Highlights 

  • WVE-007 is designed to reduce fat while maintaining muscle mass. 
  • Preclinical results show reduced inflammation and improved insulin sensitivity in fat tissue. 
  • The INLIGHT trial shows dose-dependent Activin E reductions reaching up to 85%. 

Wave Life Sciences Ltd. (NASDAQ:WVE), a clinical-stage biotechnology company developing RNA-based therapeutics, announced plans to present preclinical findings on its investigational obesity candidate WVE-007 (INHBE GalNAc-siRNA) at ObesityWeek® 2025, hosted by The Obesity Society in Atlanta. 

Preclinical Findings 

WVE-007 targets INHBE mRNA, a gene linked to obesity and metabolic regulation. Individuals with naturally low INHBE levels tend to have reduced visceral fat, improved glucose and triglyceride profiles, and a lower likelihood of developing type 2 diabetes or cardiovascular conditions. The therapy seeks to lower Activin E levels to promote fat loss without compromising lean muscle. 

In preclinical diet-induced obesity mouse studies: 

  • A single dose of INHBE GalNAc-siRNA produced statistically significant weight loss compared to placebo, reducing visceral fat and adipocyte size, with no observed muscle loss. 
  • The therapy reduced total macrophage infiltration by 41%, pro-inflammatory macrophages by 80%, and fibrosis by 58% in visceral fat tissue—changes consistent with improved metabolic health. 
  • When administered with semaglutide, WVE-007 doubled total weight loss in mice and prevented weight regain after semaglutide withdrawal. 

Clinical Progress: INLIGHT Trial 

The company’s INLIGHT first-in-human clinical trial is evaluating WVE-007 in adults with overweight or obese. Recent data from the study revealed dose-dependent reductions in Activin E levels of up to 85% one month after a single dose—exceeding the levels linked to weight loss in preclinical models. 

In Cohort 1 (75 mg), these reductions were sustained for six months post-dose. WVE-007 was well tolerated, and an independent monitoring committee approved expansion of Cohort 4 (600 mg) and further dose escalation. 

Erik Ingelsson, MD, PhD, Chief Scientific Officer of Wave Life Sciences, commented: 

“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... 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.” 

Upcoming Milestones 

Wave Life Sciences plans multiple clinical data updates from the INLIGHT trial through 2025 and 2026, including results related to body composition and body weight.  

The INLIGHT study continues to assess safety, tolerability, pharmacokinetics, biomarkers, and metabolic indicators in adults with a BMI between 28–35 and A1c under 5.9, to evaluate WVE-007’s potential as a long-acting therapeutic approach for obesity management.