Assistant Managing Editor

The challenge in treating cancer has been delivering cell-killing agents to tumors while sparing normal tissue, and Cyterix Pharmaceuticals Inc., an April 2010 start-up, is moving toward the clinic with a new targeted approach by taking advantage of extra-hepatic cytochrome P450.

While cytochrome P450 enzymes have been recognized for a while on normal tissues – in fact, they're also the major enzymes involved in drug metabolism and have been responsible for more than one Phase I failure in the world of biotech R&D – the extra-hepatic cytochrome P450s, identified by the Human Genome Project, are linked specifically to tumors.

Those enzymes, which the firm has dubbed OncoCYP, are overexpressed during the malignant progression of most cancers and are found both on solid tumors and hematological malignancies, said Cyterix co-founder and CEO Steven Everett, who invented the firm's prodrug discovery approach while serving as the head of drug discovery and translational research at the University of Dundee in Scotland.

Everett's co-founders also brought expertise to the table. Paul Ortiz de Montellano, who serves on the scientific advisory board, was well versed in cytochrome P450 biochemistry, while the late John Curd had formerly held the chief medical officer position at Threshold Pharmaceuticals Inc., a company working on prodrug technology.

Cyterix's platform was licensed exclusively from the Dundee university, going straight from academia to the start-up in what Everett called a "very smooth" transaction. The new firm then settled in the San Francisco area, where Everett had accepted a position as an adjunct faculty member at the University of California, San Francisco.

Its U.S. location also put the company in close proximity to venture capital firms, which helped when Cyterix went out seeking its first round of funding. Earlier this month, it closed a $9.2 million Series A round from the Column Group and SV Life Sciences, both of San Francisco.

"There are not so many early stage investors these days," Everett acknowledged, but said the initial funding should support investigational new drug application-enabling studies with the lead programs, while allowing the firm to further build out its platform.

The Series A should last Cyterix a couple of years, though the current investors have indicated that they might be willing to step up for a Series B round if needed next year, he added. And they've "taken a broader view of the technology," beyond the lead compound.

Cyterix' two lead programs consist of prodrugs, each containing different, though approved cytotoxic agents. The prodrug technology is designed so that the agents remain inactive in prodrug form, preventing harm to healthy tissue. The cytotoxic drugs, however, are activated by the OncoCYP on tumor cells.

Once they are activated, they "fragment to release a warhead, which kills the tumor cells," Everett said, offering the analogy that it's both "carpet and precision bombing."

Plus, if the prodrug can deliver that warhead to the tumor only, that would allow for greater doses of the cytotoxic agent to be administered.

Cyterix has not disclosed specific cancer indications, and Everett said Phase I trials likely will involve all comers "because the target enzyme has a high frequency in many different types. We're less worried about picking [a particular cancer]," he added. "We want to make sure we're picking patients with sufficient levels of enzyme."

Because patients' tumor cells will need to carry the OncoCYP enzyme, a companion diagnostic likely will be developed as well.

Cyterix expects to complete investigational new drug application-enabling studies by mid-2012 and move into the clinic by early 2013.

For now, Cyterix is running pretty lean. "We have a minimum number of employees and a lot of consultants," Everett said. Though, as programs "advance it the next six months, we'll be building out the firm."