OXiGENE's Zybrestat Reported to Have Anti-Leukemic Effects in Preclinical Studies Published in 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, at http://bloodjournal.hematologylibrary.org/cgi/content/abstract/ blood-2007-05-089219v1. (Due to its length, this URL may need to be copied/pasted into your Internet browser's address field. Remove the extra space if one exists.) Dr. Rafii is the Arthur Belfer Professor of Medicine and a Howard Hughes Medical Institute Investigator.
The authors hypothesized that because 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 this novel therapeutic candidate."
About ZYBRESTAT (combretastatin A4 phosphate / CA4P)
ZYBRESTAT(TM) is currently being evaluated in a pivotal registration study in anaplastic thyroid cancer (ATC) under a Special Protocol Assessment agreement with the U.S. Food and Drug Administration (FDA). OXiGENE believes that ZYBRESTAT is poised to become the first therapeutic product in a novel class of small-molecule drug candidates called vascular disrupting agents (VDAs). Through interaction with vascular endothelial cell cytoskeletal proteins, ZYBRESTAT selectively targets and collapses tumor vasculature, thereby depriving the tumor of oxygen and causing death of tumor cells. In clinical studies, ZYBRESTAT has demonstrated potent and selective activity against tumor vasculature, as well as clinical activity against ATC and other solid tumors.
OXiGENE is a clinical-stage biopharmaceutical company developing novel therapeutics to treat cancer and eye diseases. The company's major focus is developing vascular disrupting agents (VDAs) that selectively disrupt abnormal blood vessels associated with solid tumor progression and visual impairment. OXiGENE is dedicated to leveraging its intellectual property and therapeutic development expertise to bring life-extending and -enhancing medicines to patients.
Safe Harbor Statement
This news release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Any or all of the forward-looking statements in this press release may turn out to be wrong. Forward-looking statements can be affected by inaccurate assumptions OXiGENE might make or by known or unknown risks and uncertainties. Additional information concerning factors that could cause actual results to materially differ from those in the forward-looking statements is contained in OXiGENE's reports to the Securities and Exchange Commission, including OXiGENE's Form 10-K, 10-Q and 8-K reports. However, OXiGENE undertakes no obligation to publicly update forward-looking statements, whether because of new information, future events or otherwise. Please refer to our Annual Report on Form 10-K for the fiscal year ended December 31, 2006.
Shari Annes, 650-888-0902
Posted: November 2007