AVI BioPharma Announces Clinical Study Results Providing the First Definitive Evidence of Antisense Efficacy in Humans.

Business Editors and Health/Medical Writers

PORTLAND, Ore.--(BW HealthWire)--May 7, 2002

NEUGENE Antisense Targeting Liver Enzyme Cytochrome P450 Alters

Gene Expression

AVI BioPharma, Inc. (Nasdaq:AVII)(Nasdaq:AVIIW)(Nasdaq:AVIIZ) today announced potentially far-reaching results from a clinical study targeting a critical liver enzyme, showing that the company's proprietary NEUGENE(R) antisense can be used to regulate drug metabolism.

The results come from a recently completed 96-patient study in which AVI's NEUGENE antisense compound was used to target cytochrome P450 3A4, an enzyme responsible for the metabolic breakdown of approximately 50 percent of current FDA-approved drugs. As predicted, inhibition of the expression of cytochrome P450 significantly changed the metabolism of a test drug, BuSpar(R) (buspirone HCl, USP, Bristol-Myers Squibb), in trial participants.

"This study provides the first clear evidence that antisense can change gene expression in humans," said Patrick L. Iversen, Ph.D., AVI's senior vice president of research and development. "This is important since virtually all human diseases are related to gene expression and we have now established that antisense can predictably alter gene expression in man. Formal evidence of how this technology works is critical because it establishes the platform advantages of NEUGENE antisense compounds."

AVI obtained evidence of antisense efficacy by manipulating the metabolism of BuSpar(R) in trial participants. As a result, this study also provides a platform for regulating the metabolism of a wide variety of drugs used in the treatment of cancer, cardiovascular disease, inflammation and infection.

"These exciting results confirm two key elements of AVI's antisense technology platform," said Denis R. Burger, Ph.D., AVI's CEO. "First and foremost, we believe this is the first formal proof that antisense works in man. But equally important is the significant down-regulation of drug metabolism in humans, an effect that could be used enhance efficacy, adjust dosing regimens, and improve the safety profile of certain drugs. It also may be used to improve the pharmacokinetics of drugs coming off patent, thereby gaining new patent life."

The trial subjects were divided into two groups, with the first group establishing the safety of the NEUGENE treatment via dose escalations with two routes of administration. In that portion of the trial, there were no drug-associated toxicities in any of the 48 patients, all of whom were monitored for adverse events, organ function and laboratory results.

"This was a large, first-in-man study of an antisense drug targeting an important liver enzyme," said David H. Mason, Jr., M.D., AVI's senior vice president of clinical development and regulatory affairs. "This was one of the cleanest studies of its type, from a safety point of view, that I have observed in 15 years of doing clinical studies. It provides further support for our observations that NEUGENE antisense agents are very well tolerated."

The second group of 48 subjects was tested for the effect of down-regulating the target enzyme, and that enzyme's relationship to the pharmacokinetics (PK) of BuSpar. When the PK of BuSpar in each subject was compared before and after NEUGENE administration, AVI demonstrated that cytochrome P450 was inhibited in a dose-dependent fashion as measured by the altered metabolism of BuSpar.

Together, these data show that NEUGENE antisense was transported by the bloodstream, entered the liver, and was taken up by liver cells in sufficient concentration to find the messenger RNA target and form an inhibitory duplex, which blocked ribosomal synthesis of new enzyme. This resulted in a predictable down-regulation of drug metabolism, expressed as a longer half-life and increased blood level of BuSpar in the patient population.

Together with preclinical studies, AVI has now shown sequence-specific inhibition of cytochrome P450 in four species, including man. Publication of the preclinical work has appeared in Current Opinion on Molecular Therapeutics 3(3): 2001. At the American Society for Pharmacology and Experimental Therapeutics meeting held recently in New Orleans, AVI presented supporting data showing that NEUGENE antisense altered the metabolism of paclitaxel and cyclosporin in a predictable manner. The current study will be presented at scientific forums later this year and submitted for publication in peer-reviewed medical and scientific journals.

Metabolic systems such as the family of cytochrome P450 enzymes process thousands of compounds in the body. CYP3A4, a member of the P450 family, is responsible for metabolism of about 50 percent of clinically-relevant drugs and is the most important and widely implicated enzyme in the arena of drug metabolism and disposition.

Buspirone, the drug used in this trial, is typically used to treat anxiety disorders and is sold in the United States by Bristol-Myers under the trade name BuSpar. The clinical trial was conducted in Northern Ireland by MDS Harris, a contract research organization that has conducted previous studies for AVI in the United States.

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(R), 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(TM), 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 Phase I/II trials for cancer and polycystic kidney disease. AVI has recently completed a Phase I NEUGENE antisense study that successfully down-regulated the liver enzyme cytochrome P450 and modified drug metabolism. 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.