Slide 1: Wave Life Sciences Corporate Presentation
Exhibit 99.1 Wave Life Sciences Corporate Presentation September 5, 2023
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: Emerging leader in RNA medicines
Emerging leader in RNA medicines Multi-modal drug Differentiated, clinical- Strategic collaborations to discovery and stage RNA medicines expand and advance development platform to pipeline with first-in- pipeline (GSK and Takeda) address new areas of class RNA editing disease biology programs RNA e
Slide 4: RNA medicines allow matching disease target to therapeutic modality
RNA medicines allow matching disease target to therapeutic modality RNA Base Editing Splicing Silencing • Efficient editing of RNA bases • Restore RNA transcripts and • Degradation of RNA transcripts to restore or modulate turn on protein production to turn off protein production protein production
Slide 5: Potential for best-in-class RNAi enabled by Wave's PRISM platform
Potential for best-in-class RNAi enabled by Wave’s PRISM platform • First in vivo study of unconjugated siRNAs • Unprecedented Ago2 loading following demonstrated 70-90% APP silencing across administration of single subcutaneous dose six brain regions in mouse CNS at 8 weeks Ago2 Ago2 l l ooa adindi
Slide 6: Proprietary PN chemistry enhances potency across modalities
Proprietary PN chemistry enhances potency across modalities RNA Editing Splicing Silencing % Editing % Skipping Target knockdown (% remaining) 100 80 60 40 20 0 -8 -6 -4 -2 0 2 10 10 10 10 10 10 Concentration (µM) Concentration (µM) Ranked by potency of reference PS/PO compound Ranked by potency of
Slide 7: Robust RNA medicines pipeline including first-in-class RNA editing programs
Robust RNA medicines pipeline including first-in- class RNA editing programs Patient population Program Discovery Preclinical Clinical Rights (US & Europe) RNA EDITING WVE-006 GSK exclusive 200K SERPINA1 (AATD) global license Multiple undisclosed 100% global - SPLICING WVE-N531 100% global 2.3K Phas
Slide 8: WVE-N531 Duchenne muscular dystrophy
WVE-N531 Duchenne muscular dystrophy
Slide 9: Duchenne muscular dystrophy
Duchenne muscular dystrophy • Genetic mutation in dystrophin gene Disease State Restored State prevents the production of dystrophin Dysfunctional Splicing Exon Skipping Oligo protein, a critical component of healthy Mutant pre-mRNA Mutant pre-mRNA muscle function 50 51 53 54 55 50 51 53 54 55 • Imp
Slide 10: Extended survival in dKO preclinical model supports potential of exon-skipping therapeutics
Extended survival in dKO preclinical model supports potential of exon-skipping therapeutics for DMD PN chemistry improved function and survival in dKO mice dKO survival studies in literature Restored muscle and respiratory 100% survival at time of study termination function to wild-type levels 300 2
Slide 11: Preclinical data supported advancing WVE-N531 to clinical development
Preclinical data supported advancing WVE-N531 to clinical development WVE-N531 reached high concentrations in heart and WVE-N531: Dystrophin diaphragm in NHP restoration of up to 71% in vitro Western Blot normalized to primary healthy human myoblast lysate Conc (uM) % Dystrophin Dystrophin Vinculin
Slide 12: In multidose portion of study, patients received three biweekly 10 mg/kg doses
In multidose portion of study, patients received three biweekly 10 mg/kg doses Single ascending intra-patient doses Multidosing at 10 mg/kg every other week Weeks 0 2 4 6 Muscle 10 mg/kg 10 mg/kg 10 mg/kg 10 mg/kg Biopsy Initial cohort Period before initiating 6 mg/kg multidosing (~1 – 2 months) •Bo
Slide 13: WVE-N531 in DMD: Delivered positive proof-of-concept data in 4Q 2022
WVE-N531 in DMD: Delivered positive proof-of-concept data in 4Q 2022 Tissue % Exon Dystrophin • High exon skipping and Tissue Patient concentration skipping by Western blot muscle concentrations Source (µg/g) by RT-PCR (% of normal) after three biweekly 10 mg/kg doses 1 Deltoid 85.5 61.5 0.24 • Simi
Slide 14: Initiating Part B, a potentially registrational Phase 2 clinical trial of WVE-N531
Initiating Part B, a potentially registrational Phase 2 clinical trial of WVE-N531 Screening Biweekly Dosing (10 mg/kg IV) Safety Follow-up • Functional • Biopsy after 24 weeks of • Biopsy after 48 weeks of assessment treatment treatment • Functional assessment • Functional assessment • Design of Pa
Slide 15: GSK Collaboration and WVE-006 for Alpha-1 antitrypsin deficiency (AATD)
GSK Collaboration and WVE-006 for Alpha-1 antitrypsin deficiency (AATD)
Slide 16: Strategic collaboration with GSK to develop transformative RNA medicines
Strategic collaboration with GSK to develop transformative RNA medicines for genetically defined diseases Multiple value drivers to Wave ü $170 million upfront to 1 Milestone / royalties Milestone / royalties Genetic targets Wave (cash and equity ) Wave to leverage GSK granted exclusive global GSK t
Slide 17: WVE-006: Designed to correct mutant SERPINA1 transcript to address liver and lung manifestations
WVE-006: Designed to correct mutant SERPINA1 transcript to address both liver and lung manifestations of AATD WVE-006 designed to correct WVE-006 ADAR editing approach to address key goals of AATD treatment: Z allele mRNA to enable M-AAT protein to be produced 2) Reduce Z-AAT 1) Restore circulating,
Slide 18: WVE-006 in AATD: First-in-class RNA editing candidate approaching the clinic
WVE-006 in AATD: First-in-class RNA editing candidate approaching the clinic Potentially comprehensive approach to address both lung and liver manifestations of AATD Increased AAT protein Confirmed restored Demonstrated functionality in NSG-PiZ mice wild-type M-AAT protein of M-AAT protein WVE-006 t
Slide 19: WVE-006 decreases lobular inflammation and PAS-D globule size
WVE-006 decreases lobular inflammation and PAS-D globule size, prevents increase in hepatocyte turnover Fibrosis à Cirrhosis à Hepatocellular Carcinoma Correction of gain-of-function liver phenotypes Lobular inflammation Mitoses PAS-D-positive globule size (NSG PiZ mice, week 13) (NSG PiZ mice, week
Slide 20: AIMer-directed editing is highly specific in mice
AIMer-directed editing is highly specific in mice No bystander editing observed on SERPINA1 transcript RNA editing only detected at PiZ mutation site in SERPINA1 transcript RNA editing across transcriptome (mouse liver) (mouse liver) C 0% SERPINA1 PBS (PiZ mutation site) T 100% C 48.2% AATD AIMer T
Slide 21: WVE-003 Huntington's Disease
WVE-003 Huntington’s Disease
Slide 22: mHTT toxic effects lead to neurodegeneration; loss of wtHTT may contribute to HD
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 (
Slide 23: WVE-003: First-in-class allele-selective candidate for HD
WVE-003: First-in-class allele-selective candidate for HD Reductions in mean CSF mHTT and preservation of wtHTT • mHTT protein reductions observed in pooled analysis of single dose cohorts in observed in single dose cohorts SELECT-HD clinical study (Sep. 2022) wtHTT protein levels mHTT protein level
Slide 24: AIMers RNA base editing capability
AIMers RNA base editing capability
Slide 25: Proof-of-concept preclinical RNA editing data published in Nature Biotechnology
Proof-of-concept preclinical RNA editing data published in Nature Biotechnology (March 2022) • Specificity in vitro & in vivo (NHPs) • GalNAc conjugation • In vitro-in vivo translation (NHPs) • Foundational AIMer SAR AIMers detected in liver of NHP at Day 50 Substantial and durable editing in NHP AD
Slide 26: Expanding addressable disease target space using AIMers
Expanding addressable disease target space using AIMers to activate pathways and upregulate expression Correct G-to-A driver mutations with AIMers Modulate protein interactions with AIMers Modulate protein- Restore or correct Achieved protein interaction protein function POC Upregulate expression WV
Slide 27: Modulation of protein-protein interactions: AIMers enable activation of gene pathway in vivo
Modulation of protein-protein interactions: AIMers enable activation of gene pathway in vivo with single edit 27 n=2; Primary hepatocytes 48h of treatment with the indicated dose concentration of AIMers
Slide 28: Upregulation: AIMers can edit RNA motifs to restore or upregulate gene expression
Upregulation: AIMers can edit RNA motifs to restore or upregulate gene expression RNA binding proteins recognize sequence motifs to regulate various mRNA properties Stability Transport Processing Protein production • Enhance or inhibit • Intracellular localization • Splicing • Translational efficien
Slide 29: AIMers upregulate mRNA and downstream serum protein in vivo
AIMers upregulate mRNA and downstream serum protein in vivo above anticipated threshold Target A mRNA editing mRNA upregulation Protein upregulation (undisclosed liver 7 days post-initial dose 7 days post-initial dose 7 days post-initial dose target) GalNAc AIMer GalNAc AIMer GalNAc AIMer 20 • High
Slide 30: Anticipated upcoming milestones
Anticipated upcoming milestones
Slide 31: Anticipated upcoming milestones
Anticipated upcoming milestones RNA ANTISENSE SPLICING RNAi EDITING SILENCING WVE-006 for AATD WVE-N531 for DMD WVE-003 for HD Newest modality in Wave Most advanced RNA editing Potential best-in-class First-in-class platform candidate & potential best-in- approach with highest exon wild-type hunting
Slide 32: Realizing a brighter future for people affected by genetic diseases
Realizing a brighter future for people affected by genetic diseases For more information: Kate Rausch, Investor Relations InvestorRelations@wavelifesci.com 617.949.4827 32