AB1 in Adult Patients With Sickle Cell Disease (SCD)

Prior treatment

• Experienced severe sepsis or septic shock within the previous 12 weeks
• Febrile illness in the 1 week prior to baseline visit
• Acute complications due to SCD (i.e., hospitalization, acute pain, or acute chest syndrome) in the 28 days prior to screening visit
• Plans for hospitalization, surgery, or other major procedures during the duration of the study or between screening and baseline
• Moribund or any concurrent disease (e.g., hepatic, renal, cardiac, metabolic) of such severity that death within 24 weeks is likely
• Concurrent diagnosis of malignancy including MDS, leukemia, or an abnormal karyotype
• Blood transfusion in the 28 days prior to screening visit or between screening and baseline visits
• Current treatment with Oxbryta or Adakveo (must be off therapy for 30 days for Oxbryta with no plans to restart and off therapy for 3 months for Adakveo with no plans to restart)
• Other experimental or investigational drug therapy in the past 28 days -

Other illness

• Altered mental status or recurrent seizures requiring anti-seizure medications
• New York Heart Association (NYHA) class III/IV status
• Participant is on chronic transfusion therapy (e.g., for history of TIA or stroke) and medically contraindicated to discontinue transfusions (unless multiple allo-antibodies prevent the patient from getting transfusions as scheduled)
• Known history of illicit drug or alcohol abuse within the past 12 months.

Lab values

• ALT ≥2X the upper limit of normal or albumin <2.0 mg/dL or direct (conjugated) bilirubin ≥ 1.5 mg/dl*
• Serum creatinine >2.9 mg/dL and calculated creatinine clearance <30 mL/min# *
• Platelet count >800 x 109/L OR <150 x 109/L*
• Absolute neutrophil count <1.5 x 109/L*

Other

• Currently pregnant or breastfeeding
• Female of active childbearing potential$ who is unwilling or unable to adhere to the contraception requirements specified in the protocol
• Male with female partner(s) of childbearing potential$ who is unwilling or unable to adhere to the contraception requirements specified in the protocol
• Known Vitamin-B12, folate, or iron deficiency
• Eastern Co-operative Oncology Group (ECOG) performance status ≥3

• Written, informed consent
• Age 18 to 45 years of age, inclusive at screening
• Confirmed SS or S-b0-thalassemia SCD
• Sickle crisis rate of 2-10 within the past year with no crisis in the last 28 days
• HbF <8.6% of total Hb at screening
• Regular compliance with comprehensive care and previous therapy -