 Investigational product IP will be administered orally with approximately 240 mL of noncarbonated, room-temperature water. Subjects will enter the clinic prior to the evening meal on the day before dosing Day -1 and will take a single oral dose of AG-221 at Hour 0 on the dosing day Day 1, following a 10 hour overnight fast. After the dose is administered, subjects will be observed for 7 days to assess the acute safety profile before the next higher, protocol specified dose cohorts can enroll. The Sponsor and Investigator will review all available safety information prior to escalation to the next cohort to ensure that no safety issues exist. 