Wave Life Sciences (WVE) Study result summary

Key interim Phase 1 results and clinical impact

• A single 240 mg dose of WVE-007 led to significant, placebo-adjusted reductions in visceral fat (−14%), total fat (−5.3%), waist circumference (−3.3%), and body weight (−1%) at six months, with lean mass preserved or increased (+2%).

• Durable, dose-dependent suppression of Activin E was observed, with up to 88% mean maximum reduction and over 70% suppression maintained for at least seven months, supporting potential for once or twice-yearly dosing.

• All reductions were placebo-adjusted and statistically significant (p < 0.05).

• Greater fat loss was observed in participants with higher baseline visceral fat, with the 400 mg cohort showing a −5% reduction in visceral fat at three months.

• WVE-007 was generally safe and well tolerated, with only mild or moderate adverse events, no serious safety signals, and no discontinuations through 600 mg.

Mechanism and clinical rationale

• WVE-007 is a GalNAc-siRNA targeting INHBE, reducing Activin E to promote adipocyte lipolysis and fat loss while preserving muscle, unlike current incretin therapies.

• Human genetic data show INHBE loss-of-function carriers have lower visceral fat, improved metabolic profiles, and reduced risk of type 2 diabetes and cardiovascular disease.

• Suppression of Activin E is correlated with reductions in BMI, abdominal fat, and fasting insulin.

• Preclinical data indicate WVE-007 induces fat loss and improves insulin sensitivity, with additive effects when combined with GLP-1 therapies.

• The approach is orthogonal to GLP-1s, which often cause muscle loss and require frequent dosing; WVE-007 may enable infrequent dosing and is positioned as a potential add-on or maintenance therapy.

Study design and participant characteristics

• Phase 1 (SAD) included otherwise healthy adults with BMI ~32 kg/m² and lower baseline visceral fat than typical phase II/III obesity studies; no diet or exercise modifications were made.

• Baseline characteristics differed between 240 mg and 400 mg cohorts, with the latter having lower BMI and visceral fat.

• Placebo arms did not include lifestyle interventions, isolating the drug effect.

• Improvements in body composition were achieved without diet or exercise modifications.

• Visceral fat-to-muscle ratio improved more with WVE-007 than with semaglutide, and was on par with bimagrumab, despite a healthier baseline population.