uniQure N.V. · NASDAQ:QURE
uniQure — Investor Presentation (April 2023)
56 slides from uniQure's investor presentation, April 2023
Slide 1: Leadership in Gene Therapy
Leadership in Gene Therapy Corporate Presentation April 2023 Charles, Huntington’s disease patient advocate
Slide 2: Our mission: curative, one-time administered genomic medicines
Our mission is to deliver curative, one-time administered genomic medicines that transform the lives of patients. Reimagining the future through ingenuity and innovation. Ron, a clinical trial patient for etranacogene dezaparvovec LL EEAA DEDRESRHSI P H IIPN IGNE N GEE N THEETRH AE RAPY PY AAPP R I
Slide 3: Our history of innovation
our history of innovation A gene therapy pioneer with a 25-year history and deeply engrained culture of innovation across an increasingly validated platform First First First First First LEADERSHIP IN GENE THERAPY APRIL 2023 | 3
Slide 4: A case study in delivering value through innovation
a case study in delivering value through innovation Pursuing hemophilia B with a first and potential best-in-class gene therapy ~5 years 2017 2020 2022/2023 Announced transition Completed dosing in HEMGENIX® approved to AMT-061 HOPE-B pivotal study in the U.S. and EU 2018 2020 Initiated Ph 2b dose-
Slide 5: Leading the gene therapy revolution
leading the gene therapy revolution • Validated technology platform • Industry-leading manufacturing capabilities • Broad pipeline of first/best-in-class gene therapies • Strong financial position • Numerous near-term milestones • One to two-year Huntington’s disease data from U.S. Ph 1/2 • One-year
Slide 6: Manufacturing excellence for global, commercial opportunities
manufacturing excellence for global, commercial opportunities Establishing larger scale and highly cost-effective capabilities to address more prevalent disorders COGS LEADERSHIP IN GENE THERAPY APRIL 2023 | 6
Slide 7: Expanding our capabilities
expanding our capabilities Completed construction of a second cGMP manufacturing facility in Amsterdam that will complement commercial manufacturing in Lexington, Massachusetts. Amsterdam, NL Lexington, MA 111,000 sq ft (~290 FTEs) 100,000 sq ft (~200 FTEs) Research Process Development Process Devel
Slide 8: Our areas of focus
our areas of focus AAV Engine: Leveraging our leading technology platform to develop and commercialize products targeting the CNS and liver CNS Liver AAV Technology Engine Manufacturing & Enabling Tools LLEEAA DDEE RSRH SIHPI P I NI N G EGNEENTEH T EHRA EPRYA P Y AAPPRRI LI L 22002233 | 8
Slide 9: Reimagining the R&D pipeline
reimagining the R&D pipeline Doubling the pipeline in 5 years 5-year Pipeline 3-4 Phase 3 commercial 5-8 Phase 1/2 programs 7-12 preclinical Goals: programs programs LEADERSHIP IN GENE THERAPY APRIL 2023 | 9
Slide 10: Reimagining the R&D pipeline: key criteria
reimagining 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 LLEEAA DDEE RSRH SIHPI P I NI N G EGNEENTEH T EHRA EPRYA P Y AAPPRRIILL 22002233 | 10
Slide 11: Recent transactions
recent transactions In January 2023, completed global licensing deal for AMT-162 (formerly APB-102), a clinical stage gene therapy for SOD1 ALS • $10 million up-front cash payment • Up to $45 million upon achievement of regulatory approvals and pre- specified annual net sales milestones • Tiered roy
Slide 12: Our Research and Development Pipeline
Our Research and Development Pipeline Preclinical Phase 1/2 Phase 3 INDICAT IONS CSL Behring partnership APPROVED HEMOPHILIA B etranacogene dezaparvovec (AMT-061) HUNTINGTON’S DISEASE (AMT-130) Proprietary program s AMYOTROPHIC LATERAL SCLEROSIS – SOD1 (AMT-162) TEMPORAL LOBE EPILEPSY (AMT-260)
Slide 13: Strong execution across all programs in 2022
strong execution across all programs in 2022 ✓ FDA approval of HEMEGENIX® Hemophilia B ✓ Received $55 million in additional milestone payments from CSL Behring ✓ Positive CHMP opinion for European approval ✓ Announced 12-month data on lower-dose cohort in Phase I/II trial of AMT-130 Huntington’s ✓ E
Slide 14: HEMGENIX
HEMGENIX | R etranacogene dezaparvovec-drlb
Slide 15: HEMGENIX approved by the FDA and EMA
CSL’s HEMGENIX was approved by the FDA in November 2022 and by ® the EMA in February 2023 • First and only FDA and EMA-approved gene therapy for adults with hemophilia B who: • Currently use factor IX prophylaxis therapy, or • Have current or historical life-threatening bleeding, or • Have repeated,
Slide 16: HOPE-B pivotal trial: improvement in average bleeding rate
HOPE-B pivotal trial: improvement in average bleeding rate (ABR) Compared with ≥ 6-month lead-in period, mean ABR for all bleeds during Month 7-24 post-treatment was significantly reduced by 64%. • Mean ABR lead-in period vs Months 7-24: 4.18 vs 1.51; p=0.0002 • The bleed reduction that satisfied th
Slide 17: HOPE-B pivotal trial: FIX activity levels over 24 months
HOPE-B pivotal trial: FIX activity levels over 24 months Mean (standard deviation [SD]; minimum-maximum) FIX activity levels were sustained throughout 24 months post-treatment. • Month 6: 39.0% (±18.7; 8.2-97.1) (n=51) • Month 18: 36.9% (±21.4; 4.5-122.9) (n=50) • Month 24: 36.7% (±19.0; 4.7-99.2) (
Slide 18: HOPE-B pivotal trial: most frequent adverse events
HOPE-B pivotal trial: most frequent adverse events (all causality ≥13%) The safety profile is consistent with previously presented data • Most AEs were mild (76.1%; moderate: 20.6%; severe 3.2%) Alanine aminotransferase increase (with or without increased aspartate transaminase) occurred in 11 parti
Slide 19: Strong, future economics from CSL Behring
strong, future economics from CSL Behring Global licensing agreement 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 2021 • $1.45B in regulatory and commercial milestones • Near term mile
Slide 20: Huntington's Disease AMT-130
Huntington’s Disease AMT-130 Charles, Huntington’s disease patient advocate
Slide 21: Huntington's disease: 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./EU1 • Initially described based upon characteristic chorea • Dystonia, incoordination, ataxia, and later rigidity and bradykinesia contribute to fun
Slide 22: 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 23: Two ongoing studies in the U.S., EU and UK
two ongoing studies in the U.S., EU and UK CT-AMT-130-01 (Phase Ia/II) CT-AMT-130-02 (Phase Ib/II) double-blind sham-controlled open-label 26 Patients 15 Patients Low-dose 6e12 High-dose 6e13 Surgical Low-dose 6e12 High-dose 6e13 AMT-130 AMT-130 Adaption AMT-130 AMT-130 (6 Drug, 4 Control) (10 Drug,
Slide 24: Encouraging 12-month data from lower dose cohort
encouraging 12-month data from lower dose cohort in U.S. Ph I/II study • AMT-130 was generally well-tolerated at lower dose, with no reported adverse drug reactions or serious unexpected suspected adverse reactions • CSF NfL increased as expected following surgical administration of AMT-130 and near
Slide 25: NfL levels near baseline at 12 months in treated patients
NfL levels near baseline at 12-months in treated patients Neurofilament Light Chain (NfL) Concentration in Cerebral Spinal Fluid (CSF) 900% Percentage Change from Baseline in CSF NfL 800% 700% Low Dose 1 600% Low Dose 2 from Baseline 500% Low Dose 3 400% Low Dose 4 Low Dose 5 300% Low Dose 6 200% Sh
Slide 26: Declines in CSF mHTT support target engagement
declines in CSF mHTT support target engagement 250 Percent Change in mHTT from Baseline 200 Percent Change mHTT 150 Low Dose 100 80.64 64.88 Control 49.81 50 1.89 0 -3.68 -13.17 -22.5 -16.81 -50 -26.42 -53.82 -100 Month 1 Month 3 Month 6 Month 9 Month 12 N= 4 3 3 3 4 3 4 3 4 3 LEADERSHIP IN GENE THE
Slide 27: AMT-130 appears well tolerated in U.S. low-dose cohort
AMT-130: appears to be well tolerated with no significant related safety issues in U.S. low-dose cohort • No adverse drug reactions were reported • No serious unexpected suspected adverse reactions were reported • Two serious adverse events were reported, both in the peri-operative period: • Deep ve
Slide 28: AMT-130: U.S. Ph I/II clinical update 2Q23
AMT-130: U.S. ph I/II clinical update 2Q23 Low-dose cohort High-dose cohort 10 patients 16 patients • 6 treated • 10 treated Followed up to 2 years Followed up to 1 year • 4 control* • 6 control* * Control groups are followed out to the 12-month blinding period only LEADERSHIP IN GENE THERAPY APRIL
Slide 29: AMT-130: U.S. Ph I/II clinical update 2Q23 measures
AMT-130: U.S. ph I/II clinical update 2Q23 General Biomarkers • Safety • Nf-L (neurofilament light) • Overall tolerability • mHTT in CSF Imaging Functional • Volumetric MRI • Motor function LEADERSHIP IN GENE THERAPY APRIL 2023 | 29
Slide 30: AMT-130: Ph I/II clinical data anticipated over next 12-18 months
AMT-130: ph I/II clinical data anticipated over next 12-18 months 2Q 2023 2H 2023 2024 • U.S. ph I/II clinical update • EU ph I/II clinical • EU ph I/II clinical low & higher doses update low dose update higher dose • 26 patients • 6 patients • 9 patients • Followed up to 2 years • Followed up to 1
Slide 31: AMT-130: Ph I/II clinical data anticipated over next 12-18 months
AMT-130: ph I/II clinical data anticipated over next 12-18 months • Several clinical data announcements featuring longer duration and larger number of evaluable patients • Data on all 41 patients in 2024 • One-year follow up on all patients • Up to three-year follow up on low-dose cohort • Opportuni
Slide 32: AMT-260 for Refractory Temporal Lobe Epilepsy
AMT-260 for Refractory Temporal Lobe Epilepsy
Slide 33: Refractory temporal lobe epilepsy (rTLE)
refractory temporal lobe epilepsy (rTLE) • TLE is the most common type of focal epilepsy1 • 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 p
Slide 34: AMT-260: an AAV9-LinQURE targeting GRIK2
AMT-260: an AAV9-LinQURE™ targeting GRIK2, the kainate glutamate receptor • AAV9 delivery of engineered miRNAs to reduce the expression of a glutamate receptor subtype that triggers seizures in focal epilepsies • AMT-260 targets the GluK2 subunit of the kainate receptors Guide Guide strand 1 strand
Slide 35: Kainate receptor activation triggers epileptic activity
kainate receptor activation triggers epileptic activity Repeated GluK2 stimulation accumulate over time Cumulative depolarization Sustain activity of GluK2 = cause for epileptic activity EPSPKA Repeated AMPA stimulation does not accumulate over time EPSPAMPA Artinian et al 2011 LEADERSHIP IN GENE TH
Slide 36: AMT-260: dose-dependent miRNA expression in mouse hippocampus
AMT-260: shows a dose-dependent increase in the expression of miRNAs in mouse hippocampus vector genome miR38R miR3bR 10 8 1×10 6 1×10 6 Genome Copies/ug DNA copies/ng total RNA 10 7 copies/ng total RNA 1×10 5 1×10 5 10 6 1×10 4 1×10 4 10 5 10 4 1×10 3 1×10 3 10 3 1×10 2 1×10 2 10 2 1×10 1 1×10 1 10
Slide 37: AMT-260 inhibits epileptic activity in pilocarpine mouse model
AMT-260: inhibits epileptic activity also improves health in the pilocarpine mouse model of TLE CL110 vs CL080 Before AMT-260 After AMT-260 30 ✱✱✱✱ Number of seizures/day 20 10 0 0 l ro 26 nt T- Copy of post only co M Copy of Racine_scale results A ✱✱✱✱ 15 10000 ✱✱✱✱ ✱✱✱ ✱✱✱✱ Distance traveled (cm)
Slide 38: AMT-260: suppression of epileptic activity in patient hippocampal slices
AMT-260: suppression of spontaneous epileptic activity in hippocampal slices from patients with refractory TLE Electrophysiological recordings on hippocampus resected from patient with rTLE Hippocampal slices prepared from patients transduced with control vectors and AMT-260 AMT-260 suppresses epile
Slide 39: AMT-260 reduces GRIK2 expression by 90% in NHP hippocampus
AMT-260: reduces GRIK2 gene expression by 90% in the hippocampus of non-human primates Knock down of GRIK2 mRNA in the The higher the expression of miRNA hippocampus is proportional to the in hippocampal neurons the lower expression of the miRNAs the expression of GRIK2 GRIK2 mRNA fold change (ΔΔCt)
Slide 40: Advancing AMT-260 into Clinical Development
Advancing AMT-260 into Clinical Development
Slide 41: AMT-260: route of administration demonstrated focal biodistribution
AMT-260: route of administration demonstrated focal biodistribution Injection accuracy Transduction efficacy in NHPs in NHP hippocampus Purple – Hippocampus Yellow – Gadoteridol Red - Trajectory Injection into effected brain areas Post-administration demonstrated full is targeted and accurate transd
Slide 42: AMT-260: targeted patient population for Phase 1/2 study
AMT-260: targeted patient population for phase 1/2 study Temporal Lobe Epilepsy (TLE) Targeted Phase 1/2 Population a subsection of focal epilepsy Development Focus Mesial (MTLE) Drug-resistant / • Hippocampal sclerosis* Refractory TLE *Considered pathologies for Phase (approx. 60% of all TLE patien
Slide 43: AMT-260: anticipated Phase 1/2 clinical study
AMT-260: anticipated phase 1/2 clinical study Study Overview • Objective: assess safety, tolerability and efficacy • Multi-center, open-label, controlled, randomized 2:1 over standard of care* • Subjects 1-month baseline period • Dose-finding of 2 cohorts with a total of 24 patients Patient enrollme
Slide 44: AMT-260: anticipated Phase 1/2 clinical study design
AMT-260: anticipated phase 1/2 clinical study Phase 1/2 open-label against standard of care to establish safety, dose and evaluate efficacy Cohort 1 – 12 patients (8 dosed, 4 control) Subject 1&2 Subject 3-5 Subject 6-10 Subject 11&12 1 dosed, 1 control 2 dosed, 1 control 3 dosed, 2 control 2 dosed
Slide 45: AMT-260: anticipated Phase 1/2 endpoints
AMT-260: anticipated phase 1/2 endpoints Clinical Parameters Biomarkers • Safety • Long–term EEG monitoring • Seizure count/reduction • Interictal discharges Imaging (MRI and PET) Biosensor data • Hippocampal volume • Continuous health monitoring • Metabolic function via smart watch LEADERSHIP IN GE
Slide 46: AMT-260: potential clinical timelines
AMT-260: potential clinical timelines 2022 2023 IND enabling Initiation of studies Phase 1/2 study 2023 2024 Expected IND Initial data cut of submission Phase 1/2 Study LEADERSHIP IN GENE THERAPY APRIL 2023 | 46
Slide 47: Amyotrophic Lateral Sclerosis (SOD1 ALS) AMT-162
Amyotrophic Lateral Sclerosis (SOD1 ALS) AMT-162 LEADERSHIP IN GENE THERAPY APRIL 2023 | 47
Slide 48: SOD1 Amyotrophic Lateral Sclerosis (ALS)
SOD1 Amyotrophic Lateral Sclerosis (ALS) • ALS (aka Lou Gehrig’s disease) is a progressive neurodegenerative disease that results in loss of motor neurons, involuntary movement, and death • Average age of diagnosis is mid 50’s; average lifespan of 2-4 years1 • Most cases are sporadic but ~10% are fo
Slide 49: SOD1 genetics and pathophysiology
SOD1 genetics and pathophysiology Mutations in SOD1 are a toxic gain of function that can affect many aspects of neuronal biology • More than 100 Pathogenic SOD-1 have been identified. • Mutations are concentrated in a few regions of the protein. • Mutations can be both dominant and recessive. • Mos
Slide 50: AMT-162 (formerly APB-102) for SOD1-ALS
AMT-162 (formerly APB-102) for SOD1-ALS • Recombinant AAVrh10 vector expresses an artificial micro ribonucleic acid (miRNA) designed to knock down the expression of SOD1 • Intrathecally administered • In vivo mouse data demonstrates greatly enhanced survival • In vivo mouse and NHP data supports bio
Slide 51: Strategic rationale for global licensing with Apic Bio
strategic rationale for global licensing with Apic Bio • Aligns with current neurodegenerative focus of pipeline and highly complementary with AMT-161 program for ALS caused by mutations in c9orf72 gene • Expands uniQure's ALS familial franchise allowing for synergistic clinical development and pote
Slide 52: Global licensing details
global licensing details • $10 million up-front cash payment • Up to $45 million upon achievement of regulatory approvals and pre- specified annual net sales milestones • Tiered royalties of a percentage of net sales starting in the mid-single to low double digits LEADERSHIP IN GENE THERAPY APRIL 20
Slide 53: Near-term milestones
uniQure ? ae Near-term. milestones...
Slide 54: Well-funded to meet our future needs
well-funded to meet our future needs Significant cash runway to advance our pipeline $393M* of cash, cash equivalents and investment securities Runway to mid-2024 +$175M in near-term milestones Extends runway into 1H 2025 +$1.3B in potential other milestones + royalties Extends runway into 2026 and
Slide 55: Key value drivers in 2023
key value drivers in 2023 ✓ European approval of HEMGENIX® Hemophilia B • CSL commercial launches in U.S. and Europe • Milestone payments up to $175 million for first product sales • Complete EU patient enrollment in Phase Ib/II clinical trial • Announce clinical update from U.S. Ph I/II trial Hunti
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