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Mirna Inks Deal to Use Marina's Smarticle Delivery Technology with miRNA Mimics


By Doug Macron

Mirna Therapeutics this week announced that it has acquired the rights to use Marina Biotech's Smarticle liposomal delivery technology with a number of its therapeutic microRNA mimics, including its lead liver cancer candidate.

Under the terms of the deal, Mirna will be fully responsible for the development and commercialization of oncology drugs incorporating the technology, although Marina will provide certain undisclosed preclinical and process-development assistance.

Marina stands to receive up to $63 million in upfront fees and clinical and commercial milestones, as well as royalties on product sales. Specific terms of the deal were not disclosed.

Smarticles are fully charge-reversible liposome particles originally developed by Novosom. In mid-2010, Marina acquired the rights to the technology for roughly $5 million in stock (GSN 7/29/2010).

“Given the challenge of effectively delivering oligonucleotides to target tissues, we devoted considerable effort to identifying an optimal delivery technology that would allow for systemic administration of our potent miRNA tumor suppressors and which is already in clinical testing,” Mirna President and CEO Paul Lammers said in a statement. “We believe the Smarticles technology solves the delivery challenge for us.”

Indeed, Mirna has been evaluating different delivery technologies for its miRNA mimics for some time, including an internally developed neutral lipid-emulsion that was ultimately deemed not yet ready for the clinic and two of Silence Therapeutics' delivery approaches (GSN 10/27/2011).

In the end, Mirna determined that the Smarticle technology was the best bet for its first clinical candidate — a mimic of miR-34 designed to treat liver cancer and which is expected to enter phase I testing in early 2013.

“The zwitterion, pH-sensitivity aspect of Smarticles provides charge flexibility of the technology, which helps in ... tissue targeting and ... release by endosomes in the cytoplasm,” Lammers told Gene Silencing News in an e-mail this week. At the same time, the particles have proven to be efficient enough to allow Mirna to maintain efficacy with lower doses of the drug.

Late last year, Mirna presented data  showing that five different miRNA mimics with tumor-suppressor activity could “significantly” inhibit tumor growth in a mouse model of the disease (GSN 11/17/2011). Although it was not disclosed at the time, Mirna confirmed this week that the miRNA molecules were formulated with the Smarticle technology.

Although Mirna is currently focused on advancing its miR-34 mimic into human testing first, Lammers noted that the company has also tested the Smarticles with four of its other pipeline candidates with positive results.

He added that the company is currently working to show that it can deliver its miRNA mimics beyond the liver and has already seen signs of uptake in “not only several highly vascularized tissues such as lung, spleen, kidney, but also to more difficult organs such as pancreas, ovaries, and lymph nodes.”

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