Alongside tiny data drop, Caribou plans dose escalation for its first off-the-shelf CAR-T trial
In May, Caribou Biosciences shared impressive early data on its first trial for an off-the-shelf CAR-T therapy, disclosing that four of five patients suffering from B cell non-Hodgkin’s lymphoma had a complete response.
With its EHA presentation coming up Saturday, the Jennifer Doudna-founded biotech has unwrapped more data on its lead candidate. As of May, the biotech has results from one more patient in its Phase I trial — a sixth patient who had an initial complete response, but saw their cancer progress three months after receiving the CAR-T infusion.
Two other patients in the trial also reached complete response until the cancer progressed at six months after treatment. On the other hand, one patient in the trial has had ongoing complete response for twelve months.
Numbers-wise, that puts Caribou’s anti-CD19 CAR-T therapy at six of six patients responding to the treatment and two of five with complete response at the six-month mark.
When asked about durability, Caribou president and CEO Rachel Haurwitz told Endpoints News: “We’re encouraged that at this point we see a 40% 6-month CR rate — I think that’s quite promising. I recognize this is a small number of patients and early data, so [durability] is obviously something we are continuing to keep an eye on.
“It’s also why we’re dose-escalating to dose level two with a specific focus on durability,” Haurwitz continued.
Investors did not feel the same way. Caribou’s stock $CRBU had been trading up around 30% since the first news dropped in May, though all in all it has dropped more than 40% since the Berkeley, CA-based biotech went public in July. In reaction to this updated data, Caribou was trading down over 16% before the markets opened. Soon after the markets opened, Caribou fell below where it was prior to the May announcement, down 34% from one day ago.
SVB analysts had a less reactionary view, maintaining that Caribou’s candidate was “early but competitive, though debate rages on durability.” SVB’s Mani Foroohar and Rick Bienkowski wrote:
Questions around expansion/PK kinetics continue to simmer beneath the surface, but our view is that this update shows enough evidence of clinical efficacy with a modest absolute dose yielding a small tail of persistent cells.
Moving forward, the biotech will test a second dose level that has twice the number of CAR-T cells as the first.
Safety-wise, four of the six patients suffered from grade 3 adverse events, with three instances of low white blood cell counts, one of neutropenia and one of ICANS.
Unlike autologous CAR-T therapies available now, allogeneic CAR-T therapies don’t have to be made with the T cells of each individual patient. In a climate where doctors have to weigh which patients get personalized CAR-T therapy and which don’t, as reported by STAT News, an off-the-shelf cancer treatment would be a colossal breakthrough.
A host of other biotechs are working on off-the-shelf CAR-T therapies. On Wednesday, Precision BioSciences announced interim Phase I/II results on its anti-CD19 therapy that featured serious safety concerns and four patient deaths. While Precision said it is headed to the FDA later this year and aims to become the first allogeneic CAR-T approved, one analyst called the biotech’s pipeline “lackluster.”
Following a three-month clinical hold, Allogene restarted clinical trials for its off-the-shelf CAR-Ts in January of this year. The biotech has a Phase II trial in relapsed/refractory large B cell lymphoma planned for this year.
According to Caribou, what makes its therapy different is its additional PD-1 knockout, which is meant to make the treatment last longer. It also uses a CRISPR system known as chRDNA, pronounced as “chardonnay,” which is supposed to be more specific and prevent unwanted mutations — the concern that resulted in Allogene’s clinical hold.
The chRDNA method uses DNA-RNA hybrid guides to direct the nuclease, the DNA cutter, to its location, whereas earlier versions of CRISPR featured RNA-only guides. “It’s the inclusion of DNA in the guides that dramatically improves the specificity of genome editing,” Haurwitz said.
Caribou could enroll up to 50 patients on its ANTLER Phase I trial, though the biotech said it is not disclosing the current number of patients it has enrolled. Haurwitz said vaguely that the biotech will disclose additional trial data before the end of the year.
This article has been updated with additional information on the trial and stock and analyst reactions, as well as to clarify when Caribou went public.