Expanding its oncology pipeline, ProlX Pharmaceuticals Corp. acquired access to a class of early stage cancer compounds through agreements with three research labs.

The Tucson, Ariz.-based company licensed worldwide development and commercialization rights to the phosphatidylinositol-3 (PI3) kinase inhibitor wortmannin and semi-synthetic viridin analogues covered in a number of patents jointly owned by the University of Arizona, the University of Pittsburgh and the Burnham Institute in La Jolla, Calif.

"We're a company that's developing novel cancer therapeutics in the redox and survival-signaling arena," ProlX CEO Lynn Kirkpatrick told BioWorld Today. "So these agents being PI3 kinase fits very well in both the molecular targets that we're developing agents against, as well as in the development phase of our pipeline."

She said the newly licensed technology was developed through a National Cancer Institute program - the National Cooperative Discovery Program - to which ProlX contributes as a sponsor of the academic institutes. In return for access to the PI3 kinase technology, the company agreed to share revenues with the three institutions if it commercializes any of the agents covered under the license.

To that end, ProlX plans to continue the preclinical development of the lead agent in the PI3 kinase series, PX-866, and file an investigational new drug application late next year.

The company describes the semi-synthetic viridin analogue as a biologically stable, broad-spectrum product with pharmacokinetics that induce prolonged inhibition of tumor-PI3-kinase signaling following both oral and intravenous administration. Preclinical data published in the July 2004 issue of Molecular Cancer Therapeutics demonstrated PX-866's in vivo antitumor activity against ovarian and lung cancer human xenograft tumor models, and showed the agent potentiates the antitumor activity of cancer therapeutics and other treatment modalities.

"We definitely feel that from the biology of this type of agent," Kirkpatrick said, "that there is a lot of potential for utilizing it maybe as a single agent, but certainly in combinations where there are other targeted agents. Specifically, we know that these are in the colorectal area and lung cancers."

She said the discovery and development company, which employs a full-time staff of 10, eventually would look toward a partner for the compound's late-stage development. Privately held ProlX was founded in 1996 by Kirkpatrick, a chemist, as well as cancer pharmacologists Garth Powis and John Lazo. Powis serves as chairman, while Lazo sits on the company's scientific advisory board.

The company has sustained operations to date primarily through government grants, but Kirkpatrick acknowledged that a need for a first round of private financing could be on the horizon to fund operations going forward.

"We're actively examining a number of [funding] routes at this time," she said.

The company's lead candidate is PX-12, an inhibitor of thioredoxin that recently was evaluated in a Phase I trial. The company said thioredoxin is a human oncogene that adversely affects patient survival.

A Phase I trial is pending for the hypoxia-inducible factor-1-alpha inhibitor, PX-478. It is designed to prevent HIF-1-alpha induction, a process that stimulates the formation of new blood vessels, and starve the tumor of oxygen by preventing angiogenesis.

ProlX's preclinical pipeline includes PX-316, a product that inhibits AKT, which when activated provides a survival signal that protects cancer cells from apoptosis. The newly licensed PI3-kinase program also includes a number of backup molecules that are in preclinical development.

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