PASADENA, Calif.–(BUSINESS WIRE)–Feb. 25, 2025–Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced preclinical results on ARO-ALK7, the company’s investigational RNA interference (RNAi) therapeutic targeting Activin receptor-like kinase 7 (ALK7) being developed as a potential treatment for obesity. The results were presented in a poster at the Keystone Symposia on Obesity and Adipose Tissue held February 23–26, 2025 in Banff, AB, Canada.
ARO-ALK7 is the first RNAi-based therapy to directly target a gene expressed in adipose tissue and highlights Arrowhead’s leadership in the delivery of siRNA to multiple tissues and cell types throughout the body utilizing its proprietary and differentiated Targeted RNAi Molecule (TRiM™) platform. Arrowhead received regulatory clearance to initiate a Phase 1/2a clinical trial of ARO-ALK7 in New Zealand, which the company anticipates will begin dosing in the second quarter of 2025.
“Human genetic studies support ALK7 as a promising therapeutic target for the treatment of obesity. Loss-of-function ALK7 variants have been associated with improved body composition, protection from type 2 diabetes, and reduced risk of cardiovascular disease. While incretin-based therapies are the current frontline pharmacotherapeutics for obesity and metabolic outcomes, issues concerning significant loss of lean mass, adverse GI events at high dose levels, and disproportional fat mass gain after cessation of the therapies remain a challenge for many patients,” said James Hamilton, M.D., MBA, Chief Medical Officer and Head of R&D. “In preclinical studies in rodents and non-human primates, ARO-ALK7 demonstrated dose-dependent and durable reductions in ALK7 mRNA expression in adipose tissue. Pharmacological studies in diet-induced obese mouse models demonstrate that ALK7 silencing in adipose tissue led to improved body composition, with an approximate 50% reduction in fat mass with preservation of lean mass. Furthermore, co-treatment of tirzepatide, a GLP-1/GIP receptor co-agonist, with ALK7 siRNA enhanced the therapeutic benefits versus tirzepatide monotherapy, with additive effects on body weight and fat mass reduction while ameliorating the significant loss of lean mass associated with tirzepatide monotherapy. Lastly, body fat loss in mice with ALK7 silencing was attributed to increased energy expenditure and lipolysis without a change in food intake, suggesting that the effect was due to fat being metabolized as opposed to caloric reduction.”
About ARO-ALK7
ARO-ALK7 is designed to silence adipocyte expression of the ACVR1C gene to reduce the production of Activin receptor-like kinase 7 (ALK7), which acts as a receptor in a pathway that regulates energy homeostasis in adipose tissue. In large genetic datasets, reduced ACVR1C expression has been associated with healthier adipose distribution and reduced risk of obesity-related metabolic complications. Treatment with investigational ARO-ALK7 has the potential to reduce visceral adiposity and improve lipid and glycemic parameters.
About the AROALK7-1001 Phase 1/2a Study
AROALK7-1001 is a Phase 1/2a first-in-human dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ARO-ALK7 in up to 90 adult volunteers with obesity. Part 1 of the study is designed to assess single and multiple doses of ARO-ALK7 monotherapy, and Part 2 of the study is designed to assess ARO-ALK7 in combination with tirzepatide, a subcutaneously administered GLP-1/GIP receptor co-agonist that has been approved in the United States and the European Union for management type 2 diabetes mellitus since 2022 and weight management since 2023/2024 respectively.
About Arrowhead Pharmaceuticals
Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing.
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