New preclinical study shows RG-012 may provide therapeutic benefit for Alport syndrome patients

Treatment with RG-012 Protects Kidney Function and Demonstrates Additive Therapeutic Effect with Emerging Standard of Care in Preclinical Model of Alport Syndrome

Regulus Therapeutics Inc. (NASDAQ: RGLS), a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, today announced that positive new preclinical data was presented on RG-012 for the treatment of renal dysfunction in Alport syndrome patients at the American Society of Nephrology's (ASN) Kidney Week 2014 meeting being held November 11-16, 2014 in Philadelphia, PA. 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. These findings, and the new preclinical data presented at the ASN meeting, provide additional evidence that RG-012 may provide therapeutic benefit in the treatment of Alport syndrome.

In an oral presentation titled "Anti-miR-21 as a Potential Novel Therapy for Both Early and Late Stages of Alport Syndrome", Regulus' strategic alliance partner, Genzyme, a Sanofi company, presented new data demonstrating that treatment with RG-012 in a mouse model of disease improves renal function, protects against kidney damage and extents the lifespan of the mice when treatment begins at both early and late stages of the disease by reversing multiple dysregulated pathways. Further, combination studies were performed with RG-012 and ramipril, Sanofi's ACE inhibitor, a kidney protectant, to assess the therapeutic utility of adding a microRNA therapeutic to this emerging standard of care. In these preclinical studies, treatment with RG-012 was shown to protect kidney function better than ramipril alone and an additive therapeutic effect was observed in combination with ramipril.

"These data enhance the preclinical profile of RG-012 and provide us with further confidence in the potential to treat disease with microRNA therapeutics," said Neil W. Gibson, Ph.D., Chief Scientific Officer of Regulus. "Currently, we are enrolling Alport syndrome patients in ATHENA, our global natural history of disease study, and expect to initiate a Phase I study in healthy volunteers in the first half of 2015 and a Phase II proof-of-concept study thereafter."