While MedImmune and Nabi have been profitable companies in the past, and United Therapeutics has been profitable for the past two consecutive quarters, Advancis and Guilford have never posted an annual profit.

Advancis has launched two separate Phase 3 trials - one focusing on adults, and the other on children - involving its new method of delivering the ubiquitous antibiotic amoxicillin. The company's Pulsys technology is designed to deliver the antibiotic in powerful, well-defined bursts maximizing the drug's effectiveness and enabling adults and children to take lower doses.

"These clinical trials are very important for Advancis," said Gregory R. Wade, a senior research analyst who covers the Maryland company for Pacific Growth Equity LLC.

Guilford, a 10-year-old company, has two products on the market: its internally developed Gliadel wafer for certain types of brain cancer and Aggrastat, an injectable treatment for heart-attack patients that it purchased from Merck & Co.

But, like Advancis, Guilford has never turned an annual profit, though it has been around for more than a decade. That has raised the stakes for Guilford's Aquavan anesthesia candidate. The drug is in three sets of late-stage trials for use as a sedative in diagnostic and surgical procedures - a colonoscopy, for instance - that require the patient to be anesthetized for short periods, said William F. Spengler, Guilford's chief financial officer. Another test will start - and all four will finish - this year, the company said.

Because Aquavan is said to have fewer side effects and wear off more quickly than products in use, some analysts have said it could become a $200 million- a-year drug for Guilford if it's approved and brought to market.

Propofol, one of two anesthetic agents Aquavan will challenge in the marketplace, has estimated annual sales of more than $750 million. Midazolam, the other drug used for procedural sedation, has annual sales of more than $300 million, Guilford said.

The company's goal is to introduce Aquavan for sale in early 2007.

The challenge ahead is one reason that Guilford has brought in a new top management team with expertise in bringing drugs to market.

Inside Guilford, "the hope is that there is a rather large market opportunity awaiting us," said Spengler, the financial officer. "For Guilford, this is really a core program, making it [extremely] important as we enter 2005."

Although a substantial number of Maryland's life sciences firms have yet to deliver their first commercially approved product - let alone any sales or profits - the fact that so many firms have reached the last set of testing is promising for the state economy, said Bill Gust, a local venture capitalist.

"This is not at all trivial," said Gust, managing general partner for Anthem Capital Management, a Baltimore-based venture firm with headquarters in Locust Point. "When you consider how long it takes to get through drug discovery, and then Phase 1 and Phase 2 trials, just to get to get into Phase 3, the reality is that the seeds for this [emergence] were planted six, eight or even 10 years ago."