Single and Multiple Ascending Dose Study and Food Effect Study for AG181

Inclusion Criteria:

• Willing to participate in the study, give written informed consent, and comply withthe study restrictions.

• Body mass index in the range of 18.0 to 30.0 kilograms per square meter (kg/m^2).

• Weight ≥ 50 kilograms (kg) at screening.

• Healthy status as defined by the absence of evidence of any clinically significant,in the opinion of the Investigator, active or chronic disease following a detailedmedical and surgical history, a complete physical examination including vital signs, 12-lead electrocardiogram (ECG), hematology, blood chemistry, serology, andurinalysis.

• Ability and willingness to refrain from alcohol-, caffeine-, andmethylxanthine-containing beverages or food (e.g., coffee, tea, cola, chocolate,energy drinks) from 72 hours (3 days) before administration of the first dose ofstudy drug through follow-up.

• All values for hematology and clinical chemistry tests of blood and urine within thenormal range or showing no clinically relevant deviations, as judged by theInvestigator.

• For women of child bearing potential (WOCBP)*, have a negative serum pregnancy testat Screening and during admission to the clinic. a. *WOCBP are defined as sexually mature women who have not undergone ahysterectomy, bilateral oophorectomy, or tubal occlusion; or who have not beennaturally postmenopausal. WOCBP must use an acceptable method of contraception fromScreening and until 14 days or 5 half-lives of AG-181, whichever is longer, afterlast dose of AG-181. WOCBP using hormonal contraception as a highly effective formof contraception must also use an acceptable barrier method.

• Male participants with female partners of childbearing potential must use a condomduring treatment and for 14 days or 5 half-lives of AG-181, whichever is longer,after last dose of AG-181.

• Male participants must agree not to donate sperm during the study and for 14 days or 5 half-lives of AG-181, whichever is longer, after the last dose of study drug.

• Postmenopausal women are women who have not menstruated at all for at least the 12months before providing informed consent and who have an elevatedfollicle-stimulating hormone (FSH) level indicative of menopause during screening.

• Participants must have discontinued use of prescription drugs (including topicalskin preparations other than nonsteroidal/nonantibiotic nonprescriptionmoisturizers) within 2 weeks or 5 half-lives (whichever is longer) of the first doseof study drug, and over-the-counter (OTC) medication (excluding routine vitamins)within 7 days of the first dose of study drug, unless agreed as not clinicallyrelevant by the Investigator and Medical Monitor (or designee).

Exclusion Criteria:

• Women who are pregnant, lactating, or planning to attempt to become pregnant duringthis study or within 14 days or 5 half-lives of AG-181, whichever is longer, afterlast dose of study drug.

• Males with female partners who are pregnant, lactating, or planning to attempt tobecome pregnant during this study or within 14 days or 5 half-lives of AG-181,whichever is longer, after last dose of study drug.

• Prior exposure to AG-181.

• Use of any investigational drug or device within 30 days before administration ofthe first dose of study drug.

• Any disease which, in the opinion of the Investigator, poses an unacceptable risk tothe participants.

• Clinically significant history of, including treatment within an EmergencyDepartment for, any drug sensitivity, drug allergy, or food allergy, as determinedby the Investigator (such as anaphylaxis, hepatotoxicity, or treatment with steroidsor epinephrine).

• Creatinine clearance <90 milliliters per minute (mL/min) (by Cockcroft-Gaultformula) at screening.

• Aspartate aminotransferase >upper limit of normal (ULN) or alanine aminotransferase >ULN at screening.

• Use of tobacco or nicotine products in the 48 hours (2 days) prior to administrationof the first dose of study drug.

• Strenuous activity, sunbathing, and contact sports within 48 hours (2 days) prior toadministration of the first dose of study drug.

• History of donation of more than 450 milliliters (mL) of blood within 60 days priorto administration of the first dose of study drug.

• Plasma or platelet donation within 7 days prior to administration of the first doseof study drug.

• History within the 12 months before Screening of alcohol consumption exceeding 2standard drinks per day on average (1 standard drink=12 ounce (oz) beer, 5 oz wine,and 1.5 oz spirits). Alcohol consumption will be prohibited 72 hours prior toadministration of the first dose of study drug and until discharge.

• Positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, or anti-human immunodeficiency virus (HIV) 1 and 2 antibodies atscreening.

• Consumption of any nutrients known to modulate cytochrome P450 (CYP450) enzymesactivity (e.g., grapefruit or grapefruit juice, pomelo juice, star fruit, or Seville [blood] orange products) within 14 days prior to administration of the first dose ofstudy drug.

• Positive alcohol or drug screen (cannabinoids, amphetamines, methamphetamines, 3,4-methylenedioxy-N-methylamphetamine [ecstasy], opiates, methadone, oxycodone,phencyclidine, cocaine, cotinine, benzodiazepines, and barbiturates) at screening oradmission to the clinical facility.

• Prolonged heart rate-corrected QT interval (QTc) [heart rate-corrected QT intervalby Fridericia's formula (QTcF) >450 milliseconds (msec)] during screening and priorto first dose of study drug.

• History of long-QT syndrome, torsade de pointes, or any risk factors for torsades depointes in the opinion of the investigator.

• A history in any family member of any of the following: sudden cardiac death,unexplained death, long-QT syndrome, or death from a primary dysrhythmia potentiallyassociated with QT prolongation.