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Miragen Aims to File Two INDs in '15, Go Public in '16

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NEW YORK (GenomeWeb) – Having just pulled down $8.5 million in funding from a $21.5 million Series B round closed in early 2012, Miragen Therapeutics is gearing up to file investigational new drug applications for up to two of its proprietary microRNA drug candidates before the end of this year.

In doing so, the company is laying the groundwork for clinical studies that it hopes will generate proof-of-concept data around its therapeutic approach in order to woo investors for a planned initial public offering next year, Miragen President and CEO Bill Marshall told GenomeWeb.

Founded in 2007, Miragen is focused on developing both inhibitors and mimics of miRNAs implicated in various disorders. Though initially focused on cardiovascular disease, the company's interest has expanded into oncology and skin disorders in recent years. As a result, the firm has moved programs in hematological malignancy and fibrosis to the front of its pipeline.

Miragen's lead candidate, called MRG-106, is designed to inhibit miR-155, a miRNA associated with hematopoiesis and immunity and that has been shown to be significantly upregulated in blood cancers such as leukemia and lymphoma. In preclinical testing, Miragen has found that silencing the miRNA can induce cancer cell apoptosis.

Close behind is MRG-201, a synthetic version of miR-29 that Miragen hopes to develop first as a treatment for cutaneous and pulmonary fibrosis.

The miR-29 family regulates extracellular matrix proteins and its members have been shown to be downregulated in different types of tissue fibrosis. Last year, Miragen and collaborators at Yale University reported that miR-29 mimics could decrease collagen expression in a mouse model of pulmonary fibrosis. Encouragingly, the data also showed that treatment could both block and reverse fibrosis.

In line with what he calls the company's "beachhead approach" to drug development, Marshall said that he expects initial development of MRG-201 to be in skin conditions like scleroderma and hypertrophic scarring.

Once proof of concept is established in such indications where local delivery is appropriate, Miragen will then move onto conditions requiring more complicated systemic and, eventually, pulmonary delivery. These include major organ fibrosis and progressive systemic scleroderma, a form of the disease that affects the lungs.

As reported by GenomeWeb last year, Miragen recently kicked off its so-called 10-3-1 corporate strategy, which envisions the firm having 10 preclinically validated programs and three clinical-stage programs, as well as completing a transformative financial transaction, by the end of 2017. As part of that initiative, Miragen was aiming to file one IND — either for MRG-201 or MRG-106 — in 2015, Marshall said at the time.

Buoyed by the $8.5 million cash infusion, however, the company now expects that it could file both before year end. This, along with continued earlier-stage work with miR-155 in amyotrophic lateral sclerosis, miR-92 in peripheral artery disease, miR-208 in hypertrophic cardiomyopathy, and miR-15 in heart failure, puts Miragen on schedule with the research and development portion of its 10-3-1 plan.

The miR-208 and miR-15 programs, as well as a third undisclosed program, are partnered with France's Les Laboratoires Servier under a deal inked in 2011.

As for the financial aspect of the strategy, Marshall said that Miragen is actively working on a Series C financing round, although he declined to say how much the company is looking to raise. The money from this round, he added, would provide the resources to run the upcoming clinical trials and generate the kind of clinical data that would support an IPO "sometime in 2016."

Should it successfully float its shares next year, Miragen would become the third miRNA company to go public in the US.

In 2008, miRNA diagnostics firm Rosetta Genomics completed a $30.2 million IPO, and in 2012 Regulus Therapeutics, which develops miRNA drugs, grossed $51.8 million through its own IPO.