uniQure N.V. · NASDAQ:QURE
uniQure — Investor Presentation (September 2021)
52 slides from uniQure's investor presentation, September 2021
Slide 1: Leadership in Gene Therapy
Leadership in Gene Therapy Corporate Presentation September 2021
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 forwar
Slide 3: uniQure: our focus
uniQure: our focus AAV Engine: Leveraging our leading technology platform to develop and commercialize products targeting the CNS, liver and heart/muscle AAV Technology Engine Manufacturing & Enabling Tools L EAD LEA ERS H DERS HII PP I N INGEN E THTHERA GENE ERAP YPY S EP TEMBER SEPT 2021 EMB E R 2
Slide 4: inGENEuity: our history of innovation
inGENEuity: our history of innovation uniQure: A gene therapy pioneer with a >20-year history and deeply engrained culture of innovation across an increasingly validated platform First First First First LEA DERS HI P IN GENE THERA PY SEPT EMB E R 2021 | 4
Slide 5: inGENEuity: our history of innovation
inGENEuity: our history of innovation uniQure: A gene therapy pioneer with a >20-year history and deeply engrained culture of innovation across an increasingly validated platform 15 years 100+ patients World-class Leading LEA DERS HI P IN GENE THERA PY SEPT EMB E R 2021 | 5
Slide 6: Re-imaGENEing the R&D pipeline
Re-imaGENEing the R&D pipeline Doubling the pipeline by 2026 5-year Pipeline 3-4 Phase 3 commercial 5-8 Phase 1/ 2 programs 7-12 preclinical Goals: programs programs LEA DERS HI P IN GENE THERA PY SEPT EMB E R 2021 | 6
Slide 7: Re-imaGENEing the R&D pipeline
Re-imaGENEing the R&D pipeline Larger market opportunities built on validated targets and technologies ● Best and/or first in class ● Human validation Key criteria: ● Leverage proven technologies ● Larger indications L EAD LEA ERS H DERS HII PP I N INGEN E THTHERA GENE ERAP YPY S EP TEMBER SEPT 2021
Slide 8: Re-imaGENEing our enabling technology
Re-imaGENEing our enabling technolgy Leveraging a broad, enabling technology platform to build an optimized and differentiated pipeline Re-imagining Next-gen tools developed: What we aim to accomplish: where/how ● Novel AAV capsids ● Potent expression we deliver… ● Next-gen promoters ● Targeted deli
Slide 9: Re-imaGENEing our enabling technology
Re-imaGENEing our enabling technolgy Leveraging a broad, enabling technology platform to build an optimized and differentiated pipeline Re-imagining Next-gen tools: What we aim to accomplish: what we miQURE® (gene silencing) ● Insertion of genes deliver… goQURE (gene silence/replace) ● Suppression o
Slide 10: Re-imaGENEing our in-house manufacturing
Re-imaGENEing our in-house manufacturing Manufacturing for the future: Establishing larger scale and highly cost- effective capabilities to address more prevalent disorders LEA DERS HI P IN GENE THERA PY SEPT EMB E R 2021 | 10
Slide 11: LEA DERS HI P IN GENE THERA PY SEPT EMB E R 2021
LEA DERS HI P IN GENE THERA PY SEPT EMB E R 2021 | 11
Slide 12: Recent company progress & upcoming events
Recent company progress & upcoming events • Closed commercialization and licensing agreement with CSL • Presented 52-week data from HOPE-B pivotal trial Hemophilia B • On track to announce 78-week top-line data and prepare regulatory submissions for marketing approval • Began patient enrollment in s
Slide 13: HOPE-B 52-Week Analysis
HOPE-B 52-Week Analysis Hemophilia B Etranacogene dezaparvovec (AMT-061) Etranacogene dezaparvovec (AMT-161) A GL O BAL L EAD ER I N GEN E TH ERAP Y MAY 2021 13
Slide 14: HOPE-B pivotal trial: study design
HOPE-B pivotal trial: study design • Key inclusion criteria • Male adults ≥18 years • FIX activity ≤2% of normal • Continuous prophylaxis for ≥2 months • Key exclusion criteria • Factors that might affect the evaluation of AMT-061 efficacy or safety • FIX inhibitors • Active hepatitis B/C infection
Slide 15: HOPE-B Phase III pivotal study
Etranacogene dezaparvovec (EtranaDez): HOPE-B Phase III pivotal study • 54 patients treated as of March 2020 • Severe and moderately-severe Hemophilia B patients • Open label, single-dose, multi-center, multi-national trial • Patients with AAV5 neutralizing antibodies not excluded • Patients served
Slide 16: HOPE-B Phase III pivotal study endpoints
Etranacogene dezaparvovec (EtranaDez): HOPE-B Phase III pivotal study Primary endpoint • 52-week ABR after stable FIX expression has been achieved, compared to ABR in lead-in period • ABR will be measured from week 26 to week 78 after infusion Secondary endpoints • FIX activity at 6, 12 and 18 month
Slide 17: Overview of FIX activity up to 52 weeks
Overview of FIX activity up to 52 weeks (month 12) • FIX activity increased to a mean of 39.0% at month 6 • Change from baseline +37.8% • FIX activity maintained at a mean of 41.5% at month 12 • Change from baseline +40.3% aUncontaminated central laboratory data (the visit did not occur within 10 da
Slide 18: HOPE-B: Endogenous FIX activity to 52 weeks
HOPE-B: Endogenous FIX activity to 52 weeks 1 Stable and durable FIX activity post-etranacogene dezaparvovec treatment Following treatment, FIX activity increased rapidly to a mean of 39.0 (SD; min, max) IU/dL (±18.7; 8.2, 97.1) at Week 26 and 41.5 IU/dL (±21.7; 5.9, 113.0) at Week 52. No clinically
Slide 19: No clinically significant impact of pre-existing NABs on FIX activity
No clinically significant impact of pre-existing NABs on mean FIX activity between months 6 to 12 Analysis of all treated subjects including subject with patrial dose and with NAB titer 3212 LEA DERS HI P IN GENE THERA PY SEPT EMB E R 2021 | 19
Slide 20: Spontaneous bleeds reduced further in second six months
Spontaneous bleeds were reduced further in the second six months after treatment Sustained FIX levels were associated with significantly reduced spontaneous bleeding during the first year of follow-up Per FDA guidance, data shows all reported bleeds, even if adjudicated by the investigator to be non
Slide 21: Adjusted annualized bleeding rates reduced compared with lead-in
Adjusted annualized bleeding rates (ABR) reduced on treatment compared with lead-in period During post-treatment period of up to 2 years, 30 subjects (55.6%) had no bleeds, 39 subjects (72.2%) had no bleeds treated with FIX Lead-in period includes 33.12 observed years in 54 subjects (mean 32 weeks p
Slide 22: Substantial reductions in FIX replacement and prophylaxis
Substantial reductions in FIX replacement and use of prophylaxis when compared with lead-in At 52 weeks follow-up, compared with the lead-in period • 96% (52/54) subjects discontinued prophylaxis and remain prophylaxis-free • 96% reduction in FIX consumption in IU/year (mean reduction of 246,537 IU/
Slide 23: Post-treatment adverse events
Post-treatment adverse events • 53 subjects had 408 AEs • 39 subjects had 91 treatment related AEs • 9 subjects received steroid treatment for transaminase elevations • All discontinued steroid use prior to Week 26 • FIX activity preserved in the mild range (8%-39%) • 7 subjects had infusion related
Slide 24: A global licensing deal with CSL Behring in hemophilia B
A global licensing deal with CSL Behring in hemophilia B Transaction is a historic collaboration in gene therapy and hemophilia, with uniQure eligible to receive more than $2B in total economics • $450M upfront payment received in 2Q 2021 • $1.6B in regulatory and commercial milestones • Double-digi
Slide 25: AMT-130
AMT-130 LEA DERS HI P IN GENE THERA PY SEPT EMB E R 2021 | 25
Slide 26: Huntington's disease (HD): an overview
Huntington’s disease (HD): an overview • Autosomal dominant inherited disorder (50% risk if your parent has HD) • Affects ~25,000 patients each in U.S./EU • Initially described based upon characteristic chorea • Dystonia, incoordination, ataxia, and later rigidity and bradykinesia contribute to func
Slide 27: AMT-130: a gene therapy approach for early manifest HD
AMT-130: a gene therapy approach for early manifest HD • AAV5-miHTT (AMT-130) • Replication-deficient adeno-associated viral vector serotype 5 (AAV5) • Codes for microRNA (miRNA) that targets the HTT mRNA at exon 1 • Blocks expression of HTT protein Extensive preclinical validation Model Efficacy Sa
Slide 28: AMT-130: longitudinal data in transgenic pigs
AMT-130: longitudinal data in transgenic pigs brain CSF mHTT protein NF-L 80000 Control (naive) rAAV5-miHTT CSF NF-L (pg/mL) 60000 40000 20000 0 e d d m m m m m m m m os 14 28 3 6 9 12 15 18 21 24 -d p re • Stable miHTT expression, mHTT protein lowering, and long-term baseline NFL levels • Trend con
Slide 29: AMT-130: maximizing potential for clinical impact
AMT-130: maximizing potential for clinical impact Our approach optimizes benefit/risk tradeoff • Focused neurosurgical delivery to most relevant brain regions • Not targeting 100% knock-down or entire CNS • 50-75% maximal knock-down in striatum where benefit/risk of knockdown is clear • 25-50% corti
Slide 30: AMT-130: knocking down wtHTT and mHTT safe in adult animals
AMT-130: knocking down wildtype (wtHTT) and mutant HTT (mHTT) safe and effective in adult animals • wtHTT inactivation during adulthood does not result in any phenotype 1,2 • wtHTT + mHTT results in HD • Partial reduction of mHTT or both wtHTT/mHTT in adulthood slows disease progression and delay on
Slide 31: AMT-130: phase 1-2 study design
AMT-130: phase 1-2 study design • Double-blind, randomized, imitation-surgery • MRI, magnetic resonance imaging (sham) controlled study • 2 dose levels of AMT-130 • Cohort 1: 50%/25% striatal/cortical knockdown • Cohort 2: 75%/50% striatal/cortical knockdown • One-time bilateral stereotaxic neurosur
Slide 32: AMT-130: phase 1-2 inclusion/exclusion criteria
AMT-130: phase 1-2 initial inclusion/exclusion criteria Key inclusion criteria Key exclusion criteria • 25 to 65 years of age • Presence of an implanted deep brain stimulator devices • Early manifest HD • Total functional capacity (TFC) 9-13 • Relevant brain/spinal pathology (stage 1 or early stage
Slide 33: AMT-130: phase 1-2 proof-of-concept endpoints
AMT-130: phase 1-2 proof-of-concept endpoints Biomarkers Clinical Parameters* ● NF-L (neurofilament light) ● Total motor score ● mHTT in CSF ● Total functional capacity ● Other exploratory markers Imaging (MRI and MRS) Quantitative Motor Function ● Measures of neural function ● Finger, hand and foot
Slide 34: AMT-130: a year of exceptional progress in clinical development
AMT-130: a year of exceptional progress in clinical development 16 June 2021 First Two Cohort 2 Procedures 13 October 2020 19 June 2020 Enrollment of Next 2 Patients 05 April 2021 30 August 2021 First 2 Patients in in Phase 1-2 Clinical Trial Completion of Enrollment in First Third and Fourth Phase
Slide 35: AMT-130: EU open-label study
AMT-130: EU open-label study will augment phase 1-2 signal- detection capacity LEA DERS HI P IN GENE THERA PY SEPT EMB E R 2021 | 35
Slide 36: AMT-130: preliminary data on first 4 randomized patients
AMT-130: preliminary data on first 4 randomized patients • Safety and tolerability Subject 1&2 1:1 • Chemistry biomarkers from CSF and blood serum randomization 1 dosed • NfL – compared to baseline and control 1 control • mHTT in CSF – compared to baseline and control • Markers for inflammation and
Slide 37: Expanding the Research Pipeline
Expanding the Research Pipeline A GL O BAL L EAD ER I N GEN E TH ERAP Y MAY 2021 37
Slide 38: Spinocerebellar Ataxia Type 3 (SCA3)
Spinocerebellar Ataxia Type 3 (SCA3) Autosomal dominant disorder • Spinocerebellar ataxia type 3 (SCA3) is the most common SCA • Prevalence is 1-2:100,000 total population; ~7000 patients in the US and Europe • Average onset 37 years Symptoms • Ataxia • Dystonia/Rigidity • Muscular atrophy • Paralys
Slide 39: SCA3: mutant ataxin-3 protein forms toxic aggregates
SCA3: mutant ataxin-3 protein forms toxic aggregates leading to neurodegeneration CAG repeat ATXN3 mRNA polyQ repeat Cereb ellum Mutant Brainstem ataxin-3 protein Spinal cord SCA3 Healthy control Toxic ataxin-3 protein aggregation Cereb ellum Neurodegeneration Eichler L et al. Am J Neuroradiol (2011
Slide 40: AMT-150: AAV5-microRNA against ATXN3
AMT-150: AAV5-microRNA against ATXN3 to lower toxic ataxin-3 protein ITR ITR miQURE® Pol II promoter polyA CAG repeat ATXN3 mRNA miQURE® miQURE® Reduction of toxic ataxin-3 protein polyQ repeat Degradation of ATXN3 mRNA LEA DERS HI P IN GENE THERA PY SEPT EMB E R 2021 | 40
Slide 41: AMT-150: functional improvement in transgenic SCA3 mice
AMT-150: functional improvement in transgenic SCA3 mice after high dose cisterna magna delivery AMT-150 • Transgenic SCA3 mice with highest brainstem transduction show partial SCA3 phenotype improvement Veh WT AMT-150 Veh Q84/Q84 Total Locomotor Activity 4000 8wk Injection (Cisterna Magna) Cerebellu
Slide 42: Fabry disease: a lysosomal storage disease
Fabry disease: a lysosomal storage disease (LSD) X-linked genetic disorder • Deficiency of α-galactosidase A (GLA) • Prevalence: 1:3,700 – 80,000 live births* • Population: ~15,000 in US and Europe Symptoms • Fatigue and hearing loss • Neuropathic pain • Angiokeratomas • Corneal opacity • Cardiac di
Slide 43: AMT-191: delivers highly efficient one-time treatment
AMT-191: delivers highly efficient one-time treatment AAV5-GLA Decreased Gb3 accumulation in treated AAV5 encoding an Fabry mouse kidney α-galactosidase A (GLA) transgene cortical Gb3 medullary Gb3 WT + AAV vehicle capsid Expression cassette Fabry + vehicle ITR ITR Promoter GLA polyA Fabry + AAV5-GL
Slide 44: AMT-191: highly efficient treatment in Fabry mice
AMT-191: delivers highly efficient treatment in Fabry mice Vector DNA level GLA-activity in Liver tissue • Dose-dependent and sustained GLA protein GLA-activity (nmol/h/mg) in Fabry mouse liver 1000000 genome copies/μg DNA 10 8 100000 >3000-fold and activity levels in plasma and in liver 10 7 10 6 1
Slide 45: AMT-191: kidney and heart cross-correction in Fabry mice
AMT-191: results in kidney and heart cross-correction and phenotypical correction in Fabry mice Cross correction in kidney and heart: Lyso-Gb3 (pmol/mg protein) Gb3 levels in Kidney LysoGb3 levels in Kidney Gb3 (pmol/mg protein) • Higher GLA-activity levels 15000 14 12 10000 10 8 • Gb3 and LysoGb3 s
Slide 46: AMT-191: highly efficient increase of GLA in non-human primates
AMT-191: highly efficient increase of GLA in non-human primates GLA activity plasma Liver DNA NHP GLA-treated • High and sustained plasma GLA GLA activity nmol/h/mL activity levels without anti-GLA IgG DNA liver (copies/μg) 1000 10 8 14 Days 10 7 56 Days 800 development 10 6 10 5 600 • Increased GLA
Slide 47: Acquisition of Corlieve Therapeutics
Acquisition of Corlieve Therapeutics uniQure acquires Corlieve and advances its gene therapy to treat Temporal Lobe Epilepsy (TLE), a large indication with high unmet need • Highly compelling and strategic transaction: • Expands uniQure’s pipeline of transformational gene therapies • Strengthen’s un
Slide 48: Refractory temporal lobe epilepsy (TLE)
Refractory temporal lobe epilepsy (TLE) • TLE is the most common type of focal epilepsy • TLE is associated with damage to the temporal lobe and hyperexcitability of the hippocampus • It’s often caused by brain injury, tumors or a prolonged febrile seizure • TLE affects approximately 1.3 million peo
Slide 49: Kainate receptors are implicated in TLE
Kainate receptors are implicated in TLE Epileptic Condition CA1 Mossy fibers • Kainate receptors are excitatory glutamate Schaffer AMPA collaterals CA3 receptors receptors that are epileptogenic and Seizures believed to be aberrantly expressed in rMF the hippocampus of refractory TLE Dentate gyrus +
Slide 50: AMT-260 reduces seizures in preclinical models of TLE
AMT-260 reduces seizures in preclinical models of TLE 40 # Seizure / day 30 • AMT-260 is an AAV gene therapy that Mouse 20 delivers an engineered miRNA TLE model 10 * * targeting kainate receptors 0 • AMT-260 & AMT-261* dramatically Control AMT260 AMT261 + Control vector reduce seizures in a pilocar
Slide 51: LEA DERS HI P IN GENE THERA PY SEPT EMB E R 2021
LEA DERS HI P IN GENE THERA PY SEPT EMB E R 2021 | 51
Slide 52: Slide 52