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Prepared Witness Testimony The House Committee on Energy and Commerce
SARS: Assessment, Outlook, and Lessons Learned
Subcommittee on Oversight and Investigations
Dr. Denis R. Burger Ph.D.
Good afternoon and thank you for the introduction. I'm Denis Burger, CEO of AVI BioPharma. AVI is a biopharmaceutical company with headquarters in Portland, Oregon, with research and manufacturing facilities in Corvallis, Oregon. I'd like to thank the committee for inviting me to participate in today's hearing. It is an honor to share information about our science, technology and vision as you endeavor to understand and effectively address the spread of SARS. To begin, I'd like to turn briefly to the research and development AVI has been conducting since our company was founded in the early 1980s. AVI's drug development platform, a technology called antisense, enables us to develop therapeutics to address a range of life-threatening illnesses. Antisense technology is now beginning to reveal its potential. AVI is conducting clinical trials to evaluate antisense drugs against cardiovascular disease, polycystic kidney disease and cancer, but it is our application of antisense to viral infections in the past two years that is most relevant in our discussion of the spread and containment of SARS. I'd like to cover two key points in my testimony. First, AVI's antisense drugs target and inhibit the source of infection, not just the symptoms. In the case of SARS, the infection is caused by a single-strand RNA virus, a coronavirus. Second, the way we develop antisense drugs represents a new kind of rapid response therapeutics that we believe may have significant impact in today's threatening viral landscape. We are making specific antibiotics for viruses. AVI's NeuGene antisense drugs are like key blanks that can be cut precisely to match a disease's lock. They are made from snippets of DNA-like material known as oligonucleotides, or "oligos," the technical term for a stretch of genetic material. Each antisense drug is designed to block the activity of a particular gene or organism responsible for disease, whether human, bacterial or viral. When a NeuGene compound comes in contact with its viral target, it binds to specific portions of the sequence and, like fabric caught in a zipper, prevents the organism from replicating. Once the SARS outbreak was attributed to a human coronavirus, the scientists at AVI knew there was a good chance our technology would apply. We have spent the past several years researching the use of antisense on other single-strand RNA viruses, including hepatitis C virus, calicivirus and West Nile virus, and have had success in animal "outbreak" trials against two of those targets. In fact, we have completed preclinical testing for our West Nile virus compound and expect to file an Investigational New Drug (IND) application with the FDA later this year. Earlier this winter AVI initiated preclinical studies evaluating our antisense compounds against two animal variants of the coronavirus and achieved antiviral activity against these targets in culture. As a result, we knew that once the sequence of the new human variant was identified, we could rapidly synthesize and purify research quantities of a coronavirus antisense drug for testing in culture or in an animal model. We accomplished this in less than two weeks, a response time faster than any other technology I'm aware of. The developmental process I'm describing represents a new way to shut down viral infections. Rather than simply addressing the symptoms of the disease, NeuGenes actually slow the rate of infection by targeting and shutting down the virus's replication mechanism. This reduces viral "load" in the body and gives the immune system a chance to mount an effective response. In the case of the SARS virus, we all witnessed the rapid international effort to determine the virus's genetic structure, and we've heard about possible mutations in that structure. Another advantage of the antisense approach is that we are able to target portions of the viral sequence that we believe are conserved during mutations of the organism. This is certainly true of hepatitis C virus and the species-jumping calicivirus, two of our first viral targets, which have shown mutations. In nine clinical trials for the nonviral indications I mentioned earlier, we have achieved a positive safety record with no drug-related adverse effects to the approximately 200 patients we have treated. In the case of viral antisense drugs, the viral gene sequence we target is not found in the human genome, so the body simply does not recognize or process the drug unless the viral target is present. We have confidence in the safety profile of our antisense chemistry, but I should add that we have not yet tested viral antisense in human subjects. The importance of this type of rapid response platform for viral outbreaks should not be understated. We hope to learn a great deal from the testing of our compounds in the coming weeks and months, and have made our coronavirus antisense available on a limited basis to other WHO-affiliated laboratories. We are committed to undertaking the broadest evaluation of the compound possible, both because the demographics of the disease demand rapid and decisive response and because replication of results is critical. AVI's approach to viral therapeutics is different and new, but it is founded on 20 years of solid scientific research. We are making progress in all aspects of our development platform, but the opportunity to address a public health issue of this magnitude is work we embrace and that we plan to devote considerable resources toward. We truly hope to make a difference in the treatment of SARS, and appreciate your focus on the subject.
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