Wave Life Sciences Ltd. · NASDAQ:WVE
Wave Life Sciences — Investor Presentation (August 2025)
45 slides from Wave Life Sciences's investor presentation, Aug 5, 2025
Slide 1: Wave Life Sciences Corporate Presentation
Exhibit 99.1 Wave Life Sciences Corporate Presentation August 5, 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 3
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) Pioneering a novel RNA Potential best-in-class Leaders
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 • Multi-modal: RNA editing, RNAi, • Real-time integration of new human antisense silencing, splicing genetic insights into discovery • Best positioned to engage • Proprietary deep learning models Unm
Slide 6: Robust, diversified RNA medicines pipeline
Robust, diversified RNA medicines pipeline including first-in-class RNA editing programs IND / CTA Enabling Patient population Program Discovery Clinical Rights Studies (US & Europe) R N A E D I T I N G GSK exclusive WVE-006 (GalNAc) 200K SERPINA1 (AATD) global license GalNAc-AIMer 100% global 9M PN
Slide 7: WVE-007 GalNAc-siRNA silencing Obesity
WVE-007 GalNAc-siRNA silencing Obesity 7
Slide 8: Advancing WVE-007 as a novel, long acting, muscle sparing approach for obesity
Advancing WVE-007 as a novel, long acting, muscle sparing approach for obesity WVE-007 is a GalNAc-siRNA that targets INHBE to treat obesity • Adults with obesity have higher risk for many serious health conditions, including heart disease, type 2 1 diabetes, and some forms of cancer • GLP-1s are cu
Slide 9: Human genetic data on INHBE LoF carriers
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: INHBE GalNAc-siRNA mechanism in obesity-associated metabolic disease
INHBE GalNAc-siRNA expected to address health issues associated with pathogenesis of obesity associated metabolic disease Reduced release of Diminished activation of Increased adipose GalNAc-siRNA ACVR1C (ALK7) receptor in lipolysis shrinks hepatokine Activin E adipose tissue adipocytes Decreased ab
Slide 11: Single doses result in dose-dependent 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 ✓ ✓ ✓ Quadricep weight (Day 28) Epididymal fat weight (Day 28) * PBS INHBE GalNAc-siRNA
Slide 12: Synergy with GLP-1s and curtailing weight regain
INHBE GalNAc-siRNA can be used synergistically with GLP-1s or to curtail weight regain after the cessation of treatment with GLP-1 ~2x greater overall weight loss when added to Curtails weight regain after the cessation of GLP-1 ✓ ✓ GLP-1 p<0.05 ~2x greater weight loss Not significant Day Day Single
Slide 13: Single dose led to shrinkage of adipocytes in DIO mice
A single dose of INHBE GalNAc-siRNA led to shrinkage of adipocytes in DIO mice Mean adipocyte diameter DIO Lean PBS INHBE GalNAc-siRNA (μm) 13 Data presented at ADA Scientific Sessions June 2025 ***p<0.001
Slide 14: Lower inflammatory state of visceral adipose tissue in DIO mice
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 15: Preclinical data support potential best-in-class profile of WVE-007
Preclinical data support potential best-in-class profile and potential to use WVE- 007 across multiple treatment settings with potential for 1-2x per year dosing Monotherapy Add-on to GLP-1s Maintenance WVE-007 in addition to GLP-1 WVE-007 for patients who stop WVE-007 as a single agent therapy trea
Slide 16: INLIGHT: Phase 1 trial of WVE-007
INLIGHT: Phase 1 trial of WVE-007 in adults living with overweight or obesity, otherwise healthy Randomized, double-blind, placebo-controlled (3:1) study of ascending doses of WVE-007 SAD Cohort 5 Trial Design MAD Cohort 3 • Objective: Assess dose safety, tolerability, PK and PD SAD Cohort 4 • Key m
Slide 17: WVE-006 RNA editing (AIMers) Alpha-1 antitrypsin deficiency
WVE-006 RNA editing (AIMers) Alpha-1 antitrypsin deficiency (AATD) 17
Slide 18: Advancing WVE-006 (RNA editing) in AATD
Advancing WVE-006 (RNA editing) in AATD WVE-006: GalNAc-conjugated, subcutaneously delivered, designed to address AATD-related lung disease, liver disease, or both • AATD is a rare, inherited genetic disorder that is commonly caused by a G-to-A point mutation in the SERPINA1 gene • Characterized by
Slide 19: WVE-006 to address both liver and lung manifestations of AATD
WVE-006 to address both liver and lung manifestations of AATD WVE-006 RNA WVE-006 RNA editing approach to address editing treatment key goals of AATD treatment: Restore circulating, Reduce Z-AAT Retain M-AAT Subcutaneous 1 functional wild-type 2 protein aggregation 3 physiological injection M-AAT in
Slide 20: RestorAATion-2 clinical trial ongoing
RestorAATion-2 clinical trial in Pi*ZZ AATD patients ongoing RestorAATion-2: AATD Patients RestorAATion-1: Healthy Volunteers RestorAATion-1: Healthy Volunteers SAD → MAD Multi-dosing complete in RestorAATion-1 SAD → MAD Dose E Up to seven doses in multi-dose portion Cohort 3 Dose D Cohort 2 400 mg
Slide 21: Achieved proof-of-mechanism for RNA editing platform
Achieved proof-of-mechanism for Wave’s RNA editing platform Proof-of-mechanism achieved after a single dose in RestorAATion-2 ✓ Total AAT protein increased to a mean of 10.8 µM at day 15 ✓ Meets level that has been the basis for regulatory approval for AAT augmentation therapies ✓ Circulating wild-t
Slide 22: Wholly owned GalNAc-AIMer programs
Wholly owned GalNAc-AIMer programs Correction of PNPLA3 Strongly supported by human genetics Genetically defined liver disease ✓ Patient population: ~9 million Leverage unique platform capabilities; ✓ Building on learnings of WVE-006 Upregulation of LDLR HeFH Patient population: ~900,000, with Novel
Slide 23: WVE-N531 Splicing Duchenne muscular dystrophy
WVE-N531 Splicing Duchenne muscular dystrophy 23
Slide 24: 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 25: 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 Statisticall
Slide 26: Potential best-in-class, 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 54% Mean exon skipping induced (95% CI: 46-63%) 7.8% 1 Mean dystrophin expression (95% CI: 5.4-1
Slide 27: 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) Damage Inflammation Regeneration Fiber maturation Healthy Healthier Muscle Shift Toward Fiber é Fiber organization Maturation and uniformity of ê Stem c
Slide 28: Evidence of reversal of fibrosis
Evidence of reversal of fibrosis across majority of participants Week 24 Week 48 1 1 Participant number 2 3 4 2 3 4 5 6 7 5 6 7 28 H&E-stained sections (20X magnification). Seven paired biopsies available from week 24 and 48 for histopathology.
Slide 29: Statistically significant reductions in creatine kinase
Statistically significant reductions in creatine kinase (CK) as compared to baseline and natural history Statistically significant reduction in CK vs. ~50% CK reduction from baseline at 48 weeks C-PATH Natural History * *** ** *** *** *** Week 24 Week 0 48 Decreased CK to levels observed in milder D
Slide 30: 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 31: Changes to key cell populations and inflammatory cytokines
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 32: First evidence of reversal of fibrosis with exon skipping
First evidence of reversal of fibrosis with exon skipping treatment Week 48 showed improved organization and uniformity of myofibers Mean fibrotic muscle % Fibrotic muscle declined 28.6% at 48W declined by individual (n = 7) (n = 7) Week 24 Week 48 24 48 24 48 Time (weeks) Time (weeks) 32 Right: Mag
Slide 33: Slowing of disease progression measured by TTR and NSAA
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 3.8 second improvement 1.2 point with improvement WVE-N531 with WVE-N531 Week Week 33 Left:
Slide 34: 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 • ~40–50% of exon 53, 51, 45 skipping 40% of the DMD population amenable boys remain untreated today Increasing exon • No exon
Slide 35: Regulatory update and exon skipping franchise derisked
Regulatory update and exon skipping franchise derisked FORWARD-53 • All participants are enrolled in the ongoing open-label FORWARD-53 extension trial receiving monthly doses of WVE-N531 • Expanding FORWARD-53 to include additional boys on monthly dosing regimen REGULATORY • FDA feedback confirmed t
Slide 36: WVE-003 Allele-selective silencing Huntington's Disease
WVE-003 Allele-selective silencing Huntington’s Disease 36
Slide 37: 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 38: 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 • In the absence of wtHTT, ciliogenesis fails, disrupting CSF • Lowering mHTT i
Slide 39: 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 40: Allele-selective mHTT reduction correlating with 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 41: Caudate atrophy natural history 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 registrational Phase 2/3 study in adults with SNP3 and
Slide 42: Reimagining RNA medicines
Reimagining RNA medicines 42
Slide 43: Poised for significant and sustained growth
Poised for significant and sustained growth driven by editing and siRNA GalNAc-siRNA GalNAc-Editing Obesity HD WVE-007 (INHBE) WVE-003 AATD SNP3 WVE-006 Liver Disease DMD PNPLA3 WVE-N531 Exon 53 HeFH Add’l SNPs LDLR & APOB Add’l Exons Current pipeline has potential to treat well over 100 million pat
Slide 44: Anticipated upcoming milestones
Anticipated upcoming milestones Allele-selective siRNA RNA editing Splicing silencing WVE-007 (INHBE) WVE-006 Wholly owned WVE-N531 (Exon 53) WVE-003 (SNP3) Obesity AATD programs DMD HD 4Q 2025: 3Q 2025: 2025: 2026: 2H 2025: Deliver data from the Deliver data from the Deliver new preclinical Submit
Slide 45: For questions contact investor relations
For questions contact: investorrelations@wavelifesci.com
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