EXECUTIVE SUMMARY

• Vial’s INHBE siRNA is a first‑in‑class, liver‑targeted (GalNAc‑conjugated) siRNA therapy that silences INHBE and its gene product, Activin E
• Leading key opinion leaders (KOLs) Drs. Jason Fung, Scott Kahan, Lawrence Cheskin, and Lee Kaplan from leading institutions such as Johns Hopkins, GMU, and Dartmouth University respectively shared their insights on challenges with current GLP-1 treatments as well as the potential benefits of INHBE siRNA therapies like Vial’s
• INHBE siRNAs are designed to deliver fat‑selective weight loss while preserving lean muscle mass
• Vial’s INHBE siRNA will be investigated for its potential as both a mono-therapy and in combination with GLP-1s to offer patients flexibility on their weight loss journey

December 16, 2025 — Vial, a clinical‑stage biotech company, today announced growing enthusiasm among metabolic disease KOLs for Vial’s INHBE siRNA, a first‑in‑class, liver‑targeted (GalNAc‑conjugated) siRNA therapy that silences INHBE and its gene product, Activin E. With mounting evidence linking this pathway to energy expenditure and fat metabolism, Vial’s INHBE is emerging as a promising new approach and new siRNA therapeutic to drive quality fat loss and improved body composition, potentially complementing or exceeding the effects of GLP‑1-based therapies.

Vial’s INHBE was developed as a first‑in‑class INHBE (Activin E) siRNA to deliver fat‑selective weight loss while preserving lean muscle mass. As obesity care moves beyond “more weight loss at any cost,” leaders in the field are calling for novel therapeutics that protect muscle and bone, work through new mechanisms, and complement GLP‑1s, especially for patients looking for more generalized weight maintenance.

“If one can definitely show that you are selective for fat and you spare the muscle mass, that of course, can be clinically interesting and an advantage in the treatment of patients”

Jason Fung MD, Nephrologist, Researcher, and Best-Selling Author of "The Obesity Code"

Human genetic studies have linked reduced INHBE expression with lower visceral fat and improved cardiometabolic markers, positioning Vial’s INHBE as a differentiated, next‑generation approach that’s focused on selectively targeting fat cells and adipose tissue for quality weight loss, while maintaining lean mass.

“For many people, GLP-1s are not going to be sufficient or effective. Medications that work at the level of muscle cells, fat cells, at a hepatic level are going to be essential going forward.”

Scott Kahan MD, MPH, Director of the National Weight and Wellness and Faculty at Johns Hopkins University

Obesity leaders increasingly warn that excessive loss of muscle and bone on long‑term therapy is becoming “front and center” for patients and clinicians alike. INHBE’s novel mechanism of action is emerging as a key lever for improving body composition rather than just driving lower scale number. It has been noted that Vial’s INHBE, with its more favorable body composition profile, “would be particularly attractive to those who don't need to lose a ton of weight…or those who are looking for more of a weight maintenance strategy.” - Dr. Lawrence Cheskin, MD, a Leading Obesity Researcher and Principal Investigator at GMU and Johns Hopkins University.

Vial’s INHBE siRNA will be investigated for its potential as both a mono-therapy and in combination with GLP-1s, to offer patients flexibility on their weight loss journey. In support for this approach, Dr. Lee Kaplan MD, Director of Dartmouth Health’s Weight and Wellness Center noted that “in addition to potentially sparing lean mass, some molecules that affect this pathway [INHBE / Activin E] appear to extend fat loss.”