Aiming Probody compounds at CD71

Collaboration between AbbVie and CytomX will develop drug conjugates to deliver cytotoxic payloads to tumor cells

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NORTH CHICAGO, Ill. & SOUTH SAN FRANCISCO, Calif.—AbbVie and CytomX Therapeutics Inc. have entered into a collaboration to co-develop and co-commercialize Probody Drug Conjugates against CD71. Also known as transferrin receptor 1, CD71 is highly expressed in a number of solid and hematologic cancers, including breast, pancreatic, lung, renal, esophageal and colon. Probody compounds are designed to be efficient for delivery of cytotoxic payloads to tumor cells without harming other cells.
CytomX, an oncology-focused biopharmaceutical company pioneering a novel class of investigational antibody therapeutics, has developed the Probody technology platform, consisting of fully recombinant, masked monoclonal antibodies that have the potential to improve the therapeutic windows of emerging antibody technologies and to improve efficacy and safety for patients, according to the company. “Probody therapeutics are designed to be activated in the tumor microenvironment to enhance the tumor-targeting features of an antibody while being inert in healthy tissues,” explained Debanjan Ray, senior vice president of corporate development at CytomX.
Ray, who played a pivotal role in moving the collaboration forward, said that the companies had been talking about it for several years as the platform matured. AbbVie, a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories, attempts to develop and market advanced therapies that address some of the world’s most complex and serious diseases.
Preclinical proof-of-concept data for CytomX's Probody technology has been published in Science Translational Medicine. According to a presentation by CytomX at the American Association for Cancer Research annual meeting this year, CD71 is “ubiquitously expressed on dividing, normal (hematological precursors) and malignant cells.” It mediates iron uptake required for cell division and cannot be down-regulated by tumors. CD71 is often used as a positive control in antibody-drug conjugate (ADC) experiments. Its expression in normal dividing cells prohibits the development of a traditional ADC. In preclinical studies, “Probody drug conjugates can safely and effectively target attractive tumor antigens like CD71 which have been difficult to address with traditional ADCs due to their expression on critical normal tissues,” the presenters said.
AbbVie and CytomX have several objectives, according to Ray. CytomX is working internally to advance Probody into clinical development and then market the drug with AbbVie. Additionally, the two companies will work together to “unlock drug conjugate targets in oncology,” using Probody on targets identified by AbbVie, Ray said. CytomX will lead in the early development of Probody, AbbVie will lead in later development and commercialization and then the two companies will be involved in late-stage commercial development and co-promotion in the United States.
Global late-stage development costs will be shared. CytomX will receive an upfront payment of $30 million and possibly $470 million in development, regulatory and commercial milestones if predetermined outcomes are achieved. CytomX is eligible to receive a profit share in the United States and tiered double-digit royalties on net product sales outside of the United States. AbbVie will have exclusive worldwide rights to develop and commercialize Probody drug conjugates against up to two additional, undisclosed targets. If AbbVie pursues these targets, CytomX can receive additional milestone and royalty payments per target on any resulting products.
Dr. Steve Davidsen, vice president of oncology drug discovery at AbbVie, said, "We believe that the Probody platform provides a differentiated opportunity to combine with our strength in antibody-drug conjugates. We are encouraged by the promising preclinical data that CytomX has generated for the Probody drug conjugate programs. This collaboration will enable us to expand our innovative pipeline in antibody-drug conjugates and leverage our strength in that area to previously unexplored targets."
According to Dr. Sean McCarthy, president and CEO at CytomX, "This collaboration is another important step toward achieving CytomX's vision of transforming lives with safer, more effective therapies and allows us to further advance our broad pipeline of Probody therapeutics. AbbVie has demonstrated leadership in developing antibody-drug conjugates and we look forward to collaborating to realize the full potential of our CD71 Probody drug conjugate program and additional oncology targets."

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