Regulus to Present Late-Breaking, Expanded RG-101 Data Set for the Treatment of HCV at The International Liver Congress™ 2015 (ILC 2015)

LA JOLLA, Calif., April 9, 2015 /PRNewswire/ -- Regulus Therapeutics Inc. (NASDAQ:RGLS), a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, announced today 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 

Completed RG-101 Study Design

Regulus has evaluated RG-101 in a completed clinical study conducted in The Netherlands. 58 healthy volunteers and 32 HCV patients with multiple genotypes, liver fibrosis status and treatment history were enrolled in the four part study: (i) a single ascending-dose study in which healthy volunteer subjects received a single subcutaneous dose of RG-101, 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 4 mg/kg and 8 mg/kg or placebo; (ii) a multiple-ascending dose study in which healthy volunteer subjects received a monthly single subcutaneous dose for four months of RG-101 or placebo; (iii) a single-dose drug-drug interaction study in which healthy volunteer subjects received a single subcutaneous dose of RG-101 in combination with simeprevir (OLYSIO™), an approved direct acting antiviral; and (iv) a single-dose study in which HCV patients received either a single subcutaneous dose of RG-101 or placebo at two doses, 2 mg/kg of RG-101 (the first dose cohort) or 4 mg/kg of RG-101 (the second dose cohort), to assess the safety and viral load reduction.  The primary objective is to evaluate safety and tolerability and the secondary objectives are to evaluate pharmacokinetics, viral load reduction and any impact an oral direct acting antiviral, such as simeprevir (OLYSIO™), may have on the pharmacokinetics of RG-101. 

About microRNAs

The discovery of microRNAs in humans during the last decade is one of the most exciting scientific breakthroughs in recent history.  microRNAs are small RNA molecules, typically 20 to 25 nucleotides in length, that do not encode proteins but instead regulate gene expression. More than 800 microRNAs have been identified in the human genome, and over two-thirds of all human genes are believed to be regulated by microRNAs.  A single microRNA can regulate entire networks of genes. As such, these molecules are considered master regulators of the human genome.  microRNA expression, or function, has been shown to be significantly altered or dysregulated in many disease states, including oncology, fibrosis, metabolic diseases, immune-inflammatory diseases and HCV. Targeting microRNAs with anti-miRs, chemically modified, single-stranded oligonucleotides, offers a unique approach to treating disease by modulating entire biological pathways and may become a new and major class of drugs with broad therapeutic application.

About Regulus

Regulus Therapeutics Inc. (NASDAQ:RGLS) is a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs.  Regulus has leveraged its oligonucleotide drug discovery and development expertise to develop a well-balanced microRNA therapeutics pipeline complemented by a maturing microMarkers^SM biomarkers platform and a rich intellectual property estate to retain its domain dominant leadership in the microRNA field.  Under its 'Clinical Map Initiative', Regulus is developing RG-101, a GalNAc-conjugated anti-miR targeting microRNA-122 for the treatment of chronic hepatitis C virus infection, and RG-012, an anti-miR targeting microRNA-21 for the treatment of Alport syndrome, a life-threatening kidney disease driven by genetic mutations with no approved therapy.  Regulus is also advancing several programs toward clinical development in orphan disease indications, oncology and fibrosis.  Regulus' commitment to innovation has resulted in multiple peer-reviewed publications in notable scientific journals and has resulted in the formation of strategic alliances with AstraZeneca and Sanofi and a research collaboration with Biogen Idec focused on microRNA biomarkers.  Regulus maintains its corporate headquarters in La Jolla, CA.  For more information, please visit http://www.regulusrx.com. 

Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements associated with the expected ability of Regulus to undertake certain activities and accomplish certain goals (including with respect to development and other activities related to RG-101), the projected timeline of clinical development activities, and expectations regarding future therapeutic and commercial potential of Regulus' business plans, technologies and intellectual property related to microRNA therapeutics and biomarkers being discovered and developed by Regulus.  Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "intends," "will," "goal," "potential" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Regulus' current expectations and involve assumptions that may never materialize or may prove to be incorrect.  Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs.  These and other risks concerning Regulus' financial position and programs are described in additional detail in Regulus filings with the Securities and Exchange Commission.  All forward-looking statements contained in this press release speak only as of the date on which they were made. Regulus undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

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