Late-Breaking Oral Presentation at The International Liver Congress™ (ILC 2015) Highlights RG-101's Potent, Durable and Pan-Genotypic Effects in Diverse HCV Population

LA JOLLA, Calif., April 25, 2015 /PRNewswire/ -- Regulus Therapeutics Inc. (NASDAQ: RGLS), a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, today presented new data strengthening the profile of RG-101, a wholly-owned, GalNAc-conjugated anti-miR targeting microRNA-122 ("miR-122") for the treatment of HCV, during an oral late-breaking session at ILC 2015 in Vienna, Austria. Extended follow-up results evaluating a single subcutaneous administration of either 2 mg/kg or 4 mg/kg of RG-101 as monotherapy in HCV patients with varied genotypes, liver fibrosis status and treatment history showed that 10/22 patients had HCV RNA levels below the limit of quantification ("BLOQ") at 12 weeks and 70 percent of those patients remained BLOQ at 20 weeks (7/10).  In addition, the positive results that were previously reported from the completed clinical study of RG-101 were reviewed during the oral late-breaker.

Regulus also made several poster presentations highlighting the pharmacokinetics and pharmacodynamics of RG-101 in healthy volunteers, the preclinical pharmacokinetics, pharmacodynamics, and toxicity of RG-101, and the efficacy of RG-101 in a preclinical model of HCV.  The ILC 2015 oral presentation slides and posters related to RG-101 will be accessible at www.regulusrx.com.

"With multiple presentations at this year's ILC meeting, Regulus is pleased to tell the complete development story of RG-101, our unique microRNA therapeutic for the treatment of HCV, with positive preclinical results through impressive data in our first-in-human clinical trial," said Paul Grint, MD, Chief Medical Officer of Regulus. "All told, we believe that RG-101 is the most potent, durable and versatile compound in development to treat HCV.  In the near term, we look forward to testing the ability of RG-101 to shorten the duration of treatment to just four weeks in combination with oral agents, which is a key goal to advance the program under our 'Clinical Map Initiative' strategy."

"ILC 2015 is an extremely important meeting to advance the treatment of HCV and we are pleased to present such significant data on RG-101 in the oral late-breaking session," said Hendrik W. Reesink, M.D., Ph.D., Associate Professor in the Department of Gastroenterology and Hepatology at the Academic Medical Center in The Netherlands.  "Having so many patients with undetectable levels of virus after just a single administration so many months out is truly remarkable and these findings continue to suggest the clinical benefit of RG-101's ability to improve upon current therapies in a wide range of HCV patients.  I look forward to seeing RG-101 progress into future clinical studies."

Click here to watch Regulus' President and CEO, Kleanthis G. Xanthopoulos, Ph.D., provide additional detail on the upcoming combination studies of RG-101 for the treatment of HCV.

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. 

'Clinical Map Initiative' Goals for RG-101

Regulus' 'Clinical Map Initiative' outlines certain corporate goals to advance its microRNA therapeutics pipeline over the next several years.  Regulus plans to investigate RG-101 in combination with oral agents to potentially shorten treatment durations, optimize clinical outcomes and potentially improve responses in certain underserved HCV patient populations, and further as a single agent (multiple doses of RG-101 in specific populations).  In the near term, Regulus expects to initiate the above described studies in the second quarter of 2015 and to report interim data by the end of 2015.

Hepatitis C Virus Infection (HCV)

Hepatitis C is a result of a hepatocyte specific infection induced by the virus known as HCV.  Chronic HCV may lead to significant liver disease, including chronic active hepatitis, cirrhosis, and hepatocellular carcinoma. Up to 185 million people are chronically infected with HCV worldwide, and more than 350,000 people die from HCV annually.  The CDC estimates that there are currently approximately 3.2 million persons infected with HCV in the United States.  HCV shows significant genetic variation in worldwide populations due to its frequent rates of mutation and rapid evolution. There are six genotypes of HCV, with several subtypes within each genotype, which vary in prevalence across the different regions of the world. The response to treatment varies from individual to individual underscoring the inadequacy of existing therapies and highlights the need for combination therapies that not only target the virus but endogenous host factors as well, such as microRNA-122.  Regulus believes that its miR-122 antagonist, RG-101, may be a useful agent in emerging combination regimens to address difficult-to-treat genotypes and to potentially expand upon the current therapies available to clinicians treating HCV patients.

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. In addition, RG-125, a GalNAc-conjugated anti-miR targeting microRNA-103/107 for the treatment of NASH in patients with type 2 diabetes/pre-diabetes, has been selected for clinical development.  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 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.

OLYSIO™ is a registered trademark of Janssen Therapeutics.

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