Wave Life Sciences Ltd. · NASDAQ:WVE
Wave Life Sciences — Investor Presentation (November 2024)
38 slides from Wave Life Sciences's investor presentation, Nov 20, 2024
Slide 1: Wave Life Sciences Corporate Presentation
Exhibit 99.1 Wave Life Sciences Corporate Presentation November 20, 2024
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: 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 • Best-in-class, clinically-validated oligonucleotide chemistry (PN, stereochemistry) Differentiated RNA medicines pipeline WVE-N531 in DMD WVE-006 in
Slide 4: Wave's best-in-class multi-modal platform
Wave’s best-in-class multi-modal platform Clinically-validated oligonucleotide chemistry (including PN, stereochemistry) Editing Silencing Splicing Efficient editing of RNA bases to Degradation of RNA transcripts to Restore RNA transcripts and turn on restore or modulate protein turn off protein pro
Slide 5: Wave has driven foundational advances in nucleic acid chemistry
Wave has driven foundational advances in nucleic acid chemistry to expand platform technologies and develop next generation of RNA therapeutics Further information can be found in recent platform publications Silencing (RNase H and Ago2) Splicing Editing 5 Full list of Wave publications: https://ir.
Slide 6: Three clinical updates in 2024 demonstrate continued platform translation
Three clinical updates in 2024 demonstrate continued platform translation Clinical Clinical Therapeutic Preclinical translation trial results modalities publication 53% exon skipping, 9.0% mean muscle-adjusted Splicing 42 µg/g muscle tissue dystrophin; safe and tolerable ✓ ✓ ✓ (WVE-N531 for DMD) con
Slide 7: Robust, diversified RNA medicines pipeline including first-in-class RNA editing programs
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 RestorAATion Clinical Program 200K SERPINA1 (AATD) global license GalNAc-AI
Slide 8: WVE-006 RNA editing (AIMers) Alpha-1 antitrypsin deficiency (AATD)
WVE-006 RNA editing (AIMers) Alpha-1 antitrypsin deficiency (AATD) 8
Slide 9: WVE-006: GalNAc-conjugated AIMer designed to correct mutant SERPINA1 transcript
WVE-006: GalNAc-conjugated AIMer designed to correct mutant SERPINA1 transcript to address both liver and lung manifestations of AATD WVE-006 for AATD Wild-type M-AAT protein A SERPINA1 Z allele mRNA encodes Z-AAT protein with E342K mutation AAT is an acute phase protein Serum AAT protects lungs pre
Slide 10: RestorAATion-1 and RestorAATion-2 ongoing
RestorAATion-1 and RestorAATion-2 ongoing RestorAATion-2: AATD Patients RestorAATion-1: Healthy Volunteers RestorAATion-1: Healthy Volunteers Single ascending dose (SAD) → Multiple-ascending dose (MAD) cohorts Multidosing Dose E ongoing in Dose E Up to 7 doses Dose D Cohort 3 Dose C Cohort 2 Dose B
Slide 11: Achieved proof-of-mechanism for Wave's RNA editing platform
Achieved proof-of-mechanism for Wave’s RNA editing platform Proof-of-mechanism after a single dose in RestorAATion-2 • Circulating wild-type M-AAT protein in plasma: Mean of 6.9 µM at day 15; more than 60% of total AAT • Increases in neutrophil elastase inhibition from baseline: Consistent with prod
Slide 12: Strategic collaboration with GSK to develop transformative RNA medicines
Strategic collaboration with GSK to develop transformative RNA medicines Maximize global Advance up to eight Collaboration Expand Wave’s potential for GSK collaboration Highlights pipeline WVE-006 for AATD programs 1 • $170 million upfront Wave to advance up to Up to $525 million in Up to $2.8 billi
Slide 13: Wholly owned GalNAc-AIMer programs
Wholly owned GalNAc-AIMer programs New targets meet key criteria, expected to improve probability of success: Correction of PNPLA3 Genetically defined liver disease Strongly supported by human genetics ✓ Leverage unique platform capabilities; Upregulation of LDLR ✓ GalNAc-AIMers building on learning
Slide 14: WVE-007 (INHBE program) GalNAc-siRNA silencing Obesity and other metabolic disorders
WVE-007 (INHBE program) GalNAc-siRNA silencing Obesity and other metabolic disorders 14
Slide 15: Human genetic data demonstrate INHBE carriers have a healthy metabolic profile
Human genetic data demonstrate that INHBE heterozygous 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 Silencing INHB
Slide 16: INHBE GalNAc-RNA expected to address health issues associated with obesity
INHBE GalNAc-RNA expected to address health issues associated with pathogenesis of obesity, associated metabolic disease Release of dimerized INHBE Binds to and activates Block adipose subunits creates hepatokine ACVR1C (ALK7) receptor in lipolysis Activin E adipose tissue Activin E Activin E Increa
Slide 17: Single doses of INHBE GalNAc-siRNA result in dose-dependent weight loss
Single doses of INHBE GalNAc-siRNA result in dose-dependent weight loss and reduction of visceral fat, without affecting muscle mass Reduction in body weight Reduction in visceral fat No muscle loss ✓✓✓ Quadricep weight (Day 28) Epididymal fat weight (Day 28) * PBS INHBE GalNAc-siRNA (3 mg/kg) INHBE
Slide 18: INHBE GalNAc-siRNA can be used synergistically with GLP-1s
INHBE GalNAc-siRNA can be used synergistically with GLP-1s or to prevent weight regain after the cessation of treatment with GLP-1s ~2x greater overall weight loss when added to Prevents weight regain after the cessation of GLP-1s ✓ ✓ GLP-1s p<0.05 ~2x greater weight loss Not significant Day Day Sin
Slide 19: Preclinical data support best-in-class profile of WVE-007
Preclinical data support best-in-class profile and potential to use WVE-007 across multiple treatment settings with 1-2x a year dosing ✓ Monotherapy: as a single agent. Weight loss similar to semaglutide with no loss of muscle mass and a reduction in fat mass with preferential effect to the visceral
Slide 20: CTA expected before year-end for Phase 1 trial of WVE-007
CTA expected before year-end for Phase 1 trial of WVE-007 in adults living with overweight or obesity, otherwise healthy Randomized, double-blind, placebo-controlled study of ascending doses of WVE-007 MAD Cohort 3 Trial Design SAD Cohort 5 • Objective: Assess dose safety, tolerability, PK and PD MA
Slide 21: WVE-N531 Splicing Duchenne muscular dystrophy
WVE-N531 Splicing Duchenne muscular dystrophy 21
Slide 22: Urgent need for improved therapeutic options for the treatment of DMD
Urgent need for improved therapeutic options for the treatment of DMD Duchenne is a devastating and fatal disease • Genetic mutation in dystrophin gene prevents the production of dystrophin protein, a critical component of healthy muscle function • Impacts ~1 / 5,000 newborn boys annually; ~20,000 n
Slide 23: FORWARD-53: ongoing potentially registrational Phase 2 trial of WVE-N531
FORWARD-53: An ongoing potentially registrational open-label Phase 2 clinical trial of WVE-N531 in boys with DMD amenable to exon 53 skipping 10 mg/kg Q2W Screening Safety Follow-up N = 11 • Baseline functional • Muscle biopsy after 24 • Muscle biopsy after 48 Interim weeks of treatment weeks of tre
Slide 24: Results of interim analysis: WVE-N531 potential best-in-class for exon 53 DMD
Results of interim analysis: WVE-N531 has potential to be the best-in-class therapeutic for exon 53 DMD Highly consistent dystrophin expression Muscle delivery and extended dosing across patients intervals • 9.0% muscle-content adjusted dystrophin (5.5% • Skeletal muscle tissue concentrations of WVE
Slide 25: WVE-N531 was localized in myofiber nuclei and myogenic stem cells
WVE-N531 was localized in myofiber nuclei and 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 Dual staini
Slide 26: Dystrophin expression of up to ~14% with high consistency across participants
Dystrophin expression of up to ~14% with high consistency across participants Percentage dystrophin expression across each patient after 24 weeks of treatment 13.9% Dystrophin Adjusted for Muscle Content • Mean 9.0% absolute muscle content 12.2% 11.6% Dystrophin Unadjusted for Muscle Content adjuste
Slide 27: Unlocking Wave's best-in-class exon skipping portfolio
Unlocking Wave’s best-in-class exon skipping portfolio DMD Population WVE-N531 • Data for exons 51, 44, 52, 45 Exon 53 Not Amenable to demonstrate potential for even Skipping greater dystrophin expression 8-10% Exon 51 17% • Opportunity to address up to 11-13% 40% of population 6% Exon 44 4% Exon 52
Slide 28: WVE-003 Allele-selective silencing Huntington's Disease
WVE-003 Allele-selective silencing Huntington’s Disease 28
Slide 29: Huntington's disease is a devastating neurological disorder
Huntington's disease is a devastating neurological disorder caused by a toxic gain of function and concurrent loss of function HD-ISS stage probability and predicted clinical landmark • HD is a monogenic autosomal changes as a function of age dominant genetic disease; fully penetrant and affects ent
Slide 30: 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 31: Allele-selective lowering of mutant HTT protein of up to 46% with WVE-003
Allele-selective lowering of mutant HTT protein of up to 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 Wild-type HTT protein levels 2.00 2.00 Placebo Placebo WVE-003 30 mg WV
Slide 32: WVE-003 leads to 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 33: Regularity of caudate change makes it an ideal biomarker
Regularity of caudate change makes it an ideal biomarker for more efficient clinical development in HD • Caudate volume has a more regular, • HD-ISS Stage 2 linear change at individual level versus variability in individual trajectories with cUHDRS 1 • Wave analysis of PREDICT and TRACK-HD reinforce
Slide 34: Preservation of caudate volume offers an efficient pathway for potential accelerated approval
Preservation of caudate volume offers an efficient pathway for potential accelerated approval for HD • Received supportive initial feedback from FDA: - Recognize the severity of HD - Receptive to and engaged with Wave regarding a potential pathway to accelerated approval - Open to Wave’s plan to eva
Slide 35: Reimagining RNA medicines
Reimagining RNA medicines 35
Slide 36: Poised for significant and sustained growth driven by editing and siRNA
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 PNPLA3 DMD WVE-N531 Exon 53 LDLR & APOB Add’l SNPs Add’l Exons Wave’s platform is translating in the clinic and has potential to treat >90M patient
Slide 37: Anticipated upcoming milestones
Anticipated upcoming milestones Allele-selective GalNAc-RNA editing GalNAc-siRNA Splicing silencing WVE-006 PNPLA3 - Liver disease WVE-007 (INHBE) WVE-N531 (Exon 53) WVE-003 (SNP3) AATD LDLR, APOB - HeFH Obesity DMD HD 2025: 2025: Year-end 2024: 1Q 2025: 2H 2025: Deliver multidose Select clinical De
Slide 38: For questions contact: investorrelations@wavelifesci.com
For questions contact: investorrelations@wavelifesci.com
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