Arrowhead Pharmaceuticals to Advance Two New RNAi-Based Obesity Candidates Into Clinical Trials

Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) has unveiled promising preclinical data for two innovative RNAi-based candidates, ARO-INHBE and ARO-ALK7, which are set to enter clinical trials for treating obesity and metabolic diseases. The preclinical studies have shown that these compounds have the potential to reduce body weight and fat mass through a novel mechanism, potentially offering better preservation of lean muscle mass than existing obesity treatments. Arrowhead aims to submit clinical trial applications by the end of 2024 and begin studies in early 2025.

James Hamilton, M.D., the Chief of Discovery and Translational Medicine at Arrowhead, emphasized the significance of targeting the hepatic expression of the INHBE gene and production of the Activin E ligand, as well as the adipose tissue expression of the ALK7 gene and its receptor. These novel mechanisms hold promise for treating obesity and related metabolic diseases. In mouse models with diet-induced obesity, both ARO-INHBE and ARO-ALK7 have shown effectiveness in reducing body weight and fat mass while preserving lean muscle mass, suggesting improved body composition. Dr. Hamilton expressed optimism about engaging with regulators to advance these candidates into clinical trials.

ARO-INHBE aims to lower the hepatic expression of the INHBE gene and its secreted product, Activin E, while ARO-ALK7 targets the reduction of adipose expression of Activin receptor-like kinase 7 (ALK7). Both INHBE and ALK7 are genetically validated targets, with loss of function variants linked to a reduced risk of obesity and metabolic conditions like type 2 diabetes. These targets are part of a 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 enhance lipolysis, reduce adipose hypertrophy and dysfunction, lower visceral fat, and improve insulin resistance.

Arrowhead Pharmaceuticals is dedicated to developing therapies that address difficult-to-treat diseases by silencing the genes responsible for them. Utilizing a broad range of RNA chemistries and efficient delivery methods, Arrowhead's therapies activate the RNA interference (RNAi) mechanism to achieve rapid, deep, and lasting knockdown of target genes. RNAi is a natural cellular process that inhibits gene expression, thereby affecting protein production. Arrowhead’s RNAi-based treatments aim to harness this pathway to achieve therapeutic benefits.

The company invites interested parties to join Part IV of Arrowhead’s 2024 Summer Series of R&D Webinars, scheduled for August 14, 2024, at 2:00 PM ET. This event will feature Arrowhead management and Carel le Roux, M.D., Ph.D., from University College Dublin. Information about the live event and an archived webcast is accessible on the Events and Presentations page in the Investors section of the Arrowhead website.

Arrowhead Pharmaceuticals continues to pioneer solutions for challenging diseases through gene silencing and RNAi-based therapies, with the goal of transforming the treatment landscape for patients with obesity and metabolic diseases.