Wave Life Sciences Ltd. · NASDAQ:WVE
Wave Life Sciences — Investor Presentation (September 2017)
43 slides from Wave Life Sciences's investor presentation, Sep 18, 2017
Slide 1: Wave Life Sciences
Wave Life Sciences September 18, 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, 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 first to design and bring stereopure and allele-specific medicines to clinic 6 neurology development programs by end of 2018 3 clinical studies expected to initiate in 2017 10K+ Wave stereopure oligonucleotides created and analyzed to d
Slide 5: Pipeline spanning multiple modalities, novel targets
Pipeline spanning multiple modalities, novel targets *Estimates of U.S. prevalence and addressable population by target based on publicly available data and are approximate. *For Huntington’s disease, numbers approximate manifest and pre-manifest populations, respectively DISEASE CLINICAL NEXT ANTIC
Slide 6: Current programs
Current programs Neuromuscular diseases DMD (additional exons) Spinal muscular atrophy (SMN2) Charcot-Marie-Tooth type 1A (PMP22) Neurodegenerative movement disorders Spinocerebellar ataxia (ATXN3) Discovery engine Huntington’s disease (HTT SNP1) Huntington’s disease (HTT SNP2) Duchenne muscular dys
Slide 7: Broad platform relevance across therapeutic areas
CNS Muscle Broad platform relevance across therapeutic areas
Slide 8: Wave rational design
WAVE RATIONAL DESIGN Stereochemistry enables precise control, ability to optimize critical constructs into one defined and consistent profile Building the optimal, stereopure medicine STANDARD OLIGONUCLEOTIDE APPROACHES Pharmacologic properties include >500,000 permutations in every dose Impact: Unr
Slide 9: Creating a new class of oligonucleotides
Source: Iwamoto N, et al. Control of phosphorothioate stereochemistry substantially increases the efficacy of antisense oligonucleotides. Nature Biotechnology. 2017. Creating a new class of oligonucleotides WAVE RATIONAL DESIGN
Slide 10: Chemistry may optimize medicines across multiple dimensions
Chemistry may optimize medicines across multiple dimensions Stability of stereopure molecules with reduced PS content (liver homogenate) Oligonucleotide exposure (spinal cord) Human TLR9 activation assay with 5mC modified CpG containing MOE gapmer IL-6 MIP-1β Cytokine induction in human PBMC assay S
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 *
Slide 12: Unlocking the platform
SUPERIOR PHARMACOLOGY + SCALABLE SYNTHESIS MULTI- MODALITY BROAD IMPACT UNLOCKING THE PLATFORM Antisense RNAi Splice Correction Exon skipping Gene editing CNS Muscle Eye Liver Skin Broad addressable patient population across multiple therapeutic areas Transforming nucleic acid therapeutics
Slide 13: Neurology
Neurology Neurology STEREOCHEMISTRY WAVE
Slide 14: Huntington's Disease
Huntington’s Disease
Slide 15: Huntington's Disease: a hereditary, fatal disorder
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); accumula
Slide 16: Novel, allele-specific silencing of expanded CAG repeat
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 in mHTT gene Approach aims to lower mHTT transcript while
Slide 17: Selective reduction of mHTT mRNA & protein
Selective reduction of mHTT mRNA & protein Reporter Cell Line* Neuro HD
Slide 18: Demonstrated delivery to brain tissue
Demonstrated delivery to brain tissue WVE-120101 and WVE-120102 distribution in cynomolgus non-human primate brain following intrathecal bolus injection Demonstrated delivery to brain tissue CIC = cingulate cortex. CN = caudate nucleus. In Situ Hybridization ViewRNA stained tissue Red dots are WVE-1
Slide 19: Novel immunoassay allows quantification of mutant huntingtin
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 currently being utilized in clinical studies Mutant huntingtin:
Slide 20: Two parallel global placebo-controlled multi-ascending-dose trials
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, pharmacodynamic, clinical and MRI endpoints Two simul
Slide 21: Duchenne Muscular Dystrophy (DMD)
Duchenne Muscular Dystrophy (DMD)
Slide 22: DMD: a progressive, fatal childhood disorder
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 of healthy
Slide 23: Restoration of dystrophin production through exon skipping
Wave approach: meaningful restoration of dystrophin production through exon skipping Neuro DMD 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: improved skipping efficiency
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 isomers; indiv
Slide 25: Exon 51: increased dystrophin restoration
Dystrophin protein restoration in vitro was quantified to be between 50-100% of normal skeletal muscle tissue lysates, as compared to about 1% by drisapersen and eteplirsen analogs Exon 51: increased dystrophin restoration *Analogs dystrophin (400-427 kDa) vinculin (120 kDa) Marker Mock Drisapersen*
Slide 26: Exon 51: target engagement in healthy non-human primate
Exon 51: target engagement in healthy non-human primate 5 doses @ 30 mg/kg /week for 4 weeks healthy NHP by subcutaneous dosing Nested PCR Assay Neuro DMD Experimental conditions: Muscle tissues were collected 2 days after the last dose and fresh frozen. Total RNAs were extracted with phenol/chlorof
Slide 27: Exon 51: no apparent tissue accumulation observed
Exon 51: no apparent tissue accumulation observed 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 tissue distribution in dose dependent fashion No apparent ac
Slide 28: Exon 51: WVE-210201 clinical trial design
Clinical trials expected to initiate for WVE-210201 in Q4 2017 Protocol development in collaboration with DMD community Intend to explore intravenous and subcutaneous administration Trials to include ambulatory and non-ambulatory patients Objective is to allow inclusion of patients previously treate
Slide 29: 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 suggests initial skipping efficiency around 20% pre-optimization Exon 53:
Slide 30: C9orf72 ALS and FTD
C9orf72 Amyotrophic Lateral Sclerosis (ALS) Frontotemporal Dementia (FTD)
Slide 31: C9orf72: a critical genetic risk factor
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 common, non-inheri
Slide 32: Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis Neurodegenerative disease characterized by the progressive degeneration of motor neurons in the brain and spinal cord Affects approximately 15,000-20,000 people in the US with a median survival of 3 years C9orf72 is present in approximately 40% of familial ALS and 8-10%
Slide 33: Frontotemporal dementia
Frontotemporal dementia Progressive neuronal atrophy with loss in the frontal and temporal cortices characterized by personality and behavioral changes, as well as gradual impairment of language skills Affects approximately 55,000 people in the US Second most common form of early-onset dementia afte
Slide 34: Selective silencing of expanded C9orf72 repeat
Selective silencing of expanded C9orf72 repeat 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 regions of the nervous system critical
Slide 35: Emerging areas
Emerging areas STEREOCHEMISTRY LIFE SCIENCES
Slide 36: Pfizer hepatic collaboration
Pfizer hepatic collaboration Initiated May 2016 Exploring targets across modalities, including ASO and ssRNAi Up to 5 hepatic-metabolic programs 3 targets declared; APOC3, 2 undisclosed Option to declare 2 additional targets Access to Pfizer’s hepatic targeting technology Potentially increasing pote
Slide 37: Stereopure ASOs: improved potency, extended duration
Stereopure ASOs: improved 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 ED50 ~2.0 mg/kg ED50 0.3 mg//kg Liver Experimental description: Male human APOC3 t
Slide 38: Distribution and target engagement
Distribution and target engagement Skin Eye Distribution of oligonucleotide to key cellular Compartments following intravitreal injection in murine eye Target engagement following topical administration on human skin explant model Ophthalmology Dermatology Red dots = Oligonucleotides PBS Control oli
Slide 39: 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 40: 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 and cost-of-goods to standard ster
Slide 41: Secure patent and intellectual property position
Secure patent and intellectual property position Programs HTT candidates DMD candidates Platform Designs Compositions Stereochemistry Process development Improved activity, stability, specificity, immunogenicity Oligonucleotide compositions Monomers, key reagents Methods of synthesis ALS, FTD candid
Slide 42: Wave catalysts
Wave catalysts Initiated two clinical trials in Huntington’s disease mid-2017 Potential to be first two allele-specific disease-modifying therapies Received U.S. orphan drug designation for WVE-120101 and WVE-120102 Top line data for WVE-120101 and WVE-120102 expected 1H 2019 Expect to initiate clin
Slide 43: Realizing the potential of nucleic acid therapeutics
Realizing the potential of nucleic acid therapeutics
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