Adventures in CAR-T Racing: Crashes and Curves Edition

The exciting race to develop the first CAR-T therapy recently took some unexpected twists. Clinical-stage biotech bluebird bio (NASDAQ: BLUE) shared some highly encouraging data just eight days after two more patient deaths forced Juno Therapeutics (NASDAQ: JUNO) to halt a controversial study. Despite the drama, Kite Pharma (NASDAQ: KITE) appears to be in the lead, with plans to submit an application next year.

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Will the flames from Juno's crash spread to its peers? Do bluebird bio's results threaten the leaders? Let's take a closer look to find out.

Rocket to nowhere?

While many of us enjoyed a relaxing holiday, Juno Therapeutics investors have seen their shares fall about 33% since announcing that two more patients in the Rocket study suffered cerebral edemas that resulted in their unfortunate deaths. You might rememberthat this is the same trial the FDA briefly placed on hold over the summer due to patient deaths, then swiftly allowed to resume after Juno swapped a type of chemotherapy used to precondition patients for transfusion with JCAR015.

It's important to point out that the Rocket study enrolled adult patients with relapsed acute lymphoblastic leukemia. Options for these patients are limited, and treatment with chemotherapy cures less than 30% of adults with the disease. Once patients like those in the Rocket trial relapse following chemo, dangerous stem-cell transplants are the next step. If a stem-cell transplant fails, a patient's prognosis is extremely grim.

Because these patients lack treatment options, there's a chance the deaths are more of a setback than a total loss for this study. Juno is testing the same candidate in two earlier-stage trials with different malignancies that could help shine a light on JCAR015's risk-benefit profile. Juno shareholders will also want to keep an eye open for a thorough examination of the Rocket results to see how large a role patient frailty played in the deaths.

Isolated crash or a pileup?

Kite Pharma shares dipped slightly with news of Juno's mishap, while bluebird bio's rose a bit. The fact that Kite's lead candidate targets the same surface protein on malignant blood cells, while bluebird's CAR-T candidate zeros in on another, explains the divergence.

Although KTE-019 and JCAR015 both target CD19, it doesn't look like Kite Pharma will avoid Juno's wreckage and win the checkered flag. Kite's candidate is in a trial it contends will support an application for treatment of three forms of lymphoma, and so far, the results are encouraging. Response rates are extremely high, and there haven't been any patient deaths.

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There have been some serious side effects, though, and investors will want to look out for an in-depth presentation of interim results from this study at the upcoming American Society of Hematology meeting.

Surprise curve

Just eight days after Juno Therapeutics announced its setback, bluebird bio shared some positive data for bb2121, a CAR-T therapy that reengineers T-cells to target B-cell maturation antigen (BCMA) in multiple myeloma patients. Neither Juno nor Kite hasa candidate in clinical trials directed at this target or the malignancy, and the positive results were a pleasant surprise for oncologists and investors.

Seven of nine evaluable advanced multiple myeloma patients treated with bb2121 responded to the treatment. In two of the patients, investigators reported a complete lack of malignant cells.

The most encouraging feature of the mid-trial snapshot, though, was a lack of serious side effects across dosage levels. This suggests that, when bluebird is ready to design a study to support a new drug application, it can use the highest dose without the toxicity issues hounding CD19-directed CAR-T therapies.

Plenty of fuel

While Juno's setback is upsetting, it's important to note it has a second candidate that targets CD19, and a handful of early clinical-stage candidates with different targets. Earlier this year, Juno's partner Celgene opted to co-develop Juno's CD-19 program in return for a lot of upfront cash and half of ongoing development expenses.

During the first nine months of the year, Juno burned through $192.8 million, which suggests that the $711.7 million in working capital on its balance sheet at the end of September could see the company through a potential rough patch if JCAR015 is a total flop.

Never one to put all its eggs in one basket, Celgene also has exclusive rights to develop and commercialize bb2121, although bluebird can opt to co-develop it in return for U.S. commercialization rights. Whatever it decides, bluebird's cash runway is nearly as long as Juno's, and its more advanced non-cancer cellular therapies could provide a revenue stream long before its CAR-T candidate crosses any finish lines.

Image source: Getty Images.

Kite Pharma also has enough cash for, perhaps, another two years before it will need to raise more cash. It's planning a rolling submission for KTE-C19 that it might complete next year. If it earns an approval, the company might be able to commercialize its lead candidate without another trip to the equity tap.

While it looks like Kite Pharma will be first to send CAR-T therapy applications to regulators, bluebird might win in its own way, and Juno is hardly finished. I'm sure there'll be more twists and turns ahead, so grab a seat and enjoy the rest of the race.

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Cory Renauer has no position in any stocks mentioned. The Motley Fool owns shares of and recommends Celgene. You can follow Cory on Twitter @coryrenauer or LinkedIn for more investing insight.

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