Pipeline Broad and diversified portfolio
We seek to potentially cure serious diseases and address significant unmet medical need so that people can reach their full potential. We believe leveraging ex vivo and in vivo approaches, different delivery modalities, and multiple editing approaches will help us target a broad range of diseases, each with an urgent need for new and better treatment options.
Program
Disease
Research
Phase I-Enabling
Phase I/II
Pivotal
Hematology
Sickle cell disease
Phase I/II
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.
(BEAM-103 & BEAM-104)
Sickle cell disease,
Beta-thalassemia
Phase I-Enabling
ESCAPE (BEAM-103 & BEAM-104)
Editing Approach:
Multiplex HbF edit + CD117 edit-antibody pair
Delivery:
Ex vivo
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.
HSC editing
Sickle cell disease,
Beta-thalassemia
Research
IN VIVO HSC EDITING
Editing Approach:
Activation of HbF
Delivery:
In vivo LNP
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.
Liver-Targeted Genetic Diseases
Alpha-1 antitrypsin deficiency
Phase I/II
BEAM-302
Editing Approach:
Correction of E342K mutation
Delivery:
In vivo LNP
Clinical Trial:
Phase 1/2 Trial (Clinicaltrials.gov NCT06389877)
BEAM-302 is a liver-targeting lipid-nanoparticle (LNP) formulation of base editing reagents designed to correct the most common severe form of alpha-1 antitrypsin deficiency (AATD), which results from mutations in the Z allele, known as PiZ, caused by a single G to A point mutation in the SERPINA1 gene. A one-time A-to-G correction of the PiZ mutation with Beam’s adenine base editor has the potential to simultaneously reduce the aggregation of mutant, misfolded AAT protein that causes toxicity to the liver (Z-AAT), generate therapeutic levels of corrected protein (M-AAT), and increase total and functional AAT in circulation, thereby addressing the underlying pathophysiology of both the liver and lung disease. BEAM-302 is delivered via an intravenous infusion.
BEAM-302 is being evaluated in a Phase 1/2, open-label, dose exploration and dose expansion clinical trial to investigate its safety, tolerability, pharmacodynamics, pharmacokinetics and efficacy in AATD patients. Part A of the trial is designed to evaluate AATD patients with lung disease, and Part B will evaluate AATD patients with mild to moderate liver disease with or without lung disease. The dose expansion portions of the trial will identify the optimal dose to take forward in development.
BEAM-302 was granted orphan drug designation and Regenerative Medicine Advanced Therapy (RMAT) designation by the U.S. Food and Drug Administration.
Glycogen storage disease Ia (GSDIa)
Phase I/II
BEAM-301
Editing Approach:
Correction of R83C mutation
Delivery:
In vivo LNP
Clinical Trial:
Phase 1/2 Trial (Clinicaltrials.gov NCT06735755)
BEAM-301 is a liver-targeting LNP formulation of base editing reagents designed to correct the R83C mutation, the most prevalent disease-causing mutation for, and the mutation which results in the most severe form of glycogen storage disease Ia (GSDIa). GSDIa is an autosomal recessive disorder caused by mutations in the G6PC gene that disrupts a key enzyme, G6Pase, critical for maintaining glucose homeostasis. Inhibition of G6Pase activity results in low fasting blood glucose levels that can result in seizures and be fatal. Patients with this mutation typically require ongoing corn starch administration, without which they may enter into hypoglycemic shock within one to three hours.
BEAM-301 is being evaluated in a Phase 1/2, open-label, dose exploration and dose expansion clinical trial to investigate its safety, tolerability, pharmacodynamics, pharmacokinetics and efficacy in GSDIa patients.
Other
Autoimmune disorders and other undisclosed
Research
Undisclosed
Research
Base Editing Applications
Base editing technology is powering an emerging class of precision genetic medicines designed to overcome the limitations of existing approaches and expand the potential of genetic medicine.
Our delivery strategy is to establish a suite of clinically-validated technologies, including electroporation and nonviral and viral delivery modalities.
