Wave Life Sciences Ltd. · NASDAQ:WVE
Wave Life Sciences — Investor Presentation (January 2025)
31 slides from Wave Life Sciences's investor presentation, Jan 13, 2025
Slide 1: Wave Life Sciences Corporate Presentation
Exhibit 99.1 Wave Life Sciences Corporate Presentation January 13, 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: 2024 was a year of breakthroughs
2024 was a year of breakthroughs Achieved first-ever RNA editing in humans, advancing best-in-class treatment for AATD Pioneering RNA editing Expanded GalNAc-AIMer pipeline: unveiled three new wholly owned RNA editing programs targeting PNPLA3, LDLR, APOB Selected and advanced INHBE GalNAc-siRNA cli
Slide 5: Convergence of a best-in-class platform with genetics
The powerful convergence of a validated, best-in-class platform with genetics • Multi-modal: RNA editing, RNAi, • Real-time integration of new human antisense, splicing genetic insights into discovery • Best positioned to engage • Proprietary deep learning models Unmatched Data-driven endogenous mac
Slide 6: Differentiated RNA medicines clinical pipeline
Differentiated RNA medicines clinical pipeline WVE-007 in Obesity WVE-006 in AATD WVE-N531 in DMD WVE-003 in HD GalNAc-siRNA GalNAc-RNA editing Exon 53 splicing Allele-selective targeting INHBE oligonucleotide oligonucleotide oligonucleotide Multiple CTAs submitted since RestorAATion-2 ongoing in FO
Slide 7: Advancing WVE-007 as a novel approach for obesity
Advancing WVE-007 as a novel, long acting, muscle sparing approach for obesity WVE-007 is a GalNAc-conjugated small interfering RNA (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
Slide 8: Human genetic data show INHBE LoF carriers have 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 Silencing
Slide 9: INHBE GalNAc-RNA expected to address obesity-associated health issues
INHBE GalNAc-RNA 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 and shrink hepatokine Activin E adipose tissue adipocytes Decreased
Slide 10: 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) INH
Slide 11: INHBE GalNAc-siRNA used synergistically with GLP-1s or to prevent weight regain
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 12: 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 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 treatment with GLP-1 therapy ✓
Slide 13: 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 study of ascending doses of WVE-007 Trial Design SAD Cohort 5 • Objective: Assess dose safety, MAD Cohort 3 tolerability, PK and PD SAD Cohort 4 • Key measure
Slide 14: 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 15: 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 ADAR editing approach to address editing treatment key goals of AATD treatment: Restore circulating, Reduce Z-AAT Retain M-AAT Subcutaneous 1 2 3 functional wild-type protein aggregation physiological injection M-AAT i
Slide 16: RestorAATion-2 clinical trial in Pi*ZZ AATD patients ongoing
RestorAATion-2 clinical trial in Pi*ZZ AATD patients ongoing RestorAATion-2: AATD Patients RestorAATion-1: Healthy Volunteers RestorAATion-1: Healthy Volunteers Single ascending dose (SAD) → Multiple-ascending dose (MAD) cohorts Multi-dosing complete Dose E in RestorAAtion-1 Up to 7 doses Dose D Coh
Slide 17: Achieved proof-of-mechanism for Wave's 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 18: 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; GalNAc-AIMers building on learnings ✓ Upregulation of LDLR of WVE-006 HeFH Patient population: ~900,0
Slide 19: 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 20: FORWARD-53: Phase 2 clinical 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 10 mg/kg Q4W Screening N = 11 Extension ✓ Interim analysis • Baseline functional • Muscle biopsy after 24 • Muscle biopsy after 48 assessments we
Slide 21: WVE-N531 is the 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 22: Results of interim analysis: WVE-N531
Results of interim analysis: WVE-N531 has potential to be the best-in-class therapeutic for DMD amenable to exon 53 skipping Best-in-class dystrophin Evidence supporting Safe and expression and muscle delivery improved muscle health well tolerated • Highly consistent, mean muscle • Improvement in se
Slide 23: Unlocking Wave's best-in-class exon skipping portfolio
Unlocking Wave’s best-in-class exon skipping portfolio DMD Population • Data for exons 51, 44, 52, 45 WVE-N531 Exon 53 demonstrate potential for even Not Amenable to Skipping greater dystrophin expression 8-10% Exon 51 17% • Opportunity to address up to 11-13% 40% of population (~10,000 6% Exon 44 p
Slide 24: Advancing WVE-003 to address HD across all stages of disease
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 25: 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 26: Allele-selective lowering of mutant HTT protein 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 27: WVE-003 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 28: Natural history analysis of caudate atrophy and WVE-003 next steps
Internal analysis of natural history demonstrates 1% reduction in rate of caudate atrophy would delay onset of disability by ≥7.5-years WVE-003 next steps p<0.001 HR = 0.31 • Planning underway, including key aspects of study design, for a global, potentially registrational Phase 2/3 study in adults
Slide 29: 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 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 30: Anticipated upcoming milestones
Anticipated upcoming milestones Allele-selective siRNA RNA editing Splicing silencing PNPLA3, LDLR, APOB, WVE-007 (INHBE) WVE-006 WVE-N531 (Exon 53) WVE-003 (SNP3) additional wholly owned Obesity AATD DMD HD programs 1Q 2025: 2025: 2025: 1Q 2025: 2H 2025: Initiate dosing in Deliver multidose Deliver
Slide 31: For questions contact: investorrelations@wavelifesci.com
For questions contact: investorrelations@wavelifesci.com
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