AVI BioPharma Announces Commencement of Dosing in Clinical Trial for Duchenne Muscular Dystrophy

AVI BioPharma, Inc. (Nasdaq:AVII), today announced dosing of the first patient in a proof-of-principle clinical trial using AVI-4658, AVI’s lead drug candidate for Duchenne muscular dystrophy (DMD), based on the company’s proprietary ESPRIT (Exon Skipping Pre-RNA Interference Technology) drug platform. AVI-4658 is designed to skip exon 51 of the dystrophin gene, and thus benefit DMD patients with certain types of mutations that impair the function of dystrophin, a key protein in muscle cells. The trial is being conducted by research teams at the Imperial College London, in collaboration with the United Kingdom-based MDEX Consortium. The trial will include up to nine boys with DMD, each of whom will receive a single intramuscular (IM) administration of the drug. Two to three weeks following the injection, the muscle will be biopsied and examined for molecular evidence of corrected dystrophin production. Preclinical studies have demonstrated that AVI-4658 restores proper RNA reading frame and production of dystrophin in cells from patients with certain types of deletions in the gene that codes for dystrophin production. This trial will be the first to assess the drug’s effect in patients. The principal investigator for the U.K. study is Professor Francesco Muntoni, Department of Paediatrics, Hammersmith Hospital Campus, Imperial College, London. The coordinating investigator of the project is Professor Dominic Wells, M.A., VetMB, Ph.D., MRCVS, Department of Cellular and Molecular Neuroscience, Imperial College Faculty of Medicine. Imperial College will serve as the sponsor for the trial, with AVI BioPharma serving as its clinical development collaborator. "We are pleased that this clinical trial in DMD is now moving forward. We are simultaneously moving toward initiating clinical trials evaluating longer-term systemic administration of AVI-4658,” said K. Michael Forrest, interim chief executive officer of AVI. AVI recently announced it has received a translational research grant of $2.45 million from Charley’s Fund to support the selection and development of a lead molecule designed to skip exon 50 and restore production of functional dystrophin. This therapeutic approach is similar to that of AVI-4658, but targets patients with a different set of mutations. In addition, in November, AVI announced that the U.S. Food and Drug Administration (FDA) granted orphan drug designation for AVI-4658 for treatment of DMD. Earlier this month, the FDA also granted Fast Track status to the same product candidate. In parallel with the U.K. study, AVI is moving toward initiating clinical trials evaluating longer-term systemic administration of AVI-4658. AVI’s DMD research and development programs are being conducted in conjunction with the company’s DMD cross-licensing and development partner, Ercole Biotech Inc. About ESPRIT Technology In normal genetic function, gene transcription produces a full-length pre-RNA that is then processed to a much shorter and functional messenger RNA. The mRNA is the template for creating a protein. During pre-RNA processing, packets of useful genetic information, called exons, are snipped out of the full-length RNA and spliced together to make the functional mRNA template. AVI’s proprietary third-generation NEUGENE® chemistry can be used to target splice-joining sites in the pre-RNA, thus forcing the cell machinery to skip over targeted exons, providing altered mRNA, which in turn produces altered proteins. In some diseases, such as DMD, skipping an exon can restore a proper RNA reading frame and restore at least partial function of the protein to overcome the devastating clinical consequences of the mutation. About Duchenne Muscular Dystrophy DMD is the most common fatal genetic disorder to affect children around the world. It is a devastating and incurable muscle-wasting disease associated with specific inborn errors in the gene that expresses dystrophin, a protein that is an essential component for striated muscle function. When dystrophin is missing or nonfunctional due to a mutation in coding of the dystrophin gene, as it is in DMD, the result is membrane leakage and fiber damage, ultimately leading to degeneration and death of the muscle fiber. There is no cure or effective treatment for DMD. Approximately one in 3,500 boys is born with DMD, and an estimated 15,000 to 20,000 children are afflicted in the United States alone. About AVI BioPharma AVI BioPharma develops therapeutic products for the treatment of life–threatening diseases using third–generation NeuGene antisense drugs and ESPRIT exon skipping technology. AVI's ESPRIT technology is initially being applied to potential treatments for Duchenne muscular dystrophy. AVI's NeuGene compounds are also designed to treat cardiovascular restenosis, and aid in Coronary Artery Bypass Graft (CABG) procedures. In addition to targeting specific genes in the body, AVI's antiviral program uses NeuGene antisense compounds to combat disease by targeting single–stranded RNA viruses, including Marburg virus, Ebola Zaire virus, and H5N1 avian influenza virus. More information about AVI is available on the company's Web site at www.avibio.com. 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