Getting to the heart of the matter

SURESNES, France—The pulse is picking up in the field ofcardiovascular disease treatment, as Les Laboratoires Servier and miRagenTherapeutics Inc. have established a new agreement for the research,development and commercialization of three drug candidates for cardiovasculardisease, including miR-208 and miR-15/195, miRagen's lead programs, and oneyet-to-be-identified additional target.

Under the agreement, Servier will pay miRagen up to $45million up front, research support and near-term milestone payments over thenext three years and sales royalties based on the successful outcome of thepartnership. Adding in clinical and commercial milestones and clinicaldevelopment support for the compounds' successful development, the deal couldhave a total value of approximately $1 billion.

Servier and miRagen will collaborate on the research anddevelopment efforts up to the point of IND filing, after which Servier will beresponsible for all costs associated with global development, regulatoryapproval and commercialization of the three product candidates worldwide, withthe exception of the U.S. and Japanese markets. miRagen will retain all rightsin those two markets, and will have the option to co-sponsor any Phase IIIprograms should miRagen, alone or with a partner, decide to seek marketingapprovals for any of the targets in the United States and Japan.

"We are very pleased with this new partnership, whichdemonstrates once again our ability to explore truly innovative treatments forpatients suffering from cardiovascular diseases," Dr. Emmanuel Canet, head ofServier R&D, said in a press release.

miR-208 has been shown to play an important role in thepathogenesis and progression of heart failure, and inhibition of miR-208 hasthe potential to improve cardiac function and survival rates during heartfailure. miR-15/195 plays a role in the survival and capacity for proliferationof cardiomyocytes, and inhibiting it could stimulate cardiomyogenesis, or theformation of new heart muscle cells. Inhibiting miR-15 and sparingcardiomyocytes from death during myocardial infarction could lead to less hearttissue death and improved cardiac function following a heart attack.

As for the third target, Dr. William S. Marshall, presidentand CEO of miRagen, says it could be defined in one of two ways, noting it willeither be something in the earlier stages of development within miRagen'spipeline, or something from the broad-based discovery program miRagen andServier have for new microRNAs.

Servier represented an appealing partner, Marshall says,given its "strong commitment and development of cardiovascular drugs" andexpertise in terms of clinical "capabilities and logistics to conduct global,large-scale clinical trials in this area."

"They were a partner that demonstrated all these attributesof long-term commitment and vision," says Marshall. "It also was anear-immediate sense of a shared vision … there was an excitement demonstratedby their research teams, their development team, that really sort of synced upwell with the way that the miRagen staff felt about these programs."

Pascal Touchon, director of scientific cooperation andbusiness development at Servier, echoes the sentiment, adding that miRagen'sapproach represents "truly innovative ways to address the current medical needin cardiovascular diseases."

"From the first meetings between scientists from bothcompanies, I could feel respect, common understanding on key issues and thedesire to collaborate together for the benefit of patients," says Touchon. "Weclearly saw as well the scientific and professional approach of miRagen towardsproduct discovery and development. Also worth mentioning is the fact that theyhad obtained clear access through licenses to the necessary technologies fromuniversities and Santaris."

miRagen's lead programs both make use of Santaris Pharma'sLocked Nucleic Acid (LNA) Drug Platform, which miRagen licensed the rights toin June 2010 in order to identify drug candidates against its proprietary microRNAtargets for the treatment of cardiovascular disease. The agreement has beenexpand to allow miRagen to develop additional targets and to grant Serveraccess to the LNA technology.

Marshall notes that there is no lack of commercial potentialfor these programs, as "the latest statistics would indicate that thehealthcare costs associated with chronic heart failure are $30 billion to $40billion a year," with a five-year mortality rate of about 50 percent. Currenttherapies are all palliative, he adds, and there is a decided lack ofdisease-modifying therapies available.

"We believe that because the unique aspects of microRNAbiology mean that we affect biological networks, that we will be able toidentify disease-modifying therapies," says Marshall, "and all of thepreclinical efficacy data thus far would support the notion that we've gotsomething that's really game-changing."

Servier and Prognomixin type 2 diabetes deal

SURESNES, France—Les Laboratoires Servier of France alsoannounced last month that it has entered into a research and developmentagreement with Prognomix Inc. aimed at identifying novel targets for type 2diabetes and metabolic disease treatment.

Prognomix is a Montreal-based, privately held personalizedmedicine company that is focused on discovery and clinical application ofgenomic signatures predictive of susceptibility to diseases, theircomplications and individual therapeutic responsiveness. The company has madesignificant progress in the identification of the genomic features associatedwith complications of type 2 diabetes. Based on these findings, Prognomix hasdeveloped a prototype of a molecular diagnostic kit that will include clinical,genomic and epigenomic markers.

The companies' collaboration will rest on Prognomix'sdiscovery platform comprising genomic and bioinformatics technologies, adatabase of phenotypic and genotypic data and an assembly of results of theanalysis of these data. The knowledge base they explore was developed using thedata collected during ADVANCE, the largest clinical study ever conducted ontype 2 diabetes and of which Servier was the main sponsor.

Financial terms of the agreement were not released.

As part of the agreement, Servier will make a contractsignature fee payment and will be granted options to obtain rights to use theresults of the collaboration.