Caribou Biosciences was flying high when it enjoyed an initial 100 percent success rate with its new allogeneic CAR-T therapy in cancer patients. Unfortunately, six months later, 50 percent of the trial’s participants had suffered a relapse. Shares of Caribou plunged 13 percent upon the news, wiping out the company’s gains from that initial success.
Durability remains an industry-wide problem for chimeric antigen response T-cell therapy, otherwise known as CAR-T therapy. The infusion of genetically altered T-cells tends to be highly successful in killing cancer cells and even tumors. But then the treatment collapses in about six months, with many patients relapsing. Allogenic CAR-T therapy in particular has been having trouble with durability.
Caribou’s three main competitors in the same sector have all experienced the six-month collapse in treatment effectiveness in many patients. Researchers at Caribou thought that this latest treatment, which involved removing PD-1 receptors from its anti-CD19 CAR-T therapy, would prevent the CAR-T cell collapse at the six-month mark, allowing the patients’ immune systems to continue fighting cancer for a longer period of time.
Out of six patients in the latest Caribou “Antler” trial, three suffered relapse. One of them, a patient with large B-cell lymphoma, relapsed at the three-month mark. Two patients with mantle cell lymphoma and follicular lymphoma relapsed at the six-month mark. One patient remains cancer-free at the 12-month mark. The two remaining patients were cancer-free at the six-month mark, but the data was cut off in the study at that point.
There was some encouraging news from the Antler study, but that has been eclipsed by the 50 percent relapse rate. Caribou began the trial by infusing 40 million altered CAR-T cells in the patients. The company managed to reach a 100 percent success rate in the initial three months of the study.
One bit of good news is that the CAR-T therapy treatment seems to have maintained a good safety protocol. Two of the patients experienced grade 1 cytokines release syndrome (CRS). None of them, however, reached grade 2 CRS. Graft-versus-host disease did not present in any of the six patients. One participant did experience a grade 3 immune effector cell-associated neurotoxicity syndrome, but it resolved on its own within two days of diagnosis.
The next step will be for Caribou to double the dosage in its next trial, to 80 million altered CAR-T cells. If doubling the dosage does in fact extend the complete response rate beyond six months, it would set Caribou apart from every other CAR-T therapy company in the marketplace. This could also restore investor confidence that Caribou is on the right track in developing a longer-lasting cancer treatment.
Caribou shares fell to $7.60 when news of the 50 percent relapse rate came out. Caribou believes that the initial low dose (40 million CAR-T cells) has left room for increased dosage while maintaining the same safety standards. A regulatory filing based on the Antler study is unlikely unless Caribou can break the six-month T-cell collapse in the next trial phase.
