Third Quarter 2026 Earnings Call - WAVE LIFE SCIENCES INC

Financial Performance:

• Q3 2026 revenue reached $13.2 million, a 73.7% increase year-over-year from $7.6 million, driven by the GSK collaboration.
• Research and development expenses rose to $53.8 million in Q3 2026, compared to $45.9 million in the prior year, reflecting increased clinical program investment.
• General and administrative expenses were $25.4 million, up from $18.1 million year-over-year due to pipeline support costs.
• Net loss for the quarter was $61.9 million, widening from $53.9 million in the prior year quarter.
• Cash position ended at $431 million in cash, cash equivalents, and marketable securities, sufficient to fund operations through Q3 2028.
• A $12 million milestone payment from GSK is expected in Q4 2026 following their selection of an siRNA development candidate.

Guidance and Future Outlook:

• WVE-007 (Inhibin-E siRNA) Phase 2a monotherapy trial is ongoing with dosing underway, expecting data on body composition and fat loss trends.
• WVE-007 Phase 2a combination trial with trisepatide has been initiated; data analysis to determine cut points for 3-month or 6-month readouts will occur later in Q4.
• A Phase 2a maintenance trial for WVE-007 to prevent weight regain post-incretin discontinuation is on track to initiate in Q4 2026.
• 600 mg single-ascending dose (SAD) data for WVE-007 from the Phase 1 ENLIGHT study is expected in Q4 2026.
• WVE-006 (RNA editing for AATD) is advancing to a single registrational trial design following FDA alignment, targeting accelerated approval at 1 year and full approval at 2 years.
• 600 mg monthly dosing data for WVE-006 from the Restoration 2 trial is expected in Q4 2026 to inform final dosing and frequency for the pivotal study.
• WVE-008 (RNA editing for PNPLA3 liver disease) remains on track for a Clinical Trial Application (CTA) submission in 2026.
• An incremental $12 million milestone payment from GSK is scheduled for Q4 2026; future milestones depend on GSK's advancement of three additional programs.

Business Segments and Product Lines:

• WVE-007 (Obesity): An inhibin-E siRNA designed to drive fat loss while preserving lean muscle mass, differentiating it from GLP-1s. Targeting three settings: monotherapy, combination with incretins, and maintenance post-incretin cessation.
• WVE-006 (AATD): An RNA editing therapeutic aiming to restore dynamic AAT response, treating both lung and liver manifestations of Alpha-1 Antitrypsin Deficiency.
• WVE-008 (Liver Disease): An RNA editing candidate for PNPLA3 I148M liver disease, aiming to correct the genetic variant rather than simply silencing the gene.
• GSK Collaboration: GSK selected a new siRNA development candidate from WAVE's platform to transition into their pipeline; WAVE retains rights to WVE-006 and other non-selected assets.
• New Leadership: Monica Vinuk appointed as Chief Business Officer to expand partnering and commercialization opportunities.

Market and Competitive Landscape:

• Obesity Market: WAVE positions WVE-007 as an orthogonal alternative to GLP-1s (incretins), addressing muscle loss, GI side effects, and high discontinuation rates associated with current therapies.
• AATD Market: WVE-006 differentiates from IV augmentation (limited liver impact, no dynamic response) and DNA editing (permanent modification, safety concerns, payer challenges).
• Regulatory Trends: FDA engagement indicates a shift toward body composition metrics (visceral fat vs. total weight) and acceptance of surrogate biomarkers for accelerated approval in rare diseases.
• Platform Validation: The Nobel Prize in Chemistry recognition of stereochemistry validates WAVE's proprietary SPINA siRNA design and chiral chemistry capabilities.

Risks and Challenges:

• Clinical Trial Execution: Potential risks in achieving the 5% weight loss regulatory threshold in Phase 2a and maintaining durable dosing intervals without safety issues.
• Regulatory Uncertainty: While aligned on AATD trial design, full approval still requires confirmation of clinical outcomes over a 2-year period, albeit via a single trial.
• Safety Profile: Managing side effects at higher doses (600 mg) for long-term administration and ensuring muscle preservation in higher BMI populations.
• Competition: Rapidly evolving obesity landscape with multiple competitors and potential for shifting regulatory endpoints regarding body composition.

Management Commentary and Tone:

• Management expressed high confidence in the proprietary chemistry and platform capabilities, citing the Nobel Prize as external validation.
• Tone was optimistic and execution-focused, highlighting "expeditious" advancement of pipelines and strong alignment with regulatory bodies.
• CEO Paul Bolno emphasized the potential to "redefine the treatment landscape" in obesity and AATD.
• CFO Kyle Moran highlighted the strong cash runway and successful capital efficiency in advancing clinical programs.
• New CBO Monica Vinuk focused immediately on leveraging the portfolio for partnering opportunities and growth.

Analyst Questions and Answers:

• AATD Trial Design: Confirmed a single two-year registrational trial for WVE-006 can support both accelerated (1-year interim) and full (2-year) approval without a separate confirmatory study.
• Dosing Strategy: 600 mg data will inform final dosing and frequency; modeling suggests monthly dosing is likely, with potential for extended intervals based on total exposure.
• Body Composition: FDA engagement supports the focus on visceral fat loss and lean mass preservation as critical efficacy markers beyond scale weight.
• GSK Relationship: Described as mutually beneficial and evolving; GSK's leadership changes and portfolio strategy led to the return of certain assets (like WVE-006) while advancing others.
• Combination Therapy: WVE-007 is expected to provide additive benefits to GLP-1s, particularly for patients who do not reach weight loss goals or experience muscle loss.

Other Key Points:

• Upcoming Events: WAVE will host its annual Research Day next week, featuring Dr. Arun Sanyal to discuss PNPLA3 liver disease.
• Clinical Trial Registries: WAVE plans to leverage Alpha-1 patient registries to accelerate enrollment for the AATD registrational trial.
• Assay Validation: FDA has approved the use of WAVE's LC-MS assay for quantifying M and Z proteins in the AATD program, ensuring consistency across development phases.
• Human Genetics: Both WVE-007 and WVE-008 are strongly rooted in human genetic data, validating the biological targets (Inhibin-E and PNPLA3).
• Safety Profile: WVE-007 has shown favorable tolerability and durable dose-dependent activity in Phase 1, with no muscle loss observed in preclinical models.