Regulus obtains exclusive rights from NYU for miR-33a, 33b to treat metabolic diseases

Regulus Therapeutics Inc., a biopharmaceutical company leading the discovery and development of innovative new medicines targeting microRNAs, today announced that it has obtained exclusive rights from New York University (NYU) for intellectual property covering methods of use in modulating microRNA-33a (miR-33a) and microRNA-33b (miR-33b) for metabolic diseases such as atherosclerosis and metabolic syndrome. Regulus scientists and collaborators from NYU were the first to show that antagonizing miR-33a and miR-33b with therapeutic oligonucleotide anti-miRs have several beneficial effects, including reduction in atherosclerotic plaque and increase in levels of high density lipoprotein (HDL) cholesterol, the 'good' cholesterol. Regulus is developing microRNA therapeutics targeting both miR-33a and miR-33b.

"Regulus scientists and our collaborators at NYU have shown that dysregulation of specific microRNAs, including miR-33a and miR-33b, can drive metabolic disease processes linked to dyslipidemia and atherosclerosis, opening up the possibility of developing a new class of drugs to treat these conditions," said Kleanthis G. Xanthopoulos, Ph.D., president and CEO of Regulus. "miR-33a and miR-33b are promising targets for therapeutic intervention to treat metabolic disease. We are combining our broad and proprietary microRNA therapeutic platform with a deep understanding of microRNA biology to advance this and other programs to the clinic."

The licensed technology relates to the discoveries that miR-33a and miR-33b down-regulate target genes involved in cholesterol transport and genes related to metabolic syndrome. Inhibition of miR-33a and miR-33b by anti-miRs increase circulating HDL cholesterol, suggesting that antagonism of miR-33a and miR-33b may be protective against atherosclerosis. Atherosclerosis is a condition in which artery walls thicken as a result of build-up of fatty material such as cholesterol. This build-up causes atherosclerotic lesions or plaques that can rupture, leading to slowing or stoppage of blood flow and ultimately resulting in myocardial infarction or stroke.

Kathryn Moore, Ph.D., and colleagues at NYU, in collaboration with Regulus, have further demonstrated that anti-miR-33 treatment in mice, which have a single copy of miR-33, reduces arterial lesions in models of atherosclerosis with established atherosclerotic plaques [Rayner et al (2010) Abstract 21739, American Heart Association scientific conference]. Non-human primates and humans have two copies of miR-33 (miR-33a and miR-33b), and technologies developed at Regulus have been used to demonstrate ways to inhibit both.

"Despite the currently available treatment options for atherosclerosis and conditions that increase its risk, like metabolic syndrome, coronary artery disease remains a major killer in the developed world pointing to the need for novel therapeutic approaches such as inhibiting miR-33," said Kathryn Moore, Ph.D., associate professor in NYU Langone Medical Center Department of Medicine. "Our initial work with NYU colleague Carlos Fernandez-Hernando, Ph.D. published in Science last year and additional preclinical research performed in collaboration with Regulus have shown that antagonizing miR-33a and miR-33b with anti-miRs can have significant impact on HDL raising and atherosclerotic plaque reduction. The growing preclinical data provides confidence that a microRNA therapeutic targeting miR-33a and miR-33b can have potential impact on this unmet medical need."

In addition to the newly licensed patent rights covering therapeutic uses of targeting miR-33a and miR-33b, Regulus controls fundamental patent rights related to miR-33a and miR-33b, including compositions of matter for the miR-33a and miR-33b sequence and complement covered in the Tuschl III patent series and various chemically modified anti-miR compounds targeting miR-33a and miR-33b discovered by Regulus.