• Provision of consent

• Female patients of childbearing potential must use acceptable methods of contraception, male patients are willing to use barrier methods of contraception

⁃ Cohort A (Sickle Cell Disease Transfusion Cohort)

• Confirmed diagnosis of sickle cell disease

• Chronically red blood cell transfused (sample or exchange \[manual or via electrophoresis\]) for primary stroke prevention or due to previous stroke. Chronic red blood cell transfusion is defined as: ≥ 6 red blood cell units in the previous 24 weeks before the first dose of study treatment and no transfusion-free period for \> 35 days during that period

• At least 24 months of chronic monthly red blood cell transfusions for secondary stroke prevention/treatment of primary stroke (initial completed overt clinical stroke with documented infarction on brain computed tomography \[CT\] or magnetic resonance imaging \[MRI\])

• Prior to screening OR at least 12 months of chronic RBC transfusions for primary stroke prevention (abnormal TCD) prior to screening

• Documented adequate monthly transfusions with average HbS ≤ 45% (the upper limit of the established academic community standard) for the previous 12 weeks of red blood cell transfusions before the first dose of study treatment

⁃ Cohort B (Thalassemia Transfusion Cohort)

• Documented diagnosis of β-thalassemia, Hemoglobin E/ β-thalassemia or Hemoglobin H (α-thalassemia), or other thalassemia variant

• Chronically transfused, defined as: ≥ 6 red blood cell units in the previous 24 weeks before the first dose of study treatment and no transfusion-free period for \> 35 days during that period

⁃ Cohort C (Thalassemia Non-transfused Cohort)

• Documented diagnosis of β-thalassemia, Hemoglobin E/ β-thalassemia or Hemoglobin H (α-thalassemia), or other thalassemia variant

• Hemoglobin ≤ 10 g/dL