A Study of AG-348 in Adult Participants With Pyruvate Kinase (PK) Deficiency

Exclusion Criteria

• •1. Hb ˃ 12.0 g/dL if male, Hb ˃11.0 g/dL if female
• •2. Additional diagnosis of other congenital or acquired blood disorder
• •3. Iron overload sufficiently severe to result in cardiac, hepatic or pancreatic insufficiency
• •4. Bone marrow or stem cell transplant
• •5. Clinically symptomatic cholelithiasis or cholecystitis
• •6. Currently enrolled in any other investigational trial. Participation in the PK Deficiency Natural History Study (NCT02053480) is permitted
• •7. Exposure to any investigational drug, device or procedure within 28 days prior to screening or during trial participation
• •8. Concurrent medical condition such as poorly controlled hypertension, heart failure, active infection, frequent post-splenectomy sepsis, Hepatitis B or C, Human Immunodeficiency Virus type 1 (HIV1) or Human Immunodeficiency Virus type 2 (HIV2) infection, poorly controlled diabetes mellitus, history of primary malignancy with the exception of curatively treated nonmelanomatous skin cancer, cervical cancer of breast cancer in situ
• •9. Major surgery in the last 6 months
• •10. Psychiatric disorder that could compromise the ability of the patient to cooperate with the study
• •11. Serum bilirubin higher to the upper limit of normal attributable to factors other than hemolysis or Gilbert's Syndrome
• •12. Use of restricted products known to strongly inhibit cytochrome P450 (CYP) 3A4 metabolism within 5 days prior to Prior Day 1 dosing, or to strongly induce cytochrome P450 3A4 (CYP3A4) metabolism within 28 days prior to Day 1 dosing, or to strongly inhibit P-glycoprotein transporter within 5 days prior to Day 1 dosing, or digoxin within 5 days prior to Day 1 dosing.
• •13. Heart-rate corrected QT interval - Fridericia's method (QTcF) interval ˃ 450 ms in male, QTcF \> 470 ms in female, with the exception of patients with a left Bundle Branch Block
• •14. Cardiac arrhythmias that are clinically significant or treated with drugs that are substrates of CYP3A4
• •15. Allergy to sulfonamides if characterized by acute hemolytic anemia, anaphylaxis, rash of erythema multiforme type or Stevens-Johnson Syndrome
• •16. Any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patient's ability to participate in the study
• •17. Patients will not be permitted to enter the Extension Period if: The patient experienced AEs during the Core Period that are considered by the treating Investigator or the Sponsor's designated Medical Monitor to pose a significant safety risk to the patient if treatment were to be extended