SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--CytomX Therapeutics, the Probody™ therapeutics company, today announced the publication of preclinical data demonstrating the enhanced therapeutic index of its epidermal growth factor receptor (EGFR)-directed Probody compared to cetuximab, a currently available monoclonal antibody EGFR inhibitor approved by the U.S. Food and Drug Administration for the treatment of certain head and neck and colorectal cancers. In studies conducted in vivo in both mouse and non-human primate models, the data show that CytomX’s EGFR-directed Probody, CTX-023, remains inert in healthy tissue but is locally activated in the tumor microenvironment, resulting in similar efficacy as cetuximab, but with significantly reduced side effects. The findings, published online today in Science Translational Medicine, support the potential of CytomX’s Probody Platform to expand the therapeutic antibody target landscape and address previously undruggable targets due to toxicity in cancer, inflammation and other areas of significant unmet medical need.
“Traditional antibody therapies like cetuximab, although effective, can be limited by specific toxicities and narrow therapeutic index, which can result in decreased quality of life, as well as a decrease, interruption or discontinuation of treatment,” stated Henry Lowman, Ph.D., chief scientific officer of CytomX and senior author of the paper. “Our findings with an EGFR Probody confirm that we can retain potent in vivo efficacy, but with greatly reduced side effects by targeting antibody activity to disease tissue using our proprietary Probody Platform.”
CytomX’s Probodies are masked antibodies that remain inert in healthy tissue but are activated or “unmasked” in the disease microenvironment. EGFR is a well-validated cancer target that is highly expressed in several tumor types, but is also broadly expressed in healthy tissue, particularly skin, often resulting in debilitating toxicity (e.g. acne-like rash). The data show that when CTX-023 is administered in mouse xenograft and primary human tumor models, it reduces tumor growth to a similar extent as cetuximab. In healthy tissue and circulation, CTX-023 remains in its inert, masked form and therefore does not bind to EGFR, resulting in a significantly improved safety profile versus cetuximab. The CytomX team also investigated the safety profile of CTX-023 in non-human primates. In this study, results demonstrate that at a weekly dose of 25mg/kg for four weeks, no skin rash or redness was observed in the Probody treatment group, whereas all non-human primates treated with cetuximab showed evidence of skin toxicity.
“We are pleased to see these preclinical data on the Probody Platform published in a peer-reviewed forum,” said Sean McCarthy, D.Phil., chief executive officer of CytomX. “This paper represents yet another key milestone for the Company and illustrates the true potential of the Probody approach. As we continue to build our pipeline and advance toward the clinic we are encouraged by these data that demonstrate the potential for Probodies to expand the therapeutic window of traditional antibodies, potentially leading to safer, more effective therapies for patients.”
The Science Translational Medicine paper titled “Tumor-Specific Activation of an EGFR-Targeting Probody Enhances Therapeutic Index,” was published today online at www.ScienceTranslationalMedicine.org, and will appear in an upcoming print edition of the journal.
CytomX Therapeutics, the Probody™ therapeutics company, is dedicated to transforming lives with safer, more effective therapies. CytomX’s Probody Platform represents a disruptive approach to discovering and developing the next generation of antibody therapeutics and is enabling the development of a diversified pipeline in major unmet medical needs including cancer and inflammation. Probodies are masked antibodies that remain inert in healthy tissue but are activated specifically in the disease microenvironment. This breakthrough selectivity allows CytomX to drug previously undruggable antibody targets, unlock new therapeutic targets for antibody-drug conjugates (ADCs), and focus activity in the tumor microenvironment, thereby redefining the landscape for therapeutic antibodies. CytomX is led by a seasoned and proven management team and is financed by leading life science investors including Third Rock Ventures, Canaan Partners and the Roche Venture Fund. For more information, please visit www.cytomx.com.