Jane Hollingsworth could have remained a commercial litigator at a large Philadelphia law firm, and Terri Sebree could have stayed on the corporate ladder at a big pharmaceutical company in Chicago.

But they chucked those jobs more than a decade ago to help run, and shape, start-up life-sciences companies in the Philadelphia area. They are now on their third small company, NuPathe Inc., a specialty pharmaceutical firm they founded in 2005.

They are unusual: They are serial entrepreneurs.

"In our business, venture capital, it's all about the management team," said James Datin, Safeguard Scientifics Inc.'s executive vice president of life sciences and an investor in NuPathe. "You want people who have been there, done it before, who can build a great team around them. And if times get tough, you know how they are going to operate. Jane and Terri exhibit that to a T."

NuPathe is developing treatments and technologies for neurologic and psychiatric disorders. The Conshohocken company has raised about $20 million from investors, and is poised to begin late-stage clinical testing next year of its first product, a "smart relief" patch to deliver the migraine drug sumatriptan through the skin to headache sufferers.

The firm also has licensed a drug-delivery technology from the University of Pennsylvania as a potential treatment for Parkinson's disease.

Hollingsworth and Sebree credit their entrepreneurial bent and willingness to take risks to the example set by another woman and former colleague, Gerri Henwood. In 1985, she started IBAH Inc., a contract research organization, in her Bala Cynwyd home. It eventually expanded to more than 1,000 employees and offices in 19 countries.

"Gerri was a role model, a teacher. She showed you how to do it," said Sebree, a biochemist whose first job was in drug development at Servier Pharmaceuticals in her native Texas. She later worked at Abbott Laboratories in Chicago, where she developed drugs for psychotic disorders, epilepsy and depression. She met Henwood because Abbott was a client of IBAH.

"I found her very dynamic," said Sebree, who in 1996 opened a Chicago office for IBAH and a year later came to Philadelphia to head IBAH's U.S. operations.

Hollingsworth, who grew up in Ardmore and whose father was general counsel at the former SmithKline Beckman, spent seven years as a commercial litigator at Montgomery, McCracken, Walker & Rhoads.

"I decided I really wasn't going to be excited enough doing commercial litigation the rest of my life," she recalled. "I always had a business interest."

She searched for jobs as a corporate general counsel, and joined IBAH in 1994 in that role. Four years later, when the Blue Bell firm was bought by Omnicare Inc. for $169 million in stock, Hollingsworth and Henwood started Auxilium Pharmaceuticals. Their first employee was Sebree as head of research and development.

After Auxilium went public in 2004, Hollingsworth and Sebree left to form a new company.

"We really wanted to do a central-nervous-system specialty pharma company - neurology and psychiatry," said Hollingsworth, 49. "There's a lot of unmet need for patients, especially on the psychiatry side," said Sebree, also 49.

"Instead of finding the product, and then trying to figure out where it would work, we wanted to do it differently, take a different path."

Hence, the company's name - NuPathe.

Migraine was a therapeutic area in need of new treatments, they said. Migraine sufferers often experience nausea and vomiting, so ingesting a pill isn't always ideal.

"Our goal was to find a way to deliver the drug with a patch," Hollingsworth said.

By scouring the Internet, reading publications, attending scientific meetings, and talking to people, they found a patch technology that uses low-level electrical current to drive the medicine through the skin fast.

NuPathe is testing the technology on patients, using a GlaxoSmithKline drug, Imitrex, which will become available as a generic in a year or so.

"Our goal was to make this work in a single-use patch that you carry around with you," Hollingsworth said. "You get the migraine, take the patch out of the pack, put it on, and that's it. Then we'll have a product." The patch releases the medicine over five hours.

NuPathe, with 14 employees, has licensed another drug-delivery technology from Penn developed by psychiatry professor Steven Siegel and colleagues. Now in preclinical testing, it is a small polymer, no bigger than a grain of rice, that is injected just below the skin and slowly releases medicine over one to three months. The advantage is that patients don't have to take a daily pill or injection.

NuPathe is using that technology with an existing Parkinson's disease drug, but the technology could be used to treat other diseases.

"Right now, the treatments for Parkinson's are three times a day, or once a day," Hollingsworth said. "If we can find a way to deliver this, and maintain the constancy of the medicine over a longer period, it could be a real advancement."

NuPathe also wants to develop a product - either an actual drug or a technology - to treat schizophrenia.

Hollingsworth and Sebree invested their own money - less than $1 million - to start NuPathe. They didn't take salaries for the first year.

"Working in this kind of environment is fun because you can accomplish so much," Hollingsworth said. "Yes, you take risks. But you can have fun in what you do and really make a difference, not only to a patient - if you get a drug on the market - but to employees. And you build a business to a region."

Hollingworth, as chief executive officer, and Sebree, as president, are a rare breed. Women hold only 17 percent of senior management positions at life-sciences companies, and the numbers have not changed in the last five years, according to the Healthcare Businesswomen's Association.

Among the 56 biggest pharmaceutical and biotechnology companies, none is headed by a female CEO.

"In large industry in general in this country, you don't see women CEOs," said Brenda Gavin, managing partner at QuakerBio Ventures, a Philadelphia firm that has invested in NuPathe. "Why do women become entrepreneurs? Because it's hard to move up the ladder in the big company.

"You tend to see women CEOs more in smaller life-sciences and biotech companies," Gavin said. "They are usually willing to take the risk, go out on the ledge, and raise the money."

Contact staff writer Linda Loyd

at 215-854-2831 or lloyd@phillynews.com.