PK and Safety Study of AG-221 in Healthy Male Japanese Subjects and Healthy Male Caucasian Subjects

Inclusion Criteria: * Subjects must satisfy the following criteria to be enrolled in the study: Applicable to Japanese Subjects Only 1. Must have been born in Japan to both a Japanese mother and father and also have maternal and paternal Japanese grandparents. 2. Must understand and voluntarily sign an Informed Consent Form (ICF) written in English and Japanese prior to any study related procedures being performed and be able to adhere to restrictions and examination schedules. Applicable to Caucasian Subjects Only 1. Must understand and voluntarily sign a written Informed Consent Form (ICF) prior to any study related procedures being performed and be able to adhere to restrictions and examination schedules. 2. Non-Japanese subjects must be Caucasian. Caucasian is defined as being of European or Latin American descent (ie, White). Applicable to All Subjects 1. Healthy male subjects between 20 to 50 years of age (inclusive) 2. Must be able to communicate with the Investigator and understand and comply with the requirements of the study. 3. Must be in good health as determined by the Investigator according to past medical history, physical examination, vital signs, electrocardiogram (ECG), and laboratory tests. 4. Must have a body mass index (BMI) between 18 and 30 kg/m2 (inclusive). 5. Clinical laboratory tests must be within normal limits or considered by the Investigator to be not clinically significant. 6. Vital signs (systolic and diastolic blood pressure, pulse rate, and oral body temperature) will be assessed in the supine position after the subject has rested for at least 5 minutes. Subject must be afebrile (febrile is defined as ≥ 38 °C or 100.3° F) with vital signs within the following ranges: * Systolic blood pressure: 90 to 140 mm Hg * Diastolic blood pressure: 50 to 90 mm Hg * Pulse rate: 40 to 110 bpm 7. Must have a normal or clinically acceptable physical exam and 12-lead ECG. Subjects must have a QTcF value (Fridericia's Correction Factor) ≤ 450 msec. An ECG may be repeated up to 3 times to determine subject eligibility. 8. Subjects (with or without vasectomy) must agree to use barrier contraception (ie, latex condom or any synthetic material condom \[eg, polyurethane\] NOT made out of natural \[animal\] membrane) when engaging in sexual activity with women of childbearing potential (WCBP) while participating in the study. Subjects must refrain from sperm donations for the entire duration of the study. Exclusion Criteria: * The presence of any of the following will exclude a subject from enrollment: 1. Any serious medical condition, clinically significant laboratory abnormality, or psychiatric illness that would prevent the subject from signing the ICF and/or participating in the study. 2. Recent history (ie, within 3 years prior to dosing) of any clinically significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological or other major disorders. 3. Used any prescribed systemic or topical medication within 30 days of the first dose administration. 4. Used any non-prescribed systemic or topical medication (including herbal medicines, eg, St. John's Wort) within 7 days of the first dose administration (with the exception of vitamin/mineral supplements). 5. Subjects who have any surgical or medical conditions possibly affecting drug absorption, distribution, metabolism and excretion (ADME) or subjects who plan to have any elective or medical procedures during the conduct of the trial. 6. Exposure to an investigational drug (new chemical entity) within 30 days prior to the first dose administration or 5 half-lives of that investigational drug, if known (whichever is longer). 7. Donated blood or plasma within 8 weeks preceding the first dose administration. 8. History of multiple drug allergies (ie, 2 or more). 9. Any clinically significant allergic disease. 10. History of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual \[DSM\]) within 2 years prior to dosing, or positive drug screening test due to illicit drugs. 11. History of alcohol abuse within 2 years prior to dosing, or positive alcohol screen. 12. Subjects who smoke more than 10 cigarettes or consume the equivalent in tobacco per day. 13. Known to have hepatitis, or known to be a carrier of the HBsAg, or HCV Ab, or have a positive result to the test for HBsAg, HCV Ab, or HIV antibodies at Screening.