AbbVie Signs Off-the-Shelf CAR-T Therapy Pact with Jennifer Doudna’s Caribou Biosciences

On February 10th, Abbvie and Caribou Biosciences inked an agreement to work on one of the most powerful anticancer treatments, CAR-T therapy. Together the duo is planning to make “off-the-shelf” allogeneic CAR-T therapy immune resistant with the help of CRISPR gene-editing technology.

CAR-T cell therapy is a mode of treatment that uses engineered T cells to fight cancer. These cells can either come from the patient (autologous CAR-T therapy) or a donor (allogeneic CAR-T therapy). Donor-derived cells have many potential advantages over patient-derived cells.

Despite this, allogeneic therapies are still not approved for human use as they can be conceived as foreign and rapidly eliminated by a patient’s immune system. This problem is what AbbVie and Caribou are trying to solve by developing allogeneic CAR-T therapies that can resist a patient’s immune response.

Why is Abbvie Seeking Caribou?

Caribou Biosciences was co-founded by CRISPR pioneer and Nobel Prize winner Dr. Jennifer Doudna in 2011 and is headed by her ex-lab member, Rachel Haurwitz. The company is working on an internal pipeline of allogeneic CAR-T cell programs that target CD19, BCMA, and CD371 proteins.

Of these three, the first one is currently being evaluated in Phase 1 clinical trial as a treatment for B cell non-Hodgkin lymphoma, while the other two are still in the preclinical stage. With limited knowledge of the CAR-T cell therapies, AbbVie was seeking someone with a strong background in these therapies. Caribou is offering AbbVie the expertise in these therapies and the tools to make it a reality.

According to the agreement, Caribou will lend its next-generation Cas12a CRISPR hybrid RNA-DNA (chRDNA) genome editing and cell therapy tech to AbbVie to research and develop two new CAR-T cell therapies directed to targets specified by AbbVie. While details of these targets are still under wraps, one can make a wild guess that they are for common forms of blood cancer against which most of the approved CAR-Ts are currently directed.

AbbVie will hold exclusive rights to the chRDNA technology for the targets it has specified. The company will conduct all the clinical development, commercialization, and manufacturing activities once Caribou finishes preclinical research and development for the two programs. All the funding for preclinical R&D performed by Caribou will come from AbbVie’s pocket. If all goes well with these two programs, AbbVie can choose to add two more programs to the agreement.

In return for the CRISPR tools and expertise, AbbVie is offering Caribou $40 million upfront and $300 million in biobucks as well as royalties in case any of the treatments get regulatory OK.

Getting on the Shelf

Allogeneic CAR-T treatments are powerful anticancer therapies that offer hope to patients who have exhausted most other options. Kymriah was the first CAR-T cell therapy approved in the US, which used patient-derived T cells to treat difficult cancers. Gilead’s Yescarta and Tecartus, as well as BMS’s Breyanzi, joined the league later.

While these therapies are promising, they also present significant challenges. The cells extracted from patients must be shipped, engineered, returned, and re-infused in the patient within a short span of two to three weeks. The treatment can go completely to waste if any setback occurs during any of these steps. Moreover, the labor-intensive work that goes into editing a patient’s T cells also heavily drives up the treatments’ price tags. Kymriah is currently priced at $475,000 and Yescarta at $373,000.

On the contrary, allogeneic treatments offer several advantages. Since the cells can be extracted and stored in bulk beforehand, they can be modified and infused in multiple patients in a short time as and when needed.

For these reasons, off-the-shelf therapies have become a hot topic in biotech now. While smaller biotechs like Allogene Therapeutics, CRISPR Therapeutics, and Precision Biosciences are heavily invested in this approach of treating cancer, big names like Pfizer, Bayer, Merck, and Johnson and Johnson are not far behind. In 2018, Pfizer made a deal with Allogene to develop an allogeneic CART-therapy called UCART19.

With all said and done, off-the-shelf therapies may still take a while before they make it to the shelf. Physicians speculate that any new off-the-shelf therapy would first need to meet the current safety and efficacy of autologous CAR-Ts before they can make it to the market.

Related Article: China’s Gracell Biotechnologies, a CAR-T Therapy Company, Targets 150 Million for IPO

References

1. https://news.abbvie.com/news/press-releases/abbvie-and-caribou-biosciences-announce-collaboration-and-license-agreement-for-car-t-cell-products.htm

Author

Ruchi Jhonsa