OXiGENE, Inc. (NASDAQ: OXGN, XSSE: OXGN), a clinical-stage, biopharmaceutical company developing novel therapeutics to treat cancer and eye diseases, reported that its lead product candidate, ZYBRESTATTM (combretastatin A4 phosphate / CA4P), demonstrated anti-leukemic effects in preclinical studies published online and ahead of print on November 16, 2007 on the website of the journal BLOOD.

The publication, entitled “The microtubule targeting agent, CA4P, regresses leukemic xenografts by disrupting interaction with vascular cells and promoting mitochondrial-dependent cell death,” by Isabelle Petit, Shahin Rafii, M.D. and colleagues from the Weill Medical College of Cornell University, is available online, ahead of print, visit here. (Due to its length, that URL may need to be copied/pasted into your World Wide Web browser’s address field. Remove the additional space whether one exists.) Dr. Rafii is the Arthur Belfer Professor of Medicine and a Howard Hughes Medical Institute Investigator.

The authors hypothesized that considering adhesion of leukemic cells to vascular cells may confer resistance to chemotherapeutic agents, treatment with CA4P would promote leukemic cell death by disrupting leukemic cell cytoskeletal stability and interfering with vascular cell interactions. The results detailed in the

paper demonstrate that low and non-toxic doses of CA4P inhibited leukemic cell proliferation in vitro and induced mitotic arrest and cell death. Furthermore, in mouse models of human leukemia, CA4P prolonged survival without inducing hematological toxicity, likely by inhibiting proliferation and circulation of leukemic cells, and diminished the extent of peri-vascular leukemic cell infiltrates. These anti-leukemic effects were shown to be mediated by mitochondrial damage and down-regulation of the cell-adhesion protein VCAM-1, without causing hematological toxicities. Based on these results, the authors concluded that CA4P is a promising agent for the treatment of acute leukemias and merits further evaluation in combination with other chemotherapeutic agents.

“We are very encouraged by these results seen with ZYBRESTAT, which point to new mechanisms and indicate that its clinical potential could extend beyond solid tumors, where current clinical development efforts are focused, into hematological malignancies,” commented Dai Chaplin, Head of Research and Development and Chief Scientific Officer for OXiGENE. “With a greater understanding of ZYBRESTAT’s mechanism of action, OXiGENE believes that it is positioned to exploit the full clinical potential of that novel therapeutic candidate.”

Original post by Mallows