WVE Wave Life Sciences Ltd

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Exhibit 99.1

 

Wave Life Sciences Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update

Dosing underway in INLIGHT trial of WVE-007 in obesity with clinical data expected in 2H 2025; enrollment complete in first single dose cohort

Multi-dosing ongoing in 200 mg cohort of RestorAATion-2 clinical trial of WVE-006 in AATD with data expected in 2025; second single dose cohort initiated at 400 mg

On track to deliver FORWARD-53 48-week data in DMD and feedback from regulators in 1Q 2025

IND submission expected 2H 2025 for potentially registrational WVE-003 Phase 2/3 study in HD with caudate atrophy as a primary endpoint

Cash and cash equivalents of $302.1 million as of December 31, 2024, with runway expected into 2027

Investor conference call and webcast at 8:30 a.m. ET today

CAMBRIDGE, Mass., March 4, 2025 – 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, 2024, and provided a business update.

“2024 was an exceptional year for Wave and we’ve continued the positive momentum into 2025, with the initiation of dosing in the INLIGHT trial with WVE-007, a potentially transformative therapeutic that is uniquely positioned to address the more than one billion people living with obesity globally,” said Paul Bolno, MD, MBA, President and Chief Executive Officer at Wave Life Sciences. “WVE-007 is also Wave’s first GalNAc-siRNA to enter the clinic and utilizes our proprietary chemistry. Our expected clinical data this year will provide us with an early look into WVE-007’s potential to transform the current obesity treatment paradigm. In AATD, we have continued to advance our RestorAATion-2 clinical study of WVE-006 and data this year will demonstrate the impact of multiple doses and a higher dose level, on the production of healthy, wild-type, M-AAT protein and potentially extended dose intervals. We remain on track to report our DMD 48-week clinical results of WVE-N531 this month. With both our progress in the clinic and in advancing a broad pipeline targeting high-impact biology, we are building a leading RNA medicines company committed to improving the lives of patients and families.”

Recent Business Highlights and Expected Milestones

GalNAc-siRNA Programs

Obesity

 

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WVE-007 is a GalNAc-conjugated small interfering RNA (GalNAc-siRNA) designed to silence INHBE mRNA, an obesity target with strong evidence from human genetics. WVE-007 is Wave’s first siRNA candidate to enter clinical development and uses Wave’s best-in-class proprietary oligonucleotide chemistry.

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INLIGHT is an ongoing, first-in-human, placebo-controlled, clinical trial evaluating WVE-007 in adults living with overweight or obesity and assesses safety, tolerability, pharmacokinetics, biomarkers for target engagement, body weight and composition, and metabolic health.

 

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Today, Wave announced that it has completed enrollment in the first single dose cohort of INLIGHT.

 

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In November 2024 at ObesityWeek®, Wave presented preclinical data supporting WVE-007’s potential in multiple treatment settings with potential for dosing once or twice a year.

 

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A single dose of Wave’s INHBE siRNA led to weight loss on par with semaglutide, but with no muscle loss.

 

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When administered as an add-on to semaglutide, a single dose of Wave’s INHBE siRNA doubled the amount of weight loss.

 

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Wave’s INHBE siRNA curtailed rebound weight gain when semaglutide treatment was discontinued, highlighting its potential as an off-ramp and maintenance treatment following GLP-1 treatment.

 

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Expected milestones: Wave expects to deliver clinical data from INLIGHT in the second half of 2025, including safety, tolerability and biomarkers reflective of healthy weight loss.

GalNAc-RNA Editing Programs

AATD (Alpha-1 antitrypsin deficiency)

 

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WVE-006 is a GalNAc-conjugated, subcutaneously delivered, A-to-I RNA editing oligonucleotide (AIMer) that is uniquely designed to address alpha-1 antitrypsin deficiency (AATD)-related lung disease, liver disease, or both.

 

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RestorAATion clinical program: Wave has completed multi-dosing in healthy volunteers in the top cohort of the RestorAATion-1 study of WVE-006 at a dose level greater than those planned for any cohort in its ongoing RestorAATion-2 study. RestorAATion-2 is a Phase 1b/2a open-label study with both single and multiple ascending dose portions, which is evaluating the safety, tolerability, pharmacodynamics and pharmacokinetics of WVE-006 in individuals with AATD who have the homozygous Pi*ZZ mutation.

 

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In the first quarter of 2025, Wave initiated multi-dosing in the first cohort of RestorAATion-2, where patients are receiving 200 mg subcutaneous doses every two weeks, and initiated the second single dose cohort of RestorAATion-2 at 400 mg.

 

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In October 2024, Wave delivered proof-of-mechanism data from a single dose of WVE-006 from the first two patients in the ongoing RestorAATion-2 clinical study, representing the first-ever clinical demonstration of RNA editing in humans. Circulating wild-type M-AAT protein in plasma reached a mean of 6.9 micromolar, representing more than 60% of total AAT. Mean total AAT protein increased to 10.8 micromolar, meeting the level that has been the basis for regulatory approval for AAT augmentation therapies.

 

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Expected milestones: Wave expects to share multi-dose data for WVE-006 from RestorAATion-2 in 2025.

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New AIMer Programs

 

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In the fourth quarter of 2024, Wave unveiled three wholly owned RNA editing programs, all of which leverage GalNAc conjugation and have efficient clinical paths to proof-of-concept. These include PNPLA3 mRNA correction to potentially address the nine million homozygous individuals in the US and Europe at risk for a variety of liver diseases, and mRNA upregulation (LDLR) and mRNA correction (APOB), which together would address approximately one million people living with heterozygous familial hypercholesterolemia (HeFH) in the US and Europe.

 

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Expected milestones: Wave plans to share new preclinical data from hepatic and extra-hepatic RNA editing programs in 2025 and to initiate clinical development of additional RNA editing programs, including PNPLA3, LDLR, and APOB, in 2026.

Exon Skipping Programs

DMD (Duchenne Muscular Dystrophy)

 

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WVE-N531 is an exon skipping oligonucleotide designed to induce production of endogenous, functional dystrophin protein for the treatment of boys with Duchenne muscular dystrophy (DMD) amenable to exon 53 skipping.

 

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FORWARD-53 is an ongoing Phase 2 open-label trial of WVE-N531. Muscle biopsies are taken after 24 and 48 weeks of dosing. The primary endpoint is dystrophin protein levels, and the trial is also evaluating pharmacokinetics, digital and functional endpoints, and safety and tolerability.

 

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In January 2025, Wave announced that all boys have elected to continue treatment in the planned extension portion of the study with monthly doses of WVE-N531.

 

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In September 2024, Wave delivered positive 24-week interim results from FORWARD-53, which demonstrated highly consistent, mean muscle content-adjusted dystrophin expression of 9.0% (range: 4.6-13.9%), best-in-class muscle delivery, multiple indicators of improved muscle health, and a safe and well-tolerated profile.

 

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Expected milestones: Wave expects to deliver the 48-week FORWARD-53 data and feedback from regulators on a pathway to accelerated approval in 1Q 2025.

Antisense Silencing Programs

HD (Huntington’s disease)

 

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WVE-003 is a first-in-class, allele-selective oligonucleotide for the treatment of Huntington’s disease (HD). By reducing mHTT at the mRNA and protein level, WVE-003 addresses underlying drivers of neurodegeneration. In addition, by sparing wtHTT protein, which is critical to the health of the central nervous system, WVE-003 is uniquely positioned to address presymptomatic HD patients, as well as symptomatic patients. Preparation for a potentially registrational, global Phase 2/3 study in adults with SNP3 and HD is ongoing.

 

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In February 2025, in an oral presentation at CHDI’s 20th Annual HD Therapeutics Conference, Wave highlighted its previously presented results from the SELECT-HD clinical trial, which demonstrated the first-ever allele-selective reduction in CSF mutant huntingtin (mHTT) protein and preservation of healthy, wild-type huntingtin (wtHTT) protein with multiple doses of WVE-003, as well as a statistically significant correlation between mHTT reduction and slowing of caudate atrophy.

 

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Also at CHDI, Wave presented an internal analysis of longitudinal natural history data from TRACK-HD and PREDICT-HD demonstrating that an absolute reduction of 1% in the rate of caudate atrophy is associated with a delay of onset of disability for individuals with HD of at least 7.5 years.

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In the fourth quarter of 2024, Wave announced that it received supportive initial feedback from FDA, who recognize the severity of HD and are receptive to and engaged with Wave regarding a potential pathway to accelerated approval. FDA is open to Wave’s plan to evaluate biomarkers, including caudate atrophy, as an endpoint to assess HD progression with the potential to predict clinical outcomes.

 

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Expected milestones: Wave expects to submit an Investigational New Drug (“IND”) application for a potentially registrational Phase 2/3 study of WVE-003 in HD in the second half of 2025.

Financial Highlights

 

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Cash and cash equivalents were $302.1 million as of December 31, 2024, compared to $200.4 million as of December 31, 2023. The increase in cash year-over-year is primarily due to financing proceeds and 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 2027. Potential future milestone and other payments to Wave under its GSK collaboration are not included in its cash runway.

 

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Revenue recognized was $83.7 million for the fourth quarter of 2024 as compared to $29.1 million in the prior year quarter. Revenue recognized was $108.3 million in 2024 as compared to $113.3 million in 2023.

 

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Research and development expenses were $44.6 million in the fourth quarter of 2024 as compared to $34.1 million in the same period in 2023. Research and development expenses for the full year were $159.7 million in 2024, as compared to $130.0 million in 2023.

 

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General and administrative expenses were $16.1 million in the fourth quarter 2024 as compared to $13.7 million in the same period in 2023. General and administrative expenses for the full year were $59.0 million in 2024, as compared to $51.3 million in 2023.

 

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Net income was $29.3 million for the fourth quarter of 2024 as compared to a net loss of $16.3 million in the prior year quarter. Net loss for the full year was $97.0 million for 2024 as compared to $57.5 million in 2023.

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 2024 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 following audio-conferencing link: available here. Once registered, participants will receive the dial-in information. Following the live event, an archived version of the webcast will be available on the Wave Life Sciences website.

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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 includes editing, splicing, RNA interference and antisense silencing, providing Wave with unmatched capabilities for designing and sustainably delivering candidates that optimally address disease biology. Wave’s diversified pipeline includes clinical programs in Alpha-1 antitrypsin deficiency, Duchenne muscular dystrophy, Huntington’s disease, and Obesity, as well as several preclinical programs utilizing the company’s broad RNA therapeutics toolkit. 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 (formerly Twitter) and LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements 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, site activation, patient recruitment, patient enrollment, dosing, generation and reporting of data and completion of our clinical trials, including interactions with regulators and any potential registration based on these data, and the timing and announcement of such events; the protocol, design and endpoints of our clinical trials; the future performance and results of our programs in clinical trials; our expectations with respect to how our clinical data successes to date may predict success for our future therapeutic candidates and data readouts and may further validate our platform; preclinical activities and programs and their potential to transition into clinical-stage programs; the potential of our preclinical data to predict the behavior of our compounds in humans; regulatory submissions and timing for regulatory feedback; the progress and potential benefits of collaborations; the potential achievement of milestones under any collaborations; the potential commercial opportunities that our therapeutic candidates may address; our identification of future product candidates and their therapeutic potential; the anticipated benefits of our therapeutic candidates and pipeline compared to our competitors; addressable patient population estimates related to our therapeutic candidates; our ability to design compounds using various modalities and the anticipated benefits of that approach; the breadth and versatility of our drug discovery and development platform; the expected benefits of our stereopure oligonucleotides compared with stereorandom oligonucleotides; the potential benefits of our RNA editing capability, including our AIMers, compared to others; the potential for certain of our programs to be best-in-class or first-in-class; the status and progress of our programs relative to potential competitors; anticipated benefits of our proprietary manufacturing processes and our internal manufacturing capabilities; the benefits of RNA medicines generally; the strength of our intellectual property and the data that support our IP; 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. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including the following: our ability to finance our drug discovery and development efforts and to raise additional capital when needed; the ability of our preclinical programs to produce data sufficient to support our clinical trial applications and the timing thereof; the clinical results of our programs and the timing thereof, which may not support further development of our product candidates; actions of regulatory authorities and their receptiveness to our trial designs and accelerated approval pathways, which may affect the initiation, timing and progress of clinical trials; our effectiveness in managing interactions with regulatory

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authorities; the effectiveness of our drug discovery and development platform; the effectiveness of our RNA editing capability and our AIMers; our ability to demonstrate the therapeutic benefits of our candidates in clinical trials, including our ability to develop candidates across multiple therapeutic modalities; our dependence on third parties, including contract research organizations, contract manufacturing organizations, collaborators and partners; our ability to manufacture or contract with third parties to manufacture drug material to support our programs and growth; our ability to obtain, maintain and protect our intellectual property; our ability to enforce our patents against infringers and defend our patent portfolio against challenges from third parties; competition from others developing therapies for the indications we are pursuing; our ability to maintain the company infrastructure and personnel needed to achieve our goals; and the information under the caption “Risk Factors” contained in our most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) and in other filings we make with the SEC from time to time. We undertake no obligation to update the information contained in this press release to reflect subsequently occurring events or circumstances.

Investor Contact:

Kate Rausch

+1 617-949-4827

krausch@wavelifesci.com

Media Contact:

Alicia Suter

+1 617-949-4817

asuter@wavelifesci.com

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WAVE LIFE SCIENCES LTD. UNAUDITED CONSOLIDATED BALANCE SHEETS

(In thousands, except share amounts)

 

		December 31, 2024				December 31, 2023
Assets
Current assets:
Cash and cash equivalents		$	302,078			$	200,351
Accounts receivable			1,422				21,086
Prepaid expenses			9,544				9,912
Other current assets			7,350				4,024
Total current assets			320,394				235,373
Long-term assets:
Property and equipment, net of accumulated depreciation of $46,329 and $42,709 as of December 31, 2024 and 2023, respectively			10,128				13,084
Operating lease right-of-use assets			17,870				22,637
Restricted cash			3,760				3,699
Other assets			55				156
Total long-term assets			31,813				39,576
Total assets		$	352,207			$	274,949
Liabilities, Series A preferred shares and shareholders’ equity
Current liabilities:
Accounts payable		$	16,261			$	12,839
Accrued expenses and other current liabilities			21,081				16,828
Current portion of deferred revenue			65,972				150,059
Current portion of operating lease liability			7,638				6,714
Total current liabilities			110,952				186,440
Long-term liabilities:
Deferred revenue, net of current portion			6,099				15,601
Operating lease liability, net of current portion			17,766				25,404
Total long-term liabilities			23,865				41,005
Total liabilities		$	134,817			$	227,445
Series A preferred shares, no par value; 3,901,348 shares issued and outstanding at December 31, 2024 and 2023		$	7,874			$	7,874
Shareholders’ equity:
Ordinary shares, no par value; 153,037,286 and 119,162,234 shares issued and outstanding at December 31, 2024 and 2023, respectively		$	1,175,181			$	935,367
Additional paid-in capital			156,454				129,237
Accumulated other comprehensive loss			(262	)			(124	)
Accumulated deficit			(1,121,858	)			(1,024,850	)
Total shareholders’ equity			209,515				39,630
Total liabilities, Series A preferred shares and shareholders’ equity		$	352,207			$	274,949

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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,
		2024				2023				2024				2023
Revenue		$	83,748			$	29,056			$	108,302			$	113,305
Operating expenses:
Research and development			44,645				34,074				159,682				130,009
General and administrative			16,136				13,664				59,023				51,292
Total operating expenses			60,781				47,738				218,705				181,301
Loss from operations			22,967				(18,682	)			(110,403	)			(67,996	)
Other income, net:
Dividend income and interest income, net			3,738				1,844				10,163				7,928
Other income, net			2,548				582				3,232				1,878
Total other income, net			6,286				2,426				13,395				9,806
Income (loss) before income taxes			29,253				(16,256	)			(97,008	)			(58,190	)
Income tax benefit			—				—				—				677
Net income (loss)		$	29,253			$	(16,256	)		$	(97,008	)		$	(57,513	)
Net income (loss) attributable to ordinary shareholders, basic and diluted		$	29,253			$	(16,256	)		$	(97,008	)		$	(57,513	)
Net income (loss) per share attributable to ordinary shareholders—basic		$	0.18			$	(0.15	)		$	(0.70	)		$	(0.54	)
Weighted-average ordinary shares used in computing net income (loss) per share attributable to ordinary shareholders—basic			161,487,609				109,627,549				138,277,468				106,097,268
Net income (loss) per share attributable to ordinary shareholders—diluted		$	0.17			$	(0.15	)		$	(0.70	)		$	(0.54	)
Weighted-average ordinary shares used in computing net income (loss) per share attributable to ordinary shareholders—diluted			172,290,361				109,627,549				138,277,468				106,097,268
Other comprehensive income (loss):
Net income (loss)		$	29,253			$	(16,256	)		$	(97,008	)		$	(57,513	)
Foreign currency translation			(103	)			58				(138	)			(95	)
Comprehensive income (loss)		$	29,150			$	(16,198	)		$	(97,146	)		$	(57,608	)

Corporate Presentation March 4, 2025 Wave Life Sciences Exhibit 99.2

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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.

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To unlock the broad potential of RNA medicines to transform human health Our Mission

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Patient populations represent US and Europe; WVE-006 is partnered with GSK AATD: Alpha-1 antitrypsin deficiency DMD: Duchenne muscular dystrophy HD: Huntington’s disease *Cash runway does not include potential future milestones or other payments under GSK collaboration Building a leading RNA medicines company Leadership in allele-selective silencing Pioneering a novel RNA modality with RNA editing Best-in-class muscle delivery WVE-003 in HD WVE-N531 in DMD WVE-006 in AATD WVE-007 in Obesity Transforming the obesity treatment paradigm Multi-modal: RNA editing, RNAi, splicing, allele-selective silencing Best-in-class, clinically-validated oligonucleotide chemistry (PN, stereochemistry) Novel RNA medicines platform (PRISM®) Strong and broad IP In-house GMP manufacturing Well-capitalized with cash runway into 2027*

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The powerful convergence of a validated, best-in-class platform with genetics Unmatched toolkit to access novel biology Data-driven discovery powered by human genetics Foundation in chemistry innovation Multi-modal: RNA editing, RNAi, antisense silencing, splicing Best positioned to engage endogenous machinery Unlocking new, high-impact therapeutic targets Real-time integration of new human genetic insights into discovery Proprietary deep learning models unveiling novel targets/ target sites Accelerating time to clinic Breakthroughs in intracellular delivery Step-change in potency, distribution, durability of effect No complex delivery vehicles (AAV, LNP)

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AATD: Alpha-1 antitrypsin deficiency; DMD: Duchenne muscular dystrophy; HD: Huntington’s disease; HeFH: heterozygous familial hypercholesterolemia Robust, diversified RNA medicines pipeline including first-in-class RNA editing programs Program Discovery IND / CTA Enabling Studies Clinical Rights Patient population (US & Europe) RNA EDITING WVE-006 (GalNAc) SERPINA1 (AATD) GSK exclusive global license 200K GalNAc-AIMer PNPLA3 (liver disease) 100% global 9M GalNAc-AIMer LDLR (HeFH) 100% global 900K (30M expansion) GalNAc-AIMer APOB (HeFH) 100% global 70K RNAi WVE-007 (GalNAc) INHBE (Obesity) 100% global 175M GalNAc-siRNA Undisclosed 100% global -- SPLICING WVE-N531 Exon 53 (DMD) 100% global 2.3K Other exons (DMD) 100% global Up to 18K ALLELE-SELECTIVE SILENCING WVE-003 mHTT (HD) 100% global 25K Symptomatic (SNP3) 60K Pre-Symptomatic (SNP3) Editing for correction Editing for upregulation FORWARD-53 Trial (Phase 2) SELECT-HD Trial (Phase 1b/2a) - Trial Completed RestorAATion-2 (Phase 1b/2a) INLIGHT Trial (Phase 1)

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WVE-007 GalNAc-siRNA silencing Obesity

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Adults with obesity have higher risk for many serious health conditions, including heart disease, type 2 diabetes, and some forms of cancer1 GLP-1s are current standard of care for weight loss, but impact is often limited by: Loss of muscle mass2 Poor tolerability3 Frequent dosing4 High discontinuation rates5,6 Advancing WVE-007 as a novel, long acting, muscle sparing approach for obesity 1. CDC.gov; 2. Sargeant, et al. 2019 Endocrinol Metab (Seoul) 34, 247; 3. Ghusn and Hurtado. 2024 Obesity Pillars 12, 100127; 4. Wegovy PI; 5. Leach, et al. 2023 Prime Therapeutics Claims Analysis; 6. Gasoyan, et al. 2024 Obesity (Silver Spring) 32, 486.; GalNAc-siRNA: GalNAc-conjugated small interfering RNA WVE-007 is a GalNAc-siRNA that targets INHBE to treat obesity ~175 million adults with obesity in US and Europe

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Silencing INHBE mRNA by ≥50% is expected to recapitulate the healthy metabolic profile of heterozygous INHBE loss of function (LoF) carriers 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 Human genetic data demonstrate that heterozygous INHBE LoF carriers have a healthy metabolic profile Heterozygous INHBE LoF carriers have favorable traits: lower abdominal obesity, lower triglycerides, higher HDL-c Heterozygous INHBE LoF carriers have lower risk of Type 2 diabetes and CHD

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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 Decreased abdominal adiposity leads to weight loss and reduced risk for CVD and T2D INHBE GalNAc-siRNA expected to address health issues associated with pathogenesis of obesity associated metabolic disease GalNAc-siRNA Diminished activation of ACVR1C (ALK7) receptor in adipose tissue Increased adipose lipolysis and shrink adipocytes Reduced release of hepatokine Activin E INHBE INHBE

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Data from preclinical studies conducted in DIO mice; Stats: (left, middle, right) Linear Mixed Effects ANOVA with post hoc comparisons of marginal treatment effects vs. PBS per timepoint (left) or per tissue (middle, right) * p < 0.05 Single doses of INHBE GalNAc-siRNA result in dose-dependent weight loss and reduction of visceral fat, without affecting muscle mass, in DIO mice INHBE GalNAc-siRNA has potential as monotherapy weight loss therapeutic Quadricep weight (Day 28) Epididymal fat weight (Day 28) * -23% -40% Reduction in body weight ✓ Reduction in visceral fat ✓ No muscle loss ✓ INHBE GalNAc-siRNA (3 mg/kg) PBS INHBE GalNAc-siRNA (10 mg/kg) Single dose INHBE GalNAc-siRNA * * * * * *

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INHBE GalNAc-siRNA can be used synergistically with GLP-1s or to curtail weight regain after the cessation of treatment with GLP-1 Data from preclinical studies conducted in DIO mice; Left: 10nmol/kg in mouse is equivalent to therapeutic dose of GLP-1s in human. 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 * p < 0.05 p<0.05 Not significant PBS Semaglutide + INHBE GalNAc-siRNA Semaglutide Difference in body weight (% of PBS, same time point) Daily GLP-1 Dose INHBE GalNAc-siRNA Semaglutide Control for Semaglutide INHBE GalNAc-siRNA Control for siRNA Semaglutide + INHBE GalNAc-siRNA Daily GLP-1 Single dose INHBE GalNAc-siRNA ~2x greater weight loss Curtails weight regain after the cessation of GLP-1 ✓ Day ~2x greater overall weight loss when added to GLP-1 ✓ Day

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Curtailed rebound weight gain upon cessation of semaglutide and prevention of weight cycling, which worsens the outcomes of various metabolic diseases When administered as an add-on to semaglutide: A single dose of Wave’s INHBE GalNAc-siRNA doubled the weight loss observed with semaglutide alone Weight loss similar to semaglutide with a single dose No loss of muscle mass Reduction in fat mass with preferential effect to the visceral fat Without suppressing food intake Preclinical data support best-in-class profile and potential to use WVE-007 across multiple treatment settings with potential for 1-2x per year dosing WVE-007 as a single agent WVE-007 in addition to GLP-1 therapy WVE-007 for patients who stop treatment with GLP-1 therapy Add-on to GLP-1s Maintenance Monotherapy

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Dosing underway in INLIGHT with clinical data expected in 2H 2025; enrollment complete in SAD Cohort 1 INLIGHT: Phase 1 trial of WVE-007 in adults living with overweight or obesity, otherwise healthy Randomized, double-blind, placebo-controlled study of ascending doses of WVE-007 SAD Cohort 5 SAD Cohort 4 SAD Cohort 3 SAD Cohort 2 SAD Cohort 1 Trial Design Objective: Assess dose safety, tolerability, PK and PD Key measurements Primary: Safety and tolerability Secondary: PK, Activin E Exploratory PD: Body weight Body composition Metabolic health Biochemical markers MAD Cohort 1 MAD Cohort 2 MAD Cohort 3 SAD: single-ascending dose; MAD: multi-ascending dose

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WVE-006 RNA editing (AIMers) Alpha-1 antitrypsin deficiency (AATD)

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Advancing WVE-006 (RNA editing) in AATD AATD is a rare, inherited genetic disorder that is commonly caused by a G-to-A point mutation in the SERPINA1 gene Characterized by aggregation of mutant Z-AAT protein in hepatocytes and a lack of functional AAT in lungs People with AATD typically exhibit progressive lung damage, liver damage, or both Weekly intravenous augmentation therapy is the only treatment option for AATD in those with the lung pathology No approved therapies to address AATD liver disease 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: GalNAc-conjugated, subcutaneously delivered, designed to address AATD-related lung disease, liver disease, or both ~200K people in the US and Europe are homozygous for the Z allele

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Strnad et al., 2020 N Engl J Med 382:1443-55; Stoller et al., 1993 Alpha-1 Antitrypsin Deficiency GeneReviews. WVE-006 to address both liver and lung manifestations of AATD WVE-006 RNA editing treatment WVE-006 RNA editing approach to address key goals of AATD treatment: Infrequent dosing Subcutaneous injection (GalNAc) A à I Highly specific (no bystanders) Retain M-AAT physiological regulation Reduce Z-AAT protein aggregation in liver M-AAT secretion into bloodstream RNA correction replaces mutant Z-AAT protein with wild-type M-AAT protein Z-AAT Restore circulating, functional wild-type M-AAT M-AAT reaches lungs to protect from proteases 1 2 3

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RestorAATion-2 clinical trial in Pi*ZZ AATD patients ongoing HV: healthy volunteer; SAD: single-ascending dose; MAD: multi-ascending dose RestorAATion-2: AATD Patients  RestorAATion-1: Healthy Volunteers Dose A Cohort 1 200 mg SAD à MAD Up to seven doses in multi-dose portion Dose B Dose C Dose D Dose E Cohort 2 400 mg Cohort 3 RestorAATion-1: Healthy Volunteers SAD à MAD Multi-dosing complete in RestorAAtion-1 Multi-dosing ongoing in 200 mg cohort of RestorAATion-2; Second single dose cohort initiated at 400 mg Study key objectives Safety and tolerability Pharmacokinetics Serum M-AAT levels

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October 16, 2024 Proof-of-mechanism disclosure on first two “ZZ” AATD patients in first dose cohort of RestorAATion-2 to reach day 57 Multi-dose data from RestorAATion-2 expected in 2025 Achieved proof-of-mechanism for Wave’s RNA editing platform Proof-of-mechanism achieved after a single dose in RestorAATion-2 Total AAT protein increased to a mean of 10.8 µM at day 15 Meets level that has been the basis for regulatory approval for AAT augmentation therapies Circulating wild-type M-AAT protein reached a mean of 6.9 µM at day 15; more than 60% of total AAT Increases in total AAT from baseline and M-AAT protein were observed as early as day 3 and through day 57 Increases in neutrophil elastase inhibition from baseline were consistent with production of functional M-AAT WVE-006 well tolerated with a favorable safety profile; all AEs mild-to-moderate, no SAEs

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Expect to initiate clinical development of additional RNA editing programs, including PNPLA3, LDLR, and APOB programs in 2026 Wholly owned GalNAc-AIMer programs Patient populations are in US and Europe HeFH: heterozygous familial hypercholesterolemia Editing for correction Editing for upregulation Strongly supported by human genetics Leverage unique platform capabilities; Building on learnings of WVE-006 Novel ways of treating diseases with high unmet need Readily accessible biomarkers and ways to assess pharmacodynamics ✓ ✓ ✓ ✓ Correction of APOB HeFH Patient population: ~70,000 Correction of PNPLA3 Genetically defined liver disease Patient population: ~9 million Upregulation of LDLR HeFH Patient population: ~900,000, with expansion to ~30 million in follow on indications

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WVE-N531 Splicing Duchenne muscular dystrophy

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Advancing WVE-N531 in exon 53 amenable DMD 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 Duan, D. et al. 2021 Nat Rev Dis Primers 7, 13; Muscular Dystrophy Association; Aartsma-Rus, et al. 2009 Hum Mutat 30, 293. WVE-N531: exon skipping oligonucleotide designed to induce production of endogenous, functional dystrophin protein DMD impacts ~1 / 5,000 newborn boys annually; ~20,000 new cases annually worldwide 

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FORWARD-53: An ongoing potentially registrational open-label Phase 2 clinical trial of WVE-N531 in boys with DMD amenable to exon 53 skipping IV: Intravenous; Q2W: Every 2 Weeks; PK: Pharmacokinetics; PD: Pharmacodynamics Screening 10 mg/kg Q2W N = 11 10 mg/kg Q4W Extension Baseline functional assessments Muscle biopsy after 24 weeks of treatment Functional assessments Muscle biopsy after 48 weeks of treatment Functional assessments Key Assessments: Safety and tolerability Muscle biopsies after 24 and 48 weeks of treatment PK: Drug tissue concentrations PD: Exon-skipping, Dystrophin level (% of normal) as assessed by Western Blot Functional outcome measures 11 participants enrolled, including two from prior Part A clinical trial Pre-specified analyses in ambulatory patients Interim analysis

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WVE-N531 is the only DMD therapeutic to show uptake in myogenic stem cells Stars denote an injured myofiber Stem cell containing WVE-N531 WVE-N531 uptake in myogenic stem cells Dual staining utilizing in-situ hybridization for WVE-N531 and PAX7 immunohistochemistry for stem cells Mag: 20x Mag: 40x WVE-N531 uptake in myofiber nuclei Myocytes Myocyte nuclei containing WVE-N531 (red) In-situ hybridization for WVE-N531 Mag: 20x Mag: 40x Data from interim analysis clinical results announced September 24, 2024.

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Dystrophin data from prespecified analysis of ambulatory boys; Muscle content adjustment was done using the formula: MHC-normalized dystrophin/(total myofiber area/total area of biopsy section). Interim analysis results announced September 24, 2024. Results of interim analysis: WVE-N531 has potential to be the best-in-class therapeutic for DMD amenable to exon 53 skipping Expect to deliver 48-week FORWARD-53 data and feedback from regulators in 1Q 2025 Highly consistent, mean muscle content-adjusted dystrophin expression of 9% Muscle tissue concentrations of ~41,000 ng/g and tissue half-life of 61 days (supports monthly dosing) Preclinical data suggests higher levels of dystrophin protein expression in heart and diaphragm than skeletal muscle Best-in-class dystrophin expression and muscle delivery Improvement in serum biomarkers for muscle health Localization of WVE-N531 in myogenic stem cells Improvement in myofiber regeneration Evidence supporting improved muscle health No serious adverse events (SAEs) No discontinuations No oligonucleotide class effects Safe and well tolerated

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Aartsma-Rus, et al. 2009 Hum Mut 30, 293 Exon 45 Exon 44 Exon 52 WVE-N531 Exon 53 Exon 51 Not Amenable to Skipping 11-13% 8-10% 44% DMD Population Unlocking Wave’s best-in-class exon skipping portfolio Data for exons 51, 44, 52, 45 demonstrate potential for even greater dystrophin expression Opportunity to address up to 40% of population (~10,000 patients in US and Europe) Expect to engage regulators on a platform trial design that incorporates multiple exons

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WVE-003 Allele-selective silencing Huntington’s Disease

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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) Advancing WVE-003 to address HD across all stages of disease Pre-Symptomatic HD (~160K in US and Europe) Symptomatic HD (~65K in US and Europe) 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 >200,000 patients with HD across all disease states WVE-003 is a first-in-class, allele-selective oligonucleotide for the treatment of HD

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Saudou & Humbert 2016 Neuron; Cason et al., 2022 Nat Rev Cell Biol; Laundos et al., 2023 Front Cell Dev Biol; Kaliszewski et al., 2015 Cell Death Diff; Keryer et al., 2011 J Clin Invest Khoshnan & Patterson, 2011. Neurobiol Dis; Pogoda et al., 2021 Curr Med Chem; Hsiao et al., 2013 Hum Mol Genet Wild-type HTT (wtHTT) is critical for normal neuronal function and loss of wtHTT contributes to cellular dysfunction   Lowering mHTT is expected to restore physiological control over HTT gene expression and relieve its detrimental effect on wtHTT function In the absence of wtHTT, ciliogenesis fails, disrupting CSF flow, causing hydrocephalus Mutant HTT has a detrimental effect on wild-type HTT function Wild-type HTT is crucial for cilia health Only an allele-selective approach can ameliorate both loss-of-function and gain-of-function disruptions driven by mHTT Brain tissue Ventricle Cilia CSF flow Ependymal cell Sequestered wild-type HTT

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* p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 mHTT: mutant huntingtin protein; wtHTT: wild-type huntingtin protein From June 25, 2024 SELECT-HD disclosure Allele-selective lowering of mutant HTT protein of up to 46% with three doses of WVE-003 and preservation of wild-type HTT Durability of mHTT reductions supports potential for quarterly dosing intervals Mutant HTT protein levels Wild-type HTT protein levels Placebo WVE-003 30 mg Mutant Huntingtin Protein (fM) - Geometric Mean Ratio to Baseline +/- SE Wild-Type Huntingtin Protein (fM) - Geometric Mean Ratio to Baseline +/- SE Dose of WVE-003 Dose of WVE-003 Preservation of wtHTT mHTT reduction Day Day 2.00 1.75 1.50 1.25 1.00 0.75 0.50 2.00 1.75 1.50 1.25 1.00 0.75 0.50 1 29 57 85 113 141 169 197 1 29 57 85 113 141 169 197 Placebo WVE-003 30 mg

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WVE-003 leads to allele-selective mHTT reduction, correlating with slowing of caudate atrophy Allele-selective mHTT Silencing with wtHTT Preservation Slowing of Caudate Atrophy Functional Benefit mHTT reduction of up to 46% vs. placebo wtHTT preserved/increased throughout study Caudate atrophy is an imaging biomarker expected to predict clinical outcomes, including clinically meaningful worsening of Total Motor Score (TMS) WVE-003 trended towards less caudate atrophy vs. placebo (4.68% vs. 5.10%, not significant) Greater allele-selective mHTT reduction correlated with the slowing of caudate atrophy at 24 weeks (R = -0.50, p=0.047) Liu et al., 2023 Brain Comm

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Expect to submit IND application for potentially registrational Phase 2/3 study in 2H 2025 Analysis of natural history demonstrates that absolute reduction of 1% in rate of caudate atrophy is associated with delay of onset of disability by ≥7.5-years Wave internal analysis; TRACK-HD and PREDICT-HD are longitudinal HD natural history studies that include MRI brain imaging, clinical outcome assessments. Paulson et al., Neurosci.2014, Tabrizi et al., Lancet Neurol 2009, Tabrizi et al., Lancet Neurol 2012, Tabrizi et al., Lancet Neurol. 2013 IND: Investigational New DrugTFC: Total Functional Capacity p<0.001 HR = 0.31 Preparation ongoing for a global, potentially registrational Phase 2/3 study in adults with SNP3 and HD Using caudate atrophy as a primary endpoint Probability of TFC preservation Fast: -3.04%/year Slow: -2.04%/year Rate of Caudate Atrophy: WVE-003 next steps

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Reimagining RNA medicines

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Poised for significant and sustained growth driven by editing and siRNA  Note: Bubble size illustrative of size of total addressable US market (assuming 100% share of addressable patients) Current pipeline has potential to treat well over 100 million patients in US and Europe Obesity WVE-007 (INHBE) DMD WVE-N531 Exon 53 HD WVE-003 SNP3 GalNAc-Editing GalNAc-siRNA AATD WVE-006 Liver Disease PNPLA3 HeFH LDLR & APOB

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WVE-N531 (Exon 53) DMD WVE-003 (SNP3) HD Well-capitalized with expected cash runway into 2027 Anticipated upcoming milestones AATD: Alpha-1 antitrypsin deficiency; DMD: Duchenne muscular dystrophy; HD: Huntington’s disease; IND: Investigational New Drug 1Q 2025: Deliver 48-week FORWARD-53 data & feedback from regulators on pathway to accelerated approval 2H 2025: Submit IND application for potentially registrational Phase 2/3 using caudate atrophy as a primary endpoint WVE-006 AATD Wholly owned programs 2025: Deliver multi-dose data from RestorAATion-2 2025: Deliver new preclinical data from hepatic and extra-hepatic RNA editing programs 2026: Initiate clinical development of additional RNA editing programs RNA editing Splicing Allele-selective silencing WVE-007 (INHBE) Obesity Initiate INLIGHT first-in-human clinical trial 2H 2025: Deliver clinical data from INLIGHT siRNA

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v3.25.0.1

Document and Entity Information	Mar. 04, 2025
Cover [Abstract]
Amendment Flag	false
Entity Central Index Key	0001631574
Document Type	8-K
Document Period End Date	Mar. 04, 2025
Entity Registrant Name	WAVE LIFE SCIENCES LTD.
Entity Incorporation State Country Code	U0
Entity File Number	001-37627
Entity Tax Identification Number	98-1356880
Entity Address, Address Line One	7 Straits View #12-00
Entity Address, Address Line Two	Marina One
Entity Address, City or Town	East Tower
Entity Address, Country	SG
Entity Address, Postal Zip Code	018936
City Area Code	65
Local Phone Number	6236 3388
Written Communications	false
Soliciting Material	false
Pre Commencement Tender Offer	false
Pre Commencement Issuer Tender Offer	false
Entity Emerging Growth Company	false
Security 12b Title	$0 Par Value Ordinary Shares
Trading Symbol	WVE
Security Exchange Name	NASDAQ

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