Wave Life Sciences Corporate Presentation

Wave Life Sciences Corporate Presentation November 17, 2025

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 orachievements 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 ofrisks,

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 publiclyupdate or revise any forward-looking statements contained herein, whether as a result ofany new information, future events, changed circumstances or otherwise.

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

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) Novel approach designed to Pioneering a novel RNA Potential best-in-class Leadership in allele-reduce fat, preserve muscle

modality with RNA editing profile selective silencing WVE-007 in Obesity WVE-006 in AATD WVE-N531 in DMD WVE-003 in HD Strong and broad IP In-house GMP manufacturing Well-capitalized with cash runway into 2Q 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 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)

Robust, diversified RNA medicines pipeline including first-in-class RNA editing and RNAi programs IND / CTA Enabling Patient population

Program Discovery Clinical Rights Studies (US & Europe) RNA EDITING WVE-006 (GalNAc) GSK exclusive 200K SERPINA1 (AATD) global license WVE PNPLA3 -008 (liver (GalNAc) disease) 100% global 9M GalNAc Multiple / extra-hepatic 100% global -- RNAi

WVE-007 (GalNAc) 175M 100% global INHBE (obesity) (>1 billion globally) GalNAc / extra-hepatic 100% global -- Multiple SPLICING WVE-N531 100% global 2.3K Exon 53 (DMD) Other exons (DMD) 100% global Up to 18K ALLELE-SELECTIVE SILENCING WVE-003 25K

Symptomatic (SNP3) 100% global mHTT (HD) 60K Pre-Symptomatic (SNP3) AATD: Alpha-1 antitrypsin deficiency; DMD: Duchenne muscular dystrophy; HD: Huntington's disease

WVE-007 GalNAc siRNA silencing Obesity

Obesity is a metabolic disease with a treatment paradigm ripe for disruption Advancing WVE-007, a GalNAc-siRNA, as a novel, long acting,

muscle sparing approach for obesityAdults 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 > 1 billion people living with obesity globally 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 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

Silencing INHBE mRNA has potential to treat obesity and associated metabolic diseases Release of dimerized INHBE Binds to and activates

ACVR1C subunits creates hepatokine (ALK7) receptor in adipose tissue Block adipose Activin E lipolysis Activin E Activin E Increased abdominal adiposity leads to obesity, II II I I CVD and T2D Adipocyte ALK7 Decreased abdominal adiposity leads to

weight loss Reduction of and reduced risk for INHBE mRNA with CVD and T2D GalNAc-siRNA Diminished activation of Reduced release of Increased adipose hepatokine Activin E ACVR1C (ALK7) receptor in lipolysis and shrink adipose tissue adipocytes 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.

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 Epididymal fat weight (Day 28) Quadricep 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

Combined with GLP-1: Greater weight loss After cessation of GLP-1: Curtails weight re-gain ht point) weig p<0.05 time body in same ~2x greater PBS, weight loss of Not Difference 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. Left Stats: Linear Mixed Effects ANOVA with post hoc comparisons of marginal treatment effects of Semaglutide vs. Semaglutide + INHBE GalNAc-siRNA per time point * p <

0.05; Right Stats: Linear Mixed Effects ANOVA with post hoc comparison of Day 28 vs. Day 56 marginal effects per treatment * p < 0.05

Potent and durable Activin E reduction of greater than 70% in preclinical models delivers weight loss similar to GLP-1 Durable Activin E

reduction one-month Weight loss with INHBE GalNAc-siRNA following a single dose more gradual versus semaglutide 150 l ) tr o on 100 (%C INHBE siRNA E n tivi 50 c %A semaglutide 0 PBS semaglutide INHBE GalNAc-siRNA Single dose INHBE GalNAc-siRNA 13

Semaglutide 10 nmol/kg in mouse is equivalent to therapeutic dose of GLP-1s in human; INHBE GalNAc-siRNA 10 mg/kg dose

Treatment with INHBE GalNAc-siRNA expected to improve key measures of cardiometabolic health Measures of metabolic improvements

Reduction of INHBE mRNA and circulating Activin E Fat reduction Adipocyte Adipocyte Improved lipolysis size cardiometabolic outcomes Insulin sensitivity Proinflammatory Risk of CVD macrophages in adipose Risk of T2D Fibrosis 14

INLIGHT: Dose escalation continues in single-dose portion, follow-up ongoing from multiple therapeutic cohorts Randomized, double-blind,

placebo-controlled (3:1) study of ascending doses of WVE-007 Objective: Assess dose safety, tolerability, PK and PD SAD Cohort 5 Key study criteria: MAD Cohort 3 - HbA1c: <5.9 SAD Cohort 4 - BMI: 28 - 35 kg/m2 (SAD) 600 mg

(Expanded to n=32) Key measurements MAD Cohort 2 - Primary: Safety and tolerability SAD Cohort 3 400 mg (Expanded to n=32) - Secondary: PK, Activin E Exploratory PD: MAD Cohort 1 - SAD Cohort 2 Body weight 240 mg (Expanded to n=32)

Body composition (including DEXA) SAD Cohort 1 Biomarkers 75 mg (n=8) Multiple clinical trial sites, including US

Highly significant, dose dependent Activin E reductions following a single dose of WVE-007 Activin E change in INLIGHT -56% -75% -85%

Single dose WVE-007 (GalNAc-siRNA) 16 Figure shows sample means and SEMs. All MMRM baseline and placebo comparisons from Day 8 onwards are p<0.007. For change from baseline at day 29 all dose groups were p<0.0001. Placebo includes one

individual from 400 mg expansion.

Highly durable Activin E reductions with WVE-007 supporting dosing once or twice per year Activin E change in INLIGHT Single dose

WVE-007 (GalNAc-siRNA) 17 Figure shows sample means and SEMs. All MMRM baseline and placebo comparisons from Day 8 onwards are p<0.007. Placebo includes one individual from 400 mg expansion.

Clinical Activin E reductions after single dose of WVE-007 exceed levels leading to weight loss in preclinical studies Preclinical

studies INLIGHT clinical trial >70% Activin E reductions led to weight loss >70% Activin E reductions achieved INHBE siRNA semaglutide Daily GLP-1 Single dose WVE-007 (GalNAc-siRNA) Single dose INHBE GalNAc-siRNA Placebo WVE-007 75 mg WVE-007

240 mg WVE-007 400 mg 18 Left: semaglutide 10nmol/kg in mouse is equivalent to therapeutic dose of GLP-1s in humans

Multiple near-term clinical anticipated data updates for WVE-007, including body weight and body composition Research Day 2025 update:

WVE-007 led to dose-dependent, potent and durable Activin E reductions in INLIGHT clinical study - Activin E reductions exceed levels that led to weight loss in preclinical models - Potential for once or twice yearly dosing Generally

safe and well-tolerated to date; 600 mg ongoing (Cohort 4) Follow-up ongoing with multiple clinical data updates expected starting in 4Q 2025 4Q 2025 1Q 2026 2Q 2026 600 mg 3 month follow-up (n=32) 400 mg 3 month follow-up (n=32) 6 month

follow-up (n=32) 240 mg 3 month follow-up (n=32) 6 month follow-up (n=32) 9 month follow-up (n=32) 75 mg Follow-up (n=8)

WVE-006 RNA editing (AIMer) 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 Emphysema Treatment goal: Minimize episodic Hepatocellular Treatment goal: Decrease Bronchiectasis exacerbations and

associated damage Fibrosis Cirrhosis Carcinoma 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) 21 Strnad et al., 2020 N Engl J Med 382:1443-55; Blanco et al. 2017 Int J Chron Obstruct Pulmon Dis 12:561-69

WVE-006: Potential first-in-class, convenient therapy for AATD that addresses both liver and lung manifestations of the disease WVE-006

Restore circulating M-AAT (RNA editing) 1 2 Reduce Z-AAT protein and physiological AAT aggregation in liver protein production Proprietary chemistry Highly specific (no bystanders) Z-AAT Subcutaneous injection (GalNAc) M-AAT RNA correction replaces

mutant M-AAT reaches lungs to protect Z-AAT protein with wild-type M-AAT Infrequent dosing from proteases and reduce risk of protein to reduce risk of liver lung pathology pathology 22 Strnad et al., 2020 N Engl J Med 382:1443-55; Stoller et al.,

1993 Alpha-1 Antitrypsin Deficiency GeneReviews. M-AAT: Wild-type alpha-1 antitrypsin protein Z-AAT: mutant alpha-1 antitrypsin protein

RNA editing aims to increase M-AAT and restore physiological AAT production during acute phase response Genotype Null PiZZ PiMZ Pi*MM

No AAT protein 100% Z-AAT Z-AAT and M-AAT 100% M-AAT AAT levels increase during No No Yes Yes acute phase response Risk of lung disease Very high High Low Normal Risk of liver disease None High Low Normal >50% RNA editing > 11 M AAT

Goal: Shift PiZZ individuals to AAT biomarker profile consistent with PiMZ genotype 23

RNA editing aims to restore production of dynamic and therapeutically relevant levels of AAT protein in Pi*ZZ individuals during acute

phase response Lung damage occurs during exacerbations, when AAT protein has protective functions and is produced more AAT protein is needed for protection during acute phase response 30,100 PiZZ 30,100 PiMZ 30,000 30,000 700 CRP 700 CRP 600

plasma 600 500 in 500 400 (%) 400 300 change 300 AAT protein 200 AAT protein 200 100 Percent concentration 100 0 0 0 7 Days 14 21 0 7 14 21 Days Inflammatory stimulus Inflammatory stimulus RNA editing has potential to restore dynamic AAT response to

inflammation 24 Left: Mantovani A, Garlanda C. N Engl J Med, 2023;388:439-452; Right: Sanders et al., J COPD, 2018

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 Following WVE-006 200 mg single dose, total AAT and M-AAT increased Published data1 on CRP levels and AAT significantly in one patient during an

acute phase response levels across different genotypes Total AAT ( M) Total AAT (mg/L) AAT Z - + M-AAT levels AAT M-AAT M - CRP 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 25 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

WVE-006 enables endogenous AAT production during an acute phase response while augmentation therapy leaves patients at risk Illustrative

model of impact of acute phase response Augmentation therapy WVE-006 treatment approach Lung Protected damage lungs Endogenous AAT levels increase during acute AAT AAT phase response without need for add'l doses Serum Serum Exogenous AAT

levels are depleted before next scheduled IV dose IV dosing RNA editing dose Augmentation therapy has no impact on liver disease WVE-006 also reduces levels of Z-AAT augmentation WVE therapy -006 therapeutic goal is to maximize goal is

to AAT restore levels dynamic as dynamic AAT physiology; response is not enabled 26

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 Plasma AAT of ~13 M Wild-type M-AAT protein of 64% AAT reached >20 M during an of total, reduction in Z-AAT acute phase response Protein levels associated with lower

risk of AATD liver and 200 mg multidose cohort: lung diseases - AAT M 400 mg single dose type - WildCRP 12.8 M total AAT (mg/L) - AAT 200 mg multidoseZ 11.9 M total AAT Mutant Acute phase response due to a kidney stone 27 Circulating