MDRNA, Inc. Lead Candidate Demonstrates In Vivo Efficacy against Seasonal and Pandemic Flu Strains
- Category: DNA RNA and Cells
- Published on Wednesday, 13 August 2008 02:00
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Intranasal administration of an siRNA in a proprietary delivery system produces greater than 99% reduction in viral titers and a 100% survival benefit against Avian Flu
BOTHELL, WA, USA | August 13, 2008 | MDRNA, Inc. (Nasdaq: MRNA) announced today positive in vivo efficacy data on its proprietary RNAi-based therapeutic for the treatment of multiple strains of influenza A virus in animal models. The in vivo data were presented by Shaguna Seth, Ph.D., Associate Director at MDRNA, Inc., at the XIV International Congress of Virology in Istanbul, Turkey.
"Our Influenza Program is a superb example of the convergence of both our novel RNAi technologies and proprietary drug delivery capabilities," stated J. Michael French, Chief Executive Officer at MDRNA. "In order to accelerate development of this important lead candidate, capitalize on the significant research effort conducted by our team and fully realize its commercial potential as a therapeutic against a pandemic influenza outbreak; we are seeking a strategic partnership with a company focused in the biodefense or infectious disease area."
The data reported at the conference indicate that MDRNA's Dicer substrate siRNAs are highly active against multiple strains of influenza A virus including seasonal H3N2 and highly pathogenic H5N1 strains. The lead Dicer siRNA also elicited high inhibition activity against Tamiflu-resistant strains of influenza virus. Treatment with MDRNA's lead candidate before and after infection resulted in a 100 to 1000-fold (99%) reduction in viral titers, thus demonstrating their potential use as a therapeutic as well as a prophylactic. Formulated Dicer substrates dosed intranasally showed significant reduction in viral replication; leading to lower viral titers, decreased clinical signs, and increased survival in infected mice and ferret models of influenza. MDRNA's proprietary delivery formulations provided greater therapeutic benefit at lower siRNA dose levels, as compared to siRNA dosed without formulation.
"There is a significant need for a safe and effective therapy that can target highly pathogenic influenza strains such as Avian flu and to have that therapy stockpiled for a pandemic outbreak," said Steven C. Quay, M.D., Ph.D., Chief Scientific Officer of MDRNA. "Capitalizing on both our proprietary RNAi technologies and our proprietary drug delivery capabilities, we have developed an RNAi-based compound that can address all strains of influenza A virus by targeting conserved regions of the influenza viral genome. Ongoing and future studies, in collaboration with the U.S. Centers for Disease Control and Prevention, will continue to analyze the intranasal delivery of our Dicer substrate siRNA for influenza and provide us further insight into the strength of our therapeutic and delivery approaches."
Influenza infects millions of people worldwide and results in hundreds of thousands of deaths every year. The World Health Organization and the U.S. Centers for Disease Control and Prevention are concerned about the potential for a major global pandemic, such as the 1918 "Spanish Flu" in which up to 50 million people may have died worldwide. A global pandemic flu emerges from a sudden change in the influenza viral genome resulting in a new viral strain for which there may be no pre-existing immunity or vaccine. Vaccines currently represent the mainstay of flu prevention, but vaccines have two key limitations. First, they are developed against individual, known circulating strains of influenza and therefore may not be effective against new viral strains. Second, vaccines are produced using a lengthy process requiring incubation in chicken eggs. Hence, a vaccine against a new viral strain would not be readily available. Influenza, like many viruses, has the potential to mutate and become resistant to the very drugs developed to treat influenza. The potential advantage of RNAi therapeutics over traditional antiviral drugs is that siRNAs can be developed to target the conserved region of the influenza viral genome. This means that an RNAi therapeutic would be expected to be effective against all emerging strains of the influenza virus since the "conserved region" very rarely mutates. Therefore, it would be possible to stockpile an effective RNAi-based therapeutic in advance of a global influenza pandemic. In addition to their potential for treating a pandemic influenza outbreak, RNAi therapeutics could also serve as a treatment for the more common strains responsible for seasonal flu that can result in hospitalization and death each year.
About Dicer Substrates and RNA Interference (RNAi)
RNA interference, or RNAi, is a naturally occurring pathway inside of cells that can be used to turn off the production of a specific protein or proteins to treat a wide variety of diseases. Dicer substrates are slightly longer double stranded RNAs than conventional siRNAs and are directed to a step in RNAi process before RISC formation that produces a more potent knockdown of the targeted gene. In the case of an RNAi directed against influenza, the targets are proteins critical for viral replication. By turning off the production of such proteins, the spread of infection is prevented or slowed.
About MDRNA, Inc.
MDRNA is a biotechnology company focused on the development and commercialization of therapeutic products based on RNA interference (RNAi). Our goal is to improve human health through the development of RNAi-based compounds and drug delivery technologies that together provide superior therapeutic options for patients. Over the past decade, we have developed substantial capabilities in molecular biology, cellular biology, lipid chemistry, peptide chemistry, pharmacology and bioinformatics, which we are applying to a wide range of RNAi technologies and delivery approaches. These capabilities plus the in-licensing of key RNAi-related intellectual property have rapidly enabled us to become a leading RNAi-based therapeutics company with a pre-clinical pipeline in key therapeutic areas including oncology, metabolic disorders and inflammation. Through our capabilities, expertise and know-how, we are incorporating multiple RNAi technologies as well as peptide- and lipid-based delivery approaches into a single integrated drug discovery platform that will be the engine for our clinical pipeline as well as a versatile platform for establishing broad therapeutic partnerships with biotechnology and pharmaceutical companies. We are also investing in new technologies that we expect to lead to safer and more effective RNAi-based therapeutics while aggressively building upon our broad and extensive intellectual property estate. By combining broad expertise in siRNA science with proven delivery platforms and a strong IP position, MDRNA is well positioned as a leading RNAi-based drug discovery and development company. Additional information about MDRNA, Inc. is available at http://www.mdrnainc.com.
SOURCE: MDRNA, Inc.