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Originally published October 7, 2008 at 12:00 AM | Page modified October 7, 2008 at 11:04 AM

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Drug firms open vaults in search for TB treatment

In an unusual step, two major pharmaceuticals are allowing a Seattle lab to delve into their "molecular libraries" to find a new treatment for tuberculosis.

Seattle Times science reporter

Pharmaceutical companies aren't known for sharing trade secrets, but two of the world's biggest drugmakers have opened their vaults to a Seattle lab searching for new ways to treat tuberculosis.

Scientists at the Infectious Disease Research Initiative (IDRI) are just beginning to sort through more than 500,000 compounds in "molecular libraries" compiled by Eli Lilly and Merck.

Such libraries, which detail the structure and chemistry of potential drug components, are among pharmaceutical firms' most valuable and closely held assets, said Dr. Gail Cassell, Lilly's vice president of scientific affairs. "You might say it's like opening our heart and soul."

But the need for new TB treatments is so urgent, the drug companies were persuaded — after considerable hand-wringing — to put competitiveness aside.

"We don't want to leave any stone unturned," said Cassell, who was in Seattle Monday for a daylong symposium on TB drugs development sponsored, in part, by Lilly.

Worldwide, up to 2 billion people are infected with tuberculosis. About 1.5 million die every year from the disease, which can spread from a cough. Strains resistant to most existing drugs have turned up in nearly 50 countries, including the United States.

Latent infections

Up to 100,000 people in King County have latent TB infections, and the health department reported 161 active cases last year, the highest level since the mid-1950s.

Scouring molecular libraries is only one part of the nonprofit Lilly TB Drug Discovery Initiative, launched last year and based at IDRI in Seattle. The program is also casting a wide net for drug leads developed at universities, private labs or government research centers.

That effort has already paid off, with two promising candidates that will be tested and analyzed soon in Seattle. One, derived from a soil microbe by Japanese researchers, has already proved effective against resistant strains of TB in mice. The second candidate, developed in the UK, also appears to kill resistant TB strains but needs more basic study.

"We feel like we have a lot of momentum," Cassell said. "We're hoping that these examples will lead other companies and organizations to collaborate with us."

Lilly will not profit from any drugs developed through the initiative.

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Many health advocates criticize drug companies for their long neglect of diseases that mainly afflict the poor.

But their expertise is needed to remedy the situation, said Dr. Paul Farmer, whose work with HIV- and TB-infected people in Haiti and other parts of the developing world was described in the book "Mountains Beyond Mountains."

"It would be a real mistake if we were skeptical of the industry to the extent we didn't allow them to play the role we need them to play," said Farmer, who serves on the initiative's board of advisers.

TB drugs donated

Farmer helped persuade Lilly to donate TB drugs to poor communities and to allow factories in India and Russia to produce the medicines at lower cost.

"I think a lot of people underestimate how much goodwill there can be in a huge company," he said.

Local sentiment about Lilly was mixed in 2006 when the company paid $2.1 billion for Seattle-based Icos.

Former Icos employees

The biotech had developed a long-lasting impotence drug, Cialis, which joined Prozac as one of Lilly's biggest blockbusters.

But more than 500 Icos employees were being laid off — including a group of scientists with an interesting proposition for the pharmaceutical giant: Donate some of Icos' equipment to tuberculosis research.

The company agreed, handing over about $9 million worth of gear and $6 million in cash for five years of research.

The lab established at IDRI includes several high-speed robots, which can analyze hundreds of compounds simultaneously for anti-TB effects.

"There are only a few places around the country that can actually do that with TB," said Dr. Edward Kesicki, one of the former Icos scientists who now works in IDRI's tuberculosis lab.

That kind of speed and volume is crucial to screening large numbers of compounds.

IDRI also has a special laboratory where scientists can work with live TB bacteria.

The research focuses on the early stages of drug development: Finding out if a chemical has potential, whether it can kill bacteria in a test tube, how it works, and whether chemical tweaks can boost its potency.

Failure rate

The failure rate is high, Cassell warned.

Drug candidates that pass the initial tests will graduate to tests in animals, then people studies that would be done in cooperation with the National Institute of Allergy and Infectious Disease, which is a partner in the project.

The TB Drug Discovery Institute adds to Seattle's growing stature as a center of tuberculosis research and funding.

The Bill & Melinda Gates Foundation has spent nearly $750 million on TB research. Scientists at Seattle Biomedical Research Institute are also chasing new TB drugs.

Microsoft co-founder Paul Allen even got into the act this year, with his first global health grant: $5 million to SBRI for research on the TB bug's biology and vulnerabilities.

Sandi Doughton: 206-464-2491 or sdoughton@seattletimes.com

Copyright © 2008 The Seattle Times Company

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