BioWorld International Correspondent

PARIS - Diatos SA and Medarex Inc. signed a licensing agreement giving Diatos exclusive European rights to develop and commercialize a potential new cancer treatment.

Called Super-Leu-Dox, the therapy is in the final stages of preclinical development. Paris-based Diatos will undertake clinical development of the product in Europe, while Medarex, of Princeton, N.J., has an option to co-develop and co-commercialize it in Europe.

That option has to be exercised by the end of Phase II, and if Medarex opts to do so, the two will share all development and commercialization costs on a 50-50 basis, as well as future potential revenues from sales and sublicensing of Super-Leu-Dox in Europe.

If Medarex elects not to exercise that option, Diatos would have the right to complete the development and commercialization of the product in Europe, taking charge of all development activities and shouldering the full costs. In that event, Medarex would receive royalties on future sales. The U.S. company retains all rights to Super-Leu-Dox outside Europe.

The agreement also gives each company the right to use preclinical and clinical data generated by the other for developing the product in its territory.

The president and CEO of Diatos, John Tchelingerian, told BioWorld International that Diatos would "drive the development" of Super-Leu-Dox, and that the product would enter clinical development in Europe in 2004. But he declined to give further details about the future development timeline.

Medarex acquired its rights to Super-Leu-Dox (CPI-0004) through the acquisition of Corixa Corp.'s Tumor Activated Prodrug program. Super-Leu-Dox consists of doxorubicin (a marketed cytotoxic compound used for treating cancer) associated with a proprietary prodrug peptide. It is composed of a 4-amino-acid peptide associated with a cytotoxic agent whose activity is inhibited when it is conjugated to the peptide.

Medarex said preclinical studies showed that when prodrug molecules reach the vicinity of a tumor, the peptide is cleaved off by endopeptidase enzymes released by the cancer cells, liberating the cytotoxic compound. That then acts as an anticancer agent, exerting its cytotoxic effects locally on the cancer cells.

Diatos said the structure and tumor selectivity of Super-Leu-Dox are based on a tumor-activated prodrug approach that is similar to its own Tumor Selective Products (TSP) technology. TSP is a tetra-peptide sequence that can formulate therapeutic peptides or proteins as prodrugs. The sequence is selectively cleaved when exposed to enzymes released by cancer cells, and as a result the active molecule is delivered directly to tumor cells.

It is one component of the technology platform developed by the French company, the other being Diatos Peptide Vectors, which it uses to produce human peptide-based vectors that enter living cells and can deliver large quantities of small molecules, peptides, recombinant proteins, antibodies or polymer-based nanospheres into the cell cytoplasm and nucleus.

Tchelingerian pointed out that there was a common denominator in the respective approaches of Diatos and Medarex, insofar as both Super-Leu-Dox and TSP technology were co-invented by André Trouet at the Catholic University of Louvain in Belgium, who is Diatos' scientific adviser. Moreover, Diatos' lead compound, DTS-101, is a peptide vector-based version of doxorubicin. This is not as "mature" a product as Super-Leu-Dox, Tchelingerian said, although it is also due to enter clinical development in 2004.