Ernesto Ayala, M.D.

The purpose of this study is to evaluate the safety and efficacy of a single dose of ex vivo base-edited, autologous CD34+ human hematopoietic stem and progenitor cells (HSPCs) in patients with SCD and severe VOCs. Like allogenic HSCT, these therapies are designed to replace the patient’s bone marrow (BM) with hematopoietic stem cells (HSCs) that encode nonsickling globins. However, as an autologous therapy, BEAM-101 (the IMP in this study) has the potential advantages of eliminating the morbidity and mortality of graft-versus-host disease (GVHD) and greatly broadening access to the majority of patients who lack a matched sibling donor.

BEAM-101 utilizes base editing to introduce specific point mutations that are designed to induce the expression of therapeutic, nonsickling hemoglobin (Hb). BEAM-101 introduces point mutations in the HBG1 and HBG2 promoters, which mimic naturally occurring mutations that disrupt binding of B-cell lymphoma/leukemia 11A gene (BCL11A), a transcriptional repressor of fetal hemoglobin (HbF). Individuals with these mutations have the condition known as hereditary persistence of fetal hemoglobin (HPFH) and continue to have nonsickling HbF expression throughout their life.

The primary purpose of this study is to compare 1 year graft-versus-host disease (GVHD)-free, graft relapse-free survival (GRFS) between the two GVHD prophylaxis regimens.