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Strategies & Market Trends : Anthony @ Equity Investigations, Dear Anthony, -- Ignore unavailable to you. Want to Upgrade?

To: Mama Bear who wrote (10672)	2/11/1999 2:26:00 PM
From: Ritz	Respond to of 122087

Mama Bear: Sorry...FWIW here's the story from the Boston Globe: Folkman cancer tests get key US validation By Richard Saltus, Globe Staff, 02/11/99 fter several setbacks in efforts to duplicate dramatic tumor-shrinking experiments with anti-cancer drugs discovered by a Boston researcher, Dr. Judah Folkman, government scientists who journeyed to his laboratory say they have been able to reproduce his results. The mouse experiments by scientists from the National Cancer Institute mean that a countdown is underway toward the first human trials of the drug endostatin, Dr. Robert Wittes, deputy director of the institute, said yesterday. The researchers came to Boston's Children's Hospital to master the technical difficulties of working with the drug after they failed last fall in their first attempts to reproduce his stunning 1997 results in tumor-ridden mice. Wittes said he could not predict when human tests of the drug would start, but the cancer institute this week sent out notices to medical centers around the country inviting proposals for Phase I trials, the small initial human tests designed to find out if a drug is safe. The word was released a day after Bristol-Myers Squibb, the pharmaceutical giant, announced that it was pulling out of a partnership designed to develop angiostatin, a related anti-cancer drug that also came out of Folkman's work to block tumors from developing the blood supply they need to grow. Endostatin and a number of similar drugs called angiogenesis inhibitors have been in the spotlight. Folkman's lab showed in animal tests that they could shrink large tumors into a dormant state, with few apparent side effects. A subtle technique When the NCI scientists said last fall that they could not match Folkman's achievement using a small quantity of the drug sent from his laboratory, Folkman said it was not surprising because the drug is so sensitive to handling, storage and the way it's administered. The NCI then sent researchers to Folkman's lab in November and December to learn first-hand the subtleties of working with endostatin. Yesterday, Wittes, the National Cancer Institute's director for extramural research, said the researchers, working with endostatin made by Folkman's scientists and performing the experiments in Folkman's lab, had achieved the same shrinkage of mouse tumors. ''This substantiates the idea that these are technical issues'' that caused the initial failures of the drug to work at the institute, Wittes said. ''Now we will move to facilities in Frederick and try to reproduce the results down here.'' Endostatin is the most powerful to date of a number of angiogenesis inhibitors discovered in the laboratory headed by Folkman, who has pursued for 30 years the notion that the body produces substances that can combat tumors by cutting off their life-support system of tiny blood vessels. Used together in experiments at Children's Hospital, endostatin and the similar but less-potent angiostatin have been able to shrink tumors until they all but vanished. Children's Hospital licensed both drugs to EntreMed, a small Maryland biotech company, for further development into commercial products. EntreMed in turn sublicensed angiostatin to Bristol-Myers Squibb, while EntreMed and the National Cancer Institute concentrated on endostatin. However, the future of angiostatin was clouded by Bristol-Myers' announcement Tuesday that it was abandoning the time-consuming and costly project because it hadn't yielded a consistently effective drug. Angiostatin, in chemical terms, is an extremely large protein molecule that is difficult to synthesize. ''Array of challenges'' ''This molecule is very complex and presents an array of challenges,'' said Peggy Ballman, a Bristol-Myers spokeswoman. ''Some batches would be active at a certain level and some would not. We didn't have the information we needed to advance it'' into a stage ready for human trials. The Bristol-Myers decision means that EntreMed is now free to develop angiostatin on its own, though analysts doubted whether the company, whose stock dropped 47 percent yesterday to 12 7/8 on the news, had the resources. ''The fact that Bristol pulled out makes it that much more difficult to develop'' both angiostatin and endostatin at the same time, said Dr. Eric Ende, an analyst at Lehman Brothers in New York. EntreMed officials did not immediately return phone calls. Optimistic view Despite the setback for angiostatin, scientists working with angiogenesis inhibitors remained upbeat on the future of the drugs. Dr. Vikas P. Sukhatme, of Beth Israel Deaconess Medical Center, said it was not suprising that angiostatin was proving difficult to make. He said he and his colleagues are concentrating on endostatin, which seems to be more powerful. They reported last month that endostatin halted the growth of kidney tumors in mice, and in high doses even caused some of those tumors to shrink, further confirmation that Folkman's results were not a fluke. ''I'm very optimistic,'' Sukhatme said. ''I think in the next six months to a year we'll learn what pathways in cells these drugs affect, and we can start thinking of how to rationally combine them'' as cancer treatments. This story ran on page A01 of the Boston Globe on 02/11/99. © Copyright 1999 Globe Newspaper Company. -Ritz