Alnylam Uncovers Genetic Mutations in INHBE That Protect Against Abdominal Obesity

– Publication in Nature Communications Reports that People with Loss of Function Mutations in the INHBE Gene Have Reduced Abdominal Fat, a Favorable Metabolic Profile, and are at Lower Risk of Cardiovascular Disease and Type 2 Diabetes –

– Alnylam to Pursue INHBE as a Therapeutic Target for Cardiometabolic Disease –

Excerpt from the Press Release:

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today that the Company and collaborators have identified mutations in the INHBE gene associated with protection against abdominal obesity and metabolic syndrome – a condition impacting more than 20 percent of adults worldwide. The discovery leveraged sequencing data from more than 360,000 individuals in UK Biobank, and was published in the 13^th issue of Nature Communications. The published data show that rare mutations in the liver-expressed INHBE gene are associated with lower waist-to-hip ratio adjusted for body mass index (WHRadjBMI), a surrogate for abdominal fat that is causally linked to type 2 diabetes and coronary heart disease. Findings support the potential of INHBE to be evaluatedas a novel therapeutic target for the treatment of cardiometabolic disease. The Company plans to pursue a development candidate for INHBE and its gene product, Activin E, leveraging its liver IKARIA™ platform.

“We are thrilled that our investment in genetic databases like UK Biobank is proving to be fruitful in identifying novel targets in highly prevalent diseases with continued unmet need,” said Paul Nioi, Ph.D., Vice President, Discovery and Translational Research, and the Leader of Alnylam’s Human Genetics Group. “There is a well-established causal link between increased waist-to-hip ratio and a person’s risk of cardiometabolic conditions. By exploring the genetic determinants of waist-to-hip ratio in this study, important insights into the mechanisms that contribute to body fat distribution were uncovered helping identify potential therapeutic targets for abdominal obesity, like INHBE. The results of this exome-wide analysis suggest that targeting INHBE is predicted to have broad beneficial effects on all facets of metabolic syndrome with potential reductions in the risk of type 2 diabetes and coronary heart disease. We are currently testing this hypothesis, with the goal of pursuing a development candidate targeting INHBE in the near future.”

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