By Mary Welch

Working in genomics these days, said Scott Salka, new president and CEO of Ventana Genetics Inc., is like being dropped in the jungle with the aim of creating civilization.

"You build roads here and there and they don't connect at first, " he said. "The hope is that eventually they'll all connect and create something. Genomic research is going to pay off eventually and you have to build the infrastructure. Right now, everyone's going down a lot of paths."

Ventana, of Salt Lake City, was founded in May 1996. Last December, Warburg, Pincus & Co., of New York, invested $6 million, and Salka said another private placement, led again by Warburg, should raise between $8 million and $10 million by July. In addition, the staff will increase from 26 employees to 36 by the end of the summer, and a new 27, 000 square-foot-building (almost four times the size of the current one) will house the employees by the end of the year.

What separates Ventana from other genomic-based drug discovery firms is its approach, Salka said.

"First off, you have to realize that identifying a novel disease gene is only the first step down the path that may lead to a new target, which, in turn, may eventually yield a new drug, " he said. "At best, a gene discovery is a signpost that points researchers toward a metabolic pathway that may contain an elusive drug target.

"Not a lot is known about the mechanisms behind common diseases, " he continued. "You have to think: What happens to kick a person into a diseased state? Now, we ease the symptoms without attacking the root cause. The knowledge gained through gene discovery may lead to novel therapeutics that, really for the first time, address the root cause of diseases rather than just the systems. But it's taking longer to go from gene discovery to controlling the disease than the genomic and pharmaceutical industries anticipated."

Taking a what he called a "more pragmatic approach, " Ventana's co-founder Alexander Kamb developed a proprietary technology platform that discovers novel drug targets based on their biological activity in human cell assays. These function-based assays use "perturbagens" -- expressed peptides or small protein fragments -- to disrupt the physiological processes in mammalian cells and thereby identify novel targets for drug discovery.

Perturbagen Effects Point The Way To Targets

Ventana randomly introduces millions of different perturbagens into cell lines so that each cell is only exposed to one perturbagen. This way, the company can rapidly and efficiently scan perturbagens in millions of cells. While these cell lines may be healthy, more often they are in a diseased state. When a cell reacts in a desired way in the presence of a perturbagen, scientists know they have identified a target worthy of future study.

"We basically look for where the perturbagens moved the cells from a diseased to a normal state, " Salka said. "Our technology exploits the cell's complexity."

The next step is to recover those perturbagens, study the cellular binding partner of each to see where it interacted in the cell and quickly move to assay development and screening for small molecule drugs.

"The technology is fast, " Salka said. "We can scan millions of cells in a short period of time. We also primarily use human cells, which again sidesteps any problems of having something react one way in mice, worms, yeast or bacteria and not [that way] in humans. Again, that's an important feature is our efficiency. Today, the average time to discover a disease gene is three to five years. In that same time frame, we've passed that and are screening for small molecules with activity against highly validated targets. This of course, is of interest to pharmaceutical companies."

Salka replaced co-founder Dennis Farrar, an attorney and board member who was the company's acting CEO for a year-and-a-half. Salka joined Ventana this month from the former Sequana Therapeutics, a La Jolla, Calif.-based genomics firm, where he directed corporate development and helped raise more than $25 million in three rounds of private funding and almost $50 million in two public equity financings. Sequana was acquired by Arris Pharmaceuticals Inc., of South San Francisco, in November 1997 in a stock swap valued at $166 million. The merged companies were renamed Axys.

"I was attracted to Ventana because of its unique approach and because I'm pragmatic, " he said. "I like that speeded up timetable and the more direct approach to drug discovery. Pharmaceutical companies are interested in us because, while we're not replacing genomic research, we certainly augment it and speed it up." *