Regulus begins RG-125(AZD4076) Phase I study for treatment of NASH in patients with type 2 diabetes/pre-diabetes

Regulus Therapeutics Inc. (NASDAQ: RGLS), a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, announced today that dosing has begun in a first-in-human Phase I clinical study of RG-125(AZD4076), by its collaboration partner AstraZeneca. RG-125(AZD4076) is a GalNAc-conjugated anti-miR-103/107 oligonucleotide that has been shown to improve insulin sensitivity and glucose tolerance in animal models. RG-125(AZD4076) was jointly identified and selected as a clinical candidate in April 2015 by AstraZeneca under the companies' strategic alliance to discover, develop and commercialize microRNA therapeutics. AstraZeneca will pay Regulus $10.0 million and will assume further development of RG-125(AZD4076).

Previous research has demonstrated a causative role of microRNAs in pathophysiological processes of metabolic diseases, and increased expression of miR-103/107 in the liver has been associated with insulin resistance in people with non-alcoholic steatopheatitis (NASH), or fatty liver disease.  In mechanistic studies, RG-125(AZD4076) showed effects on biological pathways implicated in NASH progression.

"RG-125(AZD4076) acts as a novel insulin sensitizer which represents a potential new mechanism to treat patients with metabolic diseases such as type 2 diabetes and NASH," said Paul Grint, MD, President and Chief Executive Officer of Regulus. "Regulus is pleased to see the advancement of our third microRNA therapeutic program into clinical development and we look forward to working with AstraZeneca to bring this novel treatment one step closer to patients in need."

In August 2012, Regulus and AstraZeneca formed a strategic alliance to discover and develop microRNA therapeutics for cardiovascular diseases, metabolic diseases and oncology. Regulus and AstraZeneca aim to collaborate on three exclusive microRNA targets: AstraZeneca has selected miR-103/107 (RG-125(AZD4076)). In addition to the $2.5 million milestone payment for the clinical candidate selection announced in April and the $10.0 million milestone payment for RG-125(AZD4076) entering Phase I announced today, Regulus is eligible to receive future milestone payments under the terms of the strategic alliance agreement, which include significant launch and commercial milestone payments and royalties.