The hangover: Caribou's allogeneic CAR-T hit by durability doubts as half of patients relapse

Caribou Biosciences is nursing a hangover. Weeks after celebrating a 100% overall response rate, the CRISPR biotech has revealed 50% of patients relapsed within six months of receiving its allogeneic CAR-T cell therapy, sending shares into a sudden 13% dive that largely erased earlier gains.

Durability has emerged as a sectorwide issue for developers of allogeneic CAR-Ts, with Allogene, CRISPR Therapeutics and Precision Biosciences all seeing significant numbers of cancer patients relapse in the six months after treatment. Caribou has removed the PD-1 receptors from its anti-CD19 candidate, CB-010, in an attempt to reduce CAR-T cell exhaustion and maintain high anti-tumor activity for a longer duration.

The non-Hodgkin lymphoma results from the phase 1 Antler trial, presented at the European Hematology Association (EHA) congress, raise questions about the impact of Caribou’s work to increase durability. As of May 13, three of the six complete responders had relapsed. 

A diffuse large B- cell lymphoma patient relapsed at Month 3. The two other relapses, in patients with mantle cell lymphoma and follicular lymphoma, happened at Month 6. Two of the three patients with ongoing responses were at or approaching the six-month mark as of the data cutoff. The other responder was approaching, and has now passed, the 12-month mark.

The relapses overshadowed other, more encouraging aspects of the data, causing shares in Caribou to fall 13% to around $7.60 in premarket trading. The initial complete response rate rose after the pre-EHA data, climbing from four out of five in the original analysis to six out of six in the poster presentation. 

Caribou achieved that 100% complete response rate at the starting dose of 40 million CAR-T cells. Safety looks good so far. One patient suffered grade 3 immune effector cell-associated neurotoxicity syndrome that resolved in 39 hours, but none of the patients experienced graft-versus-host disease or grade 2 or greater cytokine release syndrome (CRS). Two patients had grade 1 CRS. 

Based on the data, Caribou has begun enrolling patients at the second dose level, 80 million CAR-T cells. Doubling the dose could drive longer-lasting responses, enabling Caribou to differentiate itself from the rest of the allogeneic CAR-T space and renew confidence in its approach for increasing durability.

SVB Securities came down on the side of the "bulls" on the "Cari-boo" debate, pointing to the low dose with room to escalate and the favorable complete response rate at six months. The Antler study is also "early but competitive," the firm noted. 

"The efficacy signal despite a low dose and reasonable safety paint a mosaic that for us supports dosing up as the strategy most likely to produce the best profile for an eventual regulatory filing," SVB Securities wrote. 

Editor's note: This story was updated at 1:17 p.m. ET on June 10, 2022, to include analyst commentary.