Regeneron Pharmaceuticals, Inc. and Alnylam Pharmaceuticals, Inc. announced a collaboration to identify RNAi therapeutics for the chronic liver disease nonalcoholic steatohepatitis (NASH) and potentially other related diseases. The discovery collaboration is based on a new Regeneron publication in the New England Journal of Medicine identifying for the first time a variant in the HSD17B13 gene that is associated with reduced risk of chronic liver diseases. RNA interference (RNAi) therapeutics represent a novel and innovative approach to specifically target and silence any gene involved in the cause or pathway of human disease; this approach could potentially mimic the naturally occurring loss-of-function genetic variation in HSD17B13 seen in people who are protected from NASH disease progression.

"At Alnylam, we are dedicated to advancing RNAi therapeutics as a new class of medicines for patients with few or no treatment alternatives," said John Maraganore, Ph.D., chief executive officer at Alnylam. "As we transition Alnylam toward commercialization in rare diseases, the prospect of collaborating with a scientific leader like Regeneron on innovative medicines for more prevalent diseases like NASH makes perfect strategic sense. We believe the exquisite specificity afforded by the RNAi mechanism of action and our industry-leading, proprietary GalNAc-conjugate approach for delivery to the liver is an unparalleled combination for developing an RNAi therapeutic toward genetically-validated targets in NASH."

Under the discovery collaboration, Regeneron will contribute research on the hepatocyte-expressed, genetically-validated HSD17B13 target, and Alnylam will leverage its RNAi therapeutics platform to identify compounds directed to this target. Regeneron and Alnylam intend to enter into a separate, fifty-fifty collaboration to further research, co-develop and commercialize any therapeutic product candidates that emerge from these discovery efforts.

"Our Regeneron Genetics Center is delivering new targets that will require new approaches beyond our biologics capabilities. 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," said George D. Yancopoulos, M.D., Ph.D., president and chief scientific officer of Regeneron. "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."

Chronic liver disease and cirrhosis are leading causes of morbidity and mortality in the United States, accounting for over 38,000 deaths in 2014. The most common precursors to cirrhosis are alcoholic liver disease, chronic hepatitis C and nonalcoholic fatty liver disease (NAFLD). About 3 to 12 per cent of adults in the United States have NASH, a more severe type of NAFLD, and prevalence is increasing due to rising rates of obesity. There is a great need for new medicines that treat non-viral forms of chronic liver disease, as there are currently no approved drugs for these conditions.

This is Regeneron and Alnylam's second recent collaboration founded on genetic exploration. In January 2018, Alnylam, alongside multiple other leading life sciences companies, joined Regeneron's pre-competitive consortium to sequence 500,000 individuals in the UK Biobank health resource and subsequently make the data publicly available to the global research community.

RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of today's medicines by potently silencing messenger RNA (mRNA) - the genetic precursors - that encode for disease-causing proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

Alnylam is leading the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare genetic, cardio-metabolic, and hepatic infectious diseases.

Regeneron is a leading biotechnology company that invents life-transforming medicines for people with serious diseases.