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GPC Biotech s Yeast Three-Hybrid Technology LeadCode Lures Lilly into New Collaboration

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Biotech companies with a new proteomics tool for pharma’s drug discovery box have trouble these days to get firms to pay to try it out. But GPC Biotech of Martinsried, Germany, has been successful, recently announcing that it signed up Eli Lilly to test its new yeast three-hybrid technology, LeadCode.

LeadCode, an extension of yeast two-hybrid technology, allows researchers to study small molecule-protein interactions in living cells, enabling them to identify the molecular targets of these compounds.

In the collaboration, which GPC said is its first for LeadCode, the company will be testing “a handful” of compounds Lilly has been developing in the area of metabolic diseases, according to Chris LeMasters, a manager for corporate business development at Lilly. Among metabolic diseases, Lilly is particularly interested in diabetes and obesity, he added.

The project, which Lilly regards as a pilot study, will take less than a year, according to LeMasters, and will be run on a fee-for-service basis.

LeadCode rests on technology published by Jun Liu at MIT in 1996, which GPC licensed and developed, filing its own patent applications, according to Nikolai Kley, head of research at GPC’s Waltham, Mass., facility.

The assay has essentially three components: a known protein target fused to a DNA binding domain, a test protein fused to an activation domain, and a bifunctional ligand consisting of a small molecule that binds to the known target and a compound of interest with no known target. These two are connected by a linker. If the compound of interest binds to the test protein, all three partners come together, activating a reporter gene.

LeadCode is useful to characterize compounds at various stages of development, Kley said. For example, cell-based screening assays often turn up compounds with interesting phenotypic effects, but unknown targets. Later on, the technology might help reveal targets that mediate toxic side effects. Furthermore, LeadCode could help characterize beneficial side effects of compounds.

Though LeMasters declined to reveal details about the compounds Lilly will test, he said that “for this particular group of compounds, it will be very useful to understand off-target issues.”

GPC’s German group will be working closely with Lilly’s group in Hamburg, Germany, which established the first contact between the companies. This geographical proximity, combined with GPC’s track record in other collaborations — the company has worked with Aventis Pharma, Boehringer Ingelheim, and Altana Pharmas, among others — helped persuade Lilly to sign up with them, according to LeMasters.

GPC will also use its three-hybrid technology for internal drug discovery programs: The company’s main focus is in oncology. Besides LeadCode, GPC Biotech has developed a platform for studying the effect of compounds by gene expression profiling. The 200-employee company, which was founded in Germany in 1997 and went public in 2000, has one lead product that has completed phase II clinical trials. The staff is about equally distributed between its headquarters in Martinsried and its research site in Waltham, along with about a dozen at its Princeton, NJ, site.

— JK

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