Wave Life Sciences Ltd. · NASDAQ:WVE
Wave Life Sciences — Investor Presentation (November 2025)
58 slides from Wave Life Sciences's investor presentation, Nov 17, 2025
Slide 1: Wave Life Sciences Corporate Presentation
Wave Life Sciences Corporate Presentation November 17, 2025
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
Slide 4: Building a leading RNA medicines company
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 Potent
Slide 5: Convergence of a validated platform with deep genetic insights
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 positio
Slide 6: Robust, diversified RNA medicines pipeline
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 (GalNA
Slide 7: WVE-007 GalNAc siRNA silencing Obesity
WVE-007 GalNAc siRNA silencing Obesity
Slide 8: Obesity is a metabolic disease with a treatment paradigm ripe for disruption
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 form
Slide 9: Human genetic data show INHBE LoF carriers have a healthy metabolic profile
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
Slide 10: Silencing INHBE mRNA has potential to treat obesity
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 ob
Slide 11: Single doses of INHBE GalNAc-siRNA result in weight loss in DIO mice
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/
Slide 12: INHBE GalNAc-siRNA synergistic with GLP-1s
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 Di
Slide 13: Durable Activin E reduction delivers weight loss similar to GLP-1
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 %
Slide 14: INHBE GalNAc-siRNA expected to improve cardiometabolic health
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 Ris
Slide 15: INLIGHT: Dose escalation continues
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
Slide 16: Dose dependent Activin E reductions following a single dose of WVE-007
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 ba
Slide 17: Highly durable Activin E reductions with WVE-007
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 fr
Slide 18: Clinical Activin E reductions exceed levels leading to preclinical weight loss
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 (G
Slide 19: Near-term clinical data updates for WVE-007
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 pr
Slide 20: WVE-006 RNA editing (AIMer) AATD
WVE-006 RNA editing (AIMer) Alpha-1 antitrypsin deficiency (AATD)
Slide 21: AATD impacts multiple organ systems and has limited treatment options
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 •
Slide 22: WVE-006: Potential first-in-class therapy for AATD
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
Slide 23: RNA editing aims to increase M-AAT
RNA editing aims to increase M-AAT and restore physiological AAT production during acute phase response Genotype Null Pi*ZZ Pi*MZ 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 Ri
Slide 24: RNA editing aims to restore dynamic AAT levels
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 ac
Slide 25: First demonstration of restoring physiological serum AAT production
First-ever demonstration of ability to restore physiological serum AAT production; total AAT reached 20.6 µM 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 Pu
Slide 26: WVE-006 enables endogenous AAT production versus augmentation therapy
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
Slide 27: WVE-006 achieved key treatment goals of restoring MZ phenotype
WVE-006 achieved key treatment goals of restoring MZ phenotype Total AAT levels exceeded 11 µM, production of wild-type M-AAT of greater than 50%, restored physiological AAT production Plasma AAT of ~13 µM Wild-type M-AAT protein of 64% AAT reached >20 ìM during an of total, reduction in Z-AAT acute
Slide 28: RestorAATion-2 clinical trial ongoing
RestorAATion-2 clinical trial ongoing; 400 mg MAD data expected in 1Q 2026 and 600 mg SAD and MAD data expected in 2026 RestorAATion RestorAATion -1: Healthy -1: Healthy Volunteers Volunteers RestorAATion-2: AATD Patients SAD MAD Multi-dosing complete 600 mg SAD Cohort 3 MAD Cohort 3 600 mg 600 mg;
Slide 29: WVE-008 RNA editing (AIMer) PNPLA3 I148M liver disease
WVE-008 RNA editing (AIMer) PNPLA3 I148M liver disease 29
Slide 30: RNA editing program: WVE-008 for liver disease
RNA editing program: WVE-008 (PNPLA3 AIMer) for liver disease Clinically-validated RNA editing WVE-008 for PNPLA3 I148M Efficient and consistent RNA editing • Strong foundation in human genetics Restore dynamic physiological response Over 9 million PNPLA3 I148M • homozygous patients with liver disea
Slide 31: People homozygous for PNPLA3 I148M are at high risk for liver disease
People homozygous for PNPLA3 I148M are at high risk for liver disease Over 9 million homozygous PNPLA3 I148M patients with liver disease in US and Europe Homozygous PNPLA3 I148M carriers Heterozygous carriers have 80% lower risk of liver-related death as have significantly higher risk of compared to
Slide 32: Silencing of PNPLA3 may worsen 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 33: 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 34: WVE-008: Potential first-in-class disease modifying therapy
WVE-008: Potential first-in-class, disease modifying therapy, for treatment of PNPLA3 I148M-driven liver disease WVE-008 Proprietary Subcutaneous Potential for Highly specific (RNA editing) chemistry injection (GalNAc) infrequent dosing editing Potent editing with WVE-008 Highly specific editing wit
Slide 35: AIMers achieve efficient editing of PNPLA3
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 l) l ns c e / 1500 /cell) 2 2 (pixel(pixel SE)E) y + 1000 t i S Density± Dens (meann ea Dropletet (m 500 pl PBS PNPLA3 r
Slide 36: CTA filing for WVE-008 expected in 2026
CTA filing for WVE-008 expected in 2026 • Large addressable patient population with no disease modifying treatment options targeting PNPLA3 I148M-driven liver disease • PNPLA3 preclinical data demonstrates ability to restore functional PNPLA3 with RNA editing, restoring lipid regulation for improvem
Slide 37: WVE-N531 Splicing Duchenne muscular dystrophy
WVE-N531 Splicing Duchenne muscular dystrophy 37
Slide 38: Advancing WVE-N531 in exon amenable DMD
Advancing WVE-N531 in exon 53 amenable DMD WVE-N531: exon skipping oligonucleotide designed to induce production of endogenous, functional dystrophin protein • High unmet need for therapies delivering more consistent dystrophin expression, as few patients today achieve dystrophin >5% of normal • Opp
Slide 39: FORWARD-53 48-week clinical trial results
FORWARD-53 48-week clinical trial results: WVE-N531’s potential best-in-class profile for boys amenable to exon 53 skipping ✓ Statistically significant and clinically meaningful improvement (3.8s) in Time-to-Rise vs. natural history; functional benefits on other measures including NSAA ✓ Statistical
Slide 40: Consistent dystrophin expression
Potential best-in-class, consistent dystrophin expression Potential best-in-class exon skipping Consistently exceeded levels associated with and dystrophin milder Becker phenotype Average: 24 and 48-week . adj 54% protein Mean exon skipping induced (95% CI: 46-63%) muscle & MHC dystrophin 1 7.8% Mea
Slide 41: WVE-N531 shifts dystrophic muscle towards healthy muscle
WVE-N531 appears to shift dystrophic muscle towards healthy muscle Feedback turns off regeneration (fewer stem cells and they are in resting state) Healthy Damage Inflammation Regeneration Fiber maturation Healthier Muscle Shift Toward Fiber ? Fiber organization Maturation and uniformity of ? Stem c
Slide 42: Evidence of reversal of fibrosis
Evidence of reversal of fibrosis across majority of participants Week 24 Week 48 1 1 Participant 2 3 4 2 3 4 number 5 6 7 5 6 7 42 H&E-stained sections (20X magnification). Seven paired biopsies available from week 24 and 48 for histopathology.
Slide 43: Significant reductions in creatine kinase
Statistically significant reductions in creatine kinase (CK) as compared to baseline and natural history ~50% CK reduction from baseline at 48 weeks Statistically significant reduction in CK vs. C-PATH Natural History * ** ***(U/L) *** *** (U/L) *** kinase kinase Creatine in Creatine e Chang Week 24
Slide 44: Only DMD therapeutic to show uptake in myogenic stem cells
WVE-N531 is the only DMD therapeutic to show uptake in myogenic stem cells WVE-N531 uptake in myofiber nuclei WVE-N531 uptake in myogenic stem cells Myocytes Stars denote an injured myofiber Stem cell containing WVE-N531 Mag: 40x Mag: 20x Myocyte nuclei containing WVE-N531 (red) Mag: 20x Mag: 40x Du
Slide 45: Changes to key cell populations in muscle
Changes to key cell populations in muscle and decrease in systemic inflammatory cytokines, suggesting transition to healthier muscle Progression of regenerative to mature state of muscle tissue ~20% change in density of myogenic Significant decrease (~48%) in internalized Decrease in serum MCP-1 and
Slide 46: First evidence of reversal of fibrosis with exon skipping
First evidence of reversal of fibrosis with exon skipping treatment Mean fibrotic muscle % Fibrotic muscle Week 48 showed improved organization and uniformity of myofibers declined 28.6% at 48W declined by individual (n = 7) (n = 7) Week 24 Week 48 1 tissue positive Participant positive 2 %Trichrome
Slide 47: Slowing of disease progression measured by TTR
Statistically significant and clinically meaningful slowing of disease progression as measured by TTR Functional benefits on other measures including NSAA Mean change in time-to-rise (TTR) Mean change in NSAA (points) (sec) Total TTR in 3.8 second ning NSAA improvement in with 1.2 point baseline WVE
Slide 48: Wave DMD portfolio addresses >$2.4 billion opportunity in US
Wave DMD portfolio addresses >$2.4 billion opportunity in US alone with potential for expansion Multiple drivers of value with Wave portfolio Wave portfolio addresses up to skipping 40% of the DMD population • ~40–50% of exon 53, 51, 45 amenable boys remain untreated today Increasing exon • No exon
Slide 49: WVE-003 Allele-selective silencing Huntington's Disease
WVE-003 Allele-selective silencing Huntington’s Disease 49
Slide 50: Advancing WVE-003 to address HD across all stages
Advancing WVE-003 to address HD across all stages of disease WVE-003 is a first-in-class, allele-selective oligonucleotide for the treatment of HD • HD is a monogenic autosomal dominant genetic disease; fully penetrant and affects entire brain • No current disease modifying therapies for HD • Charac
Slide 51: Wild-type HTT is critical for normal neuronal function
Wild-type HTT (wtHTT) is critical for normal neuronal function and loss of wtHTT contributes to cellular dysfunction Mutant HTT has a detrimental effect on wild-type Wild-type HTT is crucial for cilia health HTT function • Lowering mHTT is expected to restore physiological • In the absence of wtHTT,
Slide 52: Allele-selective CSF lowering of mutant HTT protein
Allele-selective CSF lowering of mutant HTT protein of up to an industry leading 46% with three doses of WVE-003 and preservation of wild-type HTT Durability of mHTT reductions supports potential for quarterly dosing intervals Mutant HTT protein levels in CSF Wild-type HTT protein levels in CSF 2.00
Slide 53: WVE-003 allele-selective mHTT reduction and slowing of caudate atrophy
WVE-003 leads to allele-selective mHTT reduction, correlating with slowing of caudate atrophy Allele-selective mHTT Slowing of Caudate Silencing with wtHTT Functional Benefit Atrophy Preservation • mHTT reduction of up to • WVE-003 trended towards • Caudate atrophy is an 46% vs. placebo less caudate
Slide 54: Caudate atrophy analysis and WVE-003 next steps
Analysis of natural history demonstrates that absolute reduction of 1% in rate of caudate atrophy is associated with delay of onset of disability by ≥7.5-years WVE-003 next steps p<0.001 HR = 0.31 • Preparation ongoing for a global, potentially preservation registrational Phase 2/3 study TFC in adul
Slide 55: Reimagining RNA medicines
Reimagining RNA medicines 55
Slide 56: Poised for significant and sustained growth driven by editing and siRNA
Poised for significant and sustained growth driven by editing and siRNA WVE-008 PNPLA3 Liver Disease Other hepatic targets RNA WVE-006 AATD Extra-hepatic targets Editing RNAi WVE-007 Obesity Other hepatic targets Extra-hepatic targets 56
Slide 57: Anticipated upcoming milestones
Anticipated upcoming milestones 4Q 2025: Deliver 3-month Cohort 2 (240 mg) and Cohort 1 (75mg) data WVE-007 (INHBE) 1Q 2026: Deliver 3-month Cohort 3 (400 mg) and 6-month Cohort 2 data siRNA Obesity 2Q 2026: Deliver 3-month Cohort 4 (600 mg) and 6-month Cohort 3 data 1Q 2026: Deliver data from the 4
Slide 58: For questions contact: investorrelations@wavelifesci.com
For questions contact: investorrelations@wavelifesci.com
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