If cures for cancer are ever found, odds favor Pharmaceutical Alley as where that merciful lightning bolt will strike humanity.
A narrow corridor stretching from Boston to northern New Jersey is the world's Silicon Valley of drug manufacturing. Upwards of 300,000 employees are concentrated here, based at the headquarters of the biggest names in the pharmaceutical industry.
Dominating the landscape are such multinational players as Merck, Pfizer, Bristol-Myers Squibb, Johnson & Johnson, GlaxoSmith-Kline, Eli Lilly, Schering-Plough and Novartis. In the shadow of the giants lie dozens of smaller companies, creating a 260-mile-long cauldron of biochemical research and marketing talent found nowhere else on Earth.
"We just had to start off here," says Lewis Metts, president and CEO of Taxolog, Inc. In 1999, Bob Holton's dreams became a brick-and-mortar reality when the company's doors opened in Fairfield, New Jersey. "If you're going to do pharmaceutical development, you need to be here, period. The recruiting is phenomenal."
Metts oversees Taxolog's day-to-day operations, and it's also his job to keep a bridle on the company's inspiration, his old college chum Holton. He's on the phone with him around sun-up every morning, and in a staff conference call at one o'clock sharp every Monday afternoon. Holton serves as the company's paid chief scientific advisor, whose dollar-a-year salary qualifies him to dream up new molecules for Metts' scientists to try to make. Holton takes his job seriouslymore than 1,000 compounds now sit in Taxolog's freezer, awaiting more testing.
When they graduated from FSU, Holton had decided on a career in academics; Metts chose industry. The pair stayed in touch over the years, and when Holton got the itch to start a company in 1995, he called the only person he trusted in the business world.
"At first I told him he couldn't be serious," Metts said. "I'd been a top level executive for so many years, and to start a company from scratch is just outside my field. I couldn't do it."
Metts, of course, did itafter getting Holton to agree to butt out of the business-end of things. "I told him just because we'd been friends a long time didn't mean we could work together. I said as soon as the business gets going, Bob, you're a technical advisor and your (keister) is out of here. And it's turned out real well."
The technique must have paid off. Last year, Taxolog won its first big contract, a multimillion-dollar licensing agreement with Wyeth Pharmaceutical (formerly American Home Products). Metts said that Taxolog is now on the fast-track to becoming the first pharmaceutical ever to put a product on a market in its first five years in business.
Taxolog's main function is to take 10-DABTaxol's mother moleculechemically alter it to make what are called taxane analogs, and then figure out a way to make them in commercial-sized batches. The company imports the chemical in bulk quantities from the same Italian company that supplies the maker of Taxol, Bristol-Myers Squibb. Wyeth's job is to take Taxolog's most promising compounds and groom them for commercial development.
Chances are that Wyeth's first product will have a fancy new name instead of the number "TL-139" that Taxolog's lead compound now wears. The celebrated molecule is now Wyeth's preeminent candidate as the world's next blockbuster cancer drug. The analog, which Wyeth has renamed MAC-321, was midway through FDA Phase I trials this summer, tests that determine toxicity tolerances in humans. Barring problems, the compound should begin Phase II testingthe stage that establishes how effective a drug is against a targeted diseasenext spring.
Metts' team is optimistic that TL-139 will make it to the marketplace and will make a large impact when it gets there. In every test so far in animals, the drug has trumped the performance of Taxol, its mother drug, and in spectacular fashion, Metts said. Against six different cancers in micebreast, nonsmall lung, colon, prostate, pancreatic and melanomathe drug wiped out every trace of the diseases, and astonishingly, often after only a single dose.
Full Circle: Many of Taxol's most promising derivatives are now tested for biological activity at North Carolina's Piedmont Research Center, only a few miles from where Taxol was discovered by scientists working in Research Triangle Park in 1966.
Testing at Piedmont Research, a bioassay contractor in North Carolina's Research Triangle, also has shown that unlike Taxol and Taxotere, the only other big taxane cancer drug on the market, TL-139 is just as effective when taken orally. The finding poses a blessing to thousands of chemotherapy patients whose only hope now must drip from IV hook-ups confined to a cancer ward.
If things stay on track, the drug "will make Taxol look like it's inactive," Metts predicted. "It's 1,000 times better than Taxol was at this same stage of development. Taxol was just the seed that got this story started."
Although he admits that a lot is riding on TL-139's success, Metts said that even if it proves too toxic in clinical trials, odds are that Taxolog's arsenal of analogs already contains even better molecules, maybe even dozens of them.
"Just in broad terms, we've got nearly 300 compounds that are better than Taxol," he said. "It's inevitable that we're going to put some of those on the market."
This fall, Taxolog's new biological science branch was scheduled to open in Tallahassee. The 23,000-square-foot research center will direct much of the company's bioassay screening work in cell cultures and mice. Also housed in the new facility will be the headquarters of Holton's MDS Research Foundation, and of the SynCure Cancer Research Foundation, a charitable cancer research organization. Both entities are now headed by another long-time Holton friend, Michael Devine, who as associate vice president for FSU in the late 1980s championed Holton's work and helped get his first Taxol patents in place and the semisynthesis process licensed to Bristol.
Sitting in his Fairfield office, Metts smiles when he talks of how he and Holton were once regarded at FSU. The two classmates shared a youthful fondness for mischief, he said, a fact that often led to trouble. Metts was caught red-handed late one night trying to wrestle an obstinate drink machine off the roof of the chemistry building. The stunt came close to getting him kicked out of school.
"We were the bad boys of the department, no question. Anytime something bad happened, it was presumed that it was either me or Bob."
Thirty years down very different roads, the pair is up to something again. This time, they're out to show the world they're the good guys after all.
"Today, we're sitting on the dominant class of oncology drugs in the world," said Metts. "The good Lord willing, we're going to cure some cancer." -F.S.