Wave Life Sciences (WVE) investor relations material

Study design and objectives

• Phase I INLIGHT trial evaluated WVE-007, a GalNAc-siRNA targeting inhibin E, in overweight or obese but otherwise healthy adults, focusing on safety, PK/PD, and exploratory body composition endpoints.

• Participants had BMI 28–35, with no diet or exercise modifications required; endpoints included DEXA-based body composition, biomarkers, and body weight.

• The study used a placebo-controlled, single ascending dose design, with cohorts at 75 mg, 240 mg, 400 mg, and 600 mg.

• Baseline characteristics differed between 240 mg and 400 mg cohorts, with the latter having lower BMI and visceral fat than typical Phase 2/3 obesity studies.

• The next phase (II/a) will enroll higher BMI (35–50) individuals with comorbidities, using a multi-dose regimen and expanded endpoints including MRI and metabolic biomarkers.

Key interim results

• A single 240 mg dose led to a 14% reduction in visceral fat, 5% reduction in total fat, 3% reduction in waist circumference, and 1% weight loss at six months, with lean mass stabilized (+2%), all placebo-adjusted and statistically significant (p<0.05).

• Durable, dose-dependent suppression of Activin E was observed for at least seven months, supporting infrequent (1–2x yearly) dosing.

• Safety profile was favorable across all cohorts, with no serious adverse events, discontinuations, or deaths, and only mild or moderate treatment-emergent adverse events.

• Improvements in body composition were observed without dietary or exercise interventions.

• Greater fat loss was seen in participants with higher baseline visceral fat; VMR improvement outperformed semaglutide and matched bimagrumab in early comparisons.

Mechanism and differentiation

• WVE-007 silences inhibin E in the liver, lowering circulating Activin E, which releases the brake on adipocyte lipolysis, promoting fat loss while preserving muscle.

• Human genetic data support the mechanism: carriers of inhibin E loss-of-function variants have healthier metabolic profiles, lower visceral fat, and reduced risk of type 2 diabetes and heart disease.

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

• The approach is orthogonal to GLP-1s/incretins, which often cause muscle loss and require frequent dosing; WVE-007 offers potential for once or twice yearly dosing and additive effects with incretins.

• The proprietary SpiNA chemistry enhances potency, durability, and selectivity, minimizing off-target effects.