Arrowhead Pharmaceuticals to Advance Two New RNAi-Based Obesity Candidates, ARO-INHBE and ARO-ALK7, Into Clinical Studies

Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today presented preclinical data and detailed its plans to advance two next generation RNAi-based candidates, ARO-INHBE and ARO-ALK7, into upcoming clinical studies for the treatment of obesity and metabolic diseases. In preclinical studies to date, these candidates demonstrated the potential to reduce body weight and fat mass with a novel mechanism of action that may lead to improved preservation of lean muscle mass compared to currently approved obesity therapies. Arrowhead plans to submit clinical trial applications with regulatory authorities for both programs by the end of 2024 with the goal of initiating clinical studies in volunteers with obesity in early 2025.

“Arrowhead believes that targeting the hepatic expression of the INHBE gene and the production of the Activin E ligand, and the adipose tissue expression of the ALK7 gene and the receptor it encodes, represent promising novel mechanisms to treat obesity and associated metabolic diseases. When studied as mono therapy and in combination with tirzepatide in diet induced obesity mouse models, ARO-INHBE and ARO-ALK7 both resulted in suppression of body weight and fat mass and, importantly, preservation of lean mass leading to improved body composition,” said James Hamilton, M.D., Chief of Discovery and Translational Medicine at Arrowhead. “Following the approval and positive clinical impact of new agents for obesity over the last few years, new therapeutic strategies with novel mechanisms of action are emerging that may represent the future in successful treatment and management of patients with obesity and associated diseases. We are in the final stages of preclinical development of ARO-INHBE and ARO-ALK7 and we are eager to engage with regulators by the end of this year to begin clinical studies of these exciting new medicines.”

ARO-INHBE is designed to reduce the hepatic expression of the INHBE gene and its secreted gene product, Activin E. ARO-ALK7 is designed to reduce the adipose expression of Activin receptor-like kinase 7 (ALK7). INHBE and ALK7 are both genetically validated targets with loss of function variants being associated with lower risk of obesity and metabolic diseases, such as type 2 diabetes. Both targets are involved in the same pathway that regulates energy homeostasis in adipose tissue​, with Activin E acting as a circulating ligand and ALK7 as a receptor on adipocytes. Intervening in this pathway with ARO-INHBE and ARO-ALK7 is believed to result in increased lipolysis, and reductions in adipose hypertrophy and dysfunction, visceral adiposity, and insulin resistance.