Arrowhead presents preclinical results on ARO-ALK7

Arrowhead (ARWR) announced preclinical results on ARO-ALK7, the company’s investigational RNA interference therapeutic targeting Activin receptor-like kinase 7 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 in Banff, AB, Canada. Single subcutaneous doses of ARO-ALK7 led to dose-dependent and durable reductions in ALK7 mRNA in abdominal fat. Approximately 80% knockdown achieved at 0.3 mg/kg. Approximately 91% knockdown achieved at 1.5 mg/kg with 75% knockdown still observed after 12 weeks ALK7 silencing in adipose tissue suppressed body weight gain and improved body composition. Body weight gain was suppressed by 40% relative to control. Approximately 50% reduction in fat mass with preservation of lean mass by DEXA imaging was observed in treated animals. Body fat loss in treated animals was mechanistically attributed to lipolysis and increased energy expenditure. No change in food intake was observed Increased oxygen consumption and heat production were observed. Increased levels of glycerol, NEFAs, and ketones were observed and animals exhibited upregulation in the expression of lipolytic genes. ALK7 silencing enhanced the therapeutic benefit of tirzepatide. Co-treatment of tirzepatide and ALK7 siRNA had additive effects on body weight and fat mass reductions. ALK7 siRNA ameliorated the loss of lean mass observed with monotherapy treatment with tirzepatide. ARO-ALK7 was generally well-tolerated with no adverse or dose-limiting findings identified in Han Wistar rats.