Arrowhead Pharma Shares Preclinical Data on RNAi-Based Obesity Program ARO-INHBE

Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR), based in Pasadena, California, has unveiled promising preclinical data on ARO-INHBE, a novel RNAi-based treatment targeting obesity and metabolic disorders. The findings were presented at the American Diabetes Association (ADA) 84th Scientific Sessions held from June 21-24 in Orlando, Florida, and virtually.

The data highlight the effectiveness of ARO-INHBE in significantly reducing the hepatic expression of the INHBE gene. This gene has emerged as a key target for advanced therapies aimed at combating obesity and metabolic diseases, based on extensive genetic studies. Arrowhead's preclinical research indicates that suppressing the INHBE gene could potentially lead to reduced body weight gain, decreased fat mass, and maintained lean mass. The company aims to seek regulatory approval by late 2024 to commence clinical trials.

James Hamilton, M.D., chief of discovery and translational medicine at Arrowhead, emphasized the need for novel therapeutic strategies in treating obesity and metabolic diseases. Current treatments often result in significant loss of lean mass and gastrointestinal issues at higher doses. ARO-INHBE offers a new approach by directly targeting the hepatic expression of the INHBE gene. Genetic studies have linked loss-of-function mutations in INHBE with lower abdominal fat and better metabolic profiles. The preclinical data presented at the ADA suggest that INHBE reduction through siRNA is a promising strategy to combat obesity and metabolic diseases, paving the way for clinical trials of ARO-INHBE.

Pharmacological studies in obese and diabetic mouse models treated with INHBE siRNA showed compelling results. There was a 95% reduction in INHBE mRNA expression, a 19% decrease in body weight compared to saline controls, a 26% reduction in fat mass, and preservation of lean mass. Furthermore, combining tirzepatide with INHBE siRNA allowed for lower doses of tirzepatide without losing its therapeutic efficacy. These findings suggest that ARO-INHBE could become a groundbreaking treatment for metabolic diseases.

Arrowhead Pharmaceuticals is also set to discuss its expanding pipeline of cardiometabolic medicines during its 2024 Summer Series of R&D Webinars. The company's leading clinical programs, including the recently completed PALISADE Phase 3 study in familial chylomicronemia with plozasiran, will be showcased on June 25, 2024. Additionally, two preclinical programs focusing on obesity and metabolic diseases, including ARO-INHBE, will be featured on August 15, 2024. Both events can be accessed through the Arrowhead website.

Arrowhead Pharmaceuticals is dedicated to developing treatments for challenging diseases by silencing the genes responsible for them. Utilizing a diverse portfolio of RNA chemistries and efficient delivery methods, Arrowhead's therapies employ the RNA interference (RNAi) mechanism to achieve rapid, deep, and lasting gene knockdown. RNAi is a natural cellular process that inhibits the expression of specific genes, thus influencing protein production. Arrowhead's RNAi-based therapies leverage this natural gene-silencing pathway to treat various conditions.