This phase 2B study is a multi-center, randomized, double-blind, placebo-controlled study. The study is designed to evaluate the efficacy of bentracimab (PB2452) in reversing the anti-platelet effects of ticagrelor as part of a dual antiplatelet regimen and to evaluate the safety and tolerability of bentracimab (PB2452) in subjects aged 50-80 years old.

A total of 205 subjects between 50-80 years old will be enrolled in the US or 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 bentracimab (PB2452) investigational study drug or placebo. Hence, a total of 154 subjects will be receiving bentracimab (PB2452) and approximately 51 subjects will be receiving placebo.

The study will consist of a Screening period, a Check-in day, an on-site Randomization/Treatment day, a 2-day on-site Follow-up period (Days 2 through 3), a Follow-up visit (Day 7), and a Final Follow-up visit (Day 35±3). 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. Seven days prior to enrollment, subjects will be administered ASA 81 mg orally once daily (QD) until the final dose on Day 1. 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 for 4 additional doses through to Day 1 (2 hours before study drug is initiated; this will be 5 total doses of ticagrelor).

On Day 1, subjects who meet all the inclusion criteria and none of the exclusion criteria will be randomized with 3:1 allocation ratio (active:placebo), to receive an IV dose of bentracimab (PB2452) or placebo 2 hours following the 5th ticagrelor dose. Subjects may be discharged from the clinical site on Day 3 and will return for a Follow-up visit on Day 7, if already discharged, and on Day 35 (±3 days). 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.

If a subject is taking a moderate or strong cytochrome P450 3A isozyme (CYP3A) inhibitor, a 36 g alternative regimen of bentracimab (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.

Inclusion Criteria:

• The subject provides written or verbal informed consent (in-person or remotely) and agrees to comply with all protocol requirements throughout study participation.
• The subject is male or female between ≥50 and ≤80 years of age.
• The subject has a body mass index between 18 and 35 kg/m2 and a weight of ≥ 50 kg but ≤ 120 kg, inclusive, at screening.
• 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 Check-in. Subjects with chronic, stable, and well-controlled medical conditions, are eligible provided they meet all other inclusion/exclusion criteria.
• The subject has specific inclusionary laboratory values at screening and check-in: white blood cell (WBC) count, platelet count, haemoglobin level, thyroid-stimulating hormone (TSH) level, and prothrombin time (PT) and partial thromboplastin time (PTT) levels within the normal range.
• Subjects taking medications for well-controlled medical conditions must have been on a stable dose for at least 30 days prior to screening visit.
• Subjects entering the study must be willing to start and/or document 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. Subjects already taking daily aspirin must suspend aspirin dosing after Day 1 until discharge from the clinical facility.
• Female subjects of childbearing potential must not be pregnant, lactating, or planning to become pregnant for 3 months after the last dose of study drug. Female subjects of childbearing potential must use two effective methods of birth control from screening and before study drug administration through to the end of the study.

Exclusion Criteria:

• In the opinion of the Investigator there are concern(s) regarding the inability of the subject to comply with study procedures and/or follow up, or, if the subject is not suitable for entry into the study.
• 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.
• 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.
• Any clinically significant abnormal findings in physical examination, vital signs, laboratory assessments, and ECG parameters identified during screening or check-in.
• Any specific contraindication to ticagrelor as described in the ticagrelor prescribing information.
• Receiving chronic treatment with nonsteroidal anti-inflammatory drugs [including aspirin (>100 mg daily), anticoagulants, or other antiplatelet agents that cannot be discontinued 14 days prior to screening including clopidogrel, prasugrel, ticlopidine, dipyridamole, or cilostazol].
• First positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus types 1 or 2 antibodies at screening.
• Has received another investigational drug within 30 days of the administration of study drug in this study or within 5 half-lives of the experimental medication, whichever is longer.
• History of severe or ongoing allergy/hypersensitivity to any biologic therapeutic agent.
• Involvement with any PhaseBio or study site employee or their close relatives (e.g., spouse, parents, siblings, or children whether biological or legally adopted).
• Previously received Bentracimab (PB2452) or had been randomized to receive study drug in an earlier cohort for this study