Dive Brief:

• Allogene Therapeutics, a leading developer of “off-the-shelf” cell therapies for cancer, will deprioritize two of its most advanced clinical trials as part of a new plan to improve on other cell-based medicines.
• The biotechnology company is dialing back work on a pair of studies that were designed to support approval of its therapy, formerly known as ALLO-501A and now cema-cel, in advanced lymphoma. Instead, the company will focus resources on a new study testing that therapy right after a widely-used regimen in recently diagnosed patients.
• The new plan will include a restructuring this quarter as well as testing another therapy in autoimmune disease next year. Company CEO David Chang said Allogene will also change “how we allocate our headcount,” but declined to provide further details. The company expects the moves to save enough cash to extend its operating runway until 2026.

Dive Insight:

Allogene has been a leader in the development of cellular treatments known as allogeneic CAR-T therapies. These drugs are derived from donor cells and seen as potentially more convenient alternatives to the personalized CAR-T therapies that are now used for some blood cancers.

But Allogene has had a rough ride since spinning out of Pfizer’s cell therapy work in 2018. While the company’s medicines showed promise treating blood cancers, they’ve had difficulty matching the results of personalized CAR-T treatments. The Food and Drug Administration also froze Allogene’s research for months to investigate a potential safety issue.

Along the way, personalized CAR-T moved into earlier lines of care. Dual-pronged antibody drugs came to market. And several other competitors emerged testing therapies in later-line lymphoma patients. Allogene shares have lost nearly 90% of their value and currently trade near all-time lows.

The company previously planned to use a pair of Phase 2 trials as evidence of how its approach stacked up in late-line lymphoma, where multiple CAR-T treatments are already used. Now it’s shifting gears towards settings where those therapies aren’t available or haven’t been as potent in testing.

“We were really looking for an opportunity to stand alone,” said research and development chief Zachary Roberts.

Allogene’s newly planned study, titled ALPHA3, is meant to do just that. It will test cema-cel in about 230 large-B cell lymphoma patients who are at risk of relapse after six cycles of a widely used drug regimen known as R-CHOP. While R-CHOP can be curative, Allogene cited data that about 30% of patients initially responding will later relapse.

Allogene claims cema-cel could boost cure rates and jump ahead of existing personalized CAR-T therapies. ALPHA3 could also show the potential for off-the-shelf treatments to be used at community cancer practices, not just the major treatment centers that typically administer cell therapies.

The study “is meeting a lot of things that hematology oncologists have been looking for,” said Chang.

Still, the reset will once again lengthen Allogene’s path. The company expected to complete enrollment in one of those older studies, ALPHA 2, by the middle of this year. That study is now deprioritized, aside from a new cohort of patients with chronic lymphocytic leukemia, a blood cancer in which CAR-T therapies haven’t been as effective.

The company is also pivoting away from its other Phase 2 trial, which is testing an antibody drug used to prepare patients for cell treatment.

Allogene plans to start enrolling patients in ALPHA3 in the middle of 2024, according to Roberts. “It will take longer,” he said, though he’s expecting recruiting to move “briskly” given the enthusiasm the company has seen from physicians.

Like some of its peers, Allogene is separately beginning to explore cell therapy in autoimmune disease. It plans to start a study next year testing a medicine that may not require standard chemotherapy preconditioning. It hasn’t said which disease it will target, though a number of other companies are evaluating CAR-T for lupus.

That’s “on our radar,” Chang said. “There’s a lot of opportunities we can think about.”