Wave Life Sciences signals INLIGHT trial data for over 100 participants by H1 2026 while advancing RNA editing pipeline

Earnings Call Insights: Wave Life Sciences Ltd. (WVE) Q3 2025

MANAGEMENT VIEW

* Paul Bolno, President, CEO & Director, highlighted the company's "first ever demonstration of activin E reductions in a clinical trial" with WVE-007, reporting "highly significant and durable human activin E reductions that exceeded levels needed in preclinical models to drive meaningful weight loss and prevent rebound weight gain following cessation of the GLP-1." Bolno emphasized the momentum in the INLIGHT clinical trial, with "over 70 participants enrolled and... well-positioned to deliver data on over 100 participants from the clinical trial sites in Europe and the U.S. in the first half of 2026."
* Bolno noted that WVE-007 was "generally safe and well tolerated," and that the data monitoring committee approved escalation to a higher dose in Cohort 5. He shared that activin E reductions were "56% for the 75-milligram cohort, 75% for the 240-milligram cohort and an 85% reduction for the 400-milligram cohort compared to baseline."
* The CEO detailed advancement in the RNA editing portfolio, reporting that WVE-006 achieved "AAT levels of up to almost 13 micromolar," with "64% of AAT was wild-type M-AAT with a corresponding 60% decrease in mutant Z-AAT protein." He said, "Most notably, we are able to restore a ZZ participants ability to respond to an acute inflammatory event with total AAT levels of greater than 20 micromolar, just 2 weeks after a single dose of 006."
* Bolno announced the new RNA editing clinical candidate, WVE-008, for PNPLA3 I148M liver disease, targeting "up to 9 million homozygous individuals living with PNPLA3 I148M liver disease in the U.S. and Europe."
* On the DMD program, Bolno stated, "We observed a statistically significant and clinically meaningful improvement of 3.8 seconds in time to rise versus natural history, which is the largest effect observed relative to any approved dystrophin restoration therapy at 48 weeks."
* CFO Kyle Moran reported, "Our revenue for the third quarter of 2025 was $7.6 million compared to negative $7.7 million in the prior year quarter." Moran added, "Research and development expenses were $45.9 million... our G&A expenses were $18.1 million... our net loss was $53.9 million for the third quarter of 2025." He stated, "We ended the third quarter of 2025 with $196.2 million in cash and cash equivalents... an additional $72.1 million in ATM proceeds and committed GSK milestones extended our expected cash runway into Q2 2027."

OUTLOOK

* Management indicated they "plan to deliver multiple near-term updates that assess blood-based biomarkers of metabolic health, body composition and weight loss across multiple cohorts." Data from the INLIGHT trial on "over 100 participants" are expected in the "first half of 2026."
* For WVE-006, dosing is ongoing in the "400-milligram multi-dose cohort," with data expected in the "first quarter of 2026." Clinical planning for WVE-008 is underway for a "CTA submission in 2026."
* Bolno stated, "We remain on track to submit an IND in 2026 for accelerated approval of N531 with a monthly dosing regimen."

FINANCIAL RESULTS

* Revenue for Q3 2025 was reported at $7.6 million, with research and development expenses at $45.9 million, G&A expenses at $18.1 million, and a net loss of $53.9 million.
* Cash and cash equivalents at quarter end were $196.2 million, supplemented by $72.1 million in ATM proceeds and GSK milestones, extending the cash runway into Q2 2027.
* The company noted that "potential future milestones and other payments to us under our GSK collaboration are not included in our cash runway."

Q&A

* Joon Lee, Truist Securities, Inc., Research Division, asked about fat mobilization post activin E knockdown and potential liver fat deposits. Bolno replied, "Preclinically, we haven't observed any changes in increased lipids and deposits in the liver. That's both in the DIO studies we've done, but also in our preclinical toxicology studies."
* Joon Lee inquired about the FDA's stance on MRI as a surrogate for Huntington's. Bolno responded, "We have... alignment with the FDA on the use of MRI as an imaging endpoint in connection with all of the other clinical data we're measuring... we're running this as a placebo-controlled study."
* Cheng Li, Oppenheimer & Co. Inc., Research Division, inquired about biomarkers and weight loss trajectory. Bolno explained that "the rapid engagement of both the target and suppression of protein happens fairly rapidly and is sustained," and Ingelsson added, "There is a trajectory."
* Salim Syed asked about the AATD program and DMD strategy. Bolno discussed differentiation from DNA editors and emphasized RNA editing's chronic disease suitability, stating, "We respond with infrequent sub-Q administration. We have no by edits. We have no off target editing, no indels."
* Madison Wynne El-Saadi, B. Riley Securities, asked for insights on the acute phase response in the AATD patient and the bifunctional construct. Bolno said, "There's no new insights other than, obviously, patient recovered," and Vargeese added, "The platform provides us an opportunity to be highly specific for both enzymes."
* Multiple analysts probed on DMD, obesity pricing, and trial design. Bolno noted no changes in FDA opinion on dystrophin endpoints and highlighted the potential for wider accessibility and durability in the obesity space.

SENTIMENT ANALYSIS

* Analysts pressed on trial design, regulatory clarity, and differentiation in RNA and siRNA approaches, with a neutral to slightly positive tone, expressing interest in the translation of preclinical results to human studies.
* Management presented a confident tone in prepared remarks and Q&A, repeatedly highlighting momentum, regulatory progress, and clinical translation: "we feel very confident in both what's driving our decision on the utility of MRI imaging caudate, but also making sure we run a well-powered, well-designed clinical trial."
* Compared to the previous quarter, the sentiment remains optimistic, with increased focus on clinical milestones and regulatory alignment.

QUARTER-OVER-QUARTER COMPARISON

* Guidance for INLIGHT was expanded, with data on "over 100 participants" now targeted for the first half of 2026, compared to previous focus on ongoing cohort expansion and initial data.
* The current quarter featured more granular disclosures of dose-dependent activin E reductions and emerging plans for WVE-008, while maintaining timelines for DMD and HD programs.
* Cash runway guidance extended into Q2 2027, compared to "into 2027" previously.
* Analysts in both quarters maintained a focus on trial design, regulatory endpoints, and competitive differentiation, but Q3 saw more questions on RNA editing and program expansion.
* Management confidence remained steady, with the current quarter emphasizing clinical translation and durable effects, especially in obesity and AATD.

RISKS AND CONCERNS

* Management acknowledged pricing dynamics in the obesity market and the need for durability and accessibility in non-incretin therapies.
* There was discussion of potential changing FDA attitudes towards endpoints in DMD and Huntington's, though Bolno stated, "we haven't seen any correspond from the FDA changing on dystrophin."
* Safety and durability of the siRNA and editing approaches were addressed, with no new safety signals reported.
* Analysts raised concerns about translation of preclinical to clinical data, off-target effects in editing, and long-term clinical durability.

FINAL TAKEAWAY

Wave Life Sciences management underscored rapid progress in their INLIGHT obesity program, with robust dose-dependent activin E reductions and a commitment to deliver clinical data on over 100 participants in the first half of 2026. The company also highlighted advancements in its RNA editing pipeline, strong engagement with regulatory authorities, and an extended cash runway supporting strategic execution across multiple clinical programs. Management remains focused on translating their proprietary platform into durable, differentiated therapies for obesity, AATD, and other indications, positioning the company for key data-driven milestones in the coming year.

Read the full Earnings Call Transcript [https://seekingalpha.com/symbol/wve/earnings/transcripts]

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