BMS looks to Probodies for select cancer targets

SOUTH SAN FRANCISCO, Calif.—CytomX Therapeutics and Bristol-Myers Squibb (BMS) have agreed to collaborate on developing and commercializing cancer immunology treatments using CytomX's proprietary Probody platform. CytomX will get $50 million up front from BMS to fund the research and will be eligible for up to $298 million in payments tied to reaching specific milestones. BMS will be given exclusive worldwide rights to develop and commercialize CytomX’s Probodies for up to four oncology targets. “This deal establishes CytomX as a key player in the cancer immunology space,” Dr. Sean McCarthy, CEO of CytomX Therapeutics, tells DDNews. “It shows clearly that the work that we're doing with this Probody platform is highly relevant in a fast-moving field that’s already having a tremendous impact on patients.”

Probodies offer an alternative to traditional antibodies that could potentially lead to safer and more effective cancer treatments. Traditional antibodies work by binding to targets in both diseased and healthy tissue, often causing patients to suffer severe side effects due to exposure to toxicity and leading physicians to limit this therapeutic approach. Probodies are able to target just the diseased tissue while remaining masked in a way that spares them from binding to healthy tissue, thereby minimizing toxicities. CytomX and BMS anticipate that Probodies could significantly expand therapeutic windows for both validated and novel targets. “Immuno-oncology offers a tremendous opportunity to change how cancer is treated, and Bristol-Myers Squibb is committed to advancing our immuno-oncology drug research and development for patients living with the disease,” said Francis Cuss, executive vice president and chief scientific officer at Bristol-Myers Squibb, in the news release about the deal. “The Probody platform has the potential to broaden discovery of innovative therapies, and the collaboration with CytomX reflects our continued leadership in immuno-oncology.”

McCarthy says the Probody approach is becoming increasingly relevant as combination therapies become increasingly prevalent. “As these combination therapies are pursued more frequently, we’re seeing that the tolerability of patients decreases,” he explains. “The Probody approach allows us to focus activity of these antibodies in the tumor and spare some of the systemic immune-system-driven side effects.”

The first of the four oncology targets to be pursued as part of the collaboration will be CTLA-4, a clinically validated immune inhibitory checkpoint receptor. The other targets have not yet been disclosed. “This will be a fairly traditional biotech-pharma alliance, but one that we expect to be highly collaborative,” says McCarthy. “Our responsibility extends to discovering and optimizing the Probodies, and Bristol-Myers Squibb will take the driver’s seat on development.”

In addition to the upfront cash provided by BMS and the $298 million tied to future milestones, CytomX could receive royalty payments on net sales of each product that is commercialized by BMS as part of the collaboration. “This is a very lucrative deal for CytomX,” says McCarthy. “The $50 million in upfront cash will provide an important opportunity to invest in developing our proprietary Probodies and advancing our own pipeline.” The deal between BMS and CytomX will not be final, however, until it receives clearance under the Hart-Scott-Rodino Antitrust Improvements Act.

CytomX’s partnership with BMS is the third major deal it has struck within one year. “We’ve seen a very active period for business development, and it's been great to see the enthusiasm and excitement in the pharma world for what we're doing,” says McCarthy. The previous two deals focused on Probody-drug conjugates (PDCs) and included partnerships with Pfizer and ImmunoGen. McCarthy notes that all three deals together could lead to total payments of up to $2 billion.

The most recent of those previous deals was the collaboration struck in January of this year with ImmunoGen, a biotechnology company that develops targeted anticancer therapies using its antibody-drug conjugate (ADC) technology. At that time, the two companies announced a multiyear strategic collaboration to develop PDC therapies for the treatment of cancer.

Under the terms of the agreement, the companies will collaborate to develop PDCs against a defined number of targets. This collaboration is notable, the companies pointed out, for the skill-pairing involved—it brings together CytomX’s proprietary antibody masking technology and tumor-selective protease substrates with ImmunoGen’s ADC cell-killing agents and engineered linkers.

Each company is to retain full development control of PDC compounds resulting from the target selection and is responsible for preclinical and clinical testing, manufacturing and commercialization. Each company is entitled to potentially receive clinical and post-approval milestone payments from the other company, as well as royalties on the sales of any marketed products resulting from this collaboration.

“This strategic collaboration with ImmunoGen is designed to allow each company to build pipeline value by capitalizing on the best of both technology platforms,” said McCarthy in January. “By combining our Probody technology with ImmunoGen’s world-class linker-payload capabilities, we will accelerate towards our vision of bringing safer, more effective therapies to patients.”

“ImmunoGen is committed to developing better therapies for the treatment of patients with cancer,” added Dr. John Lambert, executive vice president and chief scientific officer of ImmunoGen, at the time. “We believe using our state-of-the-art ADC technology with CytomX’s highly promising Probody platform will enable us to develop therapies particularly well-suited for certain challenging cancers.”