Wave Life Sciences Corporate Presentation

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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,

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"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

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

2024 was a year of breakthroughs Achieved first-ever RNA editing in

humans, advancing best-in-class treatment for AATD Pioneering RNA editing Expanded GalNAc-AIMer pipeline: unveiled three new wholly owned RNA editing programs targeting PNPLA3, LDLR, APOB Selected and advanced INHBE GalNAc-siRNA clinical candidate,

a novel, long acting, muscle sparing approach for obesity grounded in human genetics Innovating in obesity Submitted CTA for Phase 1 INLIGHT clinical trial of WVE-007 Achieved first allele-selective mutant huntingtin silencing, wild-type sparing in

clinic with WVE-003 for Huntington's disease Advancing best-in-class treatments for HD and DMD Delivered positive interim DMD clinical data for WVE-N531 with highly consistent, mean muscle content-adjusted dystrophin expression of 9% Unlocking

potential of Demonstrated proprietary PN breakthroughs for intracellular delivery and ability to silence and edit preclinically in high priority extra-hepatic tissues, including CNS PRISM platform Expect to continue momentum with multiple data

updates in 2025 and beyond 4 AATD: Alpha-1 antitrypsin deficiency HD: Huntington's disease DMD: Duchenne muscular dystrophy CTA: clinical trial application CNS: Central nervous system

The powerful convergence of a validated, best-in-class platform with

genetics Multi-modal: RNA editing, RNAi, Real-time integration of new human antisense, splicing genetic insights into discovery Best positioned to engage Proprietary deep learning models Unmatched Data-driven

endogenous machinery unveiling novel targets/ toolkit to discovery target sites Unlocking new, high-impact access novel powered by therapeutic targets Accelerating time to clinic biology human genetics Breakthroughs in

intracellular delivery Step-change in potency, distribution, Foundation in durability of effect chemistry innovation No complex delivery vehicles (AAV, LNP) 5

Differentiated RNA medicines clinical pipeline WVE-007 in Obesity

WVE-006 in AATD WVE-N531 in DMD WVE-003 in HD GalNAc-siRNA GalNAc-RNA editing Exon 53 splicing Allele-selective targeting INHBE oligonucleotide oligonucleotide oligonucleotide Multiple CTAs submitted since RestorAATion-2 ongoing in FORWARD-53 trial

ongoing; Planning underway for mid-December 2024; proof-of- Pi*ZZ AATD patients; multidose expect feedback from regulators potentially registrational concept clinical data expected data expected in 2025 and 48-week FORWARD-53 data Phase 2/3 study;

IND in 2025 in 1Q 2025 submission expected 2H 2025 ~175M people ~2,300 boys with DMD ~85K HD SNP3 patients ~200K patients with AATD living with obesity amenable to exon 53 skipping across all disease stages 6 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

Advancing WVE-007 as a novel, long acting, muscle sparing approach for

obesity WVE-007 is a GalNAc-conjugated small interfering RNA (GalNAc-siRNA) that targets INHBE to treat obesity Adults with obesity have higher risk for many serious health conditions, including heart disease, type 2 1 diabetes, and some

forms of cancer GLP-1s are current standard of care for weight loss, but impact is often limited by: 2 Loss of muscle mass 3 Poor tolerability 4 Frequent dosing 5,6 High discontinuation rates ~175 million

adults with obesity in US and Europe 7 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.

Human genetic data demonstrate that heterozygous INHBE LoF carriers have

a healthy metabolic profile Heterozygous INHBE LoF carriers have favorable traits: Heterozygous INHBE LoF carriers have lower risk of Type 2 lower abdominal obesity, lower triglycerides, higher HDL-c diabetes and CHD Silencing INHBE mRNA by

50% is expected to recapitulate the healthy metabolic profile of heterozygous INHBE loss of function (LoF) carriers 8 Akbari et al. Nat Commun. 2022 Aug 23;13(1):4844; Deaton et al. Nat Commun. 2022 Jul 27

INHBE GalNAc-RNA expected to address health issues associated with

pathogenesis of obesity, associated metabolic disease Reduced release of Diminished activation of Increased adipose GalNAc-siRNA ACVR1C (ALK7) receptor in lipolysis and shrink hepatokine Activin E adipose tissue adipocytes Decreased abdominal

adiposity leads to weight loss and reduced risk for CVD and T2D 9 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

Single doses of INHBE GalNAc-siRNA result in dose-dependent weight loss

and reduction of visceral fat, without affecting muscle mass Reduction in body weight Reduction in visceral fat No muscle loss Quadricep weight (Day 28) Epididymal fat weight (Day 28) * PBS INHBE GalNAc-siRNA (3 mg/kg)

INHBE GalNAc-siRNA (10 mg/kg) -23% -40% * * * * * * Single dose INHBE GalNAc-siRNA INHBE GalNAc-siRNA has potential as monotherapy weight loss therapeutic 10 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

INHBE GalNAc-siRNA can be used synergistically with GLP-1s or to

prevent weight regain after the cessation of treatment with GLP-1s ~2x greater overall weight loss when added to Prevents weight regain after the cessation of GLP-1s GLP-1s 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 11 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 Difference in body weight (% of PBS, same time point)

Preclinical data support best-in-class profile and potential to use

WVE-007 across multiple treatment settings with 1-2x a year dosing Monotherapy Add-on to GLP-1s Maintenance WVE-007 in addition to GLP-1 WVE-007 for patients who stop WVE-007 as a single agent therapy treatment with GLP-1 therapy Weight

loss similar to semaglutide with a single When administered as an add- Curtailed rebound weight dose on with semaglutide: gain upon cessation of No loss of muscle mass semaglutide A single dose of Wave's

Reduction in fat mass with Prevention of weight INHBE GalNAc-siRNA preferential effect to the cycling, which worsens the doubled the weight loss visceral fat outcomes of various observed with semaglutide metabolic diseases Without

suppressing food alone intake 12

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 Trial Design SAD Cohort 5 Objective: Assess dose safety, MAD Cohort 3 tolerability, PK and PD SAD Cohort 4 Key measurements

MAD Cohort 2 - Primary: Safety and Tolerability - Secondary: PK, Activin E SAD Cohort 3 - Exploratory PD: MAD Cohort 1 Body weight Body composition SAD Cohort 2 Metabolic health Biochemical markers SAD Cohort 1 Expect

to initiate dosing in INLIGHT in 1Q 2025; proof-of-concept clinical data expected in 2025 13

Advancing WVE-006 (RNA editing) in AATD WVE-006: GalNAc-conjugated,

subcutaneously delivered, designed to address AATD-related lung disease, liver disease, or both 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 ~200K people in the US and Europe are homozygous for the Z allele 14 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 to address both liver and lung manifestations of AATD WVE-006

RNA WVE-006 ADAR editing approach to address editing treatment key goals of AATD treatment: Restore circulating, Reduce Z-AAT Retain M-AAT Subcutaneous 1 2 3 functional wild-type protein aggregation physiological injection M-AAT in liver regulation

(GalNAc) Infrequent dosing Z-AAT Highly specific A I (no M-AAT reaches lungs to RNA correction replaces M-AAT secretion into bystanders) protect from proteases mutant Z-AAT protein with bloodstream wild-type M-AAT protein 15 Strnad et al.,

2020 N Engl J Med 382:1443-55; Stoller et al., 1993 Alpha-1 Antitrypsin Deficiency GeneReviews.

RestorAATion-2 clinical trial in Pi*ZZ AATD patients ongoing

RestorAATion-2: AATD Patients RestorAATion-1: Healthy Volunteers RestorAATion-1: Healthy Volunteers Single ascending dose (SAD) Multiple-ascending dose (MAD) cohorts Multi-dosing complete Dose E in RestorAAtion-1 Up to 7 doses Dose D Cohort

3 Dose C Cohort 2 Dose B Cohort 1 200 mg Dose A Study key objectives Safety and tolerability Pharmacokinetics Serum M-AAT levels 16 HV: healthy volunteer; SAD: single-ascending dose; MAD: multi-ascending dose

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 M 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 M 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 Multidose data from RestorAATion-2 expected in 2025

17 October 16, 2024 Proof-of-mechanism disclosure on first two "ZZ" AATD patients in first dose cohort of RestorAATion-2 to reach day 57

Wholly owned GalNAc-AIMer programs Correction of PNPLA3 Strongly

supported by human genetics Genetically defined liver disease Patient population: ~9 million Leverage unique platform capabilities; GalNAc-AIMers building on learnings Upregulation of LDLR of WVE-006 HeFH Patient population:

~900,000, with Completely novel ways of treating expansion to ~30 million in follow on indications diseases with high unmet need Readily accessible biomarkers and Correction of APOB approaches to assess PD, defined HeFH regulatory

paths Patient population: ~70,000 Expect to initiate clinical development of additional RNA editing programs, including PNPLA3, LDLR, and APOB programs in 2026 18 Patient populations are in US and Europe Editing for correction Editing for

upregulation HeFH: heterozygous familial hypercholesterolemia

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 19 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: An ongoing potentially registrational open-label Phase 2

clinical trial of WVE-N531 in boys with DMD amenable to exon 53 skipping 10 mg/kg Q2W 10 mg/kg Q4W Screening N = 11 Extension Interim analysis Baseline functional Muscle biopsy after 24 Muscle biopsy after 48

assessments weeks of treatment weeks of treatment Functional assessments 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 20 IV: Intravenous; Q2W: Every 2 Weeks; PK: Pharmacokinetics; PD: Pharmacodynamics

WVE-N531 is the only DMD therapeutic to show uptake in myogenic stem

cells WVE-N531 uptake in myofiber nuclei WVE-N531 uptake in myogenic stem cells Myocytes Stars denote an injured myofiber Stem cell containing WVE-N531 Mag: 40x Mag: 20x Myocyte nuclei containing WVE-N531 (red) Mag: 20x Mag: 40x Dual staining

utilizing in-situ hybridization for WVE-N531 and PAX7 In-situ hybridization for WVE-N531 immunohistochemistry for stem cells 21 Data from interim analysis clinical 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 Best-in-class dystrophin Evidence supporting Safe and expression and muscle delivery improved muscle health well tolerated Highly consistent, mean muscle Improvement in

serum biomarkers No serious adverse events (SAEs) content-adjusted dystrophin for muscle health No discontinuations expression of 9% Localization of WVE-N531 in No oligonucleotide class effects Muscle tissue

concentrations of myogenic stem cells ~41,000 ng/g and tissue half-life of Improvement in myofiber 61 days (supports monthly dosing) regeneration Preclinical data suggests higher levels of dystrophin protein expression in heart and

diaphragm than skeletal muscle Expect feedback from regulators and the 48-week FORWARD-53 data in 1Q 2025 22 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.

Unlocking Wave's best-in-class exon skipping portfolio DMD