Managing Editor

Miragen Therapeutics Inc.'s preclinical micro-RNA program for cardiovascular disease captured the attention of French pharma Les Laboratoires Servier, which agreed to license rights to two lead compounds and jointly develop a third in a deal that's valued at up to $352 million but could end up being worth much more to the small biotech.

Under the terms, Boulder, Colo.-based Miragen could receive up to $45 million over the next three years in up-front fees, research support and near-term milestones. The remaining money is tied to regulatory and commercial milestones. Beyond that, Miragen is entitled to double-digit royalties on product sales in Servier's territories, which include all markets except the U.S. and Japan.

But, perhaps more importantly, the Paris-based big pharma firm is taking on all development costs, moving lead candidates miR-208, miR-15 and the third as-yet-unidentified compound through preclinical and clinical development. Adding in those costs puts the deal's value at about $1 billion, said William S. Marshall, president and CEO.

After all, developing drugs for cardiovascular disease is no cheap undertaking. And many firms have shied away from the space simply because of the magnitude of studies involved. Amarin Corp. plc, for instance, recently reached a special protocol assessment agreement with the FDA for a cardiovascular outcomes study needed for approval of its prescription-grade fish oil candidate for dyslipidemia. That study is expected to take six years, enroll 8,000 patients and cost between $100 million and $125 million. (See BioWorld Today, Aug. 11, 2011.)

As a venture-backed biotech, trying to raise that kind of cash simply isn't practical, Marshall said. "Because [cardiovascular programs] tend to require large outcomes-based Phase III trials, we'd always looked to partner at some point."

The Servier deal might have been a little earlier than expected. Marshall said Miragen was approached by Servier after presenting early data at a scientific meeting.

But the collaboration seemed a perfect fit. Servier's commercialization efforts exclude the U.S. and Japan, so Miragen was able to retain ownership in those areas. Plus, the French firm has a "long-standing interest in cardiovascular and heart disease," and Miragen's programs offer an innovative approach in a tough space, he added.

MicroRNAs have been shown to act on entire pathways, rather than just one specific target. Miragen's lead program focuses on miR-208, which was discovered after a knockout mouse model suggested that it played a key role in pathological cardiac remodeling. A mouse missing miR-208 was not subject to that remodeling, "so that gave us an interesting target to inhibit," Marshall told BioWorld Today.

Data published last month in Circulation showed that chemically synthesized inhibitors of miR-208 were able to suppress pathological cardiac remodeling in a model of heart failure induced by chronic high blood pressure, while also enhancing cardiac function and survival.

The second program involves miR-15, which is implicated in the protection of cardiomyocytes following a heart attack. Data still are early, but they indicated that miR-15 might also have regenerative capability. "So it could both protect cardiomyocytes from death after a heart attack and offer the potential to regenerate cardiomyocytes post-myocardial infarction," Marshall said.

Miragen's lead programs were developed with help from Santaris Pharma A/S's Locked Nucleic Acid platform. Under a 2010 deal, Miragen licensed rights to the technology in exchange for a minority interest, undisclosed milestone payments and royalties. Along with its new partnership, Miragen has expanded the Santaris deal to include additional targets and to provide Servier with access, through Miragen, to the Hoersholm, Denmark-based firm's LNA technology.

With Servier taking over on miR-208 and miR-15, Miragen will be able to move forward with other programs in its pipeline, including miR-451, a target for myeloproliferative diseases that has orphan status.

"Goal one is to support the partnership," Marshall said. "Goal two is to continue to push forward with [miR-451] on our own."

Founded in 2007, Miragen has raised $12 million to date.