Wave Life Sciences Ltd. · NASDAQ:WVE
Wave Life Sciences — Investor Presentation (March 2025)
36 slides from Wave Life Sciences's investor presentation, Mar 4, 2025
Slide 1: Corporate Presentation March 4, 2025
Corporate Presentation March 4, 2025 Wave Life Sciences 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: Our Mission
To unlock the broad potential of RNA medicines to transform human health Our Mission
Slide 4: Building a leading RNA medicines company
Patient populations represent US and Europe; WVE-006 is partnered with GSK AATD: Alpha-1 antitrypsin deficiency DMD: Duchenne muscular dystrophy HD: Huntington’s disease *Cash runway does not include potential future milestones or other payments under GSK collaboration Building a leading RNA medicin
Slide 5: Convergence of a validated platform with genetics
The powerful convergence of a validated, best-in-class platform with genetics Unmatched toolkit to access novel biology Data-driven discovery powered by human genetics Foundation in chemistry innovation Multi-modal: RNA editing, RNAi, antisense silencing, splicing Best positioned to engage endogenou
Slide 6: Robust, diversified RNA medicines pipeline
AATD: Alpha-1 antitrypsin deficiency; DMD: Duchenne muscular dystrophy; HD: Huntington’s disease; HeFH: heterozygous familial hypercholesterolemia Robust, diversified RNA medicines pipeline including first-in-class RNA editing programs Program Discovery IND / CTA Enabling Studies Clinical Rights Pat
Slide 7: WVE-007 GalNAc-siRNA silencing Obesity
WVE-007 GalNAc-siRNA silencing Obesity
Slide 8: Obesity risks and limits of GLP-1s
Adults with obesity have higher risk for many serious health conditions, including heart disease, type 2 diabetes, and some forms of cancer1 GLP-1s are current standard of care for weight loss, but impact is often limited by: Loss of muscle mass2 Poor tolerability3 Frequent dosing4 High discontinuat
Slide 9: Silencing INHBE mRNA recapitulates healthy metabolic profile
Silencing INHBE mRNA by ≥50% is expected to recapitulate the healthy metabolic profile of heterozygous INHBE loss of function (LoF) carriers Akbari et al. Nat Commun. 2022 Aug 23;13(1):4844; Deaton et al. Nat Commun. 2022 Jul 27 Waist to hip ratio: waist to hip ratio adjusted for BMI; HDL-c: high-de
Slide 10: INHBE GalNAc-siRNA mechanism in obesity
1. Cell Reports (2018) 25, 1193–1203; 2. Biochemical Journal (2024) 481 547–564; 3. PNAS 2023 Vol. 120 No. 32 e2309967120; 4. Nat Commun 2022. https://doi.org/10.1038/s41467-022-32398-7; 5. Nat Commun 2022. https://doi.org/10.1038/s41467-022-31757-8 Decreased abdominal adiposity leads to weight loss
Slide 11: Single doses result in dose-dependent weight loss in DIO mice
Data from preclinical studies conducted in DIO mice; Stats: (left, middle, right) Linear Mixed Effects ANOVA with post hoc comparisons of marginal treatment effects vs. PBS per timepoint (left) or per tissue (middle, right) * p < 0.05 Single doses of INHBE GalNAc-siRNA result in dose-dependent weigh
Slide 12: INHBE GalNAc-siRNA synergy with GLP-1s
INHBE GalNAc-siRNA can be used synergistically with GLP-1s or to curtail weight regain after the cessation of treatment with GLP-1 Data from preclinical studies conducted in DIO mice; Left: 10nmol/kg in mouse is equivalent to therapeutic dose of GLP-1s in human. Stats: Linear Mixed Effects ANOVA wit
Slide 13: Curtailed rebound weight gain after semaglutide cessation
Curtailed rebound weight gain upon cessation of semaglutide and prevention of weight cycling, which worsens the outcomes of various metabolic diseases When administered as an add-on to semaglutide: A single dose of Wave’s INHBE GalNAc-siRNA doubled the weight loss observed with semaglutide alone Wei
Slide 14: INLIGHT Phase 1 trial of WVE-007
Dosing underway in INLIGHT with clinical data expected in 2H 2025; enrollment complete in SAD Cohort 1 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 SAD Cohort 5 SAD Co
Slide 15: WVE-006 RNA editing (AIMers) Alpha-1 antitrypsin deficiency
WVE-006 RNA editing (AIMers) Alpha-1 antitrypsin deficiency (AATD)
Slide 16: Advancing WVE-006 in AATD
Advancing WVE-006 (RNA editing) in AATD AATD is a rare, inherited genetic disorder that is commonly caused by a G-to-A point mutation in the SERPINA1 gene Characterized by aggregation of mutant Z-AAT protein in hepatocytes and a lack of functional AAT in lungs People with AATD typically exhibit prog
Slide 17: WVE-006 to address liver and lung manifestations of AATD
Strnad et al., 2020 N Engl J Med 382:1443-55; Stoller et al., 1993 Alpha-1 Antitrypsin Deficiency GeneReviews. WVE-006 to address both liver and lung manifestations of AATD WVE-006 RNA editing treatment WVE-006 RNA editing approach to address key goals of AATD treatment: Infrequent dosing Subcutaneo
Slide 18: RestorAATion-2 clinical trial ongoing
RestorAATion-2 clinical trial in Pi*ZZ AATD patients ongoing HV: healthy volunteer; SAD: single-ascending dose; MAD: multi-ascending dose RestorAATion-2: AATD Patients RestorAATion-1: Healthy Volunteers Dose A Cohort 1 200 mg SAD à MAD Up to seven doses in multi-dose portion Dose B Dose C Dose D Dos
Slide 19: Proof-of-mechanism for RNA editing platform
October 16, 2024 Proof-of-mechanism disclosure on first two “ZZ” AATD patients in first dose cohort of RestorAATion-2 to reach day 57 Multi-dose data from RestorAATion-2 expected in 2025 Achieved proof-of-mechanism for Wave’s RNA editing platform Proof-of-mechanism achieved after a single dose in Re
Slide 20: Additional RNA editing programs: PNPLA3, LDLR, APOB
Expect to initiate clinical development of additional RNA editing programs, including PNPLA3, LDLR, and APOB programs in 2026 Wholly owned GalNAc-AIMer programs Patient populations are in US and Europe HeFH: heterozygous familial hypercholesterolemia Editing for correction Editing for upregulation S
Slide 21: WVE-N531 Splicing Duchenne muscular dystrophy
WVE-N531 Splicing Duchenne muscular dystrophy
Slide 22: Advancing WVE-N531 in exon amenable DMD
Advancing WVE-N531 in exon 53 amenable DMD High unmet need for therapies delivering more consistent dystrophin expression, as few patients today achieve dystrophin >5% of normal Opportunity to extend dosing intervals beyond weekly standard of care to alleviate burden for patients and caregivers Need
Slide 23: FORWARD-53 Phase 2 trial design
FORWARD-53: An ongoing potentially registrational open-label Phase 2 clinical trial of WVE-N531 in boys with DMD amenable to exon 53 skipping IV: Intravenous; Q2W: Every 2 Weeks; PK: Pharmacokinetics; PD: Pharmacodynamics Screening 10 mg/kg Q2W N = 11 10 mg/kg Q4W Extension Baseline functional asses
Slide 24: WVE-N531 uptake in myogenic stem cells
WVE-N531 is the only DMD therapeutic to show uptake in myogenic stem cells Stars denote an injured myofiber Stem cell containing WVE-N531 WVE-N531 uptake in myogenic stem cells Dual staining utilizing in-situ hybridization for WVE-N531 and PAX7 immunohistochemistry for stem cells Mag: 20x Mag: 40x W
Slide 25: Interim dystrophin results in ambulatory boys
Dystrophin data from prespecified analysis of ambulatory boys; Muscle content adjustment was done using the formula: MHC-normalized dystrophin/(total myofiber area/total area of biopsy section). Interim analysis results announced September 24, 2024. Results of interim analysis: WVE-N531 has potentia
Slide 26: Best-in-class exon skipping portfolio
Aartsma-Rus, et al. 2009 Hum Mut 30, 293 Exon 45 Exon 44 Exon 52 WVE-N531 Exon 53 Exon 51 Not Amenable to Skipping 11-13% 8-10% 44% DMD Population Unlocking Wave’s best-in-class exon skipping portfolio Data for exons 51, 44, 52, 45 demonstrate potential for even greater dystrophin expression Opportu
Slide 27: WVE-003 Allele-selective silencing Huntington's Disease
WVE-003 Allele-selective silencing Huntington’s Disease
Slide 28: Advancing WVE-003 to address HD
HD is a monogenic autosomal dominant genetic disease; fully penetrant and affects entire brain No current disease modifying therapies for HD Characterized by cognitive decline, psychiatric illness, and chorea; ultimately fatal Expanded CAG triplet repeat in HTT gene results in production of mutant h
Slide 29: Importance of wild-type HTT; allele-selective approach
Saudou & Humbert 2016 Neuron; Cason et al., 2022 Nat Rev Cell Biol; Laundos et al., 2023 Front Cell Dev Biol; Kaliszewski et al., 2015 Cell Death Diff; Keryer et al., 2011 J Clin Invest Khoshnan & Patterson, 2011. Neurobiol Dis; Pogoda et al., 2021 Curr Med Chem; Hsiao et al., 2013 Hum Mol Genet Wil
Slide 30: Allele-selective lowering of mutant HTT
* p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 mHTT: mutant huntingtin protein; wtHTT: wild-type huntingtin protein From June 25, 2024 SELECT-HD disclosure 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 redu
Slide 31: mHTT reduction correlates with slowing of caudate atrophy
WVE-003 leads to allele-selective mHTT reduction, correlating with slowing of caudate atrophy Allele-selective mHTT Silencing with wtHTT Preservation Slowing of Caudate Atrophy Functional Benefit mHTT reduction of up to 46% vs. placebo wtHTT preserved/increased throughout study Caudate atrophy is an
Slide 32: WVE-003 next steps: Phase 2/3 IND in 2H 2025
Expect to submit IND application for potentially registrational Phase 2/3 study in 2H 2025 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 Wave internal analysis; TRACK-HD and PREDICT-HD a
Slide 33: Reimagining RNA medicines
Reimagining RNA medicines A UE SCIENCES,
Slide 34: Poised for growth driven by editing and siRNA
Poised for significant and sustained growth driven by editing and siRNA Note: Bubble size illustrative of size of total addressable US market (assuming 100% share of addressable patients) Current pipeline has potential to treat well over 100 million patients in US and Europe Obesity WVE-007 (INHBE)
Slide 35: Cash runway into 2027 and upcoming milestones
WVE-N531 (Exon 53) DMD WVE-003 (SNP3) HD Well-capitalized with expected cash runway into 2027 Anticipated upcoming milestones AATD: Alpha-1 antitrypsin deficiency; DMD: Duchenne muscular dystrophy; HD: Huntington’s disease; IND: Investigational New Drug 1Q 2025: Deliver 48-week FORWARD-53 data & fee
Slide 36: For questions contact investor relations
For questions contact: investorrelations@wavelifesci.com
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