Uniqure N.v. · NASDAQ:QURE
Uniqure — Investor Presentation (September 2019)
35 slides from Uniqure's investor presentation, September 2019
Slide 1: Corporate Presentation September 2019
Corporate Presentation SEPTEMBER 2019 DELIVERING GENE THERAPY TO PATIENTS SEPTEMBER 2019 | 1
Slide 2: Forward-looking Statements
Forward-looking Statements This presentation contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,” “intend,” “look forward
Slide 3: Our mission statement
Our mission statement To deliver curative, one-time therapies that transform the lives of patients. DELIVERING GENE THERAPY TO PATIENTS SEPTEMBER 2019 | 3
Slide 4: Key corporate highlights
Key corporate highlights • Demonstrated clinical proof of concept in Hemophilia B; achievement of planned enrollment in HOPE-B pivotal study, with potential to be first- and best-in-class • Proprietary CNS platform with lead program AMT-130 in Huntington’s disease expected to initiate dosing in Phas
Slide 5: Our proprietary pipeline
Our proprietary pipeline D E L I V E Rwith *Collaboration I N GBristol-Myers GENE TH ERAPY TO PATIENTS Squibb SEPTEMBER 2019 | 5
Slide 6: Key corporate goals
Key corporate goals • Topline data from HOPE-B pivotal study in 2020 Hemophilia B • BLA submission in 2021 • Initiate dosing in Phase I/II study before end of 2019 Huntington’s • Preliminary biomarker data on initial patients in 2020 Hemophilia A • Submit IND for AMT-180 in 2020 • Initiate IND-enabl
Slide 7: Leading the way in AAV manufacturing
Leading the way in AAV manufacturing Large-scale AAV Manufacturing • Based in Lexington, MA, expanded to 80,000 ft2 • Proprietary 3rd generation insect cell, baculovirus • Demonstrated 500L stirred-tank production • Scalable up to 2 x 2,000L • Strong intellectual property position Potential Benefits
Slide 8: Leveraging AAV5: a potentially best-in-class vector
Leveraging AAV5: a potentially best-in-class vector AAV5 – Clinically demonstrated tolerability and clinical effects AAV5 Vector observed to date • Long-term follow-up data demonstrating safety and tolerability • 25 patients have received AAV5 across 4 clinical studies1 • Observed clinical effects i
Slide 9: Hemophilia B
Hemophilia B Etranacogene dezaparvovec (AMT-061) DELIVERING GENE THERAPY TO PATIENTS SEPTEMBER 2019 | 9
Slide 10: Executing in Hemophilia B
Executing in Hemophilia B Target product profile • Increase FIX activity into normal range • Durable and predictable outcomes Hemophilia B AMT-061 • Low risk of immune responses • Greater patient eligibility due to AAV5 NAb profile • 10-15K patients in US/EU • >$1.3B market in 20181 • Strong intelle
Slide 11: FIX activity in Phase 2b study
Etranacogene dezaparvovec (EtranaDez): FIX activity at 36 weeks post-treatment in Phase 2b study Increases in FIX activity up to 54% of normal Main Efficacy Findings: Mean FIX activity at 36 weeks of 45% of normal • Sustained increases in FIX activity Participant 1 • No bleeding events post-treatmen
Slide 12: HOPE-B Phase III pivotal study
Etranacogene dezaparvovec (EtranaDez): HOPE-B Phase III pivotal study • Achieved planned enrollment of 56 patients with severe and moderately-severe Hemophilia B • Expect to over-enroll up to six additional patients in September 2019 • Open label, single-dose, multi-center, multi-national trial • Pa
Slide 13: miQURE Gene Silencing Technology
miQURE™ Gene Silencing Technology DELIVERING GENE THERAPY TO PATIENTS SEPTEMBER 2 0 1 9 | 13
Slide 14: miQURE our unique gene silencing technology
miQURETM our unique gene silencing technology • One-time administration • Potential to degrade toxic gene products without toxic effects • Delivered with AAV and is active long term • Vector-generated miRNA in directly transduced brain cells can transfer horizontally and via the CSF to non-transduce
Slide 15: miQURE vs. gene replacement
miQURE™ vs. gene replacement Gene replacement Defect Deliver correct Correct gene gene gene function miQURE™ technology miQURE™ Reduce Toxic gene Degrade toxic impact of gene product toxic gene DELIVERING GENE THERAPY TO PATIENTS SEPTEMBER 2 0 1 9 | 15
Slide 16: miQURE: important features
miQURE™: important features • Expression from pol II promoter for tissue specificity and regulation Specificity • Liver- or brain-specific expression & Regulation • Scaffold for high processing precision and no off-target effects • No passenger strand • Expression comparable with cellular miRNAs ens
Slide 17: Huntington's Disease
Huntington’s Disease AMT-130 DELIVERING GENE THERAPY TO PATIENTS SEPTEMBER 2 0 1 9 | 17
Slide 18: Executing in Huntington's disease
Executing in Huntington’s disease Target product profile • One-time administration of disease-modifying therapy • Proprietary miQURETM silencing platform Huntington’s AMT-130 • Strong mHTT knockdown in both deep structures and cortex • 3-7 per 100K people1 • Targets full length HTT protein aggregate
Slide 19: Huntington's disease: expected progression of brain pathology
Huntington’s disease: expected progression of brain pathology Somatomotor cortex • The striatum is the primary site of Frontal Somatosensory lobe pathology cortex 2 Parietal 3 3 lobe • Premanifest stage: atrophy spreads and cortical thinning occurs 1 Occipital lobe • Motor symptoms manifest as atrop
Slide 20: AMT-130: increased median survival in exon1 mouse model
AMT-130: targeting of aberrant exon1 HTT increased in median survival in exon1 mouse model Strong increase in median survival in R6/2 HD mice NOTE: Previously reported data of Ionis/Roche in R6/2 transgenic mice was obtained with HuASOEx1, which is not the clinical candidate RG6042 R6/2 transgenic m
Slide 21: AMT-130: goal of clinical treatment to slow or halt progression
AMT-130: goal of clinical treatment to slow or halt disease progression from an early stage Penetration throughout NHP brain Vector DNA distribution 8 10 V e c t o r g e n o m e c o p ie s 7 10 p er µ g D N A 6 10 5 10 1 10 4 LLO D 3 10 P u ta m e n C a u d a t e T h a la m u s C o rte x 13 1x10 g c
Slide 22: AMT-130: strong reduction of mHTT
AMT-130: strong reduction of mHTT Libechov transgenic (tgHD) minipigs: Comparable mutant huntingtin protein • Life-span: 12-20 years knockdown at 6 and 12 months • Body weight: 50-140 kg • Brain weight: 90-100 g Cortex Striatum • Highly developed immune system 125 6 months MRI-guided CED 12 months m
Slide 23: AMT-130: goal of clinical treatment
AMT-130: goal of clinical treatment Motor diagnosis Premanifest Manifest 100 AMT-130 ← Function (%) Slow or halt disease progression I II III IV V 0 Presymptomatic Prodromal Early Moderate Advanced Adapted from Ross CA, et al. Nat Rev Neurol 2014;10:204-16 DELIVERING GENE THERAPY TO PATIENTS SEPTEMB
Slide 24: AMT-130: Phase I/II clinical trial
AMT-130: Phase I/II clinical trial Study Overview • Objectives: assess safety, tolerability and efficacy • Multicenter, randomized, double-blinded study • Controlled with imitation surgery • Two dose cohorts with a total of 26 patients • Early manifest patients with ≥ 44 CAG repeats • 18-month follo
Slide 25: AMT-130: Phase I/II clinical trial endpoints
AMT-130: Phase I/II clinical trial endpoints Efficacy Endpoints Clinical Parameters* Biomarkers • Total motor score • NF-L (neurofilament light) • Total functional capacity • mHTT in CSF • Composite score • Other exploratory markers Quantitative Motor Function Patient-reported outcomes • Finger, han
Slide 26: AMT-130: Phase I/II clinical trial design
AMT-130: Phase I/II clinical trial design Cohort 1 Cohort 2 Subject 1&2 Subject 3&4 Subject 5-10 Subject 11&12 Subject 13&14 Subject 15-26 1:1 1:1 2:1 1:1 1:1 2:1 randomization randomization randomization randomization randomization randomization 1 AMT-130 1 AMT-130 4 AMT-130 1 AMT-130 1 AMT-130 8 A
Slide 27: Research Pipeline
Research Pipeline DELIVERING GENE THERAPY TO PATIENTS SEPTEMBER 2 0 1 9 | 27
Slide 28: AMT-180: a novel approach to Hemophilia A
AMT-180: a novel approach to Hemophilia A Novel Approach • Product Construct – AAV5 including C7 Promoter and FIX-Super9™ • Super9™ is a proprietary modified FIX that, when activated through normal mechanisms, activates FX independently of FVIII Long-term and Effective in all HemA Compatible with Co
Slide 29: AMT-180: expression levels in NHPs
AMT-180: expression levels in NHPs expected to translate to therapeutically relevant FVIII mimetic activity in humans Male cynomolgus macaque h F IX p r o t e in ( % ) in N H P s n=2 250 IV, 9e13 gc/kg vehicle adapted delivery 200 AAV5-LP1-Super9™ h F IX p ro te in (% ) AAV5-P-IDAV 1) AAV5-LP1-Super
Slide 30: AMT-190: a new approach to Fabry disease
AMT-190: a new approach to Fabry disease Novel Approach • Product Construct – AAV5 including modified NAGA • Modified NAGA has therapeutic α-gal activity and gB3 reduction More effective than Patients with and without Non-immunogenic replacement therapy inhibitors • More stable in plasma • Many Fabr
Slide 31: Wild type Fabry vs Modified NAGA
Wild type Fabry Modified NAGA Fabrazyme Replagal Tajima Y et al. Am J Human Genetics 2009 DELIVERING GENE THERAPY TO PATIENTS SEPTEMBER 2 0 1 9 | 31
Slide 32: AMT-150: a gene therapy for SCA3
AMT-150: a gene therapy for SCA3 Novel Approach • AAV5, SCA3 miRNA administered by intrathecal or cisterna magna injection • Leverages HD platform and experience, including miQURE™ gene silencing technology • Potential to be first to market Cause Damage Symptoms Unmet Need • CAG repeat expansion • B
Slide 33: AMT-150: 65% ataxin-3 lowering in SCA3 mice
AMT-150: 65% ataxin-3 lowering in brainstem of SCA- concept3 mice after cisterna magna injection of miQURE™ SCA3 mouse model Up to 65% ataxin-3 lowering in SCA3 mice miQURETM Cerebellum SCA3 mouse brainstem Mutant ataxin-3 protein (%) Cisterna Magna 100 Relative to control 75 • N = 3 per group 50 *
Slide 34: Key corporate goals
Key corporate goals • Topline data from HOPE-B pivotal study in 2020 Hemophilia B • BLA submission in 2021 • Initiate dosing in Phase I/II study before end of 2019 Huntington’s • Preliminary biomarker data on initial patients in 2020 Hemophilia A • Submit IND for AMT-180 in 2020 • Initiate IND-enabl
Slide 35: uniQure
uniQure