The clinical hold for the development of BEAM-201 has been lifted, allowing investigators to assess the agent in patients with relapsed/refractory T-cell acute lymphoblastic leukemia/ T-cell lymphoblastic lymphoma.
The FDA has lifted the clinical hold and cleared the investigational new drug (IND) application for BEAM-201 for patients with relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL)/T-cell lymphoblastic lymphoma (T-LL), according to Beam Therapeutics Inc.1
BEAM-201 is a potent, specific anti-CD7, multiplex-edited, allogeneic chimeric antigen receptor (CAR) T-cell in development.
The product is made using a GMP-compliant, clinical-scale process. Here, T cells from healthy donors are base edited at the same time at 4 genomic loci. Then, they are transduced with a lentivirus coding for an anti-CD7 CAR. These cells are then universally compatible, allogeneic CD7-targeting CAR-T cells which are resistant to both fratricide and immunosuppression.2
“The FDA’s clearance of our IND for BEAM-201 is an exciting moment for Beam and for the field of gene editing, as it represents the first IND clearance for a multiplex-base edited investigational drug,” said John Evans, chief executive officer of Beam Therapeutics Inc, in the press release.
Previously in August 2022, the CAR T-cell product, BEAM-201, was placed on clinical hold by the FDA after the IND was submitted at the end of June.3
In an email from the agency in late-July, the FDA requested additional control data from genomic rearrangement assessments and further analyses of certain off-target editing experiments.4 Further, the FDA asked for more control data for a cytokine-independent growth assay and an updated investigator brochure including information from any new nonclinical studies.
Preclinical models examining BEAM-201 demonstrated potent and dose-dependent tumor control in an in vitro and in vivo xenograft model. The agent elicited 96%-99% on-target editing at clinical scale and in vivo proof of concept of tumor clearance.2
There were no detected genomic rearrangements resulting from the editing process with simultaneous quad base editing of T cells. Additionally, multiplex base editing also did not negatively affect the expansion of the cell during manufacturing.
The expression with CBE-edited cells also was decreased in the 4 target genes and there was minimal effect on other genes, including key members of the p53 pathway which are upregulated because of DNA double-stranded breaks produced by multiplex editing with nucleases.
Now with the IND cleared, the company will move forward with the development of the agent, including examining it in clinical trials of patients with T-ALL/T-LL.
“We believe the future of cell therapy involves high levels of cell engineering, enabled by multiplex base editing technology. Combining four unique edits with high efficiency, BEAM-201 has the potential to make a substantial impact for patients diagnosed with these challenging T-cell cancers, who lack innovative, new treatment options for their disease. We’re pleased that this clearance allows us to bring this novel medicine into human clinical trials, and we look forward to providing updates on next steps for the program in 2023,” added Evans in the press release.