Study to Evaluate the Effect of GBT440 Administered Orally to Patients With Sickle Cell Disease (GBT_HOPE)

This is a randomized, placebo-controlled, double blind, parallel group, multicenter study of
participants, age 12 to 65 years, with SCD. The key purpose for the study is to establish
efficacy and safety of GBT440 as compared with placebo.

Inclusion Criteria:

1. Male or female study participants with sickle cell disease

2. Participants have had at least 1 episode of vaso-occlusive crisis (VOC) in the past 12
months.

3. Age 12 to 65 years

4. Hemoglobin (Hb) ≥5.5 and ≤10.5 g/dL during screening

5. For participants taking hydroxyurea (HU), the dose of HU (mg/kg) must be stable for at
least 3 months prior to signing the ICF.

Exclusion Criteria:

1. More than 10 VOCs within the past 12 months that required a hospital, emergency room
or clinic visit

2. Patients who are receiving regularly scheduled blood (RBC) transfusion therapy (also
termed chronic, prophylactic, or preventive transfusion) or have received a RBC
transfusion for any reason within 60 days of signing the ICF

3. Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of
signing the ICF (i.e., a vaso-occlusive event cannot be within 14 days prior to
signing the ICF)

4. Hepatic dysfunction characterized by alanine aminotransferase (ALT) >4 × upper limit
of normal

5. Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit;
calculated by the central laboratory) <30 mL/min/1.73 m^2 or on chronic dialysis