A Phase 2B, Randomized, Double-blind, Multicenter, Placebo-controlled Study to Evaluate the Efficacy of Bentracimab (PB2452) in Reversing Ticagrelor in Subjects Aged 50 to 80 Years Old
Phase: PHASE2
Conditions: Healthy
Sponsor: SFJ Pharmaceuticals, Inc.

Clinical Study Protocol 
PB2452-PT-CL-0003-Phase 2b 
Version 2 dated 28May2021 
Investigational Product: PB2452 
PhaseBio Pharmaceuticals, Inc. 
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A Phase 2B, randomized, double-blind, multicenter, placebo- 
controlled study to evaluate the efficacy of PB2452 in reversing the 
antiplatelet effects of ticagrelor in subjects aged 50 to 80 years old 
PhaseBio Phase 2B ticagrelor reversal study 
Investigational Product(s) 
PB2452 
Protocol Number 
PB2452-PT-CL-0003 
Clinical Trial Registry Identifiers 
NCT04122170 
Version Number 
Amendment 2 - version 2 dated 28May2021 
Amendment 
Original Protocol - version 0 dated 16Aug2019 
Amendment 1 - version 1 dated 29Oct2020 
Regulatory References 
IND # 125267 
Principal/Site Investigator 
Not applicable 
Sponsor 
PhaseBio Pharmaceuticals, Inc. 
1 Great Valley Parkway, Suite 30 
Malvern, PA, USA 19355 
 
Medical Monitor 
John Lee, MD, PhD 
PhaseBio Pharmaceuticals, Inc. 
1 Great Valley Parkway, Suite 30 
Malvern, PA, USA 19355 
Laboratories (or other 
Medical/Technical Institutions 
Involved in the Trial) 
MLM Medical Labs 
140 Collins St. 
Memphis, TN, USA 
38112 
Frontage Labs 
700 Pennsylvania 
Dr, Exton, PA, 
USA 19341 
Medpace Central 
Laboratories 
5365 Medpace Way 
Cincinnati, OH, USA 
45227 
Confidentiality Statement 
 
This document contains Confidential Information of PhaseBio Pharmaceuticals Inc and is provided subject to 
the Non-Disclosure Agreement between your Institution and PhaseBio Pharmaceuticals Inc. where applicable. 

Clinical Study Protocol 
PB2452-PT-CL-0003-Phase 2b 
Version 2 dated 28May2021 
Investigational Product: PB2452 
PhaseBio Pharmaceuticals, Inc. 
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Confidential 
 
 
STATEMENT OF COMPLIANCE 
The study will be conducted in compliance with this clinical study protocol, Good Clinical 
Practices (GCPs) as outlined by International Conference of Harmonization (ICH) E6(R2), and 
all applicable local and national regulatory requirements. Enrollment at any clinical study site 
may not begin prior to that site receiving approval from the ethics committee of record for the 
protocol and all materials provided to potential subjects. 
Any amendments to the protocol or changes to the consent document will be approved before 
implementation of that amendment. 
The Principal Investigator will ensure that changes to the study plan as defined by this protocol 
will not be made without prior agreement from the Sponsor and documented approval from the 
ethics committee of record, unless such a change is necessary to eliminate an immediate hazard 
to the study subjects. 
All personnel involved in the conduct of this study should have completed Human Subjects 
Protection and GCP training as outlined by their governing institution. 

Clinical Study Protocol 
PB2452-PT-CL-0003-Phase 2b 
Version 2 dated 28May2021 
Investigational Product: PB2452 
PhaseBio Pharmaceuticals, Inc. 
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SPONSOR’S APPROVAL 
 
Title 
A Phase 2B, randomized, double-blind, multicenter, placebo- 
controlled study to evaluate the efficacy of PB2452 in reversing the 
antiplatelet effects of ticagrelor in subjects aged 50 to 80 years old 
Protocol Number 
PB2452-PT-CL-0003 
Version Number 
Amendment 2 - version 2 dated 28May2021 
Amendment 
Original Protocol - version 0 dated 16Aug2019 
Amendment 1 – version 1 dated 29Oct2020 
The design of this study as outlined by this protocol has been reviewed and approved by the 
Sponsor’s responsible personnel as indicated in the signature table below. 
 
Name 
Title 
Signature 
John Lee, MD, PhD 
Chief Medical Officer 
 
Name 
Title 
Signature 
Lauren Richardson 
AVP Regulatory & Quality 
Name 
Title 
Signature 
Lisa Hickey, PhD 
Senior Director Biostatistics 
 
Name 
Title 
Signature 
Susan Maloney 
Global Head Clinical Research 
Name 
Title 
Signature 
Susan Arnold, PhD 
VP, Preclinical and CMC 
 

Clinical Study Protocol 
PB2452-PT-CL-0003-Phase 2b 
Version 2 dated 28May2021 
Investigational Product: PB2452 
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INVESTIGATOR’S AGREEMENT 
I have read the protocol, appendices, and accessory materials (if applicable) related to this study 
and agree to the following: 
• To conduct this study as described by the protocol and any accessory materials (if 
applicable) 
• To conduct the study in accordance with all applicable local and national regulations, the 
requirements of the ethics committee of record for my clinical site, and Good Clinical 
Practices (GCPs) as outlined by ICH E6(R2) 
• To obtain approval for the conduct of the protocol and all related amendments (if 
applicable) and all written materials provided to subjects prior to initiating the study at 
my site based on local requirements 
• To obtain informed consent (IC) – and updated consent form where applicable and in the 
event of new information or amendments – from all subjects enrolled at my study site 
prior to initiating any study-specific procedures or administering investigational products 
to those subjects as outlined in the protocol 
• To provide a completed and signed Food and Drug Administration (FDA) form 1572 (or 
equivalent where applicable) and a financial disclosure form 
 
Name (Last Name, First Name) 
Site ID 
Institution Name 
Signature 
Date 
Please note this page will be supplied separately to all sites. Please file the signed Investigator 
Agreement form in the study binder. 

Clinical Study Protocol 
PB2452-PT-CL-0003-Phase 2b 
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Investigational Product: PB2452 
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TABLE OF CONTENTS 
STATEMENT OF COMPLIANCE ............................................................................................... 2 
SPONSOR’S APPROVAL ............................................................................................................ 3 
INVESTIGATOR’S AGREEMENT ............................................................................................. 4 
TABLE OF CONTENTS............................................................................................................... 5 
LIST OF TABLES ......................................................................................................................... 9 
LIST OF APPENDICES ................................................................................................................ 9 
1 
SYNOPSIS ....................................................................................................................... 10 
1.1 
Schedule of Events ........................................................................................................ 19 
2 
INTRODUCTION ........................................................................................................... 23 
2.1 
Background ................................................................................................................... 23 
2.1.1 
Target Indication and Population ............................................................................... 23 
2.1.2 
Description of PB2452 ............................................................................................... 23 
2.1.2.1 
Administration Regimen ......................................................................................... 24 
2.1.2.2 
Justification for Dosing Strategy ............................................................................ 24 
2.1.3 
Supportive Nonclinical Data ...................................................................................... 25 
2.1.3.1 
Pharmacology ......................................................................................................... 25 
2.1.3.2 
Toxicology .............................................................................................................. 26 
2.1.3.3 
Toxicokinetics ......................................................................................................... 26 
2.1.4 
Supportive Clinical Data ............................................................................................ 28 
2.1.4.1 
Clinical Pharmacology and Pharmacokinetics ....................................................... 28 
2.1.5 
Benefit:Risk Assessment ........................................................................................... 29 
2.1.5.1 
Additional Risks ..................................................................................................... 30 
2.1.5.2 
Benefits ................................................................................................................... 31 
2.2 
Study Rationale ............................................................................................................. 31 
3 
OBJECTIVES AND ENDPOINTS ................................................................................. 32 
3.1 
Primary Objective and Endpoint ................................................................................... 32 
3.2 
Secondary Objectives and Endpoints ........................................................................... 32 
3.2.1 
Secondary Objectives................................................................................................. 32 
3.2.2 
Secondary Endpoints ................................................................................................. 32 
3.3 
Other Prespecified Objectives Endpoints ..................................................................... 34 
3.3.1 
Other Prespecified Objectives ................................................................................... 34 

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3.3.2 
Other Prespecified Endpoints .................................................................................... 34 
4 
STUDY PLAN ................................................................................................................. 35 
4.1 
Study Design ................................................................................................................. 35 
4.2 
Design Rationale ........................................................................................................... 35 
5 
POPULATION ................................................................................................................ 36 
5.1 
Definitions .................................................................................................................... 36 
5.2 
Inclusion Criteria .......................................................................................................... 36 
5.3 
Exclusion Criteria ......................................................................................................... 37 
5.4 
Exceptions to Eligibility Criteria .................................................................................. 39 
6 
STUDY CONDUCT ........................................................................................................ 40 
6.1 
Study Procedures .......................................................................................................... 40 
6.1.1 
Screening Period ........................................................................................................ 46 
6.1.1.1 
Informed Consent Form .......................................................................................... 46 
6.1.1.2 
Demographics and General Medical and Social History ........................................ 46 
6.1.1.3 
Physical Examination ............................................................................................. 46 
6.1.1.4 
Height/Weight and Calculation of Body Mass Index ............................................. 47 
6.1.1.5 
Standard Vital Signs ............................................................................................... 47 
6.1.1.6 
12 Lead Electrocardiogram ..................................................................................... 47 
6.1.1.7 
Laboratory Testing .................................................................................................. 48 
6.1.2 
Randomization ........................................................................................................... 51 
6.1.3 
Active Treatment Period ............................................................................................ 51 
6.1.4 
Safety Follow-up Period ............................................................................................ 52 
6.1.5 
Unscheduled Visits .................................................................................................... 52 
6.1.6 
End of Study .............................................................................................................. 52 
6.1.7 
Long-term Extension ................................................................................................. 53 
6.2 
Discontinuation or Withdrawal ..................................................................................... 53 
6.2.1 
Individual Subjects..................................................................................................... 53 
6.2.1.1 
Treatment Discontinuation ..................................................................................... 53 
6.2.1.2 
Withdrawal from Study .......................................................................................... 54 
6.2.1.3 
Replacement of Subjects ......................................................................................... 54 
6.3 
Study Termination ........................................................................................................ 54 
7 
STUDY INTERVENTIONS ........................................................................................... 55 

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7.1.1 
Active Intervention .................................................................................................... 55 
7.1.1.1 
Formulation, Storage, Preparation, and Handling .................................................. 55 
7.1.1.2 
Dosing and Administration ..................................................................................... 56 
7.2 
Treatment Assignment and Bias Minimization ............................................................ 56 
7.2.1 
Treatment Allocation ................................................................................................. 56 
7.2.2 
Randomization Strategy and Procedure ..................................................................... 56 
7.2.3 
Extent and Maintenance of Blinding ......................................................................... 57 
7.2.4 
Unblinding Procedures............................................................................................... 57 
7.2.4.1 
Planned Unblinding ................................................................................................ 57 
7.2.4.2 
Unplanned or Unintentional Unblinding ................................................................ 57 
7.3 
Assessment and Verification of Compliance ................................................................ 58 
7.4 
Concomitant Therapies ................................................................................................. 58 
7.4.1 
Prohibited Therapies .................................................................................................. 58 
7.4.2 
Permitted Therapies ................................................................................................... 58 
8 
SAFETY MONITORING ................................................................................................ 60 
8.1 
Definitions .................................................................................................................... 60 
8.1.1 
Documenting Adverse Events ................................................................................... 62 
8.1.2 
Timeframe for Collection........................................................................................... 63 
8.1.3 
Classification of Events ............................................................................................. 64 
8.1.3.1 
Assessment of Severity ........................................................................................... 64 
8.2 
Reporting Adverse Events ............................................................................................ 64 
8.2.1 
Reporting to the Sponsor ........................................................................................... 64 
8.2.2 
Sponsor Regulatory Reporting of Serious Adverse Events ....................................... 65 
8.3 
Adverse Events of Special Interest ............................................................................... 65 
8.4 
Clinical Laboratory Findings ........................................................................................ 65 
8.5 
Pregnancy and Contraception ....................................................................................... 66 
8.6 
Overdose or Misuse ...................................................................................................... 67 
9 
ANALYSIS ...................................................................................................................... 68 
9.1 
Primary Hypothesis....................................................................................................... 68 
9.2 
Population ..................................................................................................................... 68 
9.2.1 
Sample Size Rationale ............................................................................................... 68 
9.2.2 
Analysis Subsets ........................................................................................................ 68 

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9.3 
Testing Procedures ........................................................................................................ 69 
9.3.1 
Analysis of the Primary Efficacy Endpoint ............................................................... 69 
9.3.2 
Analysis of Secondary Efficacy Endpoint(s) ............................................................. 70 
9.3.3 
Population Analysis ................................................................................................... 70 
9.3.3.1 
Disposition .............................................................................................................. 70 
9.3.3.2 
Demographics ......................................................................................................... 70 
9.3.3.3 
Baseline Characteristics .......................................................................................... 70 
9.3.4 
Safety Analysis .......................................................................................................... 71 
9.3.4.1 
Demographics ......................................................................................................... 71 
9.3.4.2 
Baseline Characteristics .......................................................................................... 71 
9.3.4.3 
Disposition .............................................................................................................. 71 
9.3.4.4 
Adverse Events ....................................................................................................... 71 
9.3.4.5 
Clinical Laboratory Results .................................................................................... 71 
9.3.5 
Other Prespecified Endpoint Analysis ....................................................................... 71 
9.3.6 
Pharmacokinetics Analysis ........................................................................................ 71 
9.3.7 
Pharmacodynamics Analysis ..................................................................................... 72 
9.3.8 
Immunogenicity Analysis .......................................................................................... 72 
9.4 
Planned Interim Analysis .............................................................................................. 72 
9.4.1 
Temporary Halting or Early Termination Criteria ..................................................... 72 
9.4.2 
Specified Analyses for Independent Data Monitoring Committee Review ............... 72 
9.5 
Procedures for Reporting Changes to the Planned Analysis ........................................ 72 
10 
ETHICAL CONSIDERATIONS ..................................................................................... 73 
10.1 
Good Clinical Practice .................................................................................................. 73 
10.2 
Ethics Review ............................................................................................................... 73 
10.3 
Informed Consent Form ................................................................................................ 73 
10.4 
Data Privacy .................................................................................................................. 74 
10.5 
Financial Considerations............................................................................................... 75 
10.6 
Biological Specimens and Data .................................................................................... 75 
11 
OVERSIGHT ................................................................................................................... 76 
11.1 
Independent Monitoring ............................................................................................... 76 
11.1.1 
Data and Safety Monitoring Committee .................................................................... 76 
11.2 
Quality Control and Assurance ..................................................................................... 76 

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11.2.1 
Monitoring ................................................................................................................. 76 
11.2.2 
Audits ......................................................................................................................... 77 
11.2.3 
Protocol Deviations .................................................................................................... 77 
11.2.4 
Records ...................................................................................................................... 78 
11.2.4.1 
Data Collection Instruments ................................................................................... 78 
11.2.4.2 
Data Capture and Management............................................................................... 78 
11.2.4.3 
Data Validation ....................................................................................................... 79 
11.2.4.4 
Source Documentation ............................................................................................ 79 
11.2.4.5 
Study Files .............................................................................................................. 80 
11.2.4.6 
Records Retention ................................................................................................... 80 
11.2.4.7 
Archival of Data ..................................................................................................... 80 
11.3 
Sponsor Trial Discontinuation Criteria ......................................................................... 80 
11.3.1 
Study Termination ..................................................................................................... 80 
11.3.2 
Study Site Closure ...................................................................................................... 80 
12 
PUBLICATION POLICY ............................................................................................... 82 
13 
DISEMINATION OF STUDY DATA ............................................................................ 83 
14 
FINANCING AND INSURANCE .................................................................................. 84 
15 
REFERENCES ................................................................................................................ 85 
16 
APPENDICES ................................................................................................................. 87 
 
LIST OF TABLES 
Table 1............Schedule of Events ............................................................................................... 19 
Table 2............List of Clinical Laboratory Assessments .............................................................. 49 
 
LIST OF APPENDICES 
Appendix 1 .....List of Abbreviations ........................................................................................... 88 
Appendix 2 .....Pregnancy Testing, Reporting Guidance and Contraception Methods ................ 94 
Appendix 3 .....Schedule of Events (SOE) .................................................................................... 96 
Appendix 4 .....Examples of Inhibitors of CYP3A ..................................................................... 100 

Clinical Study Protocol 
PB2452-PT-CL-0003-Phase 2b 
Version 2 dated 28May2021 
Investigational Product: PB2452 
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1 
SYNOPSIS 
 
Title 
A Phase 2B, randomized, double-blind, multicenter, placebo- 
controlled study to evaluate the efficacy of PB2452 in 
reversing the antiplatelet effects of ticagrelor in subjects aged 
50 to 80 years old 
Short Title 
PhaseBio Phase 2B ticagrelor reversal study 
Phase 
2B 
Study Design 
Randomized, Double Blind, Multicentered, Placebo Controlled 
Rationale 
PB2452 is intended to reverse the antiplatelet effects of ticagrelor 
in patients who experience major or life-threatening bleeding or 
who require urgent surgery or invasive procedure 
Population 
Approximately 200 subjects between 50 and 80 years old who are 
in good general health or who have chronic, stable, and generally 
well-controlled medical conditions are eligible. This is the age 
group most typical of patients receiving ticagrelor. It is expected 
that approximately 20% of the study population will be ≥ 65 years 
old 
Number of Subjects 
Total: Approximately 200 
Per treatment: The allocation ratio is 3:1 of active:placebo 
PB2452 arm: 150 
Placebo arm: 50 
Length of Participation 
On treatment: Approximately 16-24 hours 
On study (including Screening and follow-up): up to 83 days 
compromised of up to 45 days of pre-screening and 35+3 days of 
follow up post study drug administration. Maximum total days 
involved will be 83 days 
The study will consist of a Screening period (Days –45 to –4), a 
Check-in period (Day –3 to Day -1), an on-site 
Randomization/Treatment day (Day 1), a 2-day on-site Follow-up 
period (Days 2 through 3), a Day 7 Follow-up visit, and a final 
Follow-up visit (Day 35+3) 
Note: If needed and at the discretion of the Investigator, a subject 
may remain in the study facility beyond the scheduled Day 3 
discharge to accommodate Day 7 and/or Day 35+3 follow-up 
visits 
The estimated duration of the study for each subject, excluding 
screening, is approximately 35+3 days 
Intervention 
All subjects will be pretreated with both: 
1. Aspirin 81 mg given once daily for a total of 8 doses, from 
Day -7 to Day 1 (2 hours prior to starting the study drug on 
Day 1) 

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throughout study participation 
2. The subject is male or female between >50 and <80 years of 
age 
3. The subject has a body mass index between 18 and 35 kg/m2 
and a weight of ≥50 kg but ≤120 kg, inclusive, on first day of 
screening 
4. The subject is considered by the Investigator to be in good 
general health as determined by medical history, clinical 
laboratory test results, vital sign measurements, 12-lead ECG 
results, and physical examination findings at Screening and up 
to the time of randomization. Subjects with chronic, stable, 
and well-controlled medical conditions, are eligible provided 
they meet all other inclusion/exclusion criteria. Some 
examples of stable and well-controlled medical conditions 
include but are not limited to: 
• Hypertension controlled with no more than two 
antihypertensive drugs 
• Hyperlipidemia (defined with a Screening LDL of <190 
mg/dL) 
• Diabetes controlled with diet/exercise or treated with no 
more than 2 medications and/or Glycosylated Hemoglobin 
Hgb (HbA1c) ≤8% 
• Remote history of myocardial infarction (>3 years prior to 
screening) with no symptoms 
• Mild hepatic enzyme elevation (AST or ALT <1.5 x upper 
limit of normal (ULN) or total bilirubin <1.2 x ULN) 
5. Specific inclusionary laboratory values at Screening and 
Check-in require the following: 
• Stable white blood cell (WBC) count, platelet count, 
haemoglobin level with no clinically significant 
abnormality within the normal range as assessed by the 
Investigator 
• Thyroid stimulating hormone (TSH) level within the 
normal range, as defined by the clinical laboratory at 
screening 
• Prothrombin time (PT) and/or international normalized 
ratio (INR) levels; plus partial thromboplastin time (PTT) 
and/or partial thromboplastin time (aPTT) levels less than 
or equal to the upper limit of normal as defined by the 
clinical laboratory 

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6. Subjects taking medications for well-controlled medical 
conditions must have been on a stable dose (meaning no 
changes in dose) for at least 30 days prior to initiation of study 
drug 
7. Subjects entering the study: 
i) Who are not already taking daily aspirin must be willing 
to start an 81 mg daily dose of aspirin on Day -7 and must 
document daily dosing until the final dose is administered on 
the morning of Day 1 
ii) Who are already taking daily aspirin must be willing to 
document a daily 81 mg dose between Day -7 and Day 1 and 
must suspend further aspirin dosing until discharge from the 
study site on Day 3 
8. Female subjects of childbearing potential must not be 
pregnant, lactating, or planning to become pregnant for 
3 months after signing the informed consent, and have a 
negative serum pregnancy test at Screening and Check-in. 
Female subjects of childbearing potential must use 2 effective 
methods of birth control for 3 months after signing the 
informed consent 
Main Exclusion 
Criteria 
Subjects will be excluded from the study if they meet any of the 
following criteria: 
1. In the opinion of the Investigator there are concern(s) 
regarding the ability of the subject to comply with study 
procedures and/or follow-up, or, if the subject is not suitable 
for entry into the study 
2. History of any acute or chronic medical disorder expected to 
decrease the life expectancy of the subject to an extent where 
the subject’s study participation is affected 
3. Any clinically significant acute illness, medical/surgical 
procedure, or trauma within 4 weeks of the administration of 
study drug or any planned surgical procedure that will occur 
during the study (from Screening through the Day 35+3 follow 
up visit) 
4. Any clinically significant abnormal findings in physical 
examination, vital signs, laboratory assessments, and ECG 
parameters identified during Screening or Check-in. 
Note: abnormal results may be repeated (locally or centrally) 
for confirmation immediately after the first out of range 
measurement. Abnormal vital signs may be repeated twice if 
needed, immediately after the first abnormal result and/or after 
the subject has rested for at least 10 minutes 

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Specific vital sign exclusionary criteria occurring after 10 
minutes of supine rest are any of the following: 
• SBP <100 or >160 mm Hg 
• DBP <40 or >95 mm Hg 
• Resting HR <50 or >100 beats per minute (bpm) 
Specific exclusionary criteria for ECG parameters at Screening 
/Check-in or Day 1 are any of the following: 
• Prolonged Fridericia-corrected QT interval (QTcF) >450 
milliseconds (msec), or pause >3 seconds, or family 
history of long QT syndrome 
5. Any specific contraindication to ticagrelor as described in the 
Brilinta® prescribing information and as described below: 
• History of intracranial hemorrhage, active bleeding, or 
hypersensitivity or allergic reaction to ticagrelor or any 
component of the product 
• Any history of severe head trauma, intracranial neoplasm, 
arteriovenous malformation, aneurysm, or proliferative 
retinopathy 
• Any history of intraocular, retroperitoneal, or spinal 
bleeding 
• Having taken any oral or parenteral anticoagulant, 
including low molecular-weight heparin within 30 days of 
initiation of study drug 
• Severe hepatic impairment 
• Stool sample testing positive for occult blood within 3 
months of Screening or at any time during the Screening 
period 
6. Receiving treatment with nonsteroidal anti-inflammatory 
drugs [including aspirin (>100 mg daily), anticoagulants, or 
other antiplatelet agents, that cannot be discontinued between 
the date informed consent was signed and the end of the study 
period 
7. First positive test result for any hepatitis B (unvaccinated), 
hepatitis C, or human immunodeficiency virus types 1 or 2 
antigen or antibodies at screening 
8. Has received another investigational drug (defined as a small 
molecule or biologic compound which has not been approved 
for marketing) within 30 days of the administration of study 
drug in this study or within 5 half-lives of the experimental 
medication, whichever is longer 
9. History of severe or ongoing allergy/hypersensitivity to any 
biologic therapeutic agent 

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10. Involvement with any PhaseBio or study site employee or their 
close relatives (e.g., spouse, parents, siblings, or children 
whether biological or legally adopted) 
11. Previously received PB2452 
Primary Objective and 
Primary Endpoint 
Primary Objective: 
To demonstrate reversal of the antiplatelet effects of ticagrelor 
with intravenous PB2452 vs. placebo 
Primary Endpoint: 
The primary study endpoint is the minimum % inhibition of P2Y12 
reaction units (PRU) assessed by VerifyNow™ PRUTest™ 
(VerifyNow™, 2016) within 4 hours after the initiation of study 
drug. Percent inhibition of PRU is calculated as 100 * [(PRUbsl – 
PRUtrt)/PRUbsl] where PRUbsl refers to the PRU value measured 
before treatment with ticagrelor and PRUtrt refers to the PRU 
value measured post treatment with the study drug 
Secondary Objective(s) 
and Corresponding 
Endpoint(s) 
Secondary Objectives: 
1. To evaluate the safety, tolerability, and immunogenicity of 
PB2452 in subjects treated with ticagrelor 
2. To evaluate the pharmacokinetic (PK) profile of intravenous 
PB2452, ticagrelor, and its active metabolite (TAM) in blood 
and urine 
3. To evaluate additional parameters of PB2452-mediated 
ticagrelor reversal by assessment of PRU using the 
VerifyNow™ PRUTest™ (VerifyNow™, 2016) P2Y12 assay 
and assessment of the platelet reactivity index (PRI) using the 
Vasodilator-stimulated phosphoprotein (VASP) assay 
Secondary Endpoints: 
1. Safety, tolerability and immunogenicity will be assessed by 
monitoring and recording of adverse events (AEs), including 
infusion site and systemic infusion reactions, clinical 
laboratory test results (hematology, coagulation, serum 
chemistry, and urinalysis), vital sign measurements (systolic 
and diastolic blood pressures, body temperature, respiratory 
rate, and heart rate), 12-lead electrocardiogram (ECG) results, 
physical examination findings, and immunogenicity 
2. Plasma concentrations of total PB2452, unbound PB2452, 
total ticagrelor, total TAM, unbound ticagrelor, and unbound 
TAM, will be assessed at predetermined timepoints 
PK parameters for PB2452 include: 
• Observed maximum plasma concentration (Cmax) 

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• Area under the plasma concentration versus time curve 
(AUC) from time zero to the time of the last quantifiable 
concentration (AUC0-t) 
• Time to reach the observed maximum plasma 
concentration (Tmax) 
• AUC from time zero to 24 hours post-dose (AUC0-24) 
• AUC from time zero to 48 hours post-dose (AUC0-48) 
• Area under the plasma concentration versus time curve 
(AUC) from time zero to the time of the end of the dosing 
period (AUC0-tau) 
• AUC from time zero extrapolated to infinity (AUC0-∞; if 
data permit) 
• Terminal elimination half-life (t½; if data permit) 
• Clearance (CL; if data permit) 
• Volume of distribution (Vd) 
PK parameters for ticagrelor/TAM include: 
• Cmax 
• AUC0-last 
• Tmax 
• AUC0-24 
• AUC0-48 
• AUC0-tau 
• AUC0-∞; if data permit 
• t½; if data permit 
Urine PK endpoints: 
Pooled urine samples to assess urine PB2452, ticagrelor, and TAM 
concentrations will be collected according to predefined intervals. 
PK parameters for PB2452, ticagrelor, and TAM concentrations in 
urine for all subjects in the PK population to be calculated are: 
• Total amount of drug excreted in urine over 24 hours 
(Ae24) and over 48 hours (Ae48) 
• Ae from time t1 to t2 hours including 0 to 6, 6 to 12, 12 to 
24 and 24 to 48 hours (Aet1-t2) 
• Fraction excreted in urine from 1 to 24 hours (Fe24) and 
from 1 to 48 hours (Fe48) 
• Renal clearance (CLr) for 24 hours 
3. Additional reversal endpoints: 
• Minimum %inhibition of PRI assessed by VASP within 4 
hours after the initiation of study drug. %inhibition of PRI 
is calculated as 100 * [(PRIbsl – PRItrt)/PRIbsl]. PRIbsl refers 
to the PRI value measured before treatment with ticagrelor 

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and PRItrt refers to the PRI value measured posttreatment 
with the study drug 
• PRU AUC for the first 4 hours 
• Proportion of subjects with normalized platelet reactivity 
units within 4 hours after the initiation of study drug 
Normalized platelet reactivity is defined as PRU ≥ 180. 
• Proportion of subjects with ≥60%, ≥80%, and 100% of 
PRU response rate within 4 hours after the initiation of 
study drug. A PRU response is defined as the 100 
*(PRUtrt/PRUbsl) 
• Time to 60%, 80%, 100% of PRU response rate within 4 
hours after the initiation of study drug 
• Duration of 80% and 100% response rate by PRU 
• PRI AUC for the first 4 hours 
• Proportion of subjects with ≥60%, ≥80%, and 100% of 
PRI response rate within 4 hours after the initiation of 
study drug. A PRI response is defined as the 100 * 
(PRItrt/PRIbsl) 
• Time to 60%, 80%, 100% PRI response rate within 4 hours 
after the initiation of study drug 
• Duration of 80% and 100% response rate by PRI 
• Percent reversal of PRU within 4 hours after the initiation 
of study drug. Percent reversal is calculated as 100 
*[(PRUtrt – PRUpre-trt)/(PRUbsl – PRUpre-reversal)]. PRUpre-trt is 
defined as the PRU value prior to administration of study 
drug 
• Percent reversal of PRI within 4 hours after the initiation 
of study drug. Percent reversal is calculated as 100 * 
[(PRItrt – PRIpre-trt)/(PRIbsl – PRIpre-trt)]. PRIpre-reversal is 
defined as the PRU value prior to administration of study 
drug 
Other Prespecified 
Objective and 
Corresponding 
Endpoints 
Other Prespecified Objective: 
• Assessment of platelet function related biomarkers 
Other Prespecified Endpoints: 
• Circulating levels of P-selectin and other platelet function- 
related biomarkers at baseline and post-initiation of PB2452 
• Proportion of subjects with known single-nucleotide 
polymorphisms related to P2Y12 receptor function 

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Number of Sites 
Approximately 5-15 sites in the United States and other countries 
at the discretion of the Sponsor 
Study Duration 
Estimated start date: Q42019 
Projected stop date: 
Q42021 
Estimated duration: 
Timelines may be altered based on 
recruitment 
Committee(s) 
Not applicable 

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Outpatient 
Outpatient/In- 
Clinic 
Treatment (In- 
Clinic) 
Outpatients 
Procedure 
Screeninga 
Check-in/ 
Pretreatment 
Rand 
Subject 
DC 
FUP 
FUP 
EOS 
Study Day(s) 
–45 to – 
4 
-7 
–3 
-2 
–1 
1 
2 
3 
7 
35+3 
PD sampling (PRU/VASP)q 
X 
X 
X 
X 
Platelet function 
biomarkersr 
X 
X 
X 
X 
Serum immunogenicity 
(ADA testing)s 
X 
Xs 
X 
Xs 
Infusions site assessmentt 
X 
X 
X 
X 
X 
AEs/SAEsu 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medicationsv,w 
Xv 
Xv 
Xv 
Xv 
Xv 
Xw 
Xw 
Xw 
Xw 
Xw 
Discharge from clinicx 
X 
Xx 
Xx 
Abbreviations: AE=adverse event; ADA=anti-drug antibody; ASA= aspirin; BMI=body mass index; 
DBP=diastolic blood pressure; DC = discharged; ECG=electrocardiogram; EDC=electronic data capture; 
EOS=end of study; FUP=follow-up; HR=heart rate; PD=pharmacodynamics; PK=pharmacokinetics; 
PRU=P2Y12 reaction units; QD=once daily; Rand=Randomization; RR=respiratory rate; SAE=serious 
adverse event; SBP=systolic blood pressure; TAM=ticagrelor active metabolite AR-C124910XX; 
VASP=vasodilator-stimulated phosphoprotein 
a 
Screening Period = Days -45 to -4 (including Day -7, when ASA is started) 
b 
If verbal consent is obtained, it must be witnessed by an impartial witness. The details and full process 
to be fully documented in source documents 
Note: Any changes to site-specific processes due to COVID-19 pandemic must be fully documented 
and identified within source documents and eCRF 
c 
Serum pregnancy test for women of childbearing potential only. May utilize central or local 
laboratory as needed 
d 
Stool for occult blood test may be conducted at either the central or local laboratory as needed. 
The Day 3 stool occult sample may be collected on Day 2 if needed 
e 
A full physical examination is conducted at Screening, Day -3 and Day 35+3 
Height and weight collected at Screening and Day 35+3 only 
BMI is calculated within the electronic data capture system 
f 
Brief physical examination and querying the subject concerning any changes from baseline. A 
brief physical examination will include assessment of heart, skin, lungs, cardiovascular system, 
and abdomen, and extremities 
g 
Vital sign measurements (SBP and DBP, body temp, RR, and HR) will be collected at screening, 
check-in (Day -3), before dosing (30 to 60 minutes prior to the initiation of the study drug 

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infusion) and at 15±5, 30±10, 45±10, 60±15 min, 24 hours±15 min and 48 hours±15 min 
following initiation of study drug 
Vital Signs are also collected on Day 7 and 35+3. Vital signs at 15, 30, 45, and 60 minutes 
following infusion require only SBP and DBP, and HR 
h 
12-lead ECGs will be obtained at Screening before initiation of PB2452/placebo, pre-treatment 
Day -1, and on treatment Days 1, 2, 7 and 35+3. The specific time points for 12-lead ECG on Day 
1 and 2 will be pre-dose, 10 minutes after bolus, end of infusion, and after 24 hours (+ 30 
minutes) from initiation of infusion. ECGs will be collected anytime on Days 7 and 35+3 
i 
All scheduled clinical laboratory tests will be performed centrally with the exception of Day -1 
clinical laboratory testing which should be performed locally to provide results prior to 
randomization 
Note: There is no scheduled clinical laboratory test o Day 3. However, if required the clinical 
laboratory tests (hematology, chemistry, coagulation, and urinalysis) may be repeated if 
considered clinically significant by the Investigator based on Day 2 lab results 
j 
Local/Central laboratory results must be confirmed to ensure continued eligibility prior to 
randomization 
k 
ASA 81 mg will be taken on Days -7, -6, -5, -4, -3, -2, -1, and on Day 1 no less than 2 hours 
before study drug is started. Subjects who enter the study already taking ASA daily must 
document a daily ASA 81 mg dose between Day -7 and Day -3. Subjects will receive daily ASA 
81 mg between Day -3 (or Day -2 if the subject took ASA 81mg on Day -3 prior to Check-in) and 
Day 1 at the clinical facility and will suspend further ASA dosing until discharge from the clinical 
facility on Day 3 
l 
Beginning in the morning on Day –2, a single dose of oral ticagrelor 180 mg will be given, 
followed by oral ticagrelor 90 mg every 12 hours (or BID) for 4 additional doses through to Day 
1. The final dose of ticagrelor should occur 2 hours±15 min before study drug is initiated) 
m 
PB2452/placebo will be administered at Hour 0 of Day 1 
Infusion of PB2452/placebo is initiated on Hour 0 of Day 1 and will continue for approximately 
16 hours for a total of 18 g (180 mL), as described in the protocol and pharmacy manual. 
In subjects with known or reported concomitant use of moderate or strong CYP3A inhibitors 
(Appendix 4), an alternative 36 g (360 mL) regimen of PB2452 infused for approximately 24 
hours will be administered as directed by the pharmacy manual 
n 
A pre-ticagrelor blood sample will be collected on Day -2, within 60 mins prior to the dose of 
ticagrelor. Blood samples for determination of plasma PB2452, plasma ticagrelor/TAM and 
unbound plasma ticagrelor/TAM will be collected on Days 1 to 3 within 10 minutes prior to the 
initiation of PB2452/placebo infusion (Hour 0) and at 5, 10, 30 minutes and 1, 2, 4, 8, 12, 20, 24, 
36, and 48 hours after initiation of study drug infusion 
Plasma PK samples will also be collected on Day 7, and Day 35+3 after initiation of study drug 
infusion 
o 
Urine samples for PK ticagrelor/AR-C124910XX to be collected at i) 0 to 6 hours; ii) 6 to 12 
hours and iii) 12 to 24 hours and iv) 24 to 48 hours after the initiation of the study drug infusion 
p 
Collection of Day -2 urine PK sample is a single sample collected within 60 minutes prior to the 
first ticagrelor dose 

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q 
Blood samples for PD analysis (PRU/VASP testing) will be collected at the following timepoints: 
Day -2 and Day 1 (within 60 minutes prior to first ticagrelor dose) and Hour 0 (up to 10 minutes 
prior to PB2452/placebo infusion), 5, 10, 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after 
initiation of PB2452/placebo infusion 
If there is sufficient material leftover from PK and/or PD blood samples, additional platelet 
function-related biomarker testing, such as P-selectin, may be performed 
r 
One sample for platelet biomarker testing will be collected into a plasma tube (3.2% Na Citrate) at the 
indicated timepoints. A single Qiagen PAXgene DNA tube per subject is collected at any convenient 
sampling timepoint throughout the study. Detailed instructions are provided in the laboratory manual 
s 
Subjects may be required to return to the site for collection of additional follow-up samples, if the 
sample collected at Day 35+3 tests positive for treatment-emergent ADAs. These visits may 
occur approximately 3 months after the final study visit and approximately every 6 months 
thereafter or until antibody levels return to baseline level 
Note: serum immunogenicity sample on Day 1 must be collected prior to initiation of study drug 
infusion 
t 
Infusion site assessments will be performed for all subjects within 15 minutes before initiation of 
PB2452/placebo infusion at Hour 0, 1, 3, 24, and 48 hours after initiation of PB2452/placebo 
infusion, and on Days 7 and 35+3 
u 
All AEs/SAEs from the time of consent to Day 35+3 are to be reported, regardless of subject 
being within or outside the facility/study site 
v 
All concomitant medications (prescription, over the counter and supplements) to be collected -45 
days from the date informed consent is signed until Day 35+3. Subjects must be on a stable dose 
(meaning no changes in dose) of their medications for at least 30 days prior to initiation of study 
drug (time of randomization) 
w 
New medications and changes to dosing of existing medications can occur post Day 1 
(randomization) and are to be captured at schedule visit up to Day 35+3 
x 
Subjects are discharged from the clinic on Day 3. However, if needed and at the discretion of the 
Investigator, a subject may remain in the study facility beyond the scheduled Day 3 discharge to 
accommodate Day 7 and Day 35+3 follow-up visits. All applicable study-related assessments for 
Day 7 and Day 35+3 will occur as outlined in the protocol 

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2 
INTRODUCTION 
PB2452 is an intravenously delivered monoclonal antibody fragment (Fab) intended to reverse 
the antiplatelet effects of ticagrelor in patients who experience uncontrolled major or life- 
threatening bleeding or who require urgent surgery or invasive procedure. PB2452 (molecular 
weight 47.4 kDa) is a specific and selective recombinant human neutralizing antibody IgG1λ 
monoclonal fragment antigen-binding (Fab) antibody that binds with high affinity to ticagrelor 
and selectively to circulating ticagrelor and its major active metabolite AR-C124910XX (TAM). 
It is expressed and manufactured from Escherichia coli cells (Buchanan, 2015). 
Ticagrelor is an orally available inhibitor of platelet activity that in combination with low-dose 
acetylsalicylic acid (ASA, aspirin) has been shown to prevent recurrent thrombotic events, e.g., 
myocardial infarction (MI), stroke, and cardiovascular death, in patients with acute 
coronary syndrome (ACS) or a history of MI. Ticagrelor also reduces the rate of stent thrombosis 
in patients who have been stented for treatment of ACS. Ticagrelor is a direct-acting 
cyclopentyltriazolopyrimidine inhibitor of platelet function that selectively and reversibly binds 
and antagonizes the platelet P2Y12 receptor (Teng, 2016; van Giezen, 2009). A ticagrelor active 
metabolite (TAM) achieves a 30% to 40% plasma exposure relative to the circulating ticagrelor 
exposure in humans, (Storey R. H., 2007) and has potency similar to ticagrelor in inhibiting the 
P2Y12 receptor. 
In the management of ACS, ticagrelor treatment is initiated with a 180 mg loading dose, 
followed by 90 mg twice daily (bid) during the first year after an ACS event. After one year, if 
continued, the prescribed dosage is decreased to 60 mg bid. Ticagrelor is administered in 
combination with low-dose ASA (aspirin) as part of a regimen called dual antiplatelet therapy 
(DAPT). Although DAPT is strongly recommended in the management of patients experiencing 
an ACS event, it is also known to increase the risk of major or life-threating bleeding (Storey, 
2011). 
In the event of major bleeding in a patient on DAPT, there are limited treatment options. There 
are no approved drugs or biological agents capable of reversing the P2Y12 inhibition produced by 
ticagrelor or other P2Y12 inhibitors. Although platelet transfusion may restore platelet function in 
patients on ASA (Taylor G, 2013), it is not expected to reverse the antiplatelet effect of ticagrelor 
in patients with bleeding because of the reversibility of the ticagrelor P2Y12 receptor interaction. 
(Teng, 2016). Accordingly, the current lack of a reliable effective therapy to mitigate 
ticagrelor-induced platelet inhibition in patients who have major bleeding or who have elevated 
bleeding risk due to a requirement for urgent surgery or intervention represents a significant 
unmet need. 
2.1 
Background 
 
2.1.1 
Target Indication and Population 
The target indication for PB2452 is to reverse the antiplatelet effects of ticagrelor in adult 
ticagrelor-treated patients with major bleeding or prior to an urgent surgery or intervention. 
2.1.2 
Description of PB2452 
PB2452 (molecular weight 47.4 kDa) is a recombinant human IgG1λ monoclonal fragment 
antigen-binding (Fab) antibody that binds specifically to ticagrelor and TAM. It is produced in E. 

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reactions (IRRs), or dose-limiting toxicities (DLTs) observed as determined by the study 
Investigator and safety review committee (SRC) of the Phase 1 study. The 18 g dose level and 
16-hour infusion regimen administered in the Phase 1 study was repeated in a Phase 2A 
(PB2452-PT-CL-0002) clinical study of PB2452 in older (50-64 years old) and elderly (65-80 
years old) subjects pretreated with DAPT for 48 hours. This population is similar in age and 
background comorbidities to the target patient population treated with ticagrelor as part of DAPT 
for prior heart attack or recent coronary stent placement. Preliminary data indicate that the 
reversal and safety profiles in the Phase 2A population pretreated with DAPT was similar to the 
results observed in the Phase 1 study. 
PB2452 provided immediate and sustained reversal of the antiplatelet effects of ticagrelor with 
significant reversal observed as early as 5 min after initiation of infusion that was sustained for 
20-24 hours. These data support the 18g regimen of PB2452 infused over 16 hours and 10 min. 
In the last cohort of the Phase 2A study, healthy volunteers aged 18-50 years old were pretreated 
with a supratherapeutic 180 mg PO BID doses of ticagrelor for 48 hours. A regimen of PB2452 
consisting of a 12g bolus infused over 10 min followed immediately by 12g infused over 6 hours 
and then 12g infused over 18 hours for a total of 36g infused over a total of 24 hours and 10 min 
was found to provide immediate and sustained reversal of supratherapeutic levels of ticagrelor. 
Because this regimen of ticagrelor (180 mg BID) was found to produce circulating ticagrelor 
levels similar to ticagrelor levels occurring in the presence of ticagrelor 90 mg BID administered 
concomitantly with moderate CYP3A inhibitors (Teng R, 2013). This 36g regimen is expected to 
be appropriate for patients treated with ticagrelor who are currently taking moderate CYP3A 
inhibitors, such as, diltiazem or verapamil, and require urgent reversal of the antiplatelet effects 
of ticagrelor. 
In the current study, a larger population of older and elderly subjects (N=200), PB2452 will be 
investigated to confirm the rapid and sustained reversal profile and overall safety, tolerability, 
and immunogenicity profile of the IV regimen of 18 g infused over 16 hours. 
2.1.3 
Supportive Nonclinical Data 
Non-clinical pharmacology studies have demonstrated that PB2452 binds with high affinity and 
selectivity to the P2Y12 receptor antagonist ticagrelor and its active metabolite, TAM, 
(equilibrium dissociation constant [KD] 20 pmol/L). PB2452 rapidly neutralizes the unbound 
plasma fraction of ticagrelor and TAM, thereby reversing ticagrelor- and TAM-mediated 
inhibition of adenosine diphosphate (ADP)-induced platelet aggregation in a concentration- and 
dose-dependent manner in vitro (in human platelet-rich plasma) and in vivo (mouse and pig, 
dose-dependency data in mouse only). In mice dosed with ticagrelor to a supratherapeutic plasma 
exposure, those dosed with PB2452 administration prior to a tail cut had reduced bleeding to a 
degree comparable and not statistically different from the observation in mice not treated with 
ticagrelor (Buchanan, 2015). 
The non-clinical pharmacology profile of PB2452 supported further exploration of the use of this 
compound as a novel ticagrelor antidote therapy. Detailed descriptions of the non-clinical 
pharmacology of PB2452 may be found in the Investigators’ Brochure (IB) for PB2452. 
2.1.3.1 
Pharmacology 
The key non-clinical pharmacology study findings for PB2452 are as follows: 

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• PB2452 binds free ticagrelor and its active metabolite, TAM, selectively and with a high 
affinity (equilibrium dissociation constant [KD] 20 pmol/L) 
• PB2452 rapidly neutralizes the unbound plasma fraction of ticagrelor and TAM and thereby 
reverses ticagrelor- and TAM-mediated inhibition of ADP-induced platelet aggregation in a 
concentration- and dose-dependent manner in vitro (in human platelet-rich plasma) and in 
vivo (mouse and pig, dose-dependency data in mouse only) 
The non-clinical pharmacology profile of PB2452 supports further exploration of the use of this 
compound as a novel ticagrelor antidote therapy. For further details please refer to the current IB. 
 
2.1.3.2 
Toxicology 
Because PB2452 is directed at a non-endogenous target (i.e., ticagrelor and its metabolite TAM), 
one species was selected for the toxicology program, in accordance with ICH S6 guidelines 
(ICH, S6 (R1), 2011). The rat was selected as the relevant species, as ticagrelor and TAM exert 
similar toxicology profiles across species, metabolite profiles are comparable to those in humans, 
and the rat was a pharmacologically relevant species for ticagrelor. 
In the rat Good Laboratory Practice (GLP) toxicity study, single doses of PB2452 were 
administered intravenously to groups of rats at doses up to 2000 mg/kg. Toxicity was assessed 
either 24 hours after dosing or following 14 days of extended monitoring. Additional groups of 
animals received ticagrelor pretreatment via oral gavage at 20 mg/kg for 2 days prior to initiation 
of single IV doses of PB2452 at 0, 500, or 2000 mg/kg, approximately 4 hours (Cmax) after 
administration of ticagrelor. In this study, 2000 mg/kg PB2452 (± 20 mg/kg oral ticagrelor) was 
considered to be the no adverse effect level (NOAEL) (systemic exposures of PB2452 for the 
combined sexes; Cmax: 18100 μg/mL, AUC from zero to ∞ (AUC0-∞): 23100 μg.h/mL). Overall, 
there were no adverse effects observed following single doses of PB2452 at the highest dose 
level tested of 2000 mg/kg given IV, alone or in combination with oral ticagrelor (20 mg/kg). 
Therefore, 2000 mg/kg was considered NOAEL with a maximum plasma concentration (Cmax) of 
18100 µg/mL and an area under the plasma concentration versus time curve from time zero 
extrapolated to infinity (AUC0-∞) of 23100 µg*h/mL. The results of this GLP toxicity study 
support assessment of PB2452 in human studies (ICH, M3 (R2), 2009). 
To determine whether PB2452 would be expected to cross react with human tissues, a human 
tissue cross-reactivity study was performed using PB2452 that was tagged with a fluorescent 
marker PB2452-FITC. In this study, no staining was seen with the test article, designated 
PB2452-FITC, in any of the organ systems present in the human tissue panel. Lack of PB2452- 
FITC staining of human tissues was expected as ticagrelor, the target of PB2452, is not expected 
to be present in, or expressed by, normal human tissues and because PB2452 binds ticagrelor 
with high specificity and affinity. 
 
2.1.3.3 
Toxicokinetics 
The toxicity and PK of PB2452 were investigated following a single IV administration of 500 or 
2000 mg/kg to the rat, alone and in combination with 20 mg/kg of oral ticagrelor. An assessment 
of delayed onset toxicity and/or reversibility of toxicity was made following a 2-week extended 
monitoring phase. The key PK results were as follows: 

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• Following IV infusion dosing, PB2452 was rapidly distributed before being cleared with 
an estimated terminal half-life (T1/2) of 5.26 to 7.40 hours. Clearance (CL) was consistent 
between doses, ranging from 86.4 to 105 mL/hr/kg. The presence of ticagrelor did not 
affect the PK profile of PB2452, which was linear within the dose range tested, with dose 
proportional increases in maximum plasma concentration (Cmax) and area under the curve 
(AUC) for plasma concentration versus time 
• Concentrations of total ticagrelor and TAM increased from pre-dose concentrations 
following dosing with PB2452. While Cmax was consistent between the 500 mg/kg 
PB2452 plus 20 mg/kg ticagrelor-dosed group and 2000 mg/kg PB2452 plus 20 mg/kg 
ticagrelor-dosed group, the AUC from zero to 30 hours (AUC0-30) was greater in the 2000 
mg/kg PB2452 plus 20 mg/kg ticagrelor-dosed group, indicating that the ticagrelor and 
TAM may be cleared at a slower rate than in the 500 mg/kg PB2452 plus 20 mg/kg 
ticagrelor-dosed group. The decrease in clearance for total ticagrelor and TAM at the 
highest dose is likely to be associated with higher concentrations of circulating PB2452 
and a subsequent higher rate of complex formation. Total ticagrelor and TAM 
concentrations at follow-up (Cfollow-up), 14 days after PB2452 administration, were below 
the assay limit of quantification (BLQ). Additionally, total ticagrelor and TAM systemic 
concentrations increased immediately following dosing of PB2452 by approximately 15- 
and 20-fold, respectively, indicating that PB2452:ticagrelor and TAM complexes 
formation leads to redistribution of extravascular ticagrelor into the circulation 
(Buchanan, 2015; ICH, S6 (R1), 2011) 
• The PK of free ticagrelor and TAM as measured in the rat toxicology study were 
inconsistent, with variable pre-dose concentrations and quantifiable concentrations at 
Cfollow-up. There were no differences between groups treated with 500 mg/kg PB2452 plus 
20 mg/kg ticagrelor, 2000 mg/kg PB2452 plus 20 mg/kg ticagrelor, or the ticagrelor only 
group, and there was no identifiable trend in the data over time. This is likely to be 
associated to the limitation of the assay, as ticagrelor and TAM are highly protein bound. 
(Of note, a different research assay with a lower limit of quantification was used in the 
pharmacology studies summarized in Section 2.1.3.1, where the concentrations of free 
ticagrelor and TAM were reduced in a dose-dependent manner.) However, that the total 
ticagrelor and TAM systemic concentrations increased immediately following dosing of 
PB2452 by approximately 15- and 20-fold, respectively, demonstrates the 
pharmacodynamic (PD) effect of PB2452 binding to both ticagrelor and TAM 
The absorption, distribution, metabolism, and excretion (ADME) of PB2452 have not been 
formally assessed. However, in a pharmacology study in which pigs were dosed to a supra- 
therapeutic ticagrelor exposure on a background of ASA before PB2452 administration, urine 
was collected and total ticagrelor and TAM measured as an exploratory assessment of ticagrelor 
elimination in the presence of PB2452. The addition of PB2452 resulted in marked increases in 
mean concentrations of total ticagrelor and TAM in the urine. Because ticagrelor is mainly 
excreted in the feces, with renal excretion playing only a minor role; accordingly, in 10 animals 
treated with ticagrelor on a background of ASA, the concentrations of total ticagrelor and TAM 
in the urine were BLQ. The addition of PB2452 resulted in marked increases in mean 
concentrations of total ticagrelor and TAM in the urine, supporting the idea that PB2452 
complexation changes the ticagrelor elimination route from hepatic to renal (Buchanan, 2015). 

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2.1.4 
Supportive Clinical Data 
The first-in-human Phase 1 study (PB2452-PT-CL-0001) has been clinically completed, the 
database is locked, and final analyses are complete with the exception of exploratory endpoints. 
The safety, PK, and PD data described herein will be incorporated into a clinical study report. 
This study was a single-center, randomized, double-blind, placebo-controlled, single ascending 
dose study to evaluate the safety, tolerability, PK, and PD of PB2452 with and without ticagrelor 
pretreatment in healthy male and female subjects ages 18-50 years. Ten sequential dose cohorts 
were evaluated. Cohorts 1, 2, and 3 assessed 30 min IV infusions of PB2452 without ticagrelor 
pretreatment while Cohorts 4-10 assessed IV infusions of PB2452 after ticagrelor pretreatment. 
PB2452 was found to provide rapid, dose- and infusion duration-dependent reversal of the 
antiplatelet effects of ticagrelor. Detailed descriptions of the clinical safety, PK, and PD profiles 
of PB2452 may be found in the IB for PB2452. 
PB2452 appeared generally safe and well tolerated across a dose range of 0.1 g to 18 g. A total of 
30 adverse events occurred after initiation of PB2452 or placebo and were reported by 19 of the 
64 volunteers (30%). Of the 48 volunteers who received PB2452, 17 (35%) reported 27 adverse 
events; of the 16 volunteers who received placebo, 2 (12%) reported 3 adverse events. There 
were no dose-limiting toxic effects or infusion-related reactions (IRRs). There were no deaths or 
adverse events that led to discontinuation of the trial drug. Of the 48 volunteers who received 
PB2452, 21 (44%) had detectable anti-drug antibodies in blood obtained 7 and/or 28 days after 
exposure; 15 (31%) had been positive before they received PB2452 and 6 (12%) became positive 
after they received PB2452, albeit with low titers of 40 (in 5 volunteers) and 160 (in 1 
volunteer). Of the 16 volunteers who received placebo, 3 (19%) were positive for anti-drug 
antibodies, with 2 (12%) having preexisting antibodies. The presence of these antibodies had no 
observed effect on the safety or efficacy of PB2452 (Bhatt DL, 2019). 
The PD profile of PB2452 demonstrated that for subjects receiving steady-state ticagrelor, IV 
infusion of PB2452 (3 to18 g) restored platelet activity to approximately 100% of baseline using 
multiple assays of platelet function. The onset of reversal was rapid, occurring at the first 
assessment of platelet function following initiation of PB2452 infusion (30 minutes in cohorts 4- 
6 and 5 minutes in cohorts 7-10). The duration of ticagrelor reversal appeared to be dependent on 
the total dose and infusion duration of PB2452. At this stage of development, other than the 
reversal of ticagrelor effect described above, there are no known drug-drug interaction between 
PB2452 and other approved or investigational drugs. There have been no formal drug-drug 
interaction studies performed to date. 
2.1.4.1 
Clinical Pharmacology and Pharmacokinetics 
The PK profile of PB2452 demonstrated that mean plasma concentrations of PB2452 rapidly 
declined following the end of infusion across all cohorts. In cohorts 1-3 when PB2452 was 
administered as a 30-minute intravenous infusion in the absence of ticagrelor, elimination 
appeared to be biphasic with half-life values ranging from 1.5 to 9.2 hours for the dose range 0.1 
g to 1 g. In the presence and absence of ticagrelor, geometric mean observed maximum plasma 
concentration (Cmax) values and geometric mean area under the plasma concentration versus time 
curve (AUC) values of total PB2452 from time zero extrapolated to infinity (AUC0-∞) appeared 
to increase in a dose-proportional manner. The inter-individual variability (geometric mean 
coefficient of variation [CV%]) for Cmax and AUC0-∞ was low, ranging from 4.8% to 28.9% 
across Cohorts 1-3. 

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PB2452 produced an increase in the mean total plasma concentrations of ticagrelor and TAM 
compared to placebo, and this effect was dependent upon the dose of PB2452. Among volunteers 
who received placebo and ticagrelor pretreatment, the mean AUC0–48 for ticagrelor ranged from 
4730 to 6750 hours times nanograms per milliliter. Among volunteers who received 30-minute 
infusions of PB2452 and ticagrelor pretreatment, there was a dose-dependent increase in mean 
AUC 0–48 for ticagrelor by a factor of 2.0 to 5.6. Among volunteers who received 18 g of PB2452 
with longer infusions and ticagrelor pretreatment, the mean AUC 0–48 for ticagrelor was increased 
by a factor of 5.6. This increased ticagrelor exposure probably reflected tight binding between 
PB2452 and ticagrelor and redistribution of extravascular ticagrelor into the vascular 
compartment. 
Ticagrelor and TAM are known to be primarily metabolized hepatically with less than 1% of the 
dose cleared renally (BRILINTA (ticagrelor), 2021). As expected, PB2452 increased the renal 
clearance of ticagrelor and TAM in a dose-dependent manner presumably reflecting the 
clearance of PB2452 complexed with ticagrelor and TAM via the kidney. This is consistent with 
the preclinical PK data (Section 2.1.3.3) and is also consistent with the prediction that PB2452 
changes the primary route of ticagrelor elimination from hepatic to renal. 
2.1.5 
Benefit:Risk Assessment 
The first-in-human study of PB2452 in healthy volunteers (PB2452-PT-CL-0001) demonstrated 
that PB2452 appears to be generally safe and well tolerated when administered intravenously 
across a dose range of 0.1-18 g. The healthy volunteers who were 18-50 years were not expected 
to, nor received any benefit from administration of PB2452. Platelet function analyses showed 
that PB2452 delivered immediate and sustained reversal of ticagrelor, occurring as early as 5 
minutes after initiation of PB2452 infusions and lasting for 20-24 hours. Rapid and sustained 
ticagrelor reversal by PB2452 may provide clinically significant (CS) benefit in patients taking 
ticagrelor who experience serious bleeding or require urgent surgical procedures by supporting 
rapid hemostasis or prevention of procedure-related bleeding. 
Although treatment emergent adverse events associated with PB2452 have been mostly mild and 
infrequent with no infusion-related or hypersensitivity reactions observed in the Phase 1 study in 
healthy volunteers and in the ongoing Phase 2A study (PB2452-PT-CL-0002) in subjects 50-80 
years old, there remain potential risks related to PB2452. Infusion-related reactions (IRRs), 
infusion site reactions, and hypersensitivity-type reactions can result from exposure to 
recombinant protein drugs like PB2452 administered intravenously (IV). These risks are 
considered low and have not been observed to date and may be mitigated by predefined 
exclusion criteria and by close monitoring during and after administration. Risks may also be 
mitigated by premedication prior to receiving PB2452 which will be implemented if any study 
subject develops a Grade ≥2 IRR. Development of antibodies to PB2452 might pose issues with 
a subsequent dose of PB2452, either an amnestic immunological reaction or, in the case of 
neutralizing antibodies, reduced efficacy. However, it is considered unlikely that re- 
administration will occur. The risk of other rare unexpected adverse reactions to PB2452 is 
considered very low but cannot be excluded. 
As in previous studies with PB2452, the Phase 2B (Protocol PB2452-PT-CL-0003) study 
population will be administered low-dose ASA and ticagrelor which carries a risk of bleeding. 
The bleeding risk in study subjects is considered very low because the total duration of dual 
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bleeding will be excluded from participation in the study. Among patients who take ticagrelor for 
therapeutic benefit, there is a potential risk of disease-related thrombosis upon reversal of the 
antiplatelet effect of ticagrelor. The safety profile of PB2452 in this patient population will be 
evaluated in future clinical studies and by thorough monitoring of hemostasis parameters. In the 
current study, three platelet function assays and multiple platelet agonists will be used to monitor 
platelet function which will demonstrate both the reversal profile of PB2452 and also a potential 
prothrombotic rebound increase in platelet function. The risk of a platelet rebound effect is 
considered low and has not been observed in the Phase 1 (PB2452-PT-CL-0001) study and 
Protocol Phase 2A (PB2452-PT-CL-0002) study. 
Based on all available information concerning the risks of PB2452 and the precautions included 
in this clinical study, the risks are considered acceptable to enroll subjects 50-80 years old for 
investigation of ticagrelor reversal by PB2452. 
2.1.5.1 
Additional Risks 
PB2452 lacks an endogenous target, and in a human tissue panel cross-reactivity study utilizing 
PB2452-FITC, no staining was observed in any of the human tissues on the panel. Therefore, due 
to high binding specificity, the risk of off-target effects is considered low. 
The 14-day extended single-dose non-clinical GLP toxicology study conducted in rats with 
PB2452 doses up to 2000 mg/kg did not identify a clinically relevant safety concern. The 
maximum human dose proposed for Phase 1 was approximately 250 mg/kg. 
Potential risks based on class effects 
• Infusion site reactions: 
Possible risks associated with IV administration are redness, swelling, pain, induration, 
and sometimes infection at the administration site 
• Anaphylactic-type and infusion reactions: 
Although anaphylactic-type reactions are considered of importance due to their serious 
nature, they are rare. Acute anaphylactic reactions may include cardio-respiratory 
distress, chest pain, hypotension, dyspnea, bronchospasm, respiratory failure, urticaria, 
pruritus, angioedema, nausea, vomiting, diarrhea, hypotonia, and collapse 
• Immunogenicity: 
Development of antibodies to PB2452 might pose issues with a subsequent dose of 
PB2452, either an amnestic immunological reaction or, in the case of neutralizing 
antibodies, reduced efficacy. However, it is considered very unlikely that 
readministration will be required 
• Thrombosis: 
There is a risk of thrombosis following reversal of ticagrelor’s therapeutic antiplatelet 
effect in patients with clinical conditions at very high risk of thrombosis, such as recent 
ACS or recent placement of a coronary stent 
• Bleeding (aspirin and/or ticagrelor only): 
Volunteers receiving pre-treatment with both aspirin and ticagrelor have a risk of 
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2.1.5.2 
Benefits 
Other than frequent assessments of overall health occurring during the screening, treatment, and 
follow-up periods of this study, there are no expected benefits from participation in this study. 
2.2 
Study Rationale 
Current recommendations for management of bleeding in patients treated with antiplatelet 
therapies are suboptimal; they are mostly supportive and non-specific. Platelet transfusion, while 
useful for some antiplatelet agents, exposes patients to the known risks of blood products. 
Further, the efficacy of transfused platelets may be limited by exposure to circulating antiplatelet 
drug or metabolites if present. Moreover, it has been demonstrated that platelet transfusions do 
not reverse the effects of ticagrelor (Dalen M, 2013; Godier A, 2015; Maillard J, 2015; Teng, 
2016). 
An agent to rapidly reverse the anti-platelet effects of ticagrelor, and its active metabolite TAM, 
would fulfill an important unmet clinical need for those ticagrelor-treated patients: 
• who have major or life-threatening bleeding 
• who require urgent surgery or intervention associated with a high risk of bleeding 

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3 
OBJECTIVES AND ENDPOINTS 
The primary hypothesis for this trial is to evaluate whether intravenous PB2452 will result in 
reversal of the antiplatelet effects of ticagrelor. 
3.1 
Primary Objective and Endpoint 
Primary Objective: 
To demonstrate reversal of the antiplatelet effects of ticagrelor with intravenous PB2452 vs. 
placebo. 
 Primary Endpoint: 
The primary study endpoint is the minimum % inhibition of platelet reactivity unit (PRU) 
assessed by VerifyNow™ PRUTest™ (VerifyNow™, 2016) within 4 hours after the initiation of 
study drug. Percent inhibition of PRU is calculated as 100 * [(PRUbsl – PRUtrt)/PRUbsl] where 
PRUbsl refers to the PRU value measured before treatment with ticagrelor and PRUtrt refers to the 
PRU value measured posttreatment with the study drug. 
 Primary Endpoint Justification: 
VerifyNow™ PRUTest™ is an effective and widely used clinical assay for assessment of 
ticagrelor’s suppression of platelet function. It is a point-of-care assay that quantitatively 
assesses P2Y12 dependent platelet aggregation. Degree of aggregation is reported on a PRU scale 
of 0-350. The lower limit of normal (LLN) platelet function is 180 PRU based on the assay’s 
labeling. 
Primary Endpoint Analysis: 
Please refer to Section 9 of this protocol for further details. 
3.2 
Secondary Objectives and Endpoints 
3.2.1 
Secondary Objectives: 
1. To evaluate the safety, tolerability, and immunogenicity of PB2452 in subjects treated with 
ticagrelor 
2. To evaluate the pharmacokinetic (PK) profile of intravenous PB2452, ticagrelor, and its 
active metabolite (TAM) in blood and urine 
3. To evaluate additional parameters of PB2452-mediated ticagrelor reversal by assessment of 
PRU using the VerifyNow™ PRUTest™ (VerifyNow™, 2016) P2Y12 assay and assessment 
of the platelet reactivity index (PRI) using the Vasodilator-stimulated phosphoprotein 
(VASP) assay 
3.2.2 
Secondary Endpoints: 
1. Safety, tolerability and immunogenicity will be assessed by monitoring and recording of 
adverse events (AEs), including infusion site and systemic infusion reactions, clinical 
laboratory test results (hematology, coagulation, serum chemistry, and urinalysis), vital sign 
measurements (systolic and diastolic blood pressures, body temperature, respiratory rate, and 
heart rate), 12-lead electrocardiogram (ECG) results, physical examination findings, and 
immunogenicity 

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2. Plasma concentrations of total PB2452, unbound PB2452, total ticagrelor, total TAM, 
unbound ticagrelor, and unbound TAM, will be assessed at predetermined timepoints 
PK parameters for PB2452 include: 
• Observed maximum plasma concentration (Cmax) 
• Area under the plasma concentration versus time curve (AUC) from time zero to the time 
of the last quantifiable concentration (AUC0-t) 
• Time to reach the observed maximum plasma concentration (Tmax) 
• AUC from time zero to 24 hours post-dose (AUC0-24) 
• AUC from time zero to 48 hours post-dose (AUC0-48) 
• Area under the plasma concentration versus time curve (AUC) from time zero to the time 
of the end of the dosing period (AUC0-tau) 
• AUC from time zero extrapolated to infinity (AUC0-∞; if data permit) 
• Terminal elimination half-life (t½; if data permit) 
• Clearance (CL; if data permit) 
• Volume of distribution (Vd) 
PK parameters for ticagrelor/TAM include: 
• Cmax 
• AUC0-last 
• Tmax 
• AUC0-24 
• AUC0-48 
• AUC0-tau 
• AUC0-∞; if data permit 
• t½; if data permit 
Urine PK endpoints: 
Pooled urine samples to assess urine PB2452, ticagrelor, and TAM concentrations will be 
collected according to predefined intervals. 
PK parameters for PB2452, ticagrelor, and TAM concentrations in urine for all subjects in the 
PK population to be calculated are: 
• Total amount of drug excreted in urine at 24 hours (Ae24) and at 48 hours (Ae48) 
• ae from time t1 to t2 hours including 0 to 6, 6 to 12, 12 to 24 and 24 to 48 hours (Aet1-t2) 
• Fraction excreted in urine from 1 to 24 hours (Fe24) and from 1 to 48 hours (Fe48) 
• Renal clearance (CLr) for 24 hours 

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3. Additional reversal endpoints: 
• Minimum %inhibition of PRI assessed by VASP within 4 hours after the initiation of 
study drug. %inhibition of PRI is calculated as 100 * [(PRIbsl – PRItrt)/PRIbsl]. PRIbsl 
refers to the PRI value measured before treatment with ticagrelor and PRItrt refers to the 
PRI value measured posttreatment with the study drug 
• PRU AUC for the first 4 hours 
• Proportion of subjects with normalized platelet reactivity units within 4 hours after the 
initiation of study drug Normalized platelet reactivity is defined as PRU ≥ 180. 
• Proportion of subjects with ≥60%, ≥80%, and 100% of PRU response rate within 4 hours 
after the initiation of study drug. A PRU response is defined as the 100 *(PRUtrt/PRUbsl) 
• Time to 60%, 80%, 100% of PRU response rate within 4 hours after the initiation of 
study drug 
• Duration of 80% and 100% response rate by PRU 
• PRI AUC for the first 4 hours 
• Proportion of subjects with ≥60%, ≥80%, and 100% of PRI response rate within 4 hours 
after the initiation of study drug. A PRI response is defined as the 100 * (PRItrt/PRIbsl) 
• Time to 60%, 80%, 100% PRI response rate within 4 hours after the initiation of study 
drug 
• Duration of 80% and 100% response rate by PRI 
• Percent reversal of PRU within 4 hours after the initiation of study drug. Percent reversal 
is calculated as 100 *[(PRUtrt – PRUpre-trt)/(PRUbsl – PRUpre-reversal)]. PRUpre-trt is defined as 
the PRU value prior to administration of study drug 
• Percent reversal of PRI within 4 hours after the initiation of study drug. Percent reversal 
is calculated as 100 * [(PRItrt – PRIpre-trt)/(PRIbsl – PRIpre-trt)]. PRIpre-reversal is defined as the 
PRU value prior to administration of study drug 
3.3 
Other Prespecified Objectives Endpoints 
3.3.1 
Other Prespecified Objectives: 
 
• Assessment of platelet function related biomarkers 
3.3.2 
Other Prespecified Endpoints 
• Circulating levels of P-selectin and other platelet function-related biomarkers at baseline 
and post-initiation of PB2452 
• Proportion of subjects with known single-nucleotide polymorphisms related to P2Y12 
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4 
STUDY PLAN 
4.1 
Study Design 
This phase 2B study is a multi-center, randomized, double-blind, multicenter, placebo-controlled 
study. The study is designed to evaluate the efficacy of PB2452 in reversing the anti-platelet 
effects of ticagrelor as part of a dual antiplatelet regimen and to evaluate the safety and 
tolerability of PB2452 in subjects aged 50-80 years old. 
Approximately 200 subjects between 50-80 years old will be enrolled in the US and other 
countries at the discretion of the Sponsor across 5-15 sites. The subjects will be randomized at a 
ratio of 3:1 receiving either the PB2452 investigational study drug or placebo. Hence, a total of 
approximately 150 subjects will be receiving PB2452 and approximately 50 subjects will be 
receiving placebo. 
All subjects will be administered enteric coated aspirin 81 mg daily for at least 7 days prior to 
initiation of study drug for a total of 8 doses. Ticagrelor tablets will be administered prior to 
initiation of study drug with a 180 mg oral loading dose, followed by 90 mg bid for a total of 5 
doses of ticagrelor. Two hours following the last dose of ticagrelor on morning of Day 1, 
subjects will receive either PB2452 or a placebo administered intravenously (IV) to assess 
reversal at peak ticagrelor plasma concentrations. 
The infusion regimen is as follows: 
• An initial intravenous (IV) bolus infusion consisting of a 6 g of study drug infused over 
10 minutes followed immediately by an additional 6 g loading regimen of PB2452 
infused over 4 hours 
• A maintenance regimen of 6 g infused over 12 hours will immediately follow completion 
of the loading regimen for a total infusion time of approximately 16 hours 
If a subject is taking a moderate or strong CYP3A inhibitor, a 36 g alternative regimen of 
PB2452 will be administered intravenously starting at 2 hours after the final dose of ticagrelor: 
• An initial 12 g bolus of PB2452 infused over 10 minutes followed immediately by an 
additional 12 g loading infusion of PB2452 over 6 hours 
• A 12 g maintenance infusion of PB2452 administered over 18 hours will immediately 
follow completion of the loading regimen for a total infusion time of 24 hours and 10 
minutes 
No interim analysis or subsequent long-term extensions are planned. 
4.2 
Design Rationale 
This study uses a placebo-control to estimate the effect relative to the placebo response that 
would occur due to the decrease of ticagrelor over time. The double-blind nature of the design 
will allow for unbiased safety assessment. The use of subjects pre-treated with ASA and 
ticagrelor allows for assessment of suppressed platelet function prior to study-drug treatment 
which is required to calculate reversal. 

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5 
POPULATION 
Approximately 200 male or female subjects between 50 and 80 years old who are in good 
general health or who have chronic, stable, and generally well-controlled medical conditions will 
be evaluated across centers in the United States (US) and Canada. The Sponsor reserves the right 
to include sites in other countries if deemed necessary. 
If a subject is unable to comply with any of the study procedures before study drug dosing on 
Day 1, the subject’s participation in the study will be re-evaluated by the Investigator in 
consultation with the Sponsor; the subject may not be eligible to participate in the study. 
1. Subjects must be willing to remain at the study site at a minimum from Day 1 through 
Day 3 i.e. 48 hours following study drug dosing on Day 1 
2. Subjects must be willing to return to the clinic for Follow-up visits on Day 7 and Day 
35±3 
Note: If needed and at the discretion of the Investigator, a subject may remain in the 
study facility beyond the scheduled Day 3 discharge to accommodate Day 7 and Day 
35+3 follow-up visits 
3. Subjects must refrain from smoking or using nicotine or nicotine-containing products and 
drinking alcohol-containing products, while confined to study site 
4. Subjects must be willing to maintain their usual caloric intake and to consume only food 
and beverages provided by the clinical site while confined to the study site 
Approximately 250-300 subjects may be screened to meet the target enrollment number of 200 
subjects. Additional countries may be added at discretion of the Sponsor. 
5.1 
Definitions 
Subjects officially enter the Screening Period following provision of signing an informed consent 
(written or verbal). 
A screen failure is a consented subject who has been deemed ineligible based on 1 or more 
eligibility criteria or who has withdrawn consent prior to treatment assignment. 
Screen failures may be rescreened upon confirmation with Sponsor. Screen failures may be 
rescreened once, upon review and confirmation from the Sponsor. For examples, subjects that 
have out of range laboratory results and vital sign measurements may have repeat assessment(s) 
during the Screening period. 
An enrolled subject is one who has provided written or verbal informed consent. 
A randomized subject is one who has been randomized to a treatment group on Day 1. 
5.2 
Inclusion Criteria 
Subjects must meet all the following criteria prior to randomization: 
1. The subject provides written or verbal informed consent (in-person or remotely as applicable 
and per local requirements) and agrees to comply with all protocol requirements throughout 
study participation 
2. The subject is male or female between >50 and <80 years of age 

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3. The subject has a body mass index between 18 and 35 kg/m2 and a weight of ≥ 50 kg but ≤ 
120 kg, inclusive, on first day of screening 
4. The subject is considered by the Investigator to be in good general health as determined by 
medical history, clinical laboratory test results, vital sign measurements, 12-lead ECG results, 
and physical examination findings at Screening and up to the time of randomization. Subjects 
with chronic, stable, and well-controlled medical conditions, are eligible provided they meet 
all other inclusion/exclusion criteria. Some examples of stable and well-controlled medical 
conditions include but are not limited to: 
• Hypertension controlled with no more than two antihypertensive drugs 
• Hyperlipidemia (defined with a Screening LDL of <190 mg/dL) 
• Diabetes controlled with diet/exercise or treated with no more than 2 medications and/or 
a Glycosylated Hemoglobin Hgb (HbA1c) ≤8% 
• Remote history of myocardial infarction (> 3 years prior to screening) with no symptoms 
• Mild hepatic enzyme elevation (AST or ALT <1.5 x upper limit of normal (ULN) or total 
bilirubin <1.2 x ULN) 
5. Specific inclusionary laboratory values at Screening and Check-in require the following: 
• Stable white blood cell (WBC) count, platelet count, haemoglobin level with no clinically 
significant abnormality within the normal range as defined by the Investigator 
• Thyroid stimulating hormone (TSH) level within the normal range, as defined by the 
clinical laboratory at screening 
• Prothrombin time (PT) and/or international normalized ratio (INR) levels, plus partial 
thromboplastin time (PTT) and/or activated partial thromboplastin time (aPTT) level less 
than or equal to the upper limit of normal as defined by the clinical laboratory 
6. Subjects taking medications for well-controlled medical conditions must have been on a 
stable dose (meaning no changes in dose) for at least 30 days prior to initiation of study drug 
7. Subjects entering the study: 
i. 
Who are not already taking daily aspirin must be willing to start an 81 mg daily dose 
of aspirin on Day -7 and must document daily dosing until the final dose is administered 
on the morning of Day 1 
ii. 
Who are already taking daily aspirin must be willing to document a daily 81 mg dose 
between Day -7 and Day 1 and must suspend further aspirin dosing until discharge from 
the study on Day 3 
8. Female subjects of childbearing potential must not be pregnant, lactating, or planning to 
become pregnant for 3 months after signing the informed consent, and have a negative serum 
pregnancy test at Screening and Check-in. Female subjects of childbearing potential must use 
2 effective methods of birth control for 3 months after signing the informed consent 
5.3 
Exclusion Criteria 
Subjects will be excluded from the study if they meet any of the following criteria: 

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1. In the opinion of the Investigator there are concern(s) regarding the ability of the subject to 
comply with study procedures and/or follow-up, or, if the subject is not suitable for entry into 
the study 
2. History of any acute or chronic medical disorder expected to decrease the life expectancy of 
the subject to an extent where the subject’s study participation is affected 
3. Any clinically significant acute illness, medical/surgical procedure, or trauma within 4 weeks 
of the administration of study drug or any planned surgical procedure that will occur during 
the study (from Screening through the Day 35+3 follow up visit) 
4. Any clinically significant abnormal findings in physical examination, vital signs, laboratory 
assessments, and ECG parameters identified during Screening or Check-in 
Note: abnormal results may be repeated (locally or centrally) for confirmation immediately 
after the first out of range measurement. Abnormal vital signs may be repeated twice if 
needed, immediately after the first abnormal result and/or after the subject has rested for at 
least 10 minutes 
• Specific vital sign exclusionary criteria occurring after 10 minutes of supine rest are any 
of the following: 
• SBP <100 or >160 mm Hg 
• DBP <40 or >95 mm Hg 
• Resting HR <50 or >100 beats per minute (bpm) 
• Specific exclusionary criteria for ECG parameters at Screening/Check-in or Day 1 are 
any of the following: 
• Prolonged Fridericia-corrected QT interval (QTcF) >450 milliseconds (msec), or 
pause >3 seconds, or family history of long QT syndrome 
5. Any specific contraindication to ticagrelor as described in the Brilinta® prescribing 
information and as described below: 
• History of intracranial hemorrhage, active bleeding, or hypersensitivity or allergic 
reaction to ticagrelor or any component of the product 
• Any history of severe head trauma, intracranial neoplasm, arteriovenous malformation, 
aneurysm, or proliferative retinopathy 
• Any history of intraocular, retroperitoneal, or spinal bleeding 
• Having taken any oral or parenteral anticoagulant, including low molecular-weight 
heparin within 30 days of initiation of study drug 
• Severe hepatic impairment 
• Stool sample testing positive for occult blood within 3 months of Screening or at any 
time during the Screening period 
6. Receiving chronic treatment with nonsteroidal anti-inflammatory drugs including aspirin 
(>100 mg daily), anticoagulants, or other antiplatelet agents that cannot be discontinued 
between the date the informed consent form was signed and the end of the study period 

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7. First positive test result for any hepatitis B (unvaccinated), hepatitis C, or human 
immunodeficiency virus types 1 or 2 antigen or antibodies at screening 
8. Has received another investigational drug (defined as a small molecule or biologic compound 
which has not been approved for marketing) within 30 days of the administration of study 
drug in this study or within 5 half-lives of the experimental medication, whichever is longer 
9. History of severe or ongoing allergy/hypersensitivity to any biologic therapeutic agent 
10. Involvement with any PhaseBio or study site employee or their close relatives (e.g., spouse, 
parents, siblings, or children whether biological or legally adopted) 
11. Previously received PB2452 
5.4 
Exceptions to Eligibility Criteria 
Approval of protocol deviations to recruitment and enrollment criteria, also known as protocol 
waivers or exemptions, are not permitted. 

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6 
STUDY CONDUCT 
The Investigator will agree to perform all aspects of this study in accordance with the ethical 
principles that have their origin in the Declaration of Helsinki, ICH E6(R2): GCP, the protocol, 
and all national, state, and local laws or regulations. 
This Phase 2B study will consist of: 
• A Screening period (Days –45 to –4) 
• Pretreatment with ASA 81mg daily (Day -7 to Day 1) 
• Check-in Day–admission to study clinic (Day -3 to Day 3) 
• Pretreatment and ticagrelor treatment (Day -2 to Day 1) 
• On-site Randomization/Treatment (Day 1) 
• 2-Day on-site Follow-up period (Day 1 to Day 3) 
• Day 7 Follow-up visit (Day 7) 
• Final Follow-up visit on (Day 35+3) 
Plasma samples for PD and PK analysis of PB2452, ticagrelor and its active metabolite, (TAM) 
will be collected at Day -2, pre-dose (within 10 minutes prior to start of infusion), Day 1 and Day 
2 at 5, 10 and 30 minutes and 1, 2, 4, 8, 12, 20, 24, 36, 48 hours following initiation of the study 
drug infusion. Plasma PK samples will also be collected on Day 7, and Day 35+3 after initiation 
of study drug infusion. 
Safety and tolerability will be carefully monitored through the study. The existence of anti-drug- 
antibodies will be assessed in all subjects at Day -3, Day 1 (randomization), Day 7 and 35+3 
following administration of study drug at 3 months and then every 6 months until return to 
baseline. 
The estimated duration of the study for each subject, excluding screening, is approximately 35+3 
days. 
6.1 
Study Procedures 
After signing the ICF, subjects will have study procedures at the time points specified in the 
Schedule of Events (Appendix 3). 
Screening (Days -45 to -4) 
• Subjects sign informed consent 
• Inclusion/Exclusion criteria 
• Demographics 
• Medical history 
• Urine drug screen 
• Urine alcohol screen 
• Serum pregnancy test for women of childbearing potential 

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• Serology tests 
• Stool occult blood test 
• Full physical examination, including height and weight 
• Vital signs measured including SBP and DBP, body temperature, respiration rate (RR), 
and heart rate (HR) 
• 12-lead Electrocardiogram (ECG) 
• Clinical laboratory tests including hematology, chemistry, coagulation, and urinalysis 
• Adverse Events (AEs)/serious adverse events (SAEs) collected 
• Concomitant medications within -45 Days before subject provides informed consent. To 
include all prescription, over the counter (OTC) and supplements 
Note: For subjects who are already taking aspirin they must be willing to document a 
daily 81 mg dose between Day -7 and Day 1 and must suspend further aspirin dosing 
from Day 1 until discharge from the clinical facility on Day 3 
Screening (Day -7) 
• Start ASA 81mg (enteric coated) daily (QD) 
• Subjects who enter the study already taking ASA 81 mg daily will document a daily 
ASA 81 mg dose) 
• AEs/SAEs collected 
• Concomitant medications 
Screening (Day -6) 
• ASA 81mg QD 
Screening (Day -5) 
• ASA 81mg QD 
Screening (Day -4) 
• ASA 81mg QD 
Check-in/Pretreatment – Admission to Study Clinic - Baseline – Outpatient (Day -3) 
• ASA 81mg QD 
• Inclusion/Exclusion criteria 
• Urine drug screen 
• Urine alcohol screen 
• Serum pregnancy test for women of childbearing potential 
• Admission to study clinic 
• Full physical examination and querying the subject for changes from baseline 

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• Vital signs measured including SBP and DBP, body temperature, RR, and HR 
• Clinical laboratory tests including hematology, chemistry, coagulation, and urinalysis 
• Serum immunogenicity 
• AEs/SAEs collected 
• Concomitant medications 
Pretreatment - Baseline (Day -2) – May involve admission to study clinic as per study site’s 
policy 
• ASA 81mg QD 
• Urine sample for PK ticagrelor/AR-C124910XX within 60 minutes prior to the first 
ticagrelor dose 
• Ticagrelor administration 
• Single dose oral 180 mg (a.m.) 
• Single dose oral 90 mg 12 hours later (p.m.) 
• Blood sampling for PK plasma (Plasma PB2452/Plasma ticagrelor/TAM/Unbound 
plasma ticagrelor/TAM) within 60 minutes prior to the first ticagrelor dosing 
• Blood sampling for PD (PRU/VASP) within 60 minutes prior to the first ticagrelor dose 
• AEs/SAEs collected 
• Concomitant medications 
Pretreatment - Baseline (Day -1) – May involve admission to study clinic as per study site’s 
policy 
• ASA 81mg QD 
• No less than 2 hours before study drug is started 
• Inclusion/Exclusion criteria reconfirmed 
• 12-lead ECG 
• Local clinical laboratory tests including hematology, chemistry, coagulation, and 
urinalysis 
• Ticagrelor administration 
• Single dose oral 90 mg (a.m.) 
• Single dose oral 90 mg (p.m.) 
• Platelet biomarker sample collection (3.2% Na Citrate plasma tube) 
Note: a single Qiagen PAXgene DNA tube per subject may be collected at any 
convenient sampling timepoint throughout the study 
• AEs/SAEs collected 

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• Concomitant medications 
In-House Treatment – Randomization (Day 1) – Admission to study clinic 
• ASA 81mg QD 
• Approximately 2 hours prior to study drug administration (PB2452/placebo) 
• Vital signs measurements SBP, DBP, body temperature, RR, HR measured 30 to 60 
minutes prior to initiation of study drug (PB2452/placebo) and at 15+5 minutes, 30+10 
minutes, 45+10 minutes, 60+15 minutes and 24 hours+15 minutes, 48 hours+15 minutes 
hours following initiation of study drug infusion 
• 12-lead ECG within one hour before study drug (PB2452/placebo), after bolus, (10 
minutes), end of infusion (16 hours and 10 minutes) post initiation of the study drug 
(PB2452/placebo) 
• Serum immunogenicity blood sample 
• Ticagrelor administration 
• Single dose oral 90 mg (a.m.) 
• 2 hours+15 minutes prior to study drug administration (PB2452/placebo) 
• Review of lab results of Day -1 and the vital sign assessments of Day 1 prior to 
randomization to confirm eligibility 
• Randomization 
• Administration of PB2452 or placebo at Hour 0 
• Blood sampling for PK plasma (Plasma PB2452/Plasma ticagrelor/TAM/Unbound 
plasma ticagrelor/TAM) within 10 minutes prior to initiation of PB2452/placebo infusion 
(Hour 0), and 5, 10, 30 minutes, 1, 2, 4, 8, 12, 20, and 24 hours after initiation of study 
drug infusion 
• Blood sampling for PD sampling (PRU/VASP) within 10 minutes prior to study drug 
(PB2452/placebo) infusion at hour 0 and at 5, 10, 30 minutes and 1, 2, 4, 8, 12, 20, and 
24 hours after initiation of study drug (PB2452/placebo) 
• Pooled urine sample for PK ticagrelor/AR-C124910XX at 0 to 6, 6 to 12 and 12 to 24 
hours after the initiation of the study drug infusion 
• Infusion site assessment to be done within 15 minutes prior to the initiation of the 
PB2452/placebo infusion at Hour 0 and at 1, 3, and 24 hours after initiation of 
PB2452/placebo infusion 
• AEs/SAEs collected 
• Concomitant medications (new medications and changes in dosing of previously reported 
medications) 
In-House Treatment (Day 2) 

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• Vital signs measurements at 48 hours+15 minutes following initiation of study drug infusion 
as per Schedule of Events (Appendix 3) 
• 12-lead ECG at 24 hours (+30 minutes) post initiation of study drug (PB2452/placebo) 
infusion 
• Clinical laboratory tests including hematology, chemistry, coagulation, and urinalysis 
• Blood sampling for PK plasma (Plasma PB2452/Plasma ticagrelor/TAM/Unbound plasma 
ticagrelor/TAM) 36 and 48 hours after initiation of study drug (PB2452/placebo) 
• Blood sampling for PD sampling (PRU/VASP) 36 and 48 hours after initiation of study drug 
(PB2452/placebo) 
• Pooled urine sample for PK ticagrelor/AR-C124910XX at 24 to 48 hours after the initiation 
of the study drug infusion 
• Platelet biomarker sample collection (3.2% NaCitrate plasma tube) 
Note: a single Qiagen PAXgene DNA tube per subject may be collected at any convenient 
sampling timepoint throughout the study 
• Infusion site assessment at 48 hours after initiation of PB2452/placebo infusion 
• AEs/SAEs collected 
• Concomitant medications (new medications and changes in dosing of previously reported 
medications only) 
In-House Treatment (Day 3) 
• Brief physical examination and querying the subject for changes from baseline 
• Vital signs measurements (SBP, DBP, RR and HR) 
• Stool occult test (local or central laboratory) which may be completed on Day 2 if needed 
• Blood sampling for PK plasma (Plasma PB2452/Plasma ticagrelor/TAM/Unbound 
plasma ticagrelor/TAM) 
• Blood sampling for PD sampling (PRU/VASP) 48 hours after initiation of study drug 
(PB2452/placebo) 
• Pooled urine sample for PK ticagrelor/AR-C124910XX at 24 to 48 hours after the 
initiation of the study drug infusion 
• Infusion site assessment 
• May repeat clinical laboratory tests (hematology, chemistry, coagulation, and urinalysis) 
if considered clinically significant by the Investigator based on Day 2 lab results 
• AEs/SAEs collected 
• Concomitant medications (new medications and changes in dosing of previously reported 
medications) 
• Subjects discharged from study site/clinic 

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• If needed and at the discretion of the Investigator, a subject may remain in the study 
facility beyond the scheduled Day 3 discharge to accommodate Day 7 and Day 35+3 
follow-up visits 
Out-patient, Return to Study Site, Follow-up (Day 7) OR In-House if the Subject Remained 
at the Study Site until Day 7 
• Brief physical examination and querying the subject for changes from baseline 
• Vital signs measurements (SBP, DBP, RR, temperature and HR) 
• 12-lead ECG 
• Blood sampling for PK plasma (Plasma PB2452/Plasma ticagrelor/TAM/Unbound 
plasma ticagrelor/TAM) 
• Platelet biomarker sample collection (3.2% Na Citrate plasma tube) 
Note: a single Qiagen PAXgene DNA tube per subject may be collected at any 
convenient sampling timepoint throughout the study 
• Serum immunogenicity 
• Infusion site assessment 
• Clinical laboratory tests including hematology, chemistry, coagulation, and urinalysis 
• AEs/SAEs collected 
• Concomitant medications (new medications and changes in dosing of previously reported 
medications only) 
Out-patient, Return to Study Site, Follow-up, End of Study (Day 35±3) OR In-House if the 
Subject Remained at the Study Site until Day 35+3 
• Serum pregnancy test for women of childbearing potential only 
• Full physical examination, including height and weight 
• Vital signs measurements (SBP, DBP, temperature, RR and HR) 
• 12-lead ECG 
• Clinical laboratory tests including hematology, chemistry, coagulation, and urinalysis 
• Blood sampling for PK plasma (Plasma PB2452/Plasma ticagrelor/TAM/Unbound 
plasma ticagrelor/TAM) 
• Platelet biomarker sample collection (3.2% Na Citrate plasma tube) 
Note: a single Qiagen PAXgene DNA tube per subject may be collected at any 
convenient sampling timepoint throughout the study 
• Serum immunogenicity 
• If anti-drug antibodies are detected, then a follow up visit 3 months post end of study 
(i.e. Day 35+3) is required. These samples are to be taken every 6 months until anti- 
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• Infusion site assessment 
• AEs/SAEs collected 
• Concomitant medications (new medications and changes in dosing) 
Out-patient, Return to Study Site, Follow-up, 3 months post EOS (Month 4) – If ADA 
Positive 
• Serum immunogenicity 
• If anti-drug antibodies are detected at EOS visit, then a follow up visit 3 months post 
end of study (i.e. Day 35+3) must be collected 
Out-patient, Return to Study Site, Follow-up, 6 months post last visit (Month 10) – If ADA 
Positive 
• Serum immunogenicity 
• If anti-drug antibodies are detected at the follow up month 4 visit, blood samples are 
to be taken every 6 months until anti-drug antibodies are no longer present or until 
levels return to pre-dose state 
6.1.1 
Screening Period 
6.1.1.1 
Informed Consent Form 
All subjects must provide written or witnessed verbal informed consent prior to participating in 
any Screening evaluations or any other study activities. 
The Investigator or his/her approved designee must explain the nature of the study protocol and 
associated risks to the potential study subject. The potential subject must be allowed sufficient 
time to review the information and to ask questions. The date that the informed consent form is 
signed, a brief description of the consent process (i.e., questions asked by the subject) and the 
name of the individual who obtained the consent will be recorded in the subject’s source 
documentation. A copy of the signed informed consent form will be provided to each subject. 
The date and confirmation that informed consent was obtained will be recorded in the electronic 
case report from (eCRF). 
6.1.1.2 
Demographics and General Medical and Social History 
Subject demographic information and medical history will be recorded at Screening Days (-45 to 
-4). Demographic information will include date of birth, gender, race, and ethnicity. Medical 
history will include medical diagnoses, major surgical procedures within the last 3 years, and 
social history (tobacco, drug, and alcohol use). Findings will be documented in the source 
documentation and eCRF. 
6.1.1.3 
Physical Examination 
A general physical examination completed by trained staff will include at minimum an 
examination of general appearance, skin, eyes, ears, nose, throat, neck/thyroid, lungs, heart, 
upper/lower extremities, lymph nodes, abdomen, musculoskeletal system and neurological 
system. Additional systems will be evaluated as needed. 

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hysical exam findings must be recorded in the source documentation and include the date and 
name of the individual conducting the examination. Physical exam findings will be recorded in 
the eCRF. 
A brief physical examination will include assessment of heart, skin, lungs, cardiovascular 
system, and abdomen, and extremities. Interim physical examinations will be performed at the 
discretion of the Investigator, if necessary, to evaluate AEs or clinical laboratory abnormalities. 
Height and weight will be measured, at Screening and at Day 35±3. 
6.1.1.4 
Height/Weight and Calculation of Body Mass Index 
Height and weight will be measured at Screening and Day 35+3 during the physical examination 
for calculation of body mass index (BMI). BMI will be calculated within the EDC system. 
6.1.1.5 
Standard Vital Signs 
Vital signs will be measured at the time points indicated in the Schedule of Events 
(Appendix 3). Vital sign measurements will include SBP, DBP, body temperature, RR, and HR. 
The subject will have rested in a supine position for ≥10 minutes before all measurements are 
taken. 
Note: Vital signs collected during the initial 60 minutes of infusion of study drug require only the 
SBP, DBP and HR. 
The Investigator will determine whether any of the vital sign measurements are clinically 
significant (CS) or not clinically significant (NCS). Clinical significance is defined as any 
variation in results that has medical relevance and may result in an alteration in medical care 
(e.g., active observation, diagnostic measures, therapeutic measures). If a CS change from 
Screening values is noted, the CS value and reason for clinical significance will be documented 
on the AE page of the eCRF. The Investigator will continue to monitor the subject with 
additional assessments until the value has reached either the reference range or the value at 
Screening or until the Investigator determines follow-up is no longer medically necessary. 
6.1.1.6 
12 Lead Electrocardiogram 
Twelve-lead ECGs will be obtained after the subject has rested in the supine position for ≥10 
minutes at scheduled timepoints or as clinically indicated based on reported AEs or laboratory 
findings, as necessary. 
The Investigator should review and sign the ECG for any immediate issues. 
Electrocardiogram assessments will include comments concerning whether the tracings are 
normal or abnormal, rhythm, presence of arrhythmia or conduction defects, morphology, and any 
evidence of MI, or ST-segment, T-Wave, and U-Wave abnormalities. In addition, measurements 
of these intervals will be reported: RR interval, PR interval, QRS width, and uncorrected QT, 
QTcB, QTcF. The Investigator will determine whether any of the 12-lead ECG results are CS or 
NCS. 
Clinical significance is defined as any variation in results that has medical relevance and may 
result in an alteration in medical care (e.g., active observation, diagnostic measures, therapeutic 
measures). If a CS change from Screening is noted, the CS value and reason for CS will be 
documented on the AE page of the eCRF. The Investigator will continue to monitor the subject 
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values at Screening or until the Investigator determines follow-up is no longer medically 
necessary. 
The study site will provide a calibrated ECG machine for use during the study unless otherwise 
provided by the Sponsor. Site personnel must assess the quality of the ECG to ensure that the test 
was collected appropriately and to repeat the ECG if necessary (i.e., if artifact(s) are present). 
6.1.1.7 
Laboratory Testing 
All scheduled clinical laboratory tests will be performed by Medpace with the exception of Day - 
1 clinical laboratory testing which should be performed locally to provide results prior to 
randomization. Pharmacokinetic and immunogenicity testing will be performed by Frontage 
Labs, Exton, Pennsylvania. Blood will be collected at the time points indicated in the Schedule 
of Events (Appendix 3) and will be prepared using standard procedures defined in the laboratory 
manual. Repeat clinical laboratory tests of scheduled Medpace tests may be performed locally or 
centrally at the discretion of the Investigator, if deemed necessary, to evaluate inclusion and 
exclusion criteria, for urgent safety assessments, or to follow-up on clinical laboratory 
abnormalities. The local clinical laboratory used to perform tests must provide laboratory 
certification and the reference ranges for all clinical laboratory parameters. 
Abnormal clinical laboratory values will be flagged as either high or low (or normal or 
abnormal) based on the reference ranges for each laboratory parameter. The Investigator 
will determine whether any of the abnormal high or low results are CS or NCS. 
Clinical significance is defined as any variation in results that has medical relevance and may 
result in an alteration in medical care (e.g., active observation, diagnostic measures, therapeutic 
measures). If a CS change from the Screening value is noted, the CS value and etiology or reason 
for clinical significance will be documented on the AE page of the eCRF. The Investigator will 
continue to monitor the subject with additional assessments until the values have reached either 
the reference range or the values at Screening or until the Investigator determines that follow-up 
is no longer medically necessary. 
When scheduled procedures overlap at the same time point (see Schedule of Events - Appendix 
3), there must be planning to collect the specific information within the designated time window. 
Accordingly, the importance of these procedures are: 
1. Blood collection (whether for PD, PK, immunology, or safety) should always be 
collected at the designated time point (if possible). However, multiple collections (PD, 
PK, immunology, and safety) may be required at the same time point. Therefore, the 
recommendation is for blood to be drawn in this order: PD, PK, immunology, and safety 
(see relevant lab collection manual(s) from Medpace or MLM Medical Labs for 
additional information related to collection of PD samples). 
2. If time permits, vital sign measurements should be completed just prior to or just after 
blood collection; this may be still be done within the designated window in the Schedule 
of Events (Appendix 3). 
All clinical laboratory data will be evaluated by the Investigator (Principal or physician 
Sub-Investigator) and clinical relevance will be assessed for abnormal values and the assessment 
will be documented on the laboratory report. A copy of the reports will be maintained as part of 
the source documentation. Additionally, a copy of the report may be included with the eCRF. 

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Standard rapid urine drug Screening test kits will be supplied for local testing. The test kit may 
check (but not limited to) for drugs such as cocaine, cannabinoids, opiates, benzodiazepines, 
PCPs, amphetamines, methamphetamines, barbiturates, methadone, alcohol or additional drugs 
not listed. 
6.1.1.7.1 
Serology for HIV, Hepatitis B, and Hepatitis C 
All subjects will be screened for human immune deficiency virus (HIV) type I and II antigen or 
antibodies, hepatitis B, and hepatitis C at screening. Evaluation for HIV seropositivity will 
consist of enzyme-linked immunosorbent assay (ELISA) and, if positive, will be confirmed by 
Western blot analysis. Appropriate counseling will be made available to the subject in the event 
of a positive finding. Notification of state and federal authorities, as required by law, will be the 
responsibility of the Investigator. 
6.1.1.7.2 
Pregnancy Test 
A blood pregnancy test result from either the local or central laboratory is required for female 
subjects of childbearing potential. Results must be negative in order for subjects to be 
randomized in the study. 
6.1.1.7.3 
Follicle-Stimulating Hormone (FSH) Level 
Follicle stimulating hormone level may be performed at Screening using local or central 
laboratory, for confirmation of postmenopausal status as directed by the Investigator. 
6.1.1.7.4 
Lipid Profile 
A lipid profile includes (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], 
low-density lipoprotein-cholesterol [LDL-C], low-density lipoprotein/high-density lipoprotein 
(LDL/HDL) ratio, and triglycerides [TG]). 
6.1.1.7.5 
General Safety Laboratory Testing and Confirmation of Eligibility 
Refer to laboratory manual for processing requirements. Any laboratory result including alcohol 
and drug test results may be repeated or performed locally for clinical follow-up as needed by 
Investigator. 
The following clinical laboratory assessments will be performed: 
Table 2 
List of Clinical Laboratory Assessments 
 
Hematology 
Complete blood count (CBC) with differential 
hematocrit (hct) 
hemoglobin (Hgb) 
mean corpuscular hemoglobin (MCH) 
mean corpuscular hemoglobin concentration (MCHC) 
mean corpuscular volume (MCV) 
mean platelet volume (MPV) 
platelet count 
erythrocyte (red blood cell [RBC]) count 
total and differential leukocyte (white blood cell [WBC]) count 
Serum Chemistry 
alanine aminotransferase (ALT) 
albumin 

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alkaline phosphatase (ALP) 
aspartate aminotransferase (AST) 
bicarbonate 
bilirubin (total and direct) 
blood urea nitrogen (BUN) 
calcium 
chloride 
cholesterol 
total 
high-density lipoprotein (HDL) 
calculated low-density lipoprotein (LDL) 
creatine phosphokinase 
creatinine 
gamma-glutamyl transferase (GGT) 
glucose 
HgbA1C 
lactate dehydrogenase (LDH) 
magnesium 
phosphorus 
potassium 
sodium 
thyroid stimulating hormone (TSH; Screening only) 
total protein 
triglycerides (repeat fasting triglyceride if TG >500) 
uric acid 
Coagulation 
activated partial thromboplastin time (aPTT) 
international normalized ratio (INR) 
partial thromboplastin time (PTT) * 
prothrombin time (PT) # 
Urinalysis 
appearance 
bilirubin 
color 
glucose 
ketones 
leukocyte esterase 
reflex microscopy (at Screening and Check-in only, if dipstick is 
positive for protein or blood value ≥1+); includes 
bacteria 
casts 
crystals 
epithelial cells 
RBCs 
WBCs 
nitrites 
occult blood 
pH 
protein 
specific gravity (SpGr) 
turbidity 
urobilinogen 
Serology (Screening only) 
hepatitis B 
hepatitis C 
human immunodeficiency virus (HIV) 
types 1 and 2 antigen or antibodies 

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Other analyses 
stool for occult blood 
urine drug screen may include (not limited to and may vary based 
on the testing kits provided): 
amphetamines and methamphetamines 
barbiturates 
benzodiazepines 
cannabinoids 
cocaine 
PCPs 
opiates 
methadone 
urine alcohol 
female subjects: 
follicle-stimulating hormone (FSH; Screening only) 
serum pregnancy test (human chorionic gonadotropin) 
6.1.1.7.6 
Calculation of Estimated Glomerular Filtration Rate 
Estimated glomerular filtration rate (eGFR) will be calculated by the central laboratory from 
serum creatinine using the IDMS-Traceable MDRD formula and reported on the eCRF as 
follows. 
Estimated glomerular filtration rate will be calculated by the central laboratory from serum 
creatinine using the IDMS-Traceable MDRD formula as follows. 
Conventional units 
GFR (mL/min/1.73 m2) = 175 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African 
American) 
SI units 
GFR (mL/min/1.73 m2) = 175 x (Scr/88.4)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if 
African American) 
6.1.2 
Randomization 
This is a double-blind placebo controlled trial. For further details on randomization please refer 
to section 7.2.2. 
6.1.3 
Active Treatment Period 
Throughout the study protocol visits are noted by Days. 
All subjects will be pretreated with enteric coated aspirin (81 mg QD for at least 7 days prior to 
randomization), and ticagrelor (180 mg loading dose, followed by 90 mg bid for a total of 5 
doses of ticagrelor). The term “study drug” refers to PB2452/placebo. 
Active: PB2452 is a ticagrelor-specific human monoclonal antibody fragment which binds to 
ticagrelor and TAM with high affinity, thereby reversing the antiplatelet effects of ticagrelor. It 
has no known off-target effects. 
For this study, the investigational product will be supplied either as a lyophilized powder 
requiring reconstitution with sterile water for injection, or as a high-concentration liquid. 
PB2452 18 g intravenous infusion will consist of 6 g infused over 10 minutes followed by a 6 g 
loading dose infused over 4 hours, then a maintenance dose of 6 g infused over the next 12 hours 
immediately following completion of the loading period for a total infusion time of 
approximately 16 hours and 10 minutes. 

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Note that if a subject is taking a moderate or strong CYP3A inhibitor, a 36 g alternative regimen 
of PB2452 will be administered consisting of 12 g infused over 10 minutes followed by a 12 g 
loading dose infused over 6 hours, then a maintenance dose of 12 g infused over the next 18 
hours immediately following completion of the loading period for a total infusion time of 
approximately 24 hours and 10 minutes. 
Placebo: 0.9% sodium chloride IV infusion, to be delivered as an infusion identical to the active 
drug regimens. 
Ticagrelor: Ticagrelor 90-mg oral tablet (immediate release); administered as 180 mg (2 × 90-mg 
tablet) loading dose plus 90 mg every 12 hours for 4 additional doses. 
Aspirin: Enteric costed aspirin 81 mg oral tablet administered daily between Day -7 to the 
morning on Day 1, for a total of 8 tablets given prior to dosing with study medication. 
Subjects may resume aspirin after discharge from the study on Day 3. 
6.1.4 
Safety Follow-up Period 
All AEs must be reported in detail on the appropriate page of the eCRF from the time of consent 
through the date of the EOS Day 35+3. Adverse events must be followed until resolved or stable 
or judged by the Investigator that further follow-up is not required. 
 
6.1.5 
Unscheduled Visits 
Unscheduled visits will be performed as necessary at the discretion of the Principal Investigator 
to follow-up on Adverse Events and safety issues. All details must be captured in source 
documents and eCRF as applicable. 
6.1.6 
End of Study 
All subjects will return to the clinic at Day 35+3 to complete the end of study (EOS) visit. The 
following procedures and assessments will be performed: 
• Serum pregnancy test 
• Physical examination, full, including height and weight 
• Vital signs measured (SBP, DBP, RR, temperature and HR) 
• 12-lead ECG 
• Clinical laboratory tests including hematology, chemistry, coagulation, and urinalysis 
• Blood sampling for PK: plasma PB2452, ticagrelor, and TAM PK 
• Platelet biomarker sample collection (3.2% Na Citrate plasma tube) 
Note: a single Qiagen PAXgene DNA tube per subject may be collected at any 
convenient sampling timepoint throughout the study 
• Serum immunogenicity 
• AEs/SAEs collected 
• Concomitant medication(s) 

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6.1.7 
Long-term Extension 
There is no long-term extension. The trial concludes at the EOS (Day 35+3) visit. 
6.2 
Discontinuation or Withdrawal 
6.2.1 
Individual Subjects 
6.2.1.1 
Treatment Discontinuation 
A subject may withdraw consent and discontinue from the study at any time, for any reason, 
without prejudice to further treatment. Subject participation in the study may be stopped at any 
time at the discretion of the Investigator or at the request of the Sponsor, or if the study is 
terminated. 
The Investigator may withdraw a subject from the study if the subject: 
• Is non-compliant with the protocol 
• Experiences a serious adverse event (SAE) or intolerable adverse event (AE) that, in the 
Investigator’s opinion, requires withdrawal from the study 
• Has laboratory safety assessments that reveal CS hematological or biochemical changes 
from baseline values 
• During the course of the study and through the end of study develops symptoms or 
conditions listed in the exclusion criteria 
• Requires a medication prohibited by the protocol 
• Requests an early discontinuation for any reason 
If a subject experiences a SAE or an intolerable adverse event (AE) that requires discontinuation 
in the opinion of the Investigator or as reported by the subject, then the Investigator may confer 
with the Sponsor regarding disposition of the subject. If a subject is discontinued from treatment 
because of an AE, the event will be followed until it is resolved or until the AE is stable in the 
opinion of the Investigator. 
When a subject withdraws or is withdrawn from the study, the reason(s) for withdrawal will be 
recorded by the Investigator on the relevant page of the electronic case report form (eCRF). 
Whenever possible, any subject who withdraws from the study if willing, should continue to be 
followed according to the protocol. For example, if termination occurs earlier than planned (i.e., 
after a subject has received all or partial study drug infusion) all efforts should be made to ensure 
the remaining protocol visits are completed. If a subject refuses to return for the Follow-up visits, 
the Day 35±3 visit procedures should be completed to the extent possible, and the site should try 
contacting the subject at least 3 times by letter, certified letter, phone call, email or other 
reasonable methods. All attempts to contact subjects and the final status of subjects who fail to 
complete final assessments will be documented in the source documents. 
At the discretion of the Sponsor any subject who withdraws before completing the study, may 
potentially be replaced. Any replacement subject will be assigned to receive the same treatment 
as the subject he or she is replacing. 

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6.2.1.1.1 
Temporary Treatment Discontinuation 
Though not expected, treatment may be discontinued temporarily at the discretion of the 
Investigator. 
6.2.1.1.2 
Permanent Discontinuation of Treatment 
Treatment may be permanently discontinued at the discretion and based on clinical judgment of 
the Investigator. The Investigator is required to inform the Sponsor. 
6.2.1.2 
Withdrawal from Study 
Subjects may withdraw from the study at any time at their own request or they may be 
withdrawn at any time at the discretion of the Investigator or Sponsor for safety, behavioral, or 
administrative reasons. If a subject does not return for a scheduled visit, every effort should be 
made to contact the subject. In any circumstance, every effort should be made to document 
subject outcome, if possible. The Investigator should inquire about the reason for withdrawal and 
request that the subject return for the EOS follow-up visit (complete procedures at final safety 
visit) and follow up with the subject regarding any unresolved adverse events. 
If the subject withdraws from the study and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected. The Sponsor may retain and continue to use any data collected before such withdrawal 
of consent. 
6.2.1.3 
Replacement of Subjects 
Subjects who withdraw from the study and who do not have adequate collection of safety, 
hemodynamic and pharmacokinetic samples for evaluation of safety, PK, and PD profiles may be 
replaced at the discretion of the Sponsor. Any replacement subject will be assigned to receive the 
same treatment as the subject he or she is replacing. 
6.3 
Study Termination 
Although the Sponsor has every intention of completing the study, the Sponsor reserves the right 
to discontinue at any time for clinical or administrative reasons. 
The EOS is defined as the date on which the last subject completes the last visit; this includes the 
EOS visit and any additional long-term follow-up required for monitoring the resolution of an 
AE. The finding may be appended to the Clinical Study Report (CSR) (ICH, E3, 2015). 

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lyophilization stopper, and sealed with flip-off cap overseal. Lyophilized PB2452 is reconstituted 
to 100 mg/mL with sterile water for injection. Concentrated PB2452 liquid is supplied in a 100R 
glass vial at a concentration of 100 mg/mL using a similar container closure system. 
PB2452 must be stored in a secure area (e.g., a locked, secure, temperature-controlled unit) at 
2°C to 8°C (36°F to 46°F) protected from moisture and light with access restricted to necessary 
clinic personnel. The clinical site will be required to keep a temperature log to establish a record 
of compliance with these storage conditions. 
The Investigator will maintain accurate records of receipt of all drug supplies used in this study 
including lot numbers (if applicable) and dates of receipt. In addition, accurate records will be 
kept regarding when and how much drug is dispensed and used by each subject in the study. 
Reasons for departure from the expected dispensing regimen must also be recorded. At the 
completion of the study, to satisfy regulatory requirements regarding drug accountability, all 
drugs will be reconciled and retained or destroyed according to applicable regulations. 
 
7.1.1.2 
Dosing and Administration 
As mentioned in Section 7, dosing for the investigational product will be as follows: 
• PB2452: 18 g intravenous infusion will consist of 6 g (60 mL)infused over 10 minutes 
followed by a 6 g (60 mL) loading dose infused over 4 hours, then a maintenance dose of 
6 g (60 mL) infused over the next 12 hours immediately following completion of the 
loading period for a total dose of 18 g (180 mL) and total infusion time of approximately 
16 hours and 10 minutes. 
If a subject is taking a moderate or strong CYP3A inhibitor, a 36 g alternative regimen of 
PB2452 will be administered consisting of 12 g infused over 10 minutes followed by a 12 
g loading dose infused over 6 hours, then a maintenance dose of 12 g infused over the 
next 18 hours immediately following completion of the loading period for a total infusion 
time of approximately 24 hours and 10 minutes 
• Placebo: 0.9% sodium chloride IV infusion, to be delivered as an infusion identical to the 
active drug regimens 
For short term stability information for PB2452 please refer to the pharmacy manual. 
 
7.2 
Treatment Assignment and Bias Minimization 
Subjects will be randomized to active and placebo treatment in a blinded fashion in order to 
minimize bias with respect to safety assessments, as well as any decisions in exclusions from the 
per-protocol population due to protocol deviations. 
7.2.1 
Treatment Allocation 
Approximately 200 subjects will be randomized to PB2452 and Placebo with an allocation ratio 
of 3:1 resulting in a sample-size of 150 for the PB2452 and 50 for the Placebo arm. 
7.2.2 
Randomization Strategy and Procedure 
This study employs a simple randomization procedure without any stratification. The 
randomization will be employed via a Randomization & Trial Supply Management (RTSM) 
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7.2.3 
Extent and Maintenance of Blinding 
The treatment assignment will not be known to Investigators, research staff, or study subjects. 
The following study procedures will be in place to ensure double-blind administration of study 
treatments. 
This is a double-blind study. Neither the subjects nor the Investigator will be aware of the 
treatment assignment. Blinding will be maintained throughout the study by use of an opaque 
covering over the prepared dosage form to maintain blinding. 
To maintain the blind, only designated pharmacy staff at the study site will have access to the 
randomization code and will prepare each dose for each subject. Except as noted above, all 
members of PhaseBio will remain blinded, except the unblinded Sponsor representative(s) who 
may be contacted in case of emergencies and if it is required to break the blind. 
The study blind will be broken on completion of the clinical study and after the study database 
has been locked. If necessary (e.g., information required for enrolment in a subsequent study), a 
request may be submitted to the Sponsor to receive study treatment assignment for a subject. 
 
7.2.4 
Unblinding Procedures 
 
7.2.4.1 
Planned Unblinding 
A subject may be unblinded in the a SAE, or if there is a medical emergency when the identity of 
the drug must be known to properly treat a subject. In the event of a medical emergency 
requiring identification of the study drug administered to an individual subject, the Investigator 
will make every attempt to inform the unblinded Sponsor contact and/or the Medical Monitor to 
explain the need for breaking the code within 24 hours of performing that task. 
The Investigator will be responsible for documenting the time, date, reason for the code break, 
and the names of the personnel involved. 
7.2.4.2 
Unplanned or Unintentional Unblinding 
During the study, the blind may be broken only in emergencies when knowledge of the subject’s 
treatment group is necessary for further medical management. It is preferred (but not required) 
that the Investigator first contacts the medical monitor or PhaseBio study personnel to discuss 
options before unblinding the subject’s treatment assignment 
Unblinding of individual subjects may occur to ensure appropriate clinical management of a 
subject, for example if an SAE is considered by the Investigator as being causally related to 
study treatment OR in the event of a serious medical condition when knowledge of the study 
treatment is essential for the welfare of the subject as judged by the Investigator. 
All unplanned, emergency unblinding will be considered as a protocol deviation. The date and 
reason for the unblinding must be fully documented. 
 
A subject may continue in the study if that subject’s treatment assignment is unblinded if it 
remains appropriate for them to do so and at the Sponsor’s discretion. 
PhaseBio’s clinical or regulatory staff may request unblinding of thetreatment assignment for 
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or more regulatory agencies, a copy of the report, identifying the subject’s treatment assignment, 
may be sent to Investigators in accordance with local regulations. 
7.3 
Assessment and Verification of Compliance 
Study drug will be received, dispensed and returned to the Sponsor (unused study drug at the end 
of the study) by pharmacist or designee as applicable. Study drug will be accounted for by the 
USDD on a study drug inventory/accountability log and will include: 
• Subject ID 
• Number/time vials removed from storage 
• Date/time dose prepared 
• Amount remaining in inventory 
Inventory records will not be reviewed by the study monitor during routine monitoring visits in 
order to maintain the study blind. In order to ensure accuracy on the drug accountability logs a 
designated individual from the Sponsor will assume this task and will periodically request the 
pharmacist (designee) at the site to provide documentation to PhaseBio Pharmaceuticals, Inc. 
All doses of study drug, placebo, ticagrelor and ASA from the date of site check-in will be 
administered at the clinical site under direct observation of clinic personnel and recorded in the 
eCRF. Subjects will be required to document ASA use from Day -7 to Day 1 and provide the 
diary to the study staff upon check-in. 
The date, time, and actual dose received of study drug or placebo infusion, ticagrelor and ASA 
dosing will be recorded on the appropriate pages of the eCRF. If a subject was scheduled to 
receive any of these drugs and did not, the reason for the missed or partial dose will be recorded 
in the eCRF. 
7.4 
Concomitant Therapies 
Concomitant medications are defined as all medications taken from -45 days prior to date of 
informed consent, to Day 35+3. This is to include all medication including prescription, 
supplements, over the counter (OTC). New and changes to medications are captured at every 
visit until Day 35+3. 
Concomitant medications will be coded using the latest version of the World Health Organization 
Drug Dictionary (WHO-DD). 
7.4.1 
Prohibited Therapies 
Subjects are prohibited from taking any new prescription or over the counter (OTC) medications 
or nutritional supplements from Day -30 thru Day 3. Acetaminophen up to 2 g/day may be taken 
as needed. ). 
 
7.4.2 
Permitted Therapies 
In addition to study-required medications specified in the protocol, subjects may take 
medications to treat chronic baseline conditions, hormonal birth control and/or acetaminophen up 
to 2 g/day. If new prescription drug therapy is indicated due to an AE, a joint decision will be 
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study based on the time the new medication is to be administered, its pharmacology and PK, and 
whether the use of the medication will compromise the subject’s safety or interpretation of the 
data. It is the Investigator’s responsibility to ensure that details regarding the medication are 
accurately recorded in the eCRF. 

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8 
SAFETY MONITORING 
All observed or volunteered adverse events regardless of treatment group or suspected causal 
relationship to the study drug will be reported as described in the following sections. 
For all adverse events, the Investigator must pursue and obtain information adequate both to 
determine the outcome of the adverse event and to assess whether it meets the criteria for 
classification as a serious adverse event requiring immediate notification to PhaseBio 
Pharmaceuticals, Inc. For all adverse events, sufficient information should be obtained by the 
Investigator to determine the causality of the adverse event. The Investigator (Principal or 
physician Sub-Investigator) is required to assess causality. For all adverse events follow-up by 
the Investigator (delegate) is required until the event or its sequelae resolve or stabilize or judged 
by the Investigator to be not clinically significant (NCS). 
 
8.1 
Definitions 
Adverse event – An AE is any untoward medical occurrence associated with the use of an 
intervention in humans whether or not it is considered intervention-related. This may include 
worsening of a pre-existing medical condition (e.g., diabetes, congestive heart failure, 
rheumatoid arthritis, psoriasis) that occurs at any time after signing of the informed consent (IC). 
Examples of adverse events include, but are not limited to: 
• Clinically significant abnormal test findings 
• Clinically significant signs and symptoms 
• Clinically relevant changes in physical examination findings 
• Hypersensitivity 
• Progression/worsening of an underlying disease 
Additionally, AE reporting may also include signs or symptoms resulting from: 
• Drug overdose 
• Drug abuse 
• Drug dependency 
• Drug withdrawal 
• Drug misuse 
• Drug interactions 
• Exposure during pregnancy 
• Exposure via breast-feeding 
• Medication error 
Serious adverse event (SAE) – An event is considered “serious” if, in the view of either the 
Investigator or Sponsor, it results in any of the following outcomes: 
• Death 

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• A life-threatening AE (An event is considered “life-threatening” if, in the view of either 
the Investigator or Sponsor, its occurrence places the patient or subject at immediate risk 
of death. It does not include an AE or suspected adverse reaction (AR) that, had it 
occurred in a more severe form, might have caused death.) 
• Inpatient hospitalization or prolongation of existing hospitalization 
• NOTE: Any hospital admission will be considered an inpatient hospitalization, 
regardless of duration. An emergency room visit without hospital admission will not 
be recorded as an SAE under this criterion, nor will hospitalization for a procedure 
scheduled before signing of informed consent. However, unexpected complications 
and/or prolongation of hospitalization that occur during elective surgery should be 
recorded as adverse events and assessed for seriousness 
• Admission to the hospital for a pre-planned procedure or social or situational reasons 
(i.e., no place to stay, lives too far away to come for hospital visits) will not be 
considered inpatient hospitalizations 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• A congenital anomaly/birth defect 
• Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse 
All AEs and SAEs must be documented and recorded on eCRF upon signing of the informed 
consent form. 
An AE or suspected adverse reaction is considered “life threatening” if, in the opinion of either 
the Investigator or Sponsor, its occurrence places the subject at immediate risk of death. It does 
not include an AE or suspected adverse reaction that, had it occurred in a more severe form, 
might have caused death. 
Causality or relatedness – The relationship of an adverse event to the administration of the study 
drug is to be assessed according to the following definitions: 
No – (unrelated, not related, no relation) – The time course between the administration of 
study drug and the occurrence or worsening of the adverse event rules out a causal 
relationship and another cause (concomitant drugs, therapies, complications, etc.) is 
suspected. 
Yes – The time course between the administration of study drug and the occurrence or 
worsening of the adverse event is consistent with a causal relationship and no other cause 
(concomitant drugs, therapies, complications, etc.) can be identified. 
The following factors should also be considered: 

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The temporal sequence from study medication administration: The event should occur after the 
study medication is given. The length of time from study medication exposure to event should be 
evaluated in the clinical context of the event. 
Underlying, concomitant, intercurrent diseases: Each report should be evaluated in the context of 
the natural history and course of the disease being treated and any other disease the subject may 
have. 
Concomitant medication: The other medications the subject is taking or the treatment the subject 
receives should be examined to determine whether any of them might be recognized to cause the 
event in question. 
Known response pattern for this class of study medication: Clinical and/or preclinical data may 
indicate whether a particular response is likely to be a class effect. 
Exposure to physical and/or mental stresses: The exposure to stress might induce adverse 
changes in the recipient and provide a logical and explanation for the event. 
The pharmacology and pharmacokinetics of the study medication: The known pharmacologic 
properties (absorption, distribution, metabolism, and excretion) of the study medication should 
be considered. 
Adverse reaction (AR): An AR is any AE caused by a drug. 
Suspected adverse reaction (SAR): An SAR is any AE for which there is a reasonable possibility 
that the drug caused the AE. For the purposes of regulatory safety reporting, “reasonable 
possibility” means there is evidence to suggest a causal relationship between the drug and the 
AE. SAR implies a lesser degree of certainty about causality than AR. 
Unexpected: An event is considered unexpected if it is not listed in the IB, is not listed at the 
specificity or severity that has been observed, or, if an IB is not required or available, is not 
consistent with the risk information described in the General Investigational Plan or elsewhere in 
the IND. Unexpected also refers to events that are mentioned in the IB as occurring with a class 
of drugs or as anticipated from the pharmacological properties of the drug but are not specifically 
mentioned as occurring with the particular drug under investigation. 
For example, under this definition, hepatic necrosis would be unexpected (by virtue of greater 
severity) if the IB referred only to elevated hepatic enzymes or hepatitis. Similarly, cerebral 
thromboembolism and cerebral vasculitis would be unexpected (by virtue of greater specificity) 
if the IB listed only cerebral vascular accidents. 
 
8.1.1 
Documenting Adverse Events 
The Investigator is responsible for ensuring that all AEs and SAEs are recorded in the eCRF and 
reported to PhaseBio Pharmaceuticals, Inc. From the time informed consent is signed through to 
completion of all study procedures and assessments at the Day 35±3 visit (i.e. EOS), all AEs will 
be assessed. 
Subjects may spontaneously report and/or will be asked a standard question to elicit any 
medically related changes in their well-being. They will also be asked if they have used any new 
medications or changed concomitant medication regimens (both prescription and over-the- 
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For all SAEs, the Investigator is obligated to pursue and provide information to PhaseBio 
Pharmaceuticals, Inc. in accordance with the timeframes for reporting specified above. 
In addition, an Investigator may be requested by PhaseBio Pharmaceuticals, Inc. to obtain 
specific additional follow-up information in an expedited fashion. This information may be more 
detailed than that captured on the adverse event case report form. In general, this will include a 
description of the adverse event in sufficient detail to allow for a complete medical assessment of 
the case and independent determination of possible causality. 
Information on other possible causes of the event, such as concomitant medications and illnesses 
must be provided. In the case of a subject death, a summary of available autopsy findings must 
be submitted as soon as possible to PhaseBio Pharmaceuticals, Inc. or its designated 
representative. The Investigator must continue to follow the subject until the SAE has subsided 
or until the condition becomes chronic in nature, stabilizes (in the case of persistent impairment) 
or the subject dies. 
Within 24 hours of receipt of follow-up information, the Investigator must update the SAE form 
and submit to PhaseBio. 
8.2.2 
Sponsor Regulatory Reporting of Serious Adverse Events 
Prompt notification by the Investigator to the Sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of subjects and the safety of a study 
treatment under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Institutional Review Boards (IRB)/Independent Ethics Committees 
(IEC), and Investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSARs) according to local regulatory requirements and Sponsor policy and forwarded to 
Investigators as necessary. 
An Investigator who receives an Investigator safety report describing a SAE or other specific 
safety information e.g. summary or listing of SAE from the Sponsor will review and then file it 
along with the Investigators’ Brochure (IB) and will notify the IRB/IEC, if appropriate according 
to local requirements. Investigational sites will be responsible for notifying and reporting SAEs 
to their respective IRBs. 
8.3 
Adverse Events of Special Interest 
There are no adverse events of special interest. 
8.4 
Clinical Laboratory Findings 
Clinical laboratory tests will be performed by MedPace Central Laboratory or local laboratory 
where applicable (i.e. Day -1). Blood and urine will be collected at the time points indicated in 
the Schedule of Events (Appendix 3) and will be prepared using standard procedures. Repeat 
clinical laboratory tests a t local or central laboratory may be performed at the discretion of the 
Investigator, if necessary, to evaluate clinical laboratory abnormalities, results of which are to be 
included in the electronic data capture system or eCRF. MedPace central laboratory will provide 

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the reference ranges for all clinical laboratory parameters where applicable. Study site will 
provide the clinical laboratory parameters for any local laboratory used. 
Abnormal clinical laboratory values will be flagged as either high or low (or normal or 
abnormal) based on the reference ranges for each laboratory parameter. The Investigator 
will determine whether any of the abnormal high or low results are CS or NCS. Clinical 
significance is defined as any variation in results that has medical relevance and may result in an 
alteration in medical care (e.g., active observation, diagnostic measures, therapeutic measures). If 
a CS change from the Screening value is noted, the CS value and etiology or reason for clinical 
significance will be documented on the AE page of the eCRF. 
The criteria for determining whether an abnormal test finding should be reported as an AE are as 
follows: 
• Test result is associated with accompanying symptoms, and/or 
• Test result requires additional diagnostic testing or medical/surgical intervention, and/or 
• Test result leads to a change in study dosing or discontinuation from the study, or other 
therapy, and/or 
• Test result is considered an AE by the Investigator or Sponsor 
The Investigator will continue to monitor the subject with additional assessments until the values 
have reached either the reference range or the values at Screening or until the Investigator 
determines that follow-up is no longer medically necessary. 
8.5 
Pregnancy and Contraception 
In enrolled female subjects who are of child-bearing potential (pre-menopausal), use of 2 
effective birth control methods is required for 3 months after signing of the informed consent 
form. For definition of women of childbearing potential and of fertile men please refer to 
Appendix 2. 
Generally accepted forms of effective contraception for women include implants, injectables, 
combined oral contraceptives, intrauterine devices (IUDs), sexual abstinence, combined oral 
contraceptives with inhibition of ovulation or a partner who has been surgically sterile (e.g. by 
vasectomy) for at least 6 months. 
Acceptable methods of contraception for a male include surgical sterility (e.g. by vasectomy) for 
at least 6 months, sexual abstinence, or condoms plus spermicide. 
If the subject or partner of a subject participating in the study becomes pregnant during the study 
or within 35+3 days of last dose or discontinuing study medication, the Investigator should 
report the pregnancy to the Sponsor, or its representative, within 24 hours of being notified. 
The Exposure In-Utero form must be completed by the site. 
The subject or partner should be followed by the Investigator for 30 days post expected date of 
delivery. A separate informed consent form may be obtained which will outline the follow-up. If 
the pregnancy ends for any reason before the anticipated date, the Investigator should notify the 
Sponsor. At the completion of the pregnancy, the Investigator will document the outcome of the 
pregnancy. If the outcome of the pregnancy meets the criteria for immediate classification as an 
SAE (i.e., postpartum complication, spontaneous abortion, stillbirth, neonatal death, or 

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congenital anomaly), the Investigator should follow the procedures for reporting an SAE. 
Otherwise, a follow up Exposure In-Utero form should be completed. See Appendix 2. 
8.6 
Overdose or Misuse 
No treatment is required for overdose of PB2452, as the specificity of PB2452 for ticagrelor 
renders off-target effects extremely unlikely. Treat hypersensitivity reactions immediately with 
appropriate emergency medical care (e.g., oxygen, diphenhydramine, corticosteroids, volume 
expansion, and airway management). If a hypersensitivity reaction occurs during the infusion of 
PB2452, immediately terminate the infusion and administer appropriate treatment. 

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9 
ANALYSIS 
This is a randomized, double-blind, placebo-controlled study designed to evaluate the efficacy of 
PB2452 in reversing the anti-platelet effects of ticagrelor and to evaluate the safety and 
tolerability of PB2452 in subjects aged 50 to 80 years old. The detailed strategy for the statistical 
analysis will be documented in a Statistical Analysis Plan (SAP) before any blinding of the 
treatment code. 
9.1 
Primary Hypothesis 
Compared to placebo, PB2452 administered intravenously provides rapid and sustained reversal 
of the antiplatelet effects of ticagrelor. 
The reversal will be assessed by the primary study endpoint of minimum % inhibition of PRU 
assessed by VerifyNow™ PRUTest™ (VerifyNow™, 2016)within 4 hours after the initiation of 
study drug. Percent inhibition of PRU is calculated as 100 * [(PRUbsl – PRUtrt)/PRUbsl] where 
PRUbsl refers to the PRU value measured before treatment with ticagrelor and PRUtrt refers to the 
PRU value measured posttreatment with the study drug. 
9.2 
Population 
9.2.1 
Sample Size Rationale 
Primary efficacy endpoint will be analyzed by comparing the minimum % inhibition of PRU 
assessed by VerifyNow™ PRUTest™ (VerifyNow™, 2016)within 4 hours after the initiation of 
study drug between the PB2452 group vs placebo group. A sample size (N) of approximately 
200 subjects with 3:1 allocation ratio (active:placebo) will provide > 99% power to detect a 15% 
difference in % inhibition of PRU between PB2452 and placebo group using a two-sided test 
with type I error of 0.05 (20% standard deviation (SD) is assumed which is obtained from 
previous studies). The sample size of 200 (150 active vs 50 placebo) will provide substantial 
safety information on PB2452 in older and elderly volunteer subjects. 
Compared to placebo intravenous PB2452 results in reversal of the antiplatelet effects of 
ticagrelor. The reversal will be assessed by the primary study endpoint of minimum % inhibition 
of PRU assessed by VerifyNow™ PRUTest™ (VerifyNow™, 2016) within 4 hours after the 
initiation of study drug. Percent inhibition of PRU is calculated as 100 * [(PRUbsl – 
PRUtrt)/PRUbsl] where PRUbsl refers to the PRU value measured before treatment with ticagrelor 
and PRUtrt refers to the PRU value measured posttreatment with the study drug. 
9.2.2 
Analysis Subsets 
The results from this study will be presented using the following populations: For purposes of 
analysis, the following populations are defined: 
 
 
Population 
Description 
All Subjects 
All subjects who sign the ICF 
Modified Intention-to- Treat 
Population 
Modified Intention-to-Treat (mITT) population includes all 
subjects randomly assigned to study treatment, who take any 
amount of study drug (PB2452 or placebo). Subjects will be 

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Population 
Description 
analyzed according to the treatment they are randomized to. 
Safety Population 
The safety population includes all subjects who have received 
any amount of study drug. The safety population will be analyzed 
for all safety assessments. Subjects in the Safety population will 
be analyzed as treated. 
Per Protocol Population 
The Per Protocol (PP) population includes subjects in the safety 
population who do not have major protocol deviations and who 
complete the study. Protocol deviations will be assessed prior to 
database lock and unmasking. The PP population will be 
analyzed using observed data only for efficacy variables. 
Subjects in the PP population will be analyzed as treated. 
Pharmacokinetic Population 
The PK population includes all subjects with a measurable PK 
sample of the study drug. The PK population will be used to 
summarize all PB2452 blood concentrations. Subjects in the PK 
population will be analyzed as treated. 
The statistical analysis of safety data will be performed for the Safety population. The analysis of 
efficacy data will primarily be performed for the mITT population. The efficacy analysis based on 
the PP population will serve as sensitivity analyses. 
9.3 
Testing Procedures 
9.3.1 
Analysis of the Primary Efficacy Endpoint 
All efficacy analyses will primarily be based on the mITT population. 
The primary efficacy analysis compares the primary endpoint between PB2452 and placebo. The 
primary endpoint is defined as the minimum % inhibition of PRU assessed by VerifyNow™ 
PRUTest™ (VerifyNow™, 2016)within 4 hours (inclusive) after the initiation of study drug. 
Percent inhibition of PRU is calculated as 100 * [(PRUbsl – PRUtrt)/PRUbsl],where PRUbsl refers 
to the PRU value measured before treatment with ticagrelor and PRUtrt refers to the PRU value 
measured posttreatment with the study drug. 
Results by treatment groups will be summarized at baseline, at the timepoint where minimum is 
achieved, and percentage inhibition from baseline using descriptive statistics: N, mean, SD, 
median, minimum, and maximum. To complete the clinical picture, the % inhibition of PRU 
from baseline will be summarized at all time points using descriptive statistics. 
Hypothesis testing will also be conducted as a 2-sided test with a significance level of 0.05 to 
compare the efficacy of PB2452 and placebo. Assuming that the population median minimum % 
inhibition of PRU are expressed as µPB2452 and µPlacebo for the PB2452 and placebo groups, 
respectively, the treatment comparison to be tested is ∆= μPB2452 − μplacebo. The null (H0) and 
alternative (H1) hypotheses for each comparison are: 

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H0: ∆= 0 
vs. 
H1: ∆≠ 0 
 
This test will be conducted using an exact Wilcoxon rank-sum test. The hypothesis test for the 
primary endpoint will be performed at 2-sided α = 0.05. The Hodges-Lehman estimate of 
location shift and a 95% Hodges-Lehman confidence interval will be constructed on the 
difference in between PB2452 and placebo. 
9.3.2 
Analysis of Secondary Efficacy Endpoint(s) 
The secondary efficacy analysis compares the secondary endpoints between the two treatment 
groups. The dichotomous secondary endpoints will be compared between the treatment groups 
using Fisher’s Exact test. The continuous secondary endpoints will be compared between the two 
treatment groups using an exact Wilcoxon rank-sum test and Hodges-Lehman confidence 
interval, as used for the primary endpoint. 
9.3.3 
Population Analysis 
9.3.3.1 
Disposition 
Subject disposition will be presented for all screened subjects, including number of screen- failed 
subjects and number of subjects randomized (all subjects). 
Number and percentage of subjects in the following categories will be summarized as 
appropriate: 
• Screen failed 
• Enrolled 
• Enrolled, but not randomized 
• Randomized 
• mITT population 
• Safety population 
• Per-Protocol population 
• PK population 
Additionally, a summary on study completion status and treatment completion will be presented 
along with reasons for discontinuation if any. 
9.3.3.2 
Demographics 
The demographic and baseline characteristics will be summarized with respect to sex, age 
(years), height (cm), weight (kg), BMI (kg/m2), race, and ethnicity by treatment group. These 
summaries will be calculated for both mITT and Safety populations. 
9.3.3.3 
Baseline Characteristics 
The counts and percentage of subjects who had been on aspirin before or who initiated aspirin on 
Day -7 will be presented by treatment. Also, the platelet count at baseline will be summarized by 
treatment. 

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9.3.4 
Safety Analysis 
Safety will be assessed by examination of adverse events, physical examination findings, vital 
signs, clinical laboratory measurements, antibodies to study drug and 12 lead ECGs based on the 
Safety population. 
9.3.4.1 
Demographics 
Demographics are described in Section 9.3.3.2. 
9.3.4.2 
Baseline Characteristics 
Baseline characteristics are described in Section 9.3.3.3. 
9.3.4.3 
Disposition 
Disposition is described in Section 9.3.3.1. 
9.3.4.4 
Adverse Events 
Adverse events will be coded by preferred term and system-organ-class (SOC) using the latest 
version of the Medical Dictionary for Regulatory Activities (MedDRA). All AE data will be 
presented in data listings. Treatment-emergent AEs (TEAEs) will be summarized by treatment 
and overall, as well as by severity and relationship to study drug. TEAEs are defined as any AE 
not present before exposure to study drug or any AE already present that worsens in severity 
after exposure to study drug. All treatment-emergent SAEs, AESIs and TEAEs leading to 
discontinuation of study drug will be presented in the data listings. 
9.3.4.5 
Clinical Laboratory Results 
Actual values and changes from baseline in clinical laboratory test results will be summarized by 
treatment at each time point using descriptive statistics (number of subjects, mean, standard 
deviation, median, minimum, and maximum). Clinical laboratory test results will be presented in 
data listings as well. 
9.3.5 
Other Prespecified Endpoint Analysis 
Platelet-function biomarker data will be summarized for each time point as applicable using 
descriptive statistics (number of subjects, mean, SD, CV, median, minimum, and maximum). 
9.3.6 
Pharmacokinetics Analysis 
Plasma concentrations will be listed and summarized descriptively (number of subjects, 
arithmetic mean, SD, coefficient of variation (CV), median, minimum, and maximum). Plasma 
concentration versus time profiles for each subject will be presented graphically. The mean 
plasma concentration versus scheduled time profiles will be presented graphically both on the 
linear and semi-log scale. 
Plasma PK parameters of PB2452, ticagrelor, and TAM will be determined with noncompartmental 
methods and summarized by time point using descriptive statistics (number of subjects, mean, 
SD, CV, median, minimum, and maximum). Geometric means will be reported for AUCs and 
Cmax. Actual sampling times, rather than scheduled sampling times, will be used in all calculations of 
PK parameters. 
The urine concentrations will be listed and summarized descriptively. 

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9.3.7 
Pharmacodynamics Analysis 
Pharmacodynamic data will be summarized for each time point using descriptive statistics 
(number of subjects, mean, SD, CV, median, minimum, and maximum). Pharmacodynamic 
parameters will also be summarized for each cohort. 
9.3.8 
Immunogenicity Analysis 
The PB2454 antibodies will be summarized by visit and treatment. A listing of subjects will also 
be provided. 
If positive ADA is observed, results may be reported by ADA status for AEs, efficacy and 
pharmacokinetics. 
9.4 
Planned Interim Analysis 
No interim analysis is planned for this study. 
9.4.1 
Temporary Halting or Early Termination Criteria 
There is no plan to halt this study before completion. 
9.4.2 
Specified Analyses for Independent Data Monitoring Committee Review 
For this study, there will be no Independent Data Monitoring Committee (DMC). 
9.5 
Procedures for Reporting Changes to the Planned Analysis 
The SAP will detail the strategy for statistical analyses for this study. Any change in the plan 
described in this protocol will be highlighted in the SAP. 

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10 
ETHICAL CONSIDERATIONS 
PhaseBio Pharmaceuticals, Inc and designées will carry out all aspects of this study in 
accordance with the US Code of Federal Regulations (CFR) governing the protection of human 
subjects (21 CFR 50), IRBs (21 CFR 56), and the obligations of clinical Investigators (21 CFR 
312). U.S. Title 21 CFR on Good Clinical Practice (GCP) and ICH E6 (R2) as consistent with 
principles set forth by the Declaration of Helsinki and the International Conference on 
Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human 
Use. The study will be registered on Clinicaltrials.gov in accordance with Section 801 of the 
Food and Drug Administration (FDA) Amendments Act of 2007 (FDAAA), EudraCT (European 
Union Drug Regulating Authorities Clinical Trials) Database and in other national or 
international registries as appropriate. 
All Investigators are required to review and sign a Food and Drug Administration (FDA) Form 
1572 or equivalent and financial disclosure form and agree to follow the study according to the 
general principles of ICH and GCP guidance documents. 
10.1 
Good Clinical Practice 
The Investigator will agree to perform all aspects of this study in accordance with the ethical 
principles that have their origin in the Declaration of Helsinki, ICH E6(R2): GCP, the protocol, 
and all national, state, and local laws or regulations. 
10.2 
Ethics Review 
The study protocol and amendments, ICFs, advertisements, the Investigator’s Brochure (IB) 
and information given to study subjects will be reviewed and approved by the Institutional 
Review Board (IRB)/ Institutional Ethics Committee (IEC) of each study center prior to use. 
Each Investigator will be responsible for informing the IRB/IEC of the progress of the study and 
submitting annual reports. This study will be conducted in the US, and other countries at the 
discretion of the Sponsor. 
The study will be conducted according to general principles of the Declaration of Helsinki, 
Protection of Human Subjects (21 CFR 50), Institutional Review Boards (21 CFR 56), and 
Obligations of Clinical Investigators (21 CFR 312 Subpart D), Council forInternational 
Organizations of Medical Sciences (CIOMS) International Ethical Guidelines, and applicable 
ICH Good Clinical Practice (GCP) Guidelines, per local laws and regulations. 
To maintain confidentiality, all laboratory specimens, evaluation forms, reports and other records 
will be identified by a coded identifier only. All study records will be kept in a secure location 
where only study staff have access. The Investigator must also comply with all applicable 
privacy regulations (e.g., Health Insurance Portability and Accountability Act of 1996, General 
Data Protection Regulation (EU) 2016/679) as applicable. 
10.3 
Informed Consent Form 
Informed consent form (ICF) will be obtained in accordance with the principles of Declaration of 
Helsinki, ICH GCP, US CFR for Protection of Human Subjects, and with local regulations and 
data protection law (e.g. Health Insurance Portability and Accountability Act (HIPAA), etc.). 

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A valid, executed informed consent form will be obtained from every subject as per local 
regulations, and prior to entering the subject into the trial and conducting any screening, study 
procedures and activities. The Investigators must ensure that each subject is fully informed about 
the nature and objectives of the study, study procedures, and possible risks associated with 
participation; given ample opportunity to inquire about details of the study and freely consents to 
participation in the study. A copy of the signed and dated informed consent form or documented 
verbal consent will be given to the subject and the original will be maintained with the subject’s 
records. 
The Investigator will prepare the ICF, as per local privacy requirements and provide the 
document(s) to the Sponsor or designee for approval prior to submission to the IRB/IEC. The 
consent form generated by the Investigator must be acceptable to the Sponsor and be approved 
by the IRB/IEC. The written consent form will embody the elements of informed consent as 
described in the ICH and will also comply with applicable local regulations and sponsor 
requirements. The Investigator will send in a copy of the final IRB/IEC-approved ICF, along 
with all related correspondence to the Sponsor (or designee) for the study file. 
Subjects who are rescreened are required to sign a new ICF. 
The ICF will contain a section that addresses the use of remaining samples for exploratory 
research and genetic testing. Subjects will be told that they may withdraw their consent at any 
time and for any reason during the storage period. The subjects must be informed that if they 
revoke their consent all collected information and samples will be removed to the extent 
possible and if not already used, shared, transferred. Laboratory data may be pooled, and 
identification and removal of an individual subject’s results may not be possible. 
The subject must be informed that his/her personal study-related data willbe used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the subject. 
The subject must be informed that his/her medical records may be examined either in-person 
or remotely by Clinical Quality Assurance auditors or other authorized personnel appointed by 
the Sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
10.4 
Data Privacy 
In order to maintain subject confidentiality, only a site number, and subject number and subject 
age (or date of birth as per local regulations) will identify all study subjects on eCRFs and other 
documentation submitted to the Sponsor. 
• Subjects will be assigned a unique identifier by the Sponsor. Anysubject records or 
datasets that are transferred to the Sponsor will contain the identifier only; subject 
names or any information which would make the subject identifiable will not be 
transferred 
• The subject must be informed that his/her personal study-related data willbe used by 
the Sponsor in accordance with local data protection law. The level of disclosure 
must also be explained to the subject 
• The subject must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 

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Sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities 
The Investigator and all employees and coworkers involved in this study may not disclose or use 
for any purpose other than performance of the study, any data, record, or other unpublished, 
confidential information disclosed to those individuals for the purpose of the study. Prior written 
agreement from the Sponsor or designee must be obtained for the disclosure of any said 
confidential information to other parties. 
10.5 
Financial Considerations 
Investigators and Sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
Neither the Sponsor nor the Investigator site is financially responsible for further testing or 
treatment of any medical condition that may be detected during the Screening process. In 
addition, in the absence of specific arrangements, neither the Sponsor nor the Investigator site is 
financially responsible for further treatment of the disease under study. 
Brief overview of the trial will be published upon clinical study report completion as per 
requirements on www.clinicaltrials.gov and the European Union 536/2014 regulations for the 
public or other local sites as applicable. 
10.6 
Biological Specimens and Data 
Blood samples collected during the study for pharmacokinetic or immunogenicity analysis may 
be retained for future testing as necessary for at least 2 years post approval of the investigational 
product in any ICH country. If the Sponsor chooses to conduct further testing additional consent 
will not be obtained. The subject confidentiality will be maintained and only the site and subject 
number will identify the sample. No other linked or identifying information is maintained by the 
Sponsor. 

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11 
OVERSIGHT 
11.1 
Independent Monitoring 
11.1.1 
Data and Safety Monitoring Committee 
There is no Data Monitoring Committee (DMC) for this study. 
11.2 
Quality Control and Assurance 
• All subject activities and data relating to the study will be recorded on electronic case 
report form (eCRF) unless transmitted to the Sponsor or designee electronically (e.g., 
laboratory data). The Investigator is responsible for verifying that data entries are 
accurate and correct by electronically signing the eCRF 
• The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF 
• The Investigator must permit study-related monitoring on-site (in-person) or remote 
monitoring using electronic or paper records, quality assurance audits (in-person or 
remotely), IRB/IEC review, and regulatory agency inspection(s) and provide direct 
access to source data documents 
• The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data 
• Study monitors will perform ongoing source data verification to confirm that data entered 
into the eCRF by authorized site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of subjects are being protected; and that the 
study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH GCP, and all applicable regulatory requirements 
• Source documents provide evidence for the existence of the subject and substantiate the 
integrity of the data collected. Source documents are filed at the Investigator’s site 
• Data reported or entered on the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
Investigator may need to request previous medical records or transfer records, depending 
on the study. All medical records must be available during the monitoring visits(s) 
11.2.1 
Monitoring 
The clinical monitor, as a representative of the Sponsor, is obligated to follow the study closely. 
In doing so, the monitor will visit the Investigator and study site in-person or remotely at 
periodic intervals in addition to maintaining necessary telephone and email contact. The monitor 
will maintain current personal knowledge of the study through observation, review of study 
records and source documents, and discussion of the conduct of the study with the Investigator 
and staff. All aspects of the study will be carefully monitored by the Sponsor or designee using 
paper or electronic records as applicable in compliance with applicable government regulation 
with respect to current ICH E6(R2) guidelines and standard operating procedures (SOPs). 
The sponsor or delegate will monitor the study either in-person or remotely to verify that, 
amongst other items, the: 

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• Data are authentic, accurate, and complete 
• Safety and rights of subjects are being protected 
• Study is conducted in accordance with the currently approved protocol, any other study 
agreements, GCP and all applicable regulatory requirements 
The Investigator and the head of the medical institution (where applicable) agrees to allow the 
monitor direct access to all relevant documents. The Investigator must ensure provision of 
reasonable time, space and qualified personnel for monitoring visits. The Investigator and 
institution involved in the study will permit study-related audits, IRB/IEC review, and regulatory 
inspections by providing direct access to all study records. In the event of an audit, the 
Investigator agrees to allow the Sponsor, their representatives, the FDA, or other regulatory 
agency access to all study records on-site and in-person or remotely. The Investigator should 
promptly notify the Sponsor of any audits scheduled by any regulatory authorities and promptly 
forward to the Sponsor copies of any audit reports received. 
Access to all study and site related materials and source data either in-person or remotely is 
mandatory for the purpose of monitoring review. The Sponsor (or delegate) will perform a 
review of the e-CRFs and source documents as required. Upon completion or premature 
discontinuation of the study, the Sponsor (or delegate) will conduct site closure activities with 
the Investigator or site staff, as per local and Federal requirements, GCP, and PhaseBio (or 
delegate) procedures. 
11.2.2 
Audits 
Quality assurance audits will be performed in-person or remotely in compliance with the study 
defined audit plan. Sites may be audited (on-site and in-person) or remotely to evaluate trial 
conduct and compliance with the protocol, SOPs, GCP, and applicable regulatory requirements 
at the discretion of the Sponsor (delegate). 
11.2.3 
Protocol Deviations 
A protocol deviation occurs when the subject, Investigator, or Sponsor fails to adhere to 
significant protocol requirements affecting the inclusion, exclusion, subject safety and primary 
endpoint criteria. Protocol deviations for this study include, but are not limited to, the following: 
• Failure to meet inclusion/exclusion criteria 
• Use of a prohibited concomitant medication 
• Dosing error (a subject is not given the correct dose of study drug or placebo) 
• Unblinding 
• Failure to adhere to procedures or timing of sample collection 
• Failure to comply with Good Clinical Practice (GCP) guidelines 
• Nonadherence to FDA regulations or ICH E6(R2) guidelines 
• Nonadherence to timing of study procedures 

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The Sponsor will determine if a protocol deviation will result in withdrawal of a subject or if 
data analysis will be censored. The Sponsor does not permit protocol waivers (i.e., prospective 
protocol deviations). 
When a protocol deviation occurs, it is entered directly on the eCRF or documented by either the 
clinical monitor or project manager in accordance with the Sponsor (or delegate) SOPs and 
procedures. As applicable, an impact assessment of the deviation, determination of the need for 
any subsequent root cause analysis and corrective actions to prevent future deviations will be 
assessed and documented. The protocol deviation page on the eCRF or a separate form will be 
reviewed and signed by a Sponsor representative and the Investigator. A copy of completed 
forms will be filed in the site’s regulatory binder and in the Sponsor’s files. 
Any change, divergence, or departure from the study design or procedures defined in the 
protocol will be documented by the clinical monitor throughout the course of monitoring visits. 
The Investigator will be notified by the monitor of such situations in writing. The IRB/IEC 
should be notified of protocol deviations where appropriate, and as per IRB/IEC requirements in 
a timely manner. 
The Investigator or designee must document and explain in the subject’s source documentation 
any deviation from the approved protocol. The Investigator may implement a deviation from or a 
change to the protocol without prior IRB/IEC approval to eliminate an immediate hazard to study 
subjects. As soon as possible after such an event, the implemented deviation or change, the 
reasons for it, and any proposed protocol amendments should be submitted to the IRB/IEC for 
review and approval, to the Sponsor for agreement, and to the regulatory authorities, if required. 
11.2.4 
Records 
11.2.4.1 
Data Collection Instruments 
The Investigator will prepare and maintain adequate and accurate source documents designed to 
record all observations and other pertinent data for each subject treated with the study drug. 
Study personnel at each site will enter data from source documents corresponding to a subject’s 
visit into the protocol-specific electronic Case Report Form (eCRF) when the information 
corresponding to that visit is available. Subjects will not be identified by name in the study 
database or on any study documents to be collected by the Sponsor (or designee), but will be 
identified by a site number and subject number. 
If a correction is required for an eCRF, the time and date stamps track the person entering or 
updating eCRF data and creates an electronic audit trail. 
The Investigator is responsible for all information collected on subjects enrolled in this study. All 
data collected during the course of this study must be reviewed and verified for completeness 
and accuracy by the Investigator. Copies of final completed eCRFs will be provided 
electronically for archiving at the study site following database lock and at or prior to study 
closure. 
11.2.4.2 
Data Capture and Management 
Data must be recorded on the eCRF as the study is in progress. All site personnel must log into 
the system using their secure username and password in order to enter, review, or correct study 
data. These procedures must comply with Title 21 of the Code of Federal Regulations (21 CFR 

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Part 11), applicable ICH guidelines and local regulations. All passwords will be strictly 
confidential. Therefore, the system, and subsequently any investigative reviews, can identify 
coordinators, Investigators, and individuals who have entered or modified records, as well as the 
time and date of any modifications. There may be an internal quality review audit of the data and 
additional reviews by the clinical monitor. 
The data will be entered into a validated database. The data management group will be 
responsible for data processing, in accordance with procedural documentation. Database lock 
will occur once quality assurance procedures have been completed. 
All procedures for the handling and analysis of data will be conducted using good computing 
practices meeting FDA, ICH and applicable guidelines for the handling and analysis of data for 
clinical trials. 
11.2.4.3 
Data Validation 
Validation checks programmed within the electronic data capture (EDC) system and the eCRF, 
as well as supplemental validation performed via review of the uploaded data, will be applied to 
the data in order to ensure accurate, consistent, and reliable data. Data identified as erroneous, or 
data that are missing, will be referred to the investigative site for resolution through data queries. 
Each eCRF is presented as an electronic copy, allowing data entry by site personnel, who can add 
and edit data, add new subjects, identify and resolve discrepancies, and view records. This 
system provides immediate direct data transfer to the database, as well as immediate detection of 
discrepancies, enabling site coordinators to resolve and manage discrepancies in a timely 
manner. 
The eCRFs must be reviewed and electronically signed by the principal Investigator. 
After data have been entered a system of computerized data validation checks will be applied to 
the database on a regular basis. Queries are entered, tracked, and resolved through the EDC 
system directly. The study database will be updated in accordance with the resolved queries. All 
changes to the study database will be documented. 
11.2.4.4 
Source Documentation 
Site personnel will maintain source documentation to support subject data that is entered into the 
eCRF and participation in the study. 
Both paper and electronic medical records may be used for collection of source data. If the 
Investigator study site uses an electronic medical record system, the Investigator is required to 
ensure the system is validated and compliant with US Title 21 CFR Part 11 and applicable local 
regulatory requirements. Each person involved in the study will have an individual identification 
code and password that provides record traceability. Therefore, the system, and subsequently any 
investigative reviews, can identify coordinators, Investigators, and individuals who have entered 
or modified medical records, as well as the time and date of any modifications. There may be an 
internal quality review audit of the data and additional reviews by the clinical monitor. 
Source documentation includes but is not limited to the following types of information: current 
and past medical records generated at the Investigator site and collected from primary care or/or 
other subject providers, ICFs, records of assessments performed as part of study participation, 
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note any changes to site-specific processes due to COVID-19 pandemic must be fully 
documented and identified within source documents and eCRF. 
11.2.4.5 
Study Files 
The Investigator must make study data accessible to the monitor, other authorized 
representatives of the Sponsor (or designee), IRB/IEC, and Regulatory Agency (e.g., FDA) 
inspectors upon request. A file for each subject must be maintained that includes the signed 
Informed Consent Form or documented verbal consent, HIPAA Authorization or country- 
specific and local regulatory requirements as applicable and copies of all source documentation 
related to that subject. The Investigator must ensure the reliability and availability of source 
documents from which the information on the eCRF was derived. 
11.2.4.6 
Records Retention 
Study-related records and documents should be retained for at least 2 years after the last approval 
of a marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or for at least 2 years have elapsed since the formal 
discontinuation of clinical development of PB2452. These documents may be retained for a 
longer period if required by the applicable regulatory requirements or by an agreement with the 
Sponsor. It is the Sponsor’s responsibility to inform the Investigator/institution when these 
documents no longer need to be retained. 
 
11.2.4.7 
Archival of Data 
The database is safeguarded against unauthorized access by established security procedures; 
appropriate backup copies of the database and related software files will be maintained. 
Databases are backed up by the database administrator in conjunction with any updates or 
changes to the database. 
At critical junctures of the protocol (e.g., production of interim reports and final reports), data for 
analysis will be either frozen or locked respectively, and cleaned per established procedures. 
11.3 
Sponsor Trial Discontinuation Criteria 
Premature termination of this study or study site closure may occur because of a regulatory 
authority decision, change in opinion of the IRB/IEC, drug safety problems, or at the discretion 
of PhaseBio Pharmaceuticals, Inc. In addition, PhaseBio Pharmaceuticals, Inc. retains the right to 
discontinue development of the referenced investigational drug at any time. 
11.3.1 
Study Termination 
If the study is prematurely terminated or discontinued, PhaseBio Pharmaceuticals, Inc. will 
promptly notify the Investigator. After notification, the Investigator must contact all participating 
subjects within 5 business days. As directed by PhaseBio Pharmaceuticals, Inc. or delegate, all 
study materials must be collected and all eCRFs completed to the extent possible. 
11.3.2 
Study Site Closure 
Study sites will be closed upon study completion or at the discretion of PhaseBio (delegate). A 
study site is considered closed when all required documents and study supplies have been 
collected and a study-site closure visit has been performed. 

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The Investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include but are 
not limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the Sponsor's procedures, or GCP guidelines 
• Inadequate recruitment of subjects by the Investigator 
• Discontinuation of further study treatment development 

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12 
PUBLICATION POLICY 
The preparation and submittal for publication of manuscripts containing the study results shall be 
in accordance with a process determined by mutual written agreement among the study Sponsor 
and participating institutions. The publication or presentation of any study results shall comply 
with all applicable privacy laws, including, but not limited to, the Health Insurance Portability 
and Accountability Act of 1996 and the General Data Protection Regulation 2016/679. 
• The results of this study may be published or presented at scientific meetings. If this 
is foreseen, the Investigator agrees to submit manuscripts or abstracts to the Sponsor 
before submission. This allows the Sponsor to protect proprietary information and to 
provide comments 
• The Sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the Sponsor will generally 
support publication of multicenter studies only in their entirety and not as individual 
site data. In this case, a coordinating Investigator will be designated by mutual 
agreement 
• Authorship will be determined by mutual agreement and in line with the International 
Committee of Medical Journal Editors authorship requirements 
After completion of the study, the study data may be considered for reporting at a scientific 
meeting or for publication in a scientific journal. In these cases, the Sponsor will be responsible 
for these activities and will work with the Investigators to determine how the manuscript is 
written and edited, the number and order of authors, the publications to which it will be 
submitted, and any other related issues. The Sponsor has final approval authority over all such 
issues. 
Data from this study are the property of the Sponsor and cannot be published without their prior 
authorization; however, data and any publication thereof will not be unduly withheld. 

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13 
DISEMINATION OF STUDY DATA 
Where required by applicable regulatory requirements, an Investigator signatory will be 
identified for the approval of the clinical study report. The Investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the opportunity 
to review the complete study results at a mutually agreeable location. Phase Bio will also provide 
the Investigator with the full summary of the study results. The Investigator is encouraged to 
share the summary results with the study subjects, as appropriate. PhaseBio will provide the 
Investigator with the randomisation codes for their site only after completion of the full statistical 
analysis. The procedures and timing for public disclosure of the results summary and for 
development of a manuscript for publication will be in accordance with PhaseBio internal 
policies. 

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14 
FINANCING AND INSURANCE 
Financing and insurance information is addressed in the Clinical Trial Agreement between 
PhaseBio and the study site. 

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REFERENCES 
21 CFR Part 50. (2019, April 01). FDA Subpart A - General Provisions (§§ 50.1 - 50.3). Code of 
Federal Regulations. Retrieved from 
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm. 
Bhatt DL, P. C. (2019, March 17). Antibody-based ticagrelor reversal agent in healthy 
volunteers. N Engl J Med, 1056. doi:DOI: 10.1056/NEJMoa1901778 
BRILINTA (ticagrelor), (2021). BRILINTA (ticagrelor) tablets, for oral use: Full Prescribing 
Information. USA: FDA. Acessed May 19, 2021; Retrieved from 
https://den8dhaj6zs0e.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/565ceafd-fbe3- 
4573-9c39-19280af566ec/565ceafd-fbe3-4573-9c39-19280af566ec_viewable_rendition v.pdf 
BRILINTA (ticagrelor), (2020). BRILINTA (ticagrelor) ticagrelor tablets 60 and 90 mg 
Platelet Aggregation Inhibitor, for oral use: Product Monograph. Canada: Health Canada. 
Accessed May 19, 2021; Retrieved from https://pdf.hres.ca/dpd_pm/00060378.pdf. 
Buchanan, A. N. (2015). Structural and functional characterization of a specific antidote for 
ticagrelor. Blood, 125, 3484-90. 
Clinical Trial Facilitation Group. (2014, 09 15). Recommendations Related to Contraception and 
Pregnancy Testing in Clinical Trials. Clinical Trial Facilitation Group (CTFG), 1-13. Retrieved 
03 01, 2021, from https://www.uni-due.de/imperia/md/content/ethikkomission/kontrazeption.pdf 
Dalen M, I. T. (2013). Ticagrelor-associated bleeding in a patient undergoing surgery for acute 
type A aortic dissection. J Cardiothorac Vasc Anesth, 27(5), 55-7. 
FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public 
Health Emergency, Guidance for Industry, Investigators, and Institutional Review Boards, March 
2020, Updated on January 27, 2021, Accessed May, 19 2021; 
https://www.fda.gov/media/136238/download. 
FDA Guidance on COVID-19: Developing Drugs and Biological Products for Treatment or 
Prevention, Guidance for Industry, COVID-19: Developing Drugs and Biological Products for 
Treatment or Prevention Guidance for Industry, February 2021, Accessed May 19, 2021, 
https://www.fda.gov/media/137926/download. 
Godier A, T. G. (2015). Inefficacy of platelet transfusion to reverse ticagrelor. N Engl J Med, 
372(2), 196-7. 
Health Canada Guidance and Notice: Management of clinical trials during the COVID-19 
pandemic: Notice to clinical trial Sponsors, May 06, 2021, Accessed May 19, 2021, 
https://www.canada.ca/en/health-canada/services/drugs-health-products/drug- 
products/announcements/management-clinical-trials-during-covid-19-pandemic.html#a1. 
ICH, E. (2017, June 14). Good Clinical Practice: Integrated Addendum to ICH E6 (R1) Guidance 
for Industry. European Medicines Agency, 1-69. Retrieved May 05, 2020, from 
https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e-6-r2-guideline-good- 
clinical-practice-step-5_en.pdf. 

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ICH, E3. (2015). ICH E3: Structure and Content of Clinical Study Reports. ICH. Retrieved 
November 30, 2015, from 
https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guideline. 
ICH, M3 (R2). (2009). Guidance on Nonclinical Safety Studies for the Conduct of Human 
Clinical Trials and Marketing Authorization for Pharmaceuticals. FDA. USA: Accessed 15 
February 2016. Retrieved February 15, Accessed 2016, from 
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Multidisciplinary/ 
M3_R2/Step4/M3_R2 Guideline.pdf. 
ICH, S6 (R1). (2011). Preclinical Safety Evaluation of Biotechnology- Derived Pharmaceuticals. 
USA: PreclinAvailable at: 
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Safety/S6_R1/Step 
4/S6_R1_Guideline.pdf. Accessed 15 February 2016. 
Maillard J, C. F. (2015). Lack of effect of platelet transfusions and desmopressin on intracranial 
bleeding in a patient receiving ticagrelor. A A Case Rep, 4, 169–71. 
National Cancer Institute. (2017). Common Terminology Criteria for Adverse Events v5.0 
(CTCAE). National Cancer Institute, November 27, 2017. Available at 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_50. Accessed 
M, Bethesda. Retrieved March 16, 2018. 
Storey. (2011). New P2Y12 inhibitors. Heart, 97, 1262-7. 
Storey, R. H. (2007, Nov 06). Inhibition of platelet aggregation by AZD6140, a reversible oral 
P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary 
syndromes. JACC, 50(19), 1852-6. 
Taylor G, O. D. (2013, May). Is platelet transfusion efficient to restore platelet reactivity in 
patients who are responders to aspirin and/or clopidogrel before emergency surgery? Journal of 
Acute Care Surgery, 74(5), 1367-9. 
Teng R, M. J. (2013, Dec). Evaluation of the pharmacokinetics and pharmacodynamics of 
ticagrelor co-administered with aspirin in healthy volunteers. Platelets, 24(8), 615-24. 
doi:10.3109/09537104.2012.748185. 
Teng, R. C. (2016, Dec 14). Effects of autologous platelet transfusion on platelet inhibition in 
ticagrelor-treated and clopidogrel-treated subjects. Journal of Thromb Haemost, 14(12), 2342- 
52. 
van Giezen, J. N. (2009). Ticagrelor binds to human P2Y(12) independently from ADP but 
antagonizes ADP-induced receptor signaling and platelet aggregation. Journal of Thromb 
Haemost, 7, 1556-65. 
VerifyNow™. (2016). VerifyNow™ PRU Test Instructions for Use. Accriva Diagnostics. 
Website, F. (n.d.). FDA Website for complete lists of strong inhibitors and strong inducers of 
CYP3A. Retrieved 05 05, 2020, from www.fda.gov: Website, F. (n.d.). FDA Website for 
complete lists of strong inhibitors and strong inducers of CYP3A. Retrieved from 
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions- 
table-substrates-inhibitors-and-inducers. 

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16 
APPENDICES 
The following appendices are included: 
Appendix 1 - List of Abbreviations 
Appendix 2 - Pregnancy Testing and Reporting Guidance and Contraception Methods 
Appendix 3 – Schedule of Events (SOE) 
Appendix 4 - Examples of Inhibitors of CYP3A 

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APPENDIX 1 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
 
ACS 
acute coronary syndrome 
 
ADA 
anti-drug antibodies 
 
ADME 
ADP 
AE 
Aet1-t2 
Ae24 
Ae48 
AESI 
ALP 
ALT 
aPTT 
AR 
ASA 
absorption, distribution, metabolism, excretion 
adenosine diphosphate 
adverse event 
 
Ae from time t1 to t2 hours 
total amount of drug excreted in urine at 24 hours after dosing 
total amount of drug excreted in urine at 48 hours after dosing 
adverse events of special interest 
alkaline phosphatase 
 
alanine aminotransferase 
activated partial thromboplastin time 
 
adverse reaction 
acetylsalicylic acid 
AST 
aspartate aminotransferase 
 
AUC 
area under the plasma concentration versus time curve 
 
AUC0-24 
AUC0-30 
 
AUC0-48 
AUC0-∞ 
AUC from time zero to 24 hours after dosing 
area under the plasma concentration versus time curve from time 
zero to thirty 
area under the plasma concentration versus time curve from time 
zero to forty-eight 
area under the plasma concentration versus time curve from time 
zero extrapolated to infinity 

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AUC0-last 
 
AUC0-t 
AUC0-tau 
bid 
BL 
BLQ 
BMI 
BP 
bpm 
BUN 
CFR 
CIOMS 
CL 
area under the plasma concentration versus time curve from time 
zero to the time of the last quantifiable concentration 
area under the plasma concentration versus time curve from time 
zero to the specified time of the last quantifiable concentration 
area under the plasma concentration versus time curve from time 
zero to the time of the end of the dosing period 
twice daily 
 
baseline 
below the assay limit of quantification 
body mass index 
blood pressure 
 
beats per minute 
blood urea nitrogen 
Code of Federal Regulations 
Council for International Organizations of Medical Sciences 
clearance 
CLr 
renal clearance 
 
Cmax 
observed maximum plasma concentration 
 
COVID-19 
CS 
Coronavirus disease 2019 
clinically significant 
CSR 
clinical study report 
 
CTCAE 
common terminology criteria for adverse events 
CV 
coefficient of variation 
CYP3A 
cytochrome P450 3A 
 
DAPT 
dual antiplatelet therapy 
 
DBP 
diastolic blood pressure 
 
DLT 
dose-limiting toxicity 
 
DMC 
ECG 
data monitoring committee 
electrocardiogram 

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eCRF 
EDC 
EEA 
eGFR 
ELISA 
EOS 
EU 
EudraCT 
 
Fab 
Fe24 
Fe48 
FDA 
FDAAA 
FSH 
FUP 
g 
GCP 
GGT 
electronic case report form 
electronic data capture 
European economic area 
estimated glomerular filtration rate 
 
enzyme-linked immunosorbent assay 
end of study 
European Union 
European Union Drug Regulating Authorities Clinical Trials 
Database 
antibody fragment 
fraction excreted in urine from 1 to 24 hours after dosing 
fraction excreted in urine from 1 to 48 hours after dosing 
Food and Drug Administration 
Food and Drug Administration Amendments Act 
follicle-stimulating hormone 
follow-up 
 
gram 
Good Clinical Practice 
gamma-glutamyl transferase 
GLP 
Good Laboratory Practice 
 
Hgb 
hemoglobin 
 
HbA1c 
HBsAg 
HCV 
HDL 
HIPPA 
HIV 
Hr 
glycosylated hemoglobin Hgb 
hepatitis B surface antigen 
hepatitis C virus 
high-density lipoprotein 
Health Insurance Portability and Accountability Act 
human immunodeficiency virus 
hour 
 
HR 
heart rate 

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IB 
Investigator’s brochure 
 
IC 
ICF 
ICH 
IDMS-Traceable 
MDRD 
IEC 
INR 
IP 
IPA 
IRB 
informed consent 
informed consent form 
International Council for Harmonization 
Isotope-dilution mass spectrometry-traceable modification of diet 
in renal disease 
independent ethics committee 
international normalized ratio 
investigational product 
inhibition of platelet aggregation 
institutional review board 
IRR 
infusion-related reaction 
 
IUD 
IV 
IWRS 
kDa 
LDH 
LDL 
LLN 
max 
MCH 
MCHC 
MCV 
MDMA 
medDRA 
MI 
mITT 
msec 
intrauterine device 
intravenous- (ly) 
interactive web response system 
kilo dalton 
lactate dehydrogenase 
 
Low-density lipoprotein 
lower limit of normal 
maximum 
mean corpuscular hemoglobin 
mean corpuscular hemoglobin concentration 
mean corpuscular volume 
methylenedioxymethamphetamine 
medical dictionary for regulatory activities 
myocardial infarction 
modified intent to treat 
millisecond 
N 
sample size 

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NCS 
not clinically significant 
NOAEL 
no adverse effect level 
NSAID 
non-steroidal anti-inflammatory drugs 
OTC 
over the counter 
PD 
pharmacodynamic 
PEF 
peak expiratory flow 
PI 
Principal Investigator 
PK 
pharmacokinetic 
PO 
by mouth 
pp 
per protocol 
PRI 
platelet reactivity index 
PRU 
P2Y12 reaction units 
PT 
prothrombin time 
PT/INR 
prothrombin time/international normalized ratio 
PTT 
partial thromboplastin time 
QD 
once daily 
QTinterval 
time from the start of the Q wave to the end of the T wave 
QTcB 
Bazett-corrected QT interval 
QTcF 
Fridericia-corrected QT interval 
RBC 
red blood cells 
RR 
respiration rate 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SAR 
suspected adverse reaction 
SBP 
systolic blood pressure 
SD 
standard deviation 
SDV 
source document verification 
SOC 
system-organ-class 

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SOE 
SOP 
SpGr 
SRC 
SUSAR 
t1/2 
schedule of events 
standard operating procedure 
 
specific gravity 
safety review committee 
suspected unexpected serious adverse reaction 
terminal elimination half-life 
TAM 
ticagrelor active metabolite AR-C124910XX 
 
TEAE 
treatment-emergent adverse event 
 
TG 
Tmax 
triglycerides 
time to reach the observed maximum (peak) concentration 
 
TSH 
thyroid stimulating hormone 
 
ULN 
upper limit of normal 
 
US/USA 
United States of America 
 
VASP 
vasodilator-stimulated phosphoprotein 
 
Vd 
w/v 
WBC 
WHO-DD 
WOCBP 
volume of distribution 
weight over volume 
white blood cell 
World Health Organization drug dictionary 
women of child-bearing potential 

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APPENDIX 2 
PREGNANCY TESTING, REPORTING GUIDANCE AND 
CONTRACEPTION METHODS 
PREGNANCY TESTING 
• 
Urine pregnancy testing must be performed using the test kit provided by the central 
laboratory in accordance with instructions provided in its package insert 
• 
Serum pregnancy testing will be performed and assayed in the local and central 
laboratory as per schedule of events (Appendix 3) 
COLLECTION OF PREGNANCY INFORMATION 
Female subjects who become pregnant within 35+3 days post last dose of study drug 
• 
Investigator will collect pregnancy information on any female subject, who becomes 
pregnant while participating in this study and will complete the Exposure In-Utero form 
and submit to the Sponsor within 24 hours of learning of a subject's pregnancy 
• 
Subject will be followed to determine the outcome of the pregnancy. Any termination of 
pregnancy will be reported, regardless of fetal status (presence or absence of anomalies) 
or indication for procedure 
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy will be reported as an AE or SAE 
• 
A spontaneous abortion is always considered to be an SAE and will be reported as such 
• 
Any SAE occurring as a result of a post-study pregnancy which is considered reasonably 
related to the study treatment by the Investigator, will be reported to the Sponsor. While 
the Investigator is not obligated to actively seek this information in former study subjects, 
he or she may learn of an SAE through spontaneous reporting 
• 
Any female subject who becomes pregnant while participating will discontinue treatment 
(as applicable) 
• 
Generally, follow-up will be approximately 30 days following the estimated delivery 
date. Any termination of the pregnancy will be reported regardless of fetal status 
(presence or absence of anomalies) or indication for procedure 
Male subjects with partners who become pregnant 
• Investigator will attempt to collect pregnancy information on any male subject’s female 
partner who becomes pregnant while participating in this study and report it to PhaseBio 
within 24 hours of learning of the partner’s pregnancy 
• Partner may also be followed to determine the outcome of the pregnancy. Information on 
the status of the mother and child will be forwarded to PhaseBio 
• Generally, follow-up will be 30 days following the estimated delivery date. Any 
termination of the pregnancy will be reported regardless of fetal status (presence or 
absence of anomalies) or indication for procedure 

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CONTRACEPTION METHODS AND DEFINITIONS 
Definition of Women of Childbearing Potential and of Fertile Men 
A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and 
until becoming post-menopausal unless permanently sterile. Permanent sterilization methods 
include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Female subjects who 
have bene sterilized are not deemed to be of childbearing potential and do not need to maintain 2 
methods of contraception. 
A postmenopausal state is defined as no menses for 12 months without an alternative medical 
cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used 
to confirm a post-menopausal state in women not using hormonal contraception or hormonal 
replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH 
measurement is insufficient. 
A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy 
(CTFG, 2014) 
Recommended Methods of Contraception 
For women 
• 
Implants, injectables, combined oral contraceptives, intrauterine devices (IUDs), sexual 
abstinence, combined oral contraceptives with inhibition of ovulation or a partner who 
has been surgically sterile (e.g. by vasectomy) for at least 6 months 
For men 
• 
Surgical sterility (e.g. by vasectomy) for at least 6 months, sexual abstinence, or condoms 
plus spermicide. 
Exceptions 
• Female subjects who have been sterilized are not deemed to be of childbearing potential 
and do not need to maintain 2 methods of contraception 
• Female subjects with a male partner may each use one of the contraception methods as 
defined within Appendix 2 and Section 8.5 
• Confirmed abstinence does not require a second form of contraception 
• Follicle stimulating hormone (FSH) level may be performed at Screening using local or 
central laboratory, for confirmation of postmenopausal status as directed by the 
Investigator 

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Outpatient 
Outpatient/In- 
Clinic 
Treatment (In- 
Clinic) 
Outpatients 
Procedure 
Screeninga 
Check-in/ 
Pretreatment 
Rand 
Subject 
DC 
FUP 
FUP 
EOS 
Study Day(s) 
–45 to – 
4 
-7 
–3 
-2 
–1 
1 
2 
3 
7 
35+3 
Serum immunogenicity 
(ADA testing)s 
X 
Xs 
X 
Xs 
Infusions site assessmentt 
X 
X 
X 
X 
X 
AEs/SAEsu 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medicationsv,w 
Xv 
Xv 
Xv 
Xv 
Xv 
Xw 
Xw 
Xw 
Xw 
Xw 
Discharge from clinicx 
X 
Xx 
Xx 
Abbreviations: AE=adverse event; ADA=anti-drug antibody; ASA= aspirin; BMI=body mass index; 
DBP=diastolic blood pressure; DC = discharged; ECG=electrocardiogram; EDC=electronic data capture; 
EOS=end of study; FUP=follow-up; HR=heart rate; PD=pharmacodynamics; PK=pharmacokinetics; 
PRU=P2Y12 reaction units; QD=once daily; Rand=Randomization; RR=respiratory rate; SAE=serious 
adverse event; SBP=systolic blood pressure; TAM=ticagrelor active metabolite AR-C124910XX; 
VASP=vasodilator-stimulated phosphoprotein 
a 
Screening Period = Days -45 to -4 (including Day -7, when ASA is started) 
b 
If verbal consent is obtained, it must be witnessed by an impartial witness. The details and full process 
to be fully documented in source documents 
Note: Any changes to site-specific processes due to COVID-19 pandemic must be fully documented 
and identified within source documents and eCRF 
c 
Serum pregnancy test for women of childbearing potential only. May utilize central or local 
laboratory as needed 
d 
Stool for occult blood test may be conducted at either the central or local laboratory as needed. 
The Day 3 stool occult sample may be collected on Day 2 if needed 
e 
A full physical examination is conducted at Screening, Day -3 and Day 35+3 
Height and weight collected at Screening and Day 35+3 only 
BMI is calculated within the electronic data capture system 
f 
Brief physical examination and querying the subject concerning any changes from baseline. A 
brief physical examination will include assessment of heart, skin, lungs, cardiovascular system, 
and abdomen, and extremities 
g 
Vital sign measurements (SBP and DBP, body temp, RR, and HR) will be collected at screening, 
check-in (Day -3), before dosing (30 to 60 minutes prior to the initiation of the study drug 
infusion) and at 15±5, 30±10, 45±10, 60±15 min, 24 hours±15 min and 48 hours±15 min 
following initiation of study drug 
Vital Signs are also collected on Day 7 and 35+3. Vital signs at 15, 30, 45, and 60 minutes 
following infusion require only SBP and DBP, and HR 

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h 
12-lead ECGs will be obtained at Screening before initiation of PB2452/placebo, pre-treatment 
Day -1, and on treatment Days 1, 2, 7 and 35+3. The specific time points for 12-lead ECG on Day 
1 and 2 will be pre-dose, 10 minutes after bolus, end of infusion, and after 24 hours (+ 30 
minutes) from initiation of infusion. ECGs will be collected anytime on Days 7 and 35+3 
i 
All scheduled clinical laboratory tests will be performed centrally with the exception of Day -1 
clinical laboratory testing which should be performed locally to provide results prior to 
randomization 
Note: There is no scheduled clinical laboratory test o Day 3. However, if required the clinical 
laboratory tests (hematology, chemistry, coagulation, and urinalysis) may be repeated if 
considered clinically significant by the Investigator based on Day 2 lab results 
j 
Local/central laboratory results must be confirmed to ensure continued eligibility prior to 
randomization 
k 
ASA 81 mg will be taken on Days -7, -6, -5, -4, -3, -2, -1, and on Day 1 no less than 2 hours 
before study drug is started. Subjects who enter the study already taking ASA daily must 
document a daily ASA 81 mg dose between Day -7 and Day -3. Subjects will receive daily ASA 
81 mg between Day -3 (or Day -2 if the subject took ASA 81mg on Day -3 prior to Check-in) and 
Day 1 at the clinical facility and will suspend further ASA dosing until discharge from the clinical 
facility on Day 3 
l 
Beginning in the morning on Day –2, a single dose of oral ticagrelor 180 mg will be given, 
followed by oral ticagrelor 90 mg every 12 hours (or BID) for 4 additional doses through to Day 
1. The final dose of ticagrelor should occur 2 hours±15 min before study drug is initiated) 
m 
PB2452/placebo will be administered at Hour 0 of Day 1 
Infusion of PB2452/placebo is initiated on Hour 0 of Day 1 and will continue for approximately 
16 hours for a total of 18 g (180 mL), as described in the protocol and pharmacy manual. 
In subjects with known or reported concomitant use of moderate or strong CYP3A inhibitors 
(Appendix 4), an alternative 36 g (360 mL) regimen of PB2452 infused for approximately 24 
hours will be administered as directed by the pharmacy manual 
n 
A pre-ticagrelor blood sample will be collected on Day -2, within 60 mins prior to the dose of 
ticagrelor. Blood samples for determination of plasma PB2452, plasma ticagrelor/TAM and 
unbound plasma ticagrelor/TAM will be collected on Days 1 to 3 within 10 minutes prior to the 
initiation of PB2452/placebo infusion (Hour 0) and at 5, 10, 30 minutes and 1, 2, 4, 8, 12, 20, 24, 
36, and 48 hours after initiation of study drug infusion 
Plasma PK samples will also be collected on Day 7, and Day 35+3 after initiation of study drug 
infusion 
o 
Urine samples for PK ticagrelor/AR-C124910XX to be collected at i) 0 to 6 hours; ii) 6 to 12 
hours and iii) 12 to 24 hours and iv) 24 to 48 hours after the initiation of the study drug infusion 
p 
Collection of Day -2 urine PK sample is a single sample collected within 60 minutes prior to the 
first ticagrelor dose 
q 
Blood samples for PD analysis (PRU/VASP testing) will be collected at the following timepoints: 
Day -2 and Day 1 (within 60 minutes prior to first ticagrelor dose) and Hour 0 (up to 10 minutes 
prior to PB2452/placebo infusion), 5, 10, 30 minutes, 1, 2, 4, 8, 12, 20, 24, 36 and 48 hours after 
initiation of PB2452/placebo infusion 
If there is sufficient material leftover from PK and/or PD blood samples, additional platelet 
function-related biomarker testing, such as P-selectin, may be performed 

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r 
One sample for platelet biomarker testing will be collected into a plasma tube (3.2% Na Citrate) at the 
indicated timepoints. A single Qiagen PAXgene DNA tube per subject is collected at any convenient 
sampling timepoint throughout the study. Detailed instructions are provided in the laboratory manual 
s 
Subjects may be required to return to the site for collection of additional follow-up samples, if the 
sample collected at Day 35+3 tests positive for treatment-emergent ADAs. These visits may 
occur approximately 3 months after the final study visit and approximately every 6 months 
thereafter or until antibody levels return to baseline level 
Note: serum immunogenicity sample on Day 1 must be collected prior to initiation of study drug 
infusion 
t 
Infusion site assessments will be performed for all subjects within 15 minutes before initiation of 
PB2452/placebo infusion at Hour 0, 1, 3, 24, and 48 hours after initiation of PB2452/placebo 
infusion, and on Days 7 and 35+3 
u 
All AEs/SAEs from the time of consent to Day 35+3 are to be reported, regardless of subject 
being within or outside the facility/study site 
v 
All concomitant medications (prescription, over the counter and supplements) to be collected -45 
days from the date informed consent is signed until Day 35+3. Subjects must be on a stable dose 
(meaning no changes in dose) of their medications for at least 30 days prior to initiation of study 
drug (time of randomization) 
w 
New medications and changes to dosing of existing medications can occur post Day 1 
(randomization) and are to be captured at schedule visit up to Day 35+3 
x 
Subjects are discharged from the clinic on Day 3. However, if needed and at the discretion of the 
Investigator, a subject may remain in the study facility beyond the scheduled Day 3 discharge to 
accommodate Day 7 and Day 35+3 follow-up visits. All applicable study-related assessments for 
Day 7 and Day 35+3 will occur as outlined in the protocol 

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APPENDIX 4 
EXAMPLES OF INHIBITORS OF CYP3A 
 
 
CYP3A 
Strong Inhibitors 
boceprevir, cobicistat, danoprevir and 
ritonavir, elvitegravir and ritonavi, 
grapefruit juice, indinavir and 
ritonavir, itraconazole, ketoconazole, 
lopinavir and ritonavir, paritaprevir 
and ritonavir and (ombitasvir and/or 
dasabuvir), posaconazole, ritonavir, 
saquinavir and ritonavir, telaprevir, 
tipranavir and ritonavir, 
telithromycin, troleandomycin, 
voriconazole 
Moderate Inhibitors 
aprepitant, ciprofloxacin, conivaptan, 
crizotinib, cyclosporine, diltiazem, 
dronedarone, erythromycin, 
fluconazole, fluvoxamine, imatinib, 
tofisopam, verapamil 
Note: Investigators are advised to note the list in Appendix 4 may not be all-inclusive. Please 
refer to the following website for further guidance: 
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions- 
table-substrates-inhibitors-and-inducers (#table3-1) (Website, n.d.) periodically and as needed.