Marina Biotech (MRNA) Demonstrates In Vivo Dose-Dependent Efficacy and High Tolerability With a CRN-Substituted miRNA Antagonist

BOTHELL, WA — (Marketwire) — 10/19/11 — Marina Biotech, Inc. (NASDAQ: MRNA), a leading oligonucleotide-based drug discovery and development company, reported in vivo dose-dependent efficacy with a CRN-substituted miRNA antagonist, or antagomir, against microRNA-122 (miR-122). The efficacy in a rodent model was demonstrated by up to a 5-fold increase in AldoA, a well-known downstream gene regulated by miR-122. Downstream targets Glycogen Synthase I (GYS1) and Solute Carrier Family 7 member 1 (SLC7A1) were also elevated. The increase in these downstream gene targets was achieved by the sequestration of miR-122 by a high affinity CRN-substituted antagomir. In addition, the CRN-substituted antagomir, which was dosed for three consecutive days at up to 50 mg/kg/day, was extremely well tolerated in rodents as evidenced by normal serum chemistry parameters and no body weight changes.

“Dose-dependent and robust efficacy and tolerability at high doses are significant achievements in the development of both our CRN technology as well as our broad oligonucleotide-based drug discovery platform,” stated Richard T. Ho, M.D.-Ph.D, Executive Vice President, Research and Development at Marina Biotech. “Establishing proof-of-concept data enables us to use CRN technology for both single-stranded and double-stranded oligonucleotide-based therapeutic applications. This work also demonstrates that our proprietary CRN technology is well tolerated in a repeat dose regimen at high doses in a rodent model.”

MicroRNAs are a novel class of small non-coding RNAs that have been shown to regulate gene expression at the post-transcriptional level by binding to their target genes. The vast number of complex gene networks tightly regulated by microRNA includes cell growth, differentiation, and apoptosis. Low expression or overexpression of specific microRNAs can lead to abnormal expression of downstream target messenger RNAs causing physiological changes associated with certain disease pathologies. Inhibition of an aberrant microRNA with an antagonist, or supplementation with a microRNA mimetic, are novel approaches to develop much needed therapeutic modalities for cancers and other diseases.

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 oligonucleotide-based therapeutics to target messenger RNAs or microRNAs. These targets connect disease pathways that are typically “undruggable” or “difficult to target” with small molecules or monoclonal antibodies, and may be critical in disease areas with significant unmet needs, such as inflammation, metabolic disease, and cancers. Marina Biotech’s 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 oligonucleotide-based therapeutics utilizing multiple mechanisms of action including RNA interference (RNAi) and messenger RNA translational blocking. 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 oligonucleotide-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.

Forward-Looking Statements

Statements made in this news release may be forward-looking statements within the meaning of Federal Securities laws that are subject to certain risks and uncertainties and involve factors that may cause actual results to differ materially from those projected or suggested. Factors that could cause actual results to differ materially from those in forward-looking statements include, but are not limited to: (i) the ability of Marina Biotech to obtain additional funding; (ii) the ability of Marina Biotech to attract and/or maintain manufacturing, research, development and commercialization partners; (iii) the ability of Marina Biotech and/or a partner to successfully complete product research and development, including preclinical and clinical studies and commercialization; (iv) the ability of Marina Biotech and/or a partner to obtain required governmental approvals; and (v) the ability of Marina Biotech and/or a partner to develop and commercialize products that can compete favorably with those of competitors. Additional factors that could cause actual results to differ materially from those projected or suggested in any forward-looking statements are contained in Marina Biotech’s most recent periodic reports on Form 10-K and Form 10-Q that are filed with the Securities and Exchange Commission. Marina Biotech assumes no obligation to update and supplement forward-looking statements because of subsequent events.

Contact:
Marina Biotech, Inc.
Philip Ranker
Interim Chief Financial Officer
(425) 908-3615
pranker@marinabio.com