Less than six months after starting operations, Devgen NV, which focuses on functional genomics, has secured its first pharmaceutical partner, Janssen Pharmaceutica NV.

Ghent, Belgium-based Devgen has agreed to a drug discovery collaboration based on the model organism Caenorhabditis elegans with Janssen, a subsidiary of Johnson & Johnson, of New Brunswick, N.J.

“It is Janssen policy not to reveal details,“ said Thierry Bogaert, CEO of Devgen. “However, the partnership is an extension of an academic collaboration we have had with [Janssen] for over three years.“

Several patents have been filed as a result of the collaboration with Bogaert's laboratory at the University of Ghent.

“Last summer when we were setting up the company, we talked to Janssen,“ Bogaert told BioWorld International. “We agreed to put the collaboration on ice while Devgen was formed. We didn't want a major [collaborator] having a stake in the company because it does not help when you are trying to attract other partners. In April, we went back to Janssen and agreed to revive the relationship.“

Devgen was founded in December 1997 as a functional genomics and drug discovery company combining C. elegans genetics with biochemistry, molecular biology and high-throughput screening. It has funding of US$8.5 million from the U.K. life science venture group Abingworth Management Ltd. and the Belgian venture group GIMV. Devgen proved the power of its approach in early 1995 when, as part of the Janssen collaboration, it went from the discovery of a novel worm genetic pathway to the identification of a lead compound.

“When you look at other companies using developmental genetics as the basis of drug discovery, we have the advantage that we have got validation of our concept, and the deal with Janssen shows we are doing good stuff,“ said Bogaert.

Devgen's approach involves determining the function of genes, assigning these genes to pathways and then identifying the key switches in these pathways. The technique cannot be applied to humans or to other model organisms such as mice because it requires experimental animals to be grown in vast numbers, to have short generation times and to be amenable to rapid and detailed phenotype analysis.

While C. elegans is a suitable subject for this approach, the question remains of whether it is sufficiently similar to be used to identify human molecular switches and the drugs that act upon them. Devgen believes man is genetically a “fourfold worm.“

All genes and pathways shown to be important in cell, developmental and disease biology have been found to be conserved between worm and man. As a consequence human genes can be readily inserted into the worm genome, functionally replacing worm genes - even in complex cell and signal transduction pathways. Conversely, worm genes can be used to trigger specific biochemical processes in human cells.

Compounds that are pharmacologically active in man also act on structurally and functionally related targets in C. elegans. Worms in which the target endogenous worm gene is replaced by its human homologue provide compound screens with complex in vivo endpoints.

Bogaert said Devgen is investing significant resources in the automation of its techniques. The company is talking to other potential partners and adding value by way of its in-house discovery programs. It also is focusing on disease areas that require intervention in signaling processes between the cell surface and the cytoskeleton. These include pathologies related to cell motility and cell shape - for example, neuronal degeneration; pathologies related to apoptosis (programmed cell death), such as cancer and inflammation; and autosomal dominant polycystic kidney disease.

Devgen intends to improve existing therapies. It has singled out compounds with proven therapeutic effects and dose-limiting side effects, or unknown modes of action, and will use C. elegans to determine their biochemical pathways. Further, the company plans to use the C. elegans system to link the chemical structure of a compound to its biological activity. *

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