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Dan Halbert, Iconix s New R&D Head, on the Firm s Toxicogenomics Goals

Dan Halbert
Executive Vice President of Research and Development
Iconix Pharmaceuticals

At A Glance

Name: Dan Halbert

Position: Iconix Pharmaceuticals, Executive Vice President of Research and Development

Background: Abbott Laboratories, Director of Genomics, Bioinformatics, and Proteomics 1991-2005

Gene-Trak Systems, Director of Assay Development, 1985-1991

Education: PhD, Molecular Virology, Washington University in St. Louis, 1981

When did you officially start at Iconix?

I officially started on March 1 — [eight] days ago.

What do you hope to do in your new position?

Abbott has had a year-and-a-half relationship with Iconix. The key really is to push the understanding of compounds to an earlier stage of the drug-development process. So, that's one of the key things — to continue to drive the science at Iconix toward additional relationships with pharmaceutical and biotech companies to continue to develop the database so that it is both diagnostic and predictive of additional pathologies and toxicities. And also to look for new opportunities to take the company to another level, perhaps in the area of biomarkers, though I don't think that's entirely clear at this time.

But I think we do need to continue to build the toxicogenomics space that Iconix has really carved out successfully over the course of the last couple years.

How would you describe Iconix' toxicogenomics database in terms of the rest of the industry?

I think it's arguably the largest [toxicogenomics] database that anyone has compiled, though I might have some difficulty quoting the exact statistics after four days. As I recall, it's over 600 different compounds across a variety of different tissues in rat, and in multiple doses and timepoints, and presented to the end users in an interface that allows them to correlate gene expression information with additional information: histopathology of different tissues; clinical chemistry information; the traditional types of information that pharmaceutical companies look for on compounds.

It includes compounds of many, many marketed drugs, a number of drugs that failed either early or in the market. And the concept is that, by matching gene expression information of compounds that exist in the database, to compounds that you want to compare to the database, you can learn about potential toxicities of compounds, as well as understanding mechanisms of action for those compounds as they relate to things that we know something about in the database.

Another major effort right now is to try to move toward assays. So right now, the database is really built on rat toxicology, and we have a significant effort to develop an toxicogenomics database using isolated rat hepatocytes, so that one can look at much smaller amounts of compound — much less compound than you would need to go into animal studies. And so, we're developing that in vitro database as an addendum to the existing DrugMatrix [Iconix database], where you can apply compounds to isolated rat hepatocytes, and then measure gene expression, and compare the expression [related to] your compound with the compounds existing in the database, like you would do with the existing DrugMatrix.

No other cell types?

We have a plan to move forward, as well, with human white blood cells. But that's on the drawing board, and that's actually a huge challenge.

What else does the database feature?

The other piece of the database is — it's not just the gene expression information — we've mined the information to reveal much smaller collections of genes that have been mined as diagnostic markers of certain pathologies. So, the gene signatures are really the fine subset of gene expression information that really drives the histopathology or the relationship to the toxicology, or whatever it is. You take that database of gene expression information from 10,000 genes, and then cull out of that the limited set of genes — 25, 35, 50 genes — that are truly the essence of whatever the differences in gene expression are that relate to that particular pathology or toxicology.

Another direction that we're moving is to develop an assay — rather than looking at 10,000 genes on an array, now you can look at 35 or 40 genes on an array that will be diagnostic or predictive of a certain toxicology or a certain mechanism of action or a certain pathology.

Do you plan to make any changes in your section of the company?

One of the reasons that I joined Iconix is the quality of the science and the people. It's a very, very scientifically focused organization, and so I have no intention of changing that. I hope it continues to grow and build the science, and keeps that focus. I think that's what differentiates it from anyone else in the marketplace.

As far as I'm concerned, the way to sell a technology to someone is on the basis of the strength of the science, and the depth of the science, and the depth of the understanding of the individuals in the company. They can sit and explain to you what they see, why they see it, what it's related to, and the underlying mechanisms, and they've read the literature and understand all of those things.

I joined the company because I think it's moving in the right direction, and it's exciting, and there isn't anything I want to change right away.

What intangibles are you bringing to your new job from Abbott?

I've been working in drug discovery for 13 and a half years, and I think that understanding the drug-discovery space, understanding the relationships between the large pharmaceutical companies and their biotech partners, and having been on the other side of the table gives me a view that is unique and valuable for biotech.

I worked for a small company in the Boston area for six and a half years before I went to large pharma, so I've been on both sides. And having seen both sides, I think I have a pretty good idea of what I was getting into — good and bad.

Is there any project at Iconix that you have the most hope for?

I think the in vitro project is probably one of the biggest, one of the most important things we can do if we can move into the human surrogate marker space — white blood cells in particular — which is a body fluid we can get our hands on fairly easily. And we can use that to move closer to human toxicity, as opposed to rat, and expand into human toxicity profiling. I think that would be a real coup to do that — it's going to be a long road to get there.

How long until the rat hepatocyte database is ready?

I don't know what the status is of the number of compounds that have already been run, but it's quite far along, and we've already mined out a large number of signatures out of the database, so again I'm not positive, but I think by the end of the year everything will be as complete as we expect it to be for the first phase of the project.

Will it be saleable?

It might be ready for prime time by the end of the year at the latest, maybe even before that.

When do you think the human white blood cell surrogates will be ready?

I don't want to speculate, but I think it's certainly going to be into 2006 before we have a degree of confidence in the data that are coming out of that — and really it's proof of principle to begin with, and if that works, then we'll be building that to a greater extent.

And DrugMatrix — is that a constantly growing database?

It's constantly growing. What we're doing now is focusing on specialized areas — perhaps areas that large pharma are more interested in, kinase inhibitors, for example.

I think now we're going to expand into other tissues in the rat, but I think now — compound-wise — we'll be a little more driven.


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