BioWorld International Correspondent

Italian anticancer drug development firm Novuspharma SpA acquired full rights to an anti-angiogenesis program from its UK partner, Oxford-based Prolifix Ltd.

Terms were not disclosed, but Novuspharma, previously a 50 percent partner in the initiative, said the transaction "has virtually no impact on the financial position of the company." Project funding already has been budgeted for, and the program is in receipt of research support from the Italian government.

"We want to enlarge the breadth of the project," Novuspharma CEO Silvano Spinelli told BioWorld International. Discussions with potential collaborators at the National Cancer Institute are under way, he said.

The acquisition also widens the scope of Novuspharma's cancer strategy. The Bresso-based company has several cytotoxics in clinical development for a range of cancers. Last month, it entered a collaboration with Cephalon Inc., of West Chester, Pa., that centers on cell cycle progression and cell survival. The newly acquired program focuses on a different aspect of cancer development: the process by which new blood vessels are formed, which allows growing tumors to invade healthy tissues and eventually spread through the body.

Existing anti-angiogenesis efforts focus primarily on interfering with the formation of new vasculature, Spinelli said. "I am convinced that an anti-angiogenesis drug must have multifactorial activity to have benefits that are clinically meaningful."

The program is based on finding small-molecule inhibitors that disrupt binding of hypoxia inducible factor 1 alpha (HIF-1 alpha) to a transcription factor called p300. HIF-1 alpha is oxidized in the cytoplasm and then degraded under normal physiological conditions.

During hypoxia, when oxygen becomes scarce, that process fails to occur and HIF-1 alpha migrates to the nucleus, where it binds its subunit, ARNT (also called HIF-1 beta), and p300, and then triggers transcription of multiple genes involved in a range of key homeostatic and metabolic functions, including glucose metabolism, production of vascular endothelial growth factor, and synthesis of erythropoietin, which controls the proliferation of red blood cells. Hypoxia generally does not occur in noncancerous tissues, Spinelli said, so targeting HIF-1 alpha is likely to be selective for actively growing tumors. The big challenge is to find a molecule that can disrupt protein-protein interactions, he said.

As part of the transaction, Novuspharma obtained a validated screening system that can detect disruption of binding between an immobilized portion of the HIF-1 alpha active site and radiolabeled p300. "In principle, it is easy but difficult to standardize. It took Prolifix quite a bit of time," Spinelli said. Potential leads have been identified, although their druggability has not yet been established.