This is a dose escalation study that will be conducted in healthy volunteers. Multiple cohorts of volunteers will receive ascending oral doses of AG-348 to evaluate the safety and tolerability of a single oral dose of AG-348, the pharmacokinetics (PK) of a single dose of AG-348, and the pharmacodynamic profile of AG-348 with specific biomarkers assessed in the blood.

Inclusion Criteria:

• Healthy adult male or female subjects 18 - 60 years, in good general health who are able to understand consent and complete all study procedures.
• Female subjects of non-child bearing potential (surgically sterile or post-menopausal as confirmed by age [over 50 years], amenorrhea for 12 consecutive months and FSH).
• Male subjects who are not vasectomized must agree to use contraception up to 30 days after dosing.
• Subjects with body weight ≥50 kg; BMI ≥18.5 and ≤32 kg/m2.
• Subjects who are non-smokers and have not used nicotine containing products for at least 3 months prior to screening.
• Subjects must be willing to refrain from caffeine- or xanthene containing products (chocolate) prior to dosing through 72 hours after dosing.
• Subjects must agree to refrain from strenuous exercise prior to admission through final visit.
• Subjects must refrain from use of alcohol starting 7 days prior to admission through final visit.
• Subjects must agree not to donate blood products for duration of study participation.

Exclusion Criteria:

• Subjects who have previously received AG-348.
• Subjects with clinically relevant screening laboratory tests.
• Female subjects of childbearing potential.
• Male subjects with QTcF interval ECG > 450 msec,or female subjects with QTcF interval ECG > 470 msec.
• Subjects with a history of a serious mental illness.
• Subjects with a clinically relevant medical history or pre-existing medical condition that would interfere with the absorption, metabolism or excretion of the study drug.
• Subjects with a history of any primary malignancy (cancer). Exceptions are certain skin cancers, cervical cancer in situ or other cancers that have been curatively treated without evidence of disease for a minimum of 1 year.
• Subjects with glucose-6-phosphate-dehydrogenase (G6PD) deficiency.
• Subjects who are positive for hepatitis B, hepatitis C or HIV.
• Subjects who have undergone surgery 6 months prior to screening.
• Subjects who have a history of illicit drug use or alcoholism within the last year.
• Subjects who are participating in other concurrent clinical trial of an investigational drug, or have received another investigational agent within the last 2 months.
• Subjects with any conditions which would make the subject unsuitable for enrollment, or could interfere with the subject's participation in or completion of the study.