Bolstering its capacity in chimeric antigen receptor T (CAR-T) cell therapies as well as the high-affinity T-cell receptor (TCR) approach, Juno Therapeutics Inc. expects that its already flexible strategy next will be able "not only to insert a gene but also change or modify genes already present inside the cell," chief financial officer (CFO) Steve Harr told BioWorld Today, thanks to a pact signed with Editas Medicine Inc.

Seattle-based Juno will provide Editas, of Cambridge, Mass., with $25 million up front and as much as $22 million in research support over the next five years across three programs, with potential milestone payouts related to progress in that realm as well as regulatory and sales of more than $230 million associated with each program, plus tiered royalties if marketed products result.

"When we discussed the implementation of our technology, we highlighted a series of challenges or unanswered questions that we think it's going to be important that we tackle over the next several years," Harr said. These include "finding great targets, and by that we mean targets for our cells that discriminate between cancer tissue and normal tissue, as well as improving "how long they stick around in the body," he said. Coming up with the right cell population is vital, too. "We know that different T cells have very different biological functions," he said. "It's fundamental that we understand and control which population of T cells we're treating the patient with."

Manipulating the tumor biome is yet another matter. "Cancer sends out a number of different signals that create barriers to prevent activation of the immune system," he said. The fifth main concern is finding ways to turn the CAR-T cell off when necessary, and controlling gene expression to dial up or dial down activity in order to achieve drug-like properties. "We think gene-editing can help us with a number of those," Harr said.

Editas' CRISPR (clustered, regularly interspaced short palindromic repeats)/Cas9 (CRISPR associated protein 9) system deploys a protein-RNA complex composed of the Cas9 enzyme bound to a guide-RNA molecule designed to recognize a particular DNA sequence. The RNA molecules guide the Cas9 complex to the location in the genome that needs to be repaired, enabling knock-out, knock-down, or selective editing of defective genes in the context of their natural promoters.

"Cells can do things as therapeutics that antibodies and small molecules can't do," Juno CEO Hans Bishop told BioWorld Today. "We know that T cells can get into any tissue – there's no part of our anatomy that T cells can't access. We know that we can reprogram cells to have truly exquisite specificity. That's harder with smaller molecules. And we know that cellular therapies can also regulate dose; they can increase the dose in the presence of disease and decrease dose in the absence of disease. Of course cells are also more complicated than antibodies; they have multiple regulatory mechanism and switches," Bishop noted, and the genome-editing technology brought by Editas "allows us to reprogram the cell in whichever way get the results that would be [most] beneficial. To be successful, you have to have a very clear-sighted view of the capability that it's going to take to win, and we for sure believe that this is one of them."

BLUEBIRD REVS FOR BID WITH CELGENE

J.P. Morgan analyst Cory Kasimov said his firm "continues[s] to be encouraged by Juno's activity on the business development front, as the company adds a variety of technological capabilities" to its platform. In a research report, he added that he was "not surprised by this morning's announcement," and expects that the company "will likely continue to be active in adding to its increasing spectrum of resources. Bottom line, our thesis is unchanged: While we think it is premature (and unnecessary) to pick a winner in these early innings of the CAR-T evolution, we believe Juno's multiple sources of technology/innovation (and continuing investment in expanding its platform) may prove to be a competitive advantage over time."

CFO Harr confirmed as much, pointing out that "right now, science is moving very rapidly and in particular cell therapy and gene therapy. There's a high probability that a lot of the great science will take place outside the genome. We're always looking for those technologies as well as insight that will improve and broaden our capabilities. It comes down to quality of science as well as the quality of the partner and people who can help us implement it. We think we've [found] that with Editas, and we'll continue to look for things like this." Juno's strategy in leukemia to date has been "very encouraging," he added. In lymphoma, the progress has been "good, but we think we can make it better, and the company "still [has] to show what we can do in solid tumors," he said.

The busy space recorded another possibly lucrative deal, as Cambridge, Mass.-based Bluebird Bio Inc. sealed an arrangement with Five Prime Therapeutics Inc., of South San Francisco. The latter is providing Bluebird exclusive rights to its human antibodies to an undisclosed cancer target for hematologic malignancies and solid tumors, against which Bluebird will leverage its lentiviral gene platform therapy and CAR-T capabilities.

Five Prime collects $1.5 million up front plus more than $130 million per licensed product if certain development, regulatory and commercial goals are hit. The firm also stands to reap tiered royalties on product sales on products that emerge from the deal. Under the terms, Bluebird conducts and pays for clinical development as well as regulatory and commercial activities.

Kasimov, in a separate research report, called Bluebird's move "storing more parts in the CAR-T garage. Ahead of Bluebird's planned entry into the CAR-T space along with partner Celgene Corp. (expected in 2016), we believe it's prudent for the company to accumulate targets/technology in the midst of a rapidly evolving landscape. That said, CAR-T isn't a relevant part of the Bluebird story in the near term, and instead we see it as a potential lever for additional upside in the 2016-and-beyond time frame, when we get clarity on [the company's] CAR-T strategy." Two years ago, Bluebird entered the multi-year research and development collaboration with Celgene, of Summit, N.J. (See BioWorld Today, March 22, 2013.)

Shares of Juno (NASDAQ:JUNO) closed Wednesday at $46.84, up 39 cents. Bluebird (NASDAQ:BLUE) ended at $189.69, up $6, and Five Prime shares (NASDAQ:FPRX) finished at $22.63, up $2.96, or 15 percent.