BEAM-301

Beam Therapeutics set out to show how the precision of base-editing could produce new genetic medicines addressing a wide range of diseases. That goal may yet be realized, but the company is now narrowing its scope and slashing its headcount to ensure it has enough cash to support key programs that can demonstrate the value of the technology, and in turn create value for the company. In addition to shelving some programs, Beam said Thursday that it will lay off about 100 employees, representing 20% of the biotech’s staff. Cambridge, Massachusetts-based Beam said those cuts will be completed in the current quarter. Beam’s therapies are developed by employing base-editing, a technology that make a precise change to a single base in the genome without also causing double-stranded breaks in the DNA that can result in unwanted genetic modifications. The company’s pipeline had grown to 11 programs spanning many diseases. Beam will now focus on three indications. Sickle cell disease will be addressed by two programs, BEAM-101 and ESCAPE, which is short for engineered stem cell antibody paired evasion. ESCAPE is intended to improve on the conditioning regimen that prepares patients sickle cell disease and beta thalassemia patients for a stem cell transplant. ESCAPE is preclinical. BEAM-101 is already in the clinic. While the initial research with BEAM-101 employs ex vivo delivery to hematopoietic stem cells, the company is also exploring in vivo base-editing approaches in which an infused therapy would use lipid nanoparticles to target the stem cells, eliminating the need for the transplantation step required of ex vivo therapies. In sickle cell disease, Beam could compete against a CRISPR-gene-edited therapy from Vertex Pharmaceuticals and a Bluebird Bio gene therapy, both of which are expected to receive FDA decisions in December. In a note sent to investors, William Blair analyst Sami Corwin wrote that investor focus has largely been on BEAM-101, which is expected to yield preliminary data in 2024. “With two [sickle cell disease] gene therapies potentially being approved by the end of the year, we continue to believe the development of a targeted preconditioning or in vivo approach will be critical to Beam differentiating itself,” she said. Other programs that Beam will continue include preclinical-stage BEAM-302, an in vivo gene editing therapy for alpha-1 antitrypsin deficiency, a liver protein deficiency that leads to liver and lung damage. Beam also plans to reach the clinic with BEAM-301 for the treatment of glycogen storage disease 1a (GSD1a), a rare inherited enzyme deficiency. Beam management told Corwin that manufacturing is a strategic capability the firm wants to keep in-house, and a cell and lipid nanoparticle manufacturing facility in Research Triangle Park, North Carolina, is expected to open by the end of the year. Beam aims to find partners to continue development of some of its other programs. The company has researched the use of base-editing as a way to develop allogeneic, or off-the-shelf, cancer therapies by editing T cells from healthy donors. This research yielded the program BEAM-201, which recently dosed the first patient in a Phase 1/2 study. Beam now says it plans to develop a focused dataset with the goal of landing a partner for this program and other potential ex vivo CAR T-therapies. Beam is also pausing a hepatitis B program and intends to place it with a partner. Beam said the restructuring will lead to an estimated $6.6. million in one-time costs, mainly related to severance payments. At the end of the second quarter of this year, Beam’s cash position was $1.1 billion, which the company said was sufficient to support the company for at least the next year. Beam said this restructuring should now make that cash last into 2026. “From the beginning, Beam’s strategy has been to develop base-editing technology broadly across a diverse portfolio of programs and delivery modalities, and our science and pipeline continue to progress across the board,” Beam CEO John Evans said in a prepared statement. “In this challenging market environment, however, we need to make the difficult decision to focus our resources on those clinical programs and research areas we believe have the highest potential for near-term value creation, while continuing to build a strong company for the future.” Image: iLexx, Getty Images