Latest Caribou data add to ‘off-the-shelf’ cell therapy’s durability questions

Dive Brief:

  • Caribou Biosciences reported new results from an early-stage study evaluating an experimental lymphoma treatment that involves CRISPR gene editing, one of several so-called off-the-shelf cell therapies advancing through clinical testing.
  • All six non-Hodgkin lymphoma patients receiving a low dose of the treatment were driven into remission, and the first treated participant, who got Caribou’s drug a year ago, is still cancer-free, according to data presented Friday at the European Hematology Association meeting. Caribou also intends to test a higher dose given the safety profile it’s observed so far.
  • However, three of those six patients relapsed, one of whom saw their disease progress after three months. Those numbers have also declined from what Caribou reported last month, when four of five remissions were ongoing. Caribou shares fell 24% in early trading Friday.

Dive Insight:

The race to develop a convenient, “off-the-shelf” alternative to personalized CAR-T treatments is getting more competitive, with several different approaches each working their way through different stages of clinical testing.

Some companies are using the types of T cells involved in approved CAR-T therapies from Gilead, Novartis and Bristol Myers Squibb — just retrieved from donors, not harvested directly from patients. For example, Caribou is genetically editing donor T cells to remove a receptor, PD-1, known to help tumors evade the immune system. Others are relying on different types of immune defenders, such as “natural killer” cells or a rarer type of T cell called “gamma delta.”

Each of them aim to show they can make a treatment that matches CAR-T’s powerful, long-lasting effectiveness, without the logistical complexities that limit its use. But the bar for success is getting higher, as CAR-T treatments are moving into earlier lines of care and their developers are working on quicker manufacturing methods. Some are also having trouble proving their treatments are as durable as CAR-T and are evaluating multiple-dose regimens as a possible solution.

Caribou hasn’t gotten there yet. The results Caribou disclosed so far are in the lowest dose, and so far, the company hasn’t observed the types of safety problems that would stop it from testing higher doses that could be more potent. One patient had a serious neurological side effect that’s commonly associated with CAR-T. And two of five study participants treated at least six months ago are still in remission.

Yet the results it’s disclosed raise the same durability questions that hang over other, similar programs from Allogene Therapeutics, CRISPR Therapeutics and Precision BioSciences. And re-dosing, if it becomes necessary, exposes patients to another round of a chemotherapy-based conditioning regimen that prepares them for treatment but can be difficult to tolerate.

Precision, this week, reported that two patients in one of its clinical trials died because of suspected neurological side effects associated with such a regimen.

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