Risto-cel

Editing Approach:
Activation of fetal hemoglobin

Delivery:
Ex vivo

Clinical Trial:
Phase 1/2 BEACON Trial (Clinicaltrials.gov NCT05456880)

Ristoglogene autogetemcel (risto-cel), formerly known as BEAM-101, is an investigational autologous therapy for the treatment of severe sickle cell disease (SCD) through upregulation of non-sickling and anti-sickling fetal hemoglobin expression. The one-time therapy consists of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) that have been base-edited in the promoter regions of the HBG1/2 genes and are administered via a hematopoietic stem cell transplant procedure. The risto-cel edit is designed to inhibit the transcriptional repressor BCL11A from binding to the promoter without disrupting BCL11A expression, leading to increased production of non-sickling and anti-sickling fetal hemoglobin (HbF). HbF is the predominant hemoglobin variant during development and early life.

The safety and efficacy of risto-cel is being evaluated in the ongoing BEACON Phase 1/2 study, an open-label, single-arm, multicenter trial in adult patients with SCD with severe vaso-occlusive crises.

Risto-cel has been granted orphan drug designation and Regenerative Medicine Advanced Therapy (RMAT) designation by the U.S. Food and Drug Administration.