Regulus to Present Additional Preclinical Data Supporting RG-012 as a Novel microRNA Therapeutic in Development for Alport Syndrome at ASN's Kidney Week 2015

Regulus Therapeutics Inc. RGLS, a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs (miR), will present new preclinical data regarding RG-012, a single stranded, chemically modified oligonucleotide that binds to and inhibits the function of microRNA-21 ("miR-21"), at the American Society of Nephrology's (ASN) Kidney Week 2015 meeting being held November 3-8, 2015 in San Diego, CA. RG-012 is being developed by Regulus in a strategic alliance with Genzyme, a Sanofi company, for the treatment of Alport syndrome, a life-threatening genetic kidney disease with no approved therapy. Regulus Therapeutics Inc. Logo November 7, 2015, 10am-12pm: Novel Methodology for Assessing Inhibition of MicroRNA-21 by RG-012, a MicroRNA Therapeutic in Development for the Treatment of Kidney Dysfunction in Patients with Alport Syndrome The novel methodology allows for the direct measurement of microRNA inhibition by determining the displacement of a microRNA from actively translating polysome complexes; In both the liver and kidneys of Col4A3 deficient mice, a model that closely mimics Alport syndrome in humans, RG-012 demonstrated dose-dependent displacement of miR-21 from actively translating polysome complexes, and subsequent derepression of messenger RNA targets; and These results provide further support for the clinical development of RG-012. November 7, 2015, 10am-12pm: Nonclinical Pharmacokinetics and Toxicokinetics of RG-012, an Inhibitor of MicroRNA-21 Being Investigated for Treatment of Alport Syndrome RG-012 was characterized by rapid absorption and slow tissue elimination after subcutaneous administrations (half-life in the liver and kidney of approximately two to three weeks); RG-012 exhibited little to no potential to inhibit or induce CYP450 enzymes in vitro, reducing concerns of any potential drug-drug interactions; and These favorable preclinical pharmacokinetic and toxicokinetic properties supported initial clinical testing of RG-012 in healthy volunteers and support planned evaluations in patients with Alport syndrome. November 6, 2015, 10am-12pm: Discovery of Urine MicroRNA Biomarkers in a Pre-Clinical Model of Alport Nephropathy Regulus profiled microRNAs in urine, serum and kidney tissue of a wild type control and a preclinical model of Alport nephropathy in order to identify microRNA biomarkers with the ability to reflect disease progression; Regulus identified several urine microRNAs with highly significant differential expression in Col4A3 deficient mouse when compared to wild type mice; and These data suggest that analysis of urine may be favorable for the development of non-invasive microRNA based tests. "We are pleased to be making several presentations on our RG-012 program during this year's Kidney Week meeting that we believe further demonstrate the compound's novel mechanism and therapeutic potential to treat patients with Alport Syndrome," said Paul Grint, M.D., President and Chief Executive Officer of Regulus. "There are few treatment options for patients with this devastating and debilitating disease and we look forward to advancing RG-012 in clinical development." Alport syndrome is a life-threatening, genetic kidney disease with no approved therapy, and currently, ACE (angiotensin-converting enzyme) inhibitors are emerging as standard of care to treat proteinuria, an indicator of chronic kidney disease (CKD) in these patients. Studies have shown that miR-21 plays a role in the progression of Alport syndrome and is up-regulated in mouse disease models, other renal fibrosis models and human CKD patients. In June 2015, Regulus initiated dosing in a first-in-human Phase I clinical study to evaluate the safety, tolerability and pharmacokinetics of subcutaneous dosing of RG-012 in healthy volunteers. In addition to the Phase I clinical study, Regulus is currently enrolling Alport syndrome patients in a natural history of disease study called ATHENA. With this study, which has thirteen clinical sites worldwide, Regulus aims to learn more about the changes in renal function over time in patients with Alport syndrome. Data from the ATHENA study will provide the clinical basis for the design of a Phase II study to monitor the therapeutic effect of RG-012 on the decline in renal function and time to end-stage renal disease in Alport syndrome patients.