A Study of IMR-687 in Subjects With Sickle Cell Disease

Exclusion Criteria

• •1. Hospital discharge for sickle cell crisis or other vaso-occlusive event within the 4 days prior to randomization (Day 1).
• •2. Subjects participating in a chronic/prophylactic RBC transfusion program (i.e., regularly scheduled RBC transfusions); any transfusions within 21 days of screening or baseline Hb measurements
• •3. Subjects with HbF \>25% at screening.
• •4. Significant kidney disease (eGFR \<45mL/min) and liver dysfunction: alanine aminotransferase or aspartate aminotransferase \>3x upper limit of normal.
• •5. Body mass index (BMI) \<17.0 kg/m2 and a total body weight \<45 kg; or a BMI \>35 kg/m2.
• •6. Subjects with known active hepatitis A, hepatitis B, or hepatitis C, with active or acute event of malaria, or who are known to be positive for human immunodeficiency virus (HIV).
• •7. Stroke requiring medical intervention within 24 weeks prior to randomization (Day 1).
• •8. Prior exposure to IMR-687.
• •9. Subjects taking direct acting oral anti-coagulants (apixaban, dabigatran, rivaroxaban, edoxaban, or ticagrelor) or taking warfarin unless they stopped the treatment at least 28 days prior to randomization (Day 1).
• •10. A history of use of crizanlizumab (Adakveo®) or voxelotor (Oxbryta®) within 6 months prior to signing the informed consent.
• •11. Receipt of erythropoietin, luspatercept (Reblozyl®)or other hematopoietic growth factor treatment within 3 months of signing the ICF or anticipated need for such agents during the study.
• •12. Prior gene therapy.