical Monitor. In these cases,
a new screening number must be assigned for each subject rescreened. Rescreening should 
include all screening procedures listed in the SOEs (see Table 3 and Table 4) unless noted 
otherwise and a new ICF must be signed to confirm ongoing consent for the study.
08NYPB


	
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=6-6+
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$$"4$$#(' ,3$4,,$/("($
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=6-67
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$',3$4(4"$$$$$$"F?$9##C:'
=6-6-
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,3$4"/I$($)$",)#$/$$
4""&1#"$'
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(?/$##C  $("$$($)$
=6-6:
(%
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" $ 4   (4# #" 
##C
"$(" 0*/$(?$ 0 *$
#$ "' %(4###C	 $("(
$( 4,$$$$")$5$$$$' ,3$4,
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&($,3$4"4"$"$(("##(/)$
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$,3($(?F'
CCI
CCI
CCI
CCI
CCI
1<3%


	


 !

"#$%&' (
)* (*+
=6:
)	"#	
;290*:%),("1FO#"$4,
,$#$$$9$#$/$$  $#$:("(
9$)"$#$,$/,"&/$):'
=6:6+
)	
,3$4"),"1 #"$$$,!'' 4/
"($$(,$)9$$ "&1#"$:0
*
$$$$$  "$ #"$ 4 #
/$(4"C#(($$$$$
,3$4"/$((4#/$##C $ ("
$$($)'"4$/(4###C	$("
($($)$$$$")$5$$$$' ,3$4,$2
4"""5$/%4""""/C#5( 9($#(
/$#$:%4""""/$4"#(5'
=6:67
"/#	
,3$4"),"FO#"$$$,!'' 4/"
($$( 9"$,"F#O,"$:0* (
$$$$$"$#"$4$$$$$(
C#((
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4$ /(4###C	 $("($( $$$$
")$5$$$$' ,3$4,$24"""5$/%4""
""/C#5( 9($#(/$#$:%4"""
"/$4"#(5'
=6>
%11 (A	
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#  $ ,) ' "$ # $ 4 4" $ (C, 
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$% $) )% B   , #$    ,
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$()( "$$,3$'
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
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
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CCI
CCI
CCI
CCI
CCI
CCI
1<3%


MK-6194-002-08
Study PT101-201 Clinical Protocol
Amendment 8; 13-May-2022
PT101
Pandion Therapeutics, Inc. - Confidential
Page 57 of 157

Modification of the PK/PD sample processing and shipping details based on newly 
available data
7
STUDY ASSESSMENTS
7.1
Screening/Baseline Assessments
Only subjects who meet all eligibility criteria specified in Section 4 will be enrolled in this 
study.
Subject medical history includes a thorough review of significant past medical history, current 
conditions, review of body systems, response to prior UC treatment, and any concomitant 
medications.
7.2
Response/Efficacy Assessments
7.2.1
Mayo Score
The Mayo Score is an instrument designed to measure disease activity in patients with UC. 
The Mayo Score ranges from 0 to 12 points and consists of the following 4 subscores, each 
graded from 0 to 3, with higher scores indicating more severe disease (see Appendix 3).

Stool frequency (SF)

Rectal bleeding (RB)

Findings of flexible sigmoidoscopy

Physician global assessment (PGA)
Calculation of the SF and RB subscores requires an assessment of the subject’s bowel 
movement frequency and quantification of the amount of blood in the stool. The SF and RB
Mayo subscores will be calculated based on the subject’s Mayo Score diary data recorded in 
the week prior to the endoscopy (for modified Mayo Score) or prior to the visit (for partial 
Mayo Score) (see Section 7.2.1.1 for eDiary instructions and review).
The mucosal appearance during the sigmoidoscopic/colonoscopic portion of the endoscopic 
examination will be assessed for calculation of the Mayo endoscopic subscore based on the 
scoring system provided in Appendix 3. The endoscopic appearance will be read by both the 
Investigator and a central reader. Additional details are provided in the Central Imaging 
Management Solutions manual. Centrally read endoscopic subscores will be used for both IBT 
eligibility and the efficacy analyses. The Investigator-read endoscopic subscores will be used 
to assess eligibility for the OL and CBT phases.
The PGA subscore is assessed by the Investigator and is recorded at all study visits. The 
endoscopic subscore and the PGA must be performed by a physician qualified to perform 
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endoscopy. It is recommended that the same physician performs all such assessments for a 
particular subject throughout the study.
7.2.1.1
eDiary Instructions and Review
The SF and RB subscores are recorded daily in an eDiary. Subjects should be provided access 
to the eDiary and instructions for daily documentation of SF and RB. Additionally, all subjects 
will be provided with paper diary forms for cases where the subject doesn’t have access to a 
suitable device for eDiary capture or as backup to the eDiary in case there is an issue with the 
subject’s electronic device. Subjects should begin filling out the diary on the day of their initial 
screening visit and continue to fill it out on a daily basis throughout the remainder of the study. 
Subjects should be counseled about what is meant by normal SF: the average daily SF the 
subject experienced the last time the subject was in remission. If the subject has never been in 
remission, the normal SF is defined as the average daily SF before the initial onset of signs and 
symptoms of UC.
For the daily SF question, subjects should be counseled that a stool is defined as a visit to the 
toilet when they have either a bowel movement, pass blood only, pass mucus only, or pass 
blood and mucus. For the RB question, subjects should be counseled to select the category that
describes their most severe RB over the last 24 hours. Subjects should be counseled to select 
“No Blood Seen” if they do not have a stool during a given day.
The modified Mayo Score will be used for the purposes of determining eligibility at screening 
and efficacy assessments at Week 12, the subscores for SF and RB will be calculated based on 
the data recorded in the diary for 3 consecutive days (excluding the bowel preparation day)
during the week prior to the endoscopy. Thus, sites need to ensure subjects are entering eDiary
(preferred) or paper diary forms data daily, especially prior to an endoscopy. Subjects must be 
instructed to document SF and RB on a daily basis and site personnel should be monitoring 
subject’s compliance. For all subjects, the site will ensure that the SF and RB data are being
entered in the ediary or paper diary forms by the subject by conducting a follow up phone call 
within 3 days before the endoscopy bowel preparation day at Screening and Week 12. 
The partial Mayo Score will be assessed throughout the study and be used at Week 24 for the 
subjects in the OL phase to determine if the subject can start steroid tapering (if applicable). 
The subscore for SF and RB will be calculated based on the data recorded in the diary on 3 
days (no need to be consecutive days) during the week prior to the corresponding visit where 
the partial Mayo Score is assessed.
7.2.1.2
Endoscopy
A colonoscopy or flexible sigmoidoscopy will be performed and recorded for central reader 
review at Screening and Week 12 (or upon ET as applicable).
Screening endoscopies will occur as follows:
●
Only in subjects with a RB subscore ≥ 1, a SF subscore ≥1 and PGA ≥1 may proceed 
with screening endoscopy.
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
Clinical response (based on the partial Mayo Score): decrease in partial Mayo Score of 
≥ 2.  
Note: the clinical response based on the partial Mayo Score will be used in the decision 
to taper steroid (as applicable) at Week 24 for subjects in the OL phase.

Endoscopic improvement: Mayo endoscopic subscore of less than or equal to 1

Endoscopic remission: Mayo endoscopic subscore of 0

Mucosal healing: Geboes index score < 2 and endoscopic remission (Mayo endoscopic
subscore of 0)

Symptomatic remission: SF subscore 0 or 1 with a decrease of ≥1 point from baseline, 
and RB subscore of 0

Symptomatic response: ≥30% decrease from baseline in composite sum of SF and RB
subscores

UC-100: Composite UC-100 score (1 + 16 × Mayo SF subscore [0 to 3] + 6 × Mayo 
endoscopic subscore [0 to 3] + 1 × RHI score [0 to 33]) ranges from 1 (no disease 
activity) to 100 (severe disease activity)
7.2.3
Geboes Score and Robarts Histopathology Index 
7.2.3.1
Geboes Score
The original Geboes score (GS) is the most commonly used colon mucosal histological score 
in the UC field. It is divided into 6 grades: architectural changes (Grade 0), chronic 
inflammatory infiltrate (Grade 1), lamina propria neutrophils and eosinophils (Grade 2), 
neutrophils in epithelium (Grade 3), crypt destruction (Grade 4) and erosions or ulcerations 
(Grade 5), and each grade of the score is divided in 4 subcategories (see Appendix 4). The 
Geboes score ranges from 0 to 5.4, with higher scores indicating more severe inflammation; 
typically, UC is defined as active histological inflammation with a Geboes score of ≥2B.1 
(Ma, 2021).
7.2.3.2
Robarts Histopathology Index
The RHI is a recently validated instrument that measures histological disease activity in 
patients with UC (see Appendix 5). The RHI is divided into 4 categories: chronic inflammatory 
infiltrate, lamina propria neutrophils, neutrophils in epithelium, and erosion or ulceration (each 
ranging from 0–4). The RHI is comparable to, and often correlates with the Geboes score.
Endpoints based on the GS and RHI are defined below:

Histologic remission: Geboes index score < 2B.1 or RHI score ≤ 3, with subscores of 
0 for lamina propria neutrophils and 0 for neutrophils in epithelium
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
Histologic response: change from baseline RHI ≥ 7 points

Mucosal healing: Histologic remission (as defined by the Geboes or RHI score) and 
endoscopic remission (Mayo endoscopic subscore of 0)

UC-100: Composite UC-100 score (1 + 16 × Mayo SF subscore [0 to 3] + 6 × Mayo 
endoscopic subscore [0 to 3] + 1 × RHI score [0 to 33]) ranges from 1 (no disease 
activity) to 100 (severe disease activity) (see Appendix 6)
7.3
Patient-Reported Outcomes and Quality of Life Measures
Paper questionnaires will be used to record the following patient-reported outcomes (PRO) 
and quality of life assessments during the study:

IBDQ

SF-36
PRO and quality of life measurements are collected and evaluated in a different manner than 
AEs; therefore, no attempt will be made to resolve any apparent discrepancies between AE and 
PRO data. 
7.3.1
Inflammatory Bowel Disease Questionnaire
IBDQ is a psychometrically validated PRO instrument for measuring the disease-specific 
quality of life in patients with inflammatory bowel disease, including UC. The IBDQ 
comprises 32 items that are grouped into 4 dimensions: bowel function (loose stools, 
abdominal pain), emotional status (anger, depression, irritability), systemic symptoms (fatigue, 
altered sleep pattern) and social function (work attendance, need to cancel social events).
The 4 domains are scored as follows:

Bowel symptoms: 10 to 70

Systemic symptoms: 5 to 35

Emotional function: 12 to 84

Social function: 5 to 35
The total IBDQ score ranges from 32 to 224. For the total score and each domain, a higher 
score indicates better quality of life. A score of at least 170 corresponds to clinical remission 
and an increase of at least 16 points indicates a clinically meaningful improvement.
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7.3.2
Short Form-36 
The SF-36 is a widely used general health status questionnaire that assesses 8 domains of
functional health and well-being: Physical Functioning, Role Limitations due to Physical 
Health Problems, Bodily Pain, Social Functioning, Mental Health, Role Limitations due to 
Emotional Problems, Vitality, and General Health Perceptions. Scales are scored from 0 to 
100, with higher scores indicating a better health-related quality of life. A Physical Health 
component summary score and Mental Health component summary score are calculated from 
the 8 domain scores. The SF-36 is a psychometrically valid and reliable instrument. The 
concepts measured by the SF-36 are not specific to any age, disease, or treatment group, 
allowing comparison of relative burden of different diseases and the relative benefit of different 
treatments.
7.4
Pharmacokinetic and Immunogenicity Assessments
Blood samples for PK and ADA analyses will be collected at baseline and at the timepoints 
specified in the SOE tables in Appendix 1.
PK parameters that will be assessed include Cmax, Tmax, AUC0-t, Cmin, AUC0-inf, t½, CL/F, and 
Vd/F. ADA to PT101 will be assessed using a standard 3-tier approach to measure binding 
antibody with a screening assay, ADA titer using a confirmatory assay, and neutralizing 
antibody to PT101 in subjects with confirmed positive titers.
7.5
Pharmacodynamics and Biomarker Assessments
Blood samples for PD and biomarker analyses will be collected at baseline and at the 
timepoints specified in the SOE tables in Appendix 1.
7.5.1
Pharmacodynamic Assessments 
Whole blood will be collected for immunophenotyping (IPT) and receptor occupancy (RO)
and analyzed by flow cytometry to enumerate immune cell subsets and assess CD25 (IL-2Rα) 
RO on Tregs.
7.5.2
Biomarker Assessments
Changes in additional PT101- and UC-associated exploratory biomarkers (e.g., proteomics) 
will be assessed in serum, blood, RNA, PBMCs, stool, and colonic tissue biopsy samples.
CRP will be assayed using a validated, high-sensitivity CRP assay. FC will be evaluated in 
stool samples using a validated method. Additional tests may also be performed on the stool 
samples for additional markers related to intestinal inflammation and treatment response.
Details on collecting, aliquoting, storing and shipping samples will be detailed in the Lab 
Manual.
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7.5.2.1
Future Research
The Sponsor will also conduct future research on specimens for which consent was provided 
during this study. The objective of collecting/retaining specimens for future research is to 
explore and identify biomarkers that inform the scientific understanding of diseases (including 
UC) and/or their therapeutic treatments (including PT101).
If the subject provides documented informed consent for future research, the following 
specimens will be obtained as part of future research:

Additional blood samples (for serum)

Backup serum samples 

Backup blood samples 

Backup stool samples 

Leftover tissue samples
7.5.2.2
Genetic Analysis
Genetic analysis will be conducted on specimens for which consent was provided during the 
study. Genetic variation may impact a subject’s response to therapy, susceptibility to, severity, 
and progression of disease. Variable response to therapy may be due to genetic determinants 
that impact drug absorption, distribution, metabolism, and excretion; mechanism of action of 
the drug; disease etiology; and/or molecular subtype of the disease being treated. Samples 
collected may also be used to develop tests/assays including diagnostic tests related to the 
disease under study, related diseases, and study drug(s).
7.6
Safety Assessments
The assessment of safety during the course of this study will consist of the surveillance and 
recording of AEs including SAEs, Events of Clinical Interest (ECIs), recording of concomitant 
medication, ECG, vital signs, physical examinations and laboratory tests.
Safety will be monitored over the course of the study by a DRC as described in Section 3.
7.6.1
Adverse Events
7.6.1.1
Definitions
Adverse Event
According to the International Council for Harmonisation (ICH) E2A guideline Definitions 
and Standards for Expedited Reporting, and 21 CFR 312.32, IND Safety Reporting, an AE is 
any untoward medical occurrence in a patient or clinical investigational subject administered 
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a medicinal product and which does not necessarily have a causal relationship with this 
treatment.
The following information should be considered when determining whether or not to record a 
test result, medical condition, or other incident on the Adverse Events and Pre-existing 
Conditions eCRF:
●
From the time of informed consent through the day prior to randomization, 
only those AEs that are the result of a study protocol-specified intervention
must be recorded. A protocol-specified intervention AE is defined as an 
untoward medical event occurring as a result of a protocol mandated 
procedure.
●
All medical conditions present or ongoing before randomization should be 
recorded as part of the subject’s medical history.
●
All AEs (regardless of relationship to study drug) should be recorded from 
randomization
through the end of the safety reporting period 
(see Section 7.6.1.3). Complications that occur in association with any 
procedure should be recorded as AEs whether or not the procedure was 
protocol mandated.
●
Changes in pre-existing medical conditions and AEs, including changes in 
severity, frequency, or character, during the safety reporting period should 
be recorded.
●
In general, an abnormal laboratory value should not be recorded as an AE 
unless it is associated with clinical signs or symptoms, requires an 
intervention, results in a SAE, or results in study termination or 
interruption/discontinuation of study treatment. When recording an AE 
resulting from a laboratory abnormality, the resulting medical condition 
rather than the abnormality itself should be recorded (e.g., record “anemia” 
rather than “low hemoglobin”).
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Serious Adverse Events
An AE should be classified as an SAE if it meets one of the following criteria:
Fatal:
AE resulted in death
Life threatening:
The AEs placed the patient at immediate risk of death. This 
classification does not apply to an AE that hypothetically might 
cause death if it were more severe.
Hospitalization:
The AE resulted in hospitalization or prolonged an existing inpatient 
hospitalization. Hospitalizations for elective medical or surgical 
procedures or treatments planned before the signing of informed 
consent in the study or routine check-ups are not SAEs by this 
criterion. 
Disabling/ 
incapacitating:
An AE that resulted in a persistent or significant incapacity or 
substantial disruption of the patient’s ability to conduct normal life 
functions.
Congenital anomaly 
or birth defect:
An adverse outcome in a child or fetus of a patient exposed to the 
molecule or study treatment regimen before conception or during 
pregnancy.
Medically 
significant:
The AE did not meet any of the above criteria, but could have 
jeopardized the patient and might have required medical or surgical 
intervention to prevent one of the outcomes listed above or involves 
suspected transmission via a medicinal product of an infectious 
agent.
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Adverse Event Severity
AE severity should be graded using the NCI CTCAE, Version 5.0 (27 November 2017). The 
general categories for each grade are:
Grade 
Severity 
Alternate Description 
1 
Mild (apply event-specific NCI CTCAE 
grading criteria) 
Asymptomatic or mild symptoms; 
clinical or diagnostic observations only; 
intervention not indicated 
2 
Moderate (apply event-specific NCI 
CTCAE grading criteria) 
Minimal; local or noninvasive 
intervention indicated; limiting age 
appropriate instrumental ADL 
3 
Severe (apply event-specific NCI 
CTCAE grading criteria) 
Severe or medically significant but not 
immediately life-threatening; 
hospitalization or prolongation of 
hospitalization indicated; disabling; 
limiting self-care ADL 
4 
Very severe, life-threatening, or 
disabling (apply event-specific NCI 
CTCAE grading criteria) 
Life-threatening consequences; urgent 
intervention indicated 
5 
Death related to AE 
Death related to AE 
Abbreviations: AE=adverse event; ADL=activities of daily living; NCI CTCAE=National Cancer Institute 
Common Terminology Criteria for Adverse Events. 
Note: Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, 
taking medications, and not bedridden.
AE severity and seriousness are assessed independently. ‘Severity’ characterizes the intensity 
of an AE. ‘Serious’ is a regulatory definition and serves as a guide to the sponsor for defining 
regulatory reporting obligations (see definition for SAEs, above).
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Relationship of the Adverse Event to Study Treatment
The relationship of each AE to study treatment should be evaluated by the Investigator using 
the criteria below. If the Investigator’s opinion of not related to study drug for an SAE is given, 
an alternative cause of the event such as underlying disease(s), concomitant therapy, and other 
risk factors must be provided.
Related:
There is evidence to suggest a causal relationship between the drug 
and the AE, such as:
●A single occurrence of an event that is uncommon and known to be 
strongly associated with drug exposure 
●One or more occurrences of an event that is not commonly 
associated with drug exposure, but is otherwise uncommon in the 
population exposed to the drug 
Relationship of the Adverse Event to Study Procedure
The relationship of each AE to study procedure should be evaluated by the Investigator using 
the following criteria:
Related:
There is evidence to suggest there is a reasonable possibility of a 
causal relationship between the study procedure and the AE
Unrelated:
There is no reasonable possibility of a causal relationship between the 
study procedure and the AE
7.6.1.2
Procedures for Eliciting and Recording Adverse Events
Investigator and study personnel will report all AEs and SAEs whether elicited during patient 
questioning, discovered during physical examination, laboratory testing and/or other means by 
recording them on the eCRF, as appropriate.
Eliciting Adverse Events
An open-ended or non-directed method of questioning should be used at each study visit to 
elicit the reporting of AEs.
Recording Adverse Events
The following information should be recorded on the Adverse Events and Pre-existing 
Conditions eCRF:
●
Description including onset and resolution dates
●
Whether it met SAE criteria
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●
Severity
●
Relationship to study treatment or other causality
●
Outcome
Diagnosis vs. Signs or Symptoms
In general, the use of a unifying diagnosis is preferred to the listing out of individual symptoms.
Grouping of symptoms into a diagnosis should only be done if each component sign and/or 
symptom is a medically confirmed component of a diagnosis as evidenced by standard medical 
textbooks. If any aspect of a sign or symptom does not fit into a classic pattern of the diagnosis, 
report the individual symptom as a separate adverse event.
Recording Serious Adverse Events
For SAEs, record the event(s) on the eCRF with the seriousness criteria assessment.
The following should be considered when recording SAEs:
●
Death is an outcome of an event. The event that resulted in the death should 
be recorded and reported on both an SAE form and eCRF.
●
For hospitalizations, surgical, or diagnostic procedures, the illness leading 
to the surgical or diagnostic procedure should be recorded as the SAE, not 
the procedure itself. The procedure should be captured in the narrative as 
part of the action taken in response to the illness.
Pregnancy and Exposure During Breastfeeding
Female subjects who become pregnant must discontinue study drug. A determination regarding 
study drug discontinuation will be made by the Investigator and/or Sponsor for male subjects
with a partner pregnancy after evaluating the risks and benefits of continuing with the study.
Complete a Pregnancy Report Form for all pregnancies that occur from the time of first study 
drug dose until 30 days after the last dose of study drug(s) including any pregnancies that 
occur in the partner of a male study subject. Only report pregnancies that occur in a male 
patient’s partner if the estimated date of conception is after the male subject’s first study drug 
dose. A completed Pregnancy Report Form by the Investigator (or designee) should be 
submitted to Alimentiv Safety within 24 hours after learning of the pregnancy. Suspicion that 
study drug may have interfered with the effectiveness of a contraceptive medication must also 
be recorded as an AE.
All pregnancies will be monitored for the full duration; all perinatal and neonatal outcomes 
should be reported. Infants should be followed for a minimum of 8 weeks.
Although infant exposure during breastfeeding is not considered an AE, any infant exposure 
during breastfeeding by a subject (spontaneously reported to the investigator or their designee) 
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occurring during the study is reportable. The Sponsor should be notified within 24 hours of 
learning of the event.
Collection of data on the eCRF: All pregnancies and infant exposure during breastfeeding (as 
described above) that occur within 30 days of the last dose of study drug(s) will also be 
recorded on the Adverse Events eCRF.
Non-elective abortion, whether accidental, therapeutic, or spontaneous, should be reported as 
an SAE. Congenital anomalies or birth defects, as defined by the ‘serious’ criterion above (see 
definitions Section 7.6.1.1) should be reported as SAEs.
7.6.1.3
Reporting Periods for Adverse Events and Serious Adverse Events
The safety reporting period for all AEs and SAEs is from time of study drug randomization
through the end of treatment visit or 28 days after the last study treatment, whichever is later.
However, all AEs that are the result of a study protocol-specified intervention are to be 
recorded from the time of informed consent.
All SAEs that occur after the safety reporting period and are considered study treatment-related 
in the opinion of the Investigator should also be reported to the sponsor.
SAEs will be followed until significant changes return to baseline, the event stabilizes 
(recovering/resolving) or is no longer considered clinically significant by the investigator, or 
the patient dies or withdraws consent. All non-serious AEs will be followed through the safety 
reporting period. Certain non-serious AEs of interest may be followed until resolution, return 
to baseline, or study closure.
7.6.1.4
Serious Adverse Events Require Immediate Reporting
The Investigator (or designee) is required to complete the SAE page in the eCRF enabling 
transmission to Alimentiv Safety using the electronic data capture (EDC) system. In the event 
EDC transmission is not possible, (e.g., there are access or system problems), then the 
Investigator (or designee) must report the SAE to Alimentiv Clinical Safety by emailing or 
faxing a completed paper SAE form:
All SAEs must be reported to Alimentiv Clinical Safety group within 24 hours after the 
Investigator recognizes/classifies the event as a SAE. 
The initial SAE report should include at a minimum: subject number, a narrative description 
of the event, and an assessment by the Investigator of the intensity of the event and relationship 
of the event to study drug. The initial SAE report received from the site should be as complete 
as possible. A complete follow-up SAE report must be submitted when information not 
available at the time of the initial report becomes available. The Sponsor (or designee) may 
request SAE follow-up information. Copies of any relevant data from the hospital notes (e.g., 
ECGs, laboratory tests, discharge summary, postmortem results) should be sent to the 
addressee, if requested.
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There may be situations in which an SAE has occurred, and the Investigator has minimal 
information to include in the initial report. However, as causality assessment is one of the 
criteria used when determining regulatory reporting requirements, it is particularly important 
that the Investigator always assess causality for every event before the initial transmission of 
the SAE data. The Investigator may change his/her opinion of causality considering follow-up 
information and send an SAE follow-up report with the updated causality assessment.
The Investigator (or designee) is responsible for continuing to report to the Sponsor Clinical 
Safety any new or relevant follow-up information that he/she learns about the SAE.
The Investigator (or designee) is responsible for notifying their institutional review 
board/independent ethics committee (IRB/IEC) of SAEs that occur according to local 
regulations and guidelines.
Reports of pregnancy, exposure during breastfeeding, cancer, and ECIs (per Section 7.6.1.6), 
will be reported in the same timeframe as SAEs.
7.6.1.5
Sponsor Safety Reporting to Regulatory Authorities
Investigators are required to report all SAEs to the sponsor (see Section 7.6.1.4).
The sponsor or Alimentiv will report all SAEs to regulatory authorities as required per local 
regulatory reporting requirements. 
7.6.1.6
Events of Clinical  Interest
Selected serious and nonserious AEs are also known as ECIs and must be reported to the 
Sponsor.
ECIs for this study include:
1.
An overdose of Sponsor's product, as defined in Section 7.6.1.7
2.
An elevated AST or ALT laboratory value that is greater than or equal to 3X the ULN 
and an elevated total bilirubin laboratory value that is greater than or equal to 2X the 
ULN and, at the same time, an alkaline phosphatase laboratory value that is less than 
2X the ULN, as determined by way of protocol-specified laboratory testing or 
unscheduled laboratory testing.*
*Note: These criteria are based on available regulatory guidance documents. The purpose of 
the criteria is to specify a threshold of abnormal hepatic tests that may require an additional 
evaluation for an underlying etiology. The study-site guidance for assessment and follow up 
of these criteria can be found in Appendix 7 and in the Investigator Study File Binder (or 
equivalent).
It may also be appropriate to conduct additional evaluation for an underlying etiology in the 
setting of abnormalities of liver blood tests including AST, ALT, bilirubin, and alkaline 
08NYPB


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phosphatase that do not meet the criteria noted above. In these cases, the decision to proceed 
with additional evaluation will be made through consultation between the study investigators 
and the Sponsor. However, abnormalities of liver blood tests that do not meet the criteria noted 
above are not ECIs for this study.
3.
Skin rash or pruritis being rated by the Investigator as Grade 3 in intensity
4.
Dyspnea, all intensities
5.
Significant eosinophilia defined as AEC > 5.0 giga/L confirmed on repeat measurement 
after at least 24 hours or eosinophil-associated organ injury.
7.6.1.7
Definition and Treatment of Overdose
For purposes of this study, an overdose will be defined as any dose of any drug administered 
as part of the study exceeding the dose prescribed by the protocol. It is up to the investigator 
or the reporting physician to decide whether a dose is to be considered an overdose, in 
consultation with the Sponsor.
The Sponsor does not recommend specific treatment for an overdose. Decisions regarding dose 
interruptions or modifications will be made by the investigator in consultation with the Sponsor 
based on the clinical evaluation of the subject.
7.6.2
Clinical Laboratory Tests
The following laboratory assessments will be performed by the central lab to evaluate safety 
at scheduled timepoints during the course of the study:
●
The chemistry panel is to include the following tests: albumin, alkaline 
phosphatase, ALT, AST, blood urea nitrogen, calcium, creatinine, chloride, 
CRP, lactate dehydrogenase (LDH), phosphorus, potassium, sodium, total 
bilirubin, amylase, lipase, and uric acid.
●
Hematology panel (complete blood count [CBC] with differential). 
Differential includes neutrophils, lymphocytes, monocytes, eosinophils, 
and basophils.
●
Coagulation parameters include prothrombin time/partial thromboplastin 
time/international normalized ratio (PT/PTT/INR)
●
Creatinine clearance – the same method of assessment should be used at 
each timepoint
●
Urinalysis
○
Standard urinalysis
○
Urine protein and creatinine for urine protein/creatinine ratio
08NYPB


	
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machine that automatically calculates the heart rate (HR) and measures PR, QRS, QT, and QTc 
intervals. The correction formula to be used for QTc is Fridericia.
Triplicate ECG measurements will be obtained at the screening visit and on Day 1. On Day 1 
only, triplicate ECGs will be performed ~12 hours after study drug administration. The median 
of these measurements will be used to calculate change from baseline for safety evaluations 
(and for rechecks, if needed). Single measurements will be performed on Day 85 and ET visits.
At each time point when triplicate ECGs are required, 3 individual ECG tracings should be 
obtained at least 1 minute apart. The full set of triplicates should be completed in no more than 
6 minutes.
Special care must be taken for proper lead placement by qualified personnel. Skin should be 
clean and dry before lead placement. Subjects may need to be shaved to ensure proper lead 
placement. Female subjects may need to remove interfering garments.
During an ECG, subjects should be in a quiet setting without distractions. Subjects should rest 
in a supine position for at least 5 minutes before ECG recording and should refrain from talking 
or moving their arms or legs. 
Screening ECG read results will be used as baseline ECG to evaluate subject eligibility and 
should be maintained in the subjects source documentation for this study. Any clinically 
significant changes from the baseline ECG should be recorded as AEs and evaluated further, 
as clinically warranted. Refer to Appendix 8 for evaluation and potentially significant findings.
If prolongation of the QTc is noted, concomitant medications that prolong QTc should be held 
until the QTc is within 60 msec of baseline and the QTc is < 500 msec.
If blood sample collection and/or measurement of vital signs is scheduled at the same timepoint 
as ECG recording, the procedures should be performed in the following order: ECG, vital 
signs, blood sample collection.
7.6.6
Vital Signs
Vital signs measures include HR, BP, respiratory rate, and temperature. Weight will also be 
measured.
Vital Sign Measurements (Heart Rate, Blood Pressure, Respiratory Rate, Temperature)
Subjects should be resting in a quiet setting without distractions in a semirecumbent position 
for at least 5 minutes before having vital sign measurements obtained. Supine or seated 
positions are also acceptable (per site standard procedures) as long as the position used is 
consistent across subjects at a given site. Vital signs will include HR, systolic and diastolic BP, 
respiratory rate, and body temperature at timepoints indicated in the SOEs. The correct size of 
the BP cuff and the correct positioning on the subject’s arm is essential to increase the accuracy 
of BP measurements.
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All HR and BP will be taken as a single measurement. 
Body Temperature
Body temperature will be measured. The same method must be used for all measurements for 
each individual subject and should be the same for all subjects enrolled at a site.
7.6.7
Physical Examination
Physical examinations should include assessments of the following body parts/systems: 
abdomen, extremities, head (eyes, ears, nose, and throat), heart, lungs, neck, neurological, and 
skin.
An abbreviated or targeted interim physical examination may be done to assess areas with 
previously noted abnormalities and/or that are associated with any new complaints from the 
subject.
7.6.8
Pregnancy Testing 
For WOCBP, a serum or urine beta human chorionic gonadotropin (β-hCG) pregnancy test
will be performed at screening and before dosing. A negative pregnancy result is required 
before the subject may receive study drug. Additional pregnancy testing will be performed as 
specified in the SOEs in Appendix 1.
7.7
Appropriateness of Measurements
The safety measures that will be used in this trial are considered standard procedures for 
evaluating the potential adverse effects of study medications. Immunogenicity is commonly 
assessed for biologics; therefore, standard tests will be performed to detect the possible 
presence of specific antibodies to PT101. Pharmacokinetic assessments are also frequently 
employed in clinical studies to help characterize dose-exposure-response relationships.
Standardized and internationally accepted criteria for the evaluation of UC will be used to 
assess disease activity in this study, including the Mayo Score, the Geboes score, the RHI, and 
UC-100 (Jairath, 2019; Jauregui-Amezaga, 2017; Magro, 2020; Mosli, 2017; Pai, 2019). The 
PRO and quality of life instruments used in this study are standardized questionnaires that have 
been widely used in clinical trials in multiple countries (Irvine, 1994; Ware and 
Sherbourne, 1992; Yalcin and Bump, 2003). 
08NYPB


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8
DATA QUALITY CONTROL AND QUALITY ASSURANCE
8.1
Site Training and Monitoring Procedures
A study manual with instructions for study compliance and eCRF completion will be provided.
Prior to the enrollment of subjects at the site, the Sponsor or its designated clinical and medical 
personnel will review the following items with the Investigator and clinic staff:
●
The protocol, study objectives, eligibility requirements, study procedures, 
registration and withdrawal processes
●
Current Investigator’s Brochure/ package insert
●
Recording and reporting AEs and SAEs
●
Enrollment goals and study timelines
●
The eCRF completion process and source documentation requirements
●
Monitoring requirements
●
IRB/IEC review and approval process
●
Informed consent process
●
Good clinical practice guidelines and related regulatory documentation 
requirements
●
Key study team roles and responsibilities
●
Investigational product storage, accountability, labeling, dispensing and 
record keeping
●
Subject coding and randomization (if applicable)
●
Study samples/specimen collection, handling and shipping
●
Protocol compliance
●
Clinical study record keeping, document retention, and administrative 
requirements
Monitoring visits will occur periodically, with frequency dependent on the rate of enrollment 
and workload at each site. During monitoring visits, the Sponsor representative will review 
regulatory documentation, eCRFs, source documentation, and investigational product storage, 
preparation, and accountability. The eCRFs will be reviewed for completeness, adherence to 
the provided guidelines, and accuracy compared to the source documents. The investigators 
must ensure that the monitor is allowed to inspect all source documents pertinent to study 
08NYPB


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subjects, and must cooperate with the monitor to ensure that any problems noted in the course 
of the trial are resolved. The Investigator must maintain a comprehensive and centralized filing 
system of all study-related documentation that is suitable for inspection by the Sponsor or its 
designated monitors and by quality assurance auditors, or representatives of regulatory 
authorities.
8.2
Data Management Procedures
The Sponsor will provide CRF Completion Guidelines for eCRF data entry. Study specific 
data management procedures will be maintained in the data management plan. Queries 
resulting from edit checks and/or data verification procedures will be posted electronically in 
the eCRF.
8.3
Access to Source Data
The Investigator will permit the Sponsor’s representatives to monitor the study as frequently 
as the sponsor deems necessary to determine that protocol adherence and data recording are 
satisfactory. Appropriate measures to protect patient confidentiality are to be employed during 
monitoring. The eCRFs and related source documents will be reviewed in detail by the monitor 
at each site visit. Original source documents or certified copies are needed for review. This 
review includes inspection of data acquired as a requirement for participation in this study and 
other medical records as required to confirm that the information contained in the eCRFs, such 
as disease assessments, AEs, and concomitant medications, is complete and correct. Other 
study records, such as correspondence with the sponsor and the IRB/IEC and screening and 
drug accountability logs will also be inspected. All source data and study records must also be 
available for inspection by representatives of regulatory authorities.
8.4
Accuracy and Reliability of Data
Steps to be taken to assure the accuracy and reliability of data include:
●
The selection of qualified Investigators and appropriate study centers.
●
Review of protocol procedures with the Investigators and associated 
personnel prior to the study.
●
Periodic monitoring visits by the designated monitor(s).
●
eCRFs will be reviewed for accuracy and completeness by the designated 
monitor(s) during monitoring visits to the study centers. Any discrepancies 
will be resolved with the Investigator or designees as appropriate.
8.5
Quality Assurance Procedures
The Sponsor or its designee may conduct audits at the clinical site or other study-related 
facilities and organizations. Audit reports will be retained by the Sponsor as part of the written 
record.
08NYPB


	
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Amendment 8; 13-May-2022
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9.2
Study Endpoint Definitions
See Section 7.2 for definitions of the efficacy/response endpoints. 
9.3
Statistical and Analytical Plans
9.3.1
General Considerations
Tabulations will be produced for appropriate demographic, baseline, efficacy, and safety 
parameters. Continuous variables will be summarized by number of subjects and mean, 
standard deviation/standard error, median, minimum, and maximum values. Categorical 
variables will be summarized by number and percentage of subjects. Tests of statistical 
significance will be described in the SAP.
9.3.1.1
Subject Disposition
The number and percentage of subjects in study populations will be summarized by treatment 
group, separately for each stage. The subject disposition table will also include the number of 
subjects screened, randomized, and treated. No formal statistical comparisons will be 
performed.
Subjects who are screened but not randomized (screen failures) and the associated reasons for 
failure to randomize will be tabulated for all screened subjects. The number and percentage of 
subjects who complete the 12-week treatment period and of subjects who prematurely 
discontinue will be presented for each treatment group and pooled across treatment groups for 
the Safety Population. The reasons for premature discontinuation from treatment period as 
recorded in the eCRFs will be summarized.
9.3.1.2
Subject Characteristics
Demographic parameters (age, age group, sex, race, ethnicity, height, weight, body mass 
index) and other baseline characteristics will be summarized descriptively by treatment group 
for the intent-to-treat (ITT), full analysis set (FAS), per protocol (PP) analysis set, and safety 
analysis sets (SAF).
9.3.1.3
Protocol Deviations
Protocol deviations will be summarized by type in each treatment group. Both major and minor 
protocol deviations will be listed.
9.3.1.4
Prior and Concomitant Therapy
Prior medication is defined as any medication started before the date of study drug 
administration. A concomitant medication is defined as any medication taken on or after the 
date of study drug administration.
Prior and concomitant medications will be coded by drug name and therapeutic class using the 
World Health Organization (WHO) Drug Dictionary. Results will be tabulated by Anatomic 
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Therapeutic Class and preferred term. If a subject took a specific medication multiple times or 
took multiple medications within a specific therapeutic class, that subject will be counted only 
once for the coded drug name or therapeutic class.
9.3.1.5
Randomization and Blinding
Subjects will be randomized in a 4:1 ratio to a PT101 dose level/dosing regimen and placebo. 
The study will be conducted in a double-blind fashion, which will be described in the Clinical 
Trial Integrity Plan.
9.3.1.6
Adjustments for Covariates
Detailed methodology will be provided in the SAP.
9.3.1.7
Handling of Dropouts and Missing Data
Detailed methodology will be provided in the SAP.
9.3.1.8
Multiple Comparisons and Multiplicity
No multiplicity adjustments will be applied.
9.3.1.9
Data Transformations and Derivations
Time variables based on 2 dates (e.g., start date and end date) will be calculated as (end date –
start date + 1 [in days]) unless otherwise specified in the SAP.
Baseline values used in all statistical analyses will be the most recent non-missing 
measurement prior to the first dose of study drug unless otherwise specified in the SAP.
More detailed methodology will be provided in the SAP.
9.3.2
Analysis Sets
9.3.2.1
Intent-to-Treat Analysis Set
The ITT analysis set consists of all randomized subjects. Subjects will be included in the 
treatment group assigned at randomization regardless of the actual treatment received.
9.3.2.2
Full Analysis Set
The FAS consists of all randomized subjects who received any study drug (PT101 or placebo).
Treatment groups will be determined using the actual treatment received, regardless of the 
randomization treatment assignment.
08NYPB


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
Proportion of subjects achieving clinical remission, endoscopic improvement, 
clinical response, endoscopic remission, histologic remission, histologic response, 
mucosal healing at Week 12

Proportion of subjects achieving symptomatic remission and symptomatic response 
at assessed timepoints through Week 12
9.3.5
Exploratory Efficacy Analyses
MMRM may be used to compare change from baseline in partial Mayo Score beyond Week 12 
as well as change in PT101- and UC-associated biomarkers.
9.3.6
Pharmacokinetic and Immunogenicity Analyses
9.3.6.1
Pharmacokinetic Analyses
Serum concentrations of PT101 will be listed and summarized by treatment group using 
descriptive statistics (sample size, arithmetic mean, geometric mean, % coefficient of variation, 
standard deviation, median, minimum, and maximum). Concentration over time may also be 
plotted in semilogarithmic and linear formats. 
ADA to PT101 will be assessed using a standard 3-tier approach to measure binding antibody 
with a screening assay, ADA titer using a confirmatory assay, and neutralizing antibody to 
PT101 in subjects with confirmed positive titers. Data will be listed and summarized by 
treatment group as detailed in the SAP.
9.3.6.2
Biomarker Analyses
Relationships of biomarker parameters (e.g., baseline values, absolute and relative changes 
from baseline) to efficacy, safety, and PK parameters will be explored. Relationships and 
associated data that are determined to be of interest will be summarized. Details will be 
described separately in the SAP.
9.3.7
Safety Analyses
The safety analyses will be performed using the SAF. The safety parameters will include AEs 
and SAEs, vital sign measurements, ECG findings and clinical laboratory values. The primary 
safety analysis will include all data available for all subjects through Week 12.
9.3.7.1
Extent of Exposure
Duration of treatment will be summarized and listed. Duration of treatment, number of doses, 
and total dose will be summarized. Dose modifications will also be summarized.
9.3.7.2
Adverse Events
An overview of AEs will provide a tabulation of the incidence of all AEs, treatment-emergent 
AEs, treatment-related AEs, Grade 3 and higher AEs, SAEs, treatment-related SAEs, deaths, 
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and AEs leading to study treatment discontinuation. Adverse events will be defined as 
treatment emergent if they are newly occurring or worsen following study treatment.
AEs will be listed and summarized by Medical Dictionary for Regulatory Activities 
(MedDRA), preferred term, severity, and relationship to study drug. In the event of multiple 
occurrences of the same AE with the same preferred term in 1 subject, the AE will be counted 
once as the occurrence. The incidence of AEs will be tabulated by preferred term and treatment 
group. AEs leading to premature discontinuation of study drug will be summarized and listed 
in the same manner.
9.3.7.3
Deaths and Serious Adverse Events
SAEs will be listed and summarized in the same manner as all AEs. Events with a fatal outcome 
will be listed.
9.3.7.4
Clinical Laboratory Results
Laboratory values (e.g., chemistry, hematology, and urinalysis) may be presented graphically 
by visit. Summary statistics may be tabulated as appropriate by scheduled visit. Laboratory 
values will be listed with grade per NCI CTCAE and flagged when values are outside the 
normal reference range.
9.3.7.5
Other Safety Analyses
Vital Signs
Vital signs will be presented graphically for each vital sign by scheduled visit. Summary 
statistics and change from baseline and/or predose to postdose may be tabulated where 
appropriate.
ECG
ECG status (normal, abnormal clinically significant, or abnormal not clinically significant) 
may be summarized for each scheduled ECG, and shifts from baseline may be tabulated.
10 INFORMED CONSENT, ETHICAL REVIEW, AND REGULATORY 
CONSIDERATIONS
This study will be conducted in accordance with the Note for Guidance on Good Clinical 
Practice (ICH Harmonised Tripartite Guideline E6 (R1); FDA CFR [21 CFR § 50, 56, 312]), 
Declaration of Helsinki (Brazil 2013), and all applicable regulatory requirements.
10.1 Informed Consent
The Investigator is responsible for presenting the risks and benefits of study participation to 
the patient in simple terms using the IRB/IEC approved informed consent document and for 
ensuring patients are re-consented when the informed consent document is updated during the 
study, if required. The Investigator will ensure that documented informed consent, including 
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optional genetic analysis and future research, is obtained from each subject, or legally 
acceptable representative, if applicable to this study, by obtaining the signature and date on the 
informed consent document prior to the performance of protocol evaluations or procedures.
If informed consent is obtained from a legally acceptable representative for a subject who is 
unable to provide informed consent at study entry (if applicable), but the subject is later able 
to provide informed consent, the Investigator must obtain documented informed consent from 
the subject.
10.2 Ethical Review
The investigator will provide the Sponsor or its designee with documentation of the IRB/IEC 
approval of the protocol and the informed consent document before the study may begin at the 
investigative site(s). The name and address of the reviewing ethics committee are provided in 
the investigator file.
The Investigator will supply the following to the site’s IRB/IEC:
●
Protocol and amendments
●
Informed consent document and updates
●
Clinical Investigator’s Brochure and updates
●
Relevant curricula vitae, if required
●
Required safety and SAE reports
●
Any additional submissions required by the site’s IRB/IEC
The Investigator must provide the following documentation to the Sponsor or its designee:
●
The IRB/IEC periodic (e.g., quarterly, annual) re-approval of the protocol.
●
The IRB/IEC approvals of any amendments to the protocol or revisions to the informed 
consent document.
●
The IRB/IEC receipt of safety and SAE reports, as appropriate.
10.3 Regulatory Considerations
This study will be conducted in accordance with the protocol and ethical principles stated in 
the applicable guidelines on good clinical practice, and all applicable local and/or regional 
laws, rules, and regulations.
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10.3.1 Investigator Information
The contact information and qualifications of the Principal Investigator and Subinvestigators 
and name and address of the research facilities are included in the investigator file.
10.3.2 Protocol Amendments and Study Termination
Any Investigator-initiated changes to the protocol (with the exception of changes to eliminate 
an immediate hazard to a study patient) must be approved by the sponsor prior to seeking 
approval from the IRB/IEC, and prior to implementing. The Investigator is responsible for 
enrolling subjects who have met protocol eligibility criteria. Protocol deviations must be 
reported to the sponsor and the local IRB/IEC in accordance with IRB/IEC policies.
The Sponsor may terminate the study at any time. The IRB/IEC must be advised in writing of 
study completion or ET.
10.4 Study Documentation, Privacy and Records Retention
To protect the safety of subjects in the study and to ensure accurate, complete, and reliable 
data, the Investigator will keep records of laboratory tests, clinical notes, and medical records 
in the subjects’ files as original source documents for the study. If requested, the Investigator 
will provide the Sponsor, its licensees and collaborators, applicable regulatory agencies, and 
applicable IRB/IEC with direct access to original source documents or certified copies.
Records containing subject medical information must be handled in accordance with local and 
national laws, rules, and regulations and consistent with the terms of the informed consent 
document for the study. eCRFs and other documents to be transferred to the Sponsor should 
be completed in strict accordance with the instructions provided by the Sponsor, including the 
instructions regarding the coding of subject identities.
In compliance with local and/or regional regulations, this trial may be registered and trial 
results may be posted on public registries, such as ClinicalTrials.gov.
All study records containing subject details will identify the subject by initials (where 
permitted) and the assigned subject identification number. Subject information collected will 
comply with the applicable local laws and requirements for the protection of privacy of 
individually identifiable health information, such as the General Data Protection Regulation 
(GDPR) of the European Union.
10.5 Clinical Trial Agreement
Payments by the Sponsor to Investigators and institutions conducting the trial, requirements 
for Investigators’ insurance, the publication policy for clinical trial data, and other 
requirements are specified in the clinical trial agreement.
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11 REFERENCES
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Bradley GM, and Oliva-Hemker M (2012). Pediatric ulcerative colitis: current treatment 
approaches including role of infliximab. Biologics 6, 125-134.
Carter MJ, Lobo AJ, and Travis SP (2004). Guidelines for the management of inflammatory 
bowel disease in adults. Gut 53 Suppl 5, V1-16.
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Chang JT (2020). Pathophysiology of Inflammatory Bowel Diseases. N Engl J Med 383, 2652-
2664.
Chaparro M, Trapero-Marugán M, Moreno-Otero R, et al. (2009). Azathioprine plus ribavirin 
treatment and pancytopenia. Alimentary Pharmacology and Therapeutics 30, 962-963.
Fanton C, Furie R, Dixit N, et al.  (2020)  Selective expansion of regulatory T cells in patients 
with systemic lupus erythematosus by a novel IL-2 conjugate, NKTR-358.  Poster session 
presented at: American College of Rheumatology (ACR) Convergence  2020 Nov 5-9 [online 
meeting].  Abstract 1824.
Danese S, and Fiocchi C (2011). Ulcerative colitis. N Engl J Med 365, 1713-1725.
Harbord M, Eliakim R, Bettenworth D, et al. (2017). Third European Evidence-based 
Consensus on Diagnosis and Management of Ulcerative Colitis. Part 2: Current Management. 
J Crohns Colitis 11, 769-784.
Hartemann A, Bensimon G, Payan CA, et al. (2013). Low-dose interleukin 2 in patients with 
type 1 diabetes: a phase 1/2 randomised, double-blind, placebo-controlled trial. The Lancet 
Diabetes & Endocrinology 1, 295-305.
He J, Zhang X, Wei Y, et al. (2016). Low-dose interleukin-2 treatment selectively modulates 
CD4(+) T cell subsets in patients with systemic lupus erythematosus. Nat Med 22, 991-993.
Irvine EJ, Feagan B, Rochon J, et al. (1994). 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 106, 287-296.
Jairath V, Jeyarajah J, Zou G, et al. (2019). A composite disease activity index for early drug 
development in ulcerative colitis: development and validation of the UC-100 score. Lancet 
Gastroenterol Hepatol 4, 63-70.
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Jauregui-Amezaga A, Geerits A, Das Y, et al. (2017). A Simplified Geboes Score for 
Ulcerative Colitis. J Crohns Colitis 11, 305-313.
Jess T, Rungoe C, and Peyrin-Biroulet L (2012). Risk of colorectal cancer in patients with 
ulcerative colitis: a meta-analysis of population-based cohort studies. Clin Gastroenterol 
Hepatol 10, 639-645.
Klatzmann D, and Abbas AK (2015). The promise of low-dose interleukin-2 therapy for 
autoimmune and inflammatory diseases. Nat Rev Immunol 15, 283-294.
Koreth J, Matsuoka K, Kim HT, et al. (2011). Interleukin-2 and regulatory T cells in graft-
versus-host disease. N Engl J Med 365, 2055-2066.
Ma C, Sedano R, Almradi A, et al. (2021). An international consensus to standardize 
integration of histopathology in ulcerative colitis clinical trials. Gastroenterology.
Magro F, Lopes J, Borralho P, et al. (2020). Comparing the Continuous Geboes Score With 
the Robarts Histopathology Index: Definitions of Histological Remission and Response and 
their Relation to Faecal Calprotectin Levels. J Crohns Colitis 14, 169-175.
Mosli MH, Feagan BG, Zou G, et al. (2017). Development and validation of a histological 
index for UC. Gut 66, 50-58.
Neuenschwander B, Branson M, and Gsponer T (2008). Critical aspects of the Bayesian 
approach to phase I cancer trials. Stat Med 27, 2420-2439.
Ng SC, Shi HY, Hamidi N, et al. (2018). Worldwide incidence and prevalence of inflammatory 
bowel disease in the 21st century: a systematic review of population-based studies. Lancet 390, 
2769-2778.
Ordás I, Eckmann L, Talamini M, et al. (2012). Ulcerative colitis. Lancet 380, 1606-1619.
Pai RK, Khanna R, D'Haens GR, et al. (2019). Definitions of response and remission for the 
Robarts Histopathology Index. Gut 68, 2101-2102.
Rosenzwajg M, Churlaud G, Mallone R, et al. (2015). Low-dose interleukin-2 fosters a dose-
dependent regulatory T cell tuned milieu in T1D patients. J Autoimmun 58, 48-58.
Rosenzwajg M, Lorenzon R, Cacoub P, et al. (2018). Immunological and clinical effects of 
low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial. Ann 
Rheum Dis.
Saadoun D, Rosenzwajg M, Joly F, et al. (2011). Regulatory T-cell responses to low-dose 
interleukin-2 in HCV-induced vasculitis. N Engl J Med 365, 2067-2077.
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Tchao N,  Amouzadeh H, Sarkar N, et al. (2021)  Efavaleukin alfa, a novel IL-2 mutein, 
selectively expands regulatory T cells in patients with SLE.   Poster session presented at: 
American College of Rheumatology (ACR) Convergence  2021 Nov 5-9 [online meeting].  
Abstract 1734.
Tung J, Loftus Jr EV, Freese DK, et al. (2006). A population-based study of the frequency of 
corticosteroid resistance and dependence in pediatric patients with Crohn's disease and 
ulcerative colitis. Inflammatory Bowel Diseases 12, 1093-1100.
Turner D, and Griffiths AM (2011). Acute severe ulcerative colitis in children: a systematic 
review. Inflamm Bowel Dis 17, 440-449.
Ungaro R, Mehandru S, Allen PB, et al. (2017). Ulcerative colitis. Lancet 389, 1756-1770.
Ware JE, Jr., and Sherbourne CD (1992). The MOS 36-item short-form health survey (SF-36). 
I. Conceptual framework and item selection. Med Care 30, 473-483.
Yalcin I, and Bump RC (2003). Validation of two global impression questionnaires for 
incontinence. Am J Obstet Gynecol 189, 98-101.
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APPENDIX 2:
GUIDANCE ON CONTRACEPTION
ACCEPTABLE METHODS FOR HIGHLY EFFECTIVE BIRTH CONTROL
Male subjects, who are sexually active with a pregnant or breastfeeding woman, choose Option 1 or 2 
Option 1: Male condom with spermicide and cervical cap
Option 2: Male condom with spermicide and diaphragm 
Female subjects who are of childbearing potential AND male subjects who are sexually active with women of 
childbearing potentiala, choose any TWO of the following methods:

Hormonal methods of contraception (excluding progestin-only pills)

Intrauterine device with failure rate < 1%

Tubal ligation

Vasectomy (at least 90 days from the date of surgery with a semen analysis documenting azoospermia)

A barrier method (male or female condom with spermicide, cervical cap with spermicide, diaphragm 
with spermicide
a
A woman of childbearing potential is defined as any female who has experienced menarche and who has not undergone 
surgical sterilization (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or has not completed 
menopause. Menopause is defined clinically as 12 months of amenorrhea in a woman over age 45 in the absence of 
other biological, physiological, or pharmacological causes. 
UNACCEPTABLE METHODS OF CONTRACEPTION

Abstinence (including periodic abstinence)

No method

Withdrawal

Rhythm

Any barrier method without spermicide

Spermicide only

Progestin-only pills

Concomitant use of female and male condoms
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APPENDIX 3:
MAYO SCORING SYSTEM
Stool frequencya, d:
0 = Normal number of bowel movements 
1 = 1 to 2 bowel movements more than normal
2 = 3 to 4 bowel movements more than normal
3 = 5 or more bowel movements more than normal
Subscore, 0 to 3
Rectal bleedingb, d:
0 = No blood seen
1 = Streaks of blood with stool less than half the time
2 = Obvious blood with stool most of the time
3 = Blood alone passes
Subscore, 0 to 3
Findings on endoscopy:
0 = Normal or inactive disease
1 = Mild disease (erythema, decreased vascular pattern)
2 = Moderate disease (marked erythema, absent vascular pattern, any friability, erosions)
3 = Severe disease (spontaneous bleeding, ulceration)
Subscore, 0 to 3
Physician’s global assessmentc:
0 = Normal
1 = Mild disease
2 = Moderate disease
3 = Severe disease
Subscore, 0 to 3
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The Mayo Score ranges from 0 to 12, with higher scores indicating more severe disease
a Each subject serves as his or her own control to establish the degree of abnormality of the stool frequency
b The daily bleeding score represents the most severe bleeding of the day
c The physician’s global assessment acknowledges the 3 other criteria, the subject’s recollection of abdominal 
discomfort and general sense of wellbeing, and other observations, such as physical findings and the subject’s 
performance status
d The modified Mayo Score calculated at the Screening and Week 12 visits must use the SF and RB Mayo 
subscores recorded on the eDiary (or paper diary) over the 3 consecutive days prior to the endoscopy (excluding 
the bowel preparation day)
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APPENDIX 4:
ORIGINAL GEBOES SCORING SYSTEM
Grade 0: Architectural changes
0.0 No abnormality
0.1 Mild abnormality
0.2 Mild/moderate diffuse or multifocal abnormalities
0.3 Severe diffuse or multifocal abnormalities  
Grade 1: Chronic inflammatory infiltrate 
1.0 No increase
1.1 Mild but unequivocal increase
1.2 Moderate increase
1.3 Marked increase 
Grade 2A: Eosinophils in lamina propria
2A.0 No increase
2A.1 Mild but unequivocal increase
2A.2 Moderate increase
2A.3 Marked increase 
Grade 2B: Neutrophils in lamina propria
2B.0 No increase
2B.1 Mild but unequivocal increase
2B.2 Moderate increase
2B.3 Marked increase
Grade 3: Neutrophils in epithelium 
3.0 None
3.1 < 5% crypts involved
3.2 < 50% crypts involved
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3.3 > 50% crypts involved 
Grade 4: Crypt destruction 
4.0 None
4.1 Probable: local excess of neutrophils in part of the crypts
4.2 Probable: marked attenuation
4.3 Unequivocal crypt destruction 
Grade 5: Erosions and ulcerations
5.0 No erosion, ulceration or granulation tissue
5.1 Recovering epithelium + adjacent inflammation
5.2 Probable erosion: focally stripped
5.3 Unequivocal erosion
5.4 Ulcer or granulation tissue
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APPENDIX 5:
ROBARTS HISTOPATHOLOGY INDEX
RHI =1 x chronic inflammatory infiltrate level (4 levels) + 2 x lamina propria neutrophils 
(4 levels) + 3 x neutrophils in epithelium (4 levels) + 5 x erosion or ulceration (4 levels after 
combining Geboes 5.2 and 5.2). The RHI ranges from 0 to 33.
Chronic Inflammatory Infiltrate Level
0 = no increase
1 = mild but unequivocal increase
2 = moderate increase
3 = marked increase
Lamina Propria Neutrophils
0 = none
1 = mild but unequivocal increase
2 = moderate increase
3 = marked increase
Neutrophils in Epithelium 
0 = none
1 = < 5% crypts involved
2 = < 50% crypts involved
3 = > 50% crypts involved
Erosion or Ulceration
0 = no erosion, ulceration or granulation tissue
1 = recovering epithelium + adjacent inflammation
1 = probable erosion – focally stripped
2 = unequivocal erosion
3 = ulcer or granulation tissue
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APPENDIX 6:
COMPOSITE UC-100
Composite UC-100= (1 + 16 × Mayo Clinic stool frequency subscore [0 to 3] + 6 × Mayo 
Clinic endoscopic subscore [0 to 3] + 1 × RHI score [0 to 33])
The UC-100 ranges from 1 (no disease activity) to 100 (severe disease activity).

Mayo Clinic stool frequency subscore (Appendix 3)

Mayo Clinic endoscopic subscore (Appendix 3)

RHI score (Appendix 5) 
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APPENDIX 7:
DRUG-INDUCED LIVER INJURY GUIDANCE DOCUMENT
PURPOSE
The purpose of this appendix is to provide guidance regarding clinical follow-up and 
systematic data gathering and reporting on potential cases of drug induced liver injury (DILI) 
that meet specific agency-specified criteria (‘Hy’s Law’ criteria as discussed below) as being 
predictive of a drug’s ability to cause severe liver injury. The data collected will be used by 
the Sponsor or the Investigator to create narratives for regulatory agency reporting.
INTRODUCTION
Drug-induced hepatotoxicity is one of the most common causes of termination of drug 
development, a major reason for refusal of market authorization and for restricted use, and the 
single most important cause of the withdrawal of market authorization for products (Björnsson 
2006). Thus, drug-induced hepatotoxicity is a major concern during the discovery, 
development to post-authorization phases of the product life cycle (excerpted from Premarket 
Evaluation of Hepatotoxicity of Health Products, Ministry of Public Health, Canada, April 
2012).
As stated in the United States Food and Drug Administration (FDA) Guidance for Industry -
Drug-Induced Liver Injury: Premarketing Clinical Evaluation; hepatocellular injury (usually 
detected by serum aminotransferase elevations [AT]) can be caused by drugs that rarely, if 
ever, cause severe DILI (e.g. aspirin, tacrine, statins, and heparin) as well as by drugs that do 
cause such injury.  
The most specific predictor of a drug’s potential for severe hepatotoxicity, is the occurrence of 
hepatocellular injury (AT elevation) accompanied by increased serum total bilirubin (TBL), 
not explained by any other cause, such as viral hepatitis or exposure to other hepatotoxins, and 
without evidence of cholestasis, together with an increased incidence of AT elevations in the 
overall trial population compared to control. Increased plasma prothrombin time, or its 
international normalized ratio (INR), a consequence of reduced hepatic production of Vitamin 
K-dependent clotting factors, is another potentially useful measure of liver function that might 
suggest the potential for severe liver injury.
Recognition of the importance of altered liver function, in addition to liver injury, began with 
Hyman Zimmerman’s observation that drug-induced hepatocellular injury (i.e. AT elevation) 
accompanied by jaundice (i.e. TBL elevation) had a poor prognosis, with a 10 to 50 percent 
mortality from acute liver failure (in pretransplantation days) (Zimmerman 1978, 1999). This 
became known as "Hy's Law". This guidance describes the recommended process for 
monitoring and evaluation of subjects meeting the laboratory criteria for potential Hy’s Law 
defined as:

1) an elevated alanine transaminase (ALT) or aspartate transaminase (AST) lab value 
that is greater than or equal to three times (3X) the upper limit of normal (ULN) and

2) an elevated TBL lab value that is greater than or equal to two times (2X) ULN and
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
3) at the same time, an alkaline phosphatase (ALP) lab value that is less than 2X ULN, 
It should be noted that the guidance provided here specifically pertains to potential Hy’s 
Law cases as defined above. Due to the significant potential implications of a Hy’s Law case 
for the health of study subjects as well as for the safety profile of the investigational agent or 
agents being evaluated, study investigators must follow these guidelines for evaluation of the 
study subject, and investigation for potential alternate etiologies.        
It should also be noted that it is often appropriate to conduct additional evaluation for an 
underlying etiology in the setting of abnormalities of liver blood tests including AST, ALT, 
bilirubin, and alkaline phosphatase that are suggestive of DILI but do not meet criteria for a 
potential Hy’s Law case. In these situations, investigators should initiate appropriate evaluation 
and monitoring based on their judgment, using the guidelines below. They should 
communicate with the sponsor’s medical monitor as soon as possible. In these cases, the 
decision to proceed with additional evaluation will be made through consultation between the 
study investigators and the sponsor medical monitor. 
CLOSE OBSERVATION RECOMMENDATIONS
The following steps should be taken when a subject is observed to have an elevated AST or 
ALT lab value that is greater than or equal to 3X ULN and an elevated TBL lab value that is 
greater than or equal to 2X ULN and, at the same time, an ALP lab value that is less than 2X 
ULN, as a result of within-protocol-specific testing or unscheduled testing. 
Treatment with PT101 should be stopped if the laboratory criteria for potential Hy’s Law 
are met (Section 3.1.7 Individual Stopping Rules).  
Initiate close observation, defined below, and continue performing follow-up to resolution. 
Close observation is defined as follows: 

Repeat liver enzyme and serum bilirubin tests two (2) or three (3) times weekly.  
Frequency of retesting can decrease to once a week or less if abnormalities stabilize or 
study drug has been discontinued and the subject is asymptomatic.

Obtain a detailed history of symptoms and prior or concurrent diseases. (See Section 
4.1).

Obtain additional pertinent history informing potential alternate etiologies for the liver 
enzyme and bilirubin elevations (see below). 

Complete Stage 1 workup for potential alternate etiologies for the liver enzyme and 
bilirubin elevations (see below). 

Consider gastroenterology or hepatology consultation. 
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Note: if the etiology of the observed laboratory abnormalities becomes clear in the course of 
evaluation, the evaluation may be abbreviated as appropriate and agreed upon by the study 
investigator and sponsor medical monitor.  
EVALUATION OF POTENTIAL HY’S LAW CASES
When a subject meets criteria for being a potential Hy’s Law case (as defined above), it is 
important to thoroughly assess the subject’s history, hepatic risk factors, clinical condition and 
hepatic function until resolution (normal or baseline levels). This information is both critical 
for effect of evaluation and management of an active potential Hy’s Law case, and for 
supporting optimal assessment of drug safety.   
Accrued data pertinent to the evaluation of the potential Hy’s Law case should be recorded in 
source documents and in appropriate CRFs.  
Key elements of the evaluation to be addressed and documented in assessment
Consistent with regulatory guidance (see references) the following information must be 
gathered during evaluation of a potential Hy’s Law case, even if the subject in question is 
known to be receiving control treatment. Information should be updated as data accrues 
throughout the evaluation.  
1.  Study drug treatment including the following:
a. Time and dates from start of drug administration to start of the illness (initial 
detection of pertinent laboratory abnormalities and/or physical symptoms or signs).
b. Time and date of interruption of drug administration
2.  Narrative free text describing relevant medical history and the course of the illness.  
This should include the following elements and should clearly address timeframe (including 
onset and duration of symptoms, signs, and relevant risk factors in medical history):    
a. Pertinent history: Including history of present illness and potentially relevant past 
medical history including potential risk factors for liver disease of alternate etiologies 
(unrelated to study drug). See Table 7 and Table 8 below.    
b. Pertinent physical examination findings. See Table 7 below.    
c. Outcomes including treatment, recovery, hospitalization, liver transplant and death 
Note: The history and physical examination elements noted in Table 7 and Table 8 should be 
specifically addressed as pertinent positive or negative findings
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Table 7:
Symptoms and signs to assess during evaluation of a potential Hy’s Law 
case  
Category
Examples of Signs and Symptoms
Blood/lymphatic
Susceptibility to bleeding
Circulatory
spider nevi, abdominal varicosities, edema
Digestive/hepatic
Anorexia/appetite loss, diarrhea, bloody or black stool, light-colored stools, nausea, 
vomiting, vomiting of blood, right upper quadrant abdominal pain, enlarged and tender 
liver, jaundice, enlarged spleen, ascites
Immune
Fever
Integumentary
Rash, pruritus
Muscular
Muscle aches and pains
Nervous
Changes in mental status or level of consciousness
Urinary
Dark urine
Miscellaneous
Fatigue, malaise, weight gain, other (identify):
General 
Obesity (record weight and height)
Table 8:
Medical history elements to assess in evaluation of a potential Hy’s Law 
case.
Category
Examples of Confounding Variables
Subject medical history
Prior history of liver injury or disease, including but not limited to 
Gilbert's syndrome, autoimmune disorders, cancer, Wilson's disease, 
NASH, alcoholic or infectious hepatitis, biliary tract disease, 
hypoxic/ischaemic hepatopathy
Family history 
Autoimmune disorder, cancer, Gilbert’s syndrome, Wilson’s disease
Substance use/abuse
Alcohol, illegal drugs, illegal intravenous (IV) drugs 
Prior & Concomitant Medications:  
Review all non-study medications 
and therapies, including: over-the-
counter (OTC), prescription. As 
appropriate, ask the subject to bring 
products/packaging to site and 
review contents.
History of recent of concomitant acetaminophen (APAP)/paracetamol 
use, excessive nonsteroidal anti-inflammatory drug (NSAID) intake, 
use of non-study drug or therapy that can cause liver damage or 
idiosyncratic adverse drug reactions
History of prior exposure to the investigational drug or similar drugs 
that could potentially have predisposed to an immune/allergic reaction 
upon exposure in the study   
Herbal and nutritional supplements
Herbal, complementary therapies, and nutritional supplements
Adulteration of products
Information on potential contamination or adulteration of food or 
other ingested products (such as nutritional supplements)
Chemical exposure
Occupational or in other situations
Potential exposure to infectious 
agents 
Infectious hepatitis, transfusion, travel (last 3 years), tattoos, sexually 
transmitted diseases, new sexual partner, shared needles
Special Diet
Special diet started since randomization. Unusual foods (e.g. foraged 
mushrooms) or special diets. Consumption of seasonal foods.
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Category
Examples of Confounding Variables
Other
Recent physical trauma, excessive exercise, or other prolonged 
physical exertion
3. All pertinent data including results of all evaluations for alternate etiologies. This 
should include all data, positive and negative, collected under Stage 1 and 2 evaluations (see
below).  
Note- laboratory data should be captured with laboratory normal ranges, and should include 
both protocol-scheduled laboratory evaluations as well as all unscheduled evaluations.  
Data collected on multiple occasions over time should ideally be displayed in a chart or graph.
If applicable, request copies of hospital discharge summaries, consultation reports, pathology 
reports, special studies (e.g. imaging or biopsy), etc.
4. Summary assessment of evaluation for potential etiologies: This should include the 
investigator’s summary impression regarding potential etiology of the observed liver function 
test abnormalities and status of the ongoing evaluation.   
5. Medical status and treatment plan: This should include the investigator’s summary 
impression regarding subject medical status and the treatment plan.
Evaluation for potential Hy’s Law cases if there are no evident alternate etiologies
Note: If a clear etiology for the laboratory abnormalities has been confirmed, Stage 1 and 2 
testing may not be required. In this case, consultation with the Sponsor medical monitor is 
required.
Stage 1 workup: should be performed within 48-72 hours: 

A detailed medical history and physical examination should be performed, including 
the elements noted in Table 7 and Table 8.    

Review aminotransferase values obtained prior to and during the study or 
administration of study medication.

Consultation with a hepatologist/gastroenterologist should be strongly considered
Perform the following laboratory tests:

Liver safety laboratories: ALT, AST, bilirubin (total and direct), alkaline phosphatase 
(ALP), gamma-glutamyl transferase (GGT)

Prothrombin Time (PT) / international normalized ratio (INR) 
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
Creatine phosphokinase (CPK)

Albumin

Complete blood count including platelet count and white blood cell count with an 
automated differential. Specific attention should be paid to eosinophil count as 
hypereosinophilia may be associated with idiosyncratic drug reactions. 

Toxicology 
screen 
for 
drugs 
of 
abuse 
(including 
ethanol) 
and 
for 
acetaminophen/paracetamol level should also be sent. Investigators may order 
additional toxicology tests as clinically indicated.

Viral hepatitis serologies (obtain appropriate consent prior to testing, if required 
locally)
o
A (IgG, IgM)
o
B (HepBs Ag, Hep Bs Ab, Hep Bc Ab)
o
C (RNA)
o
Cytomegalovirus (CMV): Viral PCR and serologies (IgG, IgM)   
o
Epstein-Barr Virus (EBV): Viral PCR and serologies (IgG, IgM)

Human Immunodeficiency Virus (HIV) testing (obtain appropriate consent prior to 
testing, if required locally)

Appropriate samples should be collected and stored for potential viral PCR testing for 
the following viruses: hepatitis E, herpes simplex, varicella and parvovirus. These 
samples should not be submitted for analysis unless testing for these pathogens is 
triggered under Stage 2 workup, or there is a specific suspicion.       

Obtain a right upper quadrant ultrasound. If ultrasound is not available, MRI or CT 
scan may be used to image liver and biliary tract.   
Stage 2 workup: Unless otherwise agreed upon by the study investigator and sponsor 
medical monitor, Stage 2 tests should be drawn within one (1) week of receiving the Stage 
1 workup results and the results of Stage 1 evaluation are negative.
Notes: 
• A specific test may be performed earlier if the investigator determines that the clinical 
presentation leads to a certain diagnosis.
• If no etiology for the liver safety test abnormalities has been identified and evaluation 
is 
progressing 
to 
Stage 
2 
workup, 
consultation 
with 
a 
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hepatologist/gastroenterologist must occur unless both the study investigator and 
sponsor medical monitor agree that there is a compelling reason that this is 
unnecessary.   
Stage 2 workup should be guided by information accrued during Stage 1 workup as well as 
expert input from a hepatologist/gastroenterologist:
The following laboratory tests and evaluations may be considered, as appropriate, for 
evaluation of a potential Hy’s Law case.  

Serologies for the following infectious agents (contain appropriate local consent):
o
Viral hepatitis D (if subject has hepatitis B)
o
Viral hepatitis E   
o
Herpes simplex
o
Toxoplasmosis
o
Varicella
o
Parvovirus

Assessments for inherited liver diseases. Ensure appropriate consent is obtained for 
any genetic testing.
o
Hemochromatosis

Iron Studies: serum ferritin, iron, total iron binding capacity

Genetic test if necessary to confirm a diagnosis. A genetic test will 
generally not be necessary if iron studies are normal.
o
Gilbert’s disease: genetic testing if there is a suspicious history and total and 
direct bilirubin measurements do not support a clear diagnosis
o
Wilson’s disease: ceruloplasmin and 24hr urinary copper
o
Alpha-1-antitrypsin deficiency: serum alpha-1-antitrypsin concentration and 
protease inhibitor (PI) typing
o
Cystic fibrosis: genetic testing
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
Tests for autoimmune hepatitis
o
Antinuclear antibody (ANA) 
o
Anti-smooth muscle antibodies
o
Anti-liver-kidney microsomal antibodies
o
Anti-soluble liver antigen antibodies
o
Anti-actin antibodies

Testing for primary biliary cirrhosis: Anti-mitochondrial antibody (if ALP or TBL 
>ULN)

Celiac disease screening including anti-tissue transglutaminase (TTG) antibody, IgA, 
and anti-endomysial (EMA) antibody if clinically indicated.  

Consider screening for cystic fibrosis if clinically indicated.   
If laboratory tests or ultrasound evidence of biliary tract obstruction, consider obtaining ERCP 
or MRCP
CONTACTS
If you have any questions, please refer to your Sponsor contact list for the following Alimentiv 
or Pandion personnel:
- Clinical Research Associate or Subsidiary Monitor
- Medical Monitor
REFERENCES

Drug-Related Hepatotoxicity, Victor J. Navarro and John R. Senior, N Engl J Med 
2006;354:7314-9

Drug-induced liver injury:Hy’s rule revisited, Einar Björnsson MD, PhD, Clinical 
Pharmacology & Therapeutics, Vol. 79, Issue 6, June 2006.

Premarket Evaluation of Hepatotoxicity of Health Products, Ministry of Public Health, 
Canada, April 2012
o
https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-
products/applications-submissions/guidance-documents/hepatotoxicity-pre-
market-evaluation.html
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o
FDA Guidance for Industry - Drug-Induced Liver Injury: Premarketing Clinical 
Evaluation, July 2009
o
www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/
Guidances/UCM174090.pdf 

Zimmerman HJ 1978 Hepatotoxicity, The Adverse Effects of Drugs and Other 
Chemicals on the Liver, Drug-induced liver disease (Appleton-Centry-Crofts, New 
York), pp 351-5.

Zimmerman HJ 1999 Hepatotoxicity, The Adverse Effects of Drugs and Other 
Chemicals on the Liver, Drug-induced liver disease (Lippincott Williams & Wilkins, 
Philadelphia), 2, pp 428-33.
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APPENDIX 8: 
12-LEAD ELECTROCARDIOGRAM ABNORMALITY 
CRITERIA
Potentially Significant 
Findings Leading to 
Screen Failure 
Potentially Significant 
Postrandomization Findings 
(clarification on action to 
take)
RHYTHM
Sinus Tachycardia
110 bpm
HR > 110 bpm and HR 
increase of ≥25 bpm from 
baseline, that is sustained for 
90 minutes or longer
Sinus Bradycardia
< 40 bpm
HR < 40 bpm and HR 
decrease of ≥5 bpm from 
baseline
Sinus Pause/Arrest
> 2.0 seconds
> 2.0 seconds
Atrial Premature Complex
1 beat
3 beats
Ventricular Premature 
Complex
All
3 beats
Ectopic Atrial Rhythm 
None
None
Junctional Rhythm
Junctional Rhythm with HR 
< 40 bpm
Junctional Rhythm with HR 
< 40 bpm
Idioventricular Rhythm
All
All
Atrial Fibrillation
All
All
Atrial Flutter
All
All
Supraventricular 
Tachycardia
All
All
Ventricular Tachycardia
All
All
AXIS
Left Axis Deviation
RBBB With LAHB
New Onset LAHB
Right Axis Deviation
RBBB With LPHB
New Onset LPHB
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Potentially Significant 
Findings Leading to 
Screen Failure 
Potentially Significant 
Postrandomization Findings 
(clarification on action to 
take)
CONDUCTION
1st Degree AV Block
PR 230 ms
PR 230 ms + Increase of 
15 ms; or PR Increase of >
25%
2nd Degree AV Block
Mobitz Type II
Mobitz Type II
3rd Degree AV Block
All
All
LBBB
All
All
RBBB
RBBB With LAHB/LPHB 
as Defined Above
New Onset RBBB (Not 
Including Rate-related)
ICRBBB (QRS < 120 ms)
No Exclusion
Nothing
Short PR/Preexcitation 
Syndrome
Delta Wave + PR < 120 ms
Delta Wave + PR < 120 ms
Other Intra-Ventricular 
Conduction Delay
QRS 130 ms
QRS 130 ms + Increase of 
10 ms
QTc (B or F)
Male
QTc 470 ms
QTc 500 ms or Increase of 
60 ms From Baseline
Female
QTc 480 ms
QTc 500 ms or Increase of 
60 ms From Baseline
HYPERTROPHY
Atrial Abnormalities
Definite Evidence of P 
Mitrale or P Pulmonale
Definite Evidence of P 
Mitrale or P Pulmonale
Ventricular Abnormalities
Voltage Criteria for LVH 
Plus Strain Pattern
Voltage Criteria for LVH 
Plus Strain Pattern
MYOCARDIAL INFARCTION
Acute or Recent
All
All
Old
All
All
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Potentially Significant 
Findings Leading to 
Screen Failure 
Potentially Significant 
Postrandomization Findings 
(clarification on action to 
take)
ST/T MORPHOLOGY
ST Elevation Suggestive of 
Myocardial Injury 
In 2 or more contiguous 
leads
In 2 or more contiguous leads
ST Depression Suggestive 
of Myocardial Ischaemia 
In 2 or more contiguous
leads
In 2 or more contiguous leads
T-wave Inversions 
Suggestive of Myocardial 
Ischaemia 
In 2 or more contiguous 
leads
In 2 or more contiguous leads
Non-specific ST-T Changes 
(In 2 or More Leads)
No exclusion
In 2 or more contiguous leads
PACEMAKER
All
All
AV=atrioventricular; bpm=beats per minute; HR=heart rate: ICRBBB=incomplete right bundle branch block; 
LAHB=left anterior hemiblock; LPHB=left posterior hemiblock; LVH=left ventricular hypertrophy; mm=millimeter; 
ms=milliseconds, PR=pulse rate; QTcB=QT correction using Bazett’s formula; QTcF=QT correction using Fridericia 
formula; RBBB=right bundle branch block; ST/T=ST-segment/T wave.
Baseline is defined as Predose Day 1
08NYPB


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1<3%


MK-6194-002-08
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Amendment 8; 13-May-2022
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APPENDIX 10:
INVESTIGATOR SIGNATURE PAGE
INVESTIGATOR STATEMENT
This study will be conducted in accordance with the following:

The ethical principles that have their origin in the Declaration of Helsinki.

International Council on Harmonisation (ICH) E6 Good Clinical Practice (GCP) 
Consolidated Guideline.

All applicable laws and regulations, including, without limitation, data privacy laws, 
clinical trial disclosure laws, and regulations.
I have read the protocol, including all appendices, and I agree it contains all necessary details 
for me and my staff to conduct this study. I will conduct this study as outlined herein. I will 
provide study personnel under my supervision access to all materials provided by Pandion 
Therapeutics. I will ensure my staff are appropriately informed of their obligations.
_________________________
_______________________
Principal Investigator Name
Signature
______________
__________
Date
Site Number
_________________________________
___________________________
Institution Name
Address of Institution
08NYPB


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PT101
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APPENDIX 11:
DOCUMENT HISTORY
Version
Date
Original
12-Mar-2021
Amendment 1
11-May-2021
Amendment 4
17-Dec-2021
Amendment 8
13-May-2022
08NYPB


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SAP_001.pdf: 
Official Protocol Title: 
NCT number: 
NCT04924114 
Document Date: 
23-Feb-2024 
A Phase 1b, Randomized, Adaptive, Double-Blind, Placebo-
Controlled, Multicenter Study to Investigate the Safety,
Tolerability, Pharmacokinetics, and Pharmacodynamics of
Multiple Doses of PT101 in Subjects with Active Ulcerative
Colitis


STATISTICAL ANALYSIS PLAN
Version: 02
Status: Final
PT101-201-StatisticalAnalysisPlan-V02
Page 1 of 63
STATISTICAL ANALYSIS PLAN
PT101-201
Version 02
23FEB2024
Status: Final
Prepared by:
Alimentiv Inc.
100 Dundas Street, Suite 200
London, Ontario, Canada
N6A 5B6
Sponsor:
Pandion Therapeutics, Inc., a wholly owned 
subsidiary of Merck & Co., Inc., Rahway, NJ, 
USA (known as MSD outside the United States 
and Canada)
134 Coolidge Ave 
Watertown, USA
MA 02472.
PPD
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PT101-201-StatisticalAnalysisPlan-V02
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APPROVAL
STATISTICAL ANALYSIS PLAN
PT101-201 
Version 02 
23FEB2024 
1 Author, signs for correctness and completeness
2 Reviewer, signs for correctness and completeness
3 Approver, signs for the release of the document
PPD
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PT101-201-StatisticalAnalysisPlan-V02
Page 3 of 63 
TABLE OF CONTENTS
TABLE OF CONTENTS ........................................................................................................................... 3 
DEFINITIONS AND ABBREVIATIONS ................................................................................................ 6 
1 
INTRODUCTION.......................................................................................................................... 8 
2 
STUDY OBJECTIVES .................................................................................................................. 8 
3 
STUDY DESIGN ............................................................................................................................ 9 
3.3.1 RANDOMIZATION.....................................................................................................10
3.3.2 BLINDING ................................................................................................................. 11 
4 
GENERAL CONSIDERATIONS FOR DATA ANALYSIS.................................................... 11 
4.2.1 INTENT-TO-TREAT ANALYSIS SET ........................................................................... 13 
4.2.2 FULL ANALYSIS SET................................................................................................ 13 
4.2.3 PER PROTOCOL ANALYSIS SET................................................................................ 13 
4.2.4 SAFETY ANALYSIS SET ............................................................................................ 13 
4.2.5 PK & BIOMARKER ANALYSIS SET ........................................................................... 13 
5 
STUDY SUBJECTS ..................................................................................................................... 14 
5.5.1 PRIOR MEDICATION................................................................................................. 17 
5.5.2 CONCOMITANT MEDICATION .................................................................................. 17 
6 
EFFICACY ANALYSES............................................................................................................. 18 
6.1.1 MAYO SCORE ........................................................................................................... 18 
6.1.2 GEBOES SCORE ........................................................................................................ 21 
6.1.3 ROBARTS HISTOPATHOLOGY INDEX ....................................................................... 21 
6.1.4 UC-100 .................................................................................................................... 21 
1.1
OBJECTIVE OF THE STATISTICAL ANALYSIS PLAN................................................................8
2.1
OBJECTIVES AND ENDPOINTS................................................................................................8
3.1
SUMMARY OF STUDY DESIGN ............................................................................................... 9
3.2
TREATMENTS....................................................................................................................... 10
3.3
RANDOMIZATION AND BLINDING........................................................................................ 10
4.1
REPORTING CONVENTIONS.................................................................................................. 11
4.2
ANALYSIS SETS ................................................................................................................... 13
4.3
HANDLING OF DATA............................................................................................................ 14
5.1
SUBJECT DISPOSITION ......................................................................................................... 16
5.2
PROTOCOL DEVIATIONS ...................................................................................................... 16
5.3
DEMOGRAPHICS AND BASELINE CHARACTERISTICS........................................................... 16
5.4
MEDICAL, SURGICAL, AND MEDICATION HISTORY ............................................................ 17
5.5
PRIOR AND CONCOMITANT MEDICATION............................................................................ 17
5.6
TREATMENT COMPLIANCE .................................................................................................. 17
6.1
DERIVATION OF EFFICACY MEASUREMENTS ...................................................................... 18
6.2
EFFICACY ENDPOINTS ......................................................................................................... 21
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6.2.1
DICHOTOMOUS EFFICACY ENDPOINTS....................................................................21
6.2.2 CONTINUOUS EFFICACY ENDPOINTS.......................................................................22
6.2.3 ADDITIONAL ANALYSES.......................................................................................... 23 
6.2.4 MISSING DATA HANDLING...................................................................................... 23 
6.2.5 SENSITIVITY ANALYSES ..........................................................................................23
7 
PHARMACOKINETIC AND PHARMACODYNAMIC ANALYSES .................................. 23 
7.3.1 IMMUNOPHENOTYPING OF CELL POPULATIONS ASSESSMENT................................ 25 
8 
BIOMARKER ANALYSES ........................................................................................................ 29 
9 
SAFETY ANALYSES ................................................................................................................. 30 
9.1.1 ADVERSE EVENT CODING........................................................................................30 
9.1.2 ADVERSE EVENT SEVERITY.....................................................................................30 
9.1.3 RELATIONSHIP OF ADVERSE EVENT TO STUDY TREATMENT .................................. 31 
9.1.4 SERIOUS ADVERSE EVENTS..................................................................................... 31 
9.1.5 TREATMENT-EMERGENT ADVERSE EVENTS............................................................ 31 
9.1.6 SUMMARIES OF TREATMENT-EMERGENT ADVERSE EVENTS .................................. 32 
10 
QUALITY OF LIFE ANALYSIS ............................................................................................... 34 
10.1.1 INFLAMMATORY BOWEL DISEASE QUESTIONNAIRE............................................... 34 
10.1.2 SHORT-FORM QUESTIONNAIRE................................................................................ 35 
11 
SUBGROUP ANALYSIS ............................................................................................................ 35 
12 
CONTINUED BLINDED TREATMENT AND OPEN-LABEL ANALYSIS ....................... 35 
13 
DRC REVIEW ............................................................................................................................. 35 
7.1
PHARMACOKINETIC ASSESSMENTS.....................................................................................23
7.2
IMMUNOGENICITY ASSESSMENTS ....................................................................................... 25
7.3
PHARMACODYNAMIC ASSESSMENTS ..................................................................................25
9.1
ADVERSE EVENTS................................................................................................................30
9.2
PHYSICAL EXAMINATION .................................................................................................... 32
9.3
VITAL SIGNS ........................................................................................................................ 33
9.4
CLINCAL LABORATORY TESTS............................................................................................ 33
9.5
ELECTROCARDIOGRAMS ...................................................................................................... 33
9.6
EVENTS OF CLINICAL INTEREST.......................................................................................... 33
13.1 ASSESSMENT OF DOSE-LIMITING TOXICITY ........................................................................ 36
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14
CHANGES FROM PROTOCOL...............................................................................................37
15 
REVISION HISTORY ................................................................................................................ 37 
APPENDIX A: SCHEDULE OF ASSESSMENTS ................................................................................ 38 
APPENDIX B: MAYO SCORE...............................................................................................................49
APPENDIX C: GEBOES SCORING ...................................................................................................... 51 
APPENDIX D: ROBARTS HISTOPATHOLOGY INDEX SCORING ............................................. 53 
APPENDIX E: QUALITY OF LIFE IN INFLAMMATORY BOWEL DISEASE QUESTIONNAIRE 
(IBDQ) ........................................................................................................................................................ 54 
LIST OF TABLES 
Table 1. Objectives and Endpoints ................................................................................................. 8 
Table 2. Data Presentation for Study Subject Information .......................................................... 15 
Table 3. Example of Calculation of Stool Frequency Subscore at Post-baseline for Mayo Scorea
............................................................................................................................................................ 20 
Table 4. Example of Calculation of Rectal Bleeding Subscore at Post-baseline for Mayo Scorea
............................................................................................................................................................ 20 
Table 5. Definition of Binary Endpoints ........................................................................................ 22 
Table 6. Definition of Continuous Efficacy Endpoints ................................................................. 22 
Table 7. Standard Pharmacokinetics Parameters ......................................................................... 24 
Table 8. Parameters and Analyses to be Reported From the Immunophenotyping Panel ....... 27 
Table 9. Definition of Biomarker Endpoints ................................................................................. 29 
Table 10. Adverse Event Severity Grading .................................................................................... 31 
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DEFINITIONS AND ABBREVIATIONS
ADA 
anti-drug antibody 
AE 
adverse event 
ATC
anatomical therapeutic chemical
AUC 
area under the curve 
AUC0-inf 
area under the curve from time 0 to infinity  
AUC0-t 
area under the curve from time 0 to time t 
BLRM 
Bayesian Logistic Regression Model 
Cmax  
maximum concentration 
CBT 
continued blinded treatment 
CRO 
contract research organization 
DLT 
dose-limiting toxicity 
DRC 
data review committee  
ECG 
electrocardiogram 
eCRF  
electronic case report form  
FAS  
full analysis set 
HCP 
health care professional 
IBDQ 
Inflammatory Bowel Disease Questionnaire 
IBT  
initial blinded treatment 
IL-5 
interleukin 5
ITT  
intent-to-treat analysis set
LOCF
last observation carried forward 
LOQ 
limit of quantitation  
MCS
Mayo score
MedDRA 
Medical Dictionary for Regulatory Activities 
MES 
Mayo endoscopic subscore 
mMCS 
modified Mayo score
MMRM
mixed-model-repeated measure 
MTD  
maximum tolerated dose 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for 
Adverse Events  
NRI
non-responder imputation 
OL 
open-label 
PD  
pharmacodynamics 
PGA 
physician global assessment  
PK 
pharmacokinetics 
pMCS
partial Mayo score
PP 
per protocol analysis set 
PT 
preferred term
RB 
rectal bleeding 
RHI 
Robarts Histopathology Index 
RO 
receptor occupancy
SAE  
serious adverse event  
SAF  
safety analysis set 
SAP  
statistical analysis plan  
SC  
subcutaneous 
sCD25 
soluble form of IL2 receptor alpha chain
SF 
stool frequency 
SOC
system organ class 
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TEAE 
treatment-emergent adverse event 
TESAE  
treatment-emergent serious adverse event 
TMF 
trial master file 
Treg  
regulatory T cell 
UC 
ulcerative colitis 
ULN 
upper limit of normal 
WHODD  
World Health Organization drug dictionary 
 
 
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1
INTRODUCTION
This is a Phase 1b, adaptive, randomized, double-blind, placebo-controlled, multiple-dose study.  This study 
will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PT101 in 
subjects with active ulcerative colitis (UC) following multiple subcutaneous (SC) doses. 
1.1 
OBJECTIVE OF THE STATISTICAL ANALYSIS PLAN 
This statistical analysis plan (SAP) describes in detail the statistical methods that will be applied to the data 
gathered in clinical trial protocol No. PT101-201. It will describe the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs), to assess the safety, PK, PD, and efficacy in 
patients with mildly to severely active UC. It will also outline the data analyses performed for the data 
review committee (DRC). This SAP will be finalized prior to database lock and the data analysis start. Any 
changes to the planned analyses (other than cosmetic) made after database lock will be documented in the 
clinical study report with rationales and details. 
Safety, PK, PD, and efficacy analyses defined within this SAP will be periodically presented to the DRC 
to inform their recommendation on dose-escalation, opening of an optional cohort, continuing the study 
without changes, modifying the study, and/or dose/regimen selection to guide future clinical development 
of PT101 as outlined in the DRC charter. Roles and responsibilities of the DRC are also described in the 
DRC charter.  
2 
STUDY OBJECTIVES 
This document will present analysis related to the primary (safety), secondary (PK, PD, immunogenicity), 
and exploratory clinical efficacy (assessment of improvement in disease activity) endpoints through 
and applicable efficacy and safety endpoints
All primary, secondary, and 
exploratory endpoints are described in more detail in Table 1. All analyses specific to exploratory 
biomarkers will be described in a separate translational analysis plan.  
2.1 
OBJECTIVES AND ENDPOINTS 
Table 1. Objectives and Endpoints 
Objectives 
Outcomes 
Primary Objectives 
Primary Endpoint 
To evaluate the safety and tolerability of 
PT101 in subjects with active UC 
following multiple SC doses  
Safety and tolerability as assessed by incidence of TEAEs, TESAEs, and 
changes in laboratory values, ECGs, physical exam findings, and vital signs 
through
Secondary Objectives
Secondary Endpoint
To assess the PK of PT101 in subjects 
with UC following multiple SC doses  
PK parameters of PT101 through
(as described in Table 7)
Change in serum concentration of PT101 over time  
To assess the PD of PT101 in subjects 
with UC following multiple SC doses  
PD parameters of PT101 through
(as described in Table 8/Table 9)
To assess the immunogenicity of PT101 
in subjects with UC following multiple 
SC doses 
Anti-drug antibodies to PT101 through
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To assess the PK/PD relationship of 
PT101 in subjects with UC following 
multiple SC doses 
 
The relationship between the PT101 PK and PD response  
 
Exploratory Objectives 
Exploratory Endpoint 
To assess improvement in disease 
activity in subjects with UC following 
multiple SC doses of PT101
Mean change from baseline in modified Mayo Score at
 
Mean change from baseline in total Mayo Score at
 
Mean change from baseline in partial Mayo Score at 
 
Mean change from baseline in Robarts Histologic Index score at
 
Mean change from baseline in UC-100 score at
 
Mean change from baseline in patient-reported outcome measures at 
o 
IBDQ 
o 
SF-36 
 
Proportion of subjects achieving clinical remission at
 
Proportion of subjects achieving endoscopic improvement at 
 
Proportion of subjects achieving clinical response at
 
Proportion of subjects achieving symptomatic remission at
 
Proportion of subjects achieving symptomatic response at
 
Proportion of subjects achieving endoscopic remission at
 
Proportion of subjects achieving histologic remission at
 
Proportion of subjects achieving histologic response at
 
Proportion of subjects achieving mucosal healing at
 
Change from baseline in partial Mayo Score beyond
 
Incidence and characterization of TEAEs and laboratory abnormalities 
beyond
To evaluate changes in PT101- and UC-
associated biomarkers following multiple 
SC doses of PT101  
 
Mean change from baseline in FC at
 
Mean change from baseline in hs-CRP levels at
 
Changes in PT101 and UC-associated biomarkers  
o 
sCD25 
o 
IL-5 
o 
IFN-y, IL1-B, IL-2, IL-4, IL-6, IL-8, IL-10, IL12p70, IL-13, 
TNF-a 
o 
TSDR FOXP3 Assay (Treg cells) 
o
TSDR CD4 Assay (CD4 T cells)
ECG = electrocardiograms; FC = fecal calprotectin; hs-CRP = high sensitivity C-reactive protein; IBDQ = 
Inflammatory Bowel Disease Questionnaire; IL-5 = interleukin 5; PD = pharmacodynamics; PK = 
pharmacokinetics; SC = subcutaneous; sCD25 = soluble form of IL2 receptor alpha chain; SF = Short Form-
36; TEAE = treatment-emergent adverse event; TESAE = treatment-emergent serious adverse event; TSDR = 
Treg-specific demethylated region; UC = ulcerative colitis 
3 
STUDY DESIGN 
3.1
SUMMARY OF STUDY DESIGN 
The study will enroll up to approximately 60 subjects with mildly to severely active UC in up to 6 cohorts 
of 10 subjects each (randomized 4:1 [PT101:placebo]) in a multiple ascending doses design. There will be 
3 planned cohorts (Cohorts 1 to 3) and up to 3 optional cohorts (Cohorts 4 to 6). Subjects in Cohort 1 will 
receive PT101 or placebo
 for a total of
 Cohorts 
2 and 3 will receive PT101 or placebo
for a total of 
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period. Subject randomization will be stratified by prior advanced therapy use (yes or no). Enrollment of 
subjects with a prior history of inadequate response, loss of response, or intolerance to 2 advanced therapies 
as assessed by the Investigator will be capped at 20% of subjects per cohort. 
Subjects who have achieved clinical response (based on the modified Mayo Score [mMCS] using the 
endoscopic subscore [MES] derived by the Investigator) at
will be eligible to enter the continued 
blinded treatment (CBT) phase of the study. Subjects in the CBT phase will receive the same treatment 
allocation (PT101 or placebo) as received during the initial blinded treatment (IBT) phase; subjects who 
received PT101 will continue receiving PT101 at the same dose/regimen. Corticosteroid tapering will be 
initiated at
of the IBT phase for subjects entering the CBT phase. Subjects who enter the CBT 
phase will receive their first dose of blinded study drug on
for both dosing regimens
Subjects who do not achieve clinical response at
will have the option to enter an open-label (OL) 
phase of the study. Subjects in the OL phase will receive PT101 at the same dose/regimen as received by 
subjects in their cohort during the IBT phase. Subjects participating in the OL phase who achieve a clinical 
response using the partial Mayo Score (pMCS) at
of the OL phase will also undergo corticosteroid 
tapering. Subjects who do not achieve a clinical response using the pMCS at
of the OL phase may 
continue on open-label treatment if it is considered in the best interest of the subject at the discretion of the 
investigator. Subjects who enter the OL phase will receive their first dose of PT101 on
for both 
dosing regimens
Subjects with insufficient data to assess clinical response at
of IBT will not be eligible to enter 
the CBT or OL phases and will be discontinued from the study.  
A DRC composed of unblinded members not involved in any way in the conduct of this trial will assess 
safety, PK, and PD data and provide recommendations on dose escalation/dosing regimen
study continuation, and enrollment of subjects into the 3 planned cohorts (Cohorts 1-3) and the 3 optional 
cohorts (Cohorts 4-6), as well as provide recommendations on dose and dosing regimen selection to inform 
future clinical development.  
The schedules of assessments are presented in Appendix A. 
3.2 
TREATMENTS 
Subjects in Cohorts 1 to 3 will receive placebo or PT101 at a dose of 
 If optional cohorts are added based on a DRC review, no subject will 
receive a dose
 
3.3
RANDOMIZATION AND BLINDING  
3.3.1 
RANDOMIZATION
The randomization schedule will be generated using an interactive web response system (IWRS). The 
investigator should assign the responsibility of unblinded health care professional (HCP) to a qualified 
person who will prepare the study drug and will not participate in the evaluation of any study subject. All 
randomization information will be stored in a secured area, accessible only by the unblinded HCP.  
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3.3.2
BLINDING
The unblinded HCP will prepare and transfer study drug (PT101 and placebo) to the investigator or qualified 
designee for study drug administration. Contact between the unblinded HCP and study subjects should be 
avoided in order to protect the blind. Blinding is accomplished by the random, masked, assignment of 
allocation numbers to the treatment groups, and by ensuring the drug supplies administered in the treatment 
groups appear identical. 
Information necessary to unblind a treatment assignment at the investigator’s site is held by the unblinded 
HCP in the form of treatment codes. Should a situation arise which requires unblinding of the treatment 
assignment, the treatment code(s) will be provided according to the process defined in the clinical trial 
integrity plan. Upon unblinding, the subject should undergo the end of study (EOS) visit if possible and be 
followed for safety purposes. In the event of an accidental unblinding of treatment assignment, the medical 
monitor should be promptly notified. At the end of the study, all records for premature unblinding must be 
returned to the sponsor and filed in the trial master file (TMF).  
Selected individuals from the sponsor, contract research organization (CRO), an independent statistician, 
and the DRC will be unblinded to treatment assignments. The purpose of having unblinded personnel is to 
monitor study conduct, prepare data for presentation to the DRC, and to facilitate planning for subsequent 
dosing cohorts. All unblinded personnel will be fire-walled from the operational study team at the sponsor 
and CRO to prevent inadvertent unblinding of treatment assignment and to minimize the risk of introducing 
bias into the study results. Designation of unblinded study personnel will be authorized by the sponsor’s 
clinical director and the lead study biostatistician. A roster of unblinded personnel will be maintained in the 
TMF and in the clinical trial integrity plan. All unblinded personnel will be trained in steps necessary to 
maintain an adequate firewall. 
4 
GENERAL CONSIDERATIONS FOR DATA ANALYSIS 
4.1 
REPORTING CONVENTIONS 
The summary tables, figures, and by-subject listings will be prepared using the following conventions: 
 
Unless otherwise specified, the baseline value is defined as the last non-missing assessment prior to the 
first dose of study treatment. The last non-missing evaluation includes unscheduled and repeat visits. 
 
If the date of interest occurs on or after the first dose/randomization date, the study day will be 
calculated as “date of interest – date of first dose/randomization + 1”. 
 
If the date of interest occurred prior to the first dose/randomization date, then study day will be 
calculated as “date of interest – date of first dose/randomization”. 
 
Both safety and efficacy analysis results will be presented using descriptive statistics. Depending on 
the parameter, the difference from baseline will either be computed using the original scale (raw change 
from baseline) or on the log scale and back transformed for reporting. 
 
Categorical data will be summarized by treatment group in terms of frequency counts and percentages.  
 
Continuous variables will be summarized by treatment group using descriptive statistics (the number 
of subjects [n], mean, median, SD, minimum, and maximum) of the values at each visit and the change 
from baseline to each visit. PK parameters and other laboratory analytes that are believed to follow an 
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approximate log-normal distribution will also be summarized by the geometric mean and coefficient of 
variation (expressed as a percent). 
 
CIs will be presented as 2-sided 95% CIs. 
 
All mean, median, and CI values will be formatted to one more decimal place than the measured values. 
SD values will be formatted to two more decimal places than the measured value. Minimum and 
maximum will be formatted to the same number of decimal places as the measured value. The 
maximum number of decimal places reported shall be four for any summary statistic. 
 
All percentages will be rounded to one decimal place. The number and percentage of responses will be 
presented in the form XX (XX.X), where the percentage is in the parentheses.  
 
Change from baseline is calculated as a post-baseline value minus the baseline value. 
 
All laboratory data will be reported using standard international units. 
 
All analyses and summary tables will include the analysis set sample size (i.e., number of subjects) in 
the column headings. 
 
Listing will include both the randomized treatment and actual treatment, if different.  
 
By-subject listings will be presented for all subjects in the relevant analysis sets, and sorted by treatment 
allocation, study site (if applicable), subject ID, date, and visit. Numeric data will be listed to the same 
number of decimal places as recorded on the electronic case report form (eCRF) or other data source. 
Data collected on log forms, such as adverse events (AEs), will be presented in chronological order 
within the subject.  
 
SAS® Software Version 9.4M5 (SAS Institute Inc., Cary, NC, USA.) is to be used for all analyses 
including tables, listings, and figures.  
 
Partial dates will be imputed as follows: 
o If day and month is missing but year is present, the 1st of July of the noted year will be used. 
o If day is missing but year and month are present, the 15th of the noted month and year will be 
used. 
 
Non-PK lab data that are continuous in nature but are less than the lower limit of quantitation (LOQ) 
or above the upper LOQ will be imputed as follows: 
o A value that is 1/10th unit less than the lower LOQ will be used for calculation of descriptive 
statistics if the datum is reported in the form of “< x” (where x is considered the lower LOQ). 
For example, if the values are reported as < 50 and < 5.0, values of 49 and 4.9, respectively, 
will be used for calculation of summary statistics. An exception to this rule is any value reported 
as < 1 or < 0.1, etc. For these, a value of 0.9 or 0.09, respectively, will be used for calculation 
of summary statistics.  
o A value that is 1/10th unit above the upper LOQ will be used for calculation of descriptive 
statistics if the datum is reported in the form of “> x” (where x is considered the upper LOQ). 
Values with decimal points will follow the same logic as above. The LOQ will be used for 
x is considered the LOQ).  
 
PT101 plasma concentration values that are equal to or below the LOQ will be interpolated to 50% of 
the lower LOQ for the analytical assay throughout the dataset. 
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Medical Dictionary for Regulatory Activities (MedDRA) version 24.0 or newest will be used to code 
AEs and medical history, World Health Organization drug dictionary (WHODD) version Sep 2021 or 
newest will be used for medication coding. 
4.2 
ANALYSIS SETS 
The following analysis sets are defined for both the periodic safety reviews and the final study analysis.  
They will consist of all randomized subjects with data available at the time of analysis and will therefore 
change with each subsequent run. 
4.2.1 
INTENT-TO-TREAT ANALYSIS SET
The intent-to-treat analysis set (ITT) consists of all randomized subjects. Subjects will be included in the 
treatment group assigned at randomization regardless of the actual treatment received. All efficacy 
endpoints will be analyzed based on the ITT. 
4.2.2 
FULL ANALYSIS SET  
The full analysis set (FAS) consists of all randomized subjects at the time of analysis who received any 
study drug (PT101 or placebo). Treatment groups will be determined using the actual treatment received, 
regardless of the randomization treatment assignment. If different from the ITT, efficacy endpoints will 
also be analyzed based on the FAS. 
4.2.3 
PER PROTOCOL ANALYSIS SET 
This study will contain two per protocol analysis sets. The first per protocol analysis set (PP1) will include 
all subjects in the FAS who were not on concomitant corticosteroids during the treatment period. The 
second per protocol analysis set (PP2) set will consist of all subjects in the FAS who did not have any major 
protocol deviations that might impact the efficacy analyses. Exclusion of subjects from the PP will be 
determined in a final blinded data review meeting that will be held prior to unblinding the randomization 
list. Reasons for exclusion will be documented for each subject. All exploratory efficacy endpoints will be 
analyzed based on the PP for the final analysis. 
4.2.4 
SAFETY ANALYSIS SET
The safety analysis set (SAF) consists of all subjects who receive at least one dose of study drug. Treatment 
groups will be determined using the actual treatment received, regardless of the randomization treatment 
assignment. The SAF is the primary analysis set for safety analyses. 
4.2.5 
PK & BIOMARKER ANALYSIS SET
The PK & biomarker analysis set will include all randomized subjects who receive at least 1 dose of study 
drug and who have at least one valid analytical result at baseline, at least one post-dose analytical result and 
had no major relevant protocol or dosing deviations that could potentially affect the PK and/or PD profile. 
The PK & biomarker analysis set will be used for the summaries of all PK, PD, and biomarker data. All 
PK, PD, and biomarker parameters are summarized in Section 7.
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4.3
HANDLING OF DATA
In general, missing data will not be imputed unless methods for handling missing data are specified. For 
purposes of the DRC safety assessment, all results will be presented ‘as observed’ with missing values not 
imputed. The handling of missing data in analyses of the efficacy endpoints is discussed in Section 6.2.4. 
If multiple valid, non-missing, continuous measurements or visits (regardless if it’s scheduled or 
unscheduled) occurring within a single visit, records will be chosen based on the following rules if a single 
value is needed: 
 
For baseline, the baseline value will be the last non-missing value prior to the first dosing of study 
drug; if multiple measurements occur on the same day, the last non-missing value prior to the time 
of first dosing of study drug will be considered as the baseline value. If these multiple 
measurements occur at the same time or the time is not available, the average of these 
measurements will be considered the baseline value.  
 
For post-baseline values: 
a. The record closest to the nominal day for that visit will be selected. 
b. If there are 2 records that are equidistant from the nominal day, the later record will be selected. 
c. If there is more than 1 record on the selected day, the average will be taken. 
If multiple valid, non-missing, categorical observations exist for one visit, records will be selected as 
follow: 
 
For baseline, the last available record prior to the first dose of study drug will be selected. If there 
are multiple records at the same time or no time recorded on the same day, the worst value will be 
selected unless otherwise specified. 
 
For post-baseline values: 
a. The record closed to the nominal day for that visit will be selected. 
b. If there are 2 records that are equidistant from the nominal day, the later record will be selected. 
c. If there is more than 1 record on the selected day, the value with the worst severity will be used. 
 
5 
STUDY SUBJECTS 
Unless otherwise specified, all available subject data will be listed and summary tables for disposition and 
protocol deviations will be presented for the SAF as described in Table 2. 
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Table 2. Data Presentation for Study Subject Information
Data 
Variables 
Presentation 
Subject Disposition 
Subject, screen failures, 
reason for screen fail, 
subject study status by 
phase (e.g., in study, 
completed, 
discontinued, etc.), 
reason for 
discontinuation,  
n of subjects screened
 
n of subjects randomized 
 
n and % of subjects included in each analysis 
set.  
 
n of subjects treated 
 
n and % of subjects who completed IBT 
phase 
 
n and % of subjects discontinued by primary 
reason for discontinuation 
 
n and % of subjects that had a protocol 
deviation in CBT/OL phase 
 
n and % of subjects in clinical response at 
 
n and % of subjects in clinical remission at 
 
n and % of subjects who enter CBT phase 
 
n and % of subjects who enter CBT phase 
and successfully taper off corticosteroids 
 
n and % of subjects who completed CBT 
phase 
 
n and % of subjects who enter OL phase 
 
n and % of subjects who completed OL 
phase 
Summary of Protocol Deviations
Subject, major/minor 
protocol deviations 
n and % of subjects that had a protocol 
deviation by treatment group. Both major 
and minor protocol deviations will be listed. 
 
Summary of Demographics and Baseline 
Disease Characteristics 
age, sex, race, ethnicity, 
height, weight, body 
mass index, duration of 
UC, prior advanced 
therapy use (yes/no), 
systemic corticosteroid 
use at baseline (yes/no)
baseline disease 
characteristics (mMCS, 
MES, RB, SF, PGA)  
n and % of subjects for each demographic 
variable 
 
Summary of Medical History
All medical events 
sorted by system organ 
class (SOC) and 
preferred term (PT) 
n and % of subjects for each medical event
Summary of Prior Medications 
All medications taken 
prior to study drug 
administration. 
n and % of subjects for each concomitant 
medication listed by ATC Classification 
level 2 and preferred term 
 
Summary of Concomitant Medications 
All medications taken 
on or after the date of 
first study drug 
administration. 
 
n and % of subjects for each concomitant 
medication listed by ATC Classification 
level 2 and preferred term 
Summary of Treatment Compliance 
Duration of exposure, 
number of doses 
received, subjects with 
>= 1 missed dose, and 
n, mean, SD, median, min, and max number 
of days on treatment 
 
n, mean, SD, median, min, and max number 
of doses given 
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number of missed doses 
will be summarized.
n and % of subjects who missed >=1 dose 
n, mean, SD, median, min, and max missed 
doses 
ATC = anatomical therapeutic chemical; CBT = continued blinded treatment; IBT = initial blinded treatment; 
max = maximum; min = minimum; N = number of subjects in a group; OL = open-label; UC = ulcerative colitis; MCS = total 
mayo clinic score; MES = mayo endoscopic subscore; RB = rectal bleeding; SF = stool frequency; PGA = physician’s global 
assessment
5.1
SUBJECT DISPOSITION  
Subject disposition will be summarized for all subjects screened in this study. Total screened subjects and 
screen failed subjects will be expressed as overall counts. A summary and by-subject listing of subject 
disposition will be provided by treatment group for each phase in the study. This summary will present 
number and percentage of subjects randomized, discontinued, and completed for each study period. The 
number of subjects in each of the analysis sets will also be included. The reasons for premature 
discontinuation from treatment period as recorded in the eCRFs will be summarized. Number of subjects 
who reach clinical response and clinical remission at
will also be summarized. 
The following by-subject listings will be provided by subject identification number in ascending order to 
support the above summary table: 
 
Reasons for premature study discontinuation 
 
Reasons for screen failure  
 
Reasons for re-screening 
5.2 
PROTOCOL DEVIATIONS 
Protocol deviations will be summarized by type in each treatment group for each study phase. The number 
and percentage of subjects with protocol deviations will be summarized as major or minor by treatment 
group.  
A by-subject listing will be provided for those subjects with any protocol deviations. A complete list of 
possible protocol deviations and how they are classified, tracked, and managed can be found in the 
PT101-201 protocol deviation plan. 
5.3 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS 
Subject demographic and baseline disease characteristics will be summarized for each treatment group and 
pooled across treatment groups. Demographic characteristics include age (years), sex (male/female), 
race/ethnicity, baseline body weight (kg), baseline height (cm), and baseline body mass index (BMI: kg/m2). 
Baseline disease characteristics include duration of UC (years), tumor necrosis factor-alpha (TNF- ) 
exposure, prior advanced therapy use (yes/no), systemic corticosteroid use at baseline (yes/no), baseline 
disease measures (mMCS, RB, SF, MES, PGA). The summary of demographic data will be provided for 
the SAF and ITT. 
Certain characteristics, that are collected at baseline or after baseline but not summarized in the 
demographic summary, will be reported as a listing.  
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5.4
MEDICAL, SURGICAL, AND MEDICATION HISTORY
Medical and surgical history will be coded using the most current available version of the MedDRA (version 
25.1 or newer) and will include all relevant surgical and medical history including UC-related 
complications, other significant conditions or diseases relevant to the disease under study. 
A summary table and by-subject listing will be provided for those subjects with any medical/surgical history 
for the SAF. No formal statistical testing is planned. 
5.5 
PRIOR AND CONCOMITANT MEDICATION 
For the purposes of subgroup identification, prior and concomitant medications will be classified into 
anatomical therapeutic chemical (ATC) drug classes using the WHODD version September 2022 or newer. 
Summaries of prior and concomitant medications will include the number and percentage of subjects by 
ATC classification level 2 and preferred term (PT). A subject will be counted only once within a given drug 
class and within a given drug name, even if he/she received the same medication at different times. If any 
prior or concomitant medication is classified into multiple ATC classes, the medication will be summarized 
separately under each of these ATC classes. The summary tables will be sorted by alphabetical order by 
drug class and drug name. In case any specific medication does not have ATC classification level 2 coded 
term, it will be summarized under “Unavailable ATC classification” category. Summaries will be based on 
the SAF. 
All prior and concomitant medications will be provided in a by-subject listing with the relevant information 
collected by treatment group. 
5.5.1 
PRIOR MEDICATION 
Prior medication is defined as any medication stopped before the date of study drug administration. If the 
stop date is unknown or incomplete and the medications cannot definitely be considered as stopped prior 
to first dosing date then the medications will be considered as concomitant medications (e.g., partial stop 
date is May 2021, first dosing date is 15 May 2021, medication will be considered as concomitant).  
5.5.2 
CONCOMITANT MEDICATION
Any medication with a start date prior to or on the first dosing date and continuing to take after the first 
dosing date or started after the first dosing date will be considered concomitant medications. If the start date 
of a medication is incomplete or missing, the medication will be assumed to be concomitant medication, 
unless the incomplete start date (month and/or year) or the stop date (complete or incomplete) clearly 
indicate that the medication stopped prior to first dosing date. Medication with completely missing start 
and stop dates will be included in the concomitant medication summary. Concomitant medications will be 
summarized for each study phase and listed. Additionally, a summary and listing of subjects who tapered 
off corticosteroids will be provided. 
5.6 
TREATMENT COMPLIANCE 
Treatment exposure will be summarized and listed using descriptive statistics. Duration of exposure, 
number of doses, and cumulative total dose given (mg) will be summarized. Dose modifications, if any, 
will be included as a listing. Total duration of exposure to study treatment is defined as follows: 
Duration of exposure during the IBT phase will be calculated as: 
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“Date of last study visit in IBT – Date of first dosing date +1”
Duration of exposure during the CBT phase will be calculated as: 
“Date of last study visit in CBT phase – Date of the CBT Visit 1 dosing of study treatment + 1” 
Duration of exposure during the OL phase will be calculated as: 
“Date of last study visit in OL – Date of the OL Visit 1 dosing of study treatment + 1” 
Frequency distributions and descriptive statistics for extent of exposure will be provided by treatment group 
for the SAF. 
 
6 
EFFICACY ANALYSES 
Efficacy analyses will be primarily based on the ITT, and the FAS, if different. The efficacy analyses will 
also be performed on the PP for confirmatory purposes.  
6.1 
DERIVATION OF EFFICACY MEASUREMENTS 
6.1.1 
MAYO SCORE 
The Mayo clinic score (MCS) is a composite index of 4 disease activity variables that measures disease 
severity in UC (Appendix B). This composite index consists of 2 subject-reported variables (stool frequency 
[SF] and rectal bleeding [RB]), a physician’s global assessment (PGA) of disease severity and findings on 
endoscopy. The individual components of the MCS are scored on a 4-point scale (0 to 3 points). These 
individual variables are summed up to give a total disease activity score that ranges from 0 to 12.  
6.1.1.1 
Modified Mayo Score 
The mMCS is defined as the total MCS without the PGA subscore and ranges from 0 to 9. 
6.1.1.2 
Partial Mayo Score 
The pMCS includes 3 components of the total MCS (bowel frequency, RB, and PGA) and excludes the 
endoscopy subscore. The pMCS score ranges from 0 to 9 with higher scores representing more severe 
disease activity.   
6.1.1.3 
Mayo Endoscopic Subscore 
The MES assesses disease activity on a 4-point scale (0 to 3 points), with higher scores representing more 
severe disease activity.  
6.1.1.4 
Calculation Rules 
For the purpose of calculation of the MCS/pMCS/mMCS and component subscores, an anchor date is 
assigned and SF and RB records (from patient diary data) prior to the anchor date are used in the calculation 
of the subscores.  
For screening and post-baseline calculation of MCS, mMCS, SF, and RB, the anchor date is considered the 
date of the endoscopy. As MES will be only evaluated during the screening visit and not on Day 1 
(randomization visit), screening MCS and MES will be used as baseline evaluation. 
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For all calculations at other visits, including randomization, the anchor date is the date of the study visit.  If 
a
endoscopy was not performed, the
study visit date will be used. Because the preparation 
for endoscopy procedure may impact the validity of the diary data, the patient reported daily SF and RB 
records collected the day of bowel preparation medication (if applicable) and on the day after endoscopy 
will not be used in the calculation of SF and RB subscores. Derivation of the SF and RB subscores based 
upon patient records is outlined in Appendix B. 
6.1.1.5 
Calculation of Screening and Post-baseline Mayo Score 
To meet the entry criteria for the enrollment purpose, the calculation of the screening SF and RB subscores 
for the purpose of calculation of screening MCS is as follows (refer to eCRF completion guidelines):  
1. SF subscore will be based on the average number of stools from the closest 3 days within the last 
7 days prior to the endoscopic procedure date, excluding the date of bowel preparation (if 
applicable) compared to the number of stools per day during the patient UC remission. 
2. RB subscore will be based on the average score from the closest 3 days within the last 7 days prior 
to the endoscopic procedure date, excluding the date of bowel preparation (if applicable). 
3. PGA subscore used in the baseline MCS is recorded during the Screening visit. 
4. MCS will be left as missing if any of four component subscores is missing. 
Subjects who have less than 3 permitted days of diary data during screening are not eligible for 
randomization. 
6.1.1.6 
Calculation of Baseline Partial Mayo Score and Post-baseline Stool Frequency, Rectal Bleeding, 
and Partial Mayo Score 
The calculation of baseline pMCS and post-baseline SF, RB, and pMCS use the study visit date as the 
anchor date. For baseline pMCS, the visit date is Day 1 (randomization visit). The calculation rules are 
described in Table 3 and Table 4 and are as follows: 
1. SF and RB subscores will be based on the average score from the closest 3 days within the last 
7 days prior to the visit day, excluding the date of bowel preparation (if applicable). 
2. PGA subscore used in the calculation of baseline pMCS is the PGA subscore recorded on Day 1 
(randomization visit). At subsequent visits, the PGA subscore used in calculation of pMCS is that 
recorded within the visit window. 
3. pMCS will be considered as missing if any of three component subscores is missing. 
For Mayo SF subscore, the excess SF is calculated as the difference between the 3-day average SF and the 
patient reported normal SF during remission. The average SF will be rounded to the nearest integer to match 
the following scorings: 
0 
Normal number of stools for this subject 
1 
1 to 2 stools more than normal 
2 
3 to 4 stools more than normal 
3 
5 or more stools than normal 
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Table 3. Example of Calculation of Stool Frequency Subscore at Post-baseline for Mayo Scorea
 
 
 
Diary Day Looking Back From Endoscopy 
Dayb
Anchor 
Day 
Validated 
Days for 
Calculation  
Average 
Subscore  
Average 
Subscore – 
Normal SF 
Final SF 
Subscore 
Normal 
SFc
 -7 
-6 
-5 
-4 
-3 
-2 
-1 
V-Day 1  
3 
Jan 
4 
Jan 
5 
Jan 
6 
Jan 
7 
Jan 
8 
Jan 
9 
Jan 
10 Jan 
Diary 
1 
15 
16 
20 
17 
15 
19 
21 
18 
X 
 -4, -3, -2,  
18.3 ~18 
18-15=3 
2 
Diary 
2  
18 
M 
M 
M 
M 
15 
18 
M 
X 
-3, -2 
Missing 
Missing 
Missingd
Diary 
3 
11 
M 
M 
M 
M 
8 
M 
M 
X 
-3 
Missing 
Missing 
Missingd
Diary 
4 
7 
M 
11 
M 
11 
15 
10 
M 
X 
-4, -3, -2 
12 
12-7=5 
3 
M = missing; pMCS = partial Mayo score; SF = stool frequency; X = non-evaluable 
a For the calculation of pMCS, consecutive days for SF are not required in the week prior to the visit.  
b Days are named related to anchor day – Visit Day; The diary data collected prior/day of endoscopy will be discarded as 
endoscopy and its preparation may impact the validity of the diary data.     
c Normal SF is defined as the average number of stools during patient remission 
d Final subscore missing due to missing consecutive day(s) in the week prior to the endoscopy day (not including the bowel 
preparation day).   
For Mayo RB Subscore, the RB average will be rounded to the nearest integer to match the following 
scorings: 
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 passes 
Table 4. Example of Calculation of Rectal Bleeding Subscore at Post-baseline for Mayo Scorea
Examples
 
 
Diary Day Looking Back From Endoscopy 
Dayb  
Anchor 
Day  
Validated Days for 
Calculation  
Average 
Subscore  
Final 
Subscore  
-7 
-6 
-5 
-4 
-3 
-2 
-1 
V-Day 1  
3 
Jan 
4 
Jan 
5 
Jan 
6 
Jan 
7 
Jan 
8 
Jan 
9 
Jan 
10 Jan 
Diary 1 
M 
M 
2 
2 
1 
2 
2 
X 
 -4, -3, -2,  
1.67 
2 
Diary 2  
M 
M 
M 
M 
0 
1 
M 
X 
-3, -2 
Missing 
Missingc 
Diary 3 
M 
M 
M 
M 
0 
M 
M 
X 
-3 
Missing 
Missingc 
Diary 4 
M 
2 
M 
2 
1 
1 
M 
X 
-4, -3, -2 
1.33 
1 
Dairy 5  
M 
M 
M 
M 
0 
M 
1 
X 
-3, -1 
Missing 
Missingc 
M = missing; pMCS = partial Mayo score; RB = rectal bleeding; X = non-evaluable
a For the calculation of pMCS, consecutive days for RB are not required in the week prior to the visit. 
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b Days are named related to anchor day – Visit Day; The diary data collected prior/day of endoscopy will be discarded as endoscopy and its 
preparation may impact the validity of the diary data.     
c Final subscore missing due to missing consecutive day (s) in the week prior to the endoscopy day (not including the bowel preparation day).
6.1.2 
GEBOES SCORE
The Geboes scoring system is a stepwise ordinal grading system for histological assessment of disease 
severity in UC (Appendix C). The scoring system progressively grades disease severity by assessing 
7 histological items. These 7 histological items are: architectural changes (Grade 0), chronic inflammatory 
infiltrate (Grade 1), lamina propria neutrophils and eosinophils (Grade 2), neutrophils in epithelium (Grade 
3), crypt destruction (Grade 4), and erosions or ulcerations (Grade 5). Each grade of the score is divided in 
4 subgrades, based upon the severity of tissue abnormalities or the extent of cell infiltration. The Geboes 
score ranges from 0 to 5.4, with higher scores indicating more severe inflammation; typically, UC is defined 
as active 
2B.1. The overall Geboes score is calculated 
as the highest grade without a zero (i.e., absence) subscore, unless all grades are zero in which case the 
score will be 0.0. For example, if Grade 3: Neutrophils in lamina propria is checked as “< 50% crypts 
involved” (3.2), Grade 4: Crypt destruction is checked as “None” (4.0), and Grade 5: Erosions and 
ulcerations is checked as “No erosion, ulceration, or granulation tissue” (5.0), the subject will be assigned 
a final Geboes score of 3. If a subject has either abnormalities in lamina propria eosinophils or lamina 
propria neutrophils, they will be assigned a score of 2. 
6.1.3 
ROBARTS HISTOPATHOLOGY INDEX
The Robarts Histopathology Index (RHI) measures histological disease activity in patients with UC 
(Appendix D). The RHI is divided into 4 categories: 1) the extent of chronic inflammatory cell infiltration, 
2) neutrophils in the lamina propria, 3) neutrophils in the epithelium, and 4) erosions and ulceration. Each 
item has 4 levels and is scored from 0 to 3 and multiplied by a weighting factor and summed to give the 
overall RHI score. The RHI score ranges from 0 to 33, with higher scores being indicative of more severe 
disease. If any one component of the RHI is found to be missing, then the overall RHI score will be set as 
missing. The equation used to calculate the RHI is shown below.
RHI =1 x chronic inflammatory infiltrate level + 2 x lamina propria neutrophils + 3 x neutrophils in 
epithelium + 5 x erosion or ulceration* 
*A Geboes Grade 5 component score of >1 is reduced by 1 point prior to be incorporated into the RHI 
calculation. 
6.1.4 
UC-100 
UC-100 is used to assess UC disease activity and is derived from the MCS and RHI variables. The UC-100 
ranges from 1 (no disease activity) to 100 (severe disease activity). If any one component score of UC-100 
is found to be missing, then the entire test score will be set as missing. 
Composite UC-100 score: (1 + 16 × SF + 6 × MES+ 1 × RHI). 
6.2 
EFFICACY ENDPOINTS 
6.2.1 
DICHOTOMOUS EFFICACY ENDPOINTS
The definitions of the dichotomous efficacy endpoints are presented in Table 5. 
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Table 5. Definition of Binary Endpoints
Binary Endpoint
Measure
Definition
Analysis Timepoint
Clinical Remission
Modified MCS
Modified MCS (SF 
1 [with or without 
decrease], RB subscore of 0, and MES
1 [where the 
definition of 1 does not include friability]) 
Endoscopic 
Improvement
MES
MES of less than or equal to 1
Clinical Response
Modified MCS
Decrease in modified MCS
30% 
from baseline, and a decrease of the Mayo RB subscore 
of at least 1 point or an absolute subscore for RB of 0 or 1 
Symptomatic 
Remission
SF, RB 
SF 
1 point from 
baseline, and RB subscore of 0
Symptomatic 
Response
SF, RB 
30% decrease from baseline in composite sum of SF 
and RB subscores
Endoscopic Remission 
MES 
MES of 0
Histologic Remission 
GHI, RHI
Geboes index score < 2B.1 or RHI score 3, with 
subscores of 0 for lamina propria neutrophils and 0 for 
neutrophils in epithelium
Histologic Response 
RHI 
Mucosal Healing
GHI, MES
GHI < 2 and endoscopic remission (MES of 0)
GHI = Geboes histologic index; MCS = Mayo score, MES = Mayo endoscopic subscore; RB = rectal bleeding; RHI = Robarts Histopathology 
Index; SF = stool frequency  
6.2.1.1 
Statistical Methods for Dichotomous Efficacy Endpoints 
The proportion of subjects achieving each of the dichotomous efficacy endpoints defined in Table 5 will be 
summarized by treatment group using frequency distribution. To compare the proportion of subjects at a 
timepoint
the Cochran-Mantel-Haenszel (CMH) method will be used, and an exact 95% CI 
will be estimated. Missing values in the categorical endpoints will be imputed as non-responders. All 
dichotomous efficacy endpoints will be listed in by-subject listings. 
6.2.2 
CONTINUOUS EFFICACY ENDPOINTS
The definitions of the continuous efficacy endpoints (mean change from baseline) are listed in  
Table 6. 
 
Table 6. Definition of Continuous Efficacy Endpoints
Measure
Definitions 
Analysis Timepoint
mMCS
Mean changes in mMCS from baseline
MCS 
Mean change in total MCS
pMCS
Mean changes in pMCS from baseline 
RHI
Mean change in RHI from baseline 
UC-100 
Mean change in UC-100 score from baseline 
pMCS
Mean changes in pMCS from baseline 
MCS = Mayo Score; mMCS = modified Mayo score; pMCS = partial Mayo Score; RHI = Robarts Histopathology Index; UC = ulcerative colitis
 
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6.2.2.1
Statistical Methods for Continuous Efficacy Endpoints
Continuous endpoints will be summarized by treatment group using descriptive statistics of the values at 
each visit and the change from baseline to each post-baseline visit. For continuous endpoints at only one 
post-baseline visit, an analysis-of-covariance (ANCOVA) will be used for analysis. The changes from 
baseline will be compared between treatments adjusted for the baseline value. 
For continuous data with repeated measures post-randomization, mixed-model-repeated measure (MMRM) 
will be used for analysis. The model will include fixed effects for treatment, visit, baseline value, and 
treatment-by-visit interaction. This analysis will be conducted by maximum likelihood methods using the 
SAS PROC MIXED procedure. Least squares means and 95% CIs will be provided for each assessment 
timepoint. 
All collected efficacy data will also be presented in a by-subject listing. 
6.2.3 
ADDITIONAL ANALYSES 
In the event of controlling covariates, logistic regression will be used to compare the proportion of subjects 
achieving an endpoint in each group (PT101 or placebo). Covariates that may be included in the model are 
oral corticosteroid use, prior advanced therapy use, and baseline measures of mMCS, MES, SF, and RB 
scores. 
6.2.4 
MISSING DATA HANDLING 
6.2.4.1 
Non-responder Imputation 
For the responder analyses described in Table 5, subjects who do not have sufficient measurements to 
determine the endpoint will be considered as non-responders (i.e., non-responder imputation [NRI]). 
Specifically, all subjects who discontinue from the study at any time prior to the assessment timepoint or 
fail to have an adequate efficacy assessment at the timepoint will be considered a non-responder. The NRI 
may be applied at any time point specified for analysis. 
6.2.5 
SENSITIVITY ANALYSES 
6.2.5.1 
Per-Protocol Analysis 
To evaluate the robustness of the efficacy analysis, the binary endpoint based on the NRI in the PP will use 
the same analysis methods for ITT as described in Section 6.2.1. 
7 
PHARMACOKINETIC AND PHARMACODYNAMIC ANALYSES 
7.1 
PHARMACOKINETIC ASSESSMENTS 
Blood samples for PK assessment will be collected as outlined in the protocol and outlined in Appendix A. 
The PK endpoints will include change in serum concentration of PT101 over time and analysis of PK 
parameters.PK parameters for PT101 will be estimated using noncompartmental analysis (NCA) methods. 
PK parameters that will be assessed are shown in Table 7. The maximum concentration (Cmax) for each 
subject will be determined along with the actual time it occurs (Tmax). As there are multiple doses given 
prior to complete elimination, the terminal elimination constant (Kel) will be estimated from the 
concentrations observed following the final concentration peak. If there exists at least one observed 
concentration following the final peak, log-linear regression will be used to estimate the slope of the 
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concentration-time curve, the absolute value of which will be the Kel. From this, the terminal elimination 
half-life (t1/2) will be estimated using the formula: 
t1/2 = ln 2/ Kel. 
The area under the concentration-time curve (AUC) from zero to infinity will be estimated in two parts: (1) 
AUC from zero to last observed concentration; and (2) AUC from last observed to infinity. 
=
+
.
The portion of the AUC up to the last observed concentration will be estimated using the log-linear 
trapezoidal method.  The incremental portions of the AUC between each observed concentration will be 
estimated individually and summed to give the AUC across the period.  The absorption phase will use a 
linear interpolation. 
= (
+
)(
). 
While the elimination phase will use a logarithmic interpolation, following the equation below. 
= ln
ln
(
). 
The portion of the AUC following the last observed concentration will be assumed to follow an 
exponential elimination dictated by the terminal elimination constant.  It will be estimated as follows: 
=
=
. 
 
Table 7. Standard Pharmacokinetics Parameters 
Name 
Description 
Cmax 
Maximum concentration in a dosing interval 
Cmin
Minimum concentration in a dosing interval 
Tmax
Time of occurrence of Cmax within a dosing interval
t1/2
Terminal elimination half-life
AUC0-t 
Area under the concentration-time curve from time 0 to the last measurable concentration 
in a dosing interval 
AUC0-inf
Area under the concentration-time curve from time 0 extrapolated to infinity 
CL/F 
Apparent total body clearance following administration 
Vd/F
Apparent volume of distribution following administration 
Serum concentrations of PT101 will be listed and summarized by treatment group using descriptive 
statistics. PK parameters will be calculated using the actual time of sample collection whereas nominal time 
will be used for graphical presentations. Summary statistics including arithmetic mean, geometric mean, % 
coefficient of variation, SD, median, minimum, and maximum of the PK parameters listed in Table 7 will 
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be summarized. All individual PK parameters will be listed in a by-subject listing. PK parameters will be 
analyzed for the PK & Biomarker analysis set.    
Graphical presentations will use the nominal time of sample collection. Mean and median concentration 
time profiles will be calculated by dose-level (cohort) and nominal time and plotted on linear and semi-log 
transformed scales. The mean profiles will include SD error bars to indicate precision in the observed mean 
concentration; median profiles will include the minimum and maximum observed values. Individual and 
mean PT101 concentration time profiles will also be produced on linear and semi-log transformed scales 
for each cohort at
 Mean and median trough concentration time 
profiles will be calculated by cohort and nominal time and plotted on linear and semi-log transformed 
scales. Individual and mean trough concentration time profiles will be plotted on linear and semi-log 
transformed scales for each cohort. 
Dose-proportionality of
will be assessed using 
a linear regression fit of ln(AUC/Cmax) versus ln(Dose) to estimate slope and confidence interval of slope. 
Natural log-transformed exposures versus natural log-transformed dose relationship for both AUC0-inf and 
Cmax will also be presented.  
7.2
IMMUNOGENICITY ASSESSMENTS
For all dosing cohorts (refer to Appendix A for dosing schedule), blood samples for immunogenicity / anti-
drug antibody (ADA) analyses will be collected. ADA to PT101 will be assessed using a standard 3-tier 
approach to measure binding antibody with a screening assay, ADA titer using a confirmatory assay, and 
neutralizing antibody to PT101 in subjects with confirmed positive titers. Summary statistics including 
number and percentage of subject ADA status and titer by dose for each cohort will be presented. A by-
subject listing of ADA status and titers by dose will also be provided. 
To assess the impact of ADA on the concentration of PT101, individual PK profiles from ADA positive 
and ADA negative subjects will be plotted on both a linear scale and log scale at their relevant dose levels 
and for each dosing regimen
 evaluated. Impact of ADA on the PD markers that will be 
the most affected by PT101 may also be graphically investigated via e.g., box plots of PT101 PK parameters 
by ADA status or ADA titer versus time profiles. Immunogenicity assessments will be analyzed for the PK 
& Biomarker analysis set.    
7.3 
PHARMACODYNAMIC ASSESSMENTS 
Blood samples for PD analyses will be collected at baseline and at the timepoints specified in the schedule 
of events tables in Appendix A. Whole blood will be collected for immunophenotyping and analyzed by 
flow cytometry to enumerate immune cell subsets.. All immunophenotypic PD data will be summarized by 
dose and sampling times. Summary statistics in each table will include arithmetic mean, geometric mean, 
% coefficient of variation, SD, median, minimum, and maximum. All PD assessments will be analyzed for 
the PK & Biomarker analysis set.    
7.3.1 
IMMUNOPHENOTYPING OF CELL POPULATIONS ASSESSMENT 
Whole blood will be collected for flow cytometry analysis to evaluate and quantify T, B, natural killer, and 
Tregs cells. Only data from Immunophenotyping flow cytometry samples that pass Merck  sample quality 
review (Pass/Fail criteria documented in Merck ELN) will be transferred from PPD for analysis. All 
reportable cell populations and calculations that will be performed are defined Table 8. 
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Immunophenotyping PD analyses listed in Table 8 will be summarized by dose group at each timepoint, 
except for maximum fold change from baseline. The maximum absolute change from baseline and 
maximum fold-change from baseline may be calculated for each cell population. Individual subject level 
immunophenotypic PD data will be provided in supplemental by-subject listings. Supplemental time course 
immunophenotyping profile figures will be developed for each cell population type assessed showing mean 
immunophenotyping parameter level with SD error bars versus time (actual day of collection), doses and 
dosing regimen. Baseline used in calculations will be defined as the average level of the screening sample 
and the Day 1 pre-dose sample. If in the event only one sample was available, that sample would be utilized 
to determine baseline. CD25 mean fluorescence intensity on Tregs will be analyzed at each timepoint.
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Table 8. Parameters and Analyses to be Reported From the Immunophenotyping Panel
Cell Population
Antigen 
Markers
Parameter
Absolute 
Count
(cell/µl) 
Percentage of 
Lymphocytes
Percent of 
Parent Cell 
Typea 
Absolute 
Change From 
Baselineb 
Fold Change 
From 
Baselinec
AUC of 
Absolute 
Change From 
Baselined 
Total T 
lymphocytes 
CD45+ CD14-
CD3+
Absolute counts 
and relative 
percentage of 
cell subsets of 
interest 
Output from 
PPD Inc 
Output from PPD 
Inc 
no 
yes 
yes 
yes 
Helper T 
lymphocytes
CD45+ CD14-
CD3+ CD4+ CD8-
Output from 
PPD Inc
Output from PPD
Inc
no
yes
yes
yes
Cytotoxic T 
lymphocytes 
CD45+ CD14-
CD3+ CD4-CD8- 
Output from 
PPD Inc 
Output from PPD
Inc 
no
yes
yes
yes
B lymphocytes 
CD45+ CD14-
CD3+ CD20+ 
CD56-
Output from 
PPD Inc
Output from PPD
Inc
no
yes
yes
yes
Natural killer cells
CD45+ CD14-
CD3+ CD20-
CD56+
Output from 
PPD Inc
Output from PPD
Inc
no
yes
yes
yes
Tregs
CD45+ CD14-
CD3+ CD4+ CD8-
CD127-/dim
FoxP3+
Output from 
PPD Inc
Output from PPD
Inc
yesc
yes
yes
yes
CD25 Total Tregs
CD45+ CD14-
CD3+ CD4+ 
CD8-
FoxP3+CD25+ 
Output from 
PPD Inc
Output from PPD 
Inc
yesc
yes
yes
yes
AUC = area under the curve; N/A = not applicable; Tconv = conventional T cell; Treg = regulatory T cell
Equations:
a Percent of Parent Cell Type: 
 
 
 
  
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Cell Population
Antigen 
Markers
Parameter
Absolute 
Count
(cell/µl)
Percentage of 
Lymphocytes
Percent of 
Parent Cell 
Typea
Absolute 
Change From 
Baselineb
Fold Change 
From 
Baselinec
AUC of 
Absolute 
Change From 
Baselined 
b Absolute Change in Cell Count from Baseline: 
c Fold Change from Baseline: 
 
 
 
 
 
 
 
 
 
 
 
 
  
d Calculated from absolute change in cell count from baseline time course profile
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8 
BIOMARKER ANALYSES 
Relationships of biomarker parameters (e.g., baseline values, changes from baseline) to efficacy, safety, 
and PK parameters will be explored. Relationships and associated data that are determined to be of interest 
will be summarized. Biomarker analysis will be analyzed for the PK & Biomarker analysis set.    
Listings and descriptive statistics (n, mean, median, SD, CV%, minimum, and maximum) will be provided 
by treatment group for each biomarker specified in Table 9 as follows: 
 
Baseline values 
 
Values at each post-baseline visit 
 
Absolute change from baseline at each post-baseline visit  
 
Fold Change from baseline at each post-baseline visit  
In addition, the following figures will be generated for sCD25, IL-5, IFN-y, IL1-B, IL-2, IL-4, IL-6, IL-8, 
IL-10, IL12p70, IL-13, TNF-a, and FOXP3, and CD4: 
 
Mean plot of absolute level aggregated and separated by treatments  
 
Mean plot of fold change from baseline aggregated and separated by treatments  
 
Mean plot of absolute change from baseline aggregated and separated by treatments 
All other biomarker analysis will be included in a separate Translational SAP. 
Table 9. Definition of Biomarker Endpoints 
Measure
Definitions 
Analysis Timepoint
FC
Mean change from baseline in fecal calprotectin
hs-CRP 
Mean change from baseline in high sensitivity C-reactive protein levels
sCD25 
Mean change from baseline in sCD25 
IL-5 
Mean change from baseline in IL-5
IFN-y 
Mean change from baseline in IFN-y
IL-1 
Mean change from baseline in IL-1
IL-2 
Mean change from baseline in IL-2
IL-4
Mean change from baseline in IL-4
IL-6 
Mean change from baseline in IL-6
IL-8
Mean change from baseline in IL-8
IL-10
Mean change from baseline in IL-10 
IL12p70 
Mean change from baseline in IL12p70 
IL-13
Mean change from baseline in IL-13 
TNF-a 
Mean change from baseline in TNF-a
FOXP3
Mean change from baseline in TSDR FOXP3 Assay (Treg cells) (% and cells/ul) 
CD4
Mean change from baseline in TSDR CD4 Assay (CD4 T cells) (% and cells/ul)
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9
SAFETY ANALYSES
The safety analyses will be performed using the SAF. The safety parameters will include treatment-
emergent AEs (TEAEs) and treatment-emergent serious AEs (TESAEs), vital sign measurements, 
electrocardiogram (ECG) findings, physical examination findings, and clinical laboratory values. The 
primary safety analysis will include all data available for all subjects at the time of the primary efficacy 
analysis data snapshot at
Safety will be evaluated via descriptive statistics. No inferential testing 
for statistical significance will be performed. 
9.1 
ADVERSE EVENTS 
9.1.1 
ADVERSE EVENT CODING
All AEs will be listed and classified according to the MedDRA, including system organ class (SOC) and 
PT. 
9.1.2 
ADVERSE EVENT SEVERITY
The severity of AEs will be graded according to the National Cancer Institute Common Terminology 
Criteria for AEs (NCI CTCAE) version 5.0 (27 November 2017). The general categories for each grade are 
presented in Table 10. 
 
 
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Table 10. Adverse Event Severity Grading
Grade 
Severity 
Alternate Description 
1 
Mild 
Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention 
not indicated 
2
Moderate
Minimal; local or non-invasive intervention indicated; limiting age-appropriate 
instrumental activities of daily living 
3
Severe
Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily 
living 
4 
Very severe, life-
threatening, or disabling 
Life-threatening consequences; urgent intervention indicated 
5 
Death related to adverse 
event 
Death related to adverse event 
9.1.3 
RELATIONSHIP OF ADVERSE EVENT TO STUDY TREATMENT 
The relationship of the AE to study treatment will be assessed by the investigator to be not related or related. 
If the investigator’s opinion of not related to study drug for an SAE is given, an alternative cause of the 
event such as underlying disease(s), concomitant therapy, and other risk factors must be provided.   
9.1.4 
SERIOUS ADVERSE EVENTS
SAEs will be identified and captured as SAEs if AEs met the definitions of SAEs that were specified in the 
study protocol (protocol section 7.6.1.1).  
9.1.5 
TREATMENT-EMERGENT ADVERSE EVENTS 
AEs will be defined as treatment-emergent if they are newly occurring or worsen following exposure to 
study treatment. All AEs reported following exposure to study treatment are considered TEAEs. 
TEAE are defined as 1 or both of the following: 
 
st study treatment start date/time; or 
 
AE onset date < 1st study treatment start date/time and either: 
o The severity worsened on or after the 1st study treatment start date/time; or 
o The event became serious on or after the 1st study start treatment date/time 
If the onset date of AE is later than the last dosing date of study treatment, then the event is considered AE 
in follow-up period. 
If the onset date of AE is incomplete and the AE stop date is not prior to the first dosing date of study 
treatment, then the month and year (or year alone if month is not recorded) of onset determine whether an 
AE is treatment-emergent. The event is considered treatment-emergent if both of the following 2 criteria 
are met: 
 
The AE onset/severity worsened is the same as or after the month and year (or year) of the first dosing 
date of study treatment, and 
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The AE onset/severity worsened is the same as or before the month and year (or year) of the last dosing 
date of study treatment 
An AE with completely missing onset and stop dates, or with the onset date missing and a stop date later 
than the first dosing date of study treatment, will be considered to be treatment-emergent. In addition, an 
AE with onset date missing and incomplete stop date with the same or later month and year (or year alone 
if month is not recorded) as the first dosing date of study treatment will be considered treatment-emergent. 
All AEs that occur after the safety reporting period and are considered study treatment-related in the opinion 
of the investigator will also be included. All non-treatment-emergent AEs will be included in the listing. 
9.1.6 
SUMMARIES OF TREATMENT-EMERGENT ADVERSE EVENTS
TEAEs will be summarized by period based on the SAF. 
A brief, high-level summary table will be presented to provide the number and percentage of subjects 
experiencing any TEAEs, any severe TEAEs, any drug-related TEAEs, any TESAEs, any drug-related 
TESAEs, any TEAEs leading to study drug interruption or discontinuation, and death.  
In addition to the above summary table, summary tables and listings of AE described below will be provided 
by period. 
 
Summary of TEAEs by SOC and PT  
 
Summary of TEAEs by SOC, PT and maximum severity  
 
Summary of s
 
 
Summary of related TEAEs to Study Treatment by SOC and PT 
 
Summary of TEAEs of Clinical Interest by SOC and PT 
 
Summary of related AEs to Study Procedure by SOC and PT 
 
Summary of serious TEAEs by SOC and PT 
 
Summary of TEAEs Leading to Premature Discontinuation by SOC and PT 
 
Summary of related TEAEs to Study Treatment by SOC and PT 
 
Summary of related Serious AEs to Study Procedure by SOC and PT 
 
Listing of all AEs 
 
Listing of serious TEAEs and death  
 
Listing of TEAEs leading to study drug interruption or discontinuation  
9.2 
PHYSICAL EXAMINATION 
A complete physical examination is performed at the screening visit and end of treatment visits. An 
abbreviated or targeted interim physical exam may be done to assess areas with previously noted 
abnormalities and/or that are associated with any new complaints from the subject. All abnormal findings 
will be presented in a by-subject listing. 
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9.3
VITAL SIGNS
Descriptive statistics will be provided by treatment group for vital signs (blood pressure (mm Hg), heart 
rate (bpm), respiratory rate, temperature, and weight (kg), as follows: 
 
Baseline values 
Values at each post-baseline visit
 
Change from baseline at each post-baseline visit 
A by-subject listing of vital signs will be provided by treatment group, subject ID number, and visit in 
chronological order. 
9.4 
CLINCAL LABORATORY TESTS 
Descriptive statistics will be provided by treatment group for each laboratory test (hematology, chemistry, 
coagulation, and urinalysis) specified in the study protocol as follows: 
 
Baseline values 
 
Values at each post-baseline visit 
 
Change from baseline at each post-baseline visit 
Shift tables will be presented by showing change in lab normal range (low, normal, and high) for clinical 
laboratory values by treatment group.  
Laboratory values will be listed in by-subject listings. Laboratory values which fall outside the reference 
ranges and have clinically significant and abnormal findings will be provided in a separate by-subject 
listing. These listings will include treatment group, subject ID, laboratory collection date/time, analyte 
name, analyte finding, and reference range.   
9.5 
ELECTROCARDIOGRAMS 
Triplicate ECG measurements will be obtained at the screening visit and on Day 1. On Day 1 only, triplicate 
ECGs will be performed ~ 12 hours after study drug administration. The median of these measurements 
will be used to calculate change from baseline for safety evaluations. The ECG assessment values at each 
visit and change from baseline to each visit will be summarized and shift tables using the normal/abnormal 
classification to compare baseline to the post-baseline visit values will be provided. In addition, a by-subject 
listings, which includes treatment group, subject ID, ECG date/time, test name, test result, and ECG 
interpretation (e.g., clinical interpretation such as normal, abnormal – not clinically significant, abnormal – 
clinically significant) will be presented. If any clinically significant ECG measurement occurs, it will be 
recorded as an AE.  
9.6 
EVENTS OF CLINICAL INTEREST 
The number and percentages of subjects with the following elevations in hepatic laboratory tests and drug 
overdoses will be summarized between treatment groups and included in a by-subject listing. 
 
An overdose of study product, defined as any dose of any drug administered as part of the study 
exceeding the dose prescribed by the protocol. 
 
ALT  3x upper limit of normal (ULN)  
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AST  3x ULN  
 
Total bilirubin level (TBL)  2xULN and alkaline phosphatase value < 2xULN 
10 QUALITY OF LIFE ANALYSIS 
10.1.1 INFLAMMATORY BOWEL DISEASE QUESTIONNAIRE
The Inflammatory Bowel Disease Questionnaire (IBDQ) is a psychometrically validated patient-reported 
outcome instrument for measuring the disease-specific quality of life in patients with inflammatory bowel 
disease, including UC. The IBDQ comprises of 32 items that are grouped into 4 dimensions: bowel function, 
emotional study (loose stools, abdominal pain), emotional status (anger, depression, irritability), systemic 
symptoms (fatigue, altered sleep pattern) and social function (work attendance, need to cancel social 
events). See Appendix E. 
The 4 domains are scored as follows: 
 
 
Bowel symptoms: 10 to 70 
 
Systemic symptoms: 5 to 35 
 
Emotional function: 12 to 84 
 
Social function: 5 to 35 
 
The total IBDQ score ranges from 32 to 224. For the total score and each domain, a higher score indicates 
better quality of life. A score of at least 170 corresponds to clinical remission and an increase of at least 
16 points indicates a clinically meaningful improvement.  
IBDQ scores will be collected based on the schedule of assessments. Summary statistics of the absolute and 
change from baseline scores for IBDQ total score and each subscale score will be displayed by treatment 
group and visit. A by-subject listing of all IBDQ scores and the subcomponents will be provided. 
IBDQ scores will be calculated as follows: 
 
The question on the same day of measurement will be used for calculation of each subscore and 
total score.  
 
For each subscore, sum of the questions will be round off to the first decimal place.  
 
IBDQ total score: sum of all questions and round off to the first decimal places.  
 
The value of each question after imputing missing data will be used for the calculation of each 
subscore.  
The instructions on how the IBDQ score is calculated in the presence of missing or incomplete information 
is provided below.  
Rules for handing missing data: 
1. If no response is given for a particular question and only one response per dimensional score is 
missing, impute the missing value to be equal to the mean score for that other item of the subscore 
2. If two or more questions are unanswered for a particular domain, then the subscore will be set to 
missing.  
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3.
If after steps 1 and 2, more than 4 questions are missing for the full IBQD, then the total IBDQ will 
be set to missing. 
10.1.2 SHORT-FORM QUESTIONNAIRE
The SF-36 is a widely used general health status questionnaire that assesses 8 domains of functional 
health and well-being: Physical Functioning, Role Limitations due to Physical Health Problems, Bodily 
Pain, Social Functioning, Mental Health, Role Limitations due to Emotional Problems, Vitality, and 
General Health Perceptions. Scales are scored from 0 to 100, with higher scores indicating a better health-
related quality of life. A Physical Health component summary score and Mental Health component 
summary score are calculated from the 8 domain scores. The SF-36 is a psychometrically valid and 
reliable instrument. The concepts measured by the SF-36 are not specific to any age, disease, or treatment 
group, allowing comparison of relative burden of different diseases and the relative benefit of different 
treatments. 
 
11 SUBGROUP ANALYSIS 
No subgroup analysis is planned. 
12 CONTINUED BLINDED TREATMENT AND OPEN-LABEL ANALYSIS 
Any efficacy, safety, PK, and PD data assessments that are completed during safety follow-up, CBT and 
OL phase will be analyzed and summary tables will be provided.  
Safety data will be analyzed based on the methods described in Section 9 PK and PD data will be analyzed 
based on the methods described in Section 7. Immunogenicity assessments outlined in Section 7.2 may also 
be further analyzed during the CBT and OL phase. Efficacy endpoints that are assessed in the CBT and OL 
phase will be analyzed based on the methods described in Section 6.2. All data for the CBT and OL phase 
will be summarized up until
or until subject’s discontinuation from the study. 
13 DRC REVIEW 
For the planning of dose-escalation, opening of an optional cohort, continuing the study without changes, 
modifying the study, and/or dose/regimen selection, a review of safety, PK, PD, and efficacy data will be 
performed by an external DRC throughout the course of the study as described in detail in the DRC Charter. 
Progression from Cohort 1 to Cohort 2 per protocol will be based on DRC recommendations from all 
available unblinded safety, PK, and PD data reviewed from Cohort 1 along with all available unblinded 
safety data (all 10 subjects [PT101: placebo 4:1] up to
in a concurrent PT101 study conducted 
in young adult healthy volunteers population (MK-6194-003). Dose escalation from Cohort 2 to Cohort 3 
will be determined only after the
in
reach
Up to 3 optional cohorts may be added following DRC 
review of all available data from the previous planned cohorts (Cohorts 1 to 3) to (a) assess additional dose 
levels of PT101
dosing regimen, and/or (b) repeat a previously studied dose 
level/dosing regimen. 
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At each DRC meeting, the committee will review cumulative AE and safety data, as well as available PK, 
PD, UC disease activity, and biomarker data from all treated patients. The analysis will be presented blinded 
for the open sessions and unblinded for the closed sessions. The study may be stopped at the discretion of 
the sponsor based on recommendations of the DRC. All necessary measures will be taken to ensure 
appropriate safety follow-up for all subjects in the trial. 
The following analysis may be provided: 
 
Section 5.1: Disposition and Subject Characteristics 
 
Section 5.3: Demographic and baseline characteristics  
 
Section 6.2.1: Dichotomous Efficacy Endpoints; clinical remission, clinical response, symptomatic 
remission, symptomatic response, endoscopic improvement, endoscopic remission, mucosal healing, 
histologic remission, histologic response. 
 
Section 6.2.2: Continuous Efficacy Endpoints;  MCS, pMCS, mMCS, RHI, UC-100.  
 
Section 7.1: Pharmacokinetic Assessments: Descriptive statistics for available PK data  
 
Section 7.2/7.3: Pharmacodynamic Assessments: Descriptive statistics for available PD data  
 
Section 8: Biomarker Analyses: Descriptive statistics for available biomarker data  
 
Section 9: Safety Analyses: Overall summary of TEAEs, TEAEs by SOC and PT, TEAEs by SOC, PT 
and maximum severity, severe (CTCAE Grade >=3) TEAEs by SOC and PT, Related TEAEs by SOC 
and PT, TESAEs by SOC and PT, descriptive statistics for ECGs, vital signs, clinical laboratory 
parameters.  
 
Section 13.1: Assessment of Dose-Limiting Toxicity: Overall listing of dose-limiting toxicity (DLT) 
AE’s. 
 
13.1 ASSESSMENT OF DOSE-LIMITING TOXICITY 
A dose-limiting toxicity (DLT) is defined as any treatment-related AE reported within
from dosing 
that meets both the following criteria:  
 
Grade 3 or higher in severity according to the NCI CTCAE, Version 5.0  
 
 
The safety of each dose level will be evaluated by examining the probability of experiencing a DLT  based 
on a Bayesian Logistic Regression Model (BLRM) (Neuenschwander, 2008) and the incidence of TEAEs, 
TESAEs, treatment-related TEAEs, and treatment-related TESAEs.  
A dose will be considered safe if the estimated probability (posterior median) of overdosing
 The 
maximum tolerated dose (MTD) will be determined according to the following rules:  
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To support the dose selection decision, results from dose toxicity modeling using a 2-parameter BLRM will 
also be considered. 
normal prior distribution, with prior means (-1.912, 0.167), prior standard deviations (2.424, 1.139), and 
prior correlation of 0.486. The target probability of toxicity is under 10% [Neuenschwander et al, 2014].  
For Cohort 1, the model will be run using all available safety data from subjects that have completed
and subsequently at the same timepoint for the 3 potential 
optional cohorts. The analysis will be performed (using appropriate software, such as East Software [Cytel 
Inc, v6.4]) based on estimation of the posterior median. The selected dose may not exceed the escalation 
with overdose control (EWOC) threshold: the posterior probability of overdosing is 0.25. The dose level(s)  
and dosing regimen with the best benefit/risk profile based on the totality of safety and efficacy data at 
will inform selection for future clinical development.  
14 CHANGES FROM PROTOCOL 
 
Last observation carried forward (LOCF) was dropped from the SAP as an MMRM analysis planned 
and LOCF would not be efficient in this case.  
 
Protocol stated that the SAP would be finalized prior to the DRC review of Cohort 1 data, but the SAP 
will not be finalized until prior to the final database lock. 
 
Physical exam findings will only be included in a by-subject listing and no change from baseline 
calculations will be done.. 
 
Removed  receptor occupancy (RO) as a secondary objective along with corresponding analysis. Upon 
thorough investigation of the assay and data generated on production samples, technical issues related 
to the assay remained unresolved resulting in failure to obtain acceptable quality data and deeming the 
RO assay an assay failure for MK-6194-002. The assay main concerns were loss of CD4 resolution in 
the majority of production samples, lack of dynamic range between background and maximal MK-
6194 signal to accurately calculate RO, and lack of true MK-6194 and Ki-67 production sample gating 
controls resulting in variable/subjective gate placement and erroneous data.  
 
 
15 REVISION HISTORY 
Version 
Effective Date 
Reason  
V01
06DEC2022 
New
V02
23FEB2024 
Updated FAS definition and removed analysis related to receptor 
occupancy. Added additional biomarkers to the analyses in Section 8. 
 
 
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APPENDIX B: MAYO SCORE
Note: The partial MCS is calculated using only the stool frequency, rectal bleeding, and physician’s global 
assessment subscores from the table below. 
Component 
Mayo Score (MCS) 
Stool Frequencya, d 
Normal number of stools for this subject
          1 to 2 stools more than normal 
          3 to 4 stools more than normal 
          5 or more stools than normal 
 
0 
1 
2 
3 
Subscore, 0 to 3 
 
Rectal bleedingb, d 
No blood seen
          Streaks of blood with stool less than half the time 
Obvious blood (more than just streaks) or streaks of blood with stool most 
of the time 
Blood alone passes 
 
0 
1 
2 
3 
Subscore, 0 to 3 
 
Findings on endoscopy 
          Normal or inactive disease 
          Mild disease (erythema, decreased vascular pattern, no friability) 
          Moderate disease (marked erythema, absent vascular pattern, friability, 
erosions) 
          Severe (spontaneous bleeding, ulceration) 
 
0 
1 
2 
3 
Subscore, 0 to 3 
 
Physician’s global assessmentc 
Normal 
Mild disease 
          Moderate disease  
          Severe disease 
 
0 
1 
2 
3 
Subscore, 0 to 3 
 
Total score 
0-12 
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b The daily bleeding score represents the most severe bleeding of the day
c The physician’s global assessment acknowledges the 3 other criteria, the subject’s recollection of abdominal 
discomfort and general sense of wellbeing, and other observations, such as physical findings and the subject’s 
performance status 
d The modified Mayo score calculated at the
visits must use the SF and RB Mayo 
subscores recorded on the eDiary (or paper diary) over the 3 consecutive days prior to the endoscopy 
(excluding the bowel preparation day) 
 
 
 
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APPENDIX C: GEBOES SCORING
 
Grade 0
Structural (architectural change)
Subgrades 
0.0 
0.1 
0.2 
0.3 
 
No abnormality 
Mild abnormality 
Mild or moderate diffuse or multifocal abnormalities 
Severe diffuse or multifocal abnormalities 
Grade 1 
Chronic inflammatory infiltrate 
Subgrades
1.0 
1.1 
1.2 
1.3 
 
No increase 
Mild but unequivocal increase 
Moderate increase 
Marked increase 
Grade 2 
Lamina propria eosinophils and neutrophils 
2A Eosinophils  
          2A.0 
          2A.1 
          2A.2 
          2A.3 
  2B Neutrophils 
          2B.0 
          2B.1 
          2B.2 
          2B.3 
 
No increase 
Mild but unequivocal increase 
Moderate increase 
Marked increase 
 
None 
Mild but unequivocal increase 
Moderate increase 
Marked increase 
Grade 3 
Neutrophils in epithelium 
3.0 
3.1 
3.2 
3.3 
None 
< 5% crypts involved 
< 50% crypts involved 
> 50% crypts involved 
Grade 4 
Crypt destruction 
4.0 
4.1 
4.2 
None 
Probable – local excess of neutrophils in part of crypt 
Probable – marked attenuation 
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4.3
Unequivocal crypt destruction
Grade 5 
Chronic inflammatory infiltrate 
5.0
5.1 
5.2 
5.3 
5.4 
No erosion, ulceration, or granulation of tissue 
Recovering epithelium + adjacent inflammation 
Probable erosion – focally stripped 
Unequivocal erosion 
Ulcer or granulation tissue 
 
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APPENDIX D: ROBARTS HISTOPATHOLOGY INDEX SCORING
Histological Variable 
Grading 
Multiplication 
Factor 
Chronic inflammatory infiltrate
0=No increase
1=Mild but unequivocal increase 
2=Moderate increase 
3=Marked increase 
X1 
Lamina propria neutrophils 
0=None 
1=Mild but unequivocal increase 
2=Moderate increase 
3=Marked increase 
X2 
Neutrophils in epithelium 
0=None 
1= < 5% crypts involved 
2= < 50% crypts involved 
3= > 50% crypts involved 
X3 
Erosion or ulceration 
0=No erosion, ulceration, or 
granulation tissue 
1=Recovering epithelium + adjacent 
inflammation 
1=Probably erosion-focally stripped 
2=Unequivocal erosion 
3=Ulcer or granulation tissue 
X5 
 
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APPENDIX E: QUALITY OF LIFE IN INFLAMMATORY BOWEL DISEASE 
QUESTIONNAIRE (IBDQ)
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