Wave Life Sciences Ltd. · NASDAQ:WVE
Wave Life Sciences — Investor Presentation (January 2017)
28 slides from Wave Life Sciences's investor presentation, Jan 6, 2017
Slide 1: Corporate Presentation January 6, 2017
Corporate Presentation January 6, 2017 Exhibit 99.1
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, business strategies, development plans, regulatory activ
Slide 3: WAVE Life Sciences Overview
WAVE Life Sciences Overview Genetic medicines company developing targeted nucleic acid therapies for patients impacted by rare diseases Rationally designed nucleic acid therapeutics optimized by stereochemistry Three lead candidates initiating clinical trials in 2017 Six development programs by end
Slide 4: WAVE Life Sciences Overview: company history and milestones
Founded Chiralgen (Japan) Takeshi Wada Ontorii (USA) Greg Verdine 2009 2013 WAVE Life Sciences Formed Paul Bolno joins as CEO 2015 Nasdaq Initial Public Offering WVE: 6.4m shares @ $16 License Tuschl ssRNAi 2016 2017 2018 Initiate Clinical Development for HD Programs Data readouts expected for 3 Lea
Slide 5: WAVE Life Sciences R&D: Core Neurology and Non-Core Portfolio
WAVE Life Sciences R&D Exploratory Platform Core Neurology Portfolio Mid 2017 Mid 2017 2H 2017 Non-Core Portfolio
Slide 6: Traditional approach yields over 500,000 different molecules per dose
An enormous number of permutations exist, often resulting in over 500,000 different molecules in every dose (e.g., 219 Antisense and Exon Skipping) Rp Sp Rp or Sp Linker Nucleotide Uncontrolled PS Modifications Introduce Chiral Centers Nucleic Acid Therapeutics Traditional Approach
Slide 7: WAVE platform enables rational design of nucleic acid therapeutics
WAVE platform enables the rational design, optimization and production of nucleic acid therapeutics, beginning with the control of stereochemistry By controlling the orientation of the chiral linkages in phosphorothioate (PS) backbone modifications, WAVE is able to optimize the interaction between a
Slide 8: WAVE Life Sciences Approach: Chemistry Platform
WAVE Optimized Isomers Stability Activity Immune Specificity WAVE Rational Design Antisense RNAi Exon skipping Target Sequence WAVE proprietary platform precisely controls oligonucleotide stereochemistry Enables the discovery of the rules governing nucleic acid based drug pharmacology Provides basis
Slide 9: WAVE chemistry enables increased stability and activity
Mipomersen WVE-2 WVE-3 WVE-5 WVE-7 WVE-6 WVE-4 WVE-1 Oligonucleotide remaining (%) Time (days) Rat liver homogenate Stability Activity WVE-5 WVE-7 WVE-3 Mipomersen WVE-4 WVE-6 WVE-2 WVE-1 Sequence ID Sequence (5’-3’) Mipomersen WVE-6 WVE-4 WVE-1 WVE-2 WVE-3 WVE-5 WVE-7 Target remaining (%) Time (min
Slide 10: WAVE chemistry allows highly specific targeting
Specificity RNA (full length) ASO RNA 13-mer RNA 7-mer RNA (full length) ASO 2.35min: 7mer 3.16min: 8mer, P-6mer 4.58min: P-7mer 5.91min: P-8mer 7.19min: 12mer 9.55min: 13mer 10.13min: P-11mer 11.14min: P-12mer, 14mer 12.11min: P-13mer 13.29min: P-14mer Others 2.45min: P-7mer 13.14: 13-mer Stereoran
Slide 11: Stereochemistry impacts immunogenicity
Immunogenicity CpG, 5mC, MOE Same modifications with optimized stereochemistry CpG, 5mC, MOE CpG, 5mC, MOE Human TLR9 assay PBMC IL-6 activation PBMC MIP-1b activation Conventional wisdom: 5-methyl C (5mC) and 2’ modification is sufficient to avoid immune activation However, substantial immune activ
Slide 12: WAVE Intellectual Property
WAVE Stereochemistry Patents Granted and Pending Foundational Chemistry Chiral Control and Design Platform Candidate Specific IP Co-exclusive license holder for single-strand RNAi (ssRNAi) patent estate Martinez J, Patkaniowska A, Urlaub H, Lührmann R, Tuschl T. Single-stranded antisense siRNAs guid
Slide 13: Co-exclusive license to single-strand RNAi patent estate
In June 2015, WAVE became the co-exclusive license holder (with Ionis Pharmaceuticals) to the single-strand RNAi patent estate (Tuschl, Zamore) Includes 19-29 nucleotides molecules; RNAi mechanism; various chemical modifications Single-stranded RNAi requires different design rules from double-strand
Slide 14: WAVE Advantages Summary
Continue to meet demand IND enabling studies GMP clinical trial supply Comparable cost of goods Potential cost-per-patient advantages (dose and schedule) Scalable Synthesis Superior Pharmacology Applicable Across Modalities Rational design of single drugs Increased activity Increased stability Incre
Slide 15: Huntington's Disease: Huntingtin gene and allele-specific approach
Huntingtin Gene (HTT) Expanded CAG repeat Wild-type (healthy) allele Mutant allele SNP associated with expanded CAG repeat SNP Enables targets for allele-specific silencing 100% 75% 25% 0% 1 2 3 4 Targeted SNP HD Patients covered Cumulative HD Patient Coverage ~80% 50% ~77% ~71% ~55% Background Auto
Slide 16: WVE-120101 Selectively Cleaves mHTT RNA
Huntington’s Disease WVE-120101 Selectively Cleaves mHTT RNA Reduced Complement Immune Response Selective Knockdown of mHTT Allele
Slide 17: WVE-120101 Selectively Reduces mHTT mRNA and Protein
Huntington’s Disease WVE-120101 Selectively Reduces mHTT mRNA and Protein
Slide 18: Distribution of WVE-120101 in Cynomolgus NHP Brain
Stereochemistry enables improved protein binding and distribution ViewRNA depicting perinuclear distribution of WVE-120101 (red) in non-human primate (NHP) deep gray matter structures following intrathecal administration WVE-120101 detectable in deep gray matter structures following intrathecal admi
Slide 19: Single Molecule Counting of mHTT
Source: Wild E, et al. Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington’s disease patients. J Clin Invest. 2015:125:1979–1986. Edward Wild, MA MB BChir PhD MRCP Principal Investigator at UCL Institute of Neurology and Consultant Neurologist at the National Hospital
Slide 20: Huntington's Disease Clinical Development Update
Refile IND for WVE-120101 and file IND for WVE-120102 in 1H 2017 with updated clinical protocols, accelerating time to multi-ascending dose (MAD) studies and potentially reducing time to proof-of-concept (POC) Updated plan informed by discussions with the FDA and new supportive data from multi-dose
Slide 21: Updated Clinical Trial Design for WVE-120101 and WVE-120102
1 Updated Clinical Trial Design for WVE-120101 and WVE-120102 Two parallel global placebo-controlled MAD trials targeting SNP-1 and SNP-2, respectively Primary Objective: Assess safety and tolerability of intrathecal doses in early manifest HD patients Additional Objectives: Exploratory pharmacokine
Slide 22: Duchenne Muscular Dystrophy (DMD)
Pre-mRNA mRNA Protein Pre-mRNA mRNA Protein Exon skipping (Potential Remedy) WAVE oligonucleotide skip Disrupted reading frame Restored reading frame Dysfunctional splicing (Disease) The Disease Fatal X-linked genetic neuromuscular disorder caused by reduction of functional dystrophin 1 in 3,500 boy
Slide 23: Duchenne Muscular Dystrophy: dose response on skipping efficiency
RNA skipping determined by quantitative RT-PCR WAVE isomers demonstrated a dose-dependent increase in skipping efficiency Dose Response on Skipping Efficiency (mRNA, in vitro) (4 Days) 10uM used for DMD protein restoration Western Blot Duchenne Muscular Dystrophy
Slide 24: Enhanced Protein Restoration using WAVE Chemistry
Enhanced Protein Restoration using WAVE Chemistry (10uM, 6 Days) Skeletal Muscle Tissue lysates Marker Mock Drisapersen Eteplirsen WV-isomer 1 WV-isomer 2 WV-isomer 3 dystrophin (400-427 kDa) Vinculin (120 kDa) DMD protein restoration by Western Blot in patient-derived myotubes Free uptake at 10uM c
Slide 25: Fold Increase of DMD Protein Restoration Compared to Eteplirsen
Fold Increase of DMD Protein Restoration Compared to Eteplirsen Percentage of DMD Protein Restoration Compared to Normal Skeletal Muscle Duchenne Muscular Dystrophy
Slide 26: Duchenne Muscular Dystrophy Clinical Development Update
Candidate selected for DMD Exon 51, WVE-210201 (WV-isomer 1) Clinical trials on track to initiate 2H 2017 Protocol development in collaboration with DMD community Trials to include ambulatory and non-ambulatory patients Patients previously treated with other exon skipping therapies will not be exclu
Slide 27: WAVE Manufacturing Capabilities
27 GMP manufacturing facility leased in Lexington, MA Increases control and visibility of our manufacturing supply chain, with potential commercial-scale capabilities by 2019 90,000 square foot facility to support future growth Supplements existing Cambridge headquarters and facilities Facility expe
Slide 28: 2017 Upcoming Catalysts
2017 Upcoming Catalysts Initiating Three Clinical Programs in 2017 Initiate two clinical trials in Huntington’s disease mid-2017 Potential to be first two allele-specific disease-modifying therapies Initiate clinical trial in DMD 2H 2017 First stereopure oligonucleotide targeting Exon 51 with potent
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