Marina Biotech Announces SMARTICLES(R)-Mediated Delivery of a Double-Stranded Oligonucleotide to Immune Cells

BOTHELL, WA--(Marketwired - May 5, 2015) - Marina Biotech, Inc. (OTCQB: MRNA), a leading nucleic acid-based drug discovery and development company focused on rare diseases, announced today that its SMARTICLES^® delivery platform delivered a double-stranded miRNA mimic to white blood cells of patients with multiple tumor types, as announced by Mirna Therapeutics, Inc. Mirna reported that a molecular analysis of white blood cells from patients treated with MRX34 showed a dose dependent repression of several key oncogenes previously identified as direct miR-34 targets including FOXP1, BCL2, HDAC1 and CTNNB1. These data suggest delivery of miR-34 into human white blood cells and engagement of several biological targets of miR-34. The complete data were presented at the 2015 Annual Meeting of the American Association for Cancer Research in April 2015.

"Hematologic malignancies represent a class of cancer with a significant prevalence and incidence. Confirmation of activity within immune cells following treatment further expands the potential for the SMARTICLES delivery technology. Importantly, SMARTICLES continues to demonstrate efficacy and safety in clinical trials for both single- and double-stranded oligonucleotides," stated Michael J. French, President and CEO of Marina Biotech. "Effective delivery of a nucleic acid cargo is essential to the regulation of target genes, whether by microRNA replacement/inhibition, exon skipping, or RNAi and other mRNA translational inhibition approaches. Although the exact mechanism by which SMARTICLES mediates delivery is under investigation, direct uptake into cells and exploiting natural pathways such as exosome transport have been observed with SMARTICLES. It's possible that both need to be present for activity in immune cells, a cell population in which it has been historically difficult to demonstrate consistent and robust oligonucleotide activity. Furthermore, control and elimination of tumors and metastases via oligonucleotide therapies may rely on direct anti-tumor activity as well as indirect immune enhancement. These results may enable the opportunity for much needed novel therapeutic approaches."

About SMARTICLES Clinical Development
Clinical achievements with SMARTICLES represent the combined experiences (a total of more than 100 patients) of licensees ProNAi Therapeutics, Vancouver, BC and Mirna Therapeutics, Inc., Austin, TX.

PNT2258, from ProNAi Therapeutics, is a proprietary formulation of a single-stranded 24-base DNAi oligonucleotide, known as PNT100, encapsulated in the SMARTICLES LNP. PNT100 DNAi targets and interferes with BCL2, an important and validated oncogene known to be dysregulated in many types of cancer. Data from an ongoing pilot Phase 2 trial of PNT2258 were reported recently at the 56th Annual Meeting of the American Society of Hematology (ASH). In this trial, which enrolled 13 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL), PNT2258 demonstrated evidence of anti-tumor activity, with 11 patients achieving a complete response (CR), partial response (PR) or stable disease (SD). Furthermore, all four of the diffuse large B-cell lymphoma (DLBCL) patients treated in this trial experienced a clinical response, including three CRs and one PR, with reported durations on study in the range of nine to more than 20 months. In December 2014, ProNAi initiated Wolverine, a Phase 2 trial for the treatment of third-line relapsed or refractory DLBCL, and the company is expected to soon initiate Brighton, a Phase 2 trial evaluating PNT2258 for the treatment of Richter's CLL.

Mirna Therapeutics' clinical compound, MRX34, is a double-stranded microRNA "mimic" of the naturally occurring tumor suppressor miR-34, which inhibits cell cycle progression and induces cancer cell death. Data from an ongoing Phase 1 clinical trial shows that MRX34 has a manageable safety profile in patients with advanced primary liver cancer (hepatocellular carcinoma), other solid tumors with liver metastasis, and hematological malignancies. A maximum tolerated dose (MTD) was established at 110 mg/m2 for MRX34 administered twice weekly for three weeks followed by one week off. Dose escalation is on-going for a second dosing regimen wherein MRX34 is administered daily for five consecutive days followed by two weeks off.

About Marina Biotech, Inc.
Marina Biotech is an oligonucleotide therapeutics company with broad drug discovery technologies providing the ability to develop proprietary single and double-stranded nucleic acid therapeutics including siRNAs, microRNA mimics, antagomirs, and antisense compounds, including messengerRNA therapeutics. These technologies were built via a roll-up strategy to discover and develop different types of nucleic acid therapeutics in order to modulate (up or down) a specific protein(s) which is either being produced too much or too little thereby causing a particular disease. We believe that the Marina Biotech technologies have unique strengths as a drug discovery engine for the development of nucleic acid-based therapeutics for rare and orphan diseases. Further, we believe Marina Biotech is the only company in the sector that has a delivery technology in human clinical trials with differentiated classes of payloads, through licensees ProNAi Therapeutics and Mirna Therapeutics, delivering single-stranded and double-stranded nucleic acid payloads, respectively. Our novel chemistries and other delivery technologies have been validated through license agreements with Roche, Novartis, MiNA, Monsanto, and Tekmira. The Marina Biotech pipeline currently includes a clinical program in Familial Adenomatous Polyposis (a precancerous syndrome) and a preclinical program in myotonic dystrophy. 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 www.marinabio.com.

Marina Biotech 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 prior to, and 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 filings with the Securities and Exchange Commission. Marina Biotech assumes no obligation to update or supplement forward-looking statements because of subsequent events.