National Editor

With one cancer drug in Phase II/III trials and another recently in-licensed, Novacea Inc. pulled down $35 million through a Series C financing to help move the compounds along.

"We haven't specifically talked about how long [the funds will last], but this substantially increases our runway," said Brad Goodwin, CEO of South San Francisco-based Novacea, which has raised $83 million since its inception in July 2001.

The privately held company's lead drug, orally administered DN-101, is based on calcitriol - the most potent active form of vitamin D - and is being tested in a Phase II/III trial for advanced prostate cancer as well as a Phase I/II trial for non-small-cell lung cancer. In animal models, calcitriol proved to be synergistic with many chemotherapy drugs.

Past research discovered that calcitriol had antitumor effects as a single agent in vitro and in vivo, and scientists at the University of Pittsburgh verified the synergy with chemotherapy, Goodwin said.

"The problem that the research community had was to translate those preclinical observations into clinical efficacy," he said, noting that Novacea met its target enrollment in the Phase II/III trial in December.

"Our plan is to follow those patients for six months after the last patient [enrolled]," Goodwin told BioWorld Today. "We should be looking at the data in the summer of this year."

The other compound, AQ4N, was in-licensed last month from Cambridge, UK-based KuDOS Pharmaceuticals Inc., and Novacea expects to start a Phase I trial in the first half of this year. The intravenous treatment is described as a topoisomerase II inhibitor and DNA intercalator in its active form, called AQ4, and it starts working only when it makes contact with hypoxic, or oxygen-starved, cells in tumors. (See BioWorld Today, Dec. 12, 2003.)

KuDOS has the drug in Phase I trials in the UK in esophageal cancer, testing AQ4N by itself and in combination with radiation. "We're currently evaluating what direction to add to that approach," Goodwin said.

"Given the stage of development DN-101 is at right now, we are currently spending at a rate that's higher on DN-101 than we will for the next year or so on AQ4N," he added.

The financing was led by Apax Partners, of London, and Eliot Charles from the firm has joined Novacea's board. Charles was director of business development at South San Francisco-based Genentech Inc., and worked with Goodwin there.

"[Apax] had been looking for a company like Novacea, a clinical-stage product story, for quite some time," Charles told BioWorld Today. "The management team is very strong. Three guys have been vice presidents of well-to-do biotech companies focused in cancer."

DN-101 proved as tantalizing to Apax as it had to Novacea.

"There's been a lot of research in the area, but there's always been some difficulty in getting the desired effects as an anticancer agent," Charles said. Goodwin noted calcitriol is approved at low doses for treatment of secondary hyperparathyroidism in chronic renal insufficiency. "It's been approved in very low doses for daily administration to maintain the normal balance of calcium in the body," he added.

Novacea's accomplishment, Charles said, "has been to come up with a way of getting the anticancer effects without getting the hypercalcemia" - the risk with calcitriol at higher doses.

"It's what they call high-dose pulsatile administration," he said, and involves timing and formulation of the compound. "It's like any other drug in a lot of ways," he added. "You have to get the right pharmacokinetics."

Also participating in the round were existing investors, including Domain Associates, of Princeton, N.J.; New Enterprise Associates, of Menlo Park, Calif.; Versant Ventures, also of Menlo Park; Sofinnova Ventures, of San Francisco; and ProQuest Investments, of Princeton.