By Nuala Moran

Special To BioWorld Today

LONDON — In what is claimed as the largest human genomics deal, deCode Genetics Inc. and Hoffman-La Roche AG have agreed to a $200-million-plus research collaboration to identify disease genes based on studies of Iceland's relatively isolated population.

The five-year deal includes an equity investment, research funding and milestone payments. The research will focus on the discovery of genes or alleles with mutations that predispose people to the development of up to 12 common diseases, including four cardiovascular diseases, four metabolic diseases and four psychiatric and neurologic diseases.

No breakdown of the financial package was given, but Kari Stefansson, founding president and CEO of deCode, told BioWorld Today that Roche "will not own a large percentage of the company."

Under terms of the deal, Roche, of Basel, Switzerland, has the right to develop small-molecule drugs against gene targets, drugs derived from gene products and diagnostics. DeCode will retain rights to gene and antisense therapies. The collaboration also will include research into pharmacogenomics. Stefansson said the agreement is exclusive for the 12 diseases, and deCode expects to sign further partners in other diseases.

DeCode Genetics, based in Reykjavik, Iceland, was founded in August 1996 with $12 million of U.S. and European venture capital.

The company draws on the extraordinary degree of 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.

Most genomics companies assemble tools for the identification of genes or gene function and then attempt to find a relevant population to which these tools can be applied.

"The tools for doing this have become widely available. The scarce resource is the population base," said Stefansson.

The entire Icelandic population is descended from a small number of founder individuals who originally settled on the island in the 7th century. Since then, there has been virtually no inward migration, so all the current inhabitants of Iceland are descended from this circumscribed genetic pool of the founders. This makes it likely that genetic variations between healthy and afflicted people are mutations that cause disease, rather than random variations resulting from different racial or ethnic backgrounds.

But Iceland's genomics assets are not limited to genetic homogeneity. One of the national passions is genealogy, and the genealogy of the entire population over the past two centuries is already held on an electronic database. In addition, there is a centralized health care system providing medical records that date back to 1915.

"This gives incredible power," said Stefansson. "For example, in one study of the genetics of asthma, matching 1,200 patients from the clinical database against the genealogy database showed up families with over 100 affected individuals."

Iceland also has a large tissue bank containing samples from all autopsies and biopsies since 1915, which Stefansson said would "give access to DNA from past generations."

Finally, the people of Iceland are highly educated and are prepared to cooperate with scientists.

DeCode has set up clinical collaborations in a wide range of common diseases with clinicians across the country. Illustrating the power of deCode's approach, the company's first success was to uncover a gene for familial essential tremor (FET).

"The deCode approach rapidly identifies genes known to be involved in specific diseases, allowing us and our partners to move quickly to target validation, screening and drug development," said Stefansson.

DeCode also is working with the Icelandic government to develop an integrated, anonymous database of genotypes, genealogy, family medical histories, disease symptoms, resource use and treatment outcomes. This database will be licensed on a nonexclusive basis. As well as helping to identify families in which specific diseases occur and trace inheritance of a disease over several generations, it will be a powerful tool for pharmacogenomics.

Icelanders Promised Free Medicines

Jonathan Knowles, president of worldwide research for Hoffman-La Roche, said the focus on the Icelandic population, "Allows us to apply one and the same initiative in genetics in the development of diagnostics, therapeutics and pharmacogenomics.

"The basic idea is to take advantage of a unique combination of qualities that the Icelandic population has, and use it to shed light on certain aspects of effective treatments for the future. We look at this agreement as the beginning of a collaboration not only between Roche and deCode Genetics, but between Roche and the Icelandic population in general."

Roche has agreed to supply Iceland with all medicines developed as a result of the collaboration, free of charge.

Stefansson said the two companies have yet to define how the collaboration will operate, but, he said, "I am keen to make it a more fluid interaction than appears typical of pharma-biotech deals. There is room for us and Roche to complement each other, and it would be silly for Roche to simply hand over the money and us to hand over the genes."

In particular, Stefansson said Roche's clinical expertise would be very important in defining phenotypes.

The prime minister of Iceland, David Oddsson, said the government will do its best to assist the two companies in achieving the goals of the collaboration. "It is extremely important for us to secure foreign investment in Icelandic companies, and I am delighted to see an investment of this size in a high-tech venture in our country," he observed. *