By Mary Welch

"It's actually pretty simple," said Alan Russell, president and CEO of AvMax Inc. "Our purpose is to get better absorption of a drug into the body's blood system."

While there are several drug companies working toward similar goals, AvMax (short for maximum availability) has developed technology that overcomes two key biological barriers in the gastrointestinal tract that are responsible for decreasing the effectiveness of many oral drugs.

Based in South San Francisco, AvMax's goal is to use naturally occurring substances to improve a drug's bioavailabilty by specifically interacting with intestinal metabolism and transport. It intends not only to increase the oral drug's absorption, but also to convert some drugs that currently can't be taken orally to that delivery method. Most anticancer drugs, for instance, are administered only by injection, and AvMax is working on changing that situation. Its lead proprietary product, currently in preclinical development, is an oral version of Taxol (paclitaxel), the leading anticancer therapy, which is marketed by New York-based Bristol-Myers Squibb Co.

The company's approach is based on the discovery that intestinal metabolism and active efflux of absorbed drugs are critical determinants of oral bioavailability and variability of systemic drug levels. The company uses substances that are deemed "generally recognized as safe," or GRAS, by the FDA, including essential oils and flavoring agents such as peppermint oil. These substances can be incorporated into drug formulations with minimal additional toxicological testing.

The private company's founder, Leslie Benet, while working at the University of California in San Francisco, discovered that the absorption of many drugs from the gut is actively prevented by the gastrointestinal proteins, P-glycoprotein (P-gp) and cytochrome P450 3A. AvMax then discovered a number of commonly ingested agents, or bioenhancers, which can selectively inhibit these two molecular mechanisms that limit the absorption of some drugs from the gastrointestinal tract into the bloodstream.

"There are two barriers in the body - defense mechanisms, really - that prevent the body from absorbing different chemicals," Russell said. "They recognize them as foreign substances and make it difficult for a drug to be absorbed. P450 breaks the drug down in the intestine and P-gp ships the drug back out to the intestines. Our technology utilizes inhibitors that allow the drug to be better absorbed, thus achieving a better and more consistent bioavailability."

Some of the company's inhibitors act on both P-gp and P450, while others inhibit only one of these proteins.

Last year, AvMax and Elan Corp. plc, of Dublin, Ireland, formed a joint venture, Avlan Pharmaceuticals, for the development and commercialization of therapeutic products using the proprietary oral drug delivery technology of both companies. AvMax owns 80.1 percent of the new company. As part of the deal, Elan made a $5 million equity investment in AvMax and will advance AvMax up to $4 million over the next two years for research funding and development expenses The joint venture currently is conducting a clinical trial in the UK for one drug, and AvMax expects another to enter trials in the UK at the end of next month.

"The development trials for these improved products will be about a one-year time frame," Russell said. "That is one of the advantages of working with GRAS inhibitors. We are developing a way that allows for better bioabsorption, which means you might be able to use a lower dose. That's why the time frame is very reasonable for development.

Benet founded AvMax in 1993 and the next year it received $500,000 in seed financing from Partech International, of San Francisco, and Szoka Capital Management. In late 1997, it received a $2.5 million investment by several institutional investors including Biotechnology Value Fund LP, of San Francisco; Four Partners LP, of New York; and Charter Ventures LP, of Palo Alto, Calif.

"Dr. Benet is a consultant for many of the pharmaceutical companies, and after he founded the company he would talk about his work and the technology with these companies," Russell said. "During 1995 to 1996, AvMax conducted several feasibility projects for these pharmaceutical companies' problem drugs. It gave AvMax experience working with a variety of drugs and allowed the technology to evolve. It was sort of a test drive for the technology that was very valuable. It also helped bring in the investors for the first round of venture capital."

The company will be seeking additional financing this year and expects to close on it in the second half. "Of course the market varies from month to month," he said. "But we have a good story, strong patent position and two trials under way or about to start. We feel very confident. What we want, long term, is to use this technology to develop new medications with pharmaceutical companies. Too often, a lead compound that has shown low or erratic bioavailability has been abandoned. We want to use our inhibitors on those compounds with the pharmaceutical companies."

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