BEAM-104

BEAM-104 is an investigational ex vivo cell therapy developed by Beam Therapeutics for the treatment of sickle cell disease and beta-thalassemia. It utilizes multiplex base editing technology to modify autologous hematopoietic stem and progenitor cells (HSPCs). The therapy involves two distinct genetic edits: the first targets the promoter region of the HBG1/2 genes to induce the expression of fetal hemoglobin (HbF), which compensates for the defective adult hemoglobin in patients. The second edit introduces a specific missense mutation in the extracellular domain of the CD117 (c-Kit) receptor. This second edit is a key component of Beam's ESCAPE (Engineered Stem Cell Antibody Paired Evasion) technology, designed to allow the edited cells to evade depletion by BEAM-103, a monoclonal antibody targeting CD117 used for non-genotoxic conditioning. This approach aims to replace traditional toxic chemotherapy-based conditioning with a more targeted, antibody-based method, potentially improving the safety profile of hematopoietic stem cell transplantation.