AstraZeneca selects Regulus' RG-125 as clinical candidate for treatment of NASH

Regulus Therapeutics Inc. (NASDAQ:RGLS), a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, announced today the selection of RG-125 (AZD4076), a GalNAc-conjugated anti-miR targeting microRNA-103/107 (“miR-103/107”) for the treatment of Non Alcoholic Steatohepatitis (“NASH) in patients with type 2 diabetes/pre-diabetes, as a clinical candidate by AstraZeneca under the companies’ strategic alliance to discover, develop and commercialize microRNA therapeutics. RG-125 (AZD4076) is the first compound from the alliance to be selected for clinical development by AstraZeneca. In connection with the candidate selection, AstraZeneca will pay Regulus $2.5 million and will assume development of the program following acceptance of an Investigational New Drug application. In the near term, Regulus and AstraZeneca plan to submit key preclinical data on the RG-125 (AZD4076) program to be presented at a scientific meeting later this year and expect to initiate a Phase I study of RG-125 (AZD4076) in humans by the end of 2015.

“Regulus is very pleased that AstraZeneca has chosen to advance a microRNA therapeutic candidate from this exciting program toward the clinic. RG-125 acts as a novel insulin sensitizer which we believe may inform a differentiated development path to treat patients with complicated metabolic disorders,” said Neil W. Gibson, Ph.D., Chief Scientific Officer of Regulus. “RG-125 represents our third clinical development candidate to arise from our novel technologies in less than two years, which confirms the productivity of our platform, achieves a key goal under our ‘Clinical Map Initiative’, and underscores our leadership in the microRNA therapeutics field.”

Marcus Schindler, Head of Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development, AstraZeneca, said:

This is a tremendous achievement for our collaboration and an exciting step for AstraZeneca to be progressing AZD4076 (RG-125), an anti-microRNA molecule, into preclinical development. This again demonstrates AstraZeneca’s commitment to innovation in science and to progress medicines for diseases with unmet medical need.

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 and member of Regulus' Scientific Advisory Board. 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. Further, inhibition of miR-103/107 with Regulus’ anti-miRs decreases liver triglycerides and steatosis, providing an opportunity to investigate RG-125 (AZD4076) to treat NASH in patients with type 2 diabetes/pre-diabetes.

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, microRNA-19, and has a contractual right to select a third microRNA target. Today, Regulus announced that AstraZeneca selected the first clinical development candidate under the alliance, RG-125 (AZD4076), targeting miR-103/107 for the treatment of NASH in patients with type 2 diabetes/pre-diabetes.

To date, under the terms of the strategic alliance, AstraZeneca has paid $28.0 million to Regulus, which includes a $25.0 million equity investment (made concurrent with Regulus’ initial public offering in October 2012) and a $3.0 million upfront payment. Regulus has earned a $2.5 million milestone payment for the clinical candidate selection announced today. In addition to these payments, Regulus is eligible to receive up to $495.5 million in future milestone payments. Under the terms of the agreement, Regulus will lead preclinical development of the programs under the strategic alliance, and if successful, could receive preclinical milestone payments. AstraZeneca will lead and fund the clinical development and commercialization of these programs. In addition, Regulus could also receive clinical milestones based on the successful development of microRNA therapies in each target area. Regulus is eligible to receive significant launch and commercial milestone payments and royalties, contingent on the successful commercialization of microRNA therapeutic products by AstraZeneca.