Vial, a clinical-stage biotechnology company, has initiated a Phase 1 trial for VIAL-INHBE, a novel INHBE (Activin E) siRNA therapy targeting obesity and other cardiometabolic diseases. The first-in-human study represents a significant milestone for the San Francisco-based company's approach to addressing limitations in current obesity treatments.
Novel siRNA Approach Targets Activin E Pathway
VIAL-INHBE is a GalNAc-conjugated INHBE (Activin E) siRNA designed with a projected six-month dosing interval. The therapy targets the INHBE pathway, which plays a role in metabolic regulation and body composition. According to Simon Burns, CEO of Vial, "The initiation of the Phase 1 trial for Vial's INHBE siRNA program is a major milestone in advancing the program."
The Phase 1 trial is structured as a first-in-human, single-ascending dose study that will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of subcutaneous VIAL-INHBE administration. The open-label study is being conducted in Australia, with interim subcutaneous safety and pharmacokinetic data expected in the first half of 2026.
Preclinical Data Shows Promise for Fat-Selective Weight Loss
Diet-induced obesity (DIO) mouse model studies demonstrated compelling results for VIAL-INHBE, showing fat-selective weight loss and lean mass preservation. The preclinical data support what the company describes as a potentially best-in-class profile relating to fat-selective weight loss, off-treatment weight maintenance, and dosing interval.
Particularly notable was the combination therapy approach tested in preclinical studies. When VIAL-INHBE was combined with a low-dose GLP-1 receptor agonist, the combination resulted in synergistic weight loss and lean mass preservation that was maintained even after GLP-1 treatment was discontinued.
Addressing Current Treatment Limitations
The development of VIAL-INHBE is positioned to address significant gaps in the current obesity treatment landscape. As explained by Preeti Sareen, Ph.D., Head of Strategy at Vial, "GLP-1s have revolutionized the obesity treatment landscape, but there remain significant unmet needs: poor GI tolerability and associated high discontinuation rates, loss of lean mass, and weight regain post-GLP-1 treatment."
The preclinical data suggest that VIAL-INHBE combined with a lower, more tolerable GLP-1 dose achieved similar total body weight loss as high-dose GLP-1 monotherapy, while preserving lean mass and attenuating weight rebound post-treatment.
Clinical Development Timeline
Following the completion of the Phase 1 trial, Vial plans to initiate a multi-region Phase 2 trial in obesity later in 2026. The company expects to share interim data from the Phase 1 trial in the first half of 2026, which will provide initial insights into the safety and pharmacokinetic profile of the therapy in humans.
Vial, founded in 2020, has raised over $100 million to date from leading life sciences investors including General Catalyst, Buckley Ventures, and Byers Capital. The company is focused on advancing a pipeline of potentially best-in-class biologics and RNA therapeutics across areas of unmet medical need.
