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

About this update from Wave Life Sciences Ltd.

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

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