Marina Biotech Reports That Licensee ProNAi Therapeutics Initiates 'Brighton' Phase II Trial of PNT2258 in Patients With Richter's Transformation

BOTHELL, WA--(Marketwired - Nov 3, 2015) - Marina Biotech, Inc. (OTCQB: MRNA), a leading nucleic acid-based drug discovery and development company focused on rare diseases, today reported that its licensee, ProNAi Therapeutics, Inc. (NASDAQ: DNAI) has enrolled the first patient into the "Brighton" study, a Phase II clinical trial evaluating PNT2258 in patients with Richter's transformation. The international multi-center trial is expected to enroll approximately 50 patients with this rare form of cancer for which there are currently no approved therapies. PNT2258 is one of two nucleic acid-based therapeutics in clinical development which are formulated with Marina Biotech's proprietary SMARTICLES^® delivery technology.

Marina Biotech further announces the issuance of Canada Patent 2,622,584, which covers the company's SMARTICLES delivery technology. The '584 patent broadly covers an amphoteric liposomal composition over a wide range of molar concentrations, with pH sensitivity for appropriate cellular uptake and release. In addition, the composition of NOV340, the clinical SMARTICLES formulation currently licensed to ProNAi Therapeutics, Inc., Mirna Therapeutics, Inc. (NASDAQ: MIRN) and MiNA Therapeutics, Ltd., is specifically covered. The claims cover liposomes for a wide range of possible nucleic acid therapeutics including single- or double-stranded payloads triggering various biological mechanisms of action. Additional claims are directed to pharmaceutical compositions and methods of use for gene silencing and treating disease. 

"ProNAi Therapeutics' progress in developing this novel BCL2 DNAi therapeutic continues to be impressive," stated J. Michael French, president and Chief Executive Officer of Marina Biotech. "The ProNAi team has advanced multiple Phase II trials with PNT2258 establishing a comprehensive approach to the development of this therapeutic with the hope of treating numerous rare and underserved oncology indications. We believe SMARTICLES will continue to emerge as the most versatile delivery technology in the nucleic acid therapeutics sector, leading to additional licensing and partnering opportunities throughout the nucleic acid therapeutics sector. We look forward to the continued success of the ProNAi team in advancing PNT2258."

The Brighton Phase II study was designed on the basis of results from a pilot Phase II study of PNT2258, which were reported at the 2014 Annual Meeting of the American Society of Hematology (ASH). The investigators for that study concluded that PNT2258 treatment was well tolerated and resulted in significant, durable responses in patients with relapsed or refractory non-Hodgkin's lymphoma (r/r NHL), with eleven of the thirteen (11/13) patients treated achieving clinical benefit with durations of response extending to 18 months and beyond. In particular, the one patient with Richter's transformation enrolled in the pilot study achieved a notable response while on PNT2258 therapy. This patient had presented with intermediate-high risk disease at baseline and was refractory to two prior chemotherapy-containing regimens for Richter's transformation. After six cycles of treatment with single-agent PNT2258, the patient experienced a complete metabolic response and remained progression free for 10 months. The Brighton study will be a multi-center, single-agent, open-label, Phase II study of PNT2258 (ClinicalTrials.gov identifier: NCT02378038), will characterize anti-tumor activity and collect safety data on approximately 50 patients with Richter's transformation. PNT2258 will be administered at 120 mg/m2 as an intravenous (IV) treatment on days 1-5 of a 21-day cycle for eight induction cycles, followed by continuing treatment administered at 100 mg/m2 administered on days 1-4 of a 28-day cycle. The primary endpoint is overall response rate and secondary outcome measures include disease control rate, duration of overall response, time to response, progression-free survival, overall survival and safety.

About PNT2258, DNAi and Richter's Transformation
ProNAi's lead DNAi product candidate, PNT2258, is a proprietary formulation of a single-stranded rationally designed 24-base DNAi oligonucleotide known as PNT100, encapsulated in a proprietary liposomal nanoparticle. After intravenous injection, PNT2258 achieves systemic distribution, delivering PNT100 into the nuclei of cancer cells where it is designed to target and interfere with the regulatory region of the BCL2 oncogene.

Richter's transformation is a highly proliferative, rapidly progressing disease affecting mostly older adults with a median survival of approximately one year, and represents a significant unmet medical need with no currently approved therapies. Although CLL is typically classified as a low-grade lymphoproliferative disorder, 3% to 11% of CLL patients will experience transformation to Richter's during the course of their disease. While there are no specific therapies approved to treat Richter's transformation, multi-agent cytotoxic drugs in combination with rituximab are typically used as a first-line treatment with limited results.

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 Therapeutics, 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.