By Mary Welch

In 1994, when they started Adolor Corp., the founders believed they could develop a number of profitable drugs with related technology, but with differing risks and profits - and could generate satisfying revenues on such products while avoiding direct competition with larger pharmaceutical companies.

"There are not a lot of areas you can do that in," said John Farrar, president and CEO of Malvern, Pa.-based Adolor. "Pain management and anti-infectives are two."

Its business strategy has served the company well. Adolor has several compounds in its pipeline, two in Phase II trials and another just starting Phase I. Adolor, with 33 employees, is focused on next-generation, centrally and peripherally acting non-addictive analgesics for hyperalgesia or inflammatory pain, pruritis (itching), and mild- moderate and moderate-severe pain.

"We decided that we could develop a number of products in the pain management arena, even though we were a small company," Farrar said. "Products could be licensed and marketed for a very small amount of money. You're taking a very high risk if you develop one product and it crashes in Phase III, and product failures are rampant in this industry."

Its lead product is ADL 2-1294, an opiate compound formulated to provide relief of hyperalgesia, which is severe inflammatory pain and pruritis. The dermal formulation is in Phase II trials. Also in Phase II trials is ADL 2-1294, but in a different formulation for an ophthalmic indication. It would be used for inflammatory pain associated with corneal abrasions and surgical procedures.

"ADL 2-1294 has the potential for providing relief without either inhibiting healing or causing the cornea to become numb," Farrar said. "Local administration of low doses of opiates into inflamed, hyperalgesic tissue can result in significantly reduced pain sensitivity without side effects. It's a phenomenon known as peripheral opiate anti-hyperalgesia."

The compound is intended for marketing as both a prescription and over-the-counter topical treatment.

In late 1997, the company signed a licensing deal with Kwang Dong Pharmaceutical Co., of Seoul, South Korea, to develop ADL 2-1294 in that country for dermal pain only. The company retained the rights for itch. To date, it is the only licensing deal the company has signed.

Farrar says that won't be the situation for long. "We are very close to a licensing deal right now for ADL 2-1294," he said.

The drug's active ingredient is loperamide, which is the active ingredient in the over-the-counter anti-diarrhea medication Imodium A-D.

"It's the only non-DEA-scheduled opiate drug in existence, because it has zero addiction potential," Farrar said. "We know it's safe, but it's been completely misunderstood for 20 years. When it was discovered, it was tested for acute pain models and its analgesic potential was misused. But we found that for simple inflammation pain models, it's remarkable."

ADL 10-010 entered Phase I trials this week. The compound stimulates the kappa opiate receptor on sensory nerves on sites of inflammation, and could be used for post-surgical pain and possibly visceral pain.

In Phase II trials is ADL 8-2698, which blocks the mu opiate receptors in the gut to prevent narcotic-induced constipation, a problem often found with cancer patients on long-term narcotic therapy. It may also be useful post-surgically.

"With ADL 8-2698, we have a preliminary demonstration of efficacy," Farrar said.

Adolor was founded from seed financing from Arch Venture Partners, of Chicago; Falcon Technology Partners L.P., of Devon, Pa.; and Weiss, Peck & Greer Venture Partners, of San Francisco. The company has raised about $30 million in three other financing rounds.

"We have about 18 months to two years of money in the bank," Farrar said. "The public market is dead but we'll probably be raising money later this year. Other partnering deals are in the works."

Adolor's main advantage, he said, is that it can lessen risk by developing several products for relatively little cost. The products in clinical trials have a market potential between $80 million to $500 million, but development costs for each compound are between $4 million to $8 million.

"That's a pretty good development cost," Farrar said. "We're not looking for a $1 billion drug like the big pharmaceutical companies. They keep looking for a big market, and complain that the market is fragmented. We have a different point of view."