This story has been updated from an earlier version to include comments from Miragen's president and CEO, and details on the company's pipeline.
Miragen Therapeutics this week said that it has obtained a $4 million extension to its previously announced Series A financing round (see RNAi News, 5/15/2008), bringing the total value of the round to $12 million.
With the added investment, the company now has enough resources to fund its planned operations, including the selection of lead drug candidates for its post-myocardial infarction remodeling and chronic heart failure programs, through 2010, Miragen President and CEO Bill Marshall told RNAi News.
New investors in the extension include Amgen Ventures, Broadview Ventures, and the Peierls Foundation, which join previous investors Atlas Venture and Boulder Ventures.
In conjunction with the financing extension, Miragen said it has also reached achieved several milestones related to the development of its miRNA-targeting technology and the establishment of an intellectual property estate, which triggered the second tranche of the original $8 million Series A.
Specifically, Miragen has been able to demonstrate and validate in vivo the miRNA targets for its two pipeline programs, and has generated a series of proprietary lead drug candidates that are now in animal testing, Marshall said. For post-myocardial infarction remodeling, the company is targeting miR-15, while miR-208 is the focus of the chronic heart failure effort.
As part of that process, the company used existing technologies that have previously been shown to inhibit miRNAs in vivo to validate its targets, he explained.
"We moved on from there to a pretty extensive panel of different types of chemical modifications and patterning that we then put through a screening process to winnow down [a series of proprietary miRNA inhibitors] to a lead series of compounds," he said.
Taking an approach Marshall described at the Center for Business Intelligence’s Executing on the Promise of RNAi conference this January, Miragen researchers then tested the lead compounds in normal animals before moving into disease models (see RNAi News, 1/29/2009).
At the conference earlier this year, Marshall called this aspect of Miragen's drug-development process "vitally important" as it ensures that an agent is capable of hitting its intended target and that an apparent therapeutic benefit isn't the result of a non-specific effect.
With that work complete, the company is now testing its lead candidates in vivo and is working to optimize about three compounds per miRNA target, a group that will later be narrowed down to two drugs, one for each program, for late-stage preclinical testing, likely in porcine models, around the end of 2010, Marshall said.
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In regards to Miragen's IP portfolio, Marshall said that the company's strategy has been to "look for intellectual property where key microRNAs have been identified, there has been function associated with them, and there is enablement to them.
"We've essentially [identified] several key patent applications in the field, exclusively licensed those, and … generated some internal intellectual property based on some novel observations," he added. "We've also worked toward some chemistry licensing, as well," and an announcement regarding a chemistry in-licensing deal is expected to come in the "next couple of weeks."
Although Miragen's top priority is its cardiovascular disease programs, the company also continues to advance earlier-stage projects in skeletal muscle disease.
Because the work in myocardial infarction and heart failure center on the cardiac muscle, the company is also interested in extending its reach into "things like the maintenance of neuromuscular synapses, as well as things like muscle atrophy," Marshall said.
"We've built the company in a way that lets us … validate a target [and] generate lead compounds" in related indications, he said. "We continue to run those sorts of processes, but we have to devote a great deal of effort on the lead candidates in the cardiovascular space."
As such, efforts in skeletal muscle disease have "lagged a little behind," he noted. Still, "we've made good progress in terms of identifying and validating targets and [are] beginning to generate interesting molecules."