Beam Therapeutics provided data on genomic rearrangement, off-target edits and from a cytokine independent growth assay to the FDA in November 2022.
The FDA has lifted the clinical hold on and cleared the investigational new drug application (IND) of Beam Therapeutics’ multiplex-base edited chimeric antigen receptor (CAR) T-cell therapy BEAM-201 for the treatment of relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL)/T cell lymphoblastic lymphoma (T-LL).1
“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,” John Evans, chief executive officer, Beam Therapeutics, said in a statement.1 “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.”
The hold was originally placed on the IND in August 2022, with the FDA later requesting genomic rearrangement assessments and data on off-target edits and from a cytokine independent growth assay in preclinical studies which Beam Therapeutics revealed they had provided in November.2,3 The company had initially submitted the IND in June 2022.
BEAM-201 is an allogeneic, anti-CD7, CAR T-cell therapy electroporated and transduced ex vivo that uses multiplex editing for high-precision editing of the cell therapy. Another of Beam’s base-editing stem cell therapies, Beam-101, is being evaluated in the phase 1/2 BEACON trial (NCT05456880), which Beam recently announced had enrolled its first patient with sickle cell disease in late November 2022.4 BEAM-101's base editing mimics single nucleotide polymorphisms that cause persistence of fetal hemoglobin to inhibit hemoglobin S polymerization. The editing is also designed to avoid double stranded breaks.
“The enrollment of the first patient in our BEACON trial is a significant step forward for Beam and for the field of base editing,” Evans said in a previous statement. “With the potency and precision of base editing, we believe BEAM-101 could be a best-in-class option for SCD patients with several advantages over other available genetic therapies. We are now focused on activating additional clinical trial sites in the US, modifying the BEACON protocol to enable expedited future patient enrollment and endpoint assessment, and finalizing our commercial-ready manufacturing process. We look forward to advancing this program for patients who suffer from the painful and debilitating consequences of SCD.”