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With Three Years of Cash in the Bank, Regulus Aims for Two INDs by 2014

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The management of Regulus Therapeutics last week provided a few new details on the company's pipeline, promising that it would have two microRNA drug candidates ready for clinical trials before the end of next year.

Speaking during Regulus' first quarterly results conference call since it went public, the executives also indicated that the firm's recent fundraising efforts have yielded enough capital to support its operations for three years, which President and CEO Kleanthis Xanthopoulos said has “significantly de-risked the financial profile of the company.”

Regulus was founded in 2007 as a joint venture between Alnylam Pharmaceuticals and Isis Pharmaceuticals to develop miRNA inhibitors as therapeutics (GSN 9/13/2007). Although the company has yet to select a molecule for clinical development, it has been very successful in establishing programs through a series of partnerships.

Among its partners are Sanofi, which is collaborating with Regulus on four miRNA therapeutics including ones in liver cancer and kidney fibrosis (GSN 6/24/2010); GlaxoSmithKline under two alliances for inflammatory diseases and hepatitis C, struck in 2008 and 2010, respectively (GSN 4/17/2008 & 2/25/2010); and, most recently, AstraZeneca on an atherosclerosis treatment (GSN 8/16/2012).

Through these deals, Regulus has raised a total of $142.8 million in partnership funding, and is eligible for an additional $106.5 million in milestones, COO Garry Menzel said during the call. Combined with the roughly $81 million generated through its October IPO (GSN 10/4/2012) and other recent transactions, this money gives the company the resources to support its planned operations “through at least the end of 2015,” he noted.

“We believe that our disciplined financial strategy will enable us to advance multiple programs towards the clinic without the need for additional equity financing,” Menzel added.

More specifically, Regulus aims to nominate two clinical candidates within the next 12 months and file at least two investigational new drug applications by 2014, Xanthopoulos said.

Perhaps the company's most advanced program is its effort in HCV, which targets miR-122. Regulus CSO Neil Gibson said during the conference call that a number of drug candidates have shown promise against different forms of the virus, and that testing in non-human primates is currently underway.

When it comes to selecting a compound for human testing, Gibson said that the company is looking for something that can work against all the different HCV subtypes, and, “perhaps more importantly, is suitable for subcutaneous administration at least once a month, and can actually provide an opportunity for those patients who are difficult to treat or who develop resistance to the current agents.”

This month, Regulus also released preclinical data from its kidney fibrosis program, reporting that oligos targeting miR-21 were able to reduce the severity of fibrosis and improve renal function in a rodent model of the hereditary kidney disorder Alport syndrome.

Earlier this year, the company presented data from its atherosclerosis studies, showing that two members of the miR-33 family help regulate cholesterol and fatty acid synthesis, and that inhibiting these miRNAs enhanced reverse cholesterol transport, promoted regression of atherosclerosis, and raised plasma high-density lipoprotein cholesterol in mice. These findings have also been translated to non-human primates, according to Regulus.

Despite all of its work with partners, Regulus remains focused on advancing a significant number of its own miRNA antagonists, Xanthopoulos noted this week.

The tie-up with AstraZeneca “kind of disturbed the balance of the proprietary versus partner programs,” he said. “Our aim is [to have] about 40 percent programs owned by Regulus and the remaining with our partners.”

Currently, Regulus has one in-house program, which is centered around the brain cancer glioblastoma multiforme, or GBM. By targeting miR-10b, the company has been able to reduce cellular proliferation by stopping cell cycle progression and inducing apoptosis in vitro.

In animal models of the disease, direct injection of miR-10b inhibitors to tumors and spinal fluid resulted in delivery to tissues of interest and target gene de-repression, suggesting a “clinically viable method of oligonucleotide delivery,” Gibson said.

He noted that miR-10b is specifically over-expressed in patients with the proneural subtype of GBM. “This means that we have the opportunity to provide personalized treatment options for different patient populations.”

To regain its balance of partnered and in-house programs, Regulus expects to initiate additional internal drug-development efforts over the next two to three years “primarily, if not exclusively, in the area of oncology,” Xanthopoulos said.

The Third Quarter

For the three-month period ended Sept. 30, Regulus posted a net loss of $5.7 million, or $15.98 per share, versus a year-ago loss of $1 million, or $11.68 a share.

Contributing to the higher loss was a $1 million year-over-year drop in total revenues to $2.8 million following the amendment of Regulus' alliance with GlaxoSmithKline earlier this year.

Increased research and development spending, which rose to $5.2 million in the third quarter this year from $3.8 million last year, and a slight increase in general and administrative costs to $1.1 million, also helped drive up Regulus' net loss.

The company had cash, cash equivalents, and short-term investments of $30.9 million at the end of the third quarter. Including the funds from the IPO and recent financing transactions, the company expects to end 2012 with more than $95 million on hand.

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