8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

Form 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): May 23, 2023

WAVE LIFE SCIENCES LTD.

(Exact name of registrant as specified in its charter)

Singapore	001-37627	98-1356880
(State or other jurisdiction of incorporation)	(Commission File Number)	(IRS Employer Identification No.)

7 Straits View #12-00, Marina One
East Tower
Singapore	018936
(Address of principal executive offices)	(Zip Code)

Registrant’s telephone number, including area code: +65 6236 3388

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company  ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.  ☐

Securities registered pursuant to Section 12(b) of the Act:

Title of each class	Trading symbol	Name of each exchange on which registered
$0 Par Value Ordinary Shares	WVE	The Nasdaq Global Market

Item 7.01 Regulation FD Disclosure.

On May 23, 2023, Wave Life Sciences Ltd. (the “Company” or “Wave”) issued a press release announcing topline data from the Company’s Phase 1b/2a FOCUS-C9 trial of WVE-004, the Company’s clinical candidate for C9orf72-associated amyotrophic lateral sclerosis (C9-ALS) and frontotemporal dementia (C9-FTD). In addition, the press release indicated that Wave will host an investor conference call at 8:30 a.m. ET on May 23, 2023 to review the FOCUS-C9 clinical trial results. A copy of the press release is attached hereto as Exhibit 99.1 and incorporated by reference herein.

In addition, 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 May 23, 2023, the Company updated its corporate presentation, which is available on the “For Investors & Media” section of the Company’s website at http://ir.wavelifesciences.com/. A copy of this presentation is also furnished as Exhibit 99.2 hereto and incorporated by reference herein.

The information in this Item 7.01 is 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 8.01 Other Events.

The information set forth in the press release referred to in Item 7.01 above, other than the fourth and fifth paragraphs thereof, is incorporated by reference into this Item 8.01 of this Current Report on Form 8-K.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits

Exhibit No.	Description
99.1	Press Release issued by Wave Life Sciences Ltd. dated May 23, 2023
99.2	Corporate Presentation of Wave Life Sciences Ltd. dated May 23, 2023
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/ Paul B. Bolno, M.D.
	Paul B. Bolno, M.D.
	President and Chief Executive Officer

Date: May 23, 2023

EX-99.1

Exhibit 99.1

Wave Life Sciences Announces Topline Results from Phase 1b/2a FOCUS-C9 Study of WVE-004 for C9orf72-associated

Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Potent and durable target engagement observed across cohorts, including with 10 mg doses administered every 12 weeks

which were also generally safe and well-tolerated

WVE-004 did not show clinical benefit compared with placebo; additionally, poly(GP) reductions did not correlate with

clinical outcomes — Wave to discontinue development of WVE-004

Wave to host investor conference call at 8:30 a.m. ET today

CAMBRIDGE, Mass., May 23, 2023 — Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage RNA medicines company committed to delivering life-changing treatments for people battling devastating diseases, today announced topline results from the Phase 1b/2a FOCUS-C9 study evaluating WVE-004 as an investigational treatment for C9orf72-associated amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). The results include data from a planned analysis of the study, where participants received multiple 10 mg doses of WVE-004 or placebo every 12 weeks (Q12W) or every 4 weeks (Q4W), as well as an additional 20 mg single dose cohort.

WVE-004 was generally safe and well-tolerated across doses, with most adverse events presenting as mild in intensity. There were no clinically meaningful changes in cerebrospinal fluid (CSF) protein or white blood cell count and no new safety signals since the previous data update in April 2022.

Robust, sustained reductions in poly(GP) from baseline were observed, with a maximal mean reduction of 48% (p<0.0001) in the Q12W dose and 50% (p=0.0001) in the Q4W dose of WVE-004. Poly(GP) is a pharmacodynamic biomarker indicating WVE-004 is lowering C9orf72 hexanucleotide repeat expansion (G₄C₂) transcripts, which are hypothesized to contribute to pathogenesis in C9-ALS/FTD. However, no clinical benefit was observed at 24 weeks, and reductions in poly(GP) were not associated with stabilization or improvement in functional outcomes. Based on these data, and in the absence of biomarkers reasonably likely to predict clinical outcomes, Wave has decided to discontinue development of WVE-004.

“Following our initial positive single dose data last year, we advanced WVE-004 with the hope that its potency and differentiated pharmacology may deliver a better result than C9orf72-targeting oligonucleotides discontinued by others in the field. While we again saw substantial reductions of poly(GP) with multiple doses, we are deeply disappointed that we were not able to see any evidence of potential benefits that would be expected to drive meaningful outcomes for these patients,” said Paul Bolno, MD, MBA, President and CEO of Wave Life Sciences. “C9-ALS/FTD is complex and made all the more challenging by the absence of a clinically validated biomarker. Our hope is that these data can help advance future research, and we are committed to sharing results with the community at an upcoming medical congress. On behalf of everyone at Wave, I wish to sincerely thank the participants, their families, the clinical sites, and our study advisory committees for their participation and support.”

Continued Dr. Bolno: “These data do reinforce that our preclinical data on target engagement and pharmacology are translating in the clinic. Looking forward, our lead programs in Huntington’s disease, Duchenne muscular dystrophy and Alpha-1 antitrypsin deficiency are designed to leverage biomarkers correlated with functional outcomes, making us more confident in the future of these programs and our emerging preclinical pipeline.”

Wave remains on track to share data from its Phase 1b/2a SELECT-HD study in Huntington’s disease investigating WVE-003 in the second half of 2023. The company is also rapidly advancing WVE-N531 for Duchenne muscular dystrophy amenable to exon 53 skipping into the potentially registrational Part B (Phase 2) clinical study, following its best-in-class exon skipping data observed in the Part A proof-of-concept study. Wave is also on track to bring the industry’s first RNA editing compound, WVE-006, into a clinical trial in Alpha-1 antitrypsin deficiency in the second half of 2023. In addition, the company continues to advance preclinical research with its modalities that restore or repair endogenous proteins, including additional RNA editing programs, and expects to share an update on its preclinical pipeline highlighting new data in the third quarter of 2023.

Topline FOCUS-C9 Results

The FOCUS-C9 study initially evaluated single doses of 10, 30 or 60 mg of WVE-004 or placebo. Based on potency and durability observed in the single dose cohorts, Wave added a 20 mg single dose cohort (n=8) and advanced 10 mg as the dose for the repeat dose phase, administered every 12 weeks (Q12W; n=8) or every four weeks (Q4W; n=5) and compared with placebo (n=7).

Participants in the Q12W cohort receive two 10 mg doses and participants in the Q4W cohort receive four 10 mg doses; participants are followed for 24 weeks. Key observations from the planned analysis of the study include:

Safety/tolerability results

• WVE-004 was generally safe and well-tolerated across the single and multidose cohorts (n=26 unique WVE-004-treated participants) and the most common adverse events (AEs) in the study were related to disease progression and intrathecal administration.

• AEs were mostly mild in intensity across all treatment groups.

• Among WVE-004-treated participants, there was one SAE in the study reported by the investigator as related to study drug that occurred in the 60 mg single dose cohort, as previously reported in April 2022. There was also one SAE reported that was procedure related. All other SAEs were associated with disease progression.

• There were no AEs indicative of antisense oligonucleotide class effects, including no clinically meaningful changes in blood chemistry or hematology.

• There was no evidence of inflammation in the CSF as indicated by no clinically meaningful changes in CSF white blood cell count or protein.

Poly(GP) results

• In the multidose cohorts, the mean, maximal poly(GP) reduction from baseline was 48% (95% CI, 0.36, 0.58; p<0.0001) for the 10 mg Q12W cohort at week 16 and 50% (95% CI: 0.29, 0.64, p=0.0001) for the 10 mg Q4W cohort at week 24.

• In the 20 mg single dose cohort, the mean, maximal poly(GP) reduction from baseline was 51% (95% CI, 0.29, 0.67; p=0.0006) at week 24.

Exploratory biomarker results: CSF neurofilament light chain (NfL)

• NfL elevations were observed in the WVE-004 20 mg single dose cohort and the 10 mg Q4W cohort; the 10 mg Q12W cohort and placebo had overlapping confidence intervals.

• There was no correlation (absolute correlation coefficient <0.1) between CSF NfL increases and ALSFRS-R change.

Exploratory clinical outcomes

• There was no benefit observed for WVE-004-treated participants compared with placebo on any exploratory clinical outcome measure, including the Revised ALS Functional Rating Scale (ALSFRS-R).

• In the Q12W cohort, there was no statistically significant difference in ALSFRS-R mean change between WVE-004 and placebo at any timepoint.

• In the Q4W cohort, participants treated with WVE-004 showed greater reduction in ALSFRS-R mean change than placebo patients at week 24 (p<0.0001); however, ALSFRS-R scores were not statistically different from the decline seen in natural history (using a matched natural history control group from the PRO-ACT database).

• Additionally, there was no benefit observed for WVE-004 treated participants with FTD compared with placebo on the Dementia Staging Instrument plus National Alzheimer’s Coordinating Center (NACC) frontotemporal lobar degeneration (FTLD) Behavior and Language Domains (CDR^® plus NACC FTLD).

• Reductions in poly(GP) did not associate with improvement on ALSFRS-R and CDR plus NACC FTLD and as such, Wave determined it will discontinue development of WVE-004, including stopping the FOCUS-C9 study and the open label extension study.

Investor Conference Call

Wave will host an investor conference call today at 8:30 a.m. ET to review the FOCUS-C9 clinical trial results. 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-and-presentations. 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.

About FOCUS-C9

The FOCUS-C9 trial is a global, multicenter, randomized, double-blind, placebo-controlled Phase 1b/2a clinical trial to assess the safety and tolerability of single- and multiple-ascending intrathecal doses of WVE-004 for people with C9-ALS and/or C9-FTD. Additional objectives include measurement of poly(GP) dipeptide repeat (DPR) proteins in the cerebrospinal fluid (CSF), plasma and CSF pharmacokinetics (PK), and exploratory biomarkers and clinical outcomes. The FOCUS-C9 trial is designed to be adaptive, with dose escalation and dosing frequency being guided by an independent committee. Support for FOCUS-C9 was provided by the Alzheimer’s Drug Discovery Foundation.

About WVE-004

WVE-004 is an antisense oligonucleotide (ASO) designed with Wave’s proprietary and best-in-class chemistry, which selectively targets transcriptional variants containing the hexanucleotide repeat expansion (G₄C₂) associated with the C9orf72 gene, thereby sparing normal C9orf72 protein.

About Wave Life Sciences

Wave Life Sciences (Nasdaq: WVE) is a clinical-stage RNA medicines company committed to delivering life-changing treatments for people battling devastating diseases. Wave aspires to develop best-in-class medicines across multiple therapeutic modalities using PRISM, the company’s proprietary discovery and drug development platform that enables the precise design, optimization, and production of stereopure oligonucleotides. Driven by a resolute sense of urgency, the Wave team is targeting a broad range of genetically defined diseases so that patients and families may realize a brighter future. To find out more, please visit www.wavelifesciences.com and follow Wave on Twitter @WaveLifeSci.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, our hope that our FOCUS-C9 data may be used to advance future research; our plans to share these results with the community at an upcoming medical congress; our expectations regarding the potential benefits and the anticipated timing of our upcoming milestones for our lead programs in Huntington’s disease, Duchenne muscular dystrophy and Alpha-1 antitrypsin deficiency and our confidence in these programs because they leverage biomarkers correlated with functional outcomes; and our expectations regarding the timing and substance of upcoming datasets from our preclinical pipeline using modalities that restore or repair endogenous proteins, including our RNA editing capability. 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 events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release and actual results may differ materially from those indicated by these forward-looking statements as a result of these risks, uncertainties and important factors, including, without limitation, the risks and uncertainties described in the section entitled “Risk Factors” in Wave’s most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as amended, and in other filings Wave makes with the SEC from time to time. Wave undertakes no obligation to update the information contained in this press release to reflect subsequently occurring events or circumstances.

Investor Contact:

Kate Rausch

617-949-4827

krausch@wavelifesci.com

Media Contact:

Alicia Suter

617-949-4817

asuter@wavelifesci.com

ALS and FTD Community Contact:

Chelley Casey

617-949-2900

ccasey@wavelifesci.com

EX-99.2

Exhibit 99.2 Wave Life Sciences Corporate Presentation May 23, 2023

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

Emerging leader in RNA medicines Multi-modal drug Differentiated, clinical- Strategic collaborations to discovery and stage RNA medicines expand and advance development platform to pipeline with first-in- pipeline (GSK and Takeda) address new areas of class RNA editing disease biology programs RNA editing, splicing and silencing Multiple pipeline and Well-capitalized with GMP manufacturing platform catalysts expected cash runway Strong and broad IP expected in 2023 and into 2025 1 beyond position Wave Life Sciences is an RNA medicines company committed to delivering life-changing treatments for people battling devastating diseases 3 3 3 1 stereopure oligonucleotides and novel backbone chemistry modifications

RNA medicines allow matching disease target to therapeutic modality RNA Base Editing Splicing Silencing • Efficient editing of RNA bases • Restore RNA transcripts and • Degradation of RNA transcripts to restore or modulate turn on protein production to turn off protein production protein production Endogenous Skip RNase H Restored Reading Frame Endogenous AGO2 Endogenous RISC ADAR enzyme Functional Protein 4

Robust RNA medicines pipeline with first-in-class RNA editing programs Patient population Program Discovery Preclinical Clinical Rights (US & Europe) RNA EDITING WVE-006 GSK exclusive 200K SERPINA1 (AATD) global license Multiple undisclosed 100% global - SPLICING WVE-N531 100% global 2.3K Phase 1/2 Exon 53 (DMD) Other exons (DMD) 100% global Up to 18K SILENCING: ANTISENSE 25K Manifest (SNP3) Takeda 50:50 WVE-003 Phase 1/2 60K Pre-Manifest mHTT (HD) Option (SNP3) Takeda 50:50 SCA3 (ATXN3) 8K Option SILENCING: RNAi Undisclosed 100% global - Through GSK collaboration, Wave can advance up to three collaboration programs and GSK can advance up to eight collaboration programs 5 AATD: Alpha-1 antitrypsin deficiency; DMD: Duchenne muscular dystrophy; HD: Huntington’s disease; SCA3: Spinocerebellar ataxia 3

WVE-N531 Duchenne muscular dystrophy

Duchenne muscular dystrophy • Genetic mutation in dystrophin gene Disease State Restored State prevents the production of dystrophin Dysfunctional Splicing Exon Skipping Oligo protein, a critical component of healthy Mutant pre-mRNA Mutant pre-mRNA muscle function 50 51 53 54 55 50 51 53 54 55 • Impacts approx. 1 in every 5,000 Skip newborn boys each year; approx. 20,000 new cases annually worldwide 50 51 53 54 55 50 51 54 55 – Approx. 8-10% are amenable to exon 53 skipping mRNA with disrupted reading frame Restored mRNA • Dystrophin protein established by FDA as Translation halted Translation continues surrogate endpoint reasonably likely to 1 predict benefit in boys for accelerated approval in DMD • Increasing amount of functional dystrophin expression over minimal amount shown with approved therapies is expected to result No dystrophin Functional in greater benefit for boys with DMD protein produced dystrophin produced 1 7 Vyondys: www.fda.gov; viltepso; www.fda.gov; Exondys; www.fda.gov; Amondys: www.fda.gov

Extended survival in dKO preclinical model supports potential of exon-skipping therapeutics for DMD PN chemistry improved function and survival in dKO mice dKO survival studies in literature Restored muscle and respiratory 100% survival at time of study termination function to wild-type levels 300 200 100 0 20 40 60 80 100 120 Stimulation Frequency (Hz) Wild-type dKO: PBS dKO: PS/PO/PN Tidal volume Time (weeks) PS/PO/PN 150 mg/kg weekly PS/PO/PN 75 mg/kg bi-weekly PS/PO 150 mg/kg weekly PBS Age (days) Wild-type dKO: PBS dKO (PS/PO/PN Note: Untreated, age-matched mdx mice had 100% survival at oligonucleotide) study termination [not shown] 8 Left: Kandasamy et al., 2022; doi: 10.1093/nar/gkac018; Right: Forand et al., 2020; doi: https://doi.org/10.1016/j.omtm.2020.03.011. Survival probability (%) 2 TVb (ml) Specific Force (Nm )

Preclinical data supported advancing WVE-N531 to clinical development WVE-N531 reached high concentrations in heart and WVE-N531: Dystrophin diaphragm in NHP restoration of up to 71% in vitro Western Blot normalized to primary healthy human myoblast lysate Conc (uM) % Dystrophin Dystrophin Vinculin 9 th 26 Annual ASGCT meeting, May 16-20, 2023

In multidose portion of study, patients received three biweekly 10 mg/kg doses Single ascending intra-patient doses Multidosing at 10 mg/kg every other week Weeks 0 2 4 6 Muscle 10 mg/kg 10 mg/kg 10 mg/kg 10 mg/kg Biopsy Initial cohort Period before initiating 6 mg/kg multidosing (~1 – 2 months) •Boys with DMD 3 mg/kg amenable to exon 53 skipping 1 mg/kg Data include: • WVE-N531 muscle • Exon skipping concentrations • Dystrophin protein • WVE-N531 localization Dose WVE-N531 10

WVE-N531 in DMD: Delivered positive proof-of-concept data in 4Q 2022 Tissue % Exon Dystrophin • High exon skipping and Tissue Patient concentration skipping by Western blot muscle concentrations Source (µg/g) by RT-PCR (% of normal) after three biweekly 10 mg/kg doses 1 Deltoid 85.5 61.5 0.24 • Similar exon skipping 2 Deltoid 33.5 49.8 0.23 regardless of mutation – Patient 1: del48-52 3 Bicep 8.3 47.9 0.34 – Patient 2: del45-52 – Patient 3: del51-52 Mean Mean muscle Mean exon dystrophin: • PK analysis indicated concentration: sk ipping: 0.27% of 42 µg/g 53% 25-day half-life in normal (BLQ) plasma • WVE-N531 appeared safe and well-tolerated Data presented March 22, 2023 at Muscular Dystrophy Association Clinical and Scientific Conference Biopsies collected ~2 weeks post-last dose (3 biweekly doses of 10 mg/kg) 42 µg/g = 6.1 µM BLQ: Below level of quantification (1%) Data cut-off: December 6, 2022 11

Initiating Part B, a potentially registrational Phase 2 clinical trial of WVE-N531 Screening Biweekly Dosing (10 mg/kg IV) Safety Follow-up • Functional • Biopsy after 24 weeks of • Biopsy after 48 weeks of assessment treatment treatment • Functional assessment• Functional assessment • Design: Phase 2, open-label, 10 mg/kg every other week, up to 10 patients • Endpoints: Dystrophin (powered for >5% of normal), safety/tolerability, pharmacokinetics, functional assessments (incl. NSAA and others) • Biopsies: – After 24 weeks of treatment – After 48 weeks of treatment • Data from Part B expected in 2024 12 IV: intravenous; NSAA: North star ambulatory assessment

GSK Collaboration and WVE-006 for Alpha-1 antitrypsin deficiency (AATD)

Strategic collaboration with GSK to develop transformative RNA medicines for genetically defined diseases Multiple value drivers to Wave ✓ $170 million upfront to 1 Milestone / royalties Milestone / royalties Genetic targets Wave (cash and equity ) Wave to leverage GSK granted exclusive global GSK to advance up to eight ✓ Additional research support GSK’s genetic license to WVE-006 for AATD collaboration programs insights funding Up to $1.2 billion in aggregate in ✓ Potential for up to $3.3 Up to $225 million in development initiation, development and launch 2 and launch milestones billion in milestones milestones ✓ Expands Wave’s pipeline Up to $300 million in sales-related Up to $1.6 billion in aggregate in Wave to advance up milestones sales-related milestones to three wholly owned collaboration programs (or more Double-digit tiered royalties as a pending agreement Tiered royalties as a percentage of Extends cash runway percentage of net sales up to high- 3 with GSK) net sales up to low-teens teens into 2025 Development and commercialization Development and commercialization responsibilities transfer to GSK after responsibilities transfer to GSK at completion of first-in-patient study development candidate First-in-class RNA Collaboration leverages Wave’s unique stereopure, TM editing program PN-chemistry containing PRISM platform, including editing, splicing, silencing (RNAi and antisense) 1 2 $120 million in cash and $50 million equity investment received in January 2023, Initiation, development, launch, and commercialization milestones for WVE-006 14 3 and programs progressed during initial 4-year research term (8 GSK collaboration programs) GSK eligible to receive tiered royalty payments and commercial milestones from Wave

WVE-006: Designed to correct mutant SERPINA1 transcript to address both liver and lung manifestations of AATD WVE-006 designed to correct WVE-006 ADAR editing approach to address key goals of AATD treatment: Z allele mRNA to enable M-AAT protein to be produced 2) Reduce Z-AAT 1) Restore circulating, 3) Retain M-AAT protein aggregation in A functional wild-type M-AAT physiological regulation liver SERPINA1 Z allele mRNA encodes Z-AAT protein with E342K mutation Z-AAT WVE-006 (GalNAc- conjugated AIMer) I(G) RNA correction replaces M-AAT reaches lungs to M-AAT secretion into mutant Z-AAT protein protect from proteases bloodstream with wild-type M-AAT protein Edited SERPINA1 mRNA enables wild- type M-AAT protein production AAT: Alpha-1 antitrypsin Strnad et al., 2020 N Engl J Med 382:1443-55; Blanco et al., 2017 Int J Chron Obstruct Pulmon Dis 12:561-69; Remih 15 et al., 2021 Curr Opin Pharmacol 59:149-56.

WVE-006 in AATD: First-in-class RNA editing candidate approaching the clinic Potentially comprehensive approach to address both lung and liver manifestations of AATD Increased AAT protein Confirmed restored Demonstrated functionality in NSG-PiZ mice wild-type M-AAT protein of M-AAT protein WVE-006 treatment results in serum AAT Overall percentages of serum AAT Serum neutrophil elastase protein levels >11 uM in NSG-PiZ mice protein isoforms in NSG-PiZ mice inhibition activity in NSG-PiZ mice (Week 13) 2000 PBS 1800 WVE-006 1600 WVE-006 (NO LOADING DOSE) 1400 1200 ~7-fold 1000 increase 800 600 11μM 400 200 0 Week CTA submissions for first-in-human study expected in 2H 2023 AATD: Alpha-1 antitrypsin deficiency; M-AAT protein: wild-type AAT protein; WVE-006 administered subcutaneously (10 mg/kg bi-weekly) in 7-week old NSG-PiZ mice (n=5 per group); Loading dose: 3 x 10 mg/kg at Day 0. Left: Liver biopsies collected at wk 13 (1 wk after last dose) and SERPINA1 editing quantified by Sanger sequencing; Right: Total 16 serum AAT protein quantified by ELISA; Stats: Two-Way ANOVA with adjustment for multiple comparisons (Tukey) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Serum AAT protein (ug/ml) (Mean, s.e.m)

Early lead (pre-optimization) AATD AIMer reduces aggregation of Z-AAT and inflammation in mouse liver Lobular inflammation (19 weeks) 15 25 **** PBS 5 * Early lead AATD AIMer p<0.0001 20 p=0.03 4 10 15 p<0.01 3 5 10 ** 2 5 1 0 4 8 19 0 0 Weeks following first dose PBS PBS AIMer AIMer Early lead pre-optimization AATD AIMer (SA1-5) administered in huADAR/SERPINA1 mice (8–10 wKs old); lower left: 20x liver images PAS-D stained, 19 weeks; Quantification of PAS-D positive staining, Stats 2-way ANOVA; Right: Quantification lobular inflammation grade (Grade based on # of inflammatory foci in lobules: Grade 0: 0; G1 1-5; G2 6-10; 17 G3 11-15; G4 ≥16) and mean globular diameter (40 largest globules/ animal) with HALO. Stats Wilcox rank-sum tests %PAS-D positive area % PAS-D positive area (mean±sem) (mean±sem) Mean diameter (mm) Mean Diameter (µm) Inflammation grade Inflammation grade

AIMer-directed editing is highly specific in mice No bystander editing observed on SERPINA1 transcript RNA editing only detected at PiZ mutation site in SERPINA1 transcript RNA editing across transcriptome (mouse liver) (mouse liver) C 0% SERPINA1 PBS (PiZ mutation site) T 100% C 48.2% AATD AIMer T 51.8% % Editing Editing site (PiZ mutation) Dose 3x10 mg/kg (days 0, 2, 4) SC with AATD AIMer (SA1 – 4). Liver biopsies day 7. RNA-seq to quantify on-target SERPINA1 editing, to quantify off-target editing reads mapped to entire mouse genome; plotted circles represent sites with LOD>3 (N=4), SERPINA1 edit site is indicated 18 Coverage Coverage

WVE-003 Huntington’s Disease

mHTT toxic effects lead to neurodegeneration; loss of wtHTT functions may also contribute to HD Huntington’s disease (HD) Healthy individual • Wild-type HTT (wtHTT) is critical for normal neuronal function • Expanded CAG triplet repeat in HTT gene results in production of mutant huntingtin protein (mHTT) wtHTT Stresses • HD is a monogenic autosomal dominant genetic disease; fully Huntington’s disease penetrant and affects entire brain • Fatal disease characterized by cognitive decline, psychiatric illness, and chorea ~50% decrease wtHTT Stresses mHTT + • 30,000 people with HD in the US in wtHTT and more than 200,000 at risk of Loss of wtHTT functions developing HD Synaptic dysfunction | Healthy CNS function Cell death | Neurodegeneration 20

WVE-003: First-in-class allele-selective candidate for HD Reductions in mean CSF mHTT and preservation of wtHTT • mHTT protein reductions observed in pooled analysis of single dose cohorts in observed in single dose cohorts SELECT-HD clinical study (Sep. 2022) wtHTT protein levels mHTT protein levels • wtHTT protein levels appear consistent with allele-selectivity • Generally safe and Reduction in mHTT protein: well-tolerated Placebo 22% from baseline 35% vs. placebo WVE-003 • Additional single-dose and (30 and 60 mg pooled*) multi-dose biomarker and safety clinical data expected in 2H 2023 Single dose Single dose of WVE-003 of WVE-003 mHTT: mutant huntingtin protein; wtHTT: wild-type huntingtin protein 21 *Pooled considering no apparent dose response between 2 cohorts; Data cut-off: August 29, 2022

AIMers RNA base editing capability

Proof-of-concept preclinical RNA editing data published in Nature Biotechnology (March 2022) • Specificity in vitro & in vivo (NHPs)• GalNAc conjugation • In vitro-in vivo translation (NHPs)• Foundational AIMer SAR AIMers detected in liver of NHP at Day 50 Substantial and durable editing in NHP ADAR editing with ACTB AIMer is (PK) liver in vivo highly specific (PD) RNA editing within full transcriptome (primary human hepatocytes) GalNAc AIMers Day 50 RNA editing ACTB in NHP GalNAc AIMers % Editing 23 RNA editing only detected at editing Monian et al., 2022 published online Mar 7, 2022; doi: 10.1038.s41587-022-01225-1 site in ACTB transcript SAR structure-activity relationship Confidence (LOD score)

Expanding addressable disease target space using AIMers to activate pathways and upregulate expression Correct G-to-A driver mutations with AIMers Modulate protein interactions with AIMers Modulate protein- Restore or correct Achieved protein interaction protein function POC Upregulate expression WVE-006 Modify function (GalNAc AIMer) AATD Post-translational modification Alter folding or processing AIMers provide dexterity, with applications beyond precise correction of genetic mutations, including upregulation of expression, modification of protein function, or alter protein stability 24 POC: proof of concept

Modulation of protein-protein interactions: AIMers enable activation of gene pathway in vivo with single edit 25 n=2; Primary hepatocytes 48h of treatment with the indicated dose concentration of AIMers

Upregulation: AIMers can edit RNA motifs to restore or upregulate gene expression RNA binding proteins recognize sequence motifs to regulate various mRNA properties Stability Transport Processing Protein production • Enhance or inhibit • Intracellular localization • Splicing • Translational efficiency • PolyA usage mRNA decay • Capping AIMer edits mRNA → “dials up” gene expression No binding RNA binding protein I(G) Edited mRNA A mRNA Decay 26

AIMers upregulate mRNA and downstream serum protein in vivo above anticipated threshold Target A mRNA editing mRNA upregulation Protein upregulation (undisclosed liver 7 days post-initial dose 7 days post-initial dose 7 days post-initial dose target) GalNAc AIMer GalNAc AIMer GalNAc AIMer 20 • High unmet need ** * with potential for 20 * ** 80 multiple large 15 indications 15 60 • Preserves endogenous protein 10 10 function 40 • Serum protein with 5 5 biomarkers of 20 pathway activation 0 • Potential benefit 3- 0 0 PBS AIMER-1 AIMER-2 PBS AIMER-1 AIMER-2 PBS AIMER-1 AIMER-2 fold+ upregulation in mouse Potential threshold for benefit ✓ In vitro to in vivo translation of mouse Target A mRNA upregulation ✓ In vivo mRNA upregulation corresponds to an upregulation of Target A protein in serum at Day 7 demonstrating proof-of-concept 27 hADAR mouse dosed subcutaneously 3 x 10 mg/kg GalNAc-conjugated AIMer or PBS days (0, 2, 4), taken down at day 7 RNA editing Percent Editing Upregulation Target A mRNA fold change Fold increase pre-post dose Serum Target A (pg/mL)

Wave’s discovery and drug development platform

Proprietary PN chemistry enhances potency across modalities RNA Editing Splicing Silencing % Editing % Skipping Target knockdown (% remaining) 100 80 60 40 20 0 -8 -6 -4 -2 0 2 10 10 10 10 10 10 Concentration (µM) Concentration (mM) Ranked by potency of reference PS/PO compound Ranked by potency of reference PS/PO compound PS/PO/PN PS/PO (Stereopure) PS/PO (Stereorandom) PS/PO reference compound PS/PN modified compound Left: Experiment was performed in iPSC-derived neurons in vitro; target mRNA levels were monitored using qPCR against a control gene (HPRT1) using a 29 linear model equivalent of the DDCt method; Middle: DMD patient-derived myoblasts treated with PS/PO or PS/PO/PN stereopure oligonucleotide under free-uptake conditions. Exon-skipping efficiency evaluated by qPCR. Right: Data from independent experiments % Editing Improved editing Improved skipping Improved knockdown

Potential for best-in-class RNAi enabled by Wave’s PRISM platform • First in vivo study of unconjugated siRNAs • Unprecedented Ago2 loading following demonstrated 70-90% APP silencing across administration of single subcutaneous dose six brain regions in mouse CNS at 8 weeks Ago2 Ago2 ll ooa adindi g ng HSD17B13 mRNA (liver, transgenic mice) (liver, transgenic mice) 25 (liver, transgenic mice) 125 Wk 2 Wk 7 Wk 14 20 100 15 75 50 10 **** * 25 * 5 0 0 2 4 6 8 10 12 14 16 0 Time (weeks) PBS Reference Wave siRNA Reference Wave siRNA RNAi is one of multiple Wave modalities being advanced in strategic research collaboration with GSK Left, Middle: Mice expressing human HSD17B13 transgene treated (3 mg/kg)siRNA or PBS, liver mRNA, guide strand concentration, Ago2 loading quantified. Stats: Two-way ANOVA with post-hoc test * P<0.05, ****P<0.0001. Liu et al., 2023 Nuc Acids Res doi: 10.1093/nar/gkad268; Right: ICV: Intracerebroventricular; APP: Amyloid precursor protein ; CNS: 30 central nervous system; B6 mice were administered PBS or 100 μg of APP siRNA by ICV injection on day 0 (n=7). Mice euthanized 8 weeks after administration. Taqman qPCR assays used for RNA PD, relative fold changes of App to Sfrs9 mRNA normalized to percentage of PBS group. All treated group show P≤0.0001 compared to PBS group in 2way ANOVA. % mRNA remaining (HSD17B13/Hprt) Fold change relative to Reference 2

Delivering on pipeline and platform catalysts RNA ANTISENSE SPLICING RNAi EDITING SILENCING WVE-006 for AATD WVE-N531 for DMD WVE-003 for HD Newest modality in Wave Most advanced RNA Potential best-in-class First-in-class platform editing candidate & approach with highest exon wild-type huntingtin protein Preclinical data suggest potential best-in-class skipping reported (wtHTT)-sparing best-in-class potential for approach for AATD approach Wave RNAi capability Dosing in potentially WVE-006 CTA registrational clinical Data expected 2H 2023 Hepatic, CNS and beyond submissions expected trial expected in 2023; in 2H 2023 data expected in 2024 Enables discussion on next steps with Takeda Expansion Expansion opportunities opportunities in liver, in other exons, as well CNS and kidney as other muscle diseases and CNS DISCOVERY PIPELINE & COLLABORATIONS Anticipate investor event in 3Q 2023 during which Wave will demonstrate how it is continuing to extend its leadership in RNA editing and share preclinical data on new wholly-owned programs Advance collaboration activities with GSK, with potential for additional cash inflows in 2023 and beyond 31

Realizing a brighter future for people affected by genetic diseases For more information: Kate Rausch, Investor Relations InvestorRelations@wavelifesci.com 617.949.4827 32

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