Wave Life Sciences (NASDAQ: WVE) doubles cash, widens 2025 loss on R&D push
Rhea-AI Filing Summary
Wave Life Sciences reported much higher cash and a larger loss for 2025 while outlining ambitious RNA programs in obesity, liver and lung disease. Cash and cash equivalents rose to
Full-year 2025 revenue was
The company highlighted WVE-007 for obesity, where a single dose showed fat loss similar to GLP‑1 drugs at three months while preserving lean mass, with data updates and a Phase 2a multidose trial planned in 2026. It also advanced WVE‑006 for alpha‑1 antitrypsin deficiency, achieving total AAT levels above 11 micromolar and dynamic increases during acute phase responses, and plans a 2026 clinical trial application for WVE‑008 in PNPLA3 I148M liver disease.
Positive
- Cash position strengthened: Cash and cash equivalents reached
$602.1 million as of December 31, 2025, up from$302.1 million a year earlier, supporting an expected cash runway into Q3 2028. - Encouraging clinical signals: WVE-007 showed single-dose fat loss similar to GLP‑1 therapies at three months with preservation of lean mass, and WVE‑006 achieved total AAT levels above 11 micromolar with dynamic increases during acute phase responses.
Negative
- Revenue decline: Full-year 2025 revenue fell to
$42.7 million from$108.3 million in 2024, reflecting significantly lower top-line contribution. - Loss more than doubled: Net loss widened to
$204.4 million in 2025 from$97.0 million in 2024, driven by higher research and development and general and administrative expenses.
Insights
Wave increased cash sharply but posted a much larger loss as revenue fell.
Wave Life Sciences ended 2025 with strong liquidity, reporting cash and cash equivalents of
However, collaboration and other revenue declined to
Pipeline data are encouraging, particularly WVE‑007’s fat-loss and muscle-preservation profile and WVE‑006’s restoration of physiologic AAT responses. The eventual financial impact will depend on upcoming 2026 data releases and regulatory feedback described in the update.
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
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Form
CURRENT REPORT
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| Title of each class |
Trading symbol |
Name of each exchange | ||
| Item 2.02 | Results of Operations and Financial Condition. |
On February 26, 2026, Wave Life Sciences Ltd. (the “Company”) announced its financial results for the quarter and year ended December 31, 2025. The full text of the press release issued in connection with the announcement is furnished as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated by reference herein.
| Item 7.01 | Regulation FD Disclosure. |
From time to time, the Company presents and/or distributes slides and presentations to the investment community to provide updates and summaries of its business. On February 26, 2026, the Company updated its corporate presentation, which is available on the “Investors” section of the Company’s website at http://ir.wavelifesciences.com/. This presentation is also furnished as Exhibit 99.2 to this Current Report on Form 8-K
The information in these Items 2.02 and 7.01 are being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that Section, nor shall they be deemed incorporated by reference into any registration statement or other filing under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in such filing.
| Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits
The following exhibits relating to Items 2.02 and 7.01 are furnished and not filed:
| Exhibit No. |
Description | |
| 99.1 | Press Release issued by Wave Life Sciences Ltd. dated February 26, 2026 | |
| 99.2 | Corporate Presentation of Wave Life Sciences Ltd. dated February 26, 2026 | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| WAVE LIFE SCIENCES LTD. | ||
| By: | /s/ Kyle Moran | |
| Kyle Moran | ||
| Chief Financial Officer | ||
Date: February 26, 2026
Exhibit 99.1
Wave Life Sciences Reports Fourth Quarter and Full Year 2025 Financial Results and Provides Business Update
On track for INLIGHT clinical data update in 1Q 2026; fat loss similar to GLP-1 observed at three months and expected to continue over time and with higher doses of WVE-007 (INHBE GalNAc-siRNA), while preserving muscle mass
Planning underway to initiate Phase 2a multidose portion of WVE-007 INLIGHT clinical trial for obesity in individuals with higher BMI and comorbidities in 1H 2026, as well as additional trials of WVE-007 as an incretin add-on and as post-incretin maintenance in 2026
Advancing regulatory engagement on potential accelerated approval pathway for WVE-006 (GalNAc-RNA editing) for AATD with feedback anticipated mid-2026; RestorAATion-2 clinical trial fully enrolled through 600 mg cohort and multiple data updates on track beginning with 400 mg multidose data in 1Q 2026
CTA submission for WVE-008 (GalNAc-RNA editing for PNPLA3 I148M liver disease) on track for 2026
Well capitalized with cash and cash equivalents of $602.1 million as of December 31, 2025 and expected cash runway into 3Q 2028
Investor conference call and webcast at 8:30 a.m. ET today
CAMBRIDGE, Mass., February 26, 2026 – Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage biotechnology company focused on unlocking the broad potential of RNA medicines to transform human health, today announced financial results for the fourth quarter and full year ended December 31, 2025, and provided a business update.
“We entered 2026 focused on executing in two priority areas: accelerating development of WVE-007, our INHBE GalNAc-siRNA for obesity, and rapidly advancing our RNA editing portfolio, which includes WVE-006 for AATD and WVE-008 for PNPLA3 liver disease. WVE-007 is enabled by our leading RNAi capabilities supported by a differentiated and proprietary SpiNA design, and has the potential to be a transformative treatment approach for obesity. Our interim INLIGHT clinical data from the lowest therapeutic single-dose cohort demonstrated fat loss on par with GLP-1, favorable safety and tolerability, as well as the potential for once or twice a year dosing,” said Paul Bolno, MD, MBA, President and Chief Executive Officer at Wave Life Sciences. “With our upcoming data update, we will have the first opportunity to assess the impact of longer follow-up and a higher dose level. We are also working rapidly towards initiating the Phase 2a multidose portion of our INLIGHT study in individuals with higher BMI and comorbidities. In addition, we are excited to investigate WVE-007 across treatment settings as an incretin add-on and post-incretin maintenance to potentially benefit more individuals living with obesity.”
Dr. Bolno added, “With WVE-006, our RNA editing therapeutic candidate for AATD, we have already achieved key AATD treatment goals including dynamic AAT production of over 20 micromolar. By correcting RNA, WVE-006 is designed to address both liver and lung manifestations of the disease with convenient, infrequent subcutaneous dosing. WVE-006 has demonstrated a favorable safety profile and comes without the irreversible, collateral
bystander edits and indels, which are associated with DNA base editing. Additionally, WVE-006 does not require LNP delivery, which may be associated with systemic and liver toxicities. WVE-006 has the potential to provide a much-needed therapeutic option for the 200,000 individuals in the U.S. and Europe living with homozygous ‘ZZ’ AATD. We have accelerated regulatory engagement and we expect to receive feedback on a potential accelerated approval pathway mid-year. Building on our clinical success in RNAi and RNA editing, we are advancing WVE-008, our PNPLA3 GalNAc-AIMer, for the nine million individuals living with homozygous PNPLA3 I148M liver disease in the U.S. and Europe, as well as a pipeline of additional hepatic and extra-hepatic siRNAs and AIMers, further supporting our vision of bringing transformative therapies to individuals living with the burden of disease.”
Recent Business Highlights and Expected Milestones
Obesity
| • | WVE-007 is an investigational GalNAc-siRNA (SpiNA design) designed to silence INHBE mRNA, a promising therapeutic strategy to treat obesity with strong evidence from human genetics. Individuals who have a protective loss-of-function variant in one copy of the INHBE gene have a healthier cardiometabolic profile, including less abdominal fat, lower triglycerides, and lower risk of type 2 diabetes and cardiovascular disease. In preclinical studies in DIO mice, a single dose of Wave’s INHBE GalNAc-siRNA led to weight loss similar to GLP-1 (semaglutide), substantial decreases in fat mass and preservation of lean mass. As an add-on to semaglutide, Wave observed double the weight loss in mice compared to semaglutide alone, and in a separate study it prevented weight regain upon cessation of semaglutide. |
| • | In December 2025, Wave announced interim results from the ongoing Phase 1, single-ascending dose portion of its INLIGHT clinical trial of WVE-007 in healthy individuals with overweight or obesity and an average BMI of 32.1 kg/m², a population with less visceral and subcutaneous fat than typical obesity studies. A single 240 mg dose of WVE-007 demonstrated improved body composition with fat loss similar to GLP-1 at three months with muscle preservation. INLIGHT does not include any diet or exercise modifications. There was sustained and robust suppression of serum Activin E supporting once-or twice-yearly dosing. WVE-007 was generally safe and well tolerated. |
| • | In the first quarter of 2026, Wave expects to deliver six-month follow-up data from Cohort 2 (240 mg) and three-month follow-up data from Cohort 3 (400 mg). |
| • | Planning is underway to initiate the Phase 2a multidose portion of INLIGHT evaluating WVE-007 as monotherapy in individuals with higher BMI and comorbidities in the first half of 2026. Assessments of the multidose portion, in addition to safety and tolerability, are expected to include serum Activin E, body weight, body composition (DEXA and MRI), and liver fat content (MRI-PDFF). |
| • | Wave also expects to initiate new clinical trials evaluating WVE-007 as an incretin add-on and as post-incretin maintenance in 2026. |
AATD (Alpha-1 antitrypsin deficiency)
| • | WVE-006 is an investigational GalNAc-conjugated, subcutaneously delivered, RNA editing oligonucleotide (AIMer) for alpha-1 antitrypsin deficiency (AATD). Clinical data from the 200 mg single and multidose cohorts and 400 mg single dose cohort of the ongoing RestorAATion-2 clinical trial have demonstrated WVE-006 achieved key AATD treatment goals, recapitulating the MZ phenotype, including the ability to dynamically generate AAT protein during an acute phase response. |
| • | In February 2026, with full control of WVE-006, Wave announced it was accelerating its regulatory engagement on a potential accelerated approval pathway. |
| • | The RestorAATion-2 clinical trial is fully enrolled through the 600 mg cohort, and dosing is ongoing. |
| • | Wave expects to deliver data from the 400 mg multidose cohort in the first quarter of 2026. Wave also expects to deliver single and multidose data from the 600 mg cohort in 2026. |
| • | Wave expects to receive regulatory feedback on a potential accelerated approval pathway mid-2026. |
PNPLA3 I148M liver disease
| • | WVE-008: Wave is building on its clinical success in RNA editing by advancing WVE-008, a GalNAc-conjugated AIMer for homozygous PNPLA3 I148M liver disease. Preparations continue to support a clinical trial application (CTA) filing for WVE-008 in 2026. |
DMD (exon 53)
| • | WVE-N531: Wave remains on track to file a New Drug Application (NDA) in 2026 to support accelerated approval of WVE-N531 with monthly dosing. |
GSK research collaboration
| • | In January 2026, GSK selected a fourth program to advance to development candidate. Under the collaboration, GSK can advance up to eight programs leveraging Wave’s PRISM® platform, with target validation work ongoing across multiple therapy areas. Assuming advancement of these programs, Wave would be eligible for up to $2.8 billion in initiation, development, launch, and commercialization milestones, as well as tiered royalties. Wave anticipates it will continue to receive milestone payments in 2026 and beyond. |
Financial Highlights
| • | Cash and cash equivalents were $602.1 million as of December 31, 2025, compared to $302.1 million as of December 31, 2024. The increase in cash year-over-year is primarily due to financing proceeds along with the receipt of milestone payments and research funding from GSK. Wave expects that its current cash and cash equivalents will be sufficient to fund operations into 3Q 2028. Potential future milestone and other payments to Wave under its GSK collaboration are not included in its cash runway. |
| • | Revenue recognized was $17.2 million for the fourth quarter of 2025 as compared to $83.7 million in the prior year quarter. Revenue recognized was $42.7 million in 2025 as compared to $108.3 million in 2024. |
| • | Research and development expenses were $52.8 million in the fourth quarter of 2025 as compared to $44.6 million in the same period in 2024. Research and development expenses for the full year were $182.8 million in 2025, as compared to $159.7 million in 2024. |
| • | General and administrative expenses were $20.9 million in the fourth quarter 2025 as compared to $16.1 million in the same period in 2024. General and administrative expenses for the full year were $75.3 million in 2025, as compared to $59.0 million in 2024. |
| • | Net loss was $53.2 million for the fourth quarter of 2025 as compared to a net income of $29.3 million in the prior year quarter. Net loss for the full year was $204.4 million for 2025 as compared to $97.0 million in 2024. |
Investor Conference Call and Webcast
Wave will host an investor conference call today at 8:30 a.m. ET to review the fourth quarter and full year 2025 financial results and pipeline updates. A webcast of the conference call can be accessed by visiting “Investor Events” on the investor relations section of the Wave Life Sciences website: https://ir.wavelifesciences.com/events-publications/events. Analysts planning to participate during the Q&A portion of the live call can join the conference call at the audio-conferencing link here. Following the live event, an archived version of the webcast will be available on the Wave Life Sciences website.
About Wave Life Sciences
Wave Life Sciences (Nasdaq: WVE) is a biotechnology company focused on unlocking the broad potential of RNA medicines to transform human health. Wave’s RNA medicines platform, PRISM®, combines multiple modalities, chemistry innovation and deep insights in human genetics to deliver scientific breakthroughs that treat both rare and common disorders. Its toolkit of RNA-targeting modalities, including RNAi (SpiNA) and RNA editing (AIMers), provides Wave with unmatched capabilities for designing and sustainably delivering candidates that optimally address disease biology. Wave’s pipeline is focused on its obesity (WVE-007), alpha-1 antitrypsin deficiency (WVE-006) and PNPLA3 I148M liver disease (WVE-008) programs, and also includes clinical programs in Duchenne muscular dystrophy and Huntington’s disease, as well as several preclinical programs utilizing the company’s versatile RNA medicines platform. Driven by the calling to “Reimagine Possible,” Wave is leading the charge toward a world in which human potential is no longer hindered by the burden of disease. Wave is headquartered in Cambridge, MA. For more information on Wave’s science, pipeline and people, please visit www.wavelifesciences.com and follow Wave on X and LinkedIn.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, concerning our goals, beliefs, expectations, strategies, objectives and plans, and other statements that are not necessarily based on historical facts, including statements regarding the following, among others: the anticipated initiation, timing, design, progress, data and announcements related to our clinical trials, including interactions with and feedback from regulators and any potential registrational submissions based on these data; the future performance and results of our programs in clinical trials, including the anticipated therapeutic benefits of such programs and our expectations with respect to how our clinical data may predict success for our future therapeutic candidates and data readouts; the potential commercialization of our programs the potential size of the markets that our therapeutics may address; preclinical activities and programs and their potential to transition into clinical-stage programs, and the timing, progress and announcement of such events; the progress and potential benefits, including the potential achievement of milestones, of collaborations and strategic partnerships; the expected benefits of our stereopure oligonucleotides compared with stereorandom oligonucleotides; the breadth and versatility of our PRISM® drug discovery and development platform; the potential benefits of our RNA-targeting modalities, including RNAi (SpiNA) and RNA editing (AIMers); the potential for certain of our programs to be best-in-class or first-in-class, or to change the existing treatment paradigm or show substantial benefits over existing standards of care; our financial performance, including the anticipated duration of our cash runway and our ability to fund future operations; our intended uses of capital; and our expectations regarding the impact of any potential global macro events on our business. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual results to differ materially from those indicated by these forward-looking statements as a result of these risks, uncertainties and important factors, including, without limitation, the clinical results and timing of our programs, which may not support further development of our product candidates; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials; our effectiveness in managing current and future clinical trials and regulatory processes; the continued development and acceptance of nucleic acid therapeutics as a class of drugs; our ability to demonstrate the therapeutic benefits of our stereopure candidates in clinical trials, including our ability to develop candidates across multiple therapeutic modalities; our ability to obtain, maintain and protect intellectual property; our ability to fund our operations and to raise additional capital as needed; competition from others developing therapies for similar uses; and any impacts on our business as a result of or related to any global economic uncertainty or market disruptions, as well as the other risks and uncertainties described in the section entitled “Risk Factors” in our most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as amended, and in other filings we make with the SEC from time to time. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. We undertake no obligation, except to the extent required by law, to update the information contained in this press release to reflect subsequently occurring events or circumstances.
Contact:
Kate Rausch
VP, Corporate Affairs and Investor Relations
+1 617-949-4827
Investors:
James Salierno
Director, Investor Relations
+1 617-949-4043
InvestorRelations@wavelifesci.com
Media:
Katie Sullivan
Senior Director, Corporate Communications
+1 617-949-2936
MediaRelations@wavelifesci.com
WAVE LIFE SCIENCES LTD.
UNAUDITED CONSOLIDATED BALANCE SHEETS
(In thousands, except share amounts)
| December 31, 2025 |
December 31, 2024 |
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| Assets |
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| Current assets: |
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| Cash and cash equivalents |
$ | 602,068 | $ | 302,078 | ||||
| Accounts receivable |
1,276 | 1,422 | ||||||
| Prepaid expenses |
8,395 | 9,544 | ||||||
| Other current assets |
3,075 | 7,350 | ||||||
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| Total current assets |
614,814 | 320,394 | ||||||
| Long-term assets: |
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| Property and equipment, net of accumulated depreciation of $49,522 and $46,329 |
7,405 | 10,128 | ||||||
| Operating lease right-of-use assets |
12,458 | 17,870 | ||||||
| Restricted cash |
3,806 | 3,760 | ||||||
| Other assets |
16 | 55 | ||||||
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| Total long-term assets |
23,685 | 31,813 | ||||||
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| Total assets |
$ | 638,499 | $ | 352,207 | ||||
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| Liabilities, Series A preferred shares and shareholders’ equity |
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| Current liabilities: |
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| Accounts payable |
$ | 15,700 | $ | 16,262 | ||||
| Accrued expenses and other current liabilities |
26,564 | 21,081 | ||||||
| Current portion of deferred revenue |
44,440 | 65,972 | ||||||
| Current portion of operating lease liability |
8,361 | 7,638 | ||||||
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| Total current liabilities |
95,065 | 110,953 | ||||||
| Long-term liabilities: |
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| Deferred revenue, net of current portion |
7,798 | 6,099 | ||||||
| Operating lease liability, net of current portion |
9,405 | 17,766 | ||||||
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| Total long-term liabilities |
17,203 | 23,865 | ||||||
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| Total liabilities |
$ | 112,268 | $ | 134,818 | ||||
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| Series A preferred shares, no par value; 3,901,348 shares issued |
$ | 7,874 | $ | 7,874 | ||||
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| Shareholders’ equity: |
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| Ordinary shares, no par value; 187,660,263 and 153,037,286 shares issued |
$ | 1,616,478 | $ | 1,175,181 | ||||
| Additional paid-in capital |
228,365 | 156,454 | ||||||
| Accumulated other comprehensive loss |
(250 | ) | (262 | ) | ||||
| Accumulated deficit |
(1,326,236 | ) | (1,121,858 | ) | ||||
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| Total shareholders’ equity |
518,357 | 209,515 | ||||||
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| Total liabilities, Series A preferred shares and shareholders’ equity |
$ | 638,499 | $ | 352,207 | ||||
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The accompanying notes are an integral part of the consolidated financial statements.
WAVE LIFE SCIENCES LTD.
UNAUDITED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE INCOME (LOSS)
(In thousands, except share and per share amounts)
| Three Months Ended December 31, | Twelve Months Ended December 31, | |||||||||||||||
| 2025 | 2024 | 2025 | 2024 | |||||||||||||
| Revenue |
$ | 17,244 | $ | 83,748 | $ | 42,727 | $ | 108,302 | ||||||||
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| Operating expenses: |
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| Research and development |
52,814 | 44,645 | 182,779 | 159,682 | ||||||||||||
| General and administrative |
20,897 | 16,136 | 75,331 | 59,023 | ||||||||||||
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| Total operating expenses |
73,711 | 60,781 | 258,110 | 218,705 | ||||||||||||
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| Income (loss) from operations |
(56,467 | ) | 22,967 | (215,383 | ) | (110,403 | ) | |||||||||
| Other income, net: |
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| Dividend income and interest income, net |
3,054 | 3,738 | 10,478 | 10,163 | ||||||||||||
| Other income, net |
234 | 2,548 | 527 | 3,232 | ||||||||||||
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| Total other income, net |
3,288 | 6,286 | 11,005 | 13,395 | ||||||||||||
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| Income (loss) before income taxes |
(53,179 | ) | 29,253 | (204,378 | ) | (97,008 | ) | |||||||||
| Income tax benefit |
— | — | — | — | ||||||||||||
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| Net income (loss) |
$ | (53,179 | ) | $ | 29,253 | $ | (204,378 | ) | $ | (97,008 | ) | |||||
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| Net income (loss) attributable to ordinary |
$ | (53,179 | ) | $ | 29,253 | $ | (204,378 | ) | $ | (97,008 | ) | |||||
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| Net income (loss) per share attributable to |
$ | (0.30 | ) | $ | 0.18 | $ | (1.21 | ) | $ | (0.70 | ) | |||||
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| Weighted-average ordinary shares used in |
180,152,207 | 161,487,609 | 168,649,795 | 138,277,468 | ||||||||||||
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| Net income (loss) per share attributable to |
$ | (0.30 | ) | $ | 0.17 | $ | (1.21 | ) | $ | (0.70 | ) | |||||
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| Weighted-average ordinary shares used in |
180,152,207 | 172,290,361 | 168,649,795 | 138,277,468 | ||||||||||||
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| Other comprehensive income (loss): |
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| Net income (loss) |
$ | (53,179 | ) | $ | 29,253 | $ | (204,378 | ) | $ | (97,008 | ) | |||||
| Foreign currency translation gain (loss) |
(60 | ) | (103 | ) | 12 | (138 | ) | |||||||||
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| Comprehensive income (loss) |
$ | (53,239 | ) | $ | 29,150 | $ | (204,366 | ) | $ | (97,146 | ) | |||||
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The accompanying notes are an integral part of the consolidated financial statements.
Exhibit 99.2 Wave Life Sciences Corporate Presentation February 26, 2026
Forward-looking statements This document contains forward-looking statements. All statements other than statements of historical facts contained in this document, including statements regarding possible or assumed future results of operations, preclinical and clinical studies, business strategies, research and development plans, collaborations and partnerships, regulatory activities and timing thereof, competitive position, potential growth opportunities, use of proceeds and the effects of competition are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors that may cause the actual results, performance or achievements of Wave Life Sciences Ltd. (the “Company”) to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “aim,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions. The forward- looking statements in this presentation are only predictions. The Company has based these forward-looking statements largely on its current expectations and projections about future events and financial trends that it believes may affect the Company’s business, financial condition and results of operations. These forward-looking statements speak only as of the date of this presentation and are subject to a number of risks, uncertainties and assumptions, including those listed under Risk Factors in the Company’s Form 10-K and other filings with the SEC, some of which cannot be predicted or quantified and some of which are beyond the Company’s control. The events and circumstances reflected in the Company’s forward-looking statements may not be achieved or occur, and actual results could differ materially from those projected in the forward-looking statements. Moreover, the Company operates in a dynamic industry and economy. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties that the Company may face. Except as required by applicable law, the Company does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. 2
Our Mission To unlock the broad potential of RNA medicines to transform human health 3
Building a leading RNA medicines company Differentiated RNA medicines Translating genetic insights into Unlocking platform and chemistry potentially best-in-class medicines emerging pipeline RNAi WVE-007 (obesity) • Extra-hepatic capabilities: • Differentiated mechanism with RNAi and RNA editing focused on fat loss and • Proprietary chemistry muscle preservation • Leveraging deep insights in human RNA editing WVE-006 (AATD) • Bifunctional modalities: genetics WVE-008 (liver disease) single oligonucleotide constructs for dual RNAi • Restoration of functional • Strong and broad IP silencing or RNAi silencing + protein production RNA editing • In-house GMP manufacturing Other modalities: DMD and HD clinical programs 1 Well capitalized with ~$602 million and expected cash runway into 3Q 2028 4 1 Potential future milestones and other payments to Wave under its GSK collaboration are not included in its cash runway
For over a decade Wave has been extending the frontiers of RNA therapies delivering breakthroughs in nucleic acid chemistry RNAi — SpiNA RNA editing — AIMer Protein reduction Ago2 loading 100% 80% 60% 40% 20% 0% C C N3U N3U Base 2’ deoxy 2’ OMe 2’ deoxy 2’ OMe Sugar Substantial improvements in potency, duration of activity, and Ago2 loading Increased RNA editing efficiency achieved with Wave’s proprietary SpiNA design with proprietary chemistry Proprietary chemistry has dramatically increased potency and durability 5 SpiNA: Stereopure interfering Nucleic Acid https://wavelifesciences.com/science/publications/ % Ugp2 mRNA editing
Robust RNA medicines pipeline with first-in-class RNAi and RNA editing programs Patient population Program Discovery IND / CTA Enabling Studies Clinical (US & Europe) R N A i ( S p i N A ) 175M WVE-007 (GalNAc) INHBE (obesity) (>1 billion globally) GalNAc / extra-hepatic -- Multiple R N A E D I T I N G ( A I M e r ) WVE-006 (GalNAc) 200K SERPINA1 (AATD) WVE-008 (GalNAc) 9M PNPLA3 (liver disease) GalNAc / extra-hepatic -- Multiple S PLI C I N G WVE-N531 2.3K Exon 53 (DMD) Other exons (DMD) Up to 18K A LLE LE - S E LE C T I V E S I LE N C I N G WVE-003 25K Symptomatic (SNP3) mHTT (HD) 60K Pre-Symptomatic (SNP3) 6 AATD: Alpha-1 antitrypsin deficiency; DMD: Duchenne muscular dystrophy; HD: Huntington’s disease
WVE-007 GalNAc-siRNA silencing Obesity 7
Obesity is a metabolic disease in need of a treatment paradigm shift Individuals living with obesity have higher risk for many serious health conditions, including heart disease, 1 type 2 diabetes, and some forms of cancer Current standard of care: GLP-1s WVE-007 Impact of GLP-1s is often limited by: INHBE GalNAc-siRNA 2 Loss of muscle mass Fat loss similar to GLP-1 at three months 3 Frequent dosing Preserves muscle 4 Poor tolerability Potential 1–2 per year dosing 5,6 High discontinuation rates Generally safe and well-tolerated Improving body composition is the future for the > 1 billion people living with obesity globally 8 1. Koenen et al. 2021 Circ Res 128, 951; 2. Sargeant, et al. 2019 Endocrinol Metab (Seoul) 34, 247; 3. Wegovy PI; 4. Ghusn and Hurtado. 2024 Obesity Pillars 12, 100127; 5. Leach, et al. 2023 Prime Therapeutics Claims Analysis; 6. Gasoyan, et al. 2024 Obesity (Silver Spring) 32, 486. Right: INLIGHT interim data for investigational WVE-007 (INHBE GalNAc-siRNA) (Presentation deck) and ADA presentation
Body composition improvements: Reducing fat, including visceral fat, while also preserving lean mass Reduce fat, including visceral fat Preserve lean mass, including muscle Increased visceral adiposity is associated Maintaining metabolic rate with many diseases including cardiometabolic disorders Insulin Improved insulin sensitivity resistance MASH Prevent weight regain Subcutaneous fat Type 2 diabetes Abdominal muscles Preserve muscle strength and function Visceral fat Chronic inflammatory diseases Cardiovascular Reduce frailty diseases 9 1. Liao, Y. et al. 2025 Front. Nutr. 11, 1517186; 2. Ibarra-Reynoso, L.d.R. et al. 2025 J. Clin. Med. 14, 8365; 3. Wu, Q-W., et al. 2025 Front. Endocrinol. 16, 1635282; 4. Galvan, B. et al. 2025 J. Funct. Morphol. Kinesiol. 10, 244. MASH: Metabolic Dysfunction Associated Steatohepatitis
Human genetic data demonstrate that heterozygous INHBE loss-of-function (LoF) carriers have a healthy metabolic profile Heterozygous INHBE LoF carriers have favorable traits: Heterozygous INHBE LoF carriers have lower risk of lower abdominal obesity, lower triglycerides, higher HDL-c Type 2 diabetes and CHD Waist to hip ratio Type 2 diabetes (abdominal obesity) Coronary heart disease Serum triglycerides 0.50 0.75 1 1.5 2.0 HDL-c Odds ratio (“good cholesterol”) Lower risk Higher risk (vs. non carriers) (vs. non carriers) ALT Favorable association with liver traits ApoB cT1 Fasting glucose ALT Visceral adipose Liver fat volume by MRI -0.4 -0.2 0 0.2 0.4 -0.50 -0.25 0 0.25 0.50 Standard deviations Standard deviations Reduction Elevation Reduction Elevation (vs. non carriers) (vs. non carriers) (vs. non carriers) (vs. non carriers) Silencing INHBE mRNA by ≥50% is expected to recapitulate the healthy metabolic profile of heterozygous INHBE LoF carriers 10 Akbari et al. Nat Commun. 2022 Aug 23;13(1):4844; Deaton et al. Nat Commun. 2022 Jul 27 Waist to hip ratio: waist to hip ratio adjusted for BMI; HDL-c: high-density lipoprotein cholesterol; ALT: alanine transaminase; ApoB: apolipoprotein B; CHD: coronary heart disease; cT1: corrected T1
Silencing INHBE mRNA has the potential to treat obesity and associated metabolic diseases Release of dimerized Binds to and activates ACVR1C Block adipose INHBE subunits creates (ALK7) receptor in adipose tissue lipolysis hepatokine Activin E Activin E Activin E Increased abdominal adiposity leads to obesity, I II I I CVD and T2D Adipocyte ALK7 Decreased abdominal adiposity leads to weight loss and reduced risk for CVD and T2D Reduction of Reduced release of Diminished activation of Increased adipose INHBE mRNA with hepatokine Activin E ACVR1C (ALK7) receptor in lipolysis and shrink GalNAc-siRNA adipose tissue adipocytes 11 1. Cell Reports (2018) 25, 1193–1203; 2. Biochemical Journal (2024) 481 547–564; 3. PNAS 2023 Vol. 120 No. 32 e2309967120; 4. Nat Commun 2022. https://doi.org/10.1038/s41467- 022-32398-7; 5. Nat Commun 2022. https://doi.org/10.1038/s41467-022-31757-8
A single dose of INHBE GalNAc-siRNA led to shrinkage of adipocytes in DIO mice Mean adipocyte diameter DIO Lean PBS INHBE GalNAc-siRNA (μm) ✱✱✱ 80 60 40 20 0 Lean DIO DIO PBS INHBE GalNAc- siRNA 12 Data presented at ADA Scientific Sessions June 2025 ***p<0.001; Day 28
A single dose of INHBE siRNA led to a lower inflammatory state of visceral adipose tissues in DIO mice, with strong suppression of pro-inflammatory M1 macrophages in visceral fat Macrophages (Mᶲ) (F4/80) Pro-inflammatory (M1) Mᶲ Anti-inflammatory (M2) Mᶲ (CD11c) (CD163) INHBE GalNAc siRNA INHBE GalNAc siRNA INHBE GalNAc siRNA PBS 3 mg/kg 10 mg/kg PBS 3 mg/kg 10 mg/kg PBS 3 mg/kg 10 mg/kg ✱ 1.0 0.8 0.6 0.4 0.2 0.0 PBS 3 mg/kg 10 mg/kg PBS 3 mg/kg 10 mg/kg PBS 3 mg/kg 10 mg/kg 13 Data presented at ADA Scientific Sessions June 2025 ***p<0.001, *p<0.05, ns=non-significant %F4/80 positive area
Lowering of inflammatory state of epiWAT visceral fat induced by single dose of INHBE siRNA resulted in 58% reduction of adipose fibrosis Reduced staining illustrates decreased tissue fibrosis Fibrosis in mouse adipose (Day 56) 10 mg/kg PBS 3 mg/kg ✱ 15 10 5 0 PBS 3 mg/kg 10 mg/kg 14 Data are means ± SEM of 6 mice. Each dot represents an individual mouse. Kruska-Wallis test with Dunn’s multiple comparisons. *P<0.05 Trichrome % Trichrome positive area
Higher circulating Activin E levels are correlated with higher BMI, higher abdominal fat, and higher fasting insulin in non-diabetic adults BMI Fasting Insulin Abdominal Fat Further supports INHBE suppression as a weight loss approach for individuals living with obesity 15 Ref: Dubey et al. Activin E levels correlate with indicators of metabolic dysfunction in humans. ObesityWeek 2025.
Treatment with WVE-007 (investigational INHBE GalNAc-siRNA) is expected to drive fat reduction and improve key measures of cardiometabolic health 1 Driving fat reduction And improving clinical outcomes Leading siRNA design (SpiNA) WVE-007 Reduction of INHBE mRNA and (INHBE GalNAc-siRNA) circulating Activin E Proprietary, Cardiometabolic clinically validated ✓ outcomes chemistry Adipocyte Adipocyte lipolysis size Risk of CVD Subcutaneous delivery Insulin ✓ (GalNAc) Risk of T2D sensitivity Proinflammatory macrophages Potential for infrequent ✓ dosing (1 – 2x year) Fibrosis 16 1. SpiNA design is derived from Liu et al., 2023 Nucleic Acids Research doi: 10.1093/nar/gkad268
Single dose of INHBE GalNAc-siRNA led to durable Activin E reductions, and sustained improvements in body composition in DIO mice Muscle Durable Activin E Reduction in fat Reduction in body weight ✓ ✓ ✓ preservation ✓ reduction Serum Activin E Epididymal fat weight Quadricep weight Single dose INHBE GalNAc-siRNA * 0.25 150 -23% 0.75 0.20 -40% INHBE siRNA 100 0.15 0.50 0.10 50 0.25 Semaglutide 0.05 0 0.00 0.00 PBS INHBE INHBE INHBE PBS Sema- PBS INHBE INHBE 10 mg/kg 3 mg/kg 3 mg/kg 10 mg/kg glutide 10 mg/kg 17 Left and right panels: Semaglutide 10 nmol/kg daily SC in mouse is equivalent to therapeutic dose of 2.4mg weekly SC in human; INHBE GalNAc-siRNA 10 mg/kg dose. All data from preclinical studies were conducted in mice fed with 60% high fat diet. Linear Mixed Effects ANOVA with post hoc comparisons of marginal treatment effects vs. PBS per tissue.* p < 0.05 Activin E (%Control) Tissue weight (g) Tissue weight (g)
WVE-007 has potential for use synergistically with GLP-1s or to curtail weight regain after the cessation of treatment with GLP-1, based on preclinical data Combined with GLP-1: Greater weight loss After cessation of GLP-1: Curtails weight regain ✓ ✓ p<0.05 ~2x greater weight loss Not significant Day Day Single dose INHBE GalNAc-siRNA Daily GLP-1 PBS Daily GLP-1 Semaglutide Semaglutide Control for Semaglutide INHBE GalNAc-siRNA Dose INHBE GalNAc-siRNA Semaglutide + Control for siRNA Semaglutide + INHBE GalNAc-siRNA INHBE GalNAc-siRNA 18 Data from preclinical studies conducted in mice fed with 60% high fat diet; Left: semaglutide10 nmol/kg daily SC in mouse is equivalent to therapeutic dose of 2.4mg weekly SC in human. Left Stats: Linear Mixed Effects ANOVA with post hoc comparisons of marginal treatment effects of Semaglutide vs. Semaglutide + INHBE GalNAc-siRNA per time point * p < 0.05; Right Stats: Linear Mixed Effects ANOVA with post hoc comparison of Day 28 vs. Day 56 marginal effects per treatment Difference in body weight (% of PBS, same time point)
INLIGHT: Clinical trial of WVE-007 in individuals living with overweight or obesity Randomized, double-blind, placebo-controlled study with multiple clinical trial sites, including US Phase 1 SAD Phase 2a MAD SAD Cohort 4 Key study criteria: 600 mg (n=32) • Individuals with higher • HbA1c: <5.9 BMI and comorbidities • BMI: 28 – 35 kg/m² • Otherwise healthy• Assessments to SAD Cohort 3 MAD Cohort 2 additionally include: 400 mg (n=32) Assessments include: ― Body composition (MRI Safety and tolerability, in addition to DEXA) PK, Activin E, body SAD Cohort 2 MAD Cohort 1 composition (DEXA), ― Liver fat (MRI-PDFF) 240 mg (n=32) biomarkers, body weight No diet or exercise SAD Cohort 1 Planning underway to modifications are 75 mg (n=8) initiate in 1H 2026 PK/PD and safety only (no DEXA) instituted Expect to deliver 6-month 240 mg SAD data and 3-month 400 mg SAD data in 1Q 2026 19 SAD: single-ascending dose; MAD: multi-ascending dose; PK: pharmacokinetics
Improvements in body composition observed at three months after a single WVE-007 dose (lowest therapeutic dose); durability supports 1-2x yearly dosing Highly durable, dose dependent, serum Activin E Reductions in visceral and total fat mass with preservation reductions support dosing once or twice per year of lean mass observed at three months Activin E change in INLIGHT Total fat mass Visceral fat mass Lean mass 50% 3.2% 4% 2.3% 25% 2% 0% p=0.02 p=0.07 0% p=0.01 -25% -0.2% -0.5% -2% -50% -4% -75% -4.5% -6% -100% 0 50 100 150 -8% Study Day Single dose WVE-007 (GalNAc-siRNA) -10% -9.4% Placebo (n=13) WVE-007 75 mg (n=6) WVE-007 240 mg (n=24) Placebo (n=8) WVE-007 240 mg (n=24) WVE-007 400 mg (n=6) 20 Left: Figure shows sample means and SEMs. All MMRM baseline and placebo comparisons from Day 8 onwards are p<0.003. Placebo includes one individual from 400 mg expansion. Green shading: >70% Activin E reductions in preclinical models led to fat loss; Right: All DEXA percentage changes and p-values are model-based, using the SAP pre-specified analysis; p-values are from tests of within-group change over time; no p values were statistically significant for placebo. % Reduction in Activin E (nM) +/- SEM % Change from Baseline
Single dose of WVE-007 led to improvements in body composition with fat loss similar to GLP-1 at three months without muscle loss 1. For INLIGHT, all DEXA percentage changes and p-values are model-based, using the SAP pre-specified analysis. 2. For BELIEVE, all data points are approximate and based on placebo- adjusted estimates extracted from figures, body weight reported as total mass, from Heymsfield SB, et al. Symposium – “Can we improve the quality of weight loss by augmenting fat mass loss while preserving lean mass? The BELIEVE study of bimagrumab + semaglutide”. Presented at: American Diabetes Association Scientific Sessions; June 20-23, 2025; Chicago. 3. Semaglutide in 21 BELIEVE study was subcutaneously administered weekly and titrated to maintenance dose. N=57 in semaglutide 2.4 mg arm, N=56 in placebo arm. 4. Within the first 12 weeks of the BELIEVE study, bimagrumab was dosed IV at baseline and week 4. N=56 in bimagrumab 10 mg/kg arm, N=56 in placebo arm. Note: The data presented above are derived from different clinical trials with differences in trial design and patient population, including with respect to BMI. As a result, cross-trial comparisons cannot be made and no head-to-head clinical trials have been conducted.
Visceral fat is associated with insulin sensitivity and incidence of MASH, type 2 diabetes and cardiovascular disease Visceral fat reduction is associated with multiple Visceral fat increases risk of 5 health benefits cardiovascular disease Health Outcome Visceral Fat Reduction Associated Benefits Improved insulin sensitivity, lower 1 Insulin Sensitivity ≥ 5% decrease in visceral fat HbA1c, better lipid profile Reduced blood pressure, improved 2 Cardiovascular Risk ≥ 5–10% decrease in visceral fat lipids, lower systemic inflammation ≥ 10% decrease in visceral fat or Significant reduction in hepatic 3 Liver Fat (Steatosis) ≥ 7–10% body weight loss triglycerides, improved liver enzymes ≥ 10% decrease in visceral fat or Resolution of steatohepatitis in up to 4 Hepatic Fibrosis ≥ 7–10% body weight loss 90%, fibrosis regression in many cases WVE-007 aims to shift body composition by reducing body fat while preserving muscle, to deliver a healthier cardiometabolic profile 22 1. Gabriely et al., Diabetes 2002; Campos et al., Diabetes & Vascular Disease Research 2019; Huang et al., Front Endocrinol 2023. 2. Cesaro et al., Front Cardiovasc Med 2023; Khawaja et al., Curr Cardiol Rep 2024; Hiuge-Shimizu et al., J Atheroscler Thromb 2011. 3. Liao et al., PLoS ONE 2023; Jung et al., Endocrinol Metab 2020; ; Krittayaphong et al., Scientific Reports 2024; Hanlon & Yuan, Clin Liver Dis 2021. 4. Liao et al., PLoS ONE 2023; Jung et al., Endocrinol Metab 2020; Vilar-Gomez et al Gastroenterology 2015.. 5. Qaio et al. Cardiovasc Diabetol 21, 225 (2022). VAI = Visceral Adiposity Index
Potential to address more than one billion individuals with obesity globally Monotherapy Add-on Maintenance Single agent in individuals Combination with incretin An off-ramp post-incretin living with obesity treatments treatments • To induce fat loss with muscle • To leverage an orthogonal • To prevent weight rebound preservation and favorable mechanism to incretins for and maintain metabolic safety and tolerability enhanced efficacy improvements upon incretin cessation Expect to initiate new trials of WVE-007 as an incretin add-on and as post-incretin maintenance in 2026 23 Phelps, NH, et al. 2024 Lancet 403, 1027
WVE-006 RNA editing (AIMer) Alpha-1 antitrypsin deficiency (AATD) 24
AATD impacts multiple organ systems and has limited treatment options • AATD is a rare, inherited genetic disorder that is commonly caused by a G-to-A point mutation in the SERPINA1 gene • Pi*ZZ genotype is leading cause of severe AATD, predisposing to progressive lung damage, liver damage or both • Aggregation of mutant Z-AAT protein in hepatocytes and a lack of functional, wild-type M-AAT drives liver and lung disease, respectively AATD Lung Disease AATD Liver Disease • Treatment goal: Minimize episodic • Treatment goal: Decrease Emphysema Hepatocellular Fibrosis → Cirrhosis → Carcinoma Bronchiectasis exacerbations and associated damage Z-AAT protein • Lung damage occurs during • Progressive liver disease exacerbations that induce an results from Z-AAT-induced inflammatory acute phase response, proteotoxic stress when more AAT protein is needed for protection • Weekly IV augmentation therapy is only treatment option• No approved therapies — No protective increase in AAT protein levels during acute phase response without additional IV infusions ~200K people in the US and Europe are homozygous for the Z allele (Pi*ZZ genotype) 25 Strnad et al., 2020 N Engl J Med 382:1443-55; Blanco et al. 2017 Int J Chron Obstruct Pulmon Dis 12:561-69
WVE-006: Potential first-in-class, convenient therapy for AATD that addresses both liver and lung manifestations of the disease WVE-006 Restore circulating M-AAT 1 2 Reduce Z-AAT protein (RNA editing) and physiological AAT ✓ ✓ aggregation in liver protein production Proprietary ✓ chemistry Highly specific ✓ Z-AAT (no bystanders) Subcutaneous ✓ M-AAT delivery (GalNAc) RNA correction replaces mutant M-AAT reaches lungs to protect Z-AAT protein with wild-type M-AAT Infrequent dosing from proteases and reduce risk of protein to reduce risk of liver ✓ lung pathology pathology 26 Strnad et al., 2020 N Engl J Med 382:1443-55; Stoller et al., 1993 Alpha-1 Antitrypsin Deficiency GeneReviews. M-AAT: Wild-type alpha-1 antitrypsin protein Z-AAT: mutant alpha-1 antitrypsin protein
RNA editing aims to increase M-AAT and restore physiological AAT production during acute phase response Genotype Null Pi*ZZ Pi*MZ Pi*MM No AAT protein 100% Z-AAT Z-AAT and M-AAT 100% M-AAT AAT levels increase during No No Yes Yes acute phase response Risk of lung disease Very high High Low Normal Risk of liver disease None High Low Normal >50% RNA editing > 11 µM AAT Goal: Shift Pi*ZZ individuals to AAT biomarker profile consistent with Pi*MZ genotype 27
RNA editing aims to restore production of dynamic and therapeutically relevant levels of AAT protein in Pi*ZZ individuals during acute phase response Lung damage occurs during exacerbations, when AAT protein has protective functions and is produced more AAT protein is needed for protection during acute phase response 30,9 10 00 0 900 30,100 Pi*MZ Pi*ZZ 30,8 00 00 0 30,8 00 00 0 700 700 CRP CRP 600 600 500 500 400 400 300 300 AAT protein AAT protein 200 200 100 100 0 0 0 7 14 21 0 7 14 21 Days Days Inflammatory stimulus Inflammatory stimulus RNA editing has potential to restore dynamic AAT response to inflammation 28 Left: Mantovani A, Garlanda C. N Engl J Med, 2023;388:439-452; Right: Sanders et al., J COPD, 2018 Percent change in plasma concentration (%)
First-ever demonstration of ability to restore physiological serum AAT production; total AAT reached 20.6 µM during acute phase response Pi*ZZ patients have a reduced capacity to produce AAT protein during an acute phase response 1 Following WVE-006 200 mg single dose, total AAT and M-AAT increased Published data on CRP levels and AAT levels across different genotypes significantly in one patient during an acute phase response Total AAT Total AAT M-AAT M-AAT CRP 0 4 8 12 SAD MAD Acute phase response due to a kidney stone AAT response in Pi*ZZ participant treated with WVE-006 mirrors Pi*MZ phenotype 29 1 - Sanders et al., J COPD, 2018 CRP: C-reactive protein Circulating M-AAT, Z-AAT, and total (M + Z) AAT protein in the serum were measured by highly selective and sensitive LC-MS/MS assays (LLOQ: 0.096 µM (M), 0.029 µM (Z)) and reported as mean participant SAD and MAD maximums M-AAT + Z-AAT (µM) CRP levels (mg/L)
WVE-006 enables endogenous AAT production during an acute phase response while augmentation therapy may leave patients at risk Illustrative model of impact of acute phase response Augmentation therapy WVE-006 treatment approach Lung Protected damage lungs Endogenous AAT levels increase during acute phase response without need for add’l doses Exogenous AAT levels are depleted before next scheduled IV dose IV dosing RNA editing dose • Augmentation therapy has no impact on liver disease• WVE-006 also reduces levels of Z-AAT WVE-006 therapeutic goal is to restore dynamic AAT physiology; augmentation therapy goal is to maximize AAT levels as dynamic response is not enabled 30 Serum AAT Serum AAT
CRP (mg/L) WVE-006 achieved key treatment goals of restoring MZ phenotype Total AAT levels exceeded 11 µM, production of wild-type M-AAT of greater than 50%, restored physiological AAT production Plasma AAT of ~13 µM Wild-type M-AAT protein of 64% AAT reached >20 μM during an of total, reduction in Z-AAT acute phase response • Protein levels associated with lower risk of AATD liver and lung diseases 400 mg single dose 12.8 µM total AAT 200 mg multidose 11.9 µM total AAT Acute phase response due to a kidney stone 31 Circulating M-AAT, Z-AAT, and total (M + Z) AAT protein in the serum were measured by highly selective and sensitive LC-MS/MS assays (LLOQ: 0.096 µM (M), 0.029 µM (Z)) and reported as mean participant SAD and MAD maximums Middle: from 200 mg MAD cohort; Right: from 200 mg SAD cohort Mutant Z-AAT Wild-type M-AAT
RestorAATion-2 clinical trial ongoing; 400 mg MAD data expected in 1Q 2026 and 600 mg SAD and MAD data expected in 2026 RestorAATion-1: Healthy Volunteers RestorAATion-2: AATD Patients RestorAATion-1: Healthy Volunteers SAD → MAD Multi-dosing complete 600 mg SAD Cohort 3 MAD Cohort 3 600 mg 600 mg; Q4W 400 mg SAD Cohort 2 MAD Cohort 2 400 mg 400 mg; Q4W 200 mg SAD Cohort 1 MAD Cohort 1 100 mg 200 mg 200 mg Q2W 30 mg Study key objectives Safety and tolerability Pharmacokinetics Serum M-AAT levels 32 HV: healthy volunteer; SAD: single-ascending dose; MAD: multi-ascending dose
WVE-008 RNA editing (AIMer) PNPLA3 I148M liver disease 33
WVE-008 for PNPLA3 I148M liver disease GalNAc-RNA editing approach uniquely aims to restore PNPLA3 function to fully address disease Homozygous PNPLA3 I148M carriers Heterozygous carriers have 80% lower risk of liver-related death as have significantly higher risk of compared to homozygous carriers 100 multiple liver diseases Homozygous I148 MASH Heterozygous I148M MAFLD 98 HR = 1.70 (0.78–3.71) AIMer editing to 96 restore heterozygous phenotype 94 Homozygous I148M HR = 8.61 (3.28–22.60) 92 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 Years of follow-up Over nine million homozygous PNPLA3 I148M patients with liver disease in US and Europe 34 1. Carlsson, B., et al. 2020 Aliment Pharmacol Ther.; 2. Unalp-Arida and Ruhl 2020 Hepatology; 3. Dong, XC, 2019 Front. Med. 4. Liver International, 2025; 45:e16133 MAFLD, Metabolic dysfunction-associated fatty liver disease; MASH, Metabolic dysfunction-associated steatohepatitis; ALD, alcoholic liver disease; AH, Alcohol-associated hepatitis; HCC, hepatocellular carcinoma Survival (%) of liver-related death
Worsening Silencing of PNPLA3 in normal liver may worsen basal physiological functions Silencing PNPLA3 increases Silencing PNPLA3 worsens steatosis in PNPLA3 siRNA exacerbates the fibrotic 1 2 iPSC-derived human liver organoids inflammation-induced liver cell death in response in hepatic stellate cells 3 human primary hepatocytes UC I148M KO UC I148M KO Control OA Functional PNPLA3 is imperative for liver health beyond improvements in steatosis 35 1. Rady, B, et al. 2021 PLoS ONE 2021; 2. Hendriks, D, et al. 2023 Nat Biotechnol; 3. Tilson, SG, et al. 2021 Hepatology Worsening
RNA editing is expected to restore PNPLA3 function to treat across the stages of liver diseases RNA editing approach ✓ PNPLA3 I148M aggravates steatosis Silencing PNPLA3 may only partially PNPLA3 correction expected to and fibrosis through gain-of-function address disease restore function, counter liver disease ATGL PNPLA3 PNPLA3 I148M CGI-58 • Creates PNPLA3 loss of function • PNPLA3 I148M accumulates on LDs, • Restores full PNPLA3 activity • ATGL partial rescue for loss PNPLA3 sequesters CGI-58, inhibits ATGL’s lipase • Restores lipid mobilization, reverses activity and lipid mobilization from ER • Silencing will not restore retinol metabolism steatosis, fibrosis, ballooning, and • Suppresses retinol metabolism in liver and inflammation • Fibrosis, ballooning, and inflammation worsens inflammation and fibrosis persist • Promotes liver fat accumulation and fibrosis through activation of stellate cells 36 ATGL: adipose triglyceride lipase; CGI-58: co-factor for ATGL; ER endoplasmic reticulum; LDs: lipid droplets; CGI-58 also called ABHD5 Liver International, 2025; 45:e16117; Human Molecular Genetics, (2014) 23(15): 4077–4085
AIMers achieve efficient editing of PNPLA3, leading to reduction of liver fat ✱✱✱✱ Significant decrease in liver fat with PNPLA3 editing in human HEPATOPAC® model with homozygous I148M ns 1500 1000 500 PBS PNPLA3 PNPLA3 siRNA AIMer 0 Decrease in liver fat with WVE-008 in monolayer model PNPLA3 siRNA PBS PNPLA3 siRNA WVE-008 37 One-way ANOVA with Dunnett post hoc test comparisons to Mock **** P< 0.0001 Mock PNPLA3 siRNA PNPLA3 AIMer 2 Lipid Droplet Density (pixel /cell) 2 Lipid Droplet Density (pixel /cell) % Lipid Droplet Density vs. PBS (mean + SE) (mean + SE) (mean ± SE)
Preclinical data support WVE-008 as potential first-in-class, disease modifying therapy, for treatment of PNPLA3 I148M liver disease Tissue exposure supports excellent Potent editing with WVE-008 Highly specific editing with WVE-008 delivery 1000 100 Semi-log scale 10 0 5 10 15 20 25 Time (day) Expect to file Clinical Trial Application (CTA) for WVE-008 in 2026 38 Left: 4-parameter log-logistic dose response curve; Middle: Analysis utilized RNA-sequencing with two separate primary human hepatocyte cell lines (PH1/2). Variant calling utilized GATK best practices for RNA variant calling using Mutect2 and display A->G evidence found when filtering for variants found in both cell lines and all doses. Liver Tissue Conc (μg/g)
Bifunctional modalities Single oligonucleotide constructs 39
Reimagining RNA medicines: Bifunctional modalities ✓ Engage both endogenous Ago2 AGO2 and ADAR enzymes, as well as AGO2 dual RNAi silencing ✓ Silence multiple targets or silence Single one target while simultaneously Single Oligonucleotide Oligonucleotide editing or upregulating another Construct Construct unique target ✓ Unlock complex indications that require engaging multiple targets ADAR AGO2 ✓ May continue to increase durability of editing 40 AIMer SpiNA SpiNA SpiNA
Other clinical programs Duchenne muscular dystrophy Huntington’s disease 41
Advancing WVE-N531 in exon 53 amenable DMD WVE-N531: exon skipping oligonucleotide designed to induce production of endogenous, functional dystrophin protein • High unmet need for therapies delivering more consistent dystrophin expression, as few patients today achieve dystrophin >5% of normal • Opportunity to extend dosing intervals beyond weekly standard of care to alleviate burden for patients and caregivers • Need to reach stem cells and distribute broadly to muscle tissues to potentially enable muscle regeneration and impact respiratory and cardiac function • WVE-N531 has Rare Pediatric Disease Designation and Orphan Drug Designation from FDA DMD impacts ~1 / 5,000 newborn boys annually; ~20,000 new cases annually worldwide 42 Duan, D. et al. 2021 Nat Rev Dis Primers 7, 13; Muscular Dystrophy Association; Aartsma-Rus, et al. 2009 Hum Mutat 30, 293.
FORWARD-53 48-week clinical trial results: WVE-N531’s potential best-in- class profile for boys amenable to exon 53 skipping Statistically significant and clinically meaningful improvement (3.8s) in Time-to-Rise vs. ✓ natural history; functional benefits on other measures including NSAA Statistically significant reductions in muscle fibrosis and CK; driven by decreases in ✓ inflammation and necrosis; transition from regenerative to mature muscle Consistent dystrophin expression averaged 7.8% between 24 and 48 weeks, with 88% of ✓ boys above 5% dystrophin; delivery to both myofibers and muscle stem cells WVE-N531 remains generally safe and well-tolerated with no Serious Adverse Events ✓ NDA filing for accelerated approval with monthly dosing planned for 2026 43 Muscle content-adjusted dystrophin
Advancing WVE-003 to address HD across all stages of disease WVE-003 is a first-in-class, allele-selective oligonucleotide for the treatment of HD • HD is a monogenic autosomal dominant genetic disease; fully penetrant and affects entire brain • No current disease modifying therapies for HD • Characterized by cognitive decline, psychiatric illness, and chorea; ultimately fatal • Expanded CAG triplet repeat in HTT gene results in production of mutant huntingtin protein (mHTT) and loss of function of wild-type huntingtin protein (wtHTT) >200,000 patients with HD across all disease states Pre-Symptomatic HD Symptomatic HD (~160K in US and Europe) (~65K in US and Europe) 44 Sources on wtHTT: 1. Leavitt 2006 2. Cattaneo 2005 3. Kumar 2016 4. Franco-Iborra 2020 5. Hamilton 2015 6. Ochaba 2014 7. Wong 2014 8. Rui 2015 9. Caviston 2007 10. Twelvetrees 2010 11. Strehlow 2007 12. Milnerwood 2010 13. Smith-Dijak 2019 14. Tousley 2019 15. Zhang 2018 16. McAdam 2020 17. Altar 1997 18. Zuccato 2001 19. Gauthier 2004 20. Ferrer 2000 21. Baquet 2004 22. Liu 2011 23. Karam 2015
WVE-003 leads to allele-selective mHTT reduction, correlating with slowing of caudate atrophy Allele-selective mHTT Slowing of Caudate Silencing with wtHTT Functional Benefit Atrophy Preservation • mHTT reduction of up to • WVE-003 trended towards • Caudate atrophy is an 46% vs. placebo less caudate atrophy vs. imaging biomarker expected placebo (4.68% vs. 5.10%, to predict clinical • wtHTT preserved/increased not significant) outcomes, including throughout study clinically meaningful worsening of Total Motor Score (TMS) Greater allele-selective mHTT reduction correlated with the slowing of caudate atrophy at 24 weeks (R = -0.50, p=0.047) 45 June 2024 SELECT-HD Clinical Trial Results; Liu et al., 2023 Brain Comm
Reimagining RNA medicines 46
Poised for significant and sustained growth driven by RNAi and RNA editing Other hepatic targets Extra-hepatic targets RNAi WVE-007 Obesity SpiNA Bifunctional single oligonucleotide constructs RNA WVE-006 AATD Editing WVE-008 Other hepatic targets AIMers PNPLA3 I148M liver disease Extra-hepatic targets 47
Anticipated upcoming milestones • Deliver 6-month 240 mg data and 3-month 400 mg data in 1Q 2026 WVE-007 • Initiate Phase 2a multidose portion of INLIGHT in individuals living (INHBE) with obesity with higher BMI and comorbidities in 1H 2026 Obesity • Initiate new trials evaluating WVE-007 as an incretin add-on and as post-incretin maintenance in 2026 • Deliver data from 400 mg multidose cohort in 1Q 2026 and deliver WVE-006 single and multidose data from 600 mg cohort in 2026 (SERPINA1) • Regulatory feedback on potential accelerated approval pathway expected mid-2026 AATD WVE-008 • File CTA for WVE-008 in 2026 PNPLA3 I148M liver disease WVE-N531 • Submit NDA to support accelerated approval of WVE-N531 with monthly dosing in 2026 (exon 53) DMD 48 BMI: body mass index AATD: alpha-1 antitrypsin deficiency DMD: Duchenne muscular dystrophy CTA: Clinical Trial Application NDA: New Drug Application.
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