By Mary Welch

Oxigene Inc. signed a deal worth up to $70 million with Bristol-Myers Squibb Co. (BMS) to develop and commercialize combretastatin anti-tumor vascular targeting agents.

¿This is a tremendously significant event, not only for Oxigene and BMS, but for cancer research in general,¿ said Akhtar Samad, a senior biotechnology analyst with Oscar Gruss & Son Inc., of New York. ¿There are maybe 15 to 20 companies working on anti-angiogenesis drugs, an area that is becoming increasingly controversial, and this is the first significant deal on a financial level between a major cancer pharmaceutical company and a biotechnology company ¿ and a virtual biotechnology company at that.¿

¿This is the biggest ¿ the major deal ¿ for Oxigene,¿ said Bjorn Nordenvall, president and CEO of the Stockholm, Sweden-based company. ¿It¿s a real milestone for us. What is particularly exciting is that Bristol-Myers Squibb, the world¿s leader in cancer, believes in our work. We believe these compounds have huge potential and, obviously, so does BMS.¿

Oxigene will receive $10 million up-front, as well as development milestones and research funding that could reach up to $60 million. In addition, Oxigene will receive royalties from any systemic drugs resulting from the collaboration.

¿It¿s a very lucrative deal for a product that¿s in Phase I/II,¿ Samad said. ¿It is a real validation of combretastatin as an anti-tumor vascular targeting platform. It¿s also important to know that Bristol validated Oxigene¿s claims for combretastatin in their own labs.¿

New York-based BMS receives worldwide rights to develop compounds, including the lead compound, combretastatin A4 Prodrug (CA4P), in this new class of anticancer therapies.

¿BMS has the rights to all systemic uses, and we retained the rights to combretastatin for non-systemic uses,¿ Nordenvall said. ¿We are a research and development company and we will be investigating combretastatin for non-systemic uses. We again believe there is great potential here.¿

BMS now will take full responsibility for developing combretastatin compounds, including CA4P, with the exception of the three ongoing Phase I/II trials of CA4P. ¿They will be in the driver¿s seat, and we¿ll be in the back,¿ Nordenvall said.

Combretastatin compounds, including CA4P, may selectively target existing blood vessels at tumor sites, which cut off the tumor¿s blood supply and deprive it of oxygen and other necessary nutrients. CA4P is being developed for potential use either as a stand-alone therapy for solid tumors that require blood vessels for survival, or in combination with chemotherapy and radiation to enhance the effectiveness of the treatment.

Oxigene will continue to fund and run those trials, two of which are taking place in the U.S., the other in the UK. All three trials are being conducted with the Cancer Research Campaign, of London.

Data recently presented showed that CA4P has the ability to reduce blood flow to the tumor as measured by magnetic resonance imaging.

¿In preclinical models, a single dose of CA4P could destroy up to 95 percent of solid tumor cells,¿ Nordenvall said. ¿Our Phase I/II studies are the first demonstrations in human clinical trials of an inhibitor that blocks the flow of blood within tumor-associated blood vessels. I think BMS was interested in us because we could show that CA4P can significantly decrease blood flow to tumors.¿

The current Phase I/II trials should be completed early in the first quarter of 2000, with final data released in May 2000 at the annual meeting of the American Society of Clinical Oncology. Samad, a former cancer research physician, believes BMS will start between four to six Phase II trials in advanced solid tumor cancer in the third quarter of next year.

¿They have to move rapidly,¿ he said. ¿What is the distinguishing feature of combretastatin from the basket of other anti-inhibitors is that combretastatin inhibits the flow of pre-existing blood vessels, where the others inhibit the blood flow of new vessels, and that is critical.¿

Oxigene¿s stock (NASDAQ:OXGN) closed Thursday at $17.625, down 50 cents.