BioWorld International Correspondent

TopoTarget A/S took full ownership of a monoclonal antibody development program in cancer by exercising a licensing option with Novartis AG.

Terms were not disclosed, but the financial implications are "very Benign," TopoTarget CEO Peter Buhl Jensen told BioWorld International. "The amount we had to pay here is less than the price to produce it," he said.

The molecule, called Zemab (previously ScFv[FRP5]ETA), comprises a single-chain antibody fragment tethered to a truncated form of the Pseudomonas protein exotoxin A. It targets the ERBB2/Her2 receptor, which contributes to the development of breast cancer and several other cancers, but exerts its anti-tumor effect via the bacterial toxin.

Herceptin (trastuzumab), marketed by Genentech Inc., of South San Francisco, is thought to work by blocking the Her2 receptor and preventing tumor cell growth and division, as well as by recruiting immune effector functions. However, only about 30 percent of breast cancer patients exhibit a clinical response to the therapy.

In one Phase I study, in which Zemab was injected directly into the patients' tumors, six of the 10 participants exhibited a response. One of the responders previously received Herceptin.

"It might be that Herceptin-resistant patients might also be a target for this treatment," Jensens said.

Zemab also showed hints of efficacy in a second Phase I clinical trial, in which it was administered systemically to 18 patients. They had a variety of cancers, although the majority were breast cancer patients.

The intravenous delivery route offers greater potential, Jensen said. If it is only developed for direct administration to tumors, it will stay a niche product.

TopoTarget gained the option on Zemab when it acquired G2M Cancer Drugs AG, of Frankfurt, Germany, in 2005. G2M and researchers at the University of Frankfurt previously collaborated with Basel, Switzerland-based Novartis on development of the compound.

TopoTarget's main focus is on developing small molecules for cancer indications, but its early evidence of efficacy has motivated the company to continue its development. "It works in patients - that's the best sign you can get," Jensen said.

It will be at least another year, however, before the company conducts any further clinical trials. It is first modifying the molecule for production purposes, and it will then conduct bridging studies with the newer version. "Then we'll do some Phase I studies," Jensen said. It aims to progress to Phase II studies rapidly.

Last year, the company gained European approval for its lead product, a DNA topoisomerase II inhibitor called Savene, for preventing tissue damage caused by extravasation events during anthracycline chemotherapy. It hopes to gain FDA approval for the same product in May. If approved, it will be marketed as Totect in the U.S.