Reviving the Dead

Back in 2000, my company, Gene Logic, had begun to develop a database of human surgical tissue samples analyzed with Affymetrix expression microarrays. We sold these data to major pharmaceutical companies that used it to identify and prioritize new drug targets. At that time, the excitement around genomics was in full swing. We were very enthusiastic about how this knowledge of disease could be used for new pharmaceutical and diagnostics applications.

One of the seemingly wilder ideas was using the data to identify new "unanticipated uses" for drugs that were already marketed. After all, the vast majority of our data was from tissue from surgery patients on some form of medication. For example, we had cardiovascular tissue from patients on anti-depressants and neural tissue from patients on medications that lowered cholesterol. We wondered what this deep knowledge of molecular pathways and the effects of drugs might yield. After our first several builds of the database, we started seeing what we thought might be drugs that had potentially important effects on disease processes outside the areas the drugs were being marketed for. OK, but now what?

We quickly realized that while these were interesting observations, that's probably all they were. Sure, we could take these observations to the marketer of the drug, but then what? Our management team got together and discussed the idea, and we realized we would need significantly more technology to validate these observations, and that meant tens of millions of dollars and years of development. The idea was put on hold. Better stick to the growing business of selling genomic data to large pharmaceutical companies? and that's what we did.

Then, in late 2004 I had a chance meeting with Lou Tartaglia. Lou was at Millennium Pharmaceuticals and had been there for 11 years. His background included the landmark discovery of the leptin gene involved in metabolism and he had run the company's metabolic drug discovery efforts. But now he was on to something new: taking Millennium's sophisticated drug discovery technologies and aiming them at learning more about the biology that drugs might affect. Lou described how he was thinking of applying these technologies to "reposition" failed drug candidates, and in my mind a real strategy started to click. We could couple Gene Logic's extensive human biology databases with the breadth of Millennium's technology platform to both revive dead drugs and look for new indications for drugs already on the market. (see U. Sankar, "Repositioning Companies Find Ways to Make Compounds a Commercial Success," The Scientist, 19(19):42, 2005.) The timing was right: Millennium was shifting its focus to late-stage clinical compounds, and Lou was tasked with finding a new home for the company's drug discovery technologies. By June 2005, we purchased the technology and Lou and his small team joined Gene Logic to start our new drug repositioning effort in Boston.

The business proposition we wanted to take to potential pharmaceutical partners seemed compelling: we would help them find new disease indications for late-stage drugs to help fill their pipeline. And because the stalled drugs we targeted had been sidelined at the phase II stage or later, they could potentially be returned directly into new phase II trials. If successful, we would receive meaningful milestone and royalty payments. And there seemed plenty of molecules to work on. We estimated that since 1990 there were approximately 2,000 drugs that had been discontinued in late-stage development. Now we had to sell partners on the idea. We eventually had proof-of-concept from several early projects that we could use in our pitch. By late 2005, we signed our first major deals with Pfizer and Roche to work on their discontinued drugs. Earlier this year we signed a third deal with Organon. We are underway with our assessment and if our early data holds true, a previously dead drug could be on its way to market. Stay tuned.

Mark Gessler is CEO of Gaithersburg, Md.,-based Gene Logic.