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Incara Catalytic Antioxidant Inhibits Tumor Regrowth Following Radiation Therapy

RESEARCH TRIANGLE PARK, N.C., July 14 /PRNewswire-FirstCall/ -- Incara Pharmaceuticals Corporation (BULLETIN BOARD: ICRA) has announced further data that demonstrate that the administration of a compound, AEOL 10113, from the company's class of proprietary catalytic antioxidants inhibits the regrowth of tumors following radiation therapy in a mouse model of cancer. Recent experiments, under the direction of Mark W. Dewhirst, DVM, Ph.D, at the Departments of Radiation Oncology and Pathology at Duke University Medical Center, have for the first time demonstrated that this effect results from preventing radiation induced up-regulation of hypoxia inducible factor-1 (HIF- 1). Dr. Dewhirst's group has shown that irradiated tumors produce HIF-1, initiating an angiogenesis response that enables the tumor to regrow. In an experimental mouse tumor model, when AEOL 10113 was given once a day for 3 days, it blocked HIF-1 activation in tumors following radiation therapy. This prevented angiogenesis of the tumor and tumor growth was delayed. These results were published in the May 2004 issue of the journal Cancer Cell.

"The finding of this mechanism whereby an antioxidant mimetic can turn off HIF-1 in tumors gives us a specific target to go after that is centrally important in regulation of blood vessel growth. The mechanism is specific for tumors since HIF-1 is not involved in regulating vessels in normal tissues. Thus we have an opportunity for a unique therapeutic gain in the treatment of tumors," said Dr. Dewhirst.

"Irradiated tumors adapt to the radiation damage by up-regulating the HIF- 1 mediated pathway to stimulate blood vessel regrowth and thereby enhance the tumor's blood supply. We had previously observed that AEOL 10113 protects normal tissue from radiation therapy damage. These data from Dr. Dewhirst's laboratory show a new second mode of action of our compound that makes the tumor less able to recover from radiation therapy. We are very excited by the prospects of this new mechanism of action for our compound," said James D. Crapo, M.D., Incara's CEO.

AEOL 10113 is a potent catalytic antioxidant that breaks down reactive oxygen species including superoxide, hydrogen peroxide and peroxynitrite. Compounds from Incara's antioxidant program have inhibited the growth of tumors in animal models of cancer as well as protected normal cells during animal models of radiation therapy. Incara has been awarded a Small Business Innovation Research (SBIR) Grant from the National Cancer Institute, a division of the National Institutes of Health (NIH), to study the anti-tumor and radiation-protective effects of Incara's catalytic antioxidants. Currently ongoing, the research funded by the grant will explore the ability of Incara's compound to inhibit the vascularization of tumors and to block damage to normal tissue from radiation therapy.

Incara ( http://www.incara.com/ ) is developing a new class of small molecule catalytic antioxidants that destroy oxygen-derived free radicals, believed to be an important contributor to the pathogenesis of many diseases. Incara's catalytic antioxidants have been shown to reduce damage to tissue in animal studies of ALS, stroke, cancer and chronic obstructive pulmonary disease.

Incara has filed an Investigational New Drug (IND) application with the FDA for its lead clinical compound, AEOL 10150. An IND is the first stage necessary to begin human clinical studies of compounds. The initial Phase 1 clinical trial will be for the possible treatment of amyotrophic lateral sclerosis (also known as ALS or Lou Gehrig's disease). ALS, the most common motor neuron disease, results from progressive degeneration of both upper and lower motor neurons and is usually fatal within 5 years.

The statements in this press release that are not purely statements of historical fact are forward-looking statements, and actual results might differ materially from those anticipated. These statements and other statements made elsewhere by Incara or its representatives, which are identified or qualified by words such as "intends," "likely," "will," "suggests," "expects," "might," "may," "believe," "could," "should," "would," "anticipates," "plans," "possible" or the negative of those terms or similar expressions, are based on a number of assumptions that are subject to risks and uncertainties. Important factors that could cause results to differ include risks associated with the uncertainties of scientific research, clinical trials and product development activities and the need to obtain funds for clinical trials and operations. These and other important risks are described in Incara's reports on Form 10-K, Form 10-Q and Form 8-K and its registration statements filed with the Securities and Exchange Commission. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Incara assumes no obligation to update the information in this release.

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