A Beam Therapeutics cell therapy whose precise gene editing aims to make it a better cancer fighter is now being embraced FDA clinical hold Before a single patient received an experimental treatment.
Beam submitted its investigational new drug application to regulators in late June. On Monday, Cambridge, Mass.-based Beam said it received an FDA email notifying the company of the clinical hold on the BEAM-201 treatment application. Beam said little else than the agency said it would provide a formal clinical hold letter within 30 days.
Beam develops drugs using base-editing technology that enables it to target and edit individual bases in the genome without creating double-strand breaks in DNA. CRISPR is described as molecular scissors, while Beam likens its base-editing technology to a pencil that erases genetic errors and writes the correct letters.
BEAM-201 is made from T cells from healthy donors and is used to create allogeneic or off-the-shelf therapies. Among these modifications are changes that minimize the tumor’s ability to suppress these engineered cells and prevent cell therapy from targeting a patient’s T cells, a phenomenon known as “cannibalism.”
Beam is developing BEAM-201 for the treatment of advanced acute lymphoblastic leukemia and T-cell lymphocytic lymphoma. The therapy was completed by four simultaneous edits, which the company believes makes it the first experimental cell therapy with so many edits. Following these multiple edits, lentiviruses are used to introduce genetic material that allows cells to produce chimeric antigen receptors (CARs) that target specific cancer antigens. The company said in its 2021 annual report that 91 percent of cells achieved four base edits during manufacturing in clinical trials. An estimated 77% of the cells underwent four edits and modifications to generate the CAR. In laboratory tests, Beam reported that BEAM-201 cells could kill cancer cells. In mice, the cell therapy showed a dose-dependent ability to clear or control cancer cells.
Other companies developing allogeneic T-cell therapies that offer multiple editing include Allogene Therapeutics and Cellectis. In a research note to investors on Monday, William Blair analyst Raju Prasad noted that the companies also received clinical trials, “leading us to believe that this update is likely due to issues surrounding multiple base editing of T-cell products. (Considering the new gene)-editing approach).” Prasad added that the clinical hold on Allogene was resolved in about three months, suggesting that Beam’s time frame may be similar.
Verve Therapeutics also uses Beam’s technology under a license agreement. Verve uses base editing for an in vivo treatment designed to shut down the gene encoding PCSK9, a liver protein that causes an inherited form of high cholesterol. last month, Verve on first patient In a clinical trial, testing its base editing drug VERVE-101 as a treatment for heterozygous familial hypercholesterolemia. The study is underway in New Zealand; Verve expects to receive regulatory clearance sometime in the second half of this year to begin human testing in the UK and US.
FDA lifts clinical hold on Celyad cell therapy
In other clinical hold news, the FDA has clear Celyad Oncology will resume testing of CEL-101, its experimental cell therapy for advanced colorectal cancer.
Death of two Phase 1b patients led Belgium-based Celyad to voluntarily suspend Phase 1b testing in February. Soon after, the FDA officially placed the study on clinical hold. CEL-101 is made from T cells from healthy donors. The cells are designed in a way that reduces the risk of graft-versus-host disease, a complication in which transplanted cells attack a patient’s natural cells.
A Phase 1b trial of CEL-101 is evaluating the cell therapy in combination with Merck’s blockbuster cancer immunotherapy Keytruda. The FDA lifted the clinical hold after the company changed the study’s eligibility criteria, Celyad said.
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