CEO Sean McCarthy told BioWorld Today that Cytomx Therapeutics Inc.'s deals will be "increasingly strategic," structured for purposes of "not just bringing cash in the door," and the latest – the firm's third pharma pact – with Abbvie Inc. typifies what he's talking about: "a foundational, pipeline-building" arrangement.
North Chicago-based Abbvie is paying Cytomx, of South San Francisco, $30 million up front with the promise of $470 million more if development, regulatory and commercial goals are met in the co-development of a Probody drug conjugate against CD71, also known as transferrin receptor 1, widely expressed in solid tumors and hematological cancer. Cytomx has designed Probody drugs to stay inert until activated by proteases in the tumor microenvironment, thereby sparing healthy tissue.
"The importance of this deal for the company is not just the partnership with a leading player in antibody-drug conjugates [ADCs] and the economic terms that allow us to fully fund this program and move it toward the clinic," McCarthy said. "It's also that the alliance gives us the financial flexibility to advance a fourth program" involving a PD-1 Probody.
Cytomx is leading preclinical and early clinical development of the CD71 therapy, with Abbvie taking up later stages as well as commercialization. The pair will split global late-stage development costs. Abbvie is to lead the global marketing push, with Cytomx eligible for a profit share in the U.S. plus tiered double-digit royalties on net product sales outside the country. Cytomx holds an option to co-promote in the U.S., too.
Abbvie also gets exclusive worldwide rights to develop and commercialize Probody drug conjugates for up to two additional, undisclosed targets. Should the pharma firm pursue those targets, Cytomx stands to gain milestone and royalty payments per target on any products that result.
With CD71, "we retain responsibility for filing the investigational new drug [IND] application and running the early clinical studies, which is something that was important to us because we're building the company quickly and evolving into a clinical development-stage organization," McCarthy said, noting that Cytomx "began life as a very research intensive company, and we continue to be research-based as we excavate the science around this unique platform." The firm will file an IND for its wholly owned lead asset, CX-072, a Probody therapeutic directed at PD-L1, in the second half of this year, with another IND for wholly owned CX-2009, a Probody drug conjugate directed at CD166, in the first half of next year.
Cytomx also has collaborations with New York-based Pfizer Inc. and with Bristol-Myers Squibb Co., also of New York, set up "such that the partners are responsible for the majority of the work," McCarthy said. "Our organizational obligation is relatively modest, which means that, to this point, the vast majority of our staff, our headcount, is devoted to our own, proprietary programs. It's a very careful balance, as to the degree to which one partners one's assets vs. retaining them [and] with regard to how many of your employees you want working on partnered programs. I've been with companies in the past where the majority of the company has been working on partnered programs. It's a little different here at Cytomx."
The recent American Association for Cancer Research (AACR) meeting included preclinical data with the CD71 candidate. McCarthy said CD71 "by its very biological function exists to internalize transferrin, and in doing so deliver iron to the cell. It's a really perfectly suited target to internalize antibody-drug conjugate and deliver payload into the cell. In fact, it's so good that many companies use this target as a positive control in preclinical experiments to compare other agents to. We reasoned that, with the Probody technology, we could create a therapeutic window for this target." The AACR poster showed the compound to be "highly potent in regressing a variety of tumors in preclinical models" and well tolerated, whereas a CD71 ADC turned up high hematological toxicity in monkeys, he said, "a pretty striking finding that shows preclinically that we appear to have opened a therapeutic window for this very high potential target. Those, of course, are the data that brought Abbvie to the table." Data emerged over the course of the second half of last year.
Cytomx's trio of pharma deals "feels pretty comfortable, based on the way we've grown the company thus far," McCarthy said. "Our platform is so broad, and it has applications across so many antibody modalities that it naturally lends itself to partnering." Internally, there's more in the works. "We've engineered a unique format for a Probody version of a T cell-engaging bispecific [antibody]," he said. Data were presented last year at the European Organization for Research and Treatment of Cancer meeting. "It's a very interesting platform within a platform, if you like, that has the potential to open up T-cell bispecifics into the solid tumor space, which is of high interest in the industry right now," he said. Cytomx now expects to burn only $20 million to $25 million in 2016 vs. previous guidance of $45 million to $50 million and maintained that the firm has sufficient cash through 2018.