Novartis Deal Signals Big Pharma's Entrance in CRISPR-Based Therapies

January 7, 2015

By Aaron Krol 

January 7, 2015 | There’s an episode of the sitcom 30 Rock where Steve Martin, playing a genius entrepreneur, whispers his pitch for a new business venture to a potential investor: “Wind power. Bandwidth. Chinese market.” The investor’s jaw drops with a gasp.

To the biotech community, today’s deal between pharma giant Novartis and recent startups Caribou Biosciences and Intellia Therapeutics might feel much the same: “CRISPR. Stem cells. CAR-T therapy.” Check off your disruptive biotech bingo cards.

To recap briefly, CRISPR is a rapidly emerging technique that lets scientists edit the genomes of living cells, much more flexibly and easily than ever before. In fact, CRISPR is such a leap forward in gene engineering that startups are all but tripping over each other to be the first to try it out as a drug — despite the fact that no gene therapy has ever been approved for sale in this country.

CAR-T therapy, meanwhile, is a method of fighting cancer in which a patient’s T-cells are extracted from the body, trained to attack tumor cells, grown by the billions and then administered as a drug. CAR-T treatments are still in early clinical trials, but for certain blood cancers they have been outlandishly effective in these studies, all the way up to complete responses in outright majorities of patients. While all the usual caveats about early trials apply, few cancer programs have ever managed to look so promising at such a late stage of development.

Stem cells, of course, are this close to being the cure for everything, and have been for twenty years.

Under the terms of today’s agreement, Novartis will have exclusive rights to use Intellia’s CRISPR platforms to develop CAR-T therapies; Novartis and Intellia will form a joint development plan for a CRISPR-engineered stem cell program, which could lead to drug candidates for one or both of the partners; and Novartis will also gain a non-exclusive license to all of Caribou’s intellectual property. Meanwhile, Intellia will continue to pursue its own drug pipeline, internally or with other partners, with new funding from Novartis and licenses to undisclosed Novartis patents.

Unlike Steve Martin’s venture, this one does have a natural synergy to it. CAR-T already relies on genetically manipulating T-cells, programming them to produce antigen receptors that bind to unique cancer cell proteins. CRISPR is an obvious choice of tools to handle this step. And the specific type of stem cells covered in the agreement — hematopoietic stem cells (HSCs), the precursors to blood cells — could be genetically altered to treat hereditary blood disorders, including sickle cell disease and all forms of thalassemia. The premise would be to grow patient-derived HSCs, alter them with CRISPR to correct the disease-causing mutations, and transplant them to provide a renewable source of healthy blood cells. Novartis has not actually specified that such a therapy is in the works, but it seems more than likely, especially as researchers at Johns Hopkins have already demonstrated that CRISPR can be used for highly specific editing of adult stem cells.

Novartis is already a leader in CAR-T therapy, with multiple programs in the area, including one drug that has won breakthrough status from the FDA and is now in Phase II trials for acute lymphoblastic leukemia. Caribou Biosciences and Intellia Therapeutics are both CRISPR-based startups founded in large part on the research of Jennifer Doudna, one of CRISPR’s two co-discoverers: Caribou works on basic science applications, while Intellia focuses on human therapies. In fact, Novartis was one of two major investors when Intellia was founded less than two months ago, and it’s now abundantly clear why the big pharma company was eager to get in on the ground floor with this late entrant into the CRISPR therapy space.

Exactly what intellectual property Novartis is accessing through Intellia is an open question. The only issued patent around CRISPR — currently being challenged by Doudna and others — belongs to the Broad Institute, and is being licensed to a competing company, Editas Medicine. But with a line to one of the first scientists to propose CRISPR as a gene editing technique, Intellia is in a good position to retain some key rights when all the patent disputes have shaken out. (Intellia licenses its IP from Caribou, which gets its own rights directly from Doudna’s lab at UC Berkeley.)

Regardless, the major takeaway today is that CRISPR therapies are now big business. Editas, the first company to enter the field, has seemed to prefer to strike out on its own (while not actually ruling out pharma partnerships). It’s even snatched up its own vector for in vivo therapies, a sign of serious clinical ambitions. CRISPR Therapeutics, the European counterpart to Intellia and Editas, has made it known that it would love to work with outside partners, but is yet to announce any collaborations.

The linking of Novartis and Intellia, however, brings the resources of one of the world’s largest pharmaceutical companies to bear on CRISPR for the first time. Novartis has a massive R&D budget, a lead to maintain in CAR-T, and a reputation for investing wisely in emerging technologies. There’s every reason to think it regards CRISPR as more than just a curiosity, and will be willing to spend heavily to bring the technique to the clinic.

While financial details have not been disclosed, Intellia has also stated that funding from Novartis will prop up its own R&D efforts for the five-year term of the partnership. The fledgling company now looks to be a very serious contributor to the push for CRISPR-based therapies — and that, we can hope, is good news for patients.