A Study of Etavopivat in Adults and Adolescents With Sickle Cell Disease (HIBISCUS)

Key Inclusion Criteria:

• Provision of consent

• Patient has a confirmed diagnosis of sickle cell disease

• At least 2 episodes of vaso-occlusive crises in the past 12 months

• Hemoglobin ≥ 5.5 and ≤ 10.5 g/dL (≥ 55 and ≤ 105 g/L) during screening

• Patients taking hydroxyurea, must demonstrate a stable dose for at least 90 daysprior to start of study treatment

• Patients on crizanlizumab or L-glutamine treatment at the time of consent must be ona stable dose for ≥ 12 months and must be ≥ 80% compliant with the planned regimenat the time of consent and meet the VOC eligibility criteria

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

Key Exclusion Criteria:

• More than 15 vaso-occlusive crises within the past 12 months

• Female who is breastfeeding or pregnant

• Hepatic dysfunction characterized by:

• Alanine aminotransferase (ALT) > 4.0 × upper limit of normal (ULN)

• Direct bilirubin > 3.0 × ULN

• Known HIV positivity

• Active hepatitis B or hepatitis C infection

• Severe renal dysfunction or on chronic dialysis

• History of unstable or deteriorating cardiac or pulmonary disease within 6 monthsprior to consent including but not limited to the following:

• Unstable angina pectoris or myocardial infarction or elective coronaryintervention

• Congestive heart failure requiring hospitalization

• Uncontrolled clinically significant arrhythmias

• Symptomatic pulmonary hypertension

• History of overt clinical stroke within previous 2 years or any history of anintracranial hemorrhage

• History of deep venous thrombosis requiring systemic anti-coagulation therapy for ≥ 6 weeks, occurring within 6 months prior to Day 1 of study treatment.

Prior/Concomitant Therapy

• Patients receiving regularly scheduled blood (RBC) transfusion therapy (also termedchronic, prophylactic, or preventive transfusion)

• Receiving or use of concomitant medications that are strong inducers of CYP3A4/5within 2 weeks of starting study treatment or anticipated need for such agentsduring the study

• Use of voxelotor within 28 days prior to starting study treatment or anticipatedneed for this agent during the study

• Use of an experimental selectin antagonist (eg, monoclonal antibody or smallmolecule) within 28 days of starting study treatment or anticipated need for suchagents during the study

• Use of erythropoietin or other hematopoietic growth factor treatment within 28 daysof starting study treatment or anticipated need for such agents during the study

• Receipt of prior cellular-based therapy (eg, hematopoietic cell transplant, genemodification therapy)