EntreMed’s combination therapy found effective against leukemia

The preclinical results demonstrated that ENMD-1198, administered as a single agent, is effective in significantly delaying the growth of leukemia xenografts in vivo. Combination studies with ENMD-1198 and vincristine, another microtubule targeting agent commonly used in the treatment of leukemias, demonstrated synergistic effects on leukemia cells in vitro and tolerability of doses that prolonged survival in leukemia xenograft models.

ENMD-1198, a new chemical entity derived from 2-methoxyestradiol (2ME2) was designed to decrease metabolism while retaining 2ME2’s multiple mechanisms of action, including inducing apoptosis, disrupting microtubules, and inhibiting HIF-1alpha. In prior preclinical studies, ENMD-1198, an orally active antimitotic agent, led to arrest of cell division and apoptosis in tumor cells. ENMD-1198 also exerts antiangiogenic activity that further contributes to its overall antitumor effects.

Mark Bray, vice president of research at EntreMed, said: “ENMD-1198 is currently being evaluated in a Phase I study in refractory solid tumor patients and we anticipate commencement of Phase II clinical studies in 2008.”