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Gene Logic Division Head Lou Tartaglia s Position on New Lives for Failed Drugs

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At A Glance

Name: Lou Tartaglia

Position: Senior Vice President and General Manager of Drug Repositioning and Selection, Gene Logic, 2004 — present

Background: Vice President of New Ventures and Metabolic Diseases, Millennium Pharmaceuticals 1993 — 2004

Education: PhD in Biochemistry, University of California, Berkeley, 1990

As part of its strategy to acheive "double digit" revenue growth and achieve profitability in 2007, Gene Logic will put as much as $42 million into a new drug repositioning business that aims to use the company's technical strengths to find new uses for failed drug compounds. At the core of this new business is a technology unit the company purchased from Millennium Pharmaceuticals, a transaction made final last July.

Lou Tartaglia was the head of that technology unit at Millennium, and now heads Gene Logic's drug repositioning business, with the goal of using what he has picked up from both companies to try to help bring Gene Logic back from flat revenues.

Can you tell me a little about the technology brought over from Millennium? And can you tell me how it complements what Gene Logic already has?

Sure. During my final year and a half at Millennium, I worked for the CEO, Mark Levin, with the mission of basically pulling together those technologies that would impact productivity within the pharmaceutical industry most.

It was a very nice position, because Millennium was starting to focus more and more of its resources on development of its internal pipeline, and had invested, prior to that, heavily in technologies, but was getting out of the technology solutions business. So it really left at my disposal a large number of technologies that I could essentially cherry-pick from to try to merge them together to try to address what some of us felt — myself and my vice president here at the Cambridge site, Tom Barnes — were some of the most pressing productivity issues within the industry. And that is the high degree of attrition of drugs, of failures, and what could be done about solving the attrition problem and making drugs fail less frequently.

Within Millennium?

No, the idea was that we would spin this out as a separate entity, and the original idea was that it would be an independent entity backed by venture capital that Millennium would have access to, to do partnerships with, and also have certain grab-back rights to a subset of technologies that it had particular interest in. And we actually succeeded in putting a venture syndicate together that was going to finance us with a fairly generous series A financing. But while we were putting this together, we also began discussions with Mark Levin and the senior executives, and began to realize that, as opposed to spinning out as a separate entity, being acquired by Gene Logic would be the smart thing to do.

And it was clearly the smart thing to do in the end, for a number of reasons. One being the fact that some of the technologies that we felt to be quite important in this were going to be quite expensive to develop from scratch, but Gene Logic already had them. Toxicogenomics is a good example, and very sophisticated informatics is another example. So we brought in a very complementary set of technologies that we had pulled in from Millennium and actually incubated as a department within Millennium called Horizon.

During the time that we were being incubated, we were adapting the technologies to being more compound-centric. Previously they had been developed to better understand the function of genes that Millennium had been identifying throughout the years. And we were adapting these technologies to help better define function, utility, and liabilities of chemical matter, or advanced compounds, such as clinical failures within the pharmaceutical industry.

So what sort of technologies were you employing?

There were really five different technologies that we were employing. One was in vivo imaging, which was real-time whole-animal imaging of anesthetized mice, so that you could look at molecular pharmacology throughout an entire animal in a single experiment. This was basically done by combining the state of the art of existing imaging technologies with transgenically engineered mice, to make them more of the optimal diagnostic tool for analysis of compounds, something you obviously can't do with humans. But we could optimize the mice to better meet the imaging hardware.

Another technology is metabolomics, or as we would call it, multi-analyte analytics. We hired a director of a very successful metabolomics program to head this, and Millennium spent quite a number of years in this area and in collaboration with Serion, so we were able to bring quite well-worked-out technologies in this area from Millennium to Gene Logic, as well as bring in an extremely competent director in this area from the outside.

This was mass-spectrometer based, correct? And what else did you have?

Correct. It's LCMS.

Those were two. The other was in vitro technologies, and they were really of two sorts. One was a panel of in vitro surrogate assays of disease. In other words, cell-based assays in tissue-culture systems that would provide readouts that would be predictive of disease utility. So, you would sprinkle your compound across this plate, and when you got a hit, it would be predictive of a certain disease, depending on whether you had cells that were prone to osteoporosis or diabetes, or cardiovascular disease, or so on.

Another set of in vitro assays that Millennium had developed, and spent quite a bit of time on to better understand the function of the genes it identified, was more of a cell-based pathway readout. And these were a system to identify cell-signaling pathways in different types of cells in an automated format. Millennium would transfect genes into this system to define the signaling pathways and the cell types that genes were acting through, and we basically used the system unchanged. But instead of transfecting genes, we would introduce compounds and look at what pathways and what tissues the compounds were acting in, as another way to integrate a picture that we were trying to put together about how a given compound might be used.

On the informatics side, we were also using informatics at Millennium. We became very familiar with how to apply transcriptional databases and informatics tools. But during the time of the acquisition, it became clear that Gene Logic's biorepository and technologies for interrogating the biorepository were superior. So we basically switched over to Gene Logic, even though that wasn't intitially an important fourth prong when we were working at Millennium. But now we basically use the Gene Logic systems, which are very highly developed — as you know that's what they do, so it's no big surprise.

The fifth thing is something that we call GADME for genetic ADME, which is a technology that can help address why different patients respond differently to drugs, either with regard to toxicity or efficacy. And we have a technology that helps address that variability, and what it will mean is that compounds are moved across all the drug-metabolizing enzymes and transporters in the human genome, and as we identify how the drug is differently metabolized in different people, we would be able to provide genetic tests or enzyme tests to allow patients to be dosed in a more personalized way, so as to avoid toxicity, or improve efficacy.

Another technology that we had on the drawing board was toxicogenomics, and we were going to start that up if we became an independent entity and have that all mapped out. But Gene Logic is the leader in toxicogenomics — almost defined the commercial field — so we basically rely on them for that.

The technologies that we brought — the imaging, the bioanalytes, the GADME, the in vitro technologies — [integrated with Gene Logic's] toxicogenomics, informatics, and biorepository information for drug rescuing and repositioning of compounds.

As you're probably aware, one or two compounds out of ten that enter [clinical trials] wind up being approved, and our technologies can help in that selection process, as well as rescue failures.

So, what's the business model?

We're focusing in two areas. One is finding new indications for failed compounds, and rescuing failed compounds. This rescue doesn't always have to be applied to failed compounds — you can expand the market of live drugs. So one prong of the business model is clearly defined new indications for these technologies that will either revive a project or expand the market of the existing project.

The second piece of the business model is what we call the selection piece, where we would look at very advanced clinical compounds, such as the compounds that the company is considering moving into the clinic and making decisions on which of their ten compounds in their chemical series — that look promising — could move into the clinic. We could apply our technologies to give them a sense of which compounds are most likely to succeed as they move through the clinic. A simple example is the application of toxicogenomics.

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