Regeneron and Alnylam Team up to Tackle NASH Liver Disease

Regeneron Pharmaceuticals, Inc. and Alnylam Pharmaceuticals signed a collaborationdeal to identify RNAi therapies for nonalcoholic steatohepatitis (NASH) and other possibly related liver diseases.

NASH is similar to cirrhosis of the liver, but occurs in people who drink little or no alcohol. There are currently no treatments aside from diet and exercise. The disease is linked to the obesity epidemic.

Regeneron recently published a study in The New England Journal of Medicinedescribing their use of exome sequence data and electronic health records as part of the DiscovEHR human genetic study to identify genetic variations linked to serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). They were then evaluated for correlation with chronic liver disease. What they found was a variant in HSD17B13, involved in a liver protein, that caused loss of function, was linked to reduced risk of chronic liver disease and a progression from steatosis to steatohepatitis.

Under the agreement, Regeneron will provide research on the HSD17B13 target. Alnylam will utilize its RNAi therapeutics platform to find compounds against the target. The two companies plan an equal but separate, fifty-fifty collaboration on any product candidates that are identified.

RNA interference (RNAi) is a naturally-occurring process that silences genes. Small interfering RNA (siRNA) molecules mediate RNAi and make up Alnylam’s therapeutic platform.

"We obviously saw the data and we were blown away," Alnylam’s chief executive officer, John Maraganore, told Endpoints News’ John Carroll. "This target—HSD17B13—from a human genetics perspective it really is the PCSK9 of NASH."

PCSK9 is the target of a new group of cholesterol-lowering drugs, notably Amgen's Repatha and Sanofi and Regeneron’s Praluent.

The researchers found that blocking the gene cut enzymatic activity, which decreased the risk of alcoholic cirrhosis by 73 percent, cut the risk of nonalcoholic cirrhosis by 49 percent, and lowered the risk of alcoholic liver disease by 53 percent and nonalcoholic liver disease by 30 percent, all of which led to a decreased risk of NASH.

Carroll writes, "Regeneron prides itself on moving aggressively when they find something promising for clinical development. And in Alnylam, they feel they are working with close kin in that respect. … How fast can Alnylam move here? ‘We’re not giving guidance," says Maraganore, but he says you shouldn’t be surprised if there’s a program in the clinic next year. (Yes, that is fast.)"

This deal is the two companies’ second recent collaboration. In January 2018, Alnylam and other life science companies joined Regeneron’s pre-competitive consortium to sequence 500,000 individuals in the UK Biobank health resource.

"Our Regeneron Genetics Center is delivering new targets that will require new approaches beyond our biologics capabilities," said George Yancopoulos, president and chief scientific officer of Regeneron, in a statement. "Since we are committed to following the science, we are pleased to join together with an equally science-minded company with a novel RNAi therapeutic approach that appears well-suited to impact this particular target. NASH is a major cause of death in this country, with no current treatment options. We’re eager to build on the exciting science delivered by the Regeneron team in the hopes of helping patients with debilitating and life-threatening chronic liver diseases."

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