BioWorld International Correspondent

TopoTarget A/S added a fourth clinical program to its pipeline by teaming up with NeuroSearch A/S to develop the latter's cancer compound Endovion, a chloride channel blocker.

Terms of the deal were not disclosed, but Copenhagen, Denmark-based TopoTarget takes on responsibility for funding additional preclinical and clinical development of the product. The companies will share revenues.

Also known as NS3728, Endovion previously had undergone a Phase I trial in sickle cell disease, but Ballerup, Denmark-based NeuroSearch discontinued that program in 2002. GlaxoSmithKline plc gained an option on the cancer program when it signed an alliance with NeuroSearch in December, but it subsequently decided not to exercise it.

Before moving the product into a Phase II trial, TopoTarget plans to conduct additional preclinical studies and determine the optimum cancer indications to target.

"We will study the drug in our labs and in our models to come up with a way of how to move it forward," said CEO Peter Buhl Jensen.

NeuroSearch has performed studies of the product in brain cancer in combination with temozolomide (Temodar, Schering-Plough Corp.), but TopoTarget is not committed to that option.

"We would like to see if there are other opportunities with the product," Jensen said. "It's technically a little complicated to demonstrate efficacy in brain tumors."

Previous in vivo work generated positive data in murine models of melanoma and glioblastoma, but Endovion's mechanism of action is not fully understood. It blocks a specific chloride channel that is associated with controlling cell volume.

"If volume is restricted, I could see why it could be inhibiting cell proliferation," Jensen said.

The product has potential as a combination therapy, particularly in settings in which cancers have developed resistance to existing therapies. "There are a plethora of possibilities, as I see it," Jensen said. The company aims to move the compound into a Phase II trial about a year from now.

TopoTarget has three other programs under way. Its lead compound, Topotect, an inhibitor of topoisomerase II, is undergoing a Phase III trial for treatment of extravasation following anthracycline chemotherapy. The same compound also is undergoing a Phase I study in combination with etoposide, for treatment and prevention of brain cancer. PXD101, an inhibitor of histone deacetylase, is in Phase I studies in patients with advanced solid tumors. The compound recently was the subject of an agreement with CuraGen Corp., of New Haven, Conn.

NeuroSearch said the agreement would not alter its financial forecast for the year.

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