West Coast Editor

Taking aim at cancer by way of inhibiting the Akt protein kinase, Rexahn Corp. late last month started a Phase I trial with its lead drug candidate, RX-0201.

"We're in the middle of it right now," said George Steinfels, chief business officer and senior vice president of clinical development at Rockville, Md.-based Rexahn, which was founded in 2001 and has 15 employees. "My goal is to have an abstract we can talk about in June of next year."

The clinical trial program at Georgetown University Hospital Lombardi Cancer Center in Washington tested intravenous RX-0201 to check safety and pharmacokinetics while watching for any antitumor responses.

Overactivation or overexpression apparently promotes tumor cells, blocks apoptosis and helps cancer grow more blood vessels, and RX-0201 attacks Akt's messenger RNA and protein, stopping signals so the disease can't go forward. In preclinical animal studies, the well-tolerated compound suppressed cancer growth in brain, breast, cervix, liver, lung, ovarian, prostate and stomach tumors, with no severe side effects.

Akt inhibitors hardly have gone unnoticed by other biotechnology firms, a handful of which have compounds at the preclinical stage and further along than Rexahn's. One such drug was part of New York-based Keryx Biopharmaceuticals Inc.'s buyout of Access Oncology Inc., also of New York. (See BioWorld Today, Jan. 9, 2004.)

KRX-0401 is being tested in nine Phase II single-agent trials in six tumor types, including breast, prostate, melanoma, pancreatic, sarcoma and head and neck cancer. The National Cancer Institute in Bethesda, Md., is conducting the studies under a Collaborative Research and Development Agreement.

"If you look at cancer therapy in the past, everything was cytotoxic and non-targeted," Steinfels noted. "Now, everybody's picking a target, and Akt is one of those targets that's poking its head out. Once Akt gets activated, products like Iressa, Herceptin, Erbitux may not be as effective. At the end of the day, we may be all right when we start combining these products together in a multidrug kind of cocktail," as with AIDS drugs.

Not all of Rexahn's eggs are in the Akt basket, he added. Next in the clinic will be RX-0047, which targets a site on the HIF-1 gene, blocking hybridization and, thereby, the ability of the cells to produce HIF-1, which in turn kills cancer. And there's more behind that.

"The third [effort] in line is working on cell-cycle control," Steinfels said. Everything points to refining cancer therapy as "a rifle shot as opposed to a shotgun blast," he added. "I don't see it changing. What's the alternative? [Earlier, cytotoxic approaches] have shown us you can kill cancer, but you kill the host, too."

In March 2003, Rexahn entered a research and collaboration deal with Rexgene Biotech Co. Ltd., of Seoul, South Korea, focused on registering RX-0201 for use and sale in the Republic of Korea and elsewhere in Asia. Rexahn got $1.5 million up front and the promise of royalties. Later in 2003, the firm raised $2 million from KT&G Corp., also in Korea, through a private placement of 500,000 shares, but Steinfels would not comment specifically on how long it can operate with the funds on hand.

"I have two answers to that - you never have enough money, and we have enough to operate," he said.

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