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Regulus Weighs Spinoff of microRNA Biomarker Unit

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NEW YORK (GenomeWeb) – As its recently established microRNA biomarker division makes gains with both partnered and in-house programs, Regulus Therapeutics is weighing the possibility of spinning off the unit as a standalone company that would develop and market clinical assays based on the small, non-coding RNAs.

Should it do so, Regulus' so-called microMarkers division would follow a similar course to its parent, which was established in 2007 as a joint venture between Alnylam Pharmaceuticals and Isis Pharmaceuticals but became an independent company in 2009.

In an email, Regulus President and CEO Kleanthis Xanthopoulos said that the company cannot comment on the timing of any decision, but confirmed that it is weighing all its options for microMarkers.

Meantime, the business unit continues to push ahead with efforts in colorectal cancer, kidney disease, rheumatoid arthritis, and other disease areas while trying to address the technical hurdles inherent in miRNA detection and analysis, Regulus CSO Neil Gibson told Gene Silencing News this week.

Looking to leverage its miRNA expertise beyond its core therapeutics focus, Regulus has for several years been exploring the prognostic and diagnostic potential of the ncRNAs.

This work began with the development and optimization of a platform that could "consistently and reproducibly" detect miRNAs in biofluid, along with the establishment of a baseline by which disease-associated miRNA signatures could be evaluated, Gibson said.

Using a PCR approach based on Life Technologies' QuantStudio system, Regulus analyzed blood samples from approximately 25 healthy employees, specifically looking for miRNA signatures that could be assumed to represent an undiseased state.

The result of that work was a group of 100 to 150 miRNAs that could be detected in each individual at a cycle threshold of between 15 and 28 — a benchmark Gibson called "stringent."

Regulus' work with miRNA biomarkers has continued to accelerate since then, with the company signing an agreement in 2012 to help Biogen Idec identify miRNAs that could be used to create a test to diagnosis patients with multiple sclerosis, as well as monitor patient response to treatment and track disease progression. Late last year, Regulus announced that it had thus far profiled 400 serum samples from MS patients and compared them to samples from healthy volunteers — a milestone that triggered an undisclosed milestone payment from Biogen Idec.

According to Gibson, microMarkers, which was formed in January, has also struck a similar deal with an undisclosed pharmaceutical firm in an unnamed indication. It has also received a grant from the non-profit Accelerate Brain Cancer Cure — an organization that Regulus has been working with on miRNA-based treatments for glioblastoma — to develop biomarkers for that indication.

Supported by the funding, microMarkers is working with collaborators at the University of California, San Diego to study tumor tissue, cerebrospinal fluid, and blood from brain cancer patients to see whether miRNA expression patterns in the biofluids correspond to those in diseased tissue. The investigators are also testing whether those signatures can be used to classify patients and guide treatment.

In addition to these partnered programs, microMarkers is working on projects in support of Regulus' therapeutic initiatives. For instance, Gibson said that the unit has been trying to apply its miRNA-detection and -analysis technology in urine to find biomarkers for Alport syndrome, a rare kidney disorder with no known cure that can lead to hearing loss and kidney failure. Regulus formally added the indication to its pipeline earlier this year.

At the same time, microMarkers is exploring disease areas viewed as commercially attractive irrespective of whether Regulus is working in them or not. Perhaps the most advanced of these efforts, Gibson said, is in colorectal cancer.

After surgical intervention, approximately 15 to 20 percent of colorectal cancer patients experience a recurrence of disease within 24 months, he explained. "It has not been possible to identify those patients in a reasonable timeframe before the disease recurs," and so microMarkers is attempting to profile biofluids for miRNA signatures that can show which patients have the highest risk for disease recurrence and, potentially, which are most likely to respond to a given therapy.

Gibson noted that microMarkers has also been working in rheumatoid arthritis, again to see if miRNA expression can be correlated with therapy response. For example, a subset of rheumatoid arthritis patients receiving tumor necrosis factor-alpha inhibitors will experience disease flare-ups after they discontinue treatment. "We are looking at signatures that might allow us to predict who those patients are."

Progress with these in-house programs has been promising, he added, so much so that Regulus is now dealing with the strategic question of how much of its resources should be dedicated to microMarkers at the expense of its primary therapeutics-development work. Thus far, Gibson said, the biomarker unit has two full-time employees, while receiving support from Regulus' bioinformatics and other teams.

As Regulus management is left to hash out these business-related details, microMarkers has its own scientific challenges to grapple with. Chief among these is the issue of sample retrieval and handling, which is faced by all groups working in the field but was made particularly apparent to Regulus early on in its multiple sclerosis program.

As Gibson explained, Biogen Idec provided Regulus with a large collection of patient blood samples that, upon initial analysis, "quickly broke into two groups." It was not immediately clear what caused this bifurcation until Biogen Idec disclosed that the samples had come from two institutions that used different methods of sample collection.

"That highlighted that, going forward when we're doing prospective collections, we need to make sure that everyone understands the importance of following the protocol that is provided in terms of sample collection and storage conditions," Gibson said.

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