Associate Managing Editor

Having acquired a side program a touch outside its focus, Medarex Inc. found a European licensee for it in Diatos SA, but is keeping its options open.

The cancer product, Super-Leu-Dox, was in-licensed in a $21 million deal in May 2002 with Corixa Corp. that centered on Corixa's Ultra-Potent Toxin technology. Corixa, of Seattle, was in the midst of a reorganization in which it also cut its work force by about 60 percent. Along with the Ultra-Potent technology, designed to link certain toxins to monoclonal antibodies, Medarex got other monoclonal antibody-based programs and antibody targets. (See BioWorld Today, May 28, 2002.)

"We acquired [Super-Leu-Dox] in the deal with Corixa where the main focus was the toxin technology, but this was part of the deal," said Ron Pepin, senior vice president, business development at Medarex. "It fell a little bit out of our area of immediate expertise; this was more of a small-molecule approach. We were a little less comfortable getting our arms around it then we were with the antibody parts of the deal."

Medarex, with its UltiMAb Human Antibody Development System and The UltiMAb Advantage, is not short on antibody experience, but it's not long on prodrug peptide expertise, either. Diatos, of Paris, on the other hand, has two core technology platforms - Diatos Peptide Vector and Tumor Selective Prodrug (TSP) - that are more in line with what Super-Leu-Dox is, especially given that its former chief scientific officer and current scientific advisory board member, André Trouet, co-invented both the Super-Leu-Dox and TSP technologies.

Super-Leu-Dox is doxorubicin conjugated to a prodrug peptide. In general terms, the drug is "a targeting type of strategy," Pepin told BioWorld Today.

"The peptide is a sequence that is broken down by enzymes released by tumors," he said. "The peptide is cleaved by the enzyme and the cytotoxin is then in the location where you would want it to kill the tumor. We call it the TAP technology - Tumor Activated Prodrug approach."

Explaining Diatos' interest, Pepin said, "[Diatos] was looking for a product they were comfortable with in this area and [Trouet] knew about the molecule, so it made sense for them to take the lead."

Diatos now has European rights to develop Super-Leu-Dox, which is currently in preclinical work. Medarex has an option to buy back into the compound before it reaches Phase III development, and then co-develop and co-commercialize it in Europe. Medarex retains rights in the rest of the world.

If Medarex does not opt back in, Diatos would develop the product on its own and Medarex would receive royalties.

"They are bringing it forward on their own dime," Pepin said, adding that Medarex plans to keep the remaining rights. "We'll be looking for Diatos to show proof of concept in Europe and we'll follow on with our trials in the rest of the world."

The companies would share data with each other.

Medarex's own pipeline includes MDX-010, an antibody in "several Phase II trials in melanoma and prostate cancer," Pepin said. The company expects to complete Phase II work by the end of the year and begin Phase III studies by the end of 2003 or early in 2004.

Other antibodies in the pipeline include MDX-070, targeted at prostate-specific membrane antigen, and MDX-060, targeted against CD30, "something that is useful in lymphomas," Pepin said.

Medarex's stock (NASDAQ:MEDX) rose 23 cents Tuesday to close at $3.66.