With the recent completion of a $3.6 million Series A round, start-up firm Metastatix Inc. is ready to move toward the clinic with its first program, a chemokine inhibitor designed to prevent tumor growth and cancer metastasis by blocking the CXCR4 receptor.

The financing, led by Atlanta-based H.I.G. Ventures, is expected to "take us up to filing an investigational new drug application," said Metastatix President and CEO Tony Shuker, who, along with Dennis Liotta, Mike Natchus, Jim Snyder and Hyansuk Shim, founded the company last year as a spin-out of Emory University in Atlanta.

Emory licensed to Metastatix the initial technology to develop compounds targeting CXCR4, a cell surface receptor that the founding scientists had been investigating for a few months before deciding that it was "a fantastic jumping off point for a commercial operation," Shuker said.

One of the founders, Liotta, previously had success with another compound emerging from Emory. He and two colleagues discovered Emtriva (emtricitabine), which Foster City, Calif.-based Gilead Sciences Inc. markets individually and as part of its once-daily, triple-drug regimen for HIV patients. Last year, Gilead purchased Emtriva's royalty interest from Emory in exchange for $525 million in cash. (See BioWorld Today, July 20, 2005.)

"The actual origins of [Metastatix] really were based on the fact that Dennis had been extraordinarily successful in converting academic research into commercial opportunities," Shuker told BioWorld Today, combined with the potential of CXCR4 as a biological target.

Naturally present on cells such as stem cells and liver cells, CXCR4 normally functions in growth and recovery. But, in cancer cells, it's produced "in much greater levels," Shuker said, which allows the diseased cells to "recruit blood vessels and move around the body."

It's that metastatic process, rather than the initial tumor, that often leads to the patient's death, he added.

Metastatix is developing compounds aimed at blocking CXCR4 from receiving a signal from a chemokine, specifically the SDF-1 chemokine that's found in areas such as the liver, lungs and bone marrow. The hope is that, by interrupting that signal, the compound could prevent the cancer from spreading and, possibly, from growing.

"We've been able to demonstrate in animal models that we can do both of those things successfully," Shuker said.

Unless a patient is in a diseased state, CXCR4 is expressed in very low levels, so Metastatix expects the oral, small-molecule drugs to be "extremely safe," he added.

A CXCR4 blocker likely would be administered in combination with another cancer therapy.

In addition to its cancer program, Metastatix is investigating the CXCR4 as an entry target in T-tropic HIV infection.

In that instance, the CXCR4 receptors are found on the surface of T-lymphocytes. The HIV viral particle "has a molecular probe that latches onto the CXCR4 receptor and uses that to trigger a cascade of molecular events that end up with the virus injecting its genetic information into the cell," Shuker said.

Metastatix is working on a compound to block that entry point. That program is in preclinical development.

Shuker said the company, currently staffed by seven employees, is focused on taking its molecules as far through development as possible before considering alternatives such as partnerships.

"We have a lot of confidence in this program," Shuker said, "and we hope that will give us some pretty attractive options."

To date, Metastatix has raised more than $4 million, including a research grant from the Georgia Research Alliance followed by a half-million dollar seed round from Atlanta-based Centrosome Ventures, Georgia Venture Partners, also of Atlanta, and the State of Georgia. Those existing investors also participated in the Series A.

Other Series A investors included: The Aurora Funds, of Durham, N.C.; CM Capital, of Brisbane, Australia; SR One, of West Conshohocken, Pa.; and MedImmune Ventures, of Gaithersburg, Md.

Bruce Robertson, of H.I.G. was named Metastatix chairman, and Doug Gooding, of Aurora; Ad Rawcliffe, of SR One; and Wayne Hockmeyer, of MedImmune, joined the company's board.