So far, the data with allogeneic chimeric antigen receptor (CAR) T-cell therapies say, "liquid tumors yes, solid tumors not yet," Precision Bioscience Inc.'s Chief Scientific Officer Derek Jantz told BioWorld Today, but his genome-editing firm looks to make "significant improvements to the status quo" in the potential $1.6 billion-plus, six-target cancer deal with Baxalta Inc. for allogeneic therapies.

Durham, N.C.-based Precision bags $105 million up front from Baxalta Inc., of Bannockburn, Ill., with the potential for milestone payments as high as $1.6 billion, plus royalties on worldwide sales if projects pan out. Research up to phase II trials will be handled by Precision, after which Baxalta bears the exclusive rights to opt in for later-stage development and commercialization. The first program is expected to enter the clinic late next year.

Precision will deploy its developed-in-house ARCUS technology, the backbone of which is what the firm calls the ARC Nuclease: a fully synthetic enzyme similar to a homing endonuclease, modified so that it's a better starting point for reagents. ARCUS represents "an evolution of the original gene-editing technology Precision was founded on [and] in-licensed from Duke University," Jantz said. "We've essentially spent the last 10 years evolving that into this new thing we call ARCUS." The company is "unusual, in that we didn't do our [series] A round until last year," meanwhile pulling revenues through gene-editing deals in the agriculture space, he added. "This is our first announced therapeutics deal."

Baxalta disclosed an arrangement last month with Ballerup, Denmark-based Symphogen A/S focused on up to six immune checkpoint targets.

Symphogen gained $175 million up front through the pact, plus up to $1.6 billion more in option fees and milestone payments, and the firm will fund all preclinical research as well as clinical development through phase I, at which point Baxalta will be entitled to in-license each program on a product-by-product basis. As in the deal with Precision, the two companies did not disclose the targets involved, but expect the first program to enter the clinic in 2017. (See BioWorld Today, Jan. 5, 2016.)

Checkpoint therapies "can potentially be used in combination" with CAR T drugs, noted Jantz, but "there are also some clever things that we can do to the CAR T cells themselves to make them respond differently to checkpoint signals." Research in CAR T is gathering steam for a good reason: "It's working," he said.

"You've got a lot of patients who are recovering from what appeared to be incurable cancers. The autologous therapies that are doing so well in the clinic right now are paving the way for the next generations of CAR T therapeutics," he said, as groups try using the approach on a broader spectrum of cancers and new patient populations, sometimes with novel ways of manufacturing the cells.

"The closest that's out there [to Precision's method] is what Cellectis is doing," Jantz said. Paris-based Cellectis SA made headlines last November via the three-way deal with New York-based Pfizer Inc. and Les Laboratoires Servier SAS, of Neuilly-sur-Seine, France, both firms moving quickly to secure an interest in the Cellectis UCART19 allogeneic CAR T-cell therapy, which had just gained important proof-of-concept data in acute lymphoblastic leukemia. Servier exercised a pre-existing option on the program, paid $38 million up front and could fork over more than $300 million more in milestone payments. Cellectis also stands to get research funding and sales royalties from Servier. Pfizer, for its part, took U.S. rights to the program by entering a co-development and co-commercialization deal with Servier. Financial terms on that side were not public but the two firms will split development costs. The deal deepened Pfizer's relationship with Cellectis, following the strategic alliance the two companies entered the year before, a tie-up that involves up to 15 oncology targets and up to $2.775 billion in milestones, plus $80 million up front and about $32 million in an equity investment. (See BioWorld Today, June 19, 2014, and Nov. 20, 2015.)

Cellectis' gene-editing approach is "the same concept" as Precision's, Jantz said. "We're obviously putting our own spin on it and doing things a little differently, but the general idea is the same." With CAR T, "people are having a lot of success in liquid tumors, in large part because those are the tumors that are easiest to get to," he added, and "significant technical advancements" are needed in order to tackle solid tumors. "That's an area we are very interested in," he said.

In January, Baxalta agreed to Dublin-based Shire plc's $32 billion takeover. Combining the pair will create the world leader in rare diseases, with high-margin products and operations in 100 countries.

Shire's dependence on its Vyvanse (lisdexamfetamine dimesylate) attention deficit hyperactivity disorder franchise will be lessened, with an estimated 65 percent of revenues coming from orphan drugs by 2020. Between them, specifically, the companies between them will have 60 programs in clinical development, of which more than 50 have orphan status.

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