Regulus Therapeutics (RGLS) Announces Multiple RG-101 Presentations at ILC 2015

Regulus Therapeutics (RGLS) Announces Multiple RG-101 Presentations at ILC 2015

Regulus Therapeutics (Nasdaq: RGLS) announced that multiple presentations related to RG-101, a GalNAc-conjugated anti-miR targeting microRNA-122 ("miR-122") for the treatment of chronic Hepatitis C Virus (HCV) infection, are scheduled for presentation at The International Liver Congress™ (ILC) 2015, April 22-26 in Vienna, Austria.

Investigators will present new clinical data on RG-101 in a late-breaking oral presentation titled "A Single Subcutaneous Dose of 2 mg/kg or 4 mg/kg of RG-101, a GalNAc-conjugated Oligonucleotide with Antagonist Activity Against miR-122, Results in Significant Viral Load Reductions in Chronic Hepatitis C Patients" on April 25, 2015 from 17:30-17:45 pm CET (abstracts relating to late-breaking oral presentations are embargoed until presentation). In addition, in multiple poster presentations, clinical and preclinical results will be presented on RG-101, including pharmacokinetics and pharmacodynamics in healthy volunteers, pharmacokinetics, pharmacodynamics, and toxicity in rodents and non-human primates, and efficacy in a human hepatocyte chimeric mouse model of HCV.

"Regulus and our clinical investigators are extremely pleased to be making several presentations on RG-101 for the treatment of HCV during the International Liver Congress that will further demonstrate the compound's novel mechanism and potential," said Neil W. Gibson, Ph.D., Chief Scientific Officer of Regulus. "We also look forward to showcasing the significant progress we are making in advancing microRNA therapeutics to patients with an expanded examination of RG-101's preclinical profile."

"Pharmacokinetics and Pharmacology of RG-101, a Novel GalNAc-Conjugated Oligonucleotide Targeting microRNA-122, in Healthy Volunteers" (Abstract: P1352)

Regulus will present clinical data from the healthy volunteer portion of the completed clinical study of RG-101. These data demonstrate that RG-101, tested at single doses from 0.5 mg/kg to 8 mg/kg, shows dose responsive pharmacodynamics with maximal changes at 2 mg/kg in healthy volunteers and no drug-drug interactions observed when administered in combination with the direct acting anti-viral drug simeprevir (OLYSIO™). In addition, RG-101 was well tolerated in healthy volunteers at all doses tested.

"Pharmacokinetics, Pharmacodynamics, and Toxicity Profile of RG-101, a Novel GalNAc-conjugated Hepatocyte-Targeting Inhibitor of microRNA-122, in Rodents and Cynomolgus Monkeys" (Abstract: P0907)

Regulus will present preclinical data that supports the evaluation of RG-101 in human clinical trials. RG-101 was administered subcutaneously at doses from 0.1 to 450 mg/kg in mice and 1.5 to 150 mg/kg in monkeys. Following subcutaneous administration, rapid absorption and clearance of RG-101 was observed in plasma with rapid uptake and efficient conversion to unconjugated oligonucleotide in the liver and reduced concentrations in kidney. No Observed Adverse Effect Levels (NOAELs) of 450 mg/kg and 45 mg/kg in mouse and monkey, respectively, were declared for RG-101. Taken together, the pharmacokinetic, pharamacodynamic, and toxicology profile of RG-101 suggests that conjugation of oligonucleotides to GalNAc produces significant advantages that are likely to translate to more effective and safer clinical outcomes.

"RG-101, a Novel GalNAc-conjugated Inhibitor of microRNA-122, Demonstrates Significant Viral Load Reduction and Reduces Liver Steatosis in Human Hepatocyte Chimeric Mice Infected with Genotype 1A or Hard-to-Treat Genotype 3A Hepatitis C Virus (HCV)" (Abstract: P0904)

Regulus will present preclinical data demonstrating the effects of RG-101 on HCV infection using human hepatocyte chimeric mice (PXB-Mice) infected with genotype 1A and genotype 3A HCV isolates. In this model, RG-101 was effective against multiple HCV genotypes in vivo and fatty liver (steatosis) in PXB-Mice was dramatically reduced in line with the known role of miR-122 in hepatic lipid metabolism. These results suggest that RG-101 may have additional benefits beyond reduction in HCV viral titer.

The abstracts related to the poster presentations can be accessed through the ILC/EASL website at https://events.easl.eu/EventProgramme/ILC2015/POSTER.aspx