Wave Life Sciences Ltd. · NASDAQ:WVE
Wave Life Sciences — Investor Presentation (July 2026)
50 slides from Wave Life Sciences's investor presentation, Jul 30, 2026
Slide 1: Wave Life Sciences Corporate Presentation
Wave Life Sciences Corporate Presentation July 30, 2026
Slide 2: Forward-looking statements
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, r
Slide 3: Our Mission
Our Mission To unlock the broad potential of RNA medicines to transform human health 3
Slide 4: Building a leading RNA medicines company
Building a leading RNA medicines company Differentiated RNA medicines Translating genetic insights into Unlocking platform and chemistry potentially best-in-class medicines emerging pipeline RNAi WVE-007 (obesity) • Differentiated mechanism • Extra-hepatic capabilities: focused on fat loss and with
Slide 5: Extending the frontiers of RNA therapies with nucleic acid chemistry
For over a decade Wave has been extending the frontiers of RNA therapies delivering breakthroughs in nucleic acid chemistry RNAi — SpiNA RNA editing — AIMer Protein reduction Ago2 loading 100% % Ugp2 mRNA editing 80% 60% 40% 20% 0% C C N3U N3U Base 2’ deoxy 2’ OMe 2’ deoxy 2’ OMe Sugar Substantial i
Slide 6: Robust RNA medicines pipeline with first-in-class RNAi and RNA editing programs
Robust RNA medicines pipeline with first-in-class RNAi and RNA editing programs RNAi (SpiNA) Program Discovery IND / CTA Enabling Studies Clinical Patient population INLIGHTTM trial (monotherapy) WVE-007 (GalNAc) 175M INHBE (obesity) Combination with incretins (>1 billion globally) Post-incretin mai
Slide 7: WVE-007 GalNAc-siRNA silencing: Obesity
WVE-007 GalNAc-siRNA silencing Obesity 7
Slide 8: WVE-007 potentially transformative approach for obesity
WVE-007 (investigational INHBE GalNAc-siRNA) is a potentially transformative approach for the > 1 billion people living with obesity globally Significant unmet need in obesity WVE-007 Current standard of care: Focused on caloric restriction Focused on adipocyte lipolysis and by reducing appetite and
Slide 9: Human genetic data: INHBE loss-of-function carriers have lower visceral fat
Human genetic data demonstrate that heterozygous INHBE loss-of-function (LoF) carriers have lower visceral fat and a healthier metabolic profile Heterozygous INHBE LoF carriers versus non-carriers: Favorable traits : Waist-to-hip ratio ✓ Lower abdominal obesity Visceral adipose volume by MRI ✓ Reduc
Slide 10: Silencing INHBE mRNA has the potential to treat obesity
Silencing INHBE mRNA has the potential to treat obesity and associated metabolic diseases Release of dimerized Binds to and activates ACVR1C Block adipose INHBE subunits creates (ALK7) receptor in adipose tissue lipolysis hepatokine Activin E Activin E Activin E Increased abdominal adiposity leads t
Slide 11: Higher circulating Activin E correlated with BMI, abdominal fat, insulin
Higher circulating Activin E levels are correlated with higher BMI, higher abdominal fat, and higher fasting insulin in non-diabetic adults BMI Abdominal Fat Fasting Insulin Further supports INHBE suppression as a weight loss approach for individuals living with obesity 11 Dubey et al. Activin E lev
Slide 12: WVE-007 designed to decrease fat and preserve muscle
WVE-007 is designed to improve body composition by decreasing fat and preserving muscle Subcutaneous fat Total Fat REDUCED Visceral fat Visceral Fat REDUCED Muscle Muscle PRESERVED 12
Slide 13: WVE-007 mechanism focused on lipolysis and reducing visceral fat
WVE-007’s mechanism is focused on lipolysis and directly reducing visceral and subcutaneous fat Visceral fat drives insulin resistance and Reduced visceral fat is associated with many cardiometabolic disorders multiple health benefits Visceral fat decrease • MASH ≥ 5% Improved insulin sensitivity1:
Slide 14: Key limitation of current standard of care: muscle loss
WVE-007 aims to address a key limitation of current standard of care: up to 40% of weight loss is driven by muscle loss Preservation of muscle mass is linked to many health benefits • Higher basal metabolic rate • Reduced visceral fat5,6 (BMR)1 • Prevent weight regain7,8 • Improved insulin sensitivi
Slide 15: Single dose INHBE GalNAc-siRNA shrank adipocytes in DIO mice
A single dose of INHBE GalNAc-siRNA led to shrinkage of adipocytes in DIO mice DIO Lean Mean adipocyte diameter PBS INHBE GalNAc-siRNA (μm) ✱✱✱ 80 60 40 20 0 DIO DIO Lean PBS INHBE GalNAc- siRNA 15 Data presented at ADA Scientific Sessions June 2025 ***p<0.001; Day 28
Slide 16: INHBE siRNA lowered inflammatory state of visceral adipose tissue
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 (Mᶲ) (F4/80) Pro-inflammatory (M1) Mᶲ Anti-inflammatory (M2) Mᶲ (CD11c) (CD163) INHBE GalNAc siRNA INHBE GalN
Slide 17: 58% reduction of adipose fibrosis with single dose
Lowering of inflammatory state of epiWAT visceral fat induced by single dose of INHBE siRNA resulted in 58% reduction of adipose fibrosis Reduced staining illustrates decreased tissue fibrosis Fibrosis in mouse adipose (Day 56) PBS 3 mg/kg 10 mg/kg 15 ✱ % Trichrome positive area 10 Trichrome 5 0 PBS
Slide 18: WVE-007 expected to drive fat reduction and improve cardiometabolic health
Treatment with WVE-007 (investigational INHBE GalNAc-siRNA) is expected to drive fat reduction and improve key measures of cardiometabolic health Leading siRNA design (SpiNA)1 Driving fat reduction And improving clinical outcomes WVE-007 Reduction of INHBE mRNA and (INHBE GalNAc-siRNA) circulating A
Slide 19: Durable Activin E reductions and improved body composition in DIO mice
Single dose of INHBE GalNAc-siRNA led to durable Activin E reductions, and sustained improvements in body composition in DIO mice ✓ Durable Activin E reduction ✓ Reduction in fat ✓ Muscle preservation ✓ Reduction in body weight Serum Activin E Epididymal fat weight Quadricep weight Single dose INHBE
Slide 20: WVE-007 with GLP-1s or to curtail weight regain
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 ✓ Combined with GLP-1: Greater weight loss ✓ After cessation of GLP-1: Curtails weight regain (% of PBS, same time point) Difference in body we
Slide 21: Phase 1 portion of INLIGHT trial design
Phase 1 portion of INLIGHT TM trial is investigating WVE-007 in individuals living with overweight or obesity, otherwise healthy Phase 1 lower BMI (SAD) Phase 2a high BMI (MAD) • Average BMI: 32 kg/m² SAD Cohort 4 MAD high BMI (35–50 kg/m²)+T2D cohorts • HbA1c: <5.9% 600 mg (n=32) • Otherwise health
Slide 22: Improvements in body composition at six months after single dose
Clinically meaningful improvements in body composition at six months following a single dose of WVE-007 Phase 1 otherwise healthy (SAD) Lower BMI of ~32 kg/m² Activin E change in INLIGHTTM trial Improved body composition six months following single 240 mg dose: - Significant reduction in visceral fa
Slide 23: Improvement in body composition by VMR versus semaglutide
Single dose of WVE-007 in a lower BMI population led to greater improvement in body composition by VMR versus semaglutide Visceral Fat-to-Muscle Improvement in body composition by VMR at 3 months and 6 months4 Ratio (VMR) • Established measure of body BELIEVE Phase 2 Trial composition integrating ha
Slide 24: Phase 2a INLIGHT: higher BMI population
Phase 2a INLIGHTTM trial: higher BMI population aligns with Phase 2 and 3 obesity trials, potential for continued improvements in body composition Total fat and BMI at baseline Visceral fat and BMI at baseline Phase 2 BELIEVE baseline Phase 2 BELIEVE baseline 50 (semaglutide and / or bimagrumab) 1.7
Slide 25: Phase 2a (MAD) global placebo-controlled study
Phase 2a (MAD) global, placebo-controlled study will inform further development in obesity, as well as MASH, type 2 diabetes, and other cardiometabolic diseases High BMI • Individuals with high BMI D1 D85 (35–50 kg/m2) and comorbidities Cohort 1 240 mg N=40 (3:1) • Assessments include: D1 D85 • Body
Slide 26: Combination and maintenance trials expected 2H 2026
Phase 2a portion of INLIGHT TM monotherapy trial underway; combination and maintenance trials of WVE-007 expected to initiate in 2H 2026 Monotherapy Combination Maintenance Single agent in individuals Add-on to incretin An off-ramp post-incretin living with obesity treatments treatments • To induce
Slide 27: INHBE silencing addresses additional indications
INHBE silencing provides opportunity to address additional significant indications through lowering of visceral fat Obesity ~110M PMOS ~9M Visceral fat reductions Cardiovascular disease Type 2 diabetes ~20M ~38M MASH ~23M Therapeutic indications and US patient populations 27 PMOS: Polyendocrine Meta
Slide 28: WVE-006 RNA editing (AIMer): AATD
WVE-006 RNA editing (AIMer) Alpha-1 antitrypsin deficiency (AATD) 28
Slide 29: WVE-006 potentially transformative approach for Pi*ZZ AATD
WVE-006 (investigational GalNAc-RNA editing AIMer) is a potentially transformative approach for both lung and liver manifestations of Pi*ZZ AATD Significant unmet need in AATD WVE-006 Current standard of care: Weekly IV augmentation is the Focused on RNA editing to restore only treatment for AATD lu
Slide 30: Treatment target: heterozygous MZ genotype
Treatment target: Heterozygous MZ genotype with M-AAT >50% AAT and a dynamic CRP response has low risk of liver and lung disease Serum AAT Protein Levels by Genotype1 50 Serum AAT (µM) 25 11 µM 0 Null Pi*ZZ ZZ Pi*SZ SZ Pi*MZ MZ Pi*MM MM Mean 64% M-AAT Serum AAT composition No AAT 100% Z-AAT S-AAT an
Slide 31: RNA editing expected to deliver greater impact over time
RNA editing expected to deliver even greater impact over time with continued treatment and improved liver health Pi*ZZ Pi*MZ-like Liver disease Reduce Z-AAT to prevent liver damage Z-aggregate clearance over time WVE-006 High Z-AAT aggregation ~50% M-AAT Increasing hepatocyte and liver inflammation
Slide 32: Pi*ZZ individuals have impaired AAT increase during acute-phase responses
Pi*ZZ individuals have an impaired serum AAT increase during acute-phase responses (APRs), when they need it most 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 900 30,100 Pi*ZZ
Slide 33: WVE-006 restores dynamic production of AAT
WVE-006 restores dynamic production of AAT protein as part of APRs to protect lungs from damage Illustrative Models APRs require a rapid rise in AAT levels to Standard of care prevent lung damage (augmentation AAT levels therapy) may leave • Even with augmentation patients at risk therapy, in ZZ ind
Slide 34: RestorAATion-2 trial ongoing
RestorAATion-2 trial ongoing in individuals living with Pi*ZZ AATD RestorAATion-1: RestorAATion-1: Healthy Healthy Volunteers Volunteers RestorAATion-2: AATD Patients SAD → MAD Multi-dosing complete SAD MAD 600 mg 600 mg 600 mg x 4 doses Single dose Monthly 400 mg 400 mg 400 mg x 4 doses 200 mg Sing
Slide 35: WVE-006 achieved Pi*MZ-like profile across doses
Treatment with WVE-006 achieved Pi*MZ-like profile across doses: delivering potential liver and lung benefits with a safe and convenient therapy Protecting the liver Protecting the lung Safe and convenient Generate MZ-like Total healthy, wild- dynamic AAT • Generally safe WVE-006 Reduce Z-AAT AAT ty
Slide 36: Up to 71% reduction in circulating Z-AAT
Up to 71% reduction in circulating, mutant Z-AAT supporting potential improvement in liver health SAD cohorts: Dose-dependent MAD cohorts: Similar reductions with extended dosing interval Z-AAT reductions Biweekly (200 mg x 7 doses) Monthly (400 mg x 4 doses) Mean max reduction of serum Z-AAT Mean m
Slide 37: WVE-006 generated wild-type M-AAT within MZ range
WVE-006 generated circulating wild-type M-AAT within the MZ range (up to 64%) with no bystander edits, supporting potential improvement in lung health SAD cohorts: Dose-dependent MAD cohorts: Similar M-AAT% with extended dosing interval M-AAT restoration Biweekly (200 mg x 7 doses) Monthly (400 mg x
Slide 38: Dynamic increases of AAT during acute phase responses
WVE-006 continues to demonstrate dynamic increases of AAT during acute phase responses Total AAT reached 20.6 µM two weeks post single 200 mg dose during CRP levels are correlated with AAT acute phase response elevations across RestorAATion-2 Total AAT • Two additional acute phase responses Total AA
Slide 39: WVE-006 differentiated approach compared to standard of care
WVE-006 offers a differentiated treatment approach for AATD compared to current standard of care and other therapies in clinical development Protecting the liver Protecting the lung Safe and convenient Enable dynamic Provide healthy, Infrequent Reduce Z-AAT Safe & well-tolerated AAT production wild-
Slide 40: WVE-006 differentiated value proposition; FDA meeting
WVE-006 aims to support a differentiated value proposition for Pi*ZZ individuals, HCPs, and payers Infrequent subcutaneous Reduce Z-AAT to prevent liver dosing; potential for self- disease administration WVE-006 Provide healthy, wild-type for AATD Generally safe and well M-AAT to protect lung tolera
Slide 41: WVE-008 RNA editing (AIMer): PNPLA3 I148M liver disease
WVE-008 RNA editing (AIMer) PNPLA3 I148M liver disease 41
Slide 42: WVE-008 for PNPLA3 I148M liver disease
WVE-008 for PNPLA3 I148M liver disease GalNAc-RNA editing approach uniquely aims to restore PNPLA3 function to fully address genetic liver disease Homozygous PNPLA3 I148M carriers Heterozygous carriers have 80% lower risk of liver-related death as have significantly higher risk of compared to homozy
Slide 43: Silencing PNPLA3 may worsen basal liver functions
Silencing of PNPLA3 in normal liver may worsen basal physiological functions Silencing PNPLA3 worsens steatosis in Silencing PNPLA3 increases PNPLA3 siRNA exacerbates the fibrotic iPSC-derived human liver organoids2 inflammation-induced liver cell death in response in hepatic stellate cells1 human p
Slide 44: RNA editing expected to restore PNPLA3 function
RNA editing is expected to restore PNPLA3 function to treat across the stages of liver diseases ✓ RNA editing approach PNPLA3 I148M aggravates steatosis Silencing PNPLA3 may only partially PNPLA3 correction expected to and fibrosis through gain-of-function address disease restore function, counter l
Slide 45: AIMers achieve efficient editing of PNPLA3, reducing liver fat
AIMers achieve efficient editing of PNPLA3, leading to reduction of liver fat Significant decrease in liver fat with PNPLA3 editing in ✱✱✱✱ human HEPATOPAC® model with homozygous I148M (pixel2/cell) ns Lipid Droplet Density (pixel2/cell) 1500 (mean + SE) (mean ± SE) 1000 Lipid Droplet Density 500 PB
Slide 46: Preclinical data support WVE-008 as potential first-in-class therapy
Preclinical data support WVE-008 as potential first-in-class, disease modifying therapy, for treatment of PNPLA3 I148M liver disease Potent editing with WVE-008 Highly specific editing with WVE-008 Tissue exposure supports excellent delivery 1000 Liver Tissue Conc (μg/g) 100 Semi-log scale 10 0 5 10
Slide 47: Reimagining RNA medicines
Reimagining RNA medicines 47
Slide 48: Reimagining RNA medicines: Bifunctional modalities
Reimagining RNA medicines: Bifunctional modalities SpiNA SpiNA ✓ Engage both endogenous Ago2 AGO2 and ADAR enzymes, as well as AGO2 dual RNAi silencing ✓ Silence multiple targets or silence Single one target while simultaneously Single Oligonucleotide editing or upregulating another Oligonucleotide
Slide 49: Poised for significant and sustained growth
Poised for significant and sustained growth driven by RNAi and RNA editing Other hepatic targets RNAi WVE-007 Extra-hepatic targets SpiNA Obesity Bifunctional single oligonucleotide RNA constructs WVE-006 Editing AATD AIMers WVE-008 Other hepatic targets PNPLA3 I148M liver disease Extra-hepatic targ
Slide 50: For questions contact
For questions contact: investorrelations@wavelifesci.com
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