Image source: Abd allah Foteih/flickr.

Already wielding the extremely promising CTL019 in its pipeline, Novartis (NYSE:NVS) announced a deal to license one of most envious technology platforms in biotech. In fact, the pharma giant is expected to combine this leading CAR-T therapy and the newly licensed CRISPR/Cas9 platform in a move that could give it an edge over competitors. It will mark the first time a synthetic biology tool will enter clinical trials -- no doubt a major step forward for the field. And although the small company at the heart of the deal may not be on many investors' radars, this could signal the first shot in a global biotech arms race.

What happened?
Just three months after arriving onto the scene as a company (with an investment from Novartis, no less), privately held Intellia Therapeutics formed the collaboration to develop new cell therapies based on its cutting-edge CRISPR/Cas9 technology platform. Novartis is expected to use the enzymatic genome editing tools to genetically engineer the immune cells (the "T" in "CAR-T") of cancer patients receiving its CAR-T therapy for pediatric acute lymphoblastic leukemia, or ALL, which could present efficiency and cost advantages over current viral methods.  

Financial terms of the five-year deal were not disclosed, but Alex Lash at Xconomy wrote that Intellia should have at least five years of cash on hand thanks to Novartis. The start-up could also use the funds to bring additional CRISPR/Cas9 therapeutics not included in the partnership into the clinic during the same time. Whatever Intellia chooses to do, it doesn't have to worry about finding another pharma partner if it doesn't want to.

What is CAR-T?
As I wrote recently:

The immunotherapy approach collects a cancer patient's T cells, a potent type of immune cell, and genetically engineers them to produce special surface proteins called CARs [chimeric antigen receptors], which recognize specific proteins on the surface of cancer tumor cells. Researchers grow the engineered cells to high concentrations and inject them back into a patient's body. In other words, CARs allow T cells to find cancer more selectively while limiting the damage to a patient's healthy cells, as the patient's own immune cells act as the "drug."

If you haven't heard by now, CAR-T therapies are all the rage for biopharmaceutical companies. Novartis and the University of Pennsylvania are collaborating on CTL019 for childhood ALL, which is considered the most promising pipeline asset in the nascent field. The drug cleared all signs of cancer in 27 of 30 patients -- 15 of which received no further treatment -- in an early stage trial. It's still too early to establish safety and efficacy profiles for the drug, but it's not difficult to see why investors are excited about the potential (keyword is "potential").

What is CRISPR/Cas9?
The technology has been called the "biotech discovery of the century" for several reasons, but simplicity and ease of use may top the list. Where did it come from? When a bacterial cell survives an attack from a virus, it stores bits of the invader's genetic code (called CRISPRs) into its own genome, essentially remembering the virus. In the event of a future attack, the bacterial cell generates enzymes (called Cas9 in this instance) that cut the virus at the genetic sites that match those stored. Together, the bacterial defense mechanism is called CRISPR/Cas9.

Researchers have developed ways to use the system on most any type of cell (except microalgae), but the goal isn't to cut viral DNA. Instead, CRISPR/Cas9 has been used on mammalian cells, including human cells in a petri dish, to cut out disease-causing genes and, in some cases, simultaneously insert working copies of corrupted genes. It's expected to boast key advantages over RNAi and zinc finger therapeutics, but it's also very early (key phrase is "very early").

Why might this matter?
While the genome editing tool is already being used to produce genetically engineered agricultural crops and industrial microbes, Novartis will be the first company or research team to use the technology for human therapeutics. The company plans to combine CRISPR/Cas9 with CAR-T therapies to engineer a patient's T cells more efficiently than current methods relying on decades-old genetic engineering tools. Why do that?

There are several drawbacks to current genetic engineering methods used in developmental CAR-T therapies. It can be difficult to ensure that engineered T cells retain their genetic edits after several generations, which could lead to less effective or less safe CAR-T therapies. It also increases manufacturing time and costs.

Novartis will use CRIPSR/Cas9 tools to engineer T cells in a more targeted manner (by inserting several copies of edits throughout the genome), which would make it less likely for the edits to be lost in later generations, thus potentially providing more effective CAR-T therapies for a broader population of patients. But it could get more exciting for investors. The deal includes using CRISPR/Cas9 on hematopoetic stem cells, or HSCs, which are the stem cells responsible for creating T cells in the human body. While both companies were mum on the details, the possibilities are perplexing.

For instance, instead of collecting T cells from a patient's blood, Novartis could engineer off-the-shelf HSCs to produce engineered T cells for injection. The genome editing tool could also be used to engineer HSCs present in a patient's body, or in vivo, to churn out a steady stream of cancer-fighting T cells, although this would be more difficult than drawing blood. The possibilities are exciting, but investors will have to wait for the companies to provide an update on their plans.

What does it mean for investors?
You have to be pretty ambitious to combine two of the hottest tools in biotech, especially if both are unproven in human therapeutics. The potential to use CRISPR/Cas9 to engineer HSCs, whether off-the-shelf or in vivo, is even more audacious and has the potential to take CAR-T to the next level. That could make such therapies more effective, which could also make them more accessible to an even broader population of patients. Yet, as exciting as both may be, it's important to remember that CAR-T therapies are in the early days of clinical development, while CRISPR/Cas9 tools are even less proven in the clinic. It's OK to get excited and keep your eye on developments, but don't get your expectations too high.