BioWorld International Correspondent

PARIS Genset SA plans to start clinical trials of the anti-obesity compound Famoxin in October and hopes to obtain initial results before the end of this year.

Under an agreement signed in December, the company subcontracted Eurogentec, of Liège, Belgium, to manufacture the protein, having had trouble itself in producing biologically active samples on a reproducible basis as it attempted to optimize and scale up its production process. Eurogentec just delivered its first batch of the protein and Genset will test its biological activity on both glucose and lipid metabolism over the next few weeks.

Genset’s internal difficulties in producing Famoxin have delayed its development, since the company originally intended to initiate clinical trials by the end of 2001. In July it said the target date had been pushed back to the middle of 2002, and that now has slipped by a few more months.

The Paris-based company’s external communications manager, Karine Pagès, told BioWorld International that two Phase I trials in healthy volunteers will be carried out, one of which will test the drug’s tolerance and the other to demonstrate its activity as regards sensitivity to insulin and lipid metabolism.

Metabolic disorders are one of two therapeutic areas, along with central nervous system diseases, in which Genset is focusing its drug development activities. Since late 2001 it has selected and annotated 60 putative secreted protein candidates from its library of thousands of full-length cDNAs that have therapeutic potential for metabolic disorders. Having sub-cloned them in an expression vector, the company is expressing the proteins and confirming biologically whether they are effectively secreted proteins.

After that, they will be tested for their potential role in metabolic disorders at the San Diego research center of Genset Inc., the company’s U.S. subsidiary. The active proteins could then be licensed out to other biopharmaceutical companies for development in therapeutic areas other than metabolism.

One example of that strategy was the licensing agreement concluded with Ricerca LLC, of Concord, Ohio, in March, giving it rights in oncology to a new protein, RAP-3, which was found by Genset to have potential activity in treating cancer as well as metabolic diseases.

Meanwhile, Genset has been granted a patent in the United States for its drug discovery technology. The U.S. Patent and Trademark Office issued Patent No. 6,291,182 covering methods, algorithms and software for identifying regions of the genome that contain a gene associated with any detectable trait. Genset said it is the first patent to cover biostatistical methods for confirming that a candidate genomic region harbors a gene associated with a detectable trait based on the frequency of single nucleotide polymorphism combinations known as haplotypes. The company said that many researchers now consider haplotypes to be superior to individual SNPs for the discovery of disease-related genes.

At the same time, the French company has been granted the right to apply for a U.S. patent relating to the g72 gene, a new entry point for the treatment of schizophrenia and bipolar disorder. The g72 gene was discovered as part of Genset’s joint research program with Janssen Pharmaceutica NV, a Belgium-based division of Johnson & Johnson with which Genset entered a research collaboration in September 1996 for the discovery of genes associated with schizophrenia.

The association of the g72 gene with schizophrenia was established through genotyping and biostatistical analysis, and then confirmed in a separate population using an additional, well-characterized clinical collection from schizophrenic cases and controls. Genset said the discovery of the gene revealed a novel biochemical pathway with new potential targets. Chairman and CEO André Pernet said it is only one of several promising discoveries in the field of CNS disorders the company is working on.

Genset also announced its financial results for the first quarter of 2002, when its net loss fell to EUR13.7 million (US$11.9 million) from EUR17.6 million in the corresponding three months of 2001. The only revenues earned during the period (EUR5 million) came from the sale of oligonucleotides, a business that was sold to the Poligo division of the German chemical company Degussa, of Düsseldorf, for EUR25 million in April. As of March 31, the company had cash and liquid investments totaling EUR6.8 million. But in April it received an initial payment of EUR21.9 million from Poligo and sold its 10 percent shareholding in Ceres, a Los Angeles-based plant genomics company, for EUR16.4 million. Its reserves now have swelled to EUR43.9 million.