on discovering and developing novel therapeutics directed to fundamental biologic pathways thought to drive cancer's growth, resistance, recurrence and metastases in order to improve the treatment of solid tumor cancers.
Hyperactive Wnt signaling is a key oncogenic signal in many types of cancer, and recently has been associated with resistance to cancer immunotherapeutics. OncoMed scientists have published a new manuscript in Science Advances on June 21 titled “WNT antagonists exhibit unique combinatorial anti-tumor activity with taxanes by potentiating mitotic cell death”. In this paper we describe a series of experiments in a large number of patient derived xenografts with two OncoMed developed compounds, vantictumab (anti-FZD) and ipafricept (FZD8-Fc). These two biologics are the most advanced Wnt pathway antagonists in clinical development. We discovered that these agents exhibit much better combination activity with taxanes than with other classes of chemotherapeutic agents, such as gemcitabine or platinum compounds. This is a robust phenomenon and occurs in diverse tumor types including breast, pancreatic, lung and ovarian cancers. Furthermore, we report that combination activity is enhanced by administration of the Wnt antagonist prior to taxane treatment. The combination of Wnt blockade and taxane treatment leads to a dramatic histological phenotype - mitotic cell death in tumor cells. Our hypothesis is that the unique combination activity relies on the action of taxane chemotherapy and inhibition of beta-catenin at the M phase of the cell cycle. This discovery has informed our clinical testing strategy and the mechanism of synergy has implications in understanding the role of Wnt/beta-catenin signaling in regulating the proliferation and differentiation of cancer cells.
Expertise in cancer biology, platform drug discovery technologies and sophisticated antibody engineering know-how have combined to generate a large internally discovered oncology pipeline
Five distinct clinical-stage anti-cancer drugs, several pre-clinical candidates, plus ongoing drug discovery efforts tackling challenging and unique targets sets us up for huge potential successes
Collaborations with partners provide validation of our scientific approach, access to commercial expertise and funding to advance our pipeline and enable strategic company growth
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