uniQure N.V. · NASDAQ:QURE
uniQure — Investor Presentation (November 2020)
30 slides from uniQure's investor presentation, November 2020
Slide 1: A Global Leader in Gene Therapy
A Global Leader in Gene Therapy Corporate Presentation November 2020
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: Key highlights & near-term catalysts
Key highlights & near-term catalysts • Global licensing agreement with CSL Behring announced in June Hemophilia B • Topline FIX data from fully enrolled HOPE-B pivotal study in late 2020 • BLA submission anticipated in 2021 • First four sentinel patients enrolled in Phase I/II study Huntington’s • P
Slide 4: Global leadership in AAV manufacturing
Global leadership 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 Benefi
Slide 5: Leveraging AAV5: a potentially best-in-class vector
Leveraging AAV5: a potentially best-in-class vector AAV5 – Clinically demonstrated tolerability and clinical effects observed to date AAV5 Vector • Long-term follow-up data demonstrating safety and tolerability • ~75 patients have received AAV5 across 5 clinical studies1 • Observed clinical effects
Slide 6: Hemophilia B
Hemophilia B Etranacogene dezaparvovec (AMT-061)
Slide 7: A global licensing deal with CSL Behring in hemophilia B
A global licensing deal with CSL Behring in hemophilia B • One of the largest gene therapy deals announced to date • CSL Behring is an ideal strategic partner with extensive commercial expertise in hemophilia that best positions uniQure to provide EtranaDez to the greatest number of global patients
Slide 8: A global licensing deal with CSL Behring in hemophilia B
A global licensing deal with CSL Behring in hemophilia B The transaction is a historic collaboration in gene therapy and hemophilia, with uniQure eligible to receive more than $2B in total economics • $450M upfront payment • $1.6B in regulatory and commercial milestones • Double-digit royalty paymen
Slide 9: A global licensing deal with CSL Behring in hemophilia B
A global licensing deal with CSL Behring in hemophilia B Partnership enables uniQure to leverage CSL Behring’s world-class global hemophilia commercial infrastructure • Hemophilia is a well-established, specialized and highly competitive global market • CSL Behring has been a leader in bleeding diso
Slide 10: Hemophilia B: significant financial burden and unmet medical needs
Hemophilia B: significant financial burden and unmet medical needs Disease prevalence: ~6,000 patients in the United States1 and ~14,000 patients in Europe2 Clinical burden Patient burden Economic burden Societal burden Lifelong bleeding Cumbersome ~$610,000 annual >$20 million lifetime risk with cu
Slide 11: Etranacogene dezaparvovec (AMT-061)
Etranacogene dezaparvovec (AMT-061) Key Treatment Features • Demonstrated ability to increase FIX activity to therapeutic levels • No bleeding events post-treatment • No replacement therapy for bleeds outside surgery • No requirement of immunosuppression • No exclusion of patients with pre-existing
Slide 12: AMT-060: sustained dose-dependent increases in FIX activity
AMT-060: sustained dose-dependent increases in FIX activity Cohort 1 Cohort 2 Mean FIX activity (95% CI): Mean FIX activity (95% CI): 5.1 (1.6 – 8.6) 7.5 (4.2 – 10.7) 20 20 1 (7.1) 2 (5.3) 3* (1.3) 4* (8.2) 5* (3.5) 6 (11.1) 7 (7.1) 8 (8.5) 9 (3.9) 10 (6.7) FIX activity (IU/dL) FIX activity (IU/dL)
Slide 13: Etranacogene dezaparvovec: Phase 2b sustained FIX activity in the functionally curative range
Etranacogene dezaparvovec: Phase 2b sustained FIX activity in the functionally curative range Mean FIX activity at 1 year: 41% of normal FIX activity measured by a one stage clotting assay conducted in a central lab. aPTT, activated partial thromboplastin time A GLOBAL LEADER IN GENE THERAPY NOVEMBE
Slide 14: Etranacogene dezaparvovec (EtranaDez): HOPE-B Phase III pivotal study
Etranacogene dezaparvovec (EtranaDez): HOPE-B Phase III pivotal study • Targeted dosing achieved: 54 patients treated as of March 26 • Severe and moderately-severe Hemophilia B patients • Open label, single-dose, multi-center, multi-national trial • Patients with AAV5 neutralizing antibodies not exc
Slide 15: Huntington's Disease
Huntington’s Disease AMT-130
Slide 16: Huntington's disease: prevalence and overview
Huntington’s disease: prevalence and overview • Patient population1: • Autosomal dominant neurodegenerative • ~25,000 patients in United States disorder • ~25,000 patients in Europe • Expansion of CAG trinucleotide huntingtin (HTT) exon1 • Underreported due to lack of treatment options • No disease-
Slide 17: AMT-130: major gene therapy opportunity
AMT-130: major gene therapy opportunity • One-time administration of disease-modifying therapy • Proprietary miQURETM silencing platform • Demonstrated strong knockdown at sites of pathology – striatum and cortex Huntington’s AMT-130 • Demonstrated restoration of neuronal function in diseased animal
Slide 18: AMT-130: extensive preclinical validation
AMT-130: extensive preclinical validation Model Efficacy Safety Distribution Cultured human ✓ ✓ neurons Rodents (HD rat4) ✓ ✓ (4 types HD mouse3) NHP ✓ ✓ ✓ (Non-human primate1) Pig ✓ ✓ ✓ (tgHD Minipig2) Recent publications 1. Samaranch L, et al. Gene Ther 2017;24:253-261; 5. Evers MM et al. Mol Ther
Slide 19: Huntington's disease: expected progression of brain pathology
Huntington’s disease: expected progression of brain pathology Somatomotor • The striatum is the primary site of pathology Frontal cortex Somatosensory lobe cortex 2 Parietal • Premanifest stage: atrophy spreads and 3 3 lobe cortical thinning occurs • Motor symptoms manifest as atrophy 1 Occipital in
Slide 20: AMT-130: well-tolerated and widespread distribution in the non-human primate brain
AMT-130: well-tolerated and widespread distribution in the non-human primate (NHP) brain NHP MRI-guided frontal Distribution throughout NHP brain convection-enhanced delivery Caudate nucleus Thalamus Putamen Globus pallidus Hippocampus No procedure-related neurological symptoms Putaminal delivery AA
Slide 21: AMT-130: strong reduction of mutant HTT in the minipig brain
AMT-130: strong reduction of mutant HTT in the minipig brain Libechov transgenic (tgHD) minipigs: Comparable mutant huntingtin protein • Lifespan: 12-20 years knockdown at 6 and 12 months • Body weight: 50-140 kg • Brain weight: 90-100 g • Highly developed immune system Cortex Striatum 125 6 months
Slide 22: AMT-130: neuropathology in diseased mouse model
AMT-130: neuropathology in diseased mouse model N-Acetyl Aspartate (tNAA) Myo-Inositol (MI) Neuronal integrity marker Gliosis marker 6.0 Q175FDN 7 Q175FDN Mean concentration Mean concentration 5.5 *** 6 * tNAA (mM) mI (mM) 5.0 5 4.5 4 4.0 3 10 9 09 0 11 0 11 r r l l ro ro ffe ffe X1 nt nt X1 X1 2X b
Slide 23: AMT-130: full-length and exon1 HTT lowering in striatum and cortex
AMT-130: full-length and exon1 HTT lowering in striatum and cortex in diseased mouse model Full-length HTT mRNA Full Full lenght length HTTHTTin inStriatum Striatum Full length HTT Full-length HTT in in Cortex Cortex 1.5 Relative expression to Formulation Buffer Relative expression to Formulation Bu
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 • 18-month follow-up (5 years for trea
Slide 25: AMT-130: Phase I/II clinical trial design
AMT-130: Phase I/II clinical trial design Cohort 1: 10 patients (6 dosed, 4 control) Cohort 2: 16 patients (10 dosed, 6 control) 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 randomizatio
Slide 26: AMT-130: Phase I/II efficacy endpoints
AMT-130: Phase I/II efficacy 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 tappin
Slide 27: Research Pipeline
Research Pipeline
Slide 28: Our proprietary pipeline
Our proprietary pipeline A GLOBAL LEADER IN GENE THERAPY NOVEMBER 2020 | 28
Slide 29: Key highlights & near-term catalysts
Key highlights & near-term catalysts • Global licensing agreement with CSL Behring announced in June Hemophilia B • Topline FIX data from fully enrolled HOPE-B pivotal study in late 2020 • BLA submission anticipated in 2021 • First four sentinel patients enrolled in Phase I/II study Huntington’s • P
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