Regulus Therapeutics demonstrates human proof-of-concept with microRNA therapeutic

Regulus Therapeutics Inc. (NASDAQ:RGLS), a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, today announced that it has demonstrated human proof-of-concept with a microRNA therapeutic from an ongoing clinical study evaluating RG-101, a wholly-owned, GalNac-conjugated anti-miR targeting microRNA-122 (“miR-122”), for the treatment of hepatitis C virus infection (“HCV”).  Interim results from the ongoing clinical study demonstrate that treatment with a single subcutaneous dose of 2 mg/kg of RG-101 as monotherapy resulted in significant and sustained reductions in HCV RNA in a varied group of patients, including difficult to treat genotypes and patients who experienced viral relapse after a prior IFN-containing regimen.  Additionally, RG-101 was safe and well tolerated and has demonstrated a very favorable pharmacokinetic profile to date, which may allow for combination with oral direct-acting antiviral (“DAA”) agents to treat HCV.

Interim results from the ongoing clinical study are summarized below:

In the first dose cohort of part IV of the ongoing study, 16 HCV patients were enrolled with multiple genotypes, 10 GT1s, 5 GT3s, and 1 GT4. 14 patients, 8 naïve and 6 patients who experienced viral relapse after a prior IFN-containing regimen, received a single subcutaneous dose of 2 mg/kg of RG-101 as monotherapy while 2 patients received placebo.

• In the 14 HCV treated patients, there was a mean viral load reduction of 4.1 log₁₀ at day 29 (range -5.8 log₁₀ to -2.3 log₁₀).
• 6 out of 14 patients had HCV RNA levels below the limit of quantification at day 29 and the 3 patients from this group who have reached day 57 still have HCV RNA levels below the limit of quantification.
• Viral load reduction occurs within the first 96 hours and virologic response is not influenced by IL-28 genotype.
• Due to the long-lasting and sustained virologic effect seen, the ongoing study protocol has been amended to follow patients for up to six months after dosing to evaluate the possibility for certain patients to achieve viral cure after a single dose of RG-101.
• There were no drug-drug interactions from part III of the ongoing study in which RG-101 was combined with simeprevir (OLYSIO™), an approved oral DAA (protease inhibitor), and the combination had no effect on the pharmacokinetic profile of RG-101 or simeprevir (OLYSIO™).
• RG-101 is safe and well tolerated with no serious adverse events reported to date.

“We are very excited to have demonstrated our first human proof-of-concept results with a microRNA therapeutic from the ongoing study of RG-101, which is a significant milestone in Regulus’ history, and represents a key achievement under our ‘Clinical Map Initiative’,” said Kleanthis G. Xanthopoulos, Ph.D., President and Chief Executive Officer of Regulus. 

We believe these interim data are exceptional and provide strong evidence to support the rapid advancement of RG-101 into future clinical studies, while presenting a clear opportunity for a potentially disruptive therapy to the current HCV treatment paradigm.

“RG-101 is the first microRNA therapeutic in clinical development to combine the most advanced RNA technologies from three leading RNA therapeutics companies; chemistry 2.5 from Isis, GalNAc conjugate from Alnylam, and Regulus’ unique and proprietary chemistry including the novel linker that facilitates the release of the parent oligonucleotide after hepatocyte uptake,” said Neil W. Gibson, Ph.D., Chief Scientific Officer. “We believe the innovative design of RG-101 has led to achievement of our first human proof-of-concept results, and hope these findings will advance the growth of our microRNA therapeutics pipeline.” 

“We are very pleased and encouraged with the interim results and believe these findings strongly support the rapid advancement of RG-101 into Phase II development,” said Paul Grint, M.D., Regulus’ Chief Medical Officer.

Currently, we plan to file an Investigational New Drug Application with the U.S. Food and Drug Administration in the first quarter of 2015 and plan to initiate a Phase II DAA combination study of RG-101 in HCV patients in the second quarter of 2015.  In addition, we look forward to reporting additional data from the ongoing study in the first half of next year.

“The efficacy and sustained viral response seen with a single dose of RG-101 is very promising and it was encouraging to see response across a diversity of genotypes and treatment experience in this clinical trial.  Additionally, all patients in the first cohort on active therapy demonstrated a viral response to RG-101, which is also very encouraging,” said Dr. Eric Lawitz, M.D., Vice President, Scientific and Research Development, The Texas Liver Institute, and Clinical Professor of Medicine, University of Texas Health Science Center in San Antonio.  “These findings suggest the clinical benefit of utilizing a unique mechanism of action to potentially treat difficult patient populations.  There may be an opportunity to improve upon the current real world compliance issues with therapies such as RG-101 that may be administered subcutaneously by a clinician.  I look forward to seeing RG-101 advance into future clinical trials.”