Marina Biotech Reports Significant Developments in Its Ability to Develop Both microRNA Mimetics and Antagonists
BOTHELL, WA — (MARKET WIRE) — 07/08/11 — Marina Biotech, Inc. (NASDAQ: MRNA), a leading nucleic acid-based drug discovery and development company, reported data demonstrating that its proprietary technologies, its liposomal-based delivery technology SMARTICLES® as well as its Conformationally Restricted Nucleotide (CRN) technology, support the development of both microRNA (miRNA) mimetics and antagonists. Systemic administration of a SMARTICLES formulated miRNA mimetic in an orthotopic liver tumor model demonstrated inhibition of tumor growth, as indicated by a decrease in a systemic liver tumor biomarker, alpha-feto protein, and a decrease in tumor weight of greater than 80%. In separate work, the Company demonstrated that incorporation of CRN in miRNA antagonists increased potency with an approximate 60-fold improvement in the IC50. MicroRNAs have pivotal roles in cell biology, including diseases such as inflammation and cancer, and involve both over-expression and under-expression of specific miRNAs. Thus, effective intervention may involve a mimetic to replace an under-expressed miRNA or an antagonist to inhibit the activity of an over-expressed miRNA. The data were presented by Michael V. Templin, Ph.D., Senior Vice President, Preclinical Development at Marina Biotech, Inc., at the 2nd RNAi Research & Therapeutics Conference, July 7-8, 2011 in San Francisco, CA.
“We continue to demonstrate the breadth of our nucleic acid-based drug discovery engine,” stated Dr. Templin. “Pharmaceutical companies are clearly interested in developing nucleic acid therapeutics to meet their ‘undruggable target’ needs. The ability to apply multiple oligonucleotide modalities in response to a particular undruggable target, therapeutic indication and patient phenotype is critical for an effective drug discovery engine since it provides pharma options upon which they can make decisions based on both the scientific and business risks associated with each nucleic acid-based approach. This recent data demonstrates our ability to create proprietary miRNA therapeutics; both mimetics and antagonists. We have now demonstrated the capability to develop a variety of double-stranded and single-stranded oligonucleotide compounds harnessing several biological pathways including RNA interference. This capability, provided through proprietary chemistry and delivery technologies, is unique to Marina Biotech and significantly sets us apart from others in this space.”
SMARTICLES define a novel class of liposomes: fully charge-reversible particles for delivery of active substance (siRNA, antisense, decoy, etc.) inside the cell either by local or systemic administration. SMARTICLES are designed to ensure: (1) stable passage through the bloodstream and (2) release of the nucleic acid payload within the target cell to exert its therapeutic effect.
About Conformationally Restricted Nucleotides
Conformationally Restricted Nucleotides are analogs in which a chemical bridge connects the C2′ and C4′ carbons of ribose. Ribose, a five-carbon ring-like structure, forms the central region of a nucleotide (comprised of a nucleobase, ribose, and phosphate group). The chemical bridge in the ribose of a CRN locks the ribose in a fixed position, which in turn restricts the flexibility of the nucleobase and phosphate group. Substitution of a CRN within an RNA- or DNA-based oligonucleotide has the advantages of increased hybridization affinity and enhanced resistance to nuclease degradation. CRN technology provides a direct means of developing highly potent and specific nucleic acid-based therapeutics to target messenger RNAs or microRNAs. These targets represent disease pathways that are typically “undruggable” or “difficult to target” by small molecule or monoclonal antibodies, and are appropriate for disease areas with significant unmet needs, such as inflammation, metabolic disease, and cancers. The CRN patent estate consists of two issued patents broadly covering CRN compounds and CRN containing oligonucleotides, and one pending patent application covering additional applications of CRNs.
About Marina Biotech, Inc.
Marina Biotech is a biotechnology company, focused on the development and commercialization of RNA interference- (RNAi) and RNA-based therapeutics. The Marina Biotech pipeline currently includes a clinical program in Familial Adenomatous Polyposis (a precancerous syndrome) and two preclinical programs — in bladder cancer and malignant ascites. Marina Biotech entered into an exclusive agreement with Debiopharm Group for the development and commercialization of the bladder cancer program. Marina Biotech’s goal is to improve human health through the development of RNAi and RNA-based compounds and drug delivery technologies that together provide superior therapeutic options for patients. Additional information about Marina Biotech is available at http://www.marinabio.com.
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