Wave Life Sciences (WVE) Status Update summary

Strategic and platform advancements

• Achieved first-ever clinical RNA editing with WVE-006 for AATD, and best-in-class allele-selective silencing for HD and muscle delivery for DMD.

• PRISM platform and proprietary chemistry enable modular, efficient translation from preclinical to clinical across silencing, splicing, and editing modalities.

• Five GalNAc clinical programs, including WVE-006, WVE-007, and three new RNA editing programs, are on track for 2026.

• Human genetics and AI-driven target selection increase probability of clinical success and operational efficiency.

• Cash runway extends into 2027, not including potential GSK milestones.

Clinical and pipeline updates

• WVE-003 for HD showed up to 46% mutant HTT reduction with preserved wild-type, and strong correlation with caudate atrophy, supporting accelerated approval discussions.

• WVE-007 (Inhibin beta E siRNA) demonstrated durable, preferential visceral fat loss, muscle preservation, and synergistic effects with GLP-1s in preclinical models.

• WVE-007 supports semi-annual/annual dosing, add-on to GLP-1s, and prevention of weight regain post-GLP-1 cessation.

• WVE-006 for AATD achieved >60% wild-type AAT restoration in patients, with favorable safety and potential for infrequent dosing.

• New RNA editing programs target PNPLA3 (liver disease), LDLR, and ApoB (familial hypercholesterolemia), aiming for best-in-class efficacy and broad patient impact.

Scientific and regulatory insights

• Caudate atrophy validated as a robust, HD-specific biomarker, enabling smaller, earlier-stage clinical trials and potential for accelerated registration.

• RNA editing platform enables correction of both missense and nonsense mutations, with applications in Rett syndrome and cystic fibrosis.

• Chemistry innovations (PN backbone, N3U modifications) drive improved delivery, potency, and tissue access, including CNS and extrahepatic tissues.

• AI and human genetics integration streamline target discovery, molecule design, and clinical development.

• IP portfolio and proprietary chemistry provide strong protection and differentiation in RNA editing space.