Bristol-Myers Squibb Co. is paying $50 million for rights to use Cytomx Therapeutics Inc.'s Probody platform to discover and develop up to four new immunotherapies for cancer, including one targeting CTLA-4, the same receptor targeted by BMS' melanoma fighter, Yervoy (ipilimumab).
The deal includes undisclosed additional preclinical payments and up to $298 million in milestones per target, plus potential royalties. It's Cytomx's second big pharma score after Pfizer Inc. agreed last year to pay the South San Francisco-based company $25 million up front to develop Cytomx-identified candidates. BMS has rights to substitute up to two collaboration targets.
"This is exactly the right deal at exactly the right time for Cytomx and also for BMS," Cytomx CEO Sean McCarthy told BioWorld Today, noting BMS' success in the immuno-oncology space. "They blazed a trail with Yervoy, and this field has ignited as a result of their success."
BMS, of New York, already has shown significant enthusiasm for the potential of antibody-drug conjugates. It began an ongoing relationship with San Diego-based Ambrx Inc. in 2011 that has since yielded three deals, the most recent of which provided Ambrx potential milestone payments of up to $97 million per cancer drug. (See BioWorld Today, May 6, 2013.)
The company said it was impressed by "the unique selectivity" of Probodies and their potential to create new classes of safer and more effective therapies.
Despite advancements in immuno-oncology to date, McCarthy said, there are very few targets for antibodies that present only in tumors and not in healthy tissue. Probodies, Cytomx's specialty, avoid that problem by only binding to antigens in diseased tissue. Probodies, antibodies with masked binding sites, remain inert in healthy tissue until proteases present in the tumor microenvironment break the bonds of the mask, allowing the antibodies to bind to receptors on the cells comprising the diseased tissue.
The BMS agreement is Cytomx's first revolving around Probodies alone. Its collaborations with Pfizer and Immunogen Inc. focused on Probody-drug conjugates (PDCs), combinations of cytotoxic agents with Probodies. Its June 2013 Pfizer deal also calls for as much as $610 million in milestones to develop selected PDC candidates. With a potential total value of $635 million, it was the fifth largest deal struck between a biotechnology company and a pharmaceutical company last year. (See BioWorld Today, June 7, 2013, and Dec. 30, 2013.)
McCarthy said the company is continuing to work toward its first preclinical milestone payment in that deal.
In January, Cytomx landed a multiyear, strategic collaboration with Immunogen, of Waltham, Mass. to develop PDC therapies to treat cancer. Each company in that deal retains full development control of PDC compounds resulting from its target selection and is assuming responsibility for preclinical and clinical testing, manufacturing and commercialization. (See BioWorld Today, Jan. 10, 2014.)
"Our focus over the last two or three years has been to tease out the killer applications of this technology," McCarthy said. While the PDC opportunity seemed the clearest and most tangible initial goal, he said, the company took note of the developments in cancer immunology and kept in touch with potential partners, building the key relationships that will enable Cytomx to fund development of its own pipeline.
Two preclinical candidates, both targeting jagged ligands in the Notch pathway, lead its internal program. One, CTX-033, is a Probody that blocks jagged ligand-dependent Notch signaling. In October, the company reported preclinical data showing that it demonstrated efficacy in pancreatic cancer models as both a single agent and in combination with gemcitabine. Data also showed it to be locally active in the tumor microenvironment, avoiding systemic side effects. (See BioWorld Today, Oct. 23, 2013.)
The Notch program's second candidate, CTX-1003, is a PDC that utilizes jagged ligands as tumor antigens to deliver a cytotoxic payload to tumor cells.
A DOUBLE-DEAL DAY
Further highlighting BMS' interest in the immuno-oncology space, the company also announced on Tuesday a deal with Incyte Corp. to establish a clinical trial collaboration to evaluate the safety, tolerability and preliminary efficacy of a combination of BMS' investigational PD-1 immune checkpoint inhibitor, nivolumab, and Incyte's oral indoleamine dioxygenase-1 inhibitor, INCB24360, in a phase I/II study. The companies said they'll explore multiple tumor types in the study, potentially including melanoma, non-small-cell lung, ovarian, colorectal, squamous cell carcinoma of the head and neck and diffuse large B-cell lymphoma.
Wilmington, Del.-based Incyte will conduct the co-funded study, which the companies anticipate starting in the fourth quarter. Neither partner released financial details of the collaboration. An earlier study showed that INCB24360 seems to work well with BMS' Yervoy. (See BioWorld Today, May 15, 2014.)