Posted: October 7, 2008

MDRNA Advances RNAi Pipeline With Selection of Lead Candidate for Hypercholesterolemia Program

(Nanowerk News) MDRNA, Inc. announced today that it has advanced its RNAi pipeline with the selection of a Lead Candidate in its hypercholesterolemia program targeting Apolipoprotein B (ApoB). The compound, designated MDR-04227, was developed using MDRNA's propriety drug discovery engine, which is built on a broad and enabling intellectual property estate and an in-house novel and proprietary delivery technology.
"We continue to execute on our plan to advance our therapeutic programs toward human clinical development," stated J. Michael French, President and CEO of MDRNA, Inc. "The selection of a Lead Candidate in our hypercholesterolemia program reflects the strength of our drug discovery engine, specifically the rapid advances we've made in siRNA delivery. Further, I believe the speed and efficiency by which we can develop a lead candidate demonstrates our ability to utilize this drug discovery platform to support a broad therapeutic collaboration with a pharmaceutical partner. MDRNA's unique combination of technology, in-house capability and intellectual property portfolio permits us to broadly support a potential partner's needs and develop siRNAs directed against any human gene target."
MDR-04227 is a Dicer substrate siRNA formulated with a proprietary lipid-based delivery formulation derived from the Company's DiLA2 Platform. In a preclinical animal model of hypercholesterolemia, MDR-04227 was shown to be extremely potent with an IC50 of less than 100 pM. When formulated for systemic administration using DiLA2, MDR-04227 demonstrated approximately 85% knockdown in target messenger RNA of ApoB and a similar level of reduction of serum cholesterol following a single 1 mg/kg dose of siRNA. The Company has filed numerous patent applications relating to this siRNA construct and delivery formulation.
"Our lead selection process, whose multifaceted criteria include potency, cytokine induction, on-target specificity and resistance to nuclear degradation, has led to the selection of MDR-04227," commented Steven C. Quay, M.D., Ph.D., Chairman of the Board of Directors and Chief Scientific Officer. "MDR-04227 is formulated in our DiLA2 delivery technology and optimized for systemic delivery to the liver and gastrointestinal tract. The percentage of ApoB knockdown and reduction of serum cholesterol achieved in our animal model appears to exceed data in the published literature in which effects of this magnitude required doses of more than 2 mg/kg and often up to 5 mg/kg siRNA. We believe these results are a testament to the high potency of our Dicer substrate siRNAs as well as the robustness of the DiLA2 delivery platform."
About Hypercholesterolemia and ApoB
Hypercholesterolemia is a condition characterized by high levels of cholesterol in the blood. People with hypercholesterolemia have a higher risk of developing coronary artery disease, which occurs when excess cholesterol in the bloodstream is deposited in the walls of blood vessels, particularly in the arteries that supply blood to the heart. More than 34 million American adults have elevated blood cholesterol levels.
The ApoB gene provides instructions for making two versions of the apolipoprotein B protein, a short version called apolipoprotein B-48 and a longer version known as apolipoprotein B-100. Both of these proteins are components of lipoproteins, which are particles that carry fats and fat-like substances (such as cholesterol) in the blood. Research has shown that knockdown of the ApoB gene results in a significant lowering of cholesterol in the blood. People with familial hypobetalipoproteinemia, a condition in which ApoB synthesis is greatly reduced appear to be relatively protected from heart disease.
About the DiLA2 Platform
The DiLA2 Platform is MDRNA's proprietary platform for creating novel lipids from amino acids. The platform enables MDRNA to tailor the charge, linker and acyl chains such that the properties of the liposome are optimized for delivery to the target tissue of interest. In addition, the platform is amenable to attachment of various peptides to improve a variety of delivery characteristics including nanoparticle formulation, cellular uptake, endosomal release and cell/tissue targeting.
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
Source: MDRNA (press release)
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