Study to Evaluate the Safety, Tolerability, PK, and PD of PB2452 in Healthy Volunteers

Inclusion Criteria

• The subject is male or female between 18 and 50 years of age, inclusive.
• 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.

Specific inclusionary laboratory values at screening and check-in require the following:

• Aspartate transaminase (AST), alanine transaminase (ALT), total serum bilirubin and alkaline phosphatase levels within the normal range as defined by the clinical laboratory
• White blood cell (WBC) count, platelet count and hemoglobin level within the normal range as defined by the clinical laboratory
• Thyroid stimulating hormone (TSH) level within the normal range as defined by the clinical laboratory at screening
• Prothrombin time (PT) and partial thromboplastin time (PTT) level within the normal range as defined by the clinical laboratory
• Female subjects of childbearing potential must not be pregnant, lactating, or planning to become pregnant before 3 months after the last dose of study drug, 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 (ie, oral, implantable, patch, or injectable contraceptives in combination with a condom, hormone-containing intrauterine device that has been in place for at least 2 months prior to screening in combination with a condom, double-barrier method [ie, condoms, sponge, diaphragm, or cervical cap with spermicidal gels or cream], or vasectomy for male subjects or male partners of female subjects) from 30 days before study drug administration through the end of the study. Women are considered not to be of childbearing potential if they have fulfilled one of the following criteria: documentation of irreversible surgical sterilization (ie, hysterectomy, or bilateral oophorectomy [not tubal ligation]), or postmenopausal (defined as amenorrhea for 12 consecutive months following cessation of all exogenous hormonal treatments, and documented plasma follicle-stimulating hormone level >40 IU/mL or amenorrhea for 24 consecutive months). Male subjects with partners of childbearing potential must agree to use appropriate and effective measures of contraception (eg, condom plus diaphragm with spermicide; condom plus spermicide) during the study and for 30 days after the last dose of study drug, and to refrain from donating sperm for at least 7 days prior to the first dose of study drug until at least 90 days following the last dose of study drug.
• The subject agrees to comply with all protocol requirements.
• The subject is able to provide written informed consent.

Exclusion Criteria

• History of any clinically significant acute or chronic disease or medical disorder.
• History or presence of gastrointestinal, hepatic (with the exception of Gilbert's syndrome), or renal disease or renal insufficiency (ie, estimated glomerular filtration rate <60 ml/min/1.73m2), or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study drug or any planned surgical procedure that will occur during the study (from screening through the Day 28 follow up visit).
• Any clinically significant abnormal findings in physical examination, vital signs, laboratory assessments, and ECG parameters identified during screening or check-in.
• Any history of arterial or venous thrombosis, including any of the following:
• History of transient ischemic attack, cardiovascular accident, stroke (ischemic or hemorrhagic), unstable angina, myocardial infarction, or peripheral arterial disease
• History of de