Wave Life Sciences to Present Preclinical Data Supporting Therapeutic Potential of WVE-007 for Obesity at ObesityWeek® 2025

Presentation will highlight preclinical data supporting the potential of WVE-007 (INHBE GalNAc-siRNA) as a unique approach for the treatment of obesity designed to drive fat loss while preserving muscle mass with once or twice annual dosing

In preclinical models, INHBE GalNAc-siRNA led to adipocyte shrinkage, fewer pro-inflammatory macrophages, less fibrosis, and improved insulin sensitivity in visceral adipose tissue, supporting potential for metabolic improvement

As an add-on to semaglutide, Wave’s GalNAc-siRNA doubled weight loss in mice and prevented weight regain upon cessation of semaglutide

INLIGHT clinical study evaluating WVE-007 is ongoing: last week Wave announced positive target engagement, including dose-dependent decreases in Activin E (up to 85%) observed one month post-single dose of WVE-007, exceeding the reductions seen in preclinical models that led to weight loss; highly durable reductions persisted through six-month follow-up; safe and well tolerated profile

CAMBRIDGE, Mass., Nov. 04, 2025 (GLOBE NEWSWIRE) -- Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage biotechnology company focused on unlocking the broad potential of RNA medicines to transform human health, today announced the presentation of the company’s preclinical data supporting WVE-007, its GalNAc-siRNA investigational therapeutic for obesity. The data will be highlighted on November 6 in a poster presentation at ObesityWeek®, the annual congress of The Obesity Society, in Atlanta.

WVE-007 is a GalNAc-siRNA designed to reduce fat while preserving lean mass by silencing INHBE mRNA, an obesity target with strong evidence from human genetics. People living with naturally low levels of INHBE have lower levels of unhealthy visceral fat, lower fasting glucose and triglycerides, and a lower risk of type 2 diabetes and cardiovascular disease. Silencing INHBE mRNA aims to reduce Activin E levels, thereby inducing fat loss without impacting muscle mass.

“With a strong foundation in human genetics, WVE-007 is focused on healthy weight loss driven by fat loss, in particular visceral fat loss, while preserving muscle to make meaningful improvements in cardiometabolic health, which is ultimately the main objective of any obesity medication. GLP‑1 receptor agonists have transformed obesity care, but their impact is often limited by tolerability, frequent dosing, and perhaps most importantly, loss of muscle mass,” said Erik Ingelsson, MD, PhD, Chief Scientific Officer of Wave Life Sciences. “WVE-007 is currently advancing in the INLIGHT clinical study and we announced exciting target engagement data last week, with dose-dependent and durable Activin E reductions observed in the first three dose cohorts, exceeding levels that led to weight loss in our preclinical models. We are particularly encouraged by the durability of silencing observed, which suggests our investigational therapy may only need to be dosed once or twice per year.”

ObesityWeek® poster presentation information:

Title: Targeting Adipose Lipolysis with INHBE Silencing Promotes a Healthy Weight Loss Profile in Mice (Poster-710)

Presenter: Ginnie (Hsiu-Chiung) Yang, PhD, SVP, Translational Medicine, Wave Life Sciences

Date and Time: November 6, 2025, 2:30-3:30pm ET

Location: Georgia World Congress Center (GWCC), Building A, 285 Andrew Young International Blvd NW, Atlanta, GA 30313

Wave investigated the impact of the company’s GalNAc-conjugated siRNA designed to lower the expression of INHBE mRNA in a diet-induced obesity (DIO) mouse model.

Key results are as follows:

A single dose of Wave’s GalNAc-conjugated INHBE-siRNA in mice led to statistically significant weight loss compared to placebo (PBS treatment), reductions in visceral adipose fat mass and adipocyte size compared to controls, and no loss of skeletal muscle mass, suggesting Wave’s treatment induces a healthy weight loss comprised of fat loss and preservation of lean mass.Wave’s treatment led to decreased infiltration of total and pro-inflammatory macrophages by up to 41% and 80%, respectively, and reduced fibrosis by 58% in visceral adipose tissue of DIO mice. These changes align with lower risk of cardiovascular disease and type 2 diabetes.When added to semaglutide, Wave’s GalNAc INHBE-siRNA doubled weight loss in mice and reduced weight regain upon cessation of semaglutide.

The full presentation can be accessed on the Wave Life Sciences website here.

Recent clinical progress for WVE-007:

Last week at its Research Day, Wave shared Activin E target engagement data from its ongoing, first-in-human INLIGHT clinical trial (3:1 active: placebo). One-month follow-up was available from Cohort 2 (240 mg) and Cohort 3 (400 mg), and six-month follow-up was available from Cohort 1 (75 mg). Highly significant (p