BioWorld International Correspondent

G protein-coupled receptors, the superfamily of membrane-spanning proteins involved in diverse signaling processes, are the subject of two drug discovery collaborations unveiled last week by European biotechnology firms.

Sweden's largest biotechnology company, Biovitrum AB, entered a broadly based partnership with UK firm BioFocus plc, of Sittingbourne, while Italian start-up BioXell SpA, a spin-out from Basel, Switzerland-based F. Hoffmann-La Roche Ltd., signed a pact with a Taiwanese firm, TaiGen Biotechnology Co. Ltd., of Taipei.

G protein-coupled receptors - the pharmaceutical industry's most popular targets - are the basis of approximately half of all existing drugs. Human genome data indicate the presence of up to 800 proteins, most of which are not yet characterized.

BioXell and TaiGen aim to identify small-molecule drug candidates that modulate receptors implicated in chronic inflammatory conditions. Terms were not disclosed, but there is no money changing hands in that deal, Francesco Sinigaglia, CEO of Milan-based BioXell, told BioWorld International. "We share costs and we share upside."

The Biovitrum-BioFocus pact is structured on similar lines, with a 50-50 revenue and profit split, said Terje Kalland, chief scientific officer of Stockholm-based Biovitrum. It is not tied to any particular indications, but Biovitrum has been assigned special rights to targets associated with its core focus area of metabolic disease plus oncology, which it has begun to prioritize more recently.

The deal is the first significant collaboration the Swedish company has entered since it was spun out of Pharmacia Corp., of Peapack, N.J., last year. "It's also strategically very important for Biovitrum. We see a total complementarity in the assets we have [and those of] BioFocus," Kalland told BioWorld International.

The companies are taking a chemogenomics approach to identifying the function of orphan G protein-coupled receptors and generating potential leads, based on BioFocus' library of compounds that selectively identify sequence motifs common to particular G protein-coupled receptor families and Biovitrum's extensive knowledge of orphan receptors, which it gained through Pharmacia's early access to human genome sequence data.

The agreement with TaiGen gives BioXell access to the constitutively activated receptor technology (CART), which the former firm licensed from one of its investors, Arena Pharmaceuticals Inc., of San Diego. That platform bypasses the need for knowledge of an orphan receptor's native ligand. It allows researchers to screen for small molecules that appear to interact with G protein-coupled receptors by observing their effect on genetically modified versions that are constitutively expressed in their biologically activated state because of alterations in their intercellular structure. The extracellular loops of the receptors are unchanged and hence retain their native binding characteristics. CART, Arena said, also can lead to the identification of molecules that act on G protein-coupled receptors through novel mechanisms by binding at sites other than the natural ligand binding site.

"We are particularly interested in the orphan receptors," Sinigaglia said. Under the terms of the agreement, BioXell will be responsible for target identification and testing leads, while TaiGen will be responsible for screening targets against its chemical library and identifying and optimizing leads.