By Virginia Baldwin Gilbert
Of the Post-Dispatch

January 9, 2001

Getting a new drug to market is difficult and expensive for any company. For a startup, turning promising research into a safe, effective drug is doubly difficult and expensive. Doing so outside the research and money centers of San Francisco Bay or Cambridge, Mass., can be nigh impossible.

Meet St. Louis' latest entry into Mission Impossible: MetaPhore Pharmaceuticals Inc. of Overland.

The privately held company is finishing the final paperwork for seeking approval to begin clinical trials for a new class of drugs. The first trials are planned for a drug that would increase the effectiveness and decrease the side effects of an anti-cancer drug already in use.

This means MetaPhore is hoping to begin its mission -- sort of at the stage of hearing, "your mission, should you choose to accept."

But the company has come a long way already.

The story begins with free radicals, compounds produced when our bodies use oxygen to create energy. If the term conjures up long-haired extremists bent on destruction, that wouldn't be far from the truth. Free radicals are the body's terrorists, causing inflammation and cell death. Free radicals, or oxidants, have been linked to autoimmune diseases such as Parkinson's disease, rheumatoid arthritis and several types of cancer, as well as to the effects of ordinary aging.

The body produces its own counterterrorists -- enzymes called superoxide dismutases. For years, medical researchers have tried unsuccessfully to devise a way to use natural enzymes to treat disease.

The scientists now working at MetaPhore took a different route -- they're developing synthetic superoxide dismutases that mimic the anti-oxidant qualities of the natural enzymes without many of the problems.

The research was one of several "exciting projects" that Denis Forster supervised as director of chemical sciences at Monsanto Co. in the 1990s.

In early 1998, Monsanto hired Garland Marshall to evaluate the superoxide dismutase project. Marshall is a Washington University medical school professor who heads the university's Center for Molecular Design.

Marshall was very enthusiastic. "I found (the project) both scientifically and commercially one of the most exciting opportunities I've seen in more than 30 years in consulting for the pharmaceutical industry," he said recently.

Despite Marshall's recommendation, Monsanto decided to put its money and efforts into a new drug called Celebrex. Few could question the choice financially. As a treatment for arthritis, Celebrex became the most successful new-product launch the pharmaceutical industry ever saw.

The drug, first available in January 1999, generated more than $1.4 billion in sales its first year.

Company executives suggested to Marshall if he were that high on the enzyme research, Monsanto would be willing to talk about licensing its technology. But he would have to find backers.

Marshall has a successful track record with venture capitalists. "I have the scars to prove it," he says.

Marshall started Tripos Associates in 1979 with "seed money" of $800. He sold the company, which designs, produces and maintains software for research, in 1987 for $6.7 million.

When he sold Tripos, Marshall said he would never start another compan y. "It gets in the way of doing science," he explained.

Despite that, Marshall started MetaPhore in 1995, to fund new medical research focusing on metals.

"For something totally new, it's a problem getting the initial funding" from government or traditional academic sources, Marshall said. "I had found a long time ago, that sometimes it's easier to start a company and get funding that way."

While Marshall was trying to get investors interested in superoxide dismutases, he got a call from Forster, who wanted to help. Forster had some potential backers - fellow squash players at the Racquet Club.

"That's how I got to know Denis well, playing squash," said Don C. Musick III, president of Don C. Musick Construction Co., and now on the board of directors of MetaPhore.

"Over the years, we've talked about various investments, everything from real estate to other potential life-science investments, various manufacturing companies," Musick said.

The enzyme project went beyond after-game chit-chat. Forster introduced Musick and some others to Marshall.

"All the money managers I know, the really good ones anyway, told me the dot-coms were way over-valued," Musick said. "While there was a train to be ridden, the train was not going to see the final desitnation on many of those companies.

"What we're looking at here will make the whole destination. That was the difference for me. This investment will yield benefits financially and for the betterment of life."

Forster joined MetaPhore as a senior vice president. Eventually several others made the switch, including Dennis P. Riley and Daniela Salvemini, who both had done some of the groundbreaking research on superoxide dismutases.

Last year Monsanto merged with Pharmacia Corp., which kept Monsanto's pharmaceutical business and spun off the agricultural business into a "new" Monsanto. Pharmacia retains royalty rights for any products from the superoxide dismutase research.

Investors have put about $20 million into MetaPhore so far, Forster said. If the company gets a compound through Phase 3 trials - an arduous journey expected to be completed in early 2003 if all goes well - their investment could increase many times over.


MetaPhore Pharmaceuticals Inc.

* Headquarters: Overland.

* Founded: 1995, by Garland Marshall, director of Washington University's Center for Molecular Design.

* Employees: 123 and hiring.

* Business: Medical research involving metals and their role in disease and disease treatments.

* The name: Coined from metal and ionophore, a chemical carrier of metals that allows a metal to be moved across a membrane.