Wave Life Sciences Corporate Presentation

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UNLOCKING THE BODY'S OWN ABILITY TO TREAT GENETIC DISEASE

realizing a brighter future for patients and families 3

Building a leading genetic medicines company LEVERAGING THE ONGOING

TARGETING THE TRANSCRIPTOME TO UNLOCK THE GENETIC REVOLUTION BODY'S OWN ABILITY TO TREAT GENETIC DISEASE >6,000 monogenic Increase in Innovative Platform Diversified Pipeline diseases; genetic vastly more Stereopure oligonucleotides CNS:

ALS, FTD, HD testing polygenic diseases Novel backbone modifications Muscle: DMD (PN chemistry) Hepatic diseases: AATD Silencing, splicing, and editing modalities Biomarkers to Greater assess target understanding Strong and broad IP engagement of

genetic 1 position early in disease and clinical cellular development biology Clinical Expertise GMP Manufacturing Multiple global clinical trials Internal manufacturing capable of producing Many Innovative trial designs Innovations for

oligonucleotides at scale diseases precise modification out of reach of transcriptome, for proteome and traditional interactome medicines 4 ALS: Amyotrophic lateral sclerosis; FTD: Frontotemporal dementia; HD: Huntington's disease; DMD:

Duchenne muscular dystrophy; AATD: Alpha-1 antitrypsin deficiency 1 stereopure oligonucleotides and novel backbone chemistry modifications

Wave's ability to rationally design oligonucleotides enables

access to unique disease targets PRISM backbone linkages PO PS PN (Sp) (Rp) - - O S N Phosphoryl guanidine Chirality Chirality Chirality x-ray structure None PN backbone Rp PS backbone Rp PN backbone

Sp PS backbone Sp Negative Negative Neutral example charge charge charge PO: phosphodiester PS: phosphorothioate 5

Harnessing the biological machinery in our cells to treat genetic

diseases RNA Base Editing Silencing Splicing Degradation of RNA transcripts Restore RNA transcripts and Efficient editing of RNA bases to turn off protein production turn on protein production to restore or modulate protein

production Endogenous RNase H Endogenous AGO2 RISC Endogenous Restored Reading ADAR enzyme Frame 6

Unlocking the body's own ability to treat genetic disease DESIGN

OPTIMIZE Chemistry Unique ability to construct Provides the resolution to Sequence stereopure oligonucleotides observe this structural and control three structural interplay and understand how features to efficiently engage it impacts key

pharmacological biological machinery properties Stereochemistry Built-for-Purpose Candidates to Optimally Address Disease Biology Silencing | Splicing | RNA Editing 7

Robust portfolio of stereopure, PN-modified oligonucleotides THERAPEUTIC

AREA / TARGET MODALITY DISCOVERY PRECLINICAL CLINICAL RIGHTS N N EE U U R R OL OL OG OG YY ALS and FTD WVE-004 (FOCUS-C9) C9orf72 Takeda 50:50 option Huntington's disease WVE-003 (SELECT-HD) mHTT SNP3 SCA3 ATXN3 CNS diseases Multiple DMD

WVE-N531 Exon 53 100% global H H EEP PA A TT II CC (GalNAc) AATD - lung and liver disease WVE-006 SERPINA1 Therapeutic Silencing Splicing ADAR editing (AIMers) modality ALS: Amyotrophic lateral sclerosis; FTD: Frontotemporal dementia; SCA3:

Spinocerebellar ataxia 3; CNS: Central nervous system; DMD: Duchenne muscular dystrophy; AATD: Alpha-1 antitrypsin deficiency 8

WVE-004 Amyotrophic Lateral Sclerosis (ALS) Frontotemporal Dementia

C9orf72 repeat expansions: One of the most common genetic causes of ALS

and FTD Hexanucleotide (G C )- repeat 4 2 expansions in C9orf72 gene are common autosomal dominate cause for ALS and FTD Typically 100's- 1000's of GGGGCC repeats Different manifestations across a clinical spectrum Amyotrophic Lateral

Sclerosis (ALS) Frontotemporal Dementia (FTD) Fatal neurodegenerative disease Progressive neuronal degeneration in frontal / temporal cortices Progressive degeneration of motor neurons in Personality and behavioral

changes, gradual brain and spinal cord impairment of language skills C9-specific FTD: ~10,000 patients in US C9-specific ALS: ~2,000 patients in US Including patients with C9-associated ALS, FTD or both Sources: Balendra et al, EMBO

Mol Med, 2017; Brown et al, NEJM, 2017, DeJesus-Hernandez et al, Neuron, 2011. Renton et al, Neuron, 2011. Zhu et al, Nature Neuroscience, May 2020, Stevens et al, Neurology 1998 10

WVE-004 addresses each biological aspect of C9orf72- associated ALS and

FTD RNA variants Disease drivers C9orf72 protein V1 V2 V3 C9orf72 Poly(GP) biomarker 1 Decrease in Genetic mutation Loss-of- selected as preferred beneficial function protein Reduced DPR biomarker Repeat- Wild-type expression expanded C9orf72

Abundant in CNS allele allele Dipeptide repeat proteins (DPRs) Most soluble 2 Sense: poly(GA), poly(GR) Stable expression Antisense: poly(PR), poly(PA) RAN Transcription translation Only DPR derived Sense & Antisense:

poly(GP) Gain-of- from both sense & function Pathological RNAs RNA foci antisense RNAs Mis-spliced RNA 3 Sense & Stabilized intron 1 Toxic RNA Antisense RNA Antisense aggregation WVE-004 is Variant-selective Preserves C9orf72 Reduces toxic

designed to oligonucleotide, protein expression; does gain-of-function affect multiple lowering V1 & V3 not exacerbate potential drivers of drivers of in preclinical loss-of-function driver of disease (RNA 1 toxicity studies disease foci, DPRs)

11 1 Liu et al., 2022 Mol Ther Nuc Acids doi: 10.1016/j.omtn.2022.04.007

ug of oligo / g of tissue ug of oligo / g of tissue Preclinical studies

with WVE-004 demonstrated durable reduction of poly(GP) in spinal cord and cortex 6 months after two doses Preclinical in vivo results: C9orf72 protein Six months unchanged at 6 months Spinal Spinal cord 8 150 1.5 1.5 cord ns 6 100 1.0 1.0 4 >90%

knockdown of poly(GP) DPR protein 50 0.5 0.5 2 *** ** * *** 0.0 0 0 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 PBS WVE-004 PBS WVE-004 Weeks 150 Cortex 1.5 Cortex 1.5 8 ns 100 6 1.0 1.0 4 >80% knockdown of 50 0.5 0.5

p 0.0001 poly(GP) DPR protein 2 0.0 0.0 0 0 PBS WVE-004 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 PBS WVE-004 Weeks Two doses of WVE-004 WVE-004: WVE-004: PBS Poly(GP) DPR Oligonucleotide concentration 12 Liu et al.,

2022 Molecular Therapy Nucleic Acids doi: 10.1016/j.omtn.2022.04.007; 2 x 50 ug (day 0, day 7) dosed ICV; DPRs measured by poly(GP) MSD assay. *: p 0.05 **: P 0.01, ***: P 0.001. DPR: Dipeptide repeat protein Relative poly(GP)

levels Relative poly(GP) levels (normalized to PBS) (normalized to PBS) Relative fold change Re Re la la titviv e f e f olol d c d hc aha nge ng e Relative fold change C9orf72/HPRT1 C9orf72/HPRT1 C9orf72/HPRT1 C9orf72/HPRT1

WVE-004 clinical data demonstrate successful translation of preclinical

approach to clinic Target engagement confirmed in patients PK/PD modeling using preclinical in vivo models predicted pharmacodynamically supports advancing FOCUS-C9 clinical study active starting dose Poly(GP) reduction in cortex and spinal

cord in transgenic mice with WVE-004 Sufficient concentrations of WVE-004 in cortex and spinal cord of NHP for target engagement PK: pharmacokinetic PD: pharmacodynamic; Right: Mixed model for repeated measures used to estimate geometric mean

ratio to baseline via least squares mean and to calculate p- values. P-values represented by asterisks are for within-dose group geometric mean ratios. *p 0.05, **p 0.01, ***p 0.001. Poly (GP) assay: Wilson et al., 2022 J Neurol

Neurosurg 13 Psychiatry doi:10.1136/jnnp-2021-328710. Data presented at ENCALS Meeting (June 1-3, 2022) and International Congress on Frontotemporal Dementias (Nov. 2 - 5, 2022)

Dosing ongoing in FOCUS-C9 clinical trial with multiple doses of

WVE-004 Open-label Single dose Multidose extension (OLE) 60 mg n=4 Dose and frequency to be guided by DSMB Target 30 mg engagement n=10 OLE clinical trial observed in 20 mg initiated in 4Q 2022 20 mg single dose n=10 n=10 Quarterly doses

cohorts 10 mg 10 mg 10 mg n=10 n=6 n=3 Quarterly doses 4 monthly doses Data from all cohorts in the FOCUS-C9 trial are expected in 1H 2023 14

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 16

WVE-003: Only investigational HD therapy in clinical development

designed to lower mHTT while sparing wtHTT wtHTT supports healthy brain function, WVE-003 especially in the context of stress Regulates synaptic plasticity Unique and innovative wildtype HTT- sparing oligonucleotide Supports synaptic protein

Delivered to CNS without invasive transport surgical procedures No complex delivery vehicles required Promotes neuronal survival (e.g. AAV) Designed with next-generation PN Supports cilia and CSF chemistry circulation mHTT, mutant HTT; wtHTT,

wild-type HTT; PO, phosphodiester; PS, phosphorothioate; PN, phosphoryl guanidine; wtHTT literature sources: 1. Leavitt 2006 2. Cattaneo 2005 3. Kumar 17 2016 4. Franco-Iborra 2020 5. Hamilton 2015 6. Ochaba 2014 7. Wong 2014 8. Rui 2015 9. Caviston

2007 10. Twelvetrees 2010 11. Strehlow 2007 12. Milnerwood 2010 13. Smith- Dijak 2019 14. Tousley 2019 15. Zhang 2018 16. McAdam 2020 17. Altar 1997 18. Zuccato 2001 19. Gauthier 2004 20. Ferrer 2000 21. Baquet 2004 22. Liu 2011 23. Karam

Allele-selective molecule decreases mHTT, spares wtHTT; Pan-silencer

uniformly decreases both Allele-selective activity in CNS of Hu97/18 mice mHTT wtHTT Cortex Striatum 150 150 **** * *** **** *** **** **** **** 100 100 50 50 0 0 4 8 12 4 8 12 4 8 12 4 8 12 4 8 12 4 8 12 Time (weeks) Time (weeks) Pan-silencing

Allele-selective PBS Pan-silencing Allele-selective PBS control molecule control molecule Hu97/18 mice administered 3x100 g intracerebroventricular doses PBS or oligonucleotide. Relative mHTT RNA in cortex (left) striatum (middle) or

hippocampus (right) at 4, 8 and 12-weeks post-dosing. Data are mean SD, n=8. Stats: ns non-significant, *P<0.05, **P<0.01, ***P<0.0001, 18 ****P<0.0001 versus PBS by 1-way ANOVA. mHTT, mutant HTT; wtHTT, wild-type HTT; Tubb,

tubulin Hu97/18 mouse Percentage HTT RNA expression (mHTT/Tubb - PBS)

WVE-003 (SNP3) demonstrates selective, potent, and durable reduction of

mHTT in preclinical models Selectively reduces mHTT mRNA in Durable striatal mHTT knockdown for 12 weeks in BACHD mouse model HD iPSC neurons in vitro *** **** **** **** **** **** Weeks PBS Pan-silencing WVE-003 reference compound Pan-silencing

WVE-003 reference compound Similar results in cortex Results from ND50036 iPSC-derived medium spiny neurons. Total HTT knockdown quantified by qPCR and normalized to HPRT1. Oligonucleotide or PBS [100 g ICV 19 injections through cannula on

days 1, 3, 5] delivered to BACHD transgenic. Mean SD (n=8, *P<0.0332, ***P<0.0002, ****P<0.0001 versus PBS unless otherwise noted). HPRT1, hypoxanthine-guanine phosphoribosyl transferase; iPSC, induced pluripotent stem cell; ICV,

intracerebroventricular; PBS, phosphate-buffered saline Percentage HTT mRNA Remaining

Initial clinical results indicating allele-selective target engagement

suggests translation of preclinical data Reductions in mean CSF mHTT and preservation of wtHTT observed in PK/PD modeling using preclinical pooled analysis of single dose cohorts in SELECT-HD clinical study in vivo models mHTT protein levels wtHTT

protein levels Placebo WVE-003 (30 and 60 mg Allele selectivity (Hu97/18 mice) pooled*) mHTT reduction in cortex and striatum (transgenic mice) Concentrations in NHP brain tissues sufficient for target engagement Single dose

Single dose of WVE-003 of WVE-003 or placebo or placebo 20 mHTT: mutant huntingtin protein wtHTT: wild-type huntingtin protein *Pooled considering no apparent dose response between 2 cohorts

Expanding single dose cohorts to optimize dose level based on initial

clinical results mHTT protein reductions Adapting 90 mg Expanding cohort observed in single dose clinical trial to cohorts optimize dose level 60 mg Adding patients to wtHTT protein levels appear Expanding cohort each cohort

consistent with allele- selectivity 30 mg Generally safe and well- Expanding cohort tolerated Additional single-dose biomarker and safety data are expected in 1H 2023 21 mHTT: mutant huntingtin wtHTT: wild-type huntingtin

WVE-N531 Duchenne muscular dystrophy

Duchenne muscular dystrophy Duchenne muscular dystrophy Genetic

mutation in dystrophin gene prevents the production of dystrophin protein, a critical component of healthy muscle function. Dystrophin protein established by FDA as surrogate endpoint reasonably likely to predict benefit in 1 patients for

accelerated approval in DMD - Confirmatory studies ongoing - Increasing amount of functional dystrophin expression over minimal amount shown with approved therapies is expected to result in greater benefit for patients Impacts 1

in every 5,000 newborn boys each year; 20,000 new cases annually worldwide. 1 23 Vyondys: www.fda.gov; viltepso; www.fda.gov; Exondys; www.fda.gov; Amondys: www.fda.gov

PN chemistry improved muscle exposure and survival in preclinical mouse

models PN boosted muscle concentrations after Treatment with PN-modified molecules led to 100% single dose, which correlated with survival of dKO mice at time of study termination exon-skipping activity 100 Better tissue exposure PS/PO/PN, 150 mg/kg

weekly PS/PO/PN, 75 mg/kg bi-weekly 75 PN PS/PO, 150 mg/kg weekly PBS 50 25 PN 0 0 4 8 12 16 20 24 28 32 36 40 Time (weeks) Note: Untreated, age-matched mdx mice had 100% survival at study termination [not shown] Kandasamy et al., 2022; doi:

10.1093/nar/gkac018 24 Survival probability (%)

PS/PO/PN splicing compound restores muscle and respiratory function to

wild-type levels in dKO mice Muscle Function Respiratory Function Minute Volume Tidal Volume Specific Force (EDL) 300 150 0.3 200 100 **** 0.2 **** 50 100 0.1 0 0 0.0 21 28 35 42 49 Wild-type 20 40 60 80 100 120 21 28 35 42 49 Age (days) dKO: PBS

Age (days) Stimulation Frequency (Hz) dKO: PS/PO/PN Estimated Peak Inspiratory Flow Estimated Peak Expiratory Flow Eccentric Concentration 120 10 6 Wild-type 100 8 dKO / PBS **** 80 **** 4 dKO (PS/PO/PN 6 oligonucleotide) 60 4 40 2 2 20 0 0 0 21 28

35 42 49 21 28 35 42 49 0 1 2 3 4 5 6 7 8 9 10 Age (days) Age (days) Contraction Left: Mdx/utr-/- mice received weekly subQ 150 mg/kg dose of PS/PO/PN stereopure oligonucleotide (postnatal day 10). Age-matched mdx/utr-/- littermates treated with 25

PBS, wild-type C57BL10 mice not treated. Wild-type, dKO PBS mice: 6 wks old; dKO PS/PO/PN: 28 - 41 wks old; Electrophysiology performed at Oxford University based on Goyenvalle et al., 2010 Mol Therapy; Right: Kandasamy et al., 2022; doi: