National Editor

Novacea Inc. in-licensed a Phase I cancer drug known as AQ4N from KuDOS Pharmaceuticals Inc., gaining North American rights in exchange for undisclosed development milestone payments and royalties.

"The unique thing about AQ4N is that it's inactive when you first administer it," said Brad Goodwin, Novacea's CEO. The intravenous treatment - described as a potent topoisomerase II inhibitor and DNA intercalator in its active form, called AQ4 - starts working only when it makes contact with hypoxic, or oxygen-starved, cells in tumors, thus reducing the potential for systemic toxicity.

"In general, many common tumors have regions of the cells that are hypoxic," Goodwin said. The percentage "changes over time, but it's very common to see that cells have a significant portion of their mass as hypoxic," he added.

South San Francisco-based Novacea gets an exclusive license to develop and commercialize the drug in the U.S., Canada and Mexico for all indications. KuDOS will continue to develop AQ4N in Europe and other markets outside North America. The two firms will work together on worldwide development of the jointly manufactured compound against a broad range of cancer indications. Both firms are privately held.

Preclinical data with AQ4N showed the drug enhances radiation and chemotherapy, and the Phase I study by Cambridge, UK-based KuDOS is testing it in combination with radiation against esophageal cancer. So far, 16 patients have been treated and the drug is well tolerated, with no serious drug-related adverse events. Some data have suggested the drug could be useful as a monotherapy, the company said.

In the U.S., Novacea will file an investigational new drug application next year and begin Phase I trials shortly afterward, Goodwin said. Meanwhile, the company's lead product, DN-101, continues in two Phase II programs.

An oral cancer drug containing the most potent active form of vitamin D, known as calcitriol, DN-101 is being studied in combination with Taxotere (docetaxel) against prostate cancer and lung cancer.

"The prostate cancer trial is a fairly large trial, and we're targeting to have that fully enrolled by the end of this year," with data in the summer or fall of next year, Goodwin said.

"The lung cancer trial began in the middle part of this year," he said. "We should have preliminary data in the summer of next year, and we'll follow [trial participants] for another year."

KuDOS also has a Phase II drug, Patrin, an inactivator of 06-alkylguanine DNA-alkyltransferase (AGT), which causes resistance to chemotherapy. Patrin entered the Phase II study against metastatic colorectal cancer in August, and the multicenter trial is expected to involve up to 30 patients with Stage IV metastatic colorectal carcinoma who have failed no more than two previous chemotherapeutic regimens.

KuDOS said the indication was chosen as a target for Patrin and temozolomide (sold as Temodar, from Madison, N.J.-based Schering-Plough Corp.) because such tumors express high levels of AGT.

Another Phase II study is testing Patrin in metastatic melanoma patients. The 80-patient, open-label, randomized study at eight Australian and two UK centers is designed to assess the efficacy of Patrin in combination with temozolomide compared to temozolomide alone. Results are expected at the end of next year.

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