The first abstract reports for the first time full data from a randomized Phase II trial of Combretastatin A4 Phosphate / CA4P (trademarked by OXiGENE as ZYBRESTAT(TM)) in combination with paclitaxel and carboplatin. In the abstract, lead author Dr. Wallace L. Akerley of the Huntsman Cancer Institute reports that the two dose regimens of CA4P studied, 45 mg/m2 and 63 mg/m2 in combination with paclitaxel and carboplatin, were well tolerated, demonstrated anti-tumor activity and reduced tumor blood flow by 46% and 19%, respectively. Tumor responses were observed and were similar between both dose groups, and the best overall response through cycle 6 was three partial responses (PR) and six stable disease (SD) responses as measured by RECIST criteria. Notably, the two patients with anaplastic thyroid cancer (ATC), the lead indication for ZYBRESTAT, achieved the greatest reductions in tumor blood flow (Ktrans of 73% and 79%). The study enrolled 13 patients with advanced imageable malignancies, and imaging evaluations were carried out using DCE-MRI, a standard imaging modality used to evaluate tumor blood flow and perfusion. DCE-MRI evaluations were performed prior to and 24 hours following the first dose of ZYBRESTAT. Interim data for this study was previously reported in September 2006 at The Tumor Microenvironment 10th International Workshop.
The second abstract reports for the first time initial data from early dosing cohorts in a Phase I study of OXi4503 in patients with advanced solid tumors. Lead author Dr. Danie l M. Patterson of the Mount Vernon Cancer Centre indicates that while the study had not yet reached maximum tolerated dose and recruitment is ongoing, the data to date suggest that OXi4503 is tolerated at doses up to 5 mg/m2 without dose-limiting toxicity. Changes in functional activity, as assessed with DCI-MRI and PET imaging evaluations, were observed in three of the eleven patients studied. OXi4503 is a novel, second-generation vascular disrupting agent with potential intrinsic cytotoxicity exerted through an ortho-quinone metabolite. The drug candidate is being evaluated in this Phase I dose escalation and safety study. Based on results to date, OXiGENE currently anticipates initiating further clinical studies with OXi4503 in 2007.
About Combretastatin A4 Phosphate/CA4P (ZYBRESTAT) and OXi4503
ZYBRESTAT is poised to become the first therapeutic product in a novel class of small-molecule drug candidates called vascular disrupting agents (VDAs). The Company currently anticipates starting a Phase II/III pivotal registration study with ZYBRESTAT in June 2007 under a Special Protocol Assessment agreement with the US Food and Drug Administration. Via 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. ZYBRESTAT has demonstrated potent and selective activity against tumor vasculature, as well as substantial clinical activity against ATC and other solid tumors in clinical studies to date. Our strategy for optimizing the antitumor activity of ZYBRESTAT is to combine it with other types of therapeutic modalities, including cytotoxic drugs, anti-angiogenesis drugs, and radiation therapy. The rationale for combining ZYBRESTAT with other therapeutic modalities stems from the hypothesis that agents with different and potentially complimentary mechanisms of action and with a non-overlapping toxicity profile may achi eve synergistic antitumor activity when administered concurrently. In animal studies, ZYBRESTAT has been shown to enhance the anti-tumor effects of several chemotherapeutic agents, several anti-angiogenic drugs, and radiation.
OXi4503 is a novel, second-generation vascular disrupting agent with potential intrinsic cytotoxicity exerted through an ortho-quinone metabolite. The drug candidate has demonstrated single-agent activity in human tumor xenograft models. Preclinical research with OXi4503 suggests that it not only shuts down tumor blood flow, but can also be metabolized into a compound which could assist with killing the remaining tumor cells at the periphery of the tumor by direct cytotoxic activity against tumor cells. In December 2004, the United Kingdom regulatory authorities accepted an application from our collaborators, Cancer Research UK, to initiate a dose-escalating Phase I clinical trial of OXi4503 in patients with advanced cancer. This trial is currently ongoing. In 2007, OXiGENE plans to initiate several preclinical studies to evaluate OXi4503 and possibly a Phase Ib clinical trial of OXi4503 in combination with an approved anti-angiogenic therapeutic.
About OXiGENE, Inc.
OXiGENE is a clinical-stage biotechnology company developing novel small-molecule therapeutics to treat cancer and eye diseases. The Company's major focus is the clinical advancement of drug candidates that selectively disrupt abnormal blood vessels associated with solid tumor progression and visual impairment. OXiGENE is dedicated to leveraging its intellectual property position and therapeutic development expertise to bring life saving 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 including the initiation of further clinical trials with OXi4503, the effects of combining ZYBRESTAT with other therapeutic modalities, additional mechanisms of action of OXi4503 and the safety and efficacy of our potential product candidates, ZYBRESTAT and OXi4503 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-Q, 8-K and 10-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 for a description of these risks.
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