Regulus Therapeutics reports top-line results from RG-101 clinical study for HCV treatment

Feb 9 2015

Regulus Therapeutics Inc. (NASDAQ: RGLS), a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, today announced top-line results from the 4 mg/kg cohort and additional results from the 2 mg/kg cohort in a completed 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"). Treatment with a single subcutaneous dose of 4 mg/kg of RG-101 as monotherapy resulted in significant and sustained viral load reductions in all patients, including difficult to treat genotypes, various liver fibrosis status and those who have experienced viral relapse after a prior IFN-containing regimen. To date, RG-101 continues to have a favorable safety profile with no serious adverse events or discontinuations reported in the treated HCV patients.

Top-line results from the 4 mg/kg dose cohort:

In the 4 mg/kg dose cohort, 16 HCV patients were enrolled: 14 patients, 12 naive and 2 patients who experienced viral relapse after a prior IFN-containing regimen, received a single subcutaneous dose of 4 mg/kg of RG-101 as monotherapy, and 2 patients received placebo.

• In the 14 treated HCV patients, there was a mean viral load reduction of 4.8 log₁₀ at day 29 (range -5.8 to -3.0); and
• 9 out of 14 patients had HCV RNA levels below the limit of quantification (<15 IU/ml) ("BLOQ") at day 57 and these patients will be followed up to six months to investigate the potential for viral cures following the single administration of 4 mg/kg of RG-101.

Extended follow-up results from the 2 mg/kg dose cohort:

In October 2014, Regulus reported interim efficacy and safety results and its first human proof of concept results from the 2 mg/kg cohort of the completed study evaluating RG-101 for the treatment of HCV.

• At day 85, 4 out of 14 treated patients with varied genotypes, liver fibrosis status and treatment history were Target Not Detected ("TND"); 2 of the treated patients that were BLOQ at day 57 relapsed shortly thereafter; and
• Due to the longevity of the viral responses demonstrated, the protocol is being amended to add an additional year of follow up to investigate the potential for viral cures with one single administration of RG-101.

Summary of 2 mg/kg and 4 mg/kg dose cohort results:

Treatment with a single subcutaneous dose of either 2 mg/kg or 4 mg/kg of RG-101 as monotherapy has resulted in significant and sustained viral load reductions in all patients including difficult to treat genotypes, various liver fibrosis status and those who have experienced viral relapse after a prior IFN-containing regimen. At day 57, 15 out of 28 patients treated with one single administration of either 2 mg/kg or 4 mg/kg of RG-101 had HCV RNA levels BLOQ and 12 out of these 15 treated patients were TND.

"The profile of RG-101 has been significantly enhanced with these top-line data, making it an ideal pan-genotypic asset to investigate further in combination with all classes of oral agents to shorten the duration of treatment, increase patient compliance and maintain viral response, and also as monotherapy in certain underserved HCV populations," said Kleanthis G. Xanthopoulos, Ph.D., President and CEO of Regulus. "With the promising data reported today, our confidence in our ability to treat diseases with microRNA therapeutics is higher than ever and we look forward to continuing to execute our 'Clinical Map Initiative' goals for RG-101 and our microRNA therapeutics pipeline."

"We continue to be pleased with the clinical results demonstrated with RG-101 and have a much more robust data set to inform our dual-track clinical development plans for Phase II," said Paul Grint, M.D., Chief Medical Officer of Regulus. "We have filed our pre-IND briefing book with the U.S. Food and Drug Administration and are working to file a Clinical Trial Application to conduct monotherapy and combination studies in multiple countries. In the second quarter of 2015, we look forward to initiating these studies and reporting full results from the completed study."

"These results demonstrate a significant breakthrough in the treatment of HCV," said Hendrik W. Reesink, M.D., Ph.D., Associate Professor in the Department of Gastroenterology and Hepatology at the Academic Medical Center in The Netherlands. "These landmark studies were conducted with a high level of novelty and practical clinical importance. All twenty-eight patients treated with one administration of RG-101 responded and more than 50% had HCV RNA levels below the lower limit of quantification at day 57. I look forward to seeing RG-101 rapidly advance in Phase II to test its utility in combination with oral agents and possibly as monotherapy."

SOURCE Regulus Therapeutics Inc.