The trials of Juno

IN THE pharma business, Juno Therapeutics, a small firm based in Seattle, is just a stripling. It is three years old, has not a single drug approval to its name but is nonetheless valued at $2.8 billion. That value is derived from the fact that it is on the forefront of the most promising area of cancer treatments in decades: immuno-oncology.

Juno’s edge comes from its attempts to master one of the most important parts of the immune system: the T-cell. It is developing a so-called CAR-T therapy, in which its scientists extract T-cells from a cancer patient, modify them with gene therapy so that they can recognise cancer cells, and then put them back in the patient’s body ready to attack. The process has a reputation for inducing rapid remissions in cancers of the blood for patients who have exhausted all other options.

Small, innovative biotech firms such as Juno are intriguing because nowadays they are the main engine of global drug innovation. Alexis Borisy, a partner in Third Rock Ventures, a venture-capital firm in Boston, notes that pharma companies now buy in three-quarters of their pipelines, and develop only a quarter internally. Big companies eye the little ones hungrily as their main source of future growth.

Juno is not the only biotech firm pursuing its particular technology. Kite Pharmaceuticals, based in California, is one rival. The giant Novartis is also investing. But Juno has stood out. Mark Simon, a partner at Torreya Partners, a consultancy, says that is because it is well run and has, so far, “some very positive, provocative data from the treatment of a number of tumours”. If CAR-T can move beyond its current niche into cancer more broadly the firm could help revolutionise its treatment.

It has a full line-up of experienced researchers, including from the nearby Fred Hutchinson Cancer Research Center, which helped Juno become one of the best funded biotech startups ever. There is another more subtle distinction about Juno. It is developing “next generation” versions of CAR-T. Although it is not yet clear how useful or profitable these will be, the expectation is that fine tuning such therapies will lead to even better medicines.

Despite its progress, investors balked when Celgene, a big pharma firm, paid it $1 billion in 2015 for a ten-year collaboration. It is not hard to see why they hesitated. Biotech is always inherently risky. There are big questions about whether CAR-T therapies can be extended to treat solid tumours. It is also unknown if the therapy will be durable enough to justify the side effects that can result from the treatment, as well as the high cost of such a personalised approach.

The riskiness of the biotech business was underscored this summer when a trial of Juno’s lead drug candidate, JCAR015, was put on hold after three of the patients on a trial died. Juno’s stock swooned. But the firm convinced the drug regulator that the problem came from the addition of a chemotherapy drug to the treatment, and that removing it would rule out further deaths. Six days later the trial restarted and the company’s share price revived.

The setback will nonetheless delay the approval of Juno’s first product, a treatment for acute lymphoblastic leukaemia, until 2018. It will also cost the company the bragging rights to being the very first firm to commercialise CAR-T. That now looks likely to be won by Kite Pharmaceuticals, which is aiming for the end of the year. But being first doesn’t matter, argues Hans Bishop, Juno’s boss. A few years is a “blink of an eye” in this industry, he says. That may be true, but Juno in its own first three years has made a big impact.