ENMD-2076 demonstrates antitumor activity against murine xenograft models of CRC: Study

Jun 2 2010

EntreMed, Inc. (Nasdaq: ENMD), today announced the publication of preclinical results for its clinical-stage Aurora A/angiogenic kinase inhibitor, ENMD-2076, in human colorectal cancer xenograft models.  The results of the study, conducted by EntreMed collaborators at the University of Colorado School of Medicine, were published in the June 1, 2010 issue of Clinical Cancer Research (Vol. 16, Issue 11). ENMD-2076, EntreMed's lead oncology drug candidate, is currently in a multi-center Phase 2 study in ovarian cancer patients.

ENMD-2076 demonstrated robust antitumor activity against murine xenograft models of human colorectal cancer (CRC) established from both cell lines and primary human samples.  Advanced imaging techniques including dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18FDG-positron emission tomography (18FDG-PET) were employed in the study, and revealed the strong antiproliferative, antiangiogenic, and antimetabolic activities of ENMD-2076 towards tumor cells.   ENMD-2076 induced regression of tumors in a xenograft model derived from the HT29 human colorectal cell line.  In addition, ENMD-2076 induced strong growth inhibition of tumors that were grown in murine models from KRAS mutant cancer tissue taken directly from primary or metastatic sites in CRC patients.  In contrast to cetuximab (Erbitux®), ENMD-2076 appears to be effective in both KRAS mutant and wild-type CRC tumors and therefore may represent a potential option for the enlarging population of patients with KRAS/BRAF/PI3K mutated tumors.  Results from this preclinical study, along with data from the Phase 1 study in patients with solid tumors, suggest that ENMD-2076 may have potential therapeutic benefit in the treatment of colorectal cancer.    

Dr. John Tentler, Division of Medical Oncology, University of Colorado School of Medicine, commented on the results, "We are very excited about the preclinical efficacy of ENMD-2076 against our murine models of CRC. While the antitumor effects of this compound on the human colon cancer xenografts were readily apparent, we were pleased that the imaging studies of these tumors also indicated profound changes in their vasculature and metabolism in response to ENMD-2076. It is our hope that these results translate to the patients in future clinical trials."

Dr. Mark R. Bray, Vice President Research at EntreMed commented on the paper, "In addition to demonstrating the substantial efficacy of ENMD-2076 in xenograft models of colorectal cancer in their excellent and comprehensive study, Dr. Tentler and his colleagues have illustrated the potential utility of advanced, non-invasive imaging techniques such as DCE-MRI and PET in evaluating the compound's antitumor and antiangiogenic capabilities.  These results provide invaluable information regarding the mechanism of action of ENMD-2076, and further support our goals for the clinical development of the compound.  In the Phase 1 study in which ENMD-2076 was used to treat patients with solid tumors, colorectal cancer patients were among the participants who showed clinical benefit by reductions in tumor volume and tumor markers. We continue to evaluate the therapeutic potential of this potent compound in both solid and hematological cancers and recently initiated a multi-center Phase 2 study in ovarian cancer patients."