AVI BioPharma Initiates New Round of Human Clinical Trials With NeuGene Antisense Targeting Drug Metabolism

PORTLAND, Ore. - Nov. 5, 2002 - AVI BioPharma, Inc. (Nasdaq: AVII, AVIIW, AVIIZ), today announced the initiation of two Phase I human clinical trials of its proprietary NeuGene® antisense technology. Both studies, which follow an initial phase I trial completed in March 2002, will evaluate the safety and efficacy of AVI's antisense drug AVI-4557 in modifying the function of a liver enzyme critical to the metabolism of many drugs. MDS Pharma Services, a contract research organization in Belfast, Ireland, will conduct the trials.

AVI-4557 targets the liver enzyme cytochrome P450, which regulates the breakdown of approximately 50 percent of the drugs currently approved by the Food and Drug Administration (FDA). Analysis of the initial clinical trial demonstrated the following:

  • Inhibition of the expression of the enzyme significantly changed the metabolism of a test drug, BuSpar® (buspirone hydrochloride, USP, Bristol-Myers Squibb), in a predictable manner.
  • Dose-dependent elevations in blood concentrations of NeuGenes was observed with both intravenous and subcutaneous administration.
  • AVI-4557 produced no adverse events at any dose level.

The new studies will involve higher doses of AVI-4557, as well as measurement of its effect on the metabolism of a new test drug, midazolam hydrochloride. Midazolam is typically used to relax patients before procedures such as colonoscopies or to treat seizures. It is sold under the trade name Versed™ in the United States. The studies being initiated will evaluate a single 300 mg dose and five repeated 90 mg doses (once daily for five days) of AVI-4557, delivered by intravenous infusion.

"We expect the new studies to demonstrate that NeuGene compounds are safe at higher doses and multiple repeated doses," said David H. Mason, Jr., M.D., senior vice president of Clinical Development and Regulatory Affairs at AVI. "Positive safety profiles are characteristic of morpholino antisense compounds."

"The safety and effectiveness data we expect to obtain from these studies are important to our research progress," said Denis R. Burger, Ph.D., CEO of AVI. "These studies will bolster our efforts to attract strategic alliances with pharmaceutical companies interested in improving the pharmacokinetics of their existing FDA-approved drugs, including those now coming off patent."

About AVI BioPharma

AVI BioPharma develops therapeutic products for the treatment of life-threatening diseases using two technology platforms: NeuGene antisense drugs and cancer immunotherapy. Its lead cancer agent, AVICINE®, a therapeutic cancer vaccine, has completed three Phase II trials in colorectal and pancreatic cancer and is initiating a Phase III pivotal trial in pancreatic cancer, with a supporting study in colorectal cancer. The first application of its NeuGene compounds, Resten-NG™, is designed to treat cancer, cardiovascular restenosis and other cell proliferation disorders by inhibiting the production of a cellular transcription factor, the oncogene c-myc. It is currently in Phase II trials for restenosis and in a Phase I/II trial for cancer. AVI has completed a Phase I NeuGene antisense study that successfully down-regulated the liver enzyme cytochrome P450 and modified drug metabolism, and also recently completed a Phase I/II trial in polycystic kidney disease. More information about AVI is available on the Company's Web site at http://www.avibio.com/.

"Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: The statements that are not historical facts contained in this release are forward-looking statements that involve risks and uncertainties, including, but not limited to, the results of research and development efforts, the results of preclinical and clinical testing, the effect of regulation by the FDA and other agencies, the impact of competitive products, product development, commercialization and technological difficulties, and other risks detailed in the Company's Securities and Exchange Commission filings.