BioWorld International Correspondent

LONDON - Start-up ReOx Ltd. signed a $9 million exclusive deal with an unnamed U.S. biotech for the co-development of drugs targeting cellular oxygen regulation through the transcription factor hypoxia inducible factor (HIF).

In addition to paying $9 million up front, ReOx's partner - identified only as "a premier, first-tier biopharmaceutical company" - will pay research costs, milestones and royalties on product sales.

ReOx raised £2 million (US$3.6 million) when it was spun out of The Wellcome Trust Centre for Human Genetics at Oxford University in June 2003, to commercialize research by four professors in the hydroxylase enzymes that regulate HIF and small-molecule inhibitors of those enzymes.

The founding professors have spent more than 10 years exploring how HIF coordinates the body's response to hypoxia at a cellular level. Under hypoxic conditions, HIF now is known to activate the transcription of more than 50 genes, including erythropoeitin, vascular endothelial growth factor, glucose transporters, glycolytic enzymes and other genes with products meant to either increase oxygen levels directly or help cells adapt to hypoxia. At the same time, hundreds of genes are responsive to HIF activation in any given cell.

Inadequate supply of oxygen occurs in a range of diseases, including ischemia, stroke, cancer and arthritis. For example, in breast cancer, HIF-1alpha gives tumor cells the ability to adapt to hypoxia, promoting critical steps in tumor progression and aggressiveness. Elevated levels of HIF-1alpha correlate with shorter survival times. HIF has been shown to be up-regulated in prostate, gastric and other solid tumors. Similarly, in arthritis HIF-1alpha expression has been shown to be inversely related to tissue oxygen levels, prompting inflammation and associated tissue destruction.

HIF also is implicated in bacterial infections, and it has been suggested that it could be regulated to enhance the body's production of erythropoeitin.

With such a wealth of therapeutic targets to aim at, ReOx is screening for small-molecule inhibitors of HIF hyroxylases as treatments for ischemia.

There are no treatments targeting HIF, though academic and commercial interest is growing rapidly. A spokeswoman for ReOx told BioWorld International that ReOx's partner was remaining anonymous because it did not want competitors to be aware of its interest in the field.

Barry Porter, CEO of ReOx, said the partnership was an "exceptional opportunity" for ReOx. "We believe it represents the best route to developing an HIF-regulating drug."