Wave Life Sciences Ltd. · NASDAQ:WVE
Wave Life Sciences — Investor Presentation (January 2018)
46 slides from Wave Life Sciences's investor presentation, Jan 5, 2018
Slide 1: Wave Life Sciences Corporate Presentation
Wave Life Sciences Corporate Presentation January 5, 2018
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: Genetic medicines company
Genetic medicines company Developing targeted therapies for patients impacted by rare diseases Rationally designed stereopure nucleic acid therapeutics Utilizing multiple modalities including antisense, exon skipping and RNAi 6 proprietary neurology development programs by the end of 2018 Expertise
Slide 4: Paving the way to potentially safer, more effective medicines
Paving the way to potentially safer, more effective medicines 1 6 3 10K+ first to design neurology clinical studies Wave stereopure and bring stereopure development initiated oligonucleotides and allele-specific programs in 2017 created and medicines to clinic by end of 2018 analyzed to date 5 12+ 5
Slide 5: Pipeline spanning multiple modalities, novel targets
Pipeline spanning multiple modalities, novel targets ESTIMATED U.S. ADDRESSABLE NEXT ANTICIPATED DISEASE TARGET BIOMARKER PATIENTS * MILESTONES CNS Huntington’s disease mHTT SNP1 mHTT ~10k / ~35k A Phase 1b/2a Top line data 1H 2019 Huntington’s disease mHTT SNP2 mHTT ~10k / ~35k A Phase 1b/2a Top li
Slide 6: Neurology leadership
Neurology leadership Current programs Huntington’s disease (HTT SNP1) Huntington’s disease (HTT SNP2) Duchenne muscular dystrophy (exon 51) Duchenne muscular dystrophy (exon 53) Amyotrophic lateral sclerosis (C9orf72) Frontotemporal dementia (C9orf72) Discovery engine Neuromuscular diseases DMD (add
Slide 7: Broad platform relevance across therapeutic areas
Broad platform relevance across therapeutic areas CNS Muscle 7
Slide 8: Building the optimal, stereopure medicine
Building the optimal, stereopure medicine STANDARD OLIGONUCLEOTIDE APPROACHES Pharmacologic properties include >500,000 permutations in every dose Impact: Unreliable therapeutic effects Unintended off-target effects WAVE RATIONAL DESIGN Stereochemistry enables precise control, ability to optimize cr
Slide 9: Creating a new class of oligonucleotides
Creating a new class of oligonucleotides WAVE RATIONAL DESIGN Source: Iwamoto N, et al. Control of phosphorothioate stereochemistry substantially increases the efficacy of antisense oligonucleotides. Nature Biotechnology. 2017. 9
Slide 10: Chemistry may optimize medicines across multiple dimensions
Chemistry may optimize medicines across multiple dimensions Improved Stability Stability of stereopure molecules with reduced PS content (liver homogenate) Controlled Immunogenicity Human TLR9 activation assay with 5mC modified CpG containing MOE gapmer Enhanced Delivery Stereochemistry enables enha
Slide 11: Stereochemistry is applicable across modalities
Stereochemistry is applicable across modalities Antisense RNAi Exon skipping * Stereochemistry allows for novel approaches to previously difficult diseases and inaccessible targets 11
Slide 12: Transforming nucleic acid therapeutics
Transforming nucleic acid therapeutics SUPERIOR PHARMACOLOGY + SCALABLE SYNTHESIS MULTIMODALITY Antisense RNAi Splice Correction Exon skipping Gene editing BROAD IMPACT CNS Muscle Eye Liver Skin UNLOCKING THE PLATFORM Broad addressable patient population across multiple therapeutic areas 12
Slide 13: Neurology
Neurology STEREOCHEMISTRY WAVE
Slide 14: Huntington's Disease
Huntington’s Disease 14
Slide 15: Huntington's Disease: a hereditary, fatal disorder
Neuro HD Huntington’s Disease: a hereditary, fatal disorder Autosomal dominant disease, characterized by cognitive decline, psychiatric illness and chorea; fatal No approved disease-modifying therapies Expanded CAG triplet repeat in HTT gene results in production of mutant huntingtin protein (mHTT);
Slide 16: Wave approach: novel, allele-specific silencing
Wave approach: novel, allele-specific silencing Neuro HD Utilize association between single nucleotide polymorphisms (SNPs) and genetic mutations to specifically target errors in genetic disorders, including HD. Allele-specificity possible by targeting SNPs associated with expanded long CAG repeat i
Slide 17: Two simultaneous Phase 1b/2a clinical trials
Two simultaneous Phase 1b/2a clinical trials Neuro HD Two parallel global placebo-controlled multi-ascending-dose trials for WVE-120101, WVE-120102 Primary objective: assess safety and tolerability of intrathecal doses in early manifest HD patients Additional objectives: exploratory pharmacokinetic,
Slide 18: Mutant huntingtin: a powerful, novel biomarker
Neuro HD Mutant huntingtin: a powerful, novel biomarker Novel immunoassay allows for quantification of mutant huntingtin, the cause of HD Level of mHTT detected is associated with time to onset, increased with disease progression, and predicts diminished cognitive and motor dysfunction Assay current
Slide 19: Selective reduction of mHTT mRNA & protein
Neuro HD Selective reduction of mHTT mRNA & protein Reporter Cell Line* 19
Slide 20: Demonstrated delivery to brain tissue
Neuro HD Demonstrated delivery to brain tissue WVE-120101 and WVE-120102 distribution in cynomolgus non-human primate brain following intrathecal bolus injection CIC = cingulate cortex In Situ Hybridization ViewRNA stained tissue Red dots are WVE-120101 oligonucleotide. Arrow points to nuclear and p
Slide 21: Duchenne Muscular Dystrophy (DMD)
Duchenne Muscular Dystrophy (DMD) 21
Slide 22: DMD: a progressive, fatal childhood disorder
Neuro DMD DMD: a progressive, fatal childhood disorder Fatal, X-linked genetic neuromuscular disorder characterized by progressive, irreversible loss of muscle function, including heart and lung Genetic mutation in dystrophin gene prevents the production of dystrophin protein, a critical component o
Slide 23: Wave approach: restoration of dystrophin through exon skipping
Neuro DMD Wave approach: meaningful restoration of dystrophin production through exon skipping Meaningful restoration of dystrophin production is expected to result in therapeutic benefit Exon-skipping antisense approaches may enable production of functional dystrophin protein Initial patient popula
Slide 24: Exon 51: WVE-210201 clinical program
Neuro DMD Exon 51: WVE-210201 clinical program WVE-210201 Phase 1 clinical trial initiated November 2017 – Design: Multicenter, double-blind, placebo-controlled, single ascending dose study with I.V. administration – Primary endpoint: Safety and tolerability – Inclusion criteria: ages 5 to 18, amena
Slide 25: Exon 51: improved skipping efficiency
Neuro DMD Exon 51: improved skipping efficiency RNA skipping determined by quantitative RT-PCR Wave isomers demonstrated a dose-dependent increase in skipping efficiency Free uptake at 10uM concentration of each compound with no transfection agent Same foundational stereopure chemistry for Wave isom
Slide 26: Exon 51: increased dystrophin restoration
Neuro DMD Exon 51: increased dystrophin restoration dystrophin (400-427 kDa) vinculin (120 kDa) *Analogs WVE-210201 dystrophin (400-427 kDa) vinculin (120 kDa) Dystrophin protein restoration in vitro was quantified to be between 50-100% of normal skeletal muscle tissue lysates, as compared to about
Slide 27: Exon 51: target engagement in healthy non-human primate
Neuro DMD Exon 51: target engagement in healthy non-human primate Nested PCR Assay 5 doses @ 30 mg/kg /week for 4 weeks healthy NHP by subcutaneous dosing Experimental conditions: Muscle tissues were collected 2 days after the last dose and fresh frozen. Total RNAs were extracted with phenol/chlorof
Slide 28: Exon 51: no apparent tissue accumulation observed
Neuro DMD Exon 51: no apparent tissue accumulation observed Single in-vivo I.V. dose at 30 mpk in MDX 23 mice Standard oligonucleotides tend to accumulate in liver and kidney Wave rationally designed oligonucleotides optimized to allow compound to clear more effectively WVE-210201 demonstrated wide
Slide 29: Exon 53: Stereopure lead molecules advancing toward candidate
Neuro DMD Exon 53: Stereopure lead molecules advancing toward candidate RNA skipping determined by quantitative RT-PCR Free uptake at 10uM and 3uM concentration of each compound with no transfection agent Current published clinical dystrophin levels achieved for Exon 53 are ~1% Early Exon 53 data su
Slide 30: C9orf72 ALS and FTD
C9orf72 Amyotrophic Lateral Sclerosis (ALS) Frontotemporal Dementia (FTD) 30
Slide 31: C9orf72: a critical genetic risk factor
Neuro C9orf72 C9orf72: a critical genetic risk factor C9orf72 gene provides instructions for making protein found in various tissues, with abundance in nerve cells in the cerebral cortex and motor neurons C9orf72 genetic mutations are the strongest genetic risk factor found to date for the more comm
Slide 32: Amyotrophic lateral sclerosis
Neuro C9orf72 Amyotrophic lateral sclerosis Neurodegenerative disease characterized by the progressive ~40% degeneration of motor neurons in the brain and spinal cord Affects approximately 15,000-20,000 people in the US with a median ~10% survival of 3 years C9orf72 is present in approximately 40% o
Slide 33: Frontotemporal dementia
Neuro C9orf72 Frontotemporal dementia Progressive neuronal atrophy with loss in the frontal and temporal cortices characterized by personality and behavioral changes, as well as gradual ~38% impairment of language skills 10%—50% Affects approximately 55,000 people in the US Second most common form o
Slide 34: Selective silencing in vivo of expanded C9orf72 repeat transcripts
Selective silencing in vivo of expanded Neuro C9orf72 C9orf72 repeat transcripts Wave has developed a series of highly optimized antisense compounds which selectively silence the repeat containing transcript in C9orf72 transgenic mice These compounds show target engagement across cell types and regi
Slide 35: Durable reduction of dipeptides and RNA foci in vivo
Neuro C9orf72 Durable reduction of dipeptides and RNA foci in vivo Wave’s candidate (WVE-3972-01) demonstrates durable reduction of dipeptides and reductions in RNA foci Data is consistent across blinded studies in independent laboratories (collaboration with Professor Bob Brown, U. Mass) Durable re
Slide 36: Emerging areas
Emerging areas STEREOCHEMISTRY WAVE UE SCIENCES
Slide 37: Pfizer hepatic collaboration
Liver Pfizer hepatic collaboration Initiated May 2016 40 Exploring targets across modalities, including ASO and ssRNAi $M upfront Up to 5 hepatic-metabolic programs payment 3 targets declared; APOC3, 2 undisclosed Option to declare 2 additional targets Access to Pfizer’s hepatic targeting technology
Slide 38: Stereopure ASOs: improved in vivo potency, extended duration
Liver Stereopure ASOs: improved in vivo potency, extended duration Potency equivalent to state-of-the-art GalNAc conjugated double strand RNAi (ED50 0.3 mg/kg) Demonstrated increase in durability over GalNAc conjugated stereorandom ~7 fold ED50 ~2.0 mg/kg ED50 0.3 mg//kg Dosing Days 1,3 at 5mpk Expe
Slide 39: Eye: stereopure ASOs, improved potency and duration (back of eye)
% m R N A R e m a in in g ( m M A L A T 1 / m H P R T 1 ) 1 1 1 2 5 7 0 2 5 0 5 0 5 0 5 0 Back P B S of ( — Control ) the 5 0 m g Stereopure Experimental SR 5 0 m g 1 eye 10X 5 m g week Single description: lower Stereopure 5 0 m g ASOs: % m R N A R e m a in in g intravitreal dose (m M A L A T 1 / m
Slide 40: Eye: stereopure ASOs, improved potency and duration (front of eye)
% m R N A R e m a in in g ( m M A L A T 1 / m H P R T 1 ) 1 1 1 2 5 7 0 2 5 0 5 0 5 0 5 0 Front P B S of Control (-) 5 0 m g the Stereopure Experimental SR 5 0 m g 1 eye 10X 5 m g week Single description: lower Stereopure 5 0 m g ASOs: % m R N A R e m a in in g ( m M A L A T 1 / m H P R T 1 ) intrav
Slide 41: Distribution and target engagement
Distribution and target engagement Ophthalmology Dermatology Distribution of oligonucleotide to key cellular Target engagement following topical Compartments following intravitreal injection administration on human skin explant model in murine eye Red dots = Oligonucleotides 509452-001 05Jan2018 09:
Slide 42: Enabling technologies: enhancing stereopure platform
Enabling technologies: enhancing stereopure platform Collaboration leverages ReadCoor’s proprietary FISSEQ (Florescent In-Situ Sequencing) platform designed to provide critical spatial data by combining next generation sequencing and three-dimensional imaging Developing a registry of brain cell netw
Slide 43: Scalable nucleic acid synthesis
Scalable nucleic acid synthesis Oligonucleotide synthesis capacity ranging from high throughput to large scale GMP production 90,000 square foot facility Ability to continue to meet synthesis demands of growing portfolio and increase control and visibility of product supply chain Comparable yield an
Slide 44: Secure patent and intellectual property position
Secure patent and intellectual property position Programs HTT candidates DMD candidates ALS, FTD candidates Platform Designs Compositions Stereochemistry Improved activity, Oligonucleotide Monomers, Me stability, specificity, compositions key reagents of s immunogenicity 44
Slide 45: Wave catalysts
Wave catalysts Q3 2018: data expected in DMD from Phase 1 trial for WVE-210201 – Initiated clinical trial in DMD (Exon 51) November 2017 – WVE-210201 is the first stereopure oligonucleotide targeting Exon 51 with potential to be best-in-class – Interim dystrophin readout from planned efficacy and op
Slide 46: Realizing the potential of nucleic acid therapeutics
Realizing the potential of nucleic acid therapeutics 46
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