Wave Life Sciences announces new data from INLIGHT trial

Wave Life Sciences (WVE) announced new data from the Phase 1 portion of its first-in-human INLIGHT trial evaluating WVE-007, an investigational INHBE GalNAc-siRNA, in otherwise healthy individuals living with overweight or obesity. After six months of follow-up, a single 240 mg dose led to further improvements in body composition, including fat loss with muscle preservation, with clinically meaningful reductions in visceral fat and waist circumference in a population with less fat and lower BMI than those in Phase 2 and 3 obesity studies. Silencing INHBE and its downstream gene product, Activin E, induces fat loss through lipolysis, the breakdown of triglycerides directly in adipocytes, without reducing muscle. A reduction in visceral fat of 5%-10% is associated with a significantly lower risk of developing MASH, type 2 diabetes, and cardiovascular disease. Preservation of muscle is a key differentiator from incretin treatments and muscle is linked to health benefits including higher basal metabolic rate, improved insulin sensitivity, and prevention of weight regain. In the 240 mg cohort, six-month data demonstrated further improvements in body composition following a single dose of WVE-007, with statistically significant reductions in visceral fat and clinically meaningful reductions in waist circumference, as well as reductions in body weight. There were 32 participants in the 240 mg cohort that had an average BMI of 32 kg/m2 and less visceral and subcutaneous fat than those in Phase 2 or 3 obesity studies. The improvement in body composition as measured by visceral fat-to-muscle ratio observed with a single 240 mg dose of WVE-007 in the Phase 1 INLIGHT trial was greater than that achieved with weekly 2.4 mg doses of semaglutide at six months in the BELIEVE Phase 2 clinical trial, which enrolled a higher BMI population. VMR is an established measure of body composition integrating harmful visceral fat and beneficial lean mass into a single index. Lower VMR is associated with a decreased risk of MASH, type 2 diabetes, and cardiometabolic disorders. Consistent, durable, and dose-dependent serum Activin E reductions sustained through at least seven months continue to support WVE-007’s potential for once or twice-yearly dosing, with a mean maximum reduction of up to 88%. WVE-007 continues to be generally safe and well tolerated to date up to 600 mg. There were no treatment discontinuations, and no severe or serious treatment emergent adverse events. All TEAEs in the treatment groups were mild or moderate, and all treatment-related adverse events were mild. There were no clinically meaningful changes in clinical laboratory measurements, including lipid profiles or liver function tests. In the 400 mg cohort, three-month data demonstrated placebo-adjusted reductions in visceral fat, total fat, with lean mass preservation from baseline following a single dose. Notably, the 400 mg cohort had a leaner baseline body composition, with lower BMI and more participants with healthy levels of visceral fat. A post-hoc analysis of the three-month results demonstrated a more robust and statistically significant average reduction in visceral fat in individuals with higher baseline visceral fat, similar to that observed in the 240 mg cohort. These results emphasize the impact of baseline body composition on therapeutic effect and support expectations that evaluating individuals with higher BMI and visceral fat at baseline will lead to greater improvements in body composition and weight loss. Wave is on track to initiate the Phase 2a multidose portion of INLIGHT evaluating WVE-007 as monotherapy in individuals with higher BMI and comorbidities in the second quarter of 2026. This placebo-controlled Phase 2a study will include multiple assessments over a 12-month period, including body weight, waist circumference, body composition, liver fat, HbA1c, lipid levels, CRP, and muscle function. The study is expected to demonstrate further body composition improvements, including greater fat loss with preserved muscle, and additional weight loss. The results will inform further development of WVE-007 in obesity, as well as MASH, type 2 diabetes, and cardiovascular disease. The first assessment in this portion of the trial is planned for three months after participants have received their first dose. Additional data from INLIGHT, including data from the 600 mg Phase 1 SAD cohort, are expected in 2026. Wave expects to initiate the Phase 2a multidose portion of INLIGHT in individuals with higher BMI and comorbidities in the second quarter of 2026 and initiate new clinical trials evaluating WVE-007 as an incretin add-on and as post-incretin maintenance in 2026.