SoCal's Regulus Sinks After AstraZeneca PLC Bails on Lead NASH Drug

SoCal's Regulus Sinks After AstraZeneca PLC Bails on Lead NASH Drug June 12, 2017
By Alex Keown, Breaking News Staff

LA JOLLA, Calif. – The troubles appear to be continuing for beleaguered Regulus Therapeutics . Shares of Regulus are down more than 23 percent this morning after pharma giant AstraZeneca terminated its involvement with the company’s clinical development program for the treatment of non-alcoholic steatohepatitis (NASH).

In addition to the termination of its developmental deal with AstraZeneca, the company has discontinued two drug programs, including one that has been on clinical hold for a year.

In a statement this morning, California-based Regulus announced AstraZeneca’s decision to end co-development of AZD4076(RG-125) for the treatment of NASH in Type 2 Diabetes/Pre-diabetes. AstraZeneca’s rights to AZD4076(RG-125) will fully revert to Regulus when AstraZeneca’s involvement is completely terminated. That will not occur for another 12 months, the company said this morning. The two companies have been working on development of AZD4076(RG-125) since 2015 when it was selected as a clinical candidate under AstraZeneca’s strategic alliance plans.

NASH treatments are expected to be a $40 billion market, in large part due to the increase of obesity and diabetes diagnoses. In the United States, NASH affects between 2 and 5 percent of the population. Regulus is looking to carve out its own share of this market with its experimental treatment.

That’s not all the bad news that beleaguered Regulus announced. The company also said it was discontinuing studies of its hepatitis C candidate, RG-101. The company said there is one remaining clinical trial for RG-101 in motion, but once that is complete, it will discontinue the program. Development of RG-101 has been in doubt for some time. Last year the U.S. Food and Drug Administration placed the trial on clinical hold after Regulus reported a second serious adverse event of jaundice. Regulus had initially said it intended to provide all of the necessary data to the FDA to answer questions, but in January of this year the regulatory agency requested additional expert review of liver safety data.

RG-101 is a GalNAc-conjugated anti-miR targeting microRNA-122 for the treatment of chronic hepatitis C virus infection.

In its announcement this morning, Regulus attempted to provide some of those answers surrounding RG-101. The company said it believes “a combination of factors including inhibition of conjugated bilirubin transport by RG-101, impaired baseline bilirubin transport in HCV patients and the preferential uptake of RG-101 by hepatocytes contributed to this mechanism.” The company added that additional “patient specific contributing factors” could not be excluded from the possible issues.

Additionally, Regulus discontinued its cholestatic disease treatment RGLS5040, an unconjugated inhibitor of microRNA27. The company said it discontinued the program due to the “competitive landscape” as well as “results from repeat pharmacology studies as part of IND-enabling work.”

In May, Regulus terminated 30 percent of its workforce. Chief Executive Officer Paul Grint also tendered his immediate resignation as the company undertakes a new strategic tack. At the time new CEO Joseph P. “Jay” Hagan said the company’s priorities were focused on microRNA candidate, RG-012 for the treatment of Alport Syndrome. The company is expected to begin Phase II testing and a renal biopsy by mid-2017. This morning the company said changes to the trial have been made “with the goal to accelerate patient enrollment, improve statistical power, and potentially achieve proof of mechanism data by the end of 2017.” Data from the renal biopsy study is anticipated by year-end 2017 and interim data from the Phase II study is anticipated in mid-2018.

Shares of Regulus are trading at $1.08 as of 9:49 a.m.

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