Caribou Biosciences (NASDAQ:CRBU) is advancing two off-the-shelf CAR-T cell therapy programs and expects upcoming clinical updates to help frame the next stages of development, President and Chief Executive Officer Rachel Haurwitz said during a Bank of America conference session with analyst Alec Stranahan.
Haurwitz said Caribou’s lead programs are vispa-cel, a CD19-targeted therapy for lymphoma, and CB-011, a BCMA-targeted therapy for multiple myeloma. She said phase 1 data reported late last year gave the company confidence that both programs have “best-in-class potential.”
Caribou highlights CRISPR platform and allogeneic approach
Haurwitz said Caribou’s approach is built around its proprietary next-generation CRISPR platform, which the company calls chRDNA. She said the technology is designed to produce gene-editing outcomes that are “orders of magnitude more specific” than first-generation CRISPR-Cas9.
For CB-011, Caribou uses what Haurwitz described as an immune-cloaking strategy intended to slow immune-mediated rejection of the donor-derived cells and extend the time available for anti-tumor activity. She said the persistence of CB-011 has been about twice that of uncloaked cell therapies.
For vispa-cel, the company is using a PD-1 knockout strategy. Haurwitz said the goal is to “take the brakes off” the CAR-T cells during the period they are present in the patient, which she estimated at about 30 days, and increase anti-tumor activity.
Vispa-cel phase 3 design aligned with FDA
Haurwitz said Caribou has reached alignment with the U.S. Food and Drug Administration on a phase 3 pivotal design for vispa-cel in second-line large B-cell lymphoma patients who are not receiving autologous CAR-T therapy and are not receiving autologous transplant.
She said the target population represents a major unmet need, noting that despite strong clinical and real-world data for autologous CAR-T therapies, only about 25% of second-line large B-cell lymphoma patients receive them. Haurwitz attributed the gap largely to disease progression that prevents patients from waiting for individualized therapy manufacturing, as well as geographic barriers that limit access to academic treatment centers.
The planned vispa-cel study is expected to enroll 250 patients with 1-to-1 randomization, Haurwitz said. The control arm will allow physician choice among four chemoimmunotherapy regimens: Pola-BR, Pola-R-GemOx, R-GemOx or tafasitamab. The primary endpoint will be progression-free survival, and the study will include crossover for patients who progress on the control arm.
Haurwitz said the trial cannot be blinded because the treatment approaches are clearly different: lymphodepletion and a single dose of cell therapy versus repeat cycles of chemoimmunotherapy. She said Caribou has modeled multiple scenarios and believes the 250-patient design provides high power across many assumptions.
Company sees community-setting opportunity
Haurwitz said vispa-cel could be delivered beyond major academic centers because of the efficacy and safety profile observed so far. She said Caribou expects a roughly 50/50 mix in the United States between top-tier academic institutes and sophisticated community hospitals for the phase 3 study.
She said community hospitals already using bispecific antibodies may be well positioned to deliver allogeneic CAR-T therapy because the adverse events, monitoring and standard operating procedures are similar. In some ways, she said, an allogeneic CAR-T may be easier for sites because it is delivered as a single dose, compared with repeat dosing for bispecifics.
Haurwitz also pointed to manufacturing and supply as key parts of vispa-cel’s commercial case. She said Caribou anticipates cost of goods sold at launch will be 96% lower than autologous CAR-T therapies. She also said modest HLA matching appears to support outcomes, and that Caribou’s modeling suggests roughly 10 donor lots could serve 99% of U.S. lymphoma patients with at least a two-allele match.
CB-011 update expected at EHA and later this year
For CB-011 in multiple myeloma, Haurwitz said the benchmark Caribou has heard from physicians is the ability to match or exceed bispecific antibody outcomes while offering a one-time treatment option. She said the company selected a recommended expansion dose of 450 million CAR-T cells after enrolling 48 patients in dose escalation.
Haurwitz said Caribou had already treated 12 BCMA-naive patients at that dose and observed response rates that exceeded bispecific benchmarks and approached autologous CAR-T-like outcomes. She also said 91% of those patients achieved MRD negativity.
At EHA, Caribou plans to provide longer follow-up on those patients, including response durability, Haurwitz said. The company is also enrolling dose expansion cohorts in both BCMA-naive and post-BCMA patients and has guided to dose expansion data by the end of this year.
Haurwitz said CB-011 recently received Regenerative Medicine Advanced Therapy designation from the FDA, which she said should allow earlier and more proactive engagement with the agency. She said Caribou expects to engage with regulators later this year and may provide guidance on next development steps along with dose expansion data.
Cash runway and upcoming milestones
Haurwitz said Caribou’s cash runway extends into the second half of 2027. She said the balance sheet funds CB-011 dose expansion work and startup activities for the ANTLER phase 3 pivotal trial for vispa-cel, but does not fully fund the company through that study’s readout.
Looking ahead, Haurwitz said investors should watch for EHA oral presentations for both vispa-cel and CB-011, as well as CB-011 dose expansion data by year-end. She also said Caribou is already at commercial manufacturing scale for vispa-cel and plans to use that capability for the pivotal study.
About Caribou Biosciences (NASDAQ:CRBU)
Caribou Biosciences, Inc is a clinical-stage biopharmaceutical company that leverages its proprietary CRISPR-Cas gene-editing platform to develop transformative cell therapies and in vivo treatments for a range of cancers and genetic diseases. The company’s core technology enables precise modification of cellular genomes, allowing the design of engineered T-cell and NK-cell therapies aimed at improving safety, efficacy and persistence in patients with hematologic and solid tumor malignancies. Alongside its oncology portfolio, Caribou is advancing in vivo editing programs targeting monogenic disorders, with initiatives in areas such as Duchenne muscular dystrophy and familial amyloidosis.
Established in 2011 and headquartered in Berkeley, California, Caribou Biosciences was co-founded by Nobel laureate Jennifer Doudna, one of the pioneers of CRISPR gene-editing technology.
