Wave Life Sciences Announced Positive Target Engagement Data from INLIGHT Clinical Trial of WVE-007 for Obesity During Annual Research Day

Dose-dependent mean reductions of Activin E of up to 85% one month post single dose of WVE-007 in INLIGHT clinical trial, exceeding levels that led to weight loss in preclinical models; WVE-007 is generally safe and well tolerated to date

Activin E reduction in lowest dose cohort of INLIGHT was sustained through 6 months, supporting once or twice a year dosing

Multiple clinical data updates from INLIGHT, including body composition and body weight, are anticipated starting in 4Q 2025

Additional updates included announcement of WVE-008, PNPLA3 RNA editing candidate for liver disease, with CTA submission anticipated in 2026

Preclinical data supports Wave’s emerging pipeline of hepatic and extra-hepatic RNA editing and siRNA programs; emerging modality adds capability to simultaneously edit and silence two unique targets with a single oligonucleotide construct

CAMBRIDGE, Mass., Oct. 29, 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 Activin E target engagement data from its INLIGHT clinical trial of WVE-007, a GalNAc-siRNA, for the treatment of obesity during the company’s annual analyst and investor Research Day.

“We are incredibly excited to be observing potent, durable, and dose-dependent Activin E reductions with just single doses of WVE-007 in the first three cohorts of our INLIGHT clinical trial for obesity. This indicates our preclinical data are translating and affirms we have a potential best-in-class RNAi modality enabled by our proprietary chemistry, including PN,” said Paul Bolno, MD, MBA, President and Chief Executive Officer of Wave Life Sciences. “We also continue to lead the field in RNA editing. With the successful clinical translation of WVE-006 for AATD, we are further expanding our editing pipeline and have now selected WVE-008 as our PNPLA3 RNA editing clinical candidate for liver disease. WVE-008 is on track to enter clinical development next year with the filing of a CTA. In addition to that, we are pioneering a new modality by uniting editing and silencing in a single oligonucleotide construct. With multiple planned clinical updates across our RNA editing and RNAi programs, Wave is in a unique position to unlock tremendous value from our robust RNA medicines pipeline.”

INLIGHT clinical study and target engagement update:

WVE-007 (GalNAc-siRNA): INHBE silencing approach designed to reduce fat while preserving muscle mass

• Wave’s INHBE program has a strong foundation in 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.
• In Wave’s preclinical studies of mice with diet-induced obesity (DIO), single doses of GalNAc INHBE-siRNA led to potent and durable Activin E reductions of greater than 70%, and weight loss driven by reduction in visceral fat, without affecting muscle mass. Preclinical studies also support the use of INHBE GalNAc-siRNA as an add-on to GLP-1s or to curtail weight regain following cessation of GLP-1s. These reduced Activin E levels led to adipocyte shrinkage, fewer pro-inflammatory macrophages, less fibrosis, and improved insulin sensitivity in visceral adipose tissue, linking increased lipolysis to lower cardiometabolic risk.
• Today, Wave announced highly significant, dose-dependent Activin E reductions were observed in the first three cohorts of its ongoing INLIGHT clinical trial evaluating WVE-007 (3:1 active: placebo). The trial is designed to address safety and tolerability as well as target engagement (Activin E reduction). One-month follow-up was available from Cohort 2 (240 mg) and Cohort 3 (400 mg), and six-month follow-up from Cohort 1.
• At day 29 (one month post single dose), mean Activin E reductions from baseline were all highly significant (p