Juno Therapeutics Partners with Editas Medicine on CRISPR-Engineered Cancer Immunotherapies

By Aaron Krol

May 27, 2015 | Juno Therapeutics, the immunotherapy company whose $265 million IPO last year has helped make it one of the world’s flushest biotechs, has announced a deal with Editas Medicine to co-develop cancer therapies using gene editing technology. The agreement includes a $25 million upfront payment to Editas and an additional $22 million research investment, and could balloon to as much as $700 million in milestone payments if Editas delivers on three as-yet-unspecified therapeutic programs.

The sums involved here are remarkable not just because of their size, but because Juno itself is a young company, launched barely 18 months ago, whose first therapies are not expected to reach the market until at least 2017. It’s a testament to how hypercharged the biotech funding environment has become that an “established” player like Juno is taking on a role more typical of big pharma, providing major seed money to the next generation of promising biotechs in collaborations to boost its pipeline. The Editas partnership is the second major expenditure Juno has announced just this month, after acquiring Stage Cell Therapeutics in another deal whose final cost could total in the hundreds of millions of dollars.

Juno has amassed the funding for these aggressive ventures on the back of its chimeric antigen receptor T-cell (CAR T) and T-cell receptor (TCR) therapies, two emerging technologies in which a patient’s immune cells are extracted from the body, engineered to recognize tumor cells, and readministered as cancer-fighting agents. Juno therapies in early clinical trials for leukemia and lymphoma have shown promising results, placing the company near the head of a large pack of CAR T hopefuls.

While oncologists (and investors) have high hopes for these programs, they are not without risk. The FDA is only beginning to evaluate CAR T treatments, whose powerful efficacy comes with a side effect, a massive immune response sometimes called a “cytokine storm,” that could only be acceptable in a disease as dire as cancer. Two cancer patients in Juno-sponsored trials have died from complications of these cytokine storms ― but many more have gone into complete remission, often in cases where their diseases would previously have been considered all but incurable.

Editas and Juno make a good match. The specialty of the Editas team is CRISPR, an extraordinary gene editing technique that allows scientists to make highly precise changes to the genomes of living cells, adding and removing DNA almost at will. This technique has excellent synergy with the kind of T-cell engineering performed at Juno ― the older gene editing methods currently supporting CAR T are more labor intensive, less flexible, and less precise. It’s easy to imagine CRISPR becoming the backbone of the scaled-up CAR T and TCR production processes that will be needed to give these therapies a broader reach. The combination of these technologies is also a great shortcut to the clinic for Editas: the enormous challenge of delivering CRISPR systems to the right cells in the body is not a problem in CAR T, where T-cells are extracted and reprogrammed in the lab.

Of course, with great promise comes plenty of competition, and Juno is not the first CAR T player to link up with a CRISPR partner. That distinction belongs to Novartis, the big pharma company notable for its embrace of young biotechnologies, which forged a partnership with Editas competitor Intellia Therapeutics earlier this year. Novartis, thanks to a breakthrough status designation by the FDA, should be first to market with a CAR T treatment if the agency ultimately approves its drug CTL019 for one or more types of blood cancer; Juno is close behind in its regulatory timeline.

A further wrinkle to this story: Editas and Intellia are embroiled in a patent dispute, which at heart concerns the right to administer CRISPR systems in mammalian cells. A very broad patent on this technology is currently held by the Broad Institute of MIT and Harvard and licensed to Editas, based on work performed in the MIT lab of Feng Zhang, an Editas scientific founder. That patent, and other related intellectual property, is being challenged by (among others) Jennifer Doudna, the co-discoverer of CRISPR gene editing who dropped out of Editas and is now a founding member of Intellia.

Better get used to these entanglements: as the venture capital money continues to flow into biotech, the stakes will keep getting higher for companies whose huge valuations are riding on equally huge clinical results. Juno and Novartis only recently settled their own intellectual property fight, with a royalty deal that gives Juno a small stake in Novartis’ programs.