Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced that preclinical data on ARO-INHBE, an investigational RNAi-based medicine for the treatment of obesity and metabolic diseases, were presented at the American Diabetes Association (ADA) 84^th Scientific Sessions, which were held June 21-24, in Orlando, FL, and virtually.

The preclinical results demonstrate that ARO-INHBE substantially silenced hepatic expression of the INHBE gene, which has been identified through large genetic studies as a promising target for next generation therapies to address obesity and metabolic diseases. Further, Arrowhead’s preclinical research suggests that INHBE knockdown may potentially lead to a suppression in body weight gain, loss of fat mass, and preservation of lean mass. Arrowhead plans to file for regulatory clearance in late 2024 to begin clinical studies of ARO-INHBE.

“There has been a great deal of progress with new agents to treat obesity and metabolic diseases, but significant loss of lean mass and adverse gastrointestinal events at higher dose levels have necessitated the identification of new therapeutic strategies with novel mechanisms of action,” said James Hamilton, M.D., chief of discovery and translational medicine at Arrowhead. “ARO-INHBE directly targets hepatic expression of the INHBE gene. Prior genetic studies have associated loss of function mutations in the INHBE gene with reduced levels of abdominal fat and an improved metabolic profile. Our preclinical data presented at ADA suggest that INHBE reduction with siRNA is a promising new approach to address obesity and metabolic diseases and strongly support advancing ARO-INHBE into clinical trials.”

In pharmacological studies in obese and diabetic mouse models, INHBE siRNA administration resulted in multiple promising findings, including the following:

• 95% reduction in INHBE mRNA expression
• 19% suppression of body weight compared to saline controls
• 26% loss of fat mass
• Preservation of lean mass

In addition, co-treatment of tirzepatide with INHBE siRNA allowed for the use of a lower tirzepatide dose without compromising its therapeutic effect. These encouraging results suggest that ARO-INHBE has the potential to be a novel therapeutic for metabolic disease.

Details about the ADA presentations are listed below.

American Diabetes Association 84^th Scientific Sessions – June 21-24, 2024

Title: Liver-specific silencing of INHBE with ARO-INHBE, an siRNA therapeutic, for metabolic diseases

Date: June 24, 2024

Type: Poster

Arrowhead will discuss its growing pipeline of cardiometabolic medicines at two events as part of its 2024 Summer Series of R&D Webinars. The company’s lead clinical programs, including the recently completed PALISADE Phase 3 study in familial chylomicronemia with plozasiran, will be highlighted on June 25, 2024, and two preclinical programs addressing obesity and metabolic diseases, including ARO-INHBE, will be discussed on August 15, 2024.

The ADA presentation and the Summer Series of R&D Webinars may be accessed on the Events and Presentations page in the Investors section of the Arrowhead website.

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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Source: Arrowhead Pharmaceuticals, Inc.

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