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J.P . Morgan Healthcare Conference January 13, 2026 Wave Life Sciences
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2 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.
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3 To unlock the broad potential of RNA medicines to transform human health Our Mission
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4 1 Preliminary, unaudited cash and cash equivalents of ~$602 million are as of December 31, 2025. These preliminary, unaudited r esults are subject to adjustment. Wave expects to report its final and complete fourth-quarter and full-year 2025 financial results in late February 2026, and the actual results could be different from these preliminary, unaudited financial results Well capitalized with ~$602 million1 and expected cash runway into 3Q 2028 Building a leading RNA medicines company Differentiated RNA medicines platform and chemistry • Proprietary chemistry • Leveraging deep insights in human genetics • Strong and broad IP • In-house GMP manufacturing Translating genetic insights into potentially best-in-class medicines WVE-007 (obesity) • Differentiated mechanism focused on fat loss and muscle preservation WVE-006 (AATD) WVE-008 (liver disease) • Restoration of functional protein production Unlocking emerging pipeline RNAi RNA editing Other modalities: DMD and HD clinical programs • Extra-hepatic capabilities: with RNAi and RNA editing • Novel bifunctional modality: simultaneously edit and silence with single oligonucleotide construct
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5 RNAi — SpiNA SpiNA: Stereopure interfering Nucleic Acid https://wavelifesciences.com/science/publications/ Proprietary chemistry has dramatically increased potency and durability For over a decade Wave has been extending the frontiers of RNA therapies delivering breakthroughs in nucleic acid chemistry Substantial improvements in potency, duration of activity, and Ago2 loading with Wave’s proprietary SpiNA design Protein reduction Ago2 loading Increased RNA editing efficiency achieved with proprietary chemistry C C N3U N3U Base 2’ deoxy 2’ OMe 2’ deoxy 2’ OMe Sugar % Ugp2 mRNA editing 0% 20% 40% 60% 80% 100% RNA editing — AIMer
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6 AATD: Alpha-1 antitrypsin deficiency; DMD: Duchenne muscular dystrophy; HD: Huntington’s disease Robust, diversified RNA medicines pipeline including first -in-class RNA editing and RNAi programs Program Discovery IND / CTA Enabling Studies Clinical Rights Patient population (US & Europe) R N A i WVE-007 (GalNAc) INHBE (obesity) 100% global 175M (>1 billion globally) GalNAc / extra-hepatic Multiple 100% global -- R N A E D I T I N G WVE-006 (GalNAc) SERPINA1 (AATD) GSK exclusive global license 200K WVE-008 (GalNAc) PNPLA3 (liver disease) 100% global 9M GalNAc / extra-hepatic Multiple 100% global -- S P L I C I N G WVE-N531 Exon 53 (DMD) 100% global 2.3K Other exons (DMD) 100% global Up to 18K A L L E L E- S E L E C T I V E S I L E N C I N G WVE-003 mHTT (HD) 100% global 25K Symptomatic (SNP3) 60K Pre-Symptomatic (SNP3)
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7 Strategic focus for 2026: Accelerate development of WVE -007 (INHBE) and extend leadership in RNA editing Higher dose and longer follow-up data from INLIGHT Phase 1 single dose Initiate Phase 2a multidose portion of INLIGHT (higher BMI and comorbidities) Initiate new clinical trials: add-on to incretin and post-incretin maintenance Rapidly advancing RNA editing portfolio (WVE -006 and WVE -008) Accelerating development plan for WVE-007 (multiple treatment settings) Data from 400 mg and 600 mg cohorts of RestorAATion-2 clinical trial in AATD File CTA for WVE-008 (PNPLA3) for ~nine million individuals living with liver disease Building on successful clinical translation of WVE -006
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8 1. Koenen et al. 2021 Circ Res 128, 951; 2. Sargeant, et al. 2019 Endocrinol Metab (Seoul) 34, 247; 3. Wegovy PI; 4. Ghusn and Hurtado. 2024 Obesity Pillars 12, 100127; 5. Leach, et al. 2023 Prime Therapeutics Claims Analysis; 6. Gasoyan, et al. 2024 Obesity (Silver Spring) 32, 486. Improving body composition is the future for the > 1 billion people living with obesity globally Obesity is a metabolic disease in need of a treatment paradigm shift Individuals living with obesity have higher risk for many serious health conditions, including heart disease, type 2 diabetes, and some forms of cancer1 Fat loss similar to GLP-1 at three months Preserves muscle Potential 1–2 per year dosing Generally safe and well-tolerated Current standard of care: GLP-1s (INHBE GalNAc -siRNA)Impact of GLP -1s is often limited by: Loss of muscle mass2 Frequent dosing3 Poor tolerability4 High discontinuation rates5,6 WVE-007
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9 Reduce fat, including visceral fat Body composition improvements: Reducing fat, including visceral fat, while also preserving lean mass Preserve lean mass, including muscle Increased visceral adiposity is associated with many diseases including cardiometabolic disorders Insulin resistance MASH Type 2 diabetes Chronic inflammatory diseases Cardiovascular diseases Maintaining metabolic rate Improved insulin sensitivity Prevent weight regain Preserve muscle strength and function Reduce frailty Subcutaneous fat Visceral fat Abdominal muscles 1. Liao, Y. et al. 2025 Front. Nutr. 11, 1517186; 2. Ibarra-Reynoso, L.d.R. et al. 2025 J. Clin. Med. 14, 8365; 3. Wu, Q-W., et al. 2025 Front. Endocrinol. 16, 1635282; 4. Galvan, B. et al. 2025 J. Funct. Morphol. Kinesiol. 10, 244. MASH: Metabolic Dysfunction Associated Steatohepatitis
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10 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; CHD: coronary heart disease; cT1: corrected T1 Silencing INHBE mRNA by ≥50% is expected to recapitulate the healthy metabolic profile of heterozygous INHBE LoF carriers Human genetic data demonstrate that heterozygous INHBE loss -of-function (LoF) carriers have a healthy metabolic profile Heterozygous INHBE LoF carriers have favorable traits: lower abdominal obesity, lower triglycerides, higher HDL-c Heterozygous INHBE LoF carriers have lower risk of Type 2 diabetes and CHD Waist to hip ratio (abdominal obesity) Serum triglycerides HDL-c (“good cholesterol”) ALT ApoB Fasting glucose Visceral adipose volume by MRI -0.4 -0.2 0 0.2 0.4 Standard deviations Reduction (vs. non carriers) Elevation (vs. non carriers) Type 2 diabetes Coronary heart disease 0.50 0.75 1 1.5 2.0 Odds ratio Lower risk (vs. non carriers) Higher risk (vs. non carriers) Favorable association with liver traits cT1 ALT Liver fat -0.50 -0.25 0 0.25 0.50 Standard deviations Reduction (vs. non carriers) Elevation (vs. non carriers)
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11 Release of dimerized INHBE subunits creates hepatokine Activin E Binds to and activates ACVR1C (ALK7) receptor in adipose tissue Block adipose lipolysis Increased abdominal adiposity leads to obesity, CVD and T2D Diminished activation of ACVR1C (ALK7) receptor in adipose tissue Increased adipose lipolysis and shrink adipocytes Decreased abdominal adiposity leads to weight loss and reduced risk for CVD and T2D Adipocyte ALK7 I II II Activin E Activin E Reduced release of hepatokine Activin E Reduction of INHBE mRNA with GalNAc-siRNA Silencing INHBE mRNA has potential to treat obesity and associated metabolic diseases 1. Cell Reports (2018) 25, 1193–1203; 2. Biochemical Journal (2024) 481 547 –564; 3. PNAS 2023 Vol. 120 No. 32 e2309967120; 4. Na t Commun 2022. https://doi.org/10.1038/s41467 - 022-32398-7; 5. Nat Commun 2022. https://doi.org/10.1038/s41467 -022-31757-8
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12 Ref: Dubey et al. Activin E levels correlate with indicators of metabolic dysfunction in humans. ObesityWeek 2025. Further supports INHBE suppression as a weight loss approach for individuals living with obesity Higher circulating Activin E levels are correlated with higher BMI, higher abdominal fat , and higher fasting insulin in non-diabetic adults Fasting Insulin Abdominal FatBMI
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13 Single dose of INHBE GalNAc -siRNA led to durable Activin E reductions, and sustained improvements in body composition in DIO mice Left and right panels: Semaglutide 10 nmol/kg daily SC in mouse is equivalent to therapeutic dose of 2.4mg weekly SC in human; INHBE GalNAc -siRNA 10 mg/kg dose. All data from preclinical studies were conducted in mice fed with 60% high fat diet. Linear Mixed Effects ANOVA with post hoc comparisons o f marginal treatment effects vs. PBS per tissue.* p < 0.05 INHBE siRNA Semaglutide Single dose INHBE GalNAc-siRNA Reduction in body weight✓ Durable Activin E reduction ✓ 0 50 100 150 Activin E (%Control) PBS Sema- glutide INHBE 10 mg/kg Serum Activin E Epididymal fat weight Quadricep weight Reduction in fat✓ Muscle preservation✓ 0.00 0.25 0.50 0.75 Tissue weight (g) 0.00 0.05 0.10 0.15 0.20 0.25 Tissue weight (g) PBS PBSINHBE 10 mg/kg INHBE 3 mg/kg INHBE 10 mg/kg INHBE 3 mg/kg -23% -40% *
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14 WVE-007 has potential for use synergistically with GLP -1s or to curtail weight regain after the cessation of treatment with GLP -1, based on preclinical data Data from preclinical studies conducted in mice fed with 60% high fat diet; Left: semaglutide10 nmol/kg daily SC in mouse is equivalent to therapeutic dose of 2.4mg weekly SC 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 Not significant PBS Semaglutide + INHBE GalNAc-siRNA Semaglutide Difference in body weight (% of PBS, same time point) Daily GLP-1 Dose INHBE GalNAc-siRNA Semaglutide Control for Semaglutide INHBE GalNAc-siRNA Control for siRNA Semaglutide + INHBE GalNAc-siRNA Daily GLP-1 Single dose INHBE GalNAc-siRNA ~2x greater weight loss After cessation of GLP-1: Curtails weight regain✓ Day Combined with GLP-1: Greater weight loss✓ Day
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15 INLIGHT: Clinical trial of WVE -007 in otherwise healthy individuals living with overweight or obesity SAD: single-ascending dose; MAD: multi-ascending dose; PK: pharmacokinetics; PD: pharmacodynamics Randomized, double-blind, placebo-controlled (3:1) study of ascending doses of WVE-007 Multiple clinical trial sites, including US Phase 1 SAD Portion Key study criteria: • HbA1c: <5.9 • BMI: 28 – 35 kg/m² (SAD) No diet or exercise modifications are instituted SAD Cohort 4 600 mg (n=32) SAD Cohort 3 400 mg (n=32) SAD Cohort 2 240 mg (n=32) SAD Cohort 1 75 mg (n=8) PK/PD and safety only (no DEXA) Key measurements include: • Safety and tolerability • PK • Activin E • Body composition • Biomarkers • Body weight
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16 Left: Figure shows sample means and SEMs. All MMRM baseline and placebo comparisons from Day 8 onwards are p<0.003. Placebo i ncludes one individual from 400 mg expansion. Green shading: >70% Activin E reductions in preclinical models led to fat loss; Right: All DEXA percentage changes and p -values are model-based, using the SAP pre-specified analysis; p-values are from tests of within-group change over time; no p values were statistically significant for placebo. Improvements in body composition observed at three months after a single WVE-007 dose (lowest therapeutic dose); durability supports 1-2x yearly dosing Reductions in visceral and total fat mass with preservation of lean mass observed at three months -9.4% -4.5% 3.2% -0.2% -0.5% 2.3% -10% -8% -6% -4% -2% 0% 2% 4% % Change from Baseline WVE-007 240 mg (n=24) Placebo (n=8) Visceral fat mass Total fat mass Lean mass p=0.01 p=0.07p=0.02 Highly durable, dose dependent, serum Activin E reductions support dosing once or twice per year Activin E change in INLIGHT -100% -75% -50% -25% 0% 25% 50% % Reduction in Activin E (nM) +/- SEM 0 50 100 150 Study DaySingle dose WVE-007 (GalNAc-siRNA) WVE-007 75 mg (n=6)Placebo (n=13) WVE-007 400 mg (n=6)WVE-007 240 mg (n=24)
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17 Single dose of WVE -007 led to improvements in body composition with fat loss similar to GLP-1 at three months without muscle loss 1. For INLIGHT, all DEXA percentage changes and p -values are model-based, using the SAP pre-specified analysis. 2. For BELIEVE, all data points are approximate and based on placebo - adjusted estimates extracted from figures, body weight reported as total mass, from Heymsfield SB, et al. Symposium – “Can we improve the quality of weight loss by augmenting fat mass loss while preserving lean mass? The BELIEVE study of bimagrumab + semaglutide”. Presented at: American Diabetes Association Scientific Sessions; June 20 -23, 2025; Chicago. 3. Semaglutide in BELIEVE study was subcutaneously administered weekly and titrated to maintenance dose. N=57 in semaglutide 2.4 mg arm, N=56 in placebo arm. 4. Within the first 12 weeks of the BELIEVE study, bimagrumab was dosed IV at baseline and week 4. N=56 in bimagrumab 10 mg/kg arm, N=56 in placebo arm. Note: The data presented above are derived from different clinical trials with differences in trial design and patient population, including with respect to BMI. As a result, cross-trial comparisons cannot be made and no head-to-head clinical trials have been conducted.
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18 1. Gabriely et al., Diabetes 2002; Campos et al., Diabetes & Vascular Disease Research 2019; Huang et al., Front Endocrinol 2 023. 2. Cesaro et al., Front Cardiovasc Med 2023; Khawaja et al., Curr Cardiol Rep 2024; Hiuge-Shimizu et al., J Atheroscler Thromb 2011. 3. Liao et al., PLoS ONE 2023; Jung et al., Endocrinol Metab 2020; ; Krittayaphong et al., Scientific Reports 2024; Hanlon & Yuan, Clin Liver Dis 2021. 4. Liao et al., PLoS ONE 2023; Jung et al., Endocrinol Metab 2020; Vilar-Gomez et al Gastroenterology 2015.. 5. Qaio et al. Cardiovasc Diabetol 21, 225 (2022). VAI = Visceral Adiposity Index WVE-007 aims to shift body composition by reducing body fat while preserving muscle, to deliver a healthier cardiometabolic profile Visceral fat is associated with insulin sensitivity and incidence of MASH, type 2 diabetes and cardiovascular disease Health Outcome Visceral Fat Reduction Associated Benefits Insulin Sensitivity1 ≥ 5% decrease in visceral fat Improved insulin sensitivity, lower HbA1c, better lipid profile Cardiovascular Risk2 ≥ 5–10% decrease in visceral fat Reduced blood pressure, improved lipids, lower systemic inflammation Liver Fat (Steatosis)3 ≥ 10% decrease in visceral fat or ≥ 7–10% body weight loss Significant reduction in hepatic triglycerides, improved liver enzymes Hepatic Fibrosis4 ≥ 10% decrease in visceral fat or ≥ 7–10% body weight loss Resolution of steatohepatitis in up to 90%, fibrosis regression in many cases Visceral fat increases risk of cardiovascular disease5 Visceral fat reduction is associated with multiple health benefits
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19 INLIGHT: Clinical trial of WVE -007 in otherwise healthy individuals living with overweight or obesity SAD: single-ascending dose; MAD: multi-ascending dose; PK: pharmacokinetics; PD: pharmacodynamics Randomized, double-blind, placebo-controlled (3:1) study of ascending doses of WVE-007 Multiple clinical trial sites, including US Key measurements include: Safety and tolerability, PK, Activin E, body composition, biomarkers, body weight Phase 2a MAD PortionPhase 1 SAD Portion Key study criteria: • HbA1c: <5.9 • BMI: 28 – 35 kg/m² (SAD) No diet or exercise modifications are instituted Plan to initiate in 1H 2026 In individuals with higher BMI and comorbidities SAD Cohort 4 600 mg (n=32) SAD Cohort 3 400 mg (n=32) SAD Cohort 2 240 mg (n=32) SAD Cohort 1 75 mg (n=8) PK/PD and safety only (no DEXA) MAD Cohort 2 (up to n=32) MAD Cohort 1 (up to n=32)
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20 Phelps, NH, et al. 2024 Lancet 403, 1027 Potentially transformational profile for treating obesity across multiple treatment settings Potential to address more than one billion individuals with obesity globally Add-on Maintenance Single agent in individuals living with obesity Monotherapy • To leverage an orthogonal mechanism to incretins for enhanced efficacy • To prevent weight rebound and maintain metabolic improvements upon incretin cessation Combination with incretin treatments An off-ramp post-incretin treatments • To induce fat loss with muscle preservation and favorable safety and tolerability
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21 Expect to initiate new trials of WVE-007 as an add-on to incretin and as post-incretin maintenance in 2026 Near term anticipated updates for WVE-007 1Q 2026 • 6-month follow-up data from the 240 mg single-dose cohort • 3-month follow-up data from the 400 mg single-dose cohort 2Q 2026 • 6-month follow-up data from the 400 mg single-dose cohort • 3-month follow-up data from the 600 mg single-dose cohort 1H 2026 Initiate Phase 2a MAD Portion • In individuals with higher BMI and comorbidities
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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 ~200K people in the US and Europe are homozygous for the Z allele (Pi*ZZ genotype) WVE-006: Potential first -in-class, convenient AIMer (RNA editing) for AATD that addresses both liver and lung manifestations of the disease RNA correction replaces mutant Z-AAT protein with M-AAT protein to reduce risk of liver pathology Z-AAT M-AAT reaches lungs to protect from proteases and reduce risk of lung pathology 1 2 M-AAT Restore circulating M-AAT and physiological AAT protein production Reduce Z-AAT protein aggregation in liver • AATD is a rare, inherited genetic disorder commonly caused by G-to-A point mutation • Patients are predisposed 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 ✓ ✓ Standard of care: IV augmentation therapy Standard of care: No approved therapies
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23 Heterozygous Pi*MZ AAT protein of >11uM, >50% M-AAT RNA editing aims to increase M -AAT and restore physiological AAT production during acute phase response Yes Low Low ✓Goal: ~50% editing to shift Pi*ZZ individuals to AAT function consistent with Pi*MZ genotype Homozygous Pi*ZZ No healthy M-AAT AAT levels increase during acute phase response No Risk of lung pathology High Risk of liver pathology High
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24 WVE-006 enables endogenous AAT production during an acute phase response while augmentation therapy leaves patients at risk WVE-006 therapeutic goal is to restore dynamic AAT physiology; augmentation therapy goal is to maximize AAT levels as dynamic response is not enabled Illustrative model of impact of acute phase response Serum AAT RNA editing dose Protected lungs Endogenous AAT levels increase during acute phase response without need for add’l doses Serum AAT IV dosing Lung damage Exogenous AAT levels are depleted before next scheduled IV dose Augmentation therapy WVE-006 treatment approach • Augmentation therapy has no impact on liver disease • WVE-006 also reduces levels of Z-AAT
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25 RestorAATion-2 clinical trial ongoing HV: healthy volunteer; SAD: single-ascending dose; MAD: multi-ascending dose RestorAATion-2: AATD PatientsRestorAATion-1: Healthy Volunteers 30 mg 100 mg 200 mg 400 mg 600 mg RestorAATion-1: Healthy Volunteers SAD → MAD Multi-dosing complete SAD Cohort 3 600 mg SAD Cohort 1 200 mg MAD Cohort 3 600 mg; Q4W SAD Cohort 2 400 mg MAD Cohort 2 400 mg; Q4W MAD Cohort 1 200 mg Q2W Study key objectives Safety and tolerability Pharmacokinetics Serum M-AAT levels
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26 WVE-006 achieved key treatment goals of restoring MZ phenotype 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 µM (M), 0.029 µM (Z)) and reported as mean participant SAD and MAD maximums Middle: from 200 mg MAD cohort; Right: from 200 mg SAD cohort 400 mg MAD data expected in 1Q 2026 and 600 mg SAD and MAD data expected in 2026 Total AAT levels exceeded 11 µM, production of wild-type M-AAT of greater than 50%, restored physiological AAT production Wild-type M-AATMutant Z-AAT AAT reached >20 μM during an acute phase response Plasma AAT of ~13 µM Wild-type M-AAT protein of 64% of total, reduction in Z-AAT• Protein levels associated with lower risk of AATD liver and lung diseases 400 mg single dose 12.8 µM total AAT 200 mg multidose 11.9 µM total AAT Acute phase response due to a kidney stone CRP (mg/L)
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27 RNA editing program: WVE -008 (PNPLA3 AIMer) for liver disease Clinically-validated RNA editing ✓ ✓ ✓ Efficient and consistent RNA editing Durable RNA editing supporting infrequent dosing Generally safe and well-tolerated • Strong foundation in human genetics • Over nine million homozygous PNPLA3 I148M patients with liver disease in US and Europe • GalNAc RNA editing approach uniquely aims to restore PNPLA3 function to fully address disease WVE-008 (PNPLA3)
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28 1. Carlsson, B., et al. 2020 Aliment Pharmacol Ther.; 2. Unalp-Arida and Ruhl 2020 Hepatology; 3. Dong, XC, 2019 Front. Med. 4. Liver International, 2025; 45:e16133 MAFLD, Metabolic dysfunction-associated fatty liver disease; MASH, Metabolic dysfunction-associated steatohepatitis; ALD, alcoholic liver disease; AH, Alcohol-associated hepatitis; HCC, hepatocellular carcinoma People homozygous for PNPLA3 I148M are at high risk for liver disease Over nine million homozygous PNPLA3 I148M patients with liver disease in US and Europe >50% RNA editing would support restoration of heterozygous phenotype with lower risk of liver complications and death Heterozygous carriers have 80% lower risk of liver-related death as compared to homozygous carriers Homozygous PNPLA3 I148M carriers have significantly higher risk of multiple liver diseases 0 2 4 6 8 10 12 14 16 18 20 22 24 26 Years of follow-up Survival (%) of liver-related death 0 92 94 96 98 100 Homozygous I148 Heterozygous I148M Homozygous I148M HR = 8.61 (3.28–22.60) HR = 1.70 (0.78–3.71) AIMer editing to restore heterozygous phenotype MASH MAFLD
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29 Wave’s editing approach delivers greater decreases in liver fat compared to silencing in human liver models Monolayer model Decrease in liver fat Liver fat PNPLA3 siRNA Human HEPATOPAC® model with homozygous I148M AIMer siRNAsiRNA AIMer Control Control Decrease in liver fat
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30 Left: 4-parameter log-logistic dose response curve; Middle: Analysis utilized RNA-sequencing with two separate primary human hep atocyte cell lines (PH1/2). Variant calling utilized GATK best practices for RNA variant calling using Mutect2 and display A->G evidence found when filtering for variants found in b oth cell lines and all doses. Expect to file Clinical Trial Application (CTA) for WVE-008 in 2026 WVE-008: Potential first -in-class, disease modifying therapy, for treatment of PNPLA3 I148M -driven liver disease Tissue exposure supports excellent delivery Highly specific editing with WVE-008 0 5 10 15 20 25 10 100 1000 Time (day) Liver Tissue Conc (μg/g) Semi-log scalePotent editing with WVE-008
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31 Reimagining RNA medicines: Bifunctional modality to simultaneously knockdown and edit RNA with single oligonucleotide construct SpiNA AGO2 ✓ Engage both endogenous Ago2 and ADAR enzymes ✓ Silence one target, while simultaneously editing or upregulating another unique target ✓ Unlock complex indications that require engaging multiple targets ✓ May continue to increase durability of editing AIMer ADAR Single Oligonucleotide Construct
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32 Primary human hepatocytes were treated in vitro with indicated compounds for 96 hours. Left: LDLR protein was measured using an ELISA; Stats: Welch's One-Way ANOVA with Dunnett's T3 post hoc-comparison. Right: PCKS9 transcript was measuring by qPCR using the ΔΔCt method Demonstrates potential to address complex indications that require engaging multiple targets Single GalNAc -conjugated oligonucleotide construct can simultaneously upregulate and silence protein in vitro LDLR Protein upregulation PCSK9 mRNA knockdown LDLR protein (pg)/ Total protein (ug) PBS PCSK9 SpiNA LDLR AIMer Single oligo construct PCSK9 mRNA ref. to PBS (Mean, SEM) 0 50 100 150 **** **** 0.0 0.5 1.0 1.5 PBS PCSK9 SpiNA LDLR AIMer Single oligo construct
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33 Other hepatic targets Extra-hepatic targetsWVE-007 Obesity Other hepatic targets Extra-hepatic targets Poised for significant and sustained growth driven by RNAi and RNA editing RNA Editing RNAi WVE-006 AATD WVE-008 PNPLA3 Liver Disease Bifunctional single oligonucleotide construct (RNAi+RNA editing)
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34 Anticipated upcoming milestones CTA: Clinical Trial Application; NDA: New Drug Application; IND: Investigational New Drug RNA editingSplicingAntisense RNAi WVE-N531 (Exon 53) DMD WVE-003 (SNP3) HD WVE-006 AATD WVE-007 (INHBE) Obesity WVE-008 Liver disease 1Q 2026: Deliver 3-month 400 mg data and 6-month 240 mg data 2Q 2026: Deliver 3-month 600 mg data and 6-month 400 mg data 1H 2026: Initiate Phase 2a multidose portion of INLIGHT in individuals living with obesity with higher BMI and comorbidities 2026: Initiate new trials evaluating WVE-007 as an add-on to incretin and as post-incretin maintenance 1Q 2026: Deliver data from 400 mg multidose cohort 2026: Deliver single and multidose data from 600 mg cohort 2026: File CTA for WVE-008 2026: Submit NDA to support accelerated approval of WVE-N531 with monthly dosing Submit IND application for potentially registrational Phase 2/3 study of WVE-003 in conjunction with prospective strategic partner
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