About RG-125

In April 2015, RG-125 (AZD4076), a GalNAc-conjugated anti-miR targeting microRNA-103/107 (“miR-103/107”) for the treatment of nonalcoholic steatohepatitis (“NASH”) in patients with type 2 diabetes/pre-diabetes, was selected as a clinical candidate by AstraZeneca under the companies’ strategic alliance to discover, develop and commercialize microRNA therapeutics.  The role of miR-103/107 in insulin sensitivity and resistance was first recognized by the laboratory of Dr. Markus Stoffel, Professor of the Institute of Molecular Health Sciences at ETH Zurich. In mouse models of diabetes, Regulus has demonstrated that inhibition of miR-103/107 with its anti-miRs leads to a sustained reduction in fasting glucose and fasting insulin levels.

Additionally, anti-miRs targeting miR-103/107 function as unique insulin sensitizers as determined by hyperinsulinemic-euglycemic clamp, which is a robust method for assessing insulin sensitivity.

Dosing has commenced in a first-in-human Phase I study of RG-125(AZD4076) by Regulus’ collaboration partner AstraZeneca. Regulus received a $10.0 million milestone payment from AstraZeneca, who has assumed all ongoing development of RG-125(AZD4076).

About NASH

Nonalcoholic steatohepatitis or NASH is a common, often “silent” liver disease. It resembles alcoholic liver disease, but occurs in people who drink little or no alcohol. The major feature in NASH is fat in the liver, along with inflammation and damage. Most people with NASH feel well and are not aware that they have a liver problem. Nevertheless, NASH can be severe and can lead to cirrhosis, in which the liver is permanently damaged and scarred and no longer able to work properly.

NASH affects 2 to 5 percent of Americans. An additional 10 to 20 percent of Americans have fat in their liver, but no inflammation or liver damage, a condition called “fatty liver.” Although having fat in the liver is not normal, by itself it probably causes little harm or permanent damage. If fat is suspected based on blood test results or scans of the liver, this problem is called nonalcoholic fatty liver disease (NAFLD). If a liver biopsy is performed in this case, it will show that some people have NASH while others have simple fatty liver.

Both NASH and NAFLD are becoming more common, possibly because of the greater number of Americans with obesity. In the past 10 years, the rate of obesity has doubled in adults and tripled in children. Obesity also contributes to diabetes and high blood cholesterol, which can further complicate the health of someone with NASH. Diabetes and high blood cholesterol are also becoming more common among Americans.