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Regulus Plans for New Clinical Trials, Third Drug Candidate in '15

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NEW YORK (GenomeWeb) – Officials from Regulus Therapeutics this week provided updates for the company's two lead microRNA drug programs, announcing plans for the release of additional clinical data on its hepatitis C treatment RG-101, as well as details around planned trials of the drug and the earlier-stage Alport syndrome therapy RG-012.

The firm also said that it remains on track to nominating a third clinical candidate before the end of 2015.

RG-101 is an antagonist of miR-122, the most abundant miRNA in the liver and one that has been show to play a key role in HCV replication and infection. It is delivered subcutaneously using Alnylam Pharmaceuticals' GalNAc conjugate delivery technology, which targets the asialoglycoprotein receptors expressed on the surface of hepatocytes.

To date, Regulus has generated very positive data on the compound, in October releasing data from a Phase I trial showing that single 2 mg/kg doses of the drug could trigger a mean 4.1-log reduction in viral load in HCV patients, with RNA levels falling below the limit of quantification (BLOQ) in a handful of the study participants.

Earlier this month, the company announced data from the 4 mg/kg cohort in this study, which showed that higher doses of RG-101 were associated with greater viral load reductions, and that this effect could be achieved regardless of the patients' HCV genotype, extent of their liver fibrosis, or if they had previously relapsed after receiving other therapies. The data also showed that several patients in the 2 mg/kg cohort showed no presence of HCV RNA in their blood 85 days after treatment.

Speaking during a conference call held this week to discuss the company's fourth-quarter 2014 financial results, Regulus CMO Paul Grint said that longer-term patient follow-up data from the study will be presented in April at the European Association for the Study of the Liver conference.

Meanwhile, Regulus is preparing to initiate two Phase II studies of RG-101 in the second quarter of this year. In line with Regulus' dual-track approach to RG-101's advancement, one trial will evaluate single and multiple doses of the drug in combination with direct-acting antivirals, while the other will test it as a monotherapy with once-a-month dosing.

Interim readouts from the two trials are expected by year-end, Grint said.

Meanwhile, development of RG-012 is proceeding apace, with Phase I testing in healthy volunteers on track to start in the first half of 2015.

Alport syndrome is caused by mutations in three genes that affect production of the type IV collagen family of proteins. The result is a disruption to the structure of the glomerular basement membrane, increased expression of miR-21, an increase in fibrosis, and the loss of renal function, which ultimately leads to end-stage renal disease.  Regulus' drug is designed to silence miR-21, and is also delivered using the GalNAc technology.

Grint noted that enrollment in a natural history of disease study of Alport patients, which began in September, is "going well" and that data may be available this year. The findings from this study are also expected to help Regulus identify endpoints for a Phase II proof-of-concept study of RG-012 that is slated to begin in 2015.

Notably, Sanofi has the right to option RG-012 after Regulus has demonstrated human proof of concept for the drug.

Lastly, Regulus CSO Neil Gibson said that the firm continues to plan to unveil a third clinical candidate this year, potentially from its collaboration with AstraZeneca on miR-103 and miR-107 for metabolic diseases and miR-19 in oncology; its miR-21 program in liver cancer and renal fibrosis; and its miR-221 program in liver cancer, which is partnered with Sanofi.

Fourth quarter financials

For the three-month period ended Dec. 31, 2014, Regulus posted a jump in its net loss to $22.2 million, or $.47 a share, from a loss of $1.9 million, or $.05 a share, for the fourth quarter of 2013.

Driving the loss increase were higher research and development costs, which rose to $10.5 million from $8.2 million, as well as increased general and administrative expenses, which climbed to $3.3 million from $1.9 million. The firm also reported a non-cash charge of $12.7 million related to the change in value of a convertible note.

Regulus' revenues in the fourth quarter fell to $4.2 million from $5.5 million, and consisted primarily of amortization of up-front payments received from strategic alliances and collaborations.

As of the end of 2014, Regulus had cash, cash equivalents, and short-term investments totaling $159.7 million. The company expects to end 2015 with more than $100 million.

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