Wave Life Sciences Corporate Presentation

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

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

Building a leading RNA medicines company Novel RNA medicines platform

(PRISM ) Multi-modal: RNA editing, RNAi, splicing, allele-selective silencing Potential best-in-class, clinically-validated oligonucleotide chemistry (PN, stereochemistry) Pioneering a novel RNA Potential best-in-class

Leadership in allele- Novel approach designed to modality with RNA editing reduce fat, preserve muscle profile selective silencing WVE-007 in Obesity WVE-006 in AATD WVE-N531 in DMD WVE-003 in HD Well-capitalized with cash In-house GMP manufacturing

Strong and broad IP runway into 2027* 4 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

The powerful convergence of a validated, potential best-in-class

platform with deep genetic insights Multi-modal: RNA editing, RNAi, Real-time integration of new human antisense silencing, 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

Robust, diversified RNA medicines pipeline including first-in-class RNA

editing programs IND / CTA Enabling Patient population Program Discovery Clinical Rights Studies (US & Europe) R N A E D I T I N G GSK exclusive WVE-006 (GalNAc) 200K SERPINA1 (AATD) global license GalNAc-AIMer 100% global 9M PNPLA3 (liver

disease) GalNAc-AIMer 100% global 900K (30M expansion) LDLR (HeFH) GalNAc-AIMer 100% global 70K APOB (HeFH) R N A i WVE-007 (GalNAc) 100% global 175M INHBE (Obesity) GalNAc-siRNA 100% global -- Undisclosed S PLI C I N G WVE-N531 100% global 2.3K

Exon 53 (DMD) Other exons (DMD) 100% global Up to 18K A LLE LE - S E LE C T I VE S I LE NC I NG 25K Symptomatic (SNP3) WVE-003 100% global mHTT (HD) 60K Pre-Symptomatic (SNP3) Editing for correction Editing for upregulation 6 AATD: Alpha-1

antitrypsin deficiency; DMD: Duchenne muscular dystrophy; HD: Huntington's disease; HeFH: heterozygous familial hypercholesterolemia

WVE-007 GalNAc-siRNA silencing Obesity 7

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

obesity WVE-007 is a 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 living with obesity in US and Europe 8

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

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 Odds Ratio Favorable association

with liver traits Standard Deviations Standard Deviations Silencing INHBE mRNA by 50% is expected to recapitulate the healthy metabolic profile of heterozygous INHBE loss of function (LoF) carriers 9 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; cT1: corrected T1

INHBE GalNAc-siRNA 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 shrinks hepatokine Activin E adipose tissue adipocytes Decreased abdominal adiposity

leads to weight loss and reduced risk for CVD and T2D 10 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, in DIO mice 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 Preclinical data support INHBE GalNAc-siRNA as a single agent for healthy weight loss 11 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

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

curtail weight regain after the cessation of treatment with GLP-1 ~2x greater overall weight loss when added to Curtails weight regain after the cessation of GLP-1 GLP-1 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 12 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 Difference in body weight (% of PBS, same time point)

A single dose of INHBE GalNAc-siRNA led to shrinkage of adipocytes in

DIO mice Mean adipocyte diameter DIO Lean PBS INHBE GalNAc-siRNA ( m) 13 Data presented at ADA Scientific Sessions June 2025 ***p<0.001

A single dose of INHBE siRNA led to a lower inflammatory state of

visceral adipose tissues in DIO mice, with strong suppression of pro-inflammatory M1 macrophages in visceral fat Macrophages (M ) (F4/80) Pro-inflammatory (M1) M Anti-inflammatory (M2) M (CD11c) (CD163) INHBE GalNAc siRNA INHBE

GalNAc siRNA INHBE GalNAc siRNA PBS 3 mg/kg 10 mg/kg PBS 3 mg/kg 10 mg/kg PBS 3 mg/kg 10 mg/kg 1.0 0.8 0.6 0.4 0.2 0.0 PBS 3 mg/kg 10 mg/kg PBS 3 mg/kg 10 mg/kg PBS 3 mg/kg 10 mg/kg 14 Data presented at ADA Scientific Sessions June 2025

***p<0.001, *p<0.05, ns=non-significant %F4/80 positive area

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

to use WVE- 007 across multiple treatment settings with potential for 1-2x per 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 to semaglutide: gain upon cessation of No loss of muscle mass semaglutide and A single dose of

Wave's prevention of weight Reduction in fat mass with INHBE GalNAc-siRNA cycling, which worsens the preferential effect to the doubled the weight loss outcomes of various visceral fat observed with semaglutide metabolic diseases

Without suppressing food alone intake 15

INLIGHT: Phase 1 trial of WVE-007 in adults living with overweight or

obesity, otherwise healthy Randomized, double-blind, placebo-controlled (3:1) study of ascending doses of WVE-007 SAD Cohort 5 Trial Design MAD Cohort 3 Objective: Assess dose safety, tolerability, PK and PD SAD Cohort 4 Key

measurements MAD Cohort 2 Data expected 1Q26 - Primary: Safety and tolerability SAD Cohort 3 - Secondary: PK, Activin E 400 mg (n=32) - Exploratory PD: MAD Cohort 1 Data expected 4Q25 Body weight SAD Cohort 2 Body composition 240 mg

(n=32) Metabolic health Data expected 4Q25 Biochemical markers SAD Cohort 1 75 mg (n=8) INLIGHT expansion underway; IND application cleared by FDA 16 SAD: single-ascending dose; MAD: multi-ascending dose

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

AATD impacts multiple organ systems and has limited treatment options

AATD is a rare, inherited genetic disorder that is commonly caused by a G-to-A point mutation in the SERPINA1 gene Pi*ZZ genotype is leading cause of severe AATD, predisposing to progressive lung damage, liver damage or both

Aggregation of mutant Z-AAT protein in hepatocytes and a lack of functional, wild-type M-AAT drives liver and lung disease, respectively AATD Lung Disease AATD Liver Disease Treatment goal: Minimize episodic Treatment goal: Decrease

Emphysema Hepatocellular Fibrosis Cirrhosis Carcinoma Bronchiectasis exacerbations and associated damage Z-AAT protein Lung damage occurs during Progressive liver disease exacerbations that induce an results from

Z-AAT-induced inflammatory acute phase response, proteotoxic stress when more AAT protein is needed for protection Weekly IV augmentation therapy is only treatment option No approved therapies - No protective increase in AAT

protein levels during acute phase response without additional IV infusions ~200K people in the US and Europe are homozygous for the Z allele (Pi*ZZ genotype) 18 Strnad et al., 2020 N Engl J Med 382:1443-55; Blanco et al. 2017 Int J Chron Obstruct

Pulmon Dis 12:561-69

WVE-006: Potential first-in-class, convenient therapy for AATD that

addresses both liver and lung manifestations of disease WVE-006 Restore circulating M-AAT 1 2 Reduce Z-AAT protein (RNA editing) and physiological AAT aggregation in liver protein production Proprietary chemistry Subcutaneous

injection Z-AAT (GalNAc) Highly specific A I (no bystanders) M-AAT Infrequent RNA correction replaces mutant Z- dosing M-AAT reaches lungs to protect AAT protein with wild-type M-AAT from proteases and reduce risk of protein to reduce risk

of liver lung disease disease 19 Strnad et al., 2020 N Engl J Med 382:1443-55; Stoller et al., 1993 Alpha-1 Antitrypsin Deficiency GeneReviews.

RestorAATion-1 clinical trial in healthy volunteers complete,

RestorAATion-2 clinical trial in Pi*ZZ patients ongoing RestorAATion-1: Healthy Volunteers RestorAATion-2: AATD Patients RestorAATion-1: Healthy Volunteers SAD MAD Multi-dosing complete Up to seven doses in multi-dose portion 600 mg SAD

Cohort 3 MAD Cohort 3 400 mg SAD Cohort 2 MAD Cohort 2 400 mg 400 mg; 1x/month 200 mg SAD Cohort 1 MAD Cohort 1 100 mg 200 mg 200 mg Q2W 30 mg Study key objectives Safety and tolerability Pharmacokinetics Serum M-AAT levels 20 HV: healthy volunteer;

SAD: single-ascending dose; MAD: multi-ascending dose

RestorAATion-2: WVE-006 continues to be safe and well tolerated 200 mg

SAD 200 mg MAD 400 mg SAD N=8 N=8 N=8 TEAE Category No SAEs, discontinuations or n (%) n (%) n (%) withdrawals due to TEAEs Any TEAE 6 (75.0) 5 (62.5) 5 (62.5) All TEAEs were mild to Mild 2 (25.0) 0 1 (12.5) Moderate 4 (50.0) 5

(62.5) 4 (50.0) moderate in severity Severe 0 0 0 No treatment- Any drug-related TEAE 1 (12.5) 2 (25.0) 3 (37.5) related, clinically relevant Mild 1 (12.5) 1 (12.5) 1 (12.5) changes in labs, ECG, or vital Moderate 0 1 (12.5) 2 (25.0) signs

Severe 0 0 0 Any serious TEAE 0 0 0 Any TEAE leading to 0 0 0 discontinuation Any TEAE leading to death 0 0 0 21 Data as of August 26, 2025 SAD: single ascending dose MAD: multi-ascending dose

WVE-006 achieved key treatment goals of restoring MZ phenotype Total

AAT levels exceeded 11 M, production of wild-type M-AAT of greater than 50%, restored physiological AAT production Total AAT reached 20.6 M during Total AAT of up to ~13 M Wild-type M-AAT protein of acute phase response Protein

levels associated with lower 64% of total risk of AATD liver and lung diseases 200 mg MAD Cohort 11.9 M Total AAT 400 mg SAD Cohort 12.8 M Total AAT Acute phase response due to a kidney stone 22 Circulating M-AAT, Z-AAT, and total (M +

Z) AAT protein in the serum were measured by highly selective and sensitive LC-MS/MS assays (LLOQ: 0.096 M (M), 0.029 M (Z)) and reported as mean participant SAD and MAD maximums Mutant Z-AAT Wild-type M-AAT

200 mg cohort: Consistent M-AAT increase and Z-AAT decrease observed,

MAD significantly enhances effects versus SAD Increases in neutrophil elastase inhibition from baseline confirmed production of functional M-AAT Increase in M-AAT protein 7.2 4.8 p=0.012 Follow-up Dosing period SAD MAD MAD SAD Weeks Reduction (%) in

Z-AAT protein Dosing period Follow-up p=0.011 -47.3% -60.3% SAD MAD Weeks SAD MAD 23 Circulating M-AAT, Z-AAT, and total (M + Z) AAT protein in the serum were measured by highly selective and sensitive LC-MS/MS assays (LLOQ: 0.096 M (M), 0.029

M (Z)) and reported as mean participant SAD and MAD maximums Right: black line represents median Mutant Z-AAT Wild-type M-AAT Z-AAT ( M) M-AAT ( M)

First-ever demonstration of ability to restore physiological serum AAT

production; total AAT reached 20.6 M during acute phase response Pi*ZZ patients have a reduced capacity to produce AAT protein during an acute phase response 1 Following WVE-006 200 mg single dose, total AAT and M-AAT increased Published data

on CRP levels and AAT levels across different genotypes significantly in one patient during an acute phase response Total AAT Total AAT M-AAT M-AAT CRP 0 4 8 12 SAD MAD Acute phase response due to a kidney stone AAT response in Pi*ZZ participant

treated with WVE-006 mirrors Pi*MZ phenotype 24 1 - Sanders et al., J COPD, 2018 CRP: C-reactive protein Circulating M-AAT, Z-AAT, and total (M + Z) AAT protein in the serum were measured by highly selective and sensitive LC-MS/MS assays (LLOQ:

0.096 M (M), 0.029 M (Z)) and reported as mean participant SAD and MAD maximums M-AAT + Z-AAT ( M) CRP levels (mg/L)

Data from single dose cohorts support potential to further increase

serum AAT levels with 400 mg multidose cohort and monthly dosing 400 mg SAD Cohort As compared to 200 mg SAD Cohort 12.8 M 5.3 M Increases in M-AAT protein Total AAT M-AAT Greater % of M-AAT protein Greater