Wave Life Sciences Ltd. · NASDAQ:WVE
Wave Life Sciences — Investor Presentation (October 2024)
38 slides from Wave Life Sciences's investor presentation, Oct 1, 2024
Slide 1: Wave Life Sciences Corporate Presentation
Exhibit 99.1 Wave Life Sciences Corporate Presentation October 1, 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 (PN, stereochemistry) Splicing Editing Silencing Restore RNA transcripts and turn on Efficient editing of RNA bases to Degradation of RNA transcripts to protein production restore or modulate protein turn off pr
Slide 5: 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: Proprietary chemistry continues to translate in clinic across modalities
Proprietary chemistry continues to translate in clinic across modalities, enabling first-in-class and best-in-class therapies Clinical Clinical Therapeutic Preclinical translation trial results modalities publication 53% exon skipping, 9.0% mean muscle-adjusted Splicing 42 µg/g muscle tissue dystrop
Slide 7: Robust, diversified RNA medicines pipeline
Robust, diversified RNA medicines pipeline including first-in-class RNA editing programs IND / CTA Enabling Patient population Program Discovery / Preclinical Clinical Rights Studies (US & Europe) R NA E D I T I NG GSK exclusive WVE-006 RestorAATion Clinical Program 200K SERPINA1 (AATD) global licen
Slide 8: WVE-006 + AIMers RNA editing: Alpha-1 antitrypsin deficiency
WVE-006 + AIMers RNA editing Alpha-1 antitrypsin deficiency (AATD) 8
Slide 9: WVE-006: GalNAc-conjugated AIMer 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 aims to address the large unmet need in AATD • 200,000 Pi*ZZ patients in US and Europe WVE-006 for AATD • Current standard of care is weekly IV augmentation t
Slide 10: WVE-006 in AATD: First-in-class RNA editing clinical candidate
WVE-006 in AATD: First-in-class RNA editing clinical candidate 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 treatment
Slide 11: 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 → Cirrhosis → 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 12: AIMer-directed editing is highly specific in mice
AIMer-directed editing is highly specific in mice RNA editing only detected at PiZ mutation RNA editing across transcriptome site in SERPINA1 transcript PBS SERPINA1 C 0% (PiZ mutation site) T 100% AATD AIMer C 48.2% T 51.8% Editing site % Editing (PiZ mutation) No bystander editing observed on SERP
Slide 13: RestorAATion-2 underway, proof-of-mechanism data expected 4Q 2024
RestorAATion-2 underway, proof-of-mechanism data expected in 4Q 2024 Informs dose & dose frequency RestorAATion-1: Healthy Volunteers RestorAATion-2: AATD Patients RestorAATion-1: Healthy Volunteers Single ascending dose (SAD) → Multiple-ascending dose (MAD) cohorts Dose E Up to 7 doses Dose D Cohor
Slide 14: Multiple RNA editing opportunities beyond WVE-006
Multiple RNA editing opportunities to build high-value, wholly owned pipeline beyond WVE-006 Potential to advance any combination of targets into preclinical development Hepatic (GalNAc-AIMers) Extra-Hepatic (AIMers) Target A Target B Target X Target E Target F Target G Approach Upregulation Upregul
Slide 15: Strategic collaboration with GSK
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 16: WVE-007 (INHBE program) GalNAc-siRNA silencing
WVE-007 (INHBE program) GalNAc-siRNA silencing Obesity and other metabolic disorders 16
Slide 17: Potential for best-in-class siRNA enabled by PRISM platform
Potential for best-in-class siRNA enabled by Wave’s PRISM® platform • Unprecedented Ago2 loading increases potency and Next-generation siRNA results in durability of silencing following administration of more potent and durable silencing single subcutaneous dose Ago2 loading Next generation siRNA en
Slide 18: WVE-007 INHBE silencing expected to drive healthy weight loss
Supported by human genetics, WVE-007 (INHBE GalNAc-siRNA) expected to drive healthy, sustainable weight loss INHBE silencing expected to induce fat loss, Distinct pathway as compared to GLP-1s while maintaining muscle mass 1 ✓ Weight loss with no impact on muscle mass • Silencing INHBE gene by ≥ 50%
Slide 19: WVE-007 next generation siRNA format and best-in-class profile
WVE-007 has Wave’s next generation siRNA format and best-in-class profile with infrequent dosing INHBE program: Data from DIO mouse model supports best-in-class profile and potential use of WVE-007 in multiple treatment settings ✓ Highly potent (ED50 < 1mg/kg) and durable silencing following one, lo
Slide 20: WVE-N531 Splicing: Duchenne muscular dystrophy
WVE-N531 Splicing Duchenne muscular dystrophy 20
Slide 21: Urgent need for improved therapeutic options for 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 22: FORWARD-53 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 23: Results of interim analysis of WVE-N531
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 24: WVE-N531 was safe and well tolerated
WVE-N531 was safe and well tolerated WVE-N531 10 mg/kg TEAE Category n=11 Patients (%) Any TEAE 10 (90.9) Any drug-related TEAE 3 (27.3) Mild 3 (27.3) Moderate 0 Severe 0 Any serious TEAE 0 Any severe TEAE 0 Any TEAE leading to discontinuation 0 Any TEAE leading to death 0 No Serious Adverse Events
Slide 25: Industry-leading muscle tissue concentrations and exon skipping
Industry-leading muscle tissue concentrations and exon skipping Muscle tissue concentrations Exon skipping ~41,000 ng/g 57% Tissue half-life of 61 days supports monthly dosing 25 Muscle tissue concentrations and exon skipping n=11; ~41,000 ng/g = ~5,900 nM WVE-N531 muscle concentration (ng/g, mean +
Slide 26: WVE-N531 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 27: Dystrophin expression of up to 14% with high consistency
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 adjusted
Slide 28: WVE-N531 in skeletal muscle likely underrepresents heart and diaphragm activity
WVE-N531 in skeletal muscle likely to underrepresent activity in heart and diaphragm Preclinical data: → Higher dystrophin in heart dKO: Dystrophin restoration ~9% ~12% ~17% and diaphragm, survival benefit cardiac and respiratory functional improvements WVE-N531 muscle tissue → Greater exposure in h
Slide 29: Unlocking 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 30: WVE-003 Allele-selective silencing: Huntington's Disease
WVE-003 Allele-selective silencing Huntington’s Disease 30
Slide 31: 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 32: 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 33: Allele-selective lowering of mutant HTT protein of up to 46%
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 34: WVE-003 allele-selective 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 Slowing of Caudate KD with wtHTT Functional Benefit Atrophy Preservation • mHTT reduction of up to • WVE-003 trended towards • Caudate atrophy is an 46% vs. placebo less caudate atroph
Slide 35: Preservation of caudate volume offers path to accelerated approval
Preservation of caudate volume offers an efficient pathway for potential accelerated approval for HD Draft study design:• Randomized, placebo controlled clinical study Adults with SNP3 and HD Stage 1-2 Registrational study powered to show impact on • N = ~150 caudate atrophy• 12-18 months duration A
Slide 36: Anticipated upcoming milestones
Anticipated upcoming milestones 36
Slide 37: Wave is poised for significant and sustained growth
Wave is poised for significant and sustained growth AATD WVE-006 DMD Obesity WVE-N531 WVE-007 (INHBE) Exon 53 HD Add’l GalNAc liver WVE-003 Add’l AIMer Programs Add’l Exons siRNA programs SNP3 (GalNAc liver and extra-hepatic) Add’l SNPs Wave’s platform is translating in the clinic; AATD proof-of-mec
Slide 38: For questions contact investorrelations@wavelifesci.com
For questions contact: investorrelations@wavelifesci.com
Wave Life Sciences — Investor Presentation (October 2024) on 6ix