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AbbVie Licenses Engineered Crispr Cell Process

Alaskan caribou (Orna Wachman, Pixabay)

10 Feb. 2021. Drug maker AbbVie is acquiring a technology using the gene-editing process Crispr to produce new off-the-shelf engineered T-cells as disease therapies. The deal with Chicago-based AbbVie could bring Caribou Biosciences Inc. in Berkeley, California as much as $340 million if all aspects of the multi-year agreement are met.

Caribou Biosciences develops engineered immune-system cells as cancer therapies, modified with the gene editing technology Crispr, short for clustered regularly interspaced short palindromic repeats. Crispr is a genome-editing process based on bacterial defense mechanisms that use RNA to identify and monitor precise locations in DNA. Among the company’s founders is Jennifer Doudna, professor of chemistry and biology at University of California in Berkeley, and winner with her collaborator Emmanuelle Charpentier of the Nobel Prize in Chemistry 2020. Doudna continues as a scientific adviser to Caribou Biosciences.

Caribou Biosciences advanced Crispr to resolve one of its early drawbacks, a lack of editing precision. In its first applications, Crispr used an editing enzyme called Cas9 that in some cases results in off-target edits. Caribou developed more precise RNA-DNA editing guides known as chRDNAs, pronounced “Chardonnays,” using the enzyme Cas12a. Unlike Cas9, Cas12a can edit multiple gene locations simultaneously, yet the enzyme also connects more efficiently and precisely with target DNA than Cas9 and can reverse the bindings if needed.

The company uses chRDNAs to alter T-cells and natural killer cells in the immune system, adding chimeric antigen receptors, proteins attracting antibodies that bind to and destroy blood-related and solid tumor cancer cells. Most current methods producing chimeric antigen receptor T-cells, known as CAR T-cells, genetically engineer a patient’s own T-cells, then re-infuse the altered T-cells back into the individual, with successful results for blood-related cancers in some cases.

Exclusive license for two new cell therapies

Caribou Biosciences has four engineered T-cell and natural killer cell cancer treatments in its pipeline as therapies for blood-related and solid tumor cancers. Unlike most earlier CAR T-cell therapies that use a patient’s own cells, Caribou’s treatments are designed as allogeneic or off-the-shelf therapies. One of Caribou’s treatments, code-named CB-010, is an off-the-shelf allogeneic CAR T-cell therapy for patients with relapsed or refractory B cell non-Hodgkin lymphoma, now in an early-stage clinical trial.

AbbVie has an extensive cancer therapy program, but the deal’s announcement does not specify to which diseases the Caribou Biosciences technologies are applied. The agreement provides AbbVie with an exclusive license to Caribou’s chRDNA technology to develop two new CAR T-cell therapies for targets specified by AbbVie. Caribou is responsible for some preclinical research, development, and manufacturing work, while AbbVie is responsible for clinical development, commercialization, and further manufacturing activity.

Under the deal, Caribou Biosciences is receiving an initial cash payment and equity stake from AbbVie valued at $40 million, as well as reimbursement for its preclinical work. Caribou is also eligible for $300 million in development, regulatory, and launch milestone payments, as well as further commercial milestone payments and royalties on sales.

“We believe AbbVie is an ideal partner for Caribou,” says Caribou Biosciences president and CEO Rachel Haurwitz in a statement, “as we expand upon the number of targets and diseases addressable by our technologies. Genome-edited CAR T-cell therapies hold tremendous potential for patients, and this partnership accelerates our ability to address significant unmet medical need.”

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