Treatment without toxicity

CytomX and ImmunoGen collaborate to develop PDCs to fight cancer

Ilene Schneider
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SOUTH SAN FRANCISCO, Calif.—It is often said that cancer treatment is worse than the disease. A recent collaboration is designed to make sure that the cancer-killing agents are as effective as possible while not harming healthy cells.
Bay Area California company CytomX Therapeutics and Waltham, Mass.-based ImmunoGen Inc., have teamed up in a multiyear strategic collaboration to develop highly localized cancer therapeutics that limit toxic effects elsewhere. Under the terms of the agreement, CytomX, which has developed its highly targeted Probody antimasking technology, and ImmunoGen, a biotechnology company that develops targeted anticancer therapies using its validated and potent antibody-drug conjugate (ADC) technology, will develop Probody-drug conjugate (PDC) therapies for the treatment of cancer against a defined number of targets.
Both companies will be responsible for testing, manufacturing and commercialization and retain full development control of PDC compounds resulting from its target selection. Additionally, both of the companies will get clinical and post-approval milestone payments from the other company and royalties from the sales of any marketed products developed through the partnership.
Dr. Sean McCarthy, CEO of CytomX, explains that Probodies are a potentially disruptive class of antibody therapeutics that may further broaden the opportunities for ADCs by localizing therapeutic activity to the tumor microenvironment.
“While monoclonal antibodies are designed to bind selectively to antigens, most antigens are expressed in both diseased and healthy tissue,” he said. “Off-target binding results in toxicity, but Probodies’ antimasking technology is designed to bind antibodies selectively to the target. A Probody is an antibody that is engineered so that the antigen-binding site is masked and cannot see the target. These masks are engineered so they can be removed from the antibody only by enzymes associated with the disease tissue.”
According to McCarthy, Probodies are designed to remain inert in healthy tissue but be activated specifically in the disease microenvironment. Through precise targeting of the disease microenvironment, Probodies have the potential to address diseases in ways that have not been possible to date, enabling a new level of tissue targeting, selectivity and activation.
ImmunoGen CEO and Executive Vice President, Dr. John Lambert, said in a news release about the collaboration, “We believe using our state-of-the-art ADC technology with CytomX’s highly promising Probody platform will enable us to develop therapies that are particularly well-suited for certain challenging cancers.” He explained that ImmunoGen’s ADC targeted anticancer technology is used in Roche’s Kadcyla and in multiple other ADC compounds now in clinical and preclinical testing. It includes highly potent cancer-cell killing agents developed specifically for targeted delivery to cancer cells using monoclonal antibodies and linkers engineered to keep the agent attached to the antibody in the blood stream and control its release and activation inside a cancer cell.
Immunogen's ADC cancer drugs link a monoclonal antibody that targets a specific protein found on cancer cells with a toxic payload of chemotherapy. The objective is to deliver the toxic payload inside cancer cells, so that it can do the most harm to the cancer cells while keeping the chemotherapy agent from harming healthy cells.
“This strategic collaboration with ImmunoGen is designed to allow each company to build pipeline value by capitalizing on the best of both technology platforms,” McCarthy said. “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.”
Both companies have created other collaborations in the past year. In June 2013, CytomX signed a $635 million collaboration deal with Pfizer to develop and commercialize several ADCs for cancer using the Probody drug-development platform. In October 2013, Novartis signed a $200 million agreement to license ImmunoGen’s Targeted Antibody Payload ADC technology to create new anticancer therapeutics for an undisclosed target.

Ilene Schneider

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