Wave Life Sciences Ltd. Q2 FY2025 earnings call

• Progress in RNA editing with AATD clinical program, INLIGHT obesity program, FORWARD-53 DMD trial, and HD allele-selective program. • Hired Dr. Chris Wright as CMO in May. • WVE-006 (AATD) has initial proof of mechanism data, multi-dosing completed in first cohort, data expected in 3Q and fall. • WVE-007 (INLIGHT obesity) expanded cohort 2, dosing in cohort 3, data expected in 4Q 2025 and 1Q 2026. • FORWARD-53 DMD trial showed significant improvements, plan to submit NDA in 2026. • HD program WVE-003 on track for IND submission in H2 2025 with caudate volume as primary endpoint.

Revenue for the second quarter of 2025 was $8.7 million compared to $19.7 million in the prior year quarter. Research and development expenses were $43.5 million for Q2 2025 vs $40.4 million in Q2 2024. G&A expenses were $18 million in Q2 2025 vs $14.3 million in Q2 2024. Net loss was $50.5 million in Q2 2025 vs $32.9 million in Q2 2024. Cash and cash equivalents ended Q2 2025 at $208.5 million compared to $302.1 million as of Dec 31, 2024. Revenue decrease was due to timing of GSK collaboration revenue. R&D increase was from INHBE and RNA editing programs. G&A increase was from share-based comp and other expenses.

• Expect data from RestorAATion and INLIGHT in 4Q 2025 and 1Q 2026. • Plan to submit NDA for WVE-N531 in 2026 for accelerated approval. • On track to submit IND for HD program's Phase II/III study in H2 2025. • Current cash expected to fund operations into 2027. • Potential milestones from GSK collaboration in 2025-2026 not included in cash runway.

Q: For the INHBE program, elaborate on reasons for expanding Cohort 2 over advancing to Cohort 3 sooner, relationship to DIO weight loss data, and Activin E knockdown goal.

A: Expansion to Cohort 2 driven by safety allowing dose escalation to 400mg. Cohort 2 dose modeled aligns with DIO weight loss similar to semaglutide. Confident based on preclinical and clinical translation, expecting over 50% Activin E reduction.

Q: Should we expect linear dose response for INHBE program, and impact of lean mass preservation on weight loss?

A: Model shows weight loss comparable to GLP-1s but from fat loss without impacting muscle. Confident in fat loss without muscle impact as seen in animal models.

Q: Specifics on 006 AATD dosing completion, follow-up for top line data.

A: All patients received seven 200-milligram doses with follow-up, data on track for 3Q as originally guided.

Q: Characterization of consistency of effect for 006 AATD across patients.

A: GalNAc delivery ensures consistent editing and protein production, with preclinical models and early data supporting consistency.

Q: Characterization of Activin E reduction in INHBE Cohort 1 vs preclinical modeling, dose response, and correlation with weight loss.

A: Cohort 1 Activin E reduction consistent with preclinical modeling, dose response seen in preclinical data, and correlation between Activin E reduction and weight loss expected based on preclinical and clinical translation.

Q: Target conversion rate from Z to M for 006 AATD.

A: Goal is to convert ZZ to MZ phenotype, with M protein critical to track as it's the native corrected protein, and total protein also considered.

Q: Optimization of 006 relative to other AATD RNA editing therapeutics.

A: 006 has best-in-class properties with GalNAc delivery for subcutaneous administration, optimized chemistry for editing, and differentiation from other therapies by avoiding LNPs and complex vehicles.

Q: Decision to expand INHBE Cohort 2 and go-forward dose strategy.

A: Study designed to efficiently get to therapeutic dose, with robust Activin E reduction and PK/PD modeling supporting expansion to Cohort 2, aiming to get to efficacy and activity quickly.

Q: GSK milestones related to upcoming 006 data.

A: Potential milestones from GSK in 2025-2026, but specifics on allocation not disclosed.

Q: Influence of Cohort 3 dosing assessment on INHBE timeline and disclosure.

A: Continued progress expected, with no shift in timeline for 400mg data in 1Q 2026 based on study design and progress.

Q: PK/PD conviction for 006 AATD and behavior of GalNAc AIMers vs siRNAs.

A: Confidence in PK/PD from preclinical to clinical translation, with GalNAc distribution and chemistry design supporting consistent behavior between AIMers and siRNAs.

Q: Role of blinded weight loss data in INHBE cohort expansion.

A: Blinded weight loss data not a trigger for cohort expansion, but biomarker-driven determination and safety supported expansion.

Q: Takeaways from bimagrumab Phase II data on INHBE program development.

A: Encouraging to see muscle sparing and fat reduction pathways, with INHBE's approach offering a clean pathway with favorable safety tolerability vs other weight loss programs.

Q: Thoughts on KOL feedback regarding AATD therapy reaching 22 micromolar AAT or above and acute phase response.

A: RNA editing's benefit is preserving acute phase response and creating background protective protein, with M protein critical to track for assessing editing efficiency and therapeutic levels.

Q: Baseline characteristics and key metrics for INHBE Cohort 2 and data expected in 4Q.

A: Cohort 2 includes healthy overweight individuals with BMI 20-35, data in 4Q will have at least 3 months follow-up to assess dosing kinetics and Activin E-PK relationship.

Q: Initiation of subsequent RNA editing cohorts for 006 and triggers for expansion.

A: Subsequent cohorts for 006 will be guided by data from 200mg multi-dose and 400mg single-dose studies, with safety allowing further dose escalation as needed.

Q: Enrollment in DMD open-label monthly extension cohort and NDA submission timeline.

A: Enrollment ongoing with no change to NDA submission timeline in 2026, community engaged and study on track.