Skip to main content
Premium Trial:

Request an Annual Quote

Miragen Preps for Series B, Expects First IND in 2011

Premium

By Doug Macron

Miragen Therapeutics is preparing to launch a Series B private-equity financing round that it said will provide it with enough funding to advance its two lead programs, one of which is expected to yield an investigational new drug application filing in 2011, according to a company official.

Last year, the miRNA drug shop closed a Series A round, which it said would fund its operations through 2010 (GSN 6/4/2009). With the year more than half over, the company has now set its sights on raising additional capital through the Series B, Miragen President and CEO Bill Marshall told Gene Silencing News this week.

The expected size of the round, however, is not being disclosed. The financing will be "just enough to support a couple programs moving forward and the continued operations of the company," he said.

Specifically, those programs center around inhibitors of miR-15 as a treatment for post-myocardial infarction remodeling, and miR-208 for chronic heart failure. At this point, both efforts are "neck and neck," Marshall said.

"Right now, we're doing a lot of the later-stage large animal efficacy studies with a couple of different things," and expect to be in a position to file an IND some time next year, he added. "The key is to get these pivotal studies [done, which will] give us a read on what we think are the most relevant models. Based on what we see there, that will stratify the candidates."

Although Miragen has not yet selected the IND candidate, Marshall said that he fully expects the compound will be based on Santaris Pharma's locked nucleic acid technology, for which Miragen recently acquired a license for use in developing miRNA-targeting drugs against certain cardiovascular targets, including miR-15 and miR-208 (GSN 6/24/2010).

Marshall noted that the arrangement also includes a "collaborative piece" that will allow Miragen to "leverage some of the experience that Santaris has in terms of moving that class of oligonucleotide into the appropriate IND-enabling studies and clinical development."

Although Miragen has examined a variety of compounds as miRNA inhibitors, LNAs have "a track record of safety — the molecules have been in humans on several occasions — and with the efficacy parameters we're seeing, we're going to be pushing to put them into the clinic" first, Marshall noted.

He also said that while Miragen had been considering developing the two drugs for local delivery, it is now focused on systemic dosing in part because this mode yielded good efficacy levels in animal models.

"We did a lot of studies where we were doing dose ranging in murine models … looking at both the ability of the microRNA inhibitor to inhibit its target in the heart, and also see the up-regulation of some downstream targets," Marshall explained. "We also overlaid on that some traditional pharmacology looking at the drug, its plasma clearance, [and] its tissue uptake just to make sure we were getting an amount of drug into the tissue that made sense.

"The kind of ID50s that we saw in the in vivo pharmacology studies after systemic dosing put us in the sub-1 mg/kg range with our favorite molecules," he said. In light of those data, "we've moved to a systemic administration model."

Systemic delivery also made sense for the chronic heart failure program, in which patients would need to be dosed on a regular basis, he said. At the same time, there is no issue with inhibiting miR-208 in unintended tissues because the miRNA is cardiac specific.

Marshall noted that miR-15 is found in areas other than the heart, but said that because treatment for post-MI remodeling would be done on an acute basis, long-term down-regulation of the miRNA in non-targeted tissues isn't much of a concern.

Further, Miragen has found that "the stress to the heart after myocardial infarction and the hypertrophy that ensues appears to give us some benefit in terms of uptake" of the drug to cardiomyocytes.

The Scan

J&J Booster Support

A US Food and Drug Administration advisory panel has voted to support a booster dose of Johnson & Johnson's SARS-CoV-2 vaccine, according to the Los Angeles Times.

To Keep the Cases Moving

The president of the UK Royal College of Pathologists tells the Financial Times that more investment is needed to tackle a backlog of cases.

NAS Expels Archaeologist

Science reports Luis Jaime Castillo Butters' expulsion is the first of an international member from the US National Academy of Sciences.

PLOS Papers on Angelman Syndrome-Like Cases, Salmonella Paratyphi A, SARS-CoV-2 in Brazil

In PLOS this week: exome sequencing analysis of Angelman syndrome-like cases, genetic epidemiology of Salmonella Paratyphi A, and more.