A Dose-Finding Study of Tebapivat to Assess Efficacy, and Safety in Participants With Sickle Cell Disease (SCD)

Key Inclusion Criteria:

• Documented diagnosis of SCD (HbSS, HbSC [combined heterozygosity for hemoglobins Sand C], sickle hemoglobin [HbS]/β0-thalassemia, HbS/β+-thalassemia, or other sicklecell syndrome variants).

• Hemoglobin ≥5.5 and ≤10.5 grams per decilitre (g/dL). Hemoglobin concentration mustbe based on an average of at least 2 Hb concentration measurements (separated by ≥7days) collected during the screening period.

• If taking hydroxyurea, the hydroxyurea dose must be stable for at least 90 daysbefore randomization. Discontinuation of hydroxyurea requires a 90-day washoutbefore providing informed consent.

Key Exclusion Criteria:

• Receiving regularly scheduled red blood cell (RBC) transfusion therapy (also termedchronic, prophylactic, or preventative transfusion); episodic transfusion inresponse to worsened anemia or vaso-occlusive crisis (VOC) is permitted.Additionally, a participant who requires episodic transfusion(s) may not havereceived a transfusion(s) within 60 days before providing informed consent or duringthe screening period.

• >10 sickle cell pain crisis (SCPCs) in the 12 months before providing informedconsent.

• Receiving anabolic steroids that have not been stopped for at least 4 weeks beforerandomization. Testosterone replacement therapy to treat hypogonadism is allowed;the testosterone dose and preparation must be stable for ≥10 weeks beforerandomization.

• Hospitalized for an SCPC and/or other vaso-occlusive event within 14 days beforeproviding informed consent or within 14 days before randomization. If an SCPC occursduring the screening period, the screening period may be extended with MedicalMonitor approval.

• Receiving treatment with voxelotor, crizanlizumab, or L-glutamine within 90 daysbefore randomization.

• Platelet count <lower limit of normal (LLN) for the local laboratory or <150×109/liter (L) (whichever is lower) during screening. Platelet transfusionsreceived within 28 days before consent or during screening.

• Receiving treatment with hematopoietic stimulating agents within 90 days beforerandomization.

• Prior exposure to gene therapy or prior bone marrow or stem cell transplantation,including any conditioning regimen.