Beam sheds more light on clinical hold slapped on gene-edited CAR-T

A month after announcing that the FDA had slapped a clinical hold on its phase 1-ready, gene-edited CAR-T, Beam Therapeutics is shedding more light on the move.

The FDA’s concerns about BEAM-201 are multi-faceted but include questions about the company’s gene-editing technology. The agency requested “additional control data from genomic rearrangement assessments” and “further analyses of certain off-target editing experiments,” according to a Tuesday disclosure. The FDA is also looking for more control data for a “cytokine-independent growth assay” and “updated investigator brochure that includes information regarding any new nonclinical studies.” 

The details came in a formal letter to Beam following a late-July email from the FDA. The company expects to be able to respond to the agency’s questions in the fourth quarter.

All FDA-approved CAR-Ts are derived from a patient’s own cells, a process that sacrifices time and cost for specificity. Some companies have touted that the future of this cell therapy lies instead with allogeneic alternatives, which are derived from donor cells. But it’s harder to convince your body that someone else’s cells are actually therapy.

That’s where BEAM-201 theoretically comes in. The company uses base editing technology to alter one of the four main bases that make up the human genome. That contrasts with the more popularized gene editing method, including CRISPR, which opens up the DNA helix to make larger edits. Metaphorically speaking, it’s like swapping in the correct letter in a crossword puzzle. BEAM-201 is being designed as a leukemia and lymphoma treatment targeting CD7, a protein expressed on T cells. 

Evidently, the company’s editing aspirations have been more difficult to execute than expected. In addition to addressing regulators’ questions, the company reported earlier in August that more edits than expected are necessary to make its cell therapies fully allogeneic. The revelation means that the company will no longer be nominating a second CAR-T candidate in 2022. 

Nonetheless, Beam has attracted top players to partner up, namely Pfizer which signed on to a four-year, $1.35 billion pact earlier this year, which included $300 million in upfront cash. In exchange, Beam is offering up three in vivo programs targeting rare diseases in the liver, muscle and central nervous system. Beam also linked up with Apellis Pharmaceuticals in 2021 in a $75 million collaboration. The deals have contributed to a substantial war chest, now $1.2 billion strong. 

Although its CAR-T program has taken a gut punch, the company continues to press on with its first clinical trial, testing BEAM-101 in patients with sickle cell disease. The company has not yet started recruitment but intends to do so in the second half of the year. 

Editor's note: This article was corrected Aug. 31 to note that BEAM-201 targets CD7, not CD47.