CytomX Therapeutics, an oncology-focused biopharmaceutical company based in South San Francisco developing investigational Probody™ therapeutics for the treatment of cancer, earlier today announced that Bristol-Myers Squibb has selected a third target in accordance with the companies’ strategic oncology collaboration established in May 2014. The selection triggering a $10 million milestone payment.

Under the terms of the agreement CytomX granted Bristol-Myers Squibb exclusive worldwide rights to develop and commercialize Probodies for up to four oncology targets including CTLA-4, a clinically validated immune inhibitory checkpoint receptor.

CytomX is also eligible to receive additional preclinical payments and up to $298 million in future development, regulatory and sales milestone payments for each collaboration target, as well as tiered mid-single digit rising to low-double digit royalty payments on net sales of each product commercialized by Bristol-Myers Squibb.

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“Our collaboration with Bristol-Myers Squibb has progressed very well and we are pleased to expand our collaborative work to a third target,” said Sean McCarthy, D.Phil., President and Chief Executive Officer of CytomX. “We look forward to continuing to work closely with the BMS team to advance product candidates into development.”

Immunotherapies against clinically-validated targets
Research has shown that traditional antibodies bind to unique antigens that exist in abundance on diseased tissue. However, many of these antigen targets are also found on healthy tissue. This has been a critical challenge in the development of highly potent next-generation antibody therapies, including immunotherapy combinations, antibody drug conjugates or ADCs,  T-cell engaging bispecific antibodies  (BiTe) and ProCAR-NK cell therapies. While highly specific for their target, finding some of these targets in normal, healthy tissue (e.g. skin, heart, etc) may lead to unwanted toxicity.

Investigational therapeutics developed with CytomX’s Probody platform are designed to be active in the tumor. By creating development-stage proprietary cancer immunotherapies against clinically-validated targets, as well as to develop first-in-class investigational cancer therapeutics against novel targets, the novel drugs enhance the tumor-targeting features of an antibody and reduce drug activity in healthy tissues, sparing healthy tissue. Furthermore, by restricting activity to the tumor microenvironment, investigational Probody therapeutics directed against both validated and novel targets have been shown preclinically to enable anti-tumor efficacy with an enhanced safety window, relative to traditional antibody-based therapies.

In simple terms, Probodies are modified in such a way that they are unable to bind their target unless they are cleaved by proteases, often found in and around tumors.  Because they are ‘activated’  at the site of the tumor, toxicity in normal, healthy tissue is greatly reduced.

The Probody platform is expected to have the potential to improve the combined efficacy and safety profile of monoclonal antibody modalities, including cancer immunotherapies, antibody drug conjugates and T-cell-recruiting bispecific antibodies.

The investigational Probody therapeutics being developed that address clinically-validated cancer targets in immuno-oncology, such as PD-L1, against which clinical candidate CX-072 is directed, as well as novel targets, such as CD-166, that are difficult to drug without causing damage to healthy tissues, or toxicities.

In addition to a collaboration with BMS, CytomX Therapeutics is working with other partners, including Pfizer, Immunogen and The University of Texas MD Anderson Cancer Center.