Wave Life Sciences Corporate Presentation

Wave Life Sciences Corporate Presentation January 5, 2018

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

Genetic medicines company Developing targeted therapies for patients impacted by rare

diseases Rationally designed stereopure nucleic acid therapeutics Utilizing multiple modalities including antisense, exon skipping and RNAi 6 proprietary neurology development

programs by the end of 2018 Expertise and core focus in neurology 2 Phase 1b/2a trials initiated in Huntington s disease DMD Exon 51 trial

initiated Clinical data readouts anticipated in 2019 for first 3 programs Robust R&D platform, ability to partner additional therapeutic areas Cash position $169MM as of

Paving the way to potentially safer, more effective medicines 1 6 3 10K+ first to design neurology clinical

studies Wave stereopure and bring stereopure development initiated oligonucleotides and allele-specific programs in 2017 created and medicines to clinic by end of 2018 analyzed to date 5 12+ 5 25M+ nucleic acid discovery programs therapeutic total

potentially modalities being areas under addressable patients advanced with Wave active investigation amenable to Wave s stereopure chemistry partnered and proprietary programs 4

Pipeline spanning multiple modalities, novel

U.S. ADDRESSABLE NEXT ANTICIPATED DISEASE TARGET BIOMARKER PATIENTS

* MILESTONES CNS Huntington s disease mHTT SNP1 mHTT ~10k / ~35k A Phase 1b/2a Top line data 1H 2019 Huntington s disease mHTT SNP2 mHTT ~10k / ~35k A Phase 1b/2a Top

line data 1H 2019 Amyotrophic lateral sclerosis C9orf72 dipeptide ~1,800 A Trial initiation Q4 2018 Frontotemporal dementia C9orf72 dipeptide ~7,000 A Trial

initiation Q4 2018 MUSCLE Duchenne muscular dystrophy 51 exon 51 dystrophin ~2,000 E Phase 1 Top line data Q3 2018 Duchenne muscular dystrophy 53 exon 53 dystrophin ~1,250 E Trial initiation Q1 2019

APOC3 A undisclosed A

undisclosed A A = allele-specific silencing. E = exon skipping. *Estimates of U.S. prevalence and

addressable population by target based on publicly available data and are approximate. *For Huntington s disease, numbers approximate manifest and pre-manifest populations, respectively 5

Neurology leadership Current programs Huntington s disease (HTT SNP1) Huntington s disease (HTT SNP2)

Duchenne muscular dystrophy (exon 51) Duchenne muscular dystrophy (exon 53) Amyotrophic lateral sclerosis (C9orf72) Frontotemporal dementia (C9orf72) Discovery engine Neuromuscular diseases DMD (additional exons) Spinal muscular atrophy (SMN2)

Charcot-Marie-Tooth type 1A (PMP22) Neurodegenerative movement disorders Spinocerebellar ataxia (ATXN3) Opportunities for expansion Neurodegenerative movement disorders Parkinson s disease Progressive supranuclear palsy Neurodegenerative

dementias Alzheimer s disease Developmental diseases Fragile X Batten disease Neurophysiology/ neuropsychiatry/pain Epilepsy Schizophrenia 6

Broad platform relevance across therapeutic areas CNS Muscle 7

Building the optimal, stereopure medicine STANDARD OLIGONUCLEOTIDE APPROACHES Pharmacologic properties include

>500,000 permutations in every dose Impact: Unreliable therapeutic effects Unintended off-target effects WAVE RATIONAL DESIGN Stereochemistry enables precise control, ability to optimize critical constructs

into one defined and consistent profile Impact: Potential for safer, more effective, targeted medicines that can address difficult-to-treat diseases 8

Creating a new class of oligonucleotides WAVE RATIONAL DESIGN Source: Iwamoto N, et al. Control of

phosphorothioate stereochemistry substantially increases the efficacy of antisense oligonucleotides. Nature Biotechnology. 2017. 9

Chemistry may optimize medicines across multiple dimensions Improved Stability Stability of stereopure

molecules with reduced PS content (liver homogenate) Controlled Immunogenicity Human TLR9 activation assay with 5mC modified CpG containing MOE gapmer Enhanced Delivery Stereochemistry enables enhanced delivery of oligonucleotides Oligonucleotides

exposure (spinal cord) Cytokine induction in human PBMC assay IL-6 MIP-1 ² Uptake without transfection agent between a stereopure and stereorandom

oligonucleotide Gymnotic uptake of ASOs:18h differentiating myoblasts Data represented in this slide from in vitro studies. Experimental conditions: Human TLR9 assay Source: Ohto U, et al. Structural basis of CpG and inhibitory DNA

recognition by Toll-like receptor 9, Nature 520, 702-705, 2015. Intracellular trafficking assay Cells were washed and fixed and oligos were detected by viewRNA assay and visualized on 10

immunofluorescence microscope with deconvolution capabilities. Z-stacks were taken to eliminate artifacts.

Stereochemistry is applicable across modalities Antisense RNAi Exon skipping *

Stereochemistry allows for novel approaches to previously difficult diseases and inaccessible targets 11

Transforming nucleic acid therapeutics SUPERIOR PHARMACOLOGY + SCALABLE SYNTHESIS MULTIMODALITY Antisense RNAi

Splice Correction Exon skipping Gene editing BROAD IMPACT CNS Muscle Eye Liver Skin UNLOCKING THE PLATFORM Broad addressable patient population across multiple therapeutic areas 12

Neurology CNS Muscle 13

Huntington s Disease 14

Neuro HD Huntington s Disease: a hereditary, fatal disorder Autosomal dominant disease, characterized by

cognitive decline, psychiatric illness and chorea; fatal No approved disease-modifying therapies Expanded CAG triplet repeat in HTT gene results in production of mutant huntingtin protein (mHTT); accumulation of mHTT causes progressive loss of

neurons in the brain Wildtype (healthy) HTT protein critical for neuronal function; suppression may have detrimental long-term consequences 30,000 people with Huntington s disease in the US; another 200,000 at risk of developing the condition

DNA CAG Repeat RNA RNA wildtype (healthy) allele mutant allele Normal CAG Repeat Expanded CAG Repeat Healthy protein (HTT) Mutant protein (mHTT) Sources: Auerbach W, et al. Hum Mol Genet. 2001;10:2515-2523. Dragatsis I, et al. Nat Genet. 2000;26:300-306. Leavitt BR, et al. J Neurochem. 2006;96:1121-1129. Nasir J, et al. Cell. 1995;81:811-823. Reiner A, et al. J Neurosci. 2001;21:7608-7619. White JK, et al. Nat

Genet. 1997;17:404-410. Zeitlin S, et al. Nat Genet. 1995;11:155-163. Carroll JB, et al. Mol Ther. 2011;19:2178-2185. 15

Wave approach: novel, allele-specific silencing Neuro HD Utilize association between single nucleotide

polymorphisms (SNPs) and genetic mutations to specifically target errors in genetic disorders, including HD. Allele-specificity possible by targeting SNPs associated with expanded long CAG repeat in mHTT gene Approach aims to lower mHTT transcript

while leaving healthy HTT relatively intact Potential to provide treatment for up to 70% of HD population (either oligo alone could address approximately 50% of HD population) expanded SNP 1 ~50% of patients SNP 2 ~50% of patients ~20% of patients

may carry both SNP1 AND SNP 2 Total: Due to overlap, an estimated ~70% of the total HD patient population carry SNP 1 and/or SNP 2 Source: Kaye, et al. Personalized gene silencing therapeutics for Huntington disease. Clin Genet 2014: 86: 29 36

Two simultaneous Phase 1b/2a clinical trials Neuro HD Two parallel global placebo-controlled

multi-ascending-dose trials for WVE-120101, WVE-120102 Primary objective: assess safety and tolerability of intrathecal doses in early manifest HD patients Additional

objectives: exploratory pharmacokinetic, pharmacodynamic, clinical and MRI endpoints Blood test to determine presence of SNP 1 or SNP 2 done at pre-screening Approximately 50 patients per trial Key inclusion

criteria: age 25 to 65, stage I or II HD Top line data anticipated 1H 2019 17

Neuro HD Mutant huntingtin: a powerful, novel biomarker Novel immunoassay allows for quantification of mutant

huntingtin, the cause of HD Level of mHTT detected is associated with time to onset, increased with disease progression, and predicts diminished cognitive and motor dysfunction Assay currently being utilized in clinical studies Novel approach

enables precise measurement of target engagement and effect Source: Wild E, et al. Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington s disease patients. J. Clin. Invest. 2015:125:1979 1986. Edward Wild, MA

MB BChir PhD MRCP Principal Investigator at UCL Institute of Neurology and Consultant Neurologist at the National Hospital for Neurology and Neurosurgery, London 18

Neuro HD Selective reduction of mHTT mRNA & protein Reporter Cell Line* 19

Neuro HD Demonstrated delivery to brain tissue WVE-120101 and WVE-120102 distribution in cynomolgus non-human primate brain following intrathecal bolus injection CIC = cingulate cortex In Situ Hybridization ViewRNA stained tissue Red

dots are WVE-120101 oligonucleotide. Arrow points to nuclear and perinuclear distribution of WVE- 120101 in cingulate cortex CIC = cingulate cortex. CN = caudate

nucleus. CN = caudate nucleus In Situ Hybridization ViewRNA stained tissue Red dots are WVE-120102 oligonucleotide. Arrow points to nuclear and perinuclear distribution of

WVE-120102 in caudate nucleus 20

Duchenne Muscular Dystrophy (DMD) 21

Neuro DMD DMD: a progressive, fatal childhood disorder Fatal, X-linked

genetic neuromuscular disorder characterized by progressive, irreversible loss of muscle function, including heart and lung Genetic mutation in dystrophin gene prevents the production of dystrophin protein, a critical component of healthy muscle

function Symptom onset in early childhood; one of the most serious genetic diseases in children worldwide Current disease modifying treatments have demonstrated minimal dystrophin expression and clinical benefit has not been established Impacts 1 in

every 3,500 newborn boys each year; 20,000 new cases annually worldwide 22

Neuro DMD Wave approach: meaningful restoration of dystrophin production through exon skipping Meaningful

restoration of dystrophin production is expected to result in therapeutic benefit Exon-skipping antisense approaches may enable production of functional dystrophin protein Initial patient populations are those amenable to Exon 51 and Exon 53

Neuro DMD Exon 51: WVE-210201 clinical program WVE-210201 Phase 1 clinical trial initiated November 2017 Design: Multicenter, double-blind, placebo-controlled, single ascending dose study with I.V. administration Primary endpoint: Safety and

tolerability Inclusion criteria: ages 5 to 18, amenable to exon 51 skipping Ambulatory and non-ambulatory boys eligible, including those previously treated with eteplirsen (following appropriate washout

period) Readout expected Q3 2018 Planned open-label extension (OLE) with muscle biopsy and 2-years of follow-up WVE-210201 planned efficacy study Design: Double-blind, placebo-controlled, multi-dose study assessing dystrophin expression and clinical outcomes Measurement of

dystrophin via standardized Western Blot Interim analysis of dystrophin expression in muscle biopsies Efficacy readout anticipated 2H 2019 Exploring intravenous and subcutaneous formulations for

Neuro DMD Exon 51: improved skipping efficiency RNA skipping determined by quantitative RT-PCR Wave isomers demonstrated a dose-dependent increase in skipping efficiency Free uptake at 10uM concentration of each compound with no transfection agent Same foundational stereopure chemistry for Wave

isomers; individually optimized to assess ideal profile 25

Neuro DMD Exon 51: increased dystrophin restoration dystrophin (400-427

kDa) vinculin (120 kDa) *Analogs WVE-210201 dystrophin (400-427 kDa) vinculin (120 kDa) Dystrophin protein restoration in vitro was quantified to be between 50-100% of normal skeletal muscle tissue lysates, as compared to about 1% by drisapersen and eteplirsen analogs Experimental conditions: DMD protein restoration by Western Blot in patient-derived myotubes with clear

dose effect. Free uptake at 10uM concentration of each compound with no transfection agent 26

Neuro DMD Exon 51: target engagement in healthy non-human primate

Nested PCR Assay 5 doses @ 30 mg/kg /week for 4 weeks healthy NHP by subcutaneous dosing Experimental conditions: Muscle tissues were collected 2 days after the last dose and fresh frozen. Total RNAs were extracted with phenol/chloroform and

converted to cDNA using high capacity kit. Nested PCR assay was performed and analyzed by fragment analyzer. 27

Neuro DMD Exon 51: no apparent tissue accumulation observed Single

in-vivo I.V. dose at 30 mpk in MDX 23 mice Standard oligonucleotides tend to accumulate in liver and kidney Wave rationally designed oligonucleotides optimized to

allow compound to clear more effectively WVE-210201 demonstrated wide tissue distribution in dose dependent fashion No apparent accumulation observed after

multiple doses Experimental description: Oligo quantifications in tissues were performed using hybridization ELISA assay 28

Neuro DMD Exon 53: Stereopure lead molecules advancing toward candidate RNA skipping

determined by quantitative RT-PCR Free uptake at 10uM and 3uM concentration of each compound with no transfection agent Current published clinical dystrophin

levels achieved for Exon 53 are ~1% Early Exon 53 data suggests initial skipping efficiency around 20% pre-optimization 29

C9orf72 Amyotrophic Lateral Sclerosis (ALS) Frontotemporal Dementia (FTD) 30

Neuro C9orf72 C9orf72: a critical genetic risk factor C9orf72 gene provides instructions