WAVE Life Sciences (NASDAQ:WVE) executives used the company’s fourth-quarter and full-year 2025 earnings call to highlight clinical progress in its obesity and RNA editing programs, outline upcoming data catalysts, and review year-end financial results. President and CEO Dr. Paul Bolno said 2025 delivered “positive clinical data sets in obesity and AATD,” and that management is entering 2026 focused on accelerating the WVE-007 program for obesity and advancing an RNA editing portfolio led by WVE-006 for alpha-1 antitrypsin deficiency (AATD), followed by WVE-008 for PNPLA3 I148M liver disease.
Obesity program: WVE-007 and the INLIGHT study
Wave’s lead obesity asset, WVE-007, is a GalNAc-conjugated siRNA designed to silence INHBE and lower serum Activin E, with the stated goal of improving body composition by reducing fat while preserving muscle. Bolno positioned the program as a potential next-generation approach that could address limitations he associated with GLP-1 therapies, including frequent dosing and tolerability challenges, as well as muscle loss and discontinuation.
Management reiterated interim findings previously shared from the lowest therapeutic cohort. At three months, a single 240 mg dose produced placebo-adjusted changes that included a 4% reduction in total fat, a 9.2% reduction in visceral fat, and preservation of muscle (a 0.9% increase in lean mass, according to the company). Wright said the safety profile was favorable and that durable reductions in serum Activin E supported the possibility of once- or twice-yearly dosing.
Wave said the INLIGHT study is fully dosed through a 600 mg cohort and that it expects to announce six-month follow-up data from the 240 mg cohort and three-month follow-up data from the 400 mg single-dose cohort later in the quarter. In Q&A, executives said they were not “guiding to each individual update” beyond the next near-term data release, emphasizing that all patients in the single-dose portion have already been dosed and that data will continue to accumulate over time.
Phase IIa plans and potential liver-fat readouts
Wright said Wave is preparing to start a Phase IIa multi-dose portion of INLIGHT that is expected to enroll individuals with higher BMI and comorbidities, and is on track to initiate in the first half of the year. In addition to assessments similar to the single-dose portion, the multi-dose portion is expected to include:
- MRI-based body composition measurements
- Liver fat content assessed by MRI-PDFF
Management said the added imaging could help clarify the program’s impact on liver fat. During Q&A, the company did not provide a specific liver-fat reduction “delta” expectation for WVE-007, but discussed the opportunity to evaluate monotherapy effects in a population that includes comorbidities. Bolno also pointed to the potential for broader metabolic marker evaluation in later-stage studies that include participants with higher A1C and lipid abnormalities, noting the Phase I population is “otherwise healthy,” which limits the ability to observe changes in certain biomarkers.
Wave also reiterated plans to initiate new clinical trials evaluating WVE-007 as an incretin add-on and as a post-incretin maintenance therapy in 2026. In Q&A, executives emphasized the company’s focus on body composition—specifically, fat reduction and lean mass preservation—as a key element of the product concept alongside an eventual regulatory weight-loss pathway.
RNA editing: WVE-006 in AATD and regulatory path
Wave’s lead RNA editing program, WVE-006, is a GalNAc RNA editing oligonucleotide for AATD. Bolno and Wright described AATD as a “uniquely compelling disease” for RNA editing given its single-gene cause and liver biology, and contrasted Wave’s approach with DNA editing and lipid nanoparticle-based delivery strategies. Wave said its RNA editing approach is designed to restore endogenous M-AAT protein, reduce mutant Z-AAT, and restore a more normal acute-phase response to inflammatory stress.
Wright outlined three criteria the company is pursuing in AATD:
- Maintain basal protein levels at or above 11 micromolar
- Increase circulating M-AAT protein above the 50% heterozygous MZ threshold, with corresponding reductions in Z-AAT
- Restore the physiologic AAT response to acute inflammatory events
Management referenced previously reported RestorAATion-2 data, including an observation that a ZZ participant experienced an acute inflammatory event and achieved total AAT levels greater than 20 micromolar two weeks after a single dose. The company said it is accelerating regulatory engagement now that it has full control of the program and expects regulatory feedback on a potential accelerated approval pathway in mid-2026. Executives said they anticipate a biomarker-based approach consistent with how AATD therapies have been developed, while noting they do not comment on specific FDA conversations.
Wave expects to report data from a 400 mg multi-dose cohort of RestorAATion-2 this quarter, and to report single- and multi-dose data from a 600 mg cohort in 2026.
WVE-008 for PNPLA3 I148M liver disease and DMD update
Wave said it is advancing WVE-008, a GalNAc-conjugated RNA editing candidate targeting homozygous PNPLA3 I148M liver disease, and remains on track for a CTA submission in 2026. Wright described the variant as a driver of MASH pathology and said there are no approved medicines that directly address this biology. In Q&A, Chief Scientific Officer Dr. Erik Ingelsson emphasized the company’s goal of correcting the disease-driving variant to restore enzyme function, addressing not only steatosis but also inflammatory and fibrosis-related components of liver injury.
In Duchenne muscular dystrophy, Wave reiterated it remains on track to submit an NDA in 2026 for accelerated approval of WVE-N531 with a monthly dosing regimen.
Financial results, cash runway, and collaboration revenue
Chief Financial Officer Kyle Moran reported fourth-quarter 2025 revenue of $17.2 million, down from $83.7 million in the prior-year quarter. Full-year 2025 revenue was $42.7 million versus $108.3 million in 2024. Moran attributed the decreases to revenue previously recognized upon termination of the Takeda collaboration in October 2024, partially offset by higher revenue under the company’s GSK collaboration.
Research and development expense rose to $52.8 million in Q4 2025 from $44.6 million a year earlier, and to $182.8 million for the full year from $159.7 million. General and administrative expense increased to $20.9 million in Q4 from $16.1 million, and to $75.3 million for the year from $59.0 million, with increases primarily tied to compensation-related expenses including share-based compensation.
Net loss was $53.2 million for the quarter versus net income of $29.3 million in the prior-year quarter. Full-year net loss was $204.4 million compared with a net loss of $97.0 million in 2024.
Wave ended 2025 with $602.1 million in cash and cash equivalents, which Moran said is expected to fund operations into the third quarter of 2028, excluding any potential future milestone payments from GSK. Bolno also noted that GSK selected a fourth program for development candidate advancement, and that an associated milestone payment was received in the first quarter.
About WAVE Life Sciences (NASDAQ:WVE)
WAVE Life Sciences is a clinical-stage genetic medicines company focused on the discovery and development of stereopure oligonucleotide therapies designed to address serious diseases with high unmet medical need. Leveraging proprietary chemistry and precision synthesis, WAVE engineers drug candidates with defined stereochemistry to optimize potency, safety and manufacturability. This approach aims to enhance target specificity and improve therapeutic profiles compared with traditional oligonucleotide medicines.
The company’s pipeline includes programs in neuromuscular disorders such as Duchenne muscular dystrophy and neurodegenerative conditions including Huntington’s disease, as well as early-stage cardiovascular and liver indications.
