Wave Life Sciences Ltd. · NASDAQ:WVE
Wave Life Sciences — Investor Presentation (May 2023)
34 slides from Wave Life Sciences's investor presentation, May 3, 2023
Slide 1: Wave Life Sciences Corporate Presentation
Wave Life Sciences Corporate Presentation May 3, 2023 Exhibit 99.2
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 discovery and development platform to address new areas of disease biology RNA editing, splicing and silencing Differentiated, clinical-stage RNA medicines pipeline with first-in-class RNA editing programs Strategic collaborations to expand and advan
Slide 4: RNA medicines allow matching disease target to therapeutic modality
RNA medicines allow matching disease target to therapeutic modality Silencing Splicing RNA Base Editing Degradation of RNA transcripts to turn off protein production Restore RNA transcripts and turn on protein production Efficient editing of RNA bases to restore or modulate protein production Endoge
Slide 5: Robust RNA medicines pipeline with first-in-class RNA editing programs
Program Discovery Preclinical Clinical Rights Patient population (US & Europe) RNA EDITING WVE-006 SERPINA1 (AATD) GSK exclusive global license 200K Multiple undisclosed 100% global - SPLICING WVE-N531 Exon 53 (DMD) 100% global 2.3K Other exons (DMD) 100% global Up to 18K SILENCING: ANTISENSE WVE-00
Slide 6: WVE-N531 Duchenne muscular dystrophy
WVE-N531 Duchenne muscular dystrophy
Slide 7: Duchenne muscular dystrophy
Duchenne muscular dystrophy Genetic mutation in dystrophin gene prevents the production of dystrophin protein, a critical component of healthy muscle function Impacts approx. 1 in every 5,000 newborn boys each year; approx. 20,000 new cases annually worldwide Approx. 8-10% are amenable to exon 53 sk
Slide 8: Preclinical data supported advancing WVE-N531 to clinical development
Preclinical data supported advancing WVE-N531 to clinical development Kandasamy et al., 2022; doi: 10.1093/nar/gkac018 PN chemistry improved function and survival in dKO mice WVE-N531: Dystrophin restoration of up to 71% in vitro Western Blot normalized to primary healthy human myoblast lysate Conc
Slide 9: 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 Initial cohort Boys with DMD amenable to exon 53 skipping 1 mg/kg 3 mg/kg 6 mg/kg 10 mg/kg Single ascending intra-patient doses Multidosing at 10 mg/kg every other week Weeks Dose WVE-N531 Period before initiating multido
Slide 10: 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 Patient Tissue Source Tissue concentration (µg/g) % Exon skipping by RT-PCR Dystrophin by Western blot (% of normal) 1 Deltoid 85.5 61.5 0.24 2 Deltoid 33.5 49.8 0.23 3 Bicep 8.3 47.9 0.34 Mean exon skipping: 53% Mean muscle concen
Slide 11: Initiating Part B, a potentially registrational Phase 2 trial of WVE-N531
Initiating Part B, a potentially registrational Phase 2 clinical trial of WVE-N531 Design: Phase 2, open-label, 10 mg/kg every other week, up to 10 patients Endpoints: Dystrophin (powered for >5% of normal), safety/tolerability, pharmacokinetics, functional assessments (incl. NSAA and others) Biopsi
Slide 12: GSK Collaboration and WVE-006 for Alpha-1 antitrypsin deficiency (AATD)
GSK Collaboration and WVE-006 for Alpha-1 antitrypsin deficiency (AATD)
Slide 13: Strategic collaboration with GSK
Collaboration leverages Wave’s unique stereopure, PN-chemistry containing PRISMTM platform, including editing, splicing, silencing (RNAi and antisense) Strategic collaboration with GSK to develop transformative RNA medicines for genetically defined diseases 1$120 million in cash and $50 million equi
Slide 14: WVE-006: Designed to correct mutant SERPINA1 transcript
3) Retain M-AAT physiological regulation 2) Reduce Z-AAT protein aggregation in liver WVE-006: Designed to correct mutant SERPINA1 transcript to address both liver and lung manifestations of AATD M-AAT reaches lungs to protect from proteases M-AAT secretion into bloodstream AAT: Alpha-1 antitrypsin
Slide 15: 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 in NSG-PiZ mice Demonstrated functionality of M-AAT protein Confirmed restored wild-type M-AAT protein WVE-006 t
Slide 16: Early lead AATD AIMer reduces aggregation of Z-AAT and inflammation in mouse liver
Early lead pre-optimization AATD AIMer (SA1-5) administered in huADAR/SERPINA1 mice (8–10 wKs old); lower left: 20x liver images PAS-D stained, 19 weeks; Quantification of PAS-D positive staining, Stats 2-way ANOVA; Right: Quantification lobular inflammation grade (Grade based on # of inflammatory f
Slide 17: AIMer-directed editing is highly specific in mice
RNA editing only detected at PiZ mutation site in SERPINA1 transcript (mouse liver) RNA editing across transcriptome (mouse liver) AIMer-directed editing is highly specific in mice SERPINA1 (PiZ mutation site) % Editing Dose 3x10 mg/kg (days 0, 2, 4) SC with AATD AIMer (SA1 – 4). Liver biopsies day
Slide 18: WVE-004 ALS and FTD
WVE-004 Amyotrophic Lateral Sclerosis (ALS) Frontotemporal Dementia (FTD)
Slide 19: C9orf72 repeat expansions: One of the most common genetic causes of ALS and FTD
C9orf72 repeat expansions: One of the most common genetic causes of ALS and FTD Typically 100’s-1000’s of GGGGCC repeats Amyotrophic Lateral Sclerosis (ALS) Frontotemporal Dementia (FTD) Hexanucleotide (G4C2)- repeat expansions in C9orf72 gene are common autosomal dominate cause for ALS and FTD Diff
Slide 20: Target engagement in patients supported advancing FOCUS-C9 clinical study
Target engagement in patients supported advancing FOCUS-C9 clinical study WVE-004 in C9-ALS/FTD: Successful translation of preclinical data to clinic PK/PD modeling using preclinical in vivo models predicted pharmacodynamically active starting dose Additional single- and multi-dose biomarker and saf
Slide 21: WVE-003 Huntington's Disease
WVE-003 Huntington’s Disease
Slide 22: Huntington's disease and mHTT effects
Healthy individual Huntington’s disease mHTT toxic effects lead to neurodegeneration; loss of wtHTT functions may also contribute to HD Stresses wtHTT Stresses wtHTT mHTT + ~50% decrease in wtHTT Healthy CNS function Synaptic dysfunction | Cell death | Neurodegeneration Loss of wtHTT functions Hunti
Slide 23: WVE-003: First-in-class allele-selective candidate for HD
WVE-003: First-in-class allele-selective candidate for HD mHTT protein levels Placebo WVE-003 (30 and 60 mg pooled*) wtHTT protein levels Reductions in mean CSF mHTT and preservation of wtHTT observed in pooled analysis of single dose cohorts in SELECT-HD clinical study Single dose of WVE-003 Single
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) Monian et al., 2022 published online Mar 7, 2022; doi: 10.1038.s41587-022-01225-1 SAR structure-activity relationship Specificity in vitro & in vivo (NHPs) In vitro-in vivo translation (NHPs) GalNAc conjugat
Slide 26: Expanding addressable disease target space using AIMers
Expanding addressable disease target space using AIMers to activate pathways and upregulate expression Modulate protein-protein interaction Upregulate expression Modify function Post-translational modification Alter folding or processing Restore or correct protein function Achieved POC WVE-006 (GalN
Slide 27: AIMers enable activation of gene pathway in vivo with single edit
n=2; Primary hepatocytes 48h of treatment with the indicated dose concentration of AIMers Modulation of protein-protein interactions: AIMers enable activation of gene pathway in vivo with single edit
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 Enhance or inhibit mRNA decay Stability Intracellular localization Transport Splicing Capping Processing PolyA usage Translational effi
Slide 29: AIMers upregulate mRNA and downstream serum protein in vivo
AIMers upregulate mRNA and downstream serum protein in vivo above anticipated threshold In vitro to in vivo translation of mouse Target A mRNA upregulation In vivo mRNA upregulation corresponds to an upregulation of Target A protein in serum at Day 7 demonstrating proof-of-concept mRNA upregulation
Slide 30: Wave's discovery and drug development platform
Wave’s discovery and drug development platform
Slide 31: Proprietary PN chemistry enhances potency across modalities
Silencing Proprietary PN chemistry enhances potency across modalities Improved knockdown Splicing Improved skipping Ranked by potency of reference PS/PO compound Ranked by potency of reference PS/PO compound PS/PO reference compound PS/PN modified compound % Skipping Target knockdown (% remaining) L
Slide 32: Potential for best-in-class RNAi enabled by Wave's PRISM platform
Potential for best-in-class RNAi enabled by Wave’s PRISM platform **** Left, Middle: Mice expressing human HSD17B13 transgene treated (3 mg/kg)siRNA or PBS, liver mRNA, guide strand concentration, Ago2 loading quantified. Stats: Two-way ANOVA with post-hoc test * P<0.05, ****P<0.0001. Liu et al., 20
Slide 33: Delivering on pipeline and platform catalysts
WVE-006 for AATD Most advanced RNA editing candidate & potential best-in-class approach for AATD WVE-006 CTA submissions expected in 2H 2023 Expansion opportunities in liver, CNS and kidney Newest modality in Wave platform Preclinical data suggest best-in-class potential for Wave RNAi capability Hep
Slide 34: 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
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