By Matthew Willett

Having identified targets through analysis of genes linked to schizophrenia and peripheral arterial occlusive disease, F. Hoffmann-La Roche Ltd. and deCode genetics Inc. will move their February 1998 collaboration into the discovery phase.

The move triggers milestone payments for deCode, whose Icelandic genome-wide scans for population-wide linkages identified the disease genes, but in this unique collaboration, deCode won't be the only party to profit from a therapeutic's development.

Data from the identified genes include information on molecular pathways and secreted proteins and enzymes, and the companies will focus their drug discovery work on novel targets known to be causally involved in the pathogenesis of each illness.

DeCode CEO Kari Stefansson told BioWorld Today the discovery alliance will focus on two targets. He said the advancement of the collaboration represents an important milestone for the entire drug discovery industry, since it further proves the utility of population-based target identification.

"You can take a hammer and hit a pancreas with it and that will change the expression of the genes in the pancreas, but it doesn't tell you anything about where the guy bought the hammer from," Stefansson said.

His point: Gene expression analysis isn't a definitive method for target identification. Population-based comparisons, like deCode's, he said, are.

Reykjavik, Iceland-based deCode and Roche, of Basel, Switzerland, entered the research collaboration, valued at more than $200 million, just over two years ago. The five-year agreement included an equity investment in deCode by Roche, research funding and milestone payments for the Icelandic company. (See BioWorld Today, Feb. 3, 1998.)

Roche has rights for the development of any small-molecule drugs against gene targets, drugs derived from gene products and diagnostics, and deCode retained rights to gene and antisense therapies.

Founded in 1996, deCode uses the homogeneity in Iceland's 270,000 inhabitants to uncover genes related to complex diseases. Because of the high degree of genetic similarity it is relatively easy to spot disease-related genes by comparing the DNA of healthy and afflicted groups and identifying the differences between them.

"When we look at genes we're pulling out genes that are really based on the pathogenesis of the disease," Stefansson said. "It may not give an instant drug target, but it does give us a pathway we can exploit to find an appropriate target. The important thing about what we announced is that we've isolated genes in two common diseases, and there's a target for each to take into development."

The collaboration, he added, will likely produce several more targets, and soon.

"We're working with them on nine other diseases, and we're in the final stages of pulling out genes," Stefansson said. "We expect that within a short period of time we'll release developments in other diseases, as well as this collaboration is going. It's much better than anyone dared to dream about."

But as important as additional milestones and disease targets are to deCode, Stefansson spoke most passionately about the deal's unique aspect.

Exploiting Iceland's unique population will end up benefiting the Icelanders as a whole if a therapeutic is developed as a result of the collaboration. The agreement calls for Roche to supply Iceland with all medicines developed as a result of the collaboration, free of charge.

"I can tell you that when I was negotiating with Roche I felt it would be nice to have some sort of at least symbolic gesture for the population, a token of appreciation by the pharma partner," he said. "They agreed with me, and, to my surprise, they're willing to include that in the deal. I've been criticized as 'throwing glass beads to the natives,' but I think that's offensive and ridiculous. I think every time you see an industry like the pharma industry showing a gesture of good faith and appreciation for the people it's working with we should welcome it for what it is, a gesture of appreciation for the people." n