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First-in-Class Masked Antibody Therapeutic Effective in Fighting Pancreatic Tumor Models

By BiotechDaily International staff writers
Posted on 13 Nov 2013
In research conducted with multiple preclinical models, the data indicate that a new masked antibody therapeutic has been shown to be effective in fighting pancreatic cancer models as both a single agent and in combination with gemcitabine, a currently available antimetabolite drug approved by the US Food and Drug Administration (FDA) to treat pancreatic and other cancers.

Furthermore, the data show that the agent is locally activated in the tumor microenvironment and it spares systemic side effects, such as skin toxicity associated with systemically blocking Notch pathway signaling.

CytomX Therapeutics (South San Francisco, CA, USA), a Probody therapeutics company, recently presented data demonstrating preclinical proof-of-concept of the company’s Jagged Probody blocking Jagged-dependent Notch signaling for the treatment of cancer. These data were presented for the first time at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics being held October 19-23, 2013, in Boston (MA, USA).

“The Notch pathway is centrally implicated in tumor biology and is involved in the progression of a number of cancers, including pancreatic cancer, triple negative breast cancer, and multiple myeloma,” stated Henry Lowman, PhD, chief scientific officer of CytomX and senior author of the poster. “Our anti-Jagged Probody represents a novel approach to targeting the Notch signaling pathway, and our data establish preclinical proof-of-concept that selective activation of CTX-033 in the tumor microenvironment results in robust efficacy with an acceptable therapeutic index.”

Probodies are masked antibodies that remain inert in healthy tissue but are activated or “unmasked” in the disease microenvironment. CytomX is developing a novel, first-in-class Probody program that blocks Notch signaling by both the Jagged-1 and Jagged-2 ligands locally in the tumor microenvironment.

“Following our recent publication on the Probody platform in Science Translational Medicine, these data provide further validation of our unique and highly differentiated Probody approach,” said Sean McCarthy, D.Phil., chief executive officer of CytomX. “Our Jagged Probody program showcases the value of the Probody platform in targeting a pathway that has been challenging with traditional antibodies because of healthy tissue toxicities, and we look forward to advancing this novel concept towards clinical testing.”

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.

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