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| |  Combretastatin A4 Prodrug Shows Reduction In Tumor Blood Flow In Humans BOSTON and STOCKHOLM, SWEDEN -- October 5, 1999 -- The interim results of a Phase I clinical trial show that cancer patients treated with OXiGENE Inc.’s Combretastatin A4 Prodrug (CA4P) had significantly reduced blood flow to their tumors in a dose-dependent manner as measured by nuclear magnetic resonance imaging (MRI). The study is being conducted in collaboration with the British Charity Organization, The Cancer Research Campaign, (The CRC). The results were presented at the Angiogenesis ‘99 conference, in London, by Dr. Gordon Rustin, Director of the Department of Medical Oncology at Mount Vernon Hospital, United Kingdom and a co-investigator on the study. This study is the first demonstration in human clinical trials of an inhibitor that blocks the flow of blood within tumor-associated blood vessels. The timing of the blood-flow shutdown in the patients was very similar to the timing of the shutdown observed in pre-clinical rodent studies of CA4P. These clinical results demonstrate a proof of principle with regard to CA4P’s mode of action. CA4P is an anti-tumor vascular agent. It is one of a new class of anti-cancer therapies that act by attacking a tumor’s blood supply. In vitro experiments have demonstrated CA4P’s ability to change the shape and permeability of endothelial cells, the cells that line all blood vessels, particularly those cells that are in an actively proliferating state not unlike what is observed in tumor vasculature. It is these activities that are thought to constrict tumor-associated vessels thereby inhibiting blood flow to the tumor. CA4P is different from angiogenic inhibitors now in development in that it attacks pre-existent tumor vasculature. This is an activity not seen in anti-angiogenesis inhibitors currently in clinical trials. CA4P is currently in three Phase I clinical trials, one in the UK, and two in the US. "These interim results show that we can administer CA4P to humans safely at doses that cause a significant decrease in blood flow to tumors. In preclinical models, we have seen that CA4P displays similar activities as shown here in human clinical trials, extending to, and confirming its proof of principle in man as well as in animal models," said Bjorn Nordenvall, MD, President and CEO of OXiGENE. Phase I studies are primarily undertaken to evaluate a drug’s safety. Clinical work presented here not only describes CA4P safety data, but due to CA4Ps unique mechanism of action, additionally shows CA4P’s blood flow reduction activity, i.e. proof of principle. This study, which began at the end of 1998, examined CA4P in approximately 17 patients over a dose range of 5 to 88 mg/m(2). Blood flow reduction was seen in all patients evaluated above 52 mg/m(2). Dose escalation is on-going with no toxic side effects observed in patients to date. Of interest, pain at the site of the tumor was observed in patients within two hours of administration at doses of CA4P which clearly induce blood flow reduction. Tumor pain was not observed in patients administered CA4P at levels below that which induces blood flow reduction. Interim results from one of the other two US Phase I studies will be presented by Dr. Scot Remick, Ireland Cancer Center at Case Western Reserve University and University Hospitals of Cleveland, on November 3rd at the Chemotherapy Foundation Symposium in New York.
Related Link: OXiGENE Inc.
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