Risto-cel

Risto-cel

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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.

ESCAPE
(BEAM-103 & BEAM-104)

ESCAPE (BEAM-103 & BEAM-104)

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The ESCAPE (Engineered Stem Cell Antibody Evasion) platform is comprised of two investigational drug products: BEAM-103, an anti-CD117 monoclonal antibody (mAb) that is designed to suppress and/or eliminate hematopoietic stem and progenitor cells that express CD117, and BEAM-104, a cell therapy that includes an edit to the promoter region of the HBG1/2 genes intended to elevate HbF, plus an additional edit to CD117 designed to prevent binding of BEAM-103, allowing the edited cells to function normally and evade targeting by the antibody. Together, this approach aims to provide a non-genotoxic alternative to traditional transplant myeloablative conditioning.

In vivo 
HSC editing

IN VIVO HSC EDITING

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Beam is exploring the potential for in vivo base editing programs for the treatment of sickle cell disease and beta-thalassemia. Using this approach, base editors would be delivered through intravenous infusion of lipid nanoparticles (LNP) targeted to hematopoietic stem cells, eliminating the need for transplantation.