Wave Life Sciences Ltd. · NASDAQ:WVE
Wave Life Sciences — Investor Presentation (September 2018)
38 slides from Wave Life Sciences's investor presentation, Sep 11, 2018
Slide 1: Wave Life Sciences Corporate Presentation
Wave Life Sciences Corporate Presentation September 10, 2018 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: Leading a new era of precision medicine
We are leading a new era of precision medicine in which rationally designed nucleic acid therapies are the key to delivering safer, more effective treatments for serious, genetically defined diseases
Slide 4: Architects of transformation
Architects of transformation Wave Life Sciences is a clinical-stage, genetic medicines company unlocking the potential of a proprietary chemistry platform that enables the precise design, optimization and production of stereopure nucleic acid therapies. Wave has reinvented the design, synthesis and
Slide 5: Wave rational design: building the optimal, stereopure medicine
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 6: 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 7: Optimizing potency and durability across multiple tissues
Optimizing potency and durability across multiple tissues CNS Muscle Liver MALAT1 Knockdown in Mice Knockdown of Serum hAPOC3 Protein Levels in Mice Two 5 mg/kg doses on Days 1&3 PBS Stereopure Eye MALAT1 Knockdown in Non-Human Primates Single 450 µg IVT injection 10 Weeks after single 100 µg inject
Slide 8: Stereochemistry allows for chemistry affecting immune activation
Stereochemistry allows for Human TLR9 activation assay with 5mC modified CpG containing MOE gapmer Cytokine induction in human PBMC assay Chemistry affects immune activation Complement Activation Human TLR9 Activation Cytokine Induction Complement activation in non-human primate serum assay Data rep
Slide 9: Pipeline spanning multiple modalities, novel targets
MUSCLE Pipeline spanning multiple modalities, novel targets CLINICAL NEXT ANTICIPATED MILESTONES CANDIDATE DISCOVERY ESTIMATED U.S. PREVALENCE* TARGET BIOMARKER MECHANISM PARTNER WAVE’S COMMERCIAL RIGHTS CNS A Huntington’s disease ~10k / ~35k mHTT SNP1 mHTT Phase 1b/2a Top line data H1 2019 Takeda 5
Slide 10: Huntington's Disease
Huntington’s Disease
Slide 11: 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 12: 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 13: 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 14: Selective reduction of mHTT mRNA & protein
Selective reduction of mHTT mRNA & protein Reporter Cell Line* Neuro HD
Slide 15: 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 16: Duchenne Muscular Dystrophy (DMD)
Duchenne Muscular Dystrophy (DMD)
Slide 17: 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 18: 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 19: WVE-210201 Phase 1 clinical trial and planned efficacy study
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, amenable to exon 51 skipping Ambulatory and non-ambulatory
Slide 20: 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 21: 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 22: Exon 51: in vivo target engagement of WVE-210201
Exon 51: in vivo target engagement of WVE-210201 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 extract
Slide 23: 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 24: Stereopure surrogate yields dystrophin restoration in mdx 23 mice
Wave stereopure surrogate yields substantial natural dystrophin protein restoration in mdx 23 mice 70-90% of natural dystrophin production in vivo An exon 23 skipping molecule with a similar profile to WVE-210201 Level of transcript production observed in vivo correlates strongly to what was observe
Slide 25: Exon 53: oligonucleotide rapidly distributes to muscle
Exon 53: targeting oligonucleotide rapidly distributes to muscle within 24 hours after injection Bright field view 63x oil Nucleus: Hematoxylin; Light Blue Wave oligo: ViewRNA, Fast Red Nucleus: Hoechst33342; Blue Wave oligo: Fast Red/Cy3; Pink Red Fluorescence channel view Z Stack view Data derived
Slide 26: Exon 53 program: improved skipping efficiency
RNA skipping determined by quantitative RT-PCR Free uptake at 10uM and 3uM concentration of each compound with no transfection agent Exon 53 Program: improved skipping efficiency Neuro DMD Percentage Exon 53 Skipping of Preliminary Wave Isomers WVE 53 Compound E WVE 53 Compound F WVE 53 Compound E W
Slide 27: C9orf72 ALS and FTD
C9orf72 Amyotrophic Lateral Sclerosis (ALS) Frontotemporal Dementia (FTD)
Slide 28: 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 29: 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 30: 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 31: Selective silencing in vivo of expanded C9orf72 repeat transcripts
Selective silencing in vivo of expanded 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 regions of the ner
Slide 32: Durable reduction of dipeptides and RNA foci in vivo
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) Neuro C9orf72 2-weeks 4-
Slide 33: In vivo distribution of WVE-3972-01
In vivo distribution of WVE-3972-01 8 weeks after treatment Neuro C9orf72 Experimental description: C9-BAC mice were administered 50mg of WVE-3972-01 ICV on day 1 and day 8; detection using ViewRNA. Widespread and sustained distribution in nuclei of motor neurons in the spinal cord
Slide 34: Partnerships
Partnerships
Slide 35: Collaborations with Takeda and Pfizer
*Assuming Takeda advances six programs that achieve regulatory approval and commercial sales, Wave will be eligible to receive up to $2 billion in cash milestone payments, of which more than $1 billion would be in precommercial milestone payments. $230+ million in committed cash; eligible for milest
Slide 36: Intellectual property strength: breadth and depth of patent portfolio
Intellectual property strength: breadth and depth of patent portfolio Programs HD candidates DMD candidates Platform Designs Compositions Stereochemistry Process development Improved activity, stability, specificity, immunogenicity Oligonucleotide compositions Monomers, key reagents Methods of synth
Slide 37: Upcoming Wave catalysts
Upcoming Wave catalysts Q4 2018: safety data expected in DMD from Phase 1 trial for WVE-210201 WVE-210201 is the first stereopure oligonucleotide targeting Exon 51 Received EU and US orphan drug designations and US rare pediatric disease designation Q4 2018: clinical trials expected to initiate in A
Slide 38: Realizing the potential of nucleic acid therapeutics
Realizing the potential of nucleic acid therapeutics For more information: Graham Morrell, Investor Relations gmorrell@wavelifesci.com 781.686.9600
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