JPM23: Beam hopes to sidestep sickle cell peers with next-gen gene editing

Beam Therapeutics CEO John Evans is well aware that sickle cell is a crowded area when it comes to gene therapy, but as data roll in, each candidate is beginning to differentiate itself.

“If you step back and look at the data that's starting to roll in from the various players, we can actually start to differentiate what we're seeing and, I think, identify those companies that are going to hopefully rise to the top and then some that are obviously struggling a little more,” Evans said at the J.P. Morgan Healthcare Conference Monday.

Beam has two candidates in the race: the autologous hematopoietic stem cell therapy BEAM-101 in phase 1/2 and the preclinical BEAM-102, which has been delayed as the focus shifts to the former. The company also has the ESCAPE program currently in lead optimization.

The sickle cell field was put on edge last week when Graphite Bio announced that an adverse event cropped up in a phase 1/2 trial of its gene therapy nulabeglogene autogedtemcel (nula-cel). The company has voluntarily paused its lead program to examine the data.

“Obviously, the Graphite data was very disappointing. I'm sure they are all over that. We obviously think about the health of the patient as much as possible,” Evans said.

Graphite’s therapy uses homology-directed repair, or HDR, an expansion of CRISPR technology that goes beyond cutting to actually repair DNA. The company wants to fix, rather than replace, the genetic mutation that causes sickle cell disease.

Evans said HDR has proven difficult to achieve long-term engrafting in hematopoietic stem cells. “That's been a challenge. It looks like it still is one,” he noted.

Besides Graphite, Evans and crew are watching bluebird bio and partners Vertex and CRISPR Therapeutics, which both have candidates he expects will get across the regulatory line.

“And then there's us. We're really coming along with what we view as next-generation editing technology,” Evans said. The company’s candidate is nonviral, non-cutting and does not use a nuclease, which is part of the cutting sequence. “We think that'll be very competitive.”

BEAM-101 is currently working through the BEACON trial, which enrolled its first patient in November 2022, according to a Beam press release issued before the JPM presentation. Enrollment is expected to continue through 2023, with data from one or both cohorts expected in 2024. The therapy is meant to increase fetal hemoglobin, which is linked to the underlying causes of sickle cell and beta thalassemia.

Evans said the company plans to wait until data on about 24 patients are collected.

“We want to have a really robust data set, because this is about communicating the depth of our science and that program with the sickle community and getting them excited,” he said. “So we want to make sure we do it in the right way at a scientific meeting.”

That means Beam will be plenty busy behind the scenes prepping for that rollout. Chief Scientific Officer Giuseppe Ciaramella, Ph.D., said Beam is also bolstering its manufacturing capabilities right now. The process is “very close” to being a commercially viable program already.

“Obviously the editing is important, but the entire process of manufacturing is also a strategic importance in this particular process,” Ciaramella said.

The executives also commented on the $300 million Pfizer collaboration, which was signed at the beginning of last year's virtual JPM conference. The partnership is "going great," and the Beam collab survived the Big Pharma's restructuring of its rare disease portfolio

Evans said the company has been working on all kinds of collaborations, and he's eager to see more, including technology shares and new program generation. "There's no question we will do more of both kinds," he said of potential deals to come. Beam has yet to sign deals for its internal pipeline, but Evans said that could happen. 

"I think the point would be it would be done not from a financing perspective, but primarily from a strategic perspective where we say, 'Hey, this program could reach even more patients and go even faster if we had a world-class partner on our side,'" he said. 

The company also needs to consider whether it will do commercialization alone or whether partnering would be a better choice, he noted.