SOUTH SAN FRANCISCO, Calif., Dec. 7, 2009 (GLOBE NEWSWIRE) -- OXiGENE, Inc. (Nasdaq:OXGN) (Stockholm:OXGN), a clinical-stage, biopharmaceutical company developing novel therapeutics to treat cancer and eye diseases, today announced the presentation of data from preclinical studies carried out by Christopher R. Cogle, M.D., Assistant Professor, Medicine, University of Florida, senior author on the poster. The studies were conducted in mouse xenograft and orthotopic models of acute myelogenous leukemia (AML), and showed that OXi4503, a second-generation, dual-action vascular disrupting agent (VDA), demonstrated a higher level of anti-leukemic activity when administered as a single agent or in combination with bevacizumab, an anti-VEGF antibody, than when bevacizumab was used alone. Notably, results showed that OXi4503 alone and in combination with bevacizumab showed more effectiveness in inducing regression of leukemic cells in bone marrow than bevacizumab alone or placebo. The data were presented on Saturday, December 5th, in a poster at the 2009 American Society of Hematology conference.
"The preclinical data presented by Dr. Cogel at ASH indicate the ability of OXi4503 alone and in combination with bevacizumab to inhibit the microvascular environment which promotes leukemia survival and proliferation in the bone marrow," said Peter Langecker, M.D., Ph.D., OXiGENE's Chief Executive Officer. "Combined with the promising preclinical and early clinical data we have generated with OXi4503 in solid tumors, we believe that this second-generation, dual action VDA is a valuable asset for our company and warrants continued development. OXiGENE's intention is to advance OXi4503 in solid tumors, such as liver cancer, and to explore strategies for optimizing the compound's potential in AML and other forms of leukemia."
OXi4503 Results
The data reported at ASH were presented in a poster, titled "AML Regression by Vascular Disruption with OXi4503 and Anti-Angiogenesis with bevacizumab."
To test the efficacy of OXi4503 in human AML, human leukemia cells were established in mouse xenograft models. Two models were used: a subcutaneous model and an orthotopic model where primary human leukemia cells were established in the bone marrow.
In the subcutaneous model, tumor bearing mice were randomly assigned to one of four treatment groups: control, bevacizumab alone, OXi4503 alone, and combination OXi4503 and bevacizumab. Results showed that treatment with OXi4503 significantly inhibited tumor growth and moreover, when used in combination with bevacizumab, tumor regressions were observed. These changes in tumor growth observed when OXi4503 was administered, either alone or in combination with bevacizumab, were associated with significant reductions in tumor vascularity as measured by microvessel density.
In the orthotopic model, primary human leukemia cells were introduced intravenously into the mice and after six weeks, once tumors had established in the marrow, treatment was initiated. After two weeks of treatment, mice were examined for human leukemia engraftment using flow cytometry and PCR. Leukemic cell burden was significantly decreased by treatment with OXi4503 and eliminated by the combination of OXi4503 with bevacizumab.
In summary, these results indicate that OXi4503 alone or in combination with bevacizumab produces a higher level of antitumor activity than bevacizumab alone. The key conclusions from the study as reported by the investigators were:
-- In the models used in the study, bevacizumab alone does not lead to regression of AML.
-- In the subcutaneous AML tumor model, OXi4503 alone significantly retards tumor growth. Furthermore, combining OXi4503 with bevacizumab leads to tumor regression with no reactive angiogenesis.
-- In the orthotopic model, OXi4503 alone and in combination with bevacizumab regresses AML engraftment in bone marrow, resulting in both phenotypic and molecular remissions.
A copy of the poster is available on OXiGENE's website at www.oxigene.com.
About OXi4503
OXi4503 (combretastatin A1 di-phosphate / CA1P) is a dual-mechanism vascular disrupting agent (VDA) that is being developed in clinical studies for the treatment of solid tumors. Like its structural analog, ZYBRESTAT(TM) (fosbretabulin / CA4P), OXi4503 has been observed to block and destroy tumor vasculature, resulting in extensive tumor cell death and necrosis. In addition, preclinical data indicate that OXi4503 is metabolized by oxidative enzymes (e.g., tyrosinase and peroxidases), which are elevated in many solid tumors and tumor white blood cell infiltrates, to an orthoquinone chemical species that has direct cytotoxic effects on tumor cells. Preclinical studies have shown that OXi4503 has (i) single-agent activity against a range of xenograft tumor models; and (ii) synergistic or additive effects when incorporated in various combination regimens with chemotherapy, molecularly-targeted therapies (including tumor-angiogenesis inhibitors), and radiation therapy. OXi4503 is currently being evaluated as a monotherapy in a Phase 1 dose-escalation study in patients with advanced solid tumors and as a monotherapy in a phase 1b/2a dose-escalation study in patients with solid tumors with hepatic involvement.
About OXiGENE
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 life-enhancing medicines to patients.
The OXiGENE, Inc. logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=4969
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, including, but not limited to, mechanisms of anti-leukemic action of OXi4503, the potential of OXi4503 as a single-agent therapy for certain leukemias and publication of further corroborative OXi4503 preclinical data in AML obtained by OXiGENE's collaborators. 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 reports on Form 10-K, 10-Q and 8-K. 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, 2008.