Wave Life Sciences (WVE) Jefferies London Healthcare Conference 2025 summary

Strategic focus and technology

• Emphasis on building a fully integrated RNA medicines platform targeting genetic diseases, leveraging advanced chemistry for high potency, specificity, and durability across RNA editing and siRNA modalities.

• Expansion into novel targets such as inhibin E for obesity (WVE-007) and PNPLA3 for liver disease (WVE-008), with ongoing leadership in splicing and allele-specific approaches.

• Commitment to optimizing oligonucleotide design to unlock new therapeutic modalities and best-in-class opportunities.

• Entering a data-rich period with significant readouts expected in Q4 2025 and throughout 2026.

Inhibin E program for obesity

• Inhibin E identified as a unique, genetically validated target for obesity, aiming to induce healthy fat loss without impacting lean mass.

• Preclinical and early clinical data show dose-dependent, durable reductions in activin E, translating to fat loss equivalent to GLP-1s but sparing muscle and bone.

• Human data demonstrate sustained activin E knockdown, with higher doses achieving up to 85% reduction and supporting potential for once-yearly dosing.

• Upcoming Q4 update will provide three-month data on the 240 mg cohort, including metabolic biomarkers, DEXA body composition, and initial weight loss endpoints.

• Phase 2 maintenance studies are planned to evaluate long-term weight maintenance and off-ramp strategies from incretins, with over 100 patients expected on therapy by mid-2026.

Alpha-1 antitrypsin deficiency (AATD) and RNA editing pipeline

• RNA editing platform delivers potent, durable, and specific editing in liver, with clinical data showing correction of AATD patients to near-normal M protein levels at low doses.

• Upcoming data will assess higher dose cohorts for durability and editing efficiency, focusing on M protein as the key efficacy marker.

• Platform enables rapid translation from genetic insight to clinic, with PNPLA3 program entering clinical trials in 2026 for a large population at risk of liver disease.

• Editing approach offers advantages over protein replacement and siRNA knockdown, particularly in restoring protein function and addressing substrate limitations.