EntreMed Inc. Chairman John Holaday stepped onto the ballroom dais in San Francisco's fashionable Argent Hotel, his eyes taking in the empty chairs surrounding two of the eight tables, a less-than-flattering newspaper headline of that morning still rankling.
His company had spent weeks planning to make this private luncheon for stock analysts an upbeat affair, one designed to help the Rockville company raise needed cash.
EntreMed had star billing before the 25,000 scientists, analysts and others gathered in the city for the world's largest conference on cancer treatment, and independent scientists had described results from early human tests of its anti-cancer drugs as promising.
But now a different reality confronted Holaday. A front-page USA Today headline had dismissed the type of drugs on which EntreMed was staking its survival as "disappointing," and the price of the company's shares was falling. Another company's drug, Gleevec, had grabbed the spotlight for seemingly miraculous reprieves in once-dying cancer patients.
"We thought it would be a very positive time for EntreMed," Holaday said later. "Based on unwarranted expectations ... our great news was interpreted as failure."
Like other young biopharmaceutical companies with no drugs on the market, EntreMed's struggle to succeed depends in large part on what goes on its laboratories, where scientists race to develop revolutionary drugs that painlessly attack tumors by cutting off their blood supply. But its executives face myriad daily pressures that could also determine its fate.
There can be no science without money to back it, and EntreMed must raise tens of millions a year to keep going. A veteran of moments on the brink, it has less than a year's worth of cash left. So its executives maneuver on multiple fronts.
They try to attract top researchers who can move human testing of its drugs quickly forward, producing results the government will use to decide whether to approve the drugs. They woo large drug companies to help foot the cost of developing EntreMed's products, in exchange for a cut of the profits. They court journalists and Wall Street analysts whose reports could move markets and money to EntreMed's door or harm its ability to attract both.
Small companies "can't just sit back here and think about science," said Richard W. Oliver, a Vanderbilt University management professor who teaches a biotech strategies course on the master's degree level. They are forced to do everything at once, he said, adding, "You don't just go ask someone for money. It's a courtship, and you've got to spend a lot of time doing it."
Four frenetic days
Nowhere was the frenetic pace at which EntreMed must do it all more evident than at last month's meeting of the American Society of Clinical Oncology in San Francisco, where the company marshaled nearly its entire management team.
In a four-day flurry, company executives pressed the case for their drugs and their company over breakfast, lunch, dinner and cocktails, in impromptu hallway conversations, in hotel hospitality suites and trade-show booths, in the backs of cavernous meeting halls and on city sidewalks and cellular phones.
It was unrelenting work, subject as much to fast-moving competition, the whims of investors and the news media's perspective on results as it is to the opinions of top scientists.
"There are times I get pretty frustrated," Holaday said over a meal of eel sushi the day before the Argent luncheon. But he has grown accustomed to the strain. "The magnitude of the problems gets bigger," he said. But the pressure now is "no more than then."
EntreMed was a tiny upstart when Holaday, a scientist turned chief executive officer, boarded a plane in 1993, poised to bet the company's future on a therapeutic approach others had shunned as fringe science.
Boston surgeon Judah Folkman had the idea that cancer could be treated by blocking angiogenesis, the growth of blood vessels that feed tumors. But after two years of looking for a company that would bankroll research, Folkman found that "we had no one interested at all."
Holaday and others from EntreMed impressed Folkman in a hastily arranged hotel-room pitch in Montreal, catching him before Folkman was to leave for Europe to court a large pharmaceutical company. Holaday described the EntreMed-Folkman pairing as "kind of a story of Rodney Dangerfields."
A measure of respect came as EntreMed entered three drugs based on that research - Endostatin, Angiostatin and Panzem - into a dozen clinical trials, as tests in people are known, at noted cancer centers such as Boston's Dana-Farber Cancer Institute.
The company licensed a fourth, the approved leprosy drug thalidomide, to Celgene Corp. for development as a cancer treatment, for which doctors are prescribing it. The drugs are among a new class designed to spare cancer patients toxic and even fatal side effects, leading some to believe they could make the disease manageable.