Wave Life Sciences (WVE) 44th Annual J.P. Morgan Healthcare Conference summary

Strategic vision and innovation

• Focus on unlocking the potential of RNA medicines, leveraging proprietary chemistry and deep genetic insights for rapid translation from discovery to clinical candidates.

• In-house GMP manufacturing and strong IP position enable swift clinical advancement, innovation, and scalability.

• Innovations in siRNA chemistry yield 10-15x improvement in AGO2 loading, enhancing potency and durability.

• Bifunctional oligonucleotide constructs enable simultaneous RNA editing and silencing, expanding therapeutic reach.

• Well-capitalized with approximately $602 million in cash runway into Q3 2028, supporting strategic focus on obesity and RNA editing programs.

Obesity program (INHBE siRNA)

• Lead program WVE-007 targets INHBE for obesity, showing durable fat loss and muscle preservation in preclinical and clinical studies, with potential for once or twice-yearly dosing.

• Phase 1 data demonstrate potent, durable Activin E reduction, with nearly 9.5% visceral fat loss and slight lean mass increase at three months.

• Differentiation from GLP-1s includes muscle preservation, favorable safety, and potential for combination or maintenance therapy.

• Phase 2a INLIGHT study to enroll higher BMI patients and explore monotherapy, combination, and maintenance settings.

• New clinical trials planned for WVE-007 as add-on to incretin and post-incretin maintenance in 2026.

Clinical and mechanistic insights

• INHBE silencing reduces both subcutaneous and visceral fat, with muscle preservation critical for metabolic health.

• Human genetics from UK Biobank support INHBE as a target, with 50% loss-of-function linked to improved metabolic profiles.

• Mechanism involves liver-derived Activin E acting on adipocyte ALK7 receptors to regulate fat storage; silencing promotes lipolysis.

• Preclinical and clinical data show slower but sustained weight loss compared to GLP-1s, driven by fat loss rather than muscle loss.

• Maintenance therapy with INHBE siRNA can prevent weight regain after GLP-1 cessation, independent of caloric intake.