EntreMed starts trial of ENMD-2076 in refractory multiple myeloma patients

EntreMed, Inc. has announced that it has initiated a Phase 1 study of ENMD-2076 in refractory multiple myeloma patients.

The study will be conducted at the Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana. Dr. Sherif Farag, Associate Professor, Department of Medicine, will serve as principal investigator.

Primary objectives for the dose escalation study include determining the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of ENMD-2076 when administered orally once a day in patients with multiple myeloma who are refractory to other drug therapy. The study will also assess the safety, tolerability, pharmacodynamic effects and activity of ENMD-2076 in this patient population.

Preclinical data supporting the clinical evaluation of ENMD-2076 alone and in combination in multiple myeloma were presented by Dr. Farag earlier this week at the American Society of Hematology Annual Meeting in San Francisco, CA. ENMD-2076 was shown to induce rapid apoptosis (cell death) in multiple myeloma cell lines in vitro. Significant dose-dependent antitumor activity with minimal toxicity was also induced in vivo when ENMD-2076 was administered as a single agent in multiple myeloma models. Combination studies with ENMD-2076 and lenalidomide (Revlimid(R)) in vitro indicated synergistic cytotoxic activity towards several human multiple myeloma cell lines. ENMD-2076 was shown, both in vitro and in vivo, to have minimal toxicity towards human and murine hematopoietic progenitor cells, which are essential for maintenance of an active immune system.

ENMD-2076 is an orally-active, Aurora A/angiogenic kinase inhibitor with a unique kinase selectivity profile and multiple mechanisms of action. ENMD-2076 has been shown to inhibit a distinct profile of angiogenic tyrosine kinase targets in addition to Aurora A kinase and other oncogenic proteins. Aurora kinases are key regulators of mitosis (cell division), and are often over-expressed in human cancers. In addition, ENMD-2076 is relatively selective for the Aurora A isoform in comparison to Aurora B. ENMD-2076 has shown significant cytotoxic activity preclinically towards a variety of human leukemia and myeloma cell lines, as well as towards ex vivo-treated human leukemia patient samples.

EntreMed Vice President of Research, Mark R. Bray, Ph.D., commented, "With our ongoing study in solid tumors progressing well, coupled with the initiation of the multiple myeloma study, our ENMD-2076 program is gaining substantial momentum. The work of Dr. Farag and his colleagues has provided important insights into the mechanism of action of ENMD-2076, and has strongly supported the rationale for clinical investigation of the drug candidate in hematologic malignancies such as multiple myeloma."

Carolyn F. Sidor, M.D., M.B.A., Vice President and Chief Medical Officer, commented on the Phase 1 study, "Initiation of this Phase 1 study represents continued advancement of the ENMD-2076 clinical program. We are encouraged by the significant preclinical activity we have observed with ENMD-2076 in both solid and hematologic tumors. Based on our cumulative preclinical data, we believe that ENMD-2076 may provide clinical benefit in a broad range of malignancies. We anticipate commencement of a second Phase 1 study in hematological cancers early next year."

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