Platforms in the making
Both Juno Therapeutics and Bluebird are developing drug development platforms that can be used to develop additional therapies using the same techniques.
Bluebird's lead products are based on gene therapy: Blood stem cells are taken out of the patient, infected with lentiviruses that inject copies of a gene into the cells. The gene expresses a protein that compensates for a mutation in the patient's genome. Meanwhile, the patients are exposed to drugs to kill off their mutated cells, and the cells with the new gene are put back into the patient where they engraft and start making new cells expressing the protein.
Bluebird first used this gene therapy technique with its Lenti-D therapy, which insets a gene called ATP-binding cassette subfamily D member 1 (ABCD1) into the cells to treat cerebral adrenoleukodystrophy, which is caused by mutations in the ABCD1 gene.
The biotech later improved on the gene therapy technique for its LentiGlobin treatment, which inserts the beta-globin gene. Beta-globin is a protein that's part of hemoglobin, which is responsible for carrying oxygen in blood cells. Increasing beta-globin expression can help patients with sickle cell disease and a rare blood disorder called beta-thalassemia. Both diseases are caused by mutations in the beta-globin gene.
Juno Therapeutics' CARs and TCRs platform also involves taking cells from patients, inserting genes into the cell, and returning them to the patient. But instead of using genes to correct mutations in the patients, Juno's CAR and TCR constructs are inserted into T-cells to train the immune cells to attack a tumor. Whether a CAR or TCR platform is used is determined by whether the targeting protein is expressed on the surface of the tumor cell (CAR) or internally (TCR).
Juno's lead treatment, JCAR015, targets mutant blood cells expressing CD19 to treat patients with acute lymphobastic leukemia and non-Hodgkin lymphoma, but the platform offers flexibility to target proteins in a variety of tumor types, and Juno is doing just that with multiple therapies already in the clinic.
It should be noted that Bluebird also has a CAR T cell program, but it's only in phase 1, so it doesn't factor much into the biotech's valuations. Interestingly, Celgene had a somewhat broad partnership with Bluebird for its CAR program but limited the scope of the deal to just a single target, BCMA, the target of Bluebird's lead CAR product candidate, bb2121. Bluebird has other immuno-oncology deals, including one with Kite Pharma (NASDAQ: KITE) to target tumors caused by human papillomavirus, but that's still in preclinical development.
It's all about the data
Both biotechs have had some issues with their platforms, but already have plans in place to modify the therapies, which will hopefully eliminate the problems.
Bluebird's issue stems from the average number of copies of the gene were getting into the cells, which ultimately affects the expression of the protein. The biotech has developed a new manufacturing technique that increases the copy number, which will hopefully lead to a higher cure rate. The company also suspects that the cure rate may be dependent on how well the gene therapy cells engraft when they're put back into the patient, so it's modifying that technique as well.
One of Juno's clinical trials for JCAR015 was put on hold by the Food and Drug Administration in July after two patients died. The biotech believed the deaths were linked to the addition of a chemotherapy called fludarabine, which is given before the engineered T-cells are put back into the patient. Juno told the FDA that it would stop using fludarabine, and the agency agreed to let the trial continue.
Next year will be a big year for both companies, with Bluebird reporting clinical data for patients treated using its new manufacturing process, and Juno reading out results for the trial testing JCAR015, which should be enough to gain FDA approval if it's positive.
Developing new treatment technologies is challenging, making both biotechs relatively risky. One way to mitigate that risk is by buying both companies, giving investors twice as many chances at hitting it big.
If I had to pick one, Juno appears to be the less risky of the two, scientifically speaking at least, especially with Celgene's endorsement. Just keep in mind that commercially there's likely to be a lot of competition in the CAR and TCR space, so Juno's data will not only determine whether its therapy gets onto the market, but how well it sells.