5/5/98 Wash. Post piece mentioning EntreMed / Judah Folkman connection .....................
Tuesday, May 5, 1998
Md. Firm's Stock Soars After Cancer Drug Reports
By Justin Gillis
Washington Post Staff Writer
High-profile publicity this weekend about a promising treatment for cancer at Rockville biotechnology company EntreMed Inc. triggered a speculative frenzy for the company's stock yesterday. Reporters and phone calls besieged the company, its shares more than quadrupled in value, and leading experts weighed in to discourage the notion that a cure is just around the corner.
A glowing report about the prospects for two new anti-cancer agents under development by EntreMed appeared on the front page of Sunday's New York Times. The compounds have so far been tested only in mice, in which they seem to be able to cure many kinds of cancer. However, many experimental treatments that work in mice do not have the desired effect in humans.
EntreMed's executives awoke yesterday to a worldwide media storm. They found themselves walking a tightrope, simultaneously talking up the potential of their research and trying to play down expectations that it will pay off immediately.
"We're concerned because a lot of statements are being made that are very misleading to cancer patients," said Mary Sundeen, a spokeswoman for EntreMed. "These results that have come out in the mice are incredible. But we don't know if these compounds will have any effect whatsoever in human beings."
In a statement prompted by the frenzy, the National Cancer Institute, which is working closely with EntreMed, said it was "encouraged" by animal studies of Angiostatin and Endostatin and had "made it a high priority to move research forward on these compounds." But the cancer institute added: "It is very important to emphasize that while the possibilities raised by these studies in mice are encouraging, it is not known whether Endostatin or Angiostatin will be effective in people with cancer."
In the best case, the compounds in question are not likely to enter human trials for another year or more, and even if the tests go well, it could be several years before they are licensed for use by the public.
EntreMed, which employs about 50 people, is a leader in a field that many scientists believe is among the most promising in cancer research: drugs that would starve tumors to death by blocking the growth of the blood vessels they need to expand.
The same developing body of knowledge may allow doctors to prevent a leading cause of blindness. But in that instance, too, much work remains to be done before drugs go on sale.
EntreMed was founded seven years ago in part to commercialize the work of Judah Folkman, a Harvard University researcher. He and his associates have spent decades studying the importance of blood-vessel formation and other diseases, including macular degeneration, an eye disease that can cause blindness.
But only in recent years have scientists learned enough about the inner workings of cells and developed tools that can begin to manipulate blood-vessel development.
In healthy adults, new blood vessels grow only under rare circumstances – during pregnancy, for instance, or when a wound is healing. But the formation of new vessels seems to be a fundamental element in the progress of several diseases.
Folkman has long theorized that cancers can't grow any bigger than a pea until they trick the body into growing new blood vessels. They do this by making proteins the body recognizes as signals to form the vessels. The vessels grow toward the tumor, supplying it with oxygen and nutrients and allowing it to grow to the point that it threatens the life of the patient.
A worldwide research effort is now focused on finding chemicals that can switch off these signals.
New blood-vessel formation is known to scientists as angiogenesis, and compounds that block it are known as angiogenesis inhibitors. In theory, because an adult who isn't pregnant rarely needs to grow new blood vessels, these compounds should be able to work without the nasty side effects now seen in conventional cancer treatments. In macular degeneration, they might prevent the excessive growth of blood vessels that cloud the eyes.
Some of the most recent, and most exciting, research from Folkman's laboratory is based on the strange fact that tumors themselves, once they are adequately supplied with blood, sometimes produce substances that block blood-vessel formation. In this way, a primary tumor suppresses the formation of secondary tumors that might compete with it for nutrients. As EntreMed chief executive John Holaday said, the first tumor "plays king of the hill."
Folkman's laboratory isolated two proteins, now called Angiostatin and Endostatin, that tumors sometimes produce as angiogenesis inhibitors. Given in combination to mice, the human versions of these proteins seem to be able to cure almost any kind of tumor.
EntreMed is helping to pay for Folkman's research and is working with him to bring the products to market. The company has cloned the genes that instruct cells how to make the proteins, implanted those genes into yeast, and coaxed the yeast into producing large quantities of human Angiostatin and Endostatin.
As animal tests proceed, EntreMed is working frantically to tweak this production process so that adequate quantities of the proteins can be produced for human testing.
But other compounds that block angiogenesis are much farther along in testing than Angiostatin and Endostatin, and these are showing promising results. EntreMed is working in this area, too, along with numerous other companies. EntreMed is trying to develop the drug thalidomide into a treatment for cancer and macular degeneration.
Many people remember thalidomide as a nightmare drug, responsible in the early 1960s for babies with flipper-like arms and other serious defects. Yet it has turned out to be potentially useful in several diseases for many of the very reasons that it caused birth defects. Babies whose mothers took thalidomide apparently developed the deformed limbs because the drug suppressed the formation of blood vessels in their bodies.
EntreMed is in advanced human testing of thalidomide for several types of cancer, including an aggressive brain cancer that is almost always fatal. The company has reported promising results in the scientific literature.
To patients who have cancer now, these findings are of potentially greater importance than the far-off promise of Angiostatin and Endostatin. Thalidomide is already on sale in the United States for other diseases, and nothing stops cancer patients, with a doctor's cooperation, from adding it to their drug regimens.
Stock traders yesterday seemed more interested in the prospect that EntreMed could have a lock on drugs that will prove to be outright cures. After closing Friday at just over $12 a share, the stock caught fire yesterday amid optimistic press reports. EntreMed's shares briefly touched $85, closing the trading day just short of $52. This means the company's value more than quadrupled yesterday, giving it a market capitalization of $641 million.
Holaday, the EntreMed chairman, spent the day racing from one television interview to another. He groped for the right balance between hope and realism. He recalled that his own sister and mother died of cancer, and the best efforts of science could not save them.
"As we've said before, 'cure' is a four-letter word," he said as a black limousine took him toward his latest appointment with the cameras. "It's a long way from mouse to man."
For more information about cancer treatment trials, call 1-800-4-CANCER or visit cancertrials.nci.nih.gov on the World Wide Web.
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