MDRNA, Inc. Announces Combinations of UsiRNAs in Proprietary DiLA2 Delivery Technology Show Improved Efficacy in Bladder Cancer Model

BOTHELL, WA--(Marketwire - April 28, 2010) - MDRNA, Inc. (NASDAQ: MRNA), a leading RNAi-based drug discovery and development company, today reported data demonstrating greater efficacy in tumor reduction in an orthotopic model of bladder cancer with multiple combinations of two UsiRNAs as compared to single target therapy. The data were presented by Michael V. Templin, Ph.D., Senior Vice President of Preclinical Development at MDRNA, Inc., at TIDES Oligonucleotide and Peptide® Technology and Product Development/IBC's 2nd Annual Oligonucleotide Therapeutic Discovery April 25-28, 2010 in Boston, MA.

Fibroblast Growth Factor 3 (FGFR3), HRAS and Polo-Like Kinase 1 (PLK-1) were selected based on their known molecular alterations in bladder cancer and key roles in cancer cell progression. FGFR3 and HRAS are overexpressed in non-muscle invasive bladder cancer and play a role in tumor recurrence. Survivin, a protein involved in cell division and inhibition of apoptosis, is associated with tumor pathology, and its over-expression is associated with more serious tumor classifications and therefore the potential for more severe disease. PLK1, a protein involved in cell division and tumor progression, has been shown to play a role in cell proliferation in several cancer types. The diversity in these, as well as other genes identified in bladder cancer highlights the underlying heterogeneity of cancer in general, and supports the importance of a combination approach to inhibit critical targets. MDRNA has developed highly potent UsiRNAs for each of these targets.

To assess the impact of a multi-target approach on tumor growth in vivo, a survivin UsiRNA was paired with FGFR3, HRAS, or PLK1 UsiRNAs and compared to the survivin UsiRNA alone. All UsiRNAs were encapsulated in the Company's proprietary DiLA2-based formulation, and delivered directly to the bladder (intravesical) in an orthotopic cancer model. For the survivin/PLK1 combination, tumor bioluminescence and survivin mRNA expression was notably lower (~30% for each endpoint) when compared to a survivin alone. Similar results for tumor bioluminescence and mRNA were found with the survivin/FGFR3 combination. With survivin/HRAS there was a ~40% greater decrease in tumor bioluminescence and ~50% greater inhibition of survivin mRNA.

"Advances in molecular biology and gene profiling have revealed fundamental changes in cancer cells and the potential need to inhibit multiple targets to achieve maximum therapeutic benefit," stated Barry Polisky, PhD, Chief Scientific Officer at MDRNA, Inc. "RNAi provides a highly potent and highly specific therapeutic approach for knocking down multiple targets in a single compound. Our DiLA2 platform readily allows for formulation of two UsiRNAs into a single formulation and permits functional delivery to tumor cells. A multi-target approach is likely to be required for treatment of many cancers, and thus will be a key part of MDRNA's oncology pipeline."

About MDRNA's Technology

MDRNA has a broad intellectual property estate that encompasses four key RNAi technology platforms: siRNA constructs, chemistry, nucleic acid delivery, and gene targets. The MDRNA-owned siRNA constructs and chemistry include its proprietary UsiRNA construct, which is a duplex siRNA chemically modified with non-nucleotide acyclic monomers (UNAs), and is distinct from the standard siRNA construct used by others in the industry. UsiRNAs are fully recognized by the RNAi machinery and provide for potent RNAi activity while specific placement of UNAs in a duplex siRNA minimizes potential off-target effects by the guide strand and reduces undesired passenger strand activity. Furthermore, UsiRNAs escape the surveillance mechanisms associated with cytokine induction, and provide protection from nuclease degradation.

The MDRNA delivery platforms include DiLA2 and nanoparticle forming peptides. DiLA2 is an MDRNA proprietary delivery platform of novel synthetic di-alklylated amino acid compounds used to make liposomal delivery formulations. The DiLA2 platform enables MDRNA to tailor the charge, linker and acyl chains of amino acids in order to configure liposomes for delivery to target tissues of interest. In addition, the platform is designed to permit attachment of various peptides and other targeting molecules to improve a variety of delivery characteristics. The MDRNA peptide nanoparticle platform includes exclusively in-licensed and developed IP surrounding the use of peptides for nanoparticle formulations that increase cellular uptake and endosomal release of siRNAs. MDRNA is currently biopanning its patented phage display library to identify additional peptides for targeted delivery, cellular uptake and endosomal release of siRNA.

MDRNA owns or controls 17 issued or allowed patents, and has 36 pending patent applications, 125 pending foreign patent applications and 7 PCT applications.

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 oncology. 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.

MDRNA 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 MDRNA to obtain additional funding; (ii) the ability of MDRNA to attract and/or maintain manufacturing, research, development and commercialization partners; (iii) the ability of MDRNA and/or a partner to successfully complete product research and development, including preclinical and clinical studies and commercialization; (iv) the ability of MDRNA and/or a partner to obtain required governmental approvals; (v) the ability of MDRNA and/or a partner to develop and commercialize products that can compete favorably with those of competitors; and and (vi) the failure of the stockholders of MDRNA to approve the merger with Cequent, the failure of either party to meet any of the other conditions to closing the merger, contractual restrictions on the conduct of our business included in the merger agreement, and any impact on our relationships with third parties as a result of the announcement of the proposed merger. Additional factors that could cause actual results to differ materially from those projected or suggested in any forward-looking statements are contained in MDRNA's most recent periodic reports on Form 10-K and Form 10-Q that are filed with the Securities and Exchange Commission. MDRNA assumes no obligation to update and supplement forward-looking statements because of subsequent events.