Wave Life Sciences (WVE) Study Update summary

Study Design and Objectives

• INLIGHT is a randomized, double-blind, placebo-controlled Phase 1 trial evaluating WVE-007 in overweight or mildly obese adults (BMI ~32), with no diet or exercise modifications required and balanced demographics across cohorts.

• The study assesses safety, tolerability, pharmacokinetics, pharmacodynamics, Activin E levels, and exploratory endpoints including body composition by DEXA, biomarkers, and body weight.

• Dosing cohorts included single ascending doses of 75, 240, 400, and 600 mg, with up to five single-dose cohorts planned and additional multiple-dose cohorts anticipated.

• Over 100 participants have been enrolled, and the trial is ongoing at multiple sites in the US and Europe.

• No diet or exercise modifications were instituted during the trial.

Key Interim Results

• A single 240 mg dose of WVE-007 led to a 9.4% reduction in visceral fat, 4.5% reduction in total fat mass, and a 3.2% increase in lean mass at three months, with no significant changes in the placebo group.

• Placebo-adjusted reductions in total fat mass and visceral fat were on par or greater than those seen with semaglutide at 12 weeks, but with muscle preservation.

• Durable, dose-dependent reductions in serum Activin E (>75% suppression) were observed, supporting potential for once or twice-yearly dosing.

• No serious or severe adverse events, deaths, or discontinuations were reported; all treatment-related adverse events were mild, with no clinically meaningful changes in lipids, glucose, or liver function.

• Fat loss was achieved without diet or exercise modifications and with a favorable safety and tolerability profile.

Mechanism and Differentiation

• WVE-007 is a GalNAc-siRNA targeting INHBE, reducing hepatic Activin E and promoting adipocyte lipolysis, leading to fat loss while preserving muscle.

• The approach is orthogonal to GLP-1s, focusing on body composition improvement rather than appetite suppression.

• Human genetics and preclinical data support the mechanism, showing healthier metabolic profiles in INHBE loss-of-function carriers and durable fat loss with muscle preservation in animal models.

• Proprietary SpiNA chemistry enhances potency and durability of INHBE silencing.

• WVE-007 may be used synergistically with GLP-1s or to prevent weight regain after GLP-1 cessation.