uniQure N.V. · NASDAQ:QURE
uniQure — Technical Presentation (June 2023)
43 slides from uniQure's technical presentation, Jun 21, 2023
Slide 1: Huntington's Disease Program Update AMT-130
Huntington’s Disease Program Update AMT-130 June 21, 2023
Slide 2: Forward-looking Statements
Forward-looking Statements This presentation contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical fact are forward-lookin
Slide 3: Opening Remarks
Opening Remarks Matt Kapusta Chief Executive Officer
Slide 4: Huntington's disease (HD): significant unmet medical need
Huntington’s disease (HD): significant unmet medical need • HD is an inherited, progressive neurodegenerative disease • 80,000 cases in Europe and North America with many more more at risk1 • HD strikes relatively young adults and children and progresses relentlessly leading to disability and death
Slide 5: AMT-130: key takeaways on the interim analysis
AMT-130: key takeaways on the interim analysis Promising data show early trends of a positive impact on disease progression and support continued development of AMT-130 1. AMT-130 was generally well-tolerated with a manageable safety profile 2. Patients treated with both doses of AMT-130 show early
Slide 6: AMT-130: next steps in clinical development
AMT-130: next steps in clinical development • Q3 2023: Completion of enrollment in Phase I/II trial in EU/UK • 2H 2023: Initiation of Cohort 3 in Phase I/II trial in the U.S. to investigate the effects of immunosuppression on perioperative safety • Q4 2023: Clinical update on Phase I/II trial includ
Slide 7: AMT-130 Clinical Trial Overview
AMT-130 Clinical Trial Overview Ricardo Dolmetsch, Ph.D. President of Research and Development
Slide 8: Huntington's disease (HD): significant unmet medical need
Huntington’s disease (HD): significant unmet medical need • Autosomal dominant inherited disorder (50% risk if your parent has HD) • The disease progresses from premanifest to early motor diagnosis to advanced disease over 10-15 years1 • Patients enrolled in the HD-TRX1 study are at an early to mode
Slide 9: Huntington's disease (HD): manifestation
Huntington’s disease (HD): manifestation ≥ 40 CAG Prolonged Expanded Protein Neuronal repeat HTT CAG repeat polyglutamine aggregation degeneration DNA HTT1a mRNA tract in protein Somatomotor Somatosensory cortex cortex Frontal lobe 2 Parietal 3 lobe 3 Occipital lobe 1 The shading and arrows indicate
Slide 10: AMT-130: mechanism of action in Huntington's disease
AMT-130: mechanism of action in Huntington’s disease AMT-130 is a modified AAV5 viral vector containing an HTT exon1 targeting miRNA AAV5 capsid Expression cassette HTT1a mRNA miQURE miHTT miRNA promoter polyA AMT-130 is investigational and has not been proven to be safe or effective and is not appr
Slide 11: AMT-130: direct, intra-striatal convection-enhanced delivery
AMT-130: maximizing potential for clinical impact via direct, intra-striatal convection-enhanced delivery Three stereotactic injections delivered on Real time MRI visualization using Gd each side into the putamen and caudate contrast agent nucleus, using convection enhancement. Putamen Caudate nucle
Slide 12: AMT-130: phase I/II U.S. clinical trial design
AMT-130: phase I/II U.S. clinical trial design United States Biomarkers and Endpoints Inclusion Criteria Cohorts 1 and 2 ✓ ≥40 CAG Screening visit NfL, mHTT ✓ 25 to 65 years of age ≤12 weeks Randomization ✓ Total functional capacity Baseline visit (TFC) 9-13 Day 0 Surgery ✓ Diagnostic Classification
Slide 13: AMT-130: patient enrollment overview
AMT-130: patient enrollment overview 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 Low-dose 6e12 High-dose 6e13 AMT-130 AMT-130 Cohort 3 AMT-130 AMT-130 (6 Drug, 4 Control) (10 Drug, 6 Control) (6
Slide 14: AMT-130: baseline demographic and disease characteristics balanced
AMT-130: baseline demographic and disease characteristics balanced across all groups Characteristic Control AMT-130 Low-dose AMT-130 High-dose (mean, SD, range as applicable) n = 10 n=6 n = 10 Males/Females (n) 6/4 2/4 4/6 Age at screening 47.0 (8.3), 34 - 58 49.5 (5.3), 44 - 57 47.8 (10.4), 33 - 65
Slide 15: AMT-130: safety and tolerability
AMT-130: safety and tolerability • AMT-130 was generally well-tolerated across both dose cohorts • No treatment emergent adverse events (TEAEs) led to discontinuation of patient follow-up • Most common treatment emergent adverse events were: • Procedural Headache (Control 50%, Low Dose : 57.1% High
Slide 16: AMT-130: safety and tolerability
AMT-130: safety and tolerability • Severe Adverse Events (SAEs) occurred more often in the AMT-130 treatment groups • Low dose (n=2): post-operative delirium, major depression, suicidal ideation • High dose (n=2): back pain, tension headache, CNS inflammation, post-lumbar puncture syndrome • Control
Slide 17: AMT-130: natural history comparators
AMT-130: natural history comparators with and without a minimum striatal volume Natural History Cohort 2 includes TRACK-HD patients that closely match the study’s clinical inclusion criteria. Natural History Cohort 1 is the subgroup of patients from cohort 2 that exceed the minimum striatal volumes.
Slide 18: Treated patients improved in TMS relative to controls and natural history
AMT-130: treated patients improved in TMS relative to controls and natural history 6 Change in Total Motor Score (TMS) Control 5 AMT-130 Low Dose Change in Total Motor Score (SE) AMT-130 High Dose 4 Natural History 1 (Ph. I/II criteria w/ min. striatal volumes) Natural Natural History 2 (Ph. I/II cr
Slide 19: Treated patients preserved TFC scores relative to baseline
AMT-130: treated patients preserved TFC scores relative to baseline and improved compared to controls and natural history Change in Total Functional Capacity (TFC) 1.5 Change in Total Functional Capacity (SE) Control AMT-130 Low Dose 1 AMT-130 High Dose Natural History 1 (Ph. I/II criteria w/ min. s
Slide 20: Treated patients preserved function in SWT
AMT-130: treated patients preserved function in SWT relative to baseline and improved compared to natural history Change in Stroop Word Test (SWT) 20 Control AMT-130 Low Dose Change in Stroop Word Test (SE) 15 AMT-130 High Dose Natural History 1 (Ph. I/II criteria w/ min. striatal volumes) 10 Natura
Slide 21: High-dose patients favorable to natural history in SDMT
AMT-130: high-dose treated patients are favorable to natural history and controls in SDMT Change in Symbol Digit Modalities Test (SDMT) 12 Change in Symbol Digit Modalities Test (SE) 10 8 6 4 Improvement 2 0 Natural -2 History -4 -6 Control -8 AMT-130 Low Dose -10 AMT-130 High Dose Natural History 1
Slide 22: Treated patients preserved cUHDRS relative to baseline
AMT-130: treated patients preserved cUHDRS relative to baseline and improved compared to natural history Change from Baseline in Composite Unified Huntington’s Disease Rating Scale (cUHDRS) 1.5 1 Change in cUHDRS (SE) 0.5 Improvement 0 -0.5 -1 Control AMT-130 Low Dose AMT-130 High Dose Natural -1.5
Slide 23: AMT-130: clinical and functional data conclusions
AMT-130: clinical and functional data conclusions • Based on a small number of treated patients with limited follow up, there is an early indication of a potentially positive clinical effect of AMT-130 on disease progression • Patients treated with the low-dose of AMT-130 have generally preserved fu
Slide 24: Biomarker: Neurofilament Light Chain (NfL)
Biomarker: Neurofilament Light Chain (NfL) Phase I/II U.S. Clinical Trial
Slide 25: NfL below baseline and natural history in low-dose cohort
AMT-130: NfL is below baseline and natural history in low-dose cohort and declining towards baseline in high-dose cohort Neurofilament Light Chain (NfL) percentage change from baseline 600 in Cerebrospinal Fluid (CSF) Control • As expected, CSF NfL AMT-130 Low Dose increases immediately Percentage c
Slide 26: NfL trends in treated patients continue to be encouraging
AMT-130: NfL trends in treated patients continue to be encouraging at 12- and 24-months NfL levels are below baseline in 4 of 5 evaluable low-dose patients at 24 months and 4 of 8 high-dose patients with at least 12 months of follow-up Control CSF NfL Percentage Change Low Dose CSF NfL Percentage Ch
Slide 27: AMT-130: NfL conclusions
AMT-130: NfL conclusions • As expected, an increase in CSF NfL occurred immediately after the surgical procedure • The initial NfL spikes are not dose-dependent and are likely related to the surgical intervention • CSF NfL continued to decline in the low-dose cohort and was below baseline and natura
Slide 28: Biomarker: Mutant HTT
Biomarker: Mutant HTT Phase I/II U.S. Clinical Trial
Slide 29: mHTT reduced in treated patients in low-dose cohort
AMT-130: mHTT reduced in treated patients in low-dose cohort relative to baseline and control Low-Dose Cohort vs Control mHTT Percentage Change in Low-Dose Evaluable 120 Patients 60 Percentage Change from Baseline (SE) Control 100 AMT-130 Low Dose 80 40 Percentage Change in CSF mHTT 60 40 4.7% 20 20
Slide 30: mHTT more variable in high-dose cohort
AMT-130: mHTT in CSF is more variable in high-dose cohort, some patients showing evidence of reductions High-Dose Cohort vs Control mHTT Percentage Change High-Dose 280 Evaluable Patients Control Percentage Change from Baseline (SE) AMT-130 High Dose 900 240 800 200 700 Percentage Change in CSF mHTT
Slide 31: mHTT generally above baseline in control patients
AMT-130: mHTT in CSF is generally above baseline in the control patients Control Only mHTT Percentage Change Control in Evaluable 250 Patients 120 Control Percentage Change from Baseline (SE) 200 Percentage Change in CSF mHTT 80 150 40 100 50 4.7% 0 0 -40 -50 0 3 6 9 12 15 18 Months -100 0 3 6 9 12
Slide 32: AMT-130: mHTT conclusions
AMT-130: mHTT conclusions • Interpatient variability in mHTT data is potentially related to inherent limitations of the assay • Reduction of mHTT in the low-dose cohort supports AMT-130 target engagement • High variability in mHTT was observed in the high-dose cohort, with 3 of 9 patients below base
Slide 33: Imaging Data
Imaging Data Phase I/II U.S. Clinical Trial
Slide 34: Whole brain volume is not significantly impacted by treatment
AMT-130: whole brain volume is not significantly impacted by treatment Whole Brain Volume Percentage Change 1 Control AMT-130 Low Dose 0.5 Percentage Change from Baseline AMT-130 High Dose Natural History 1 (Ph. I/II criteria w/ min. striatal volumes) 0 Natural History 2 (Ph. I/II criteria w/out min
Slide 35: AMT-130: volumetric MRI imaging
AMT-130: volumetric MRI imaging • Whole brain volume: There is no statistically significant difference between the loss of whole brain volume in patients treated with AMT-130 versus controls • Ventricular volume: Patients treated with both doses of AMT-130 have a greater increase in ventricular volu
Slide 36: Interim Analysis Conclusions
Interim Analysis Conclusions Phase I/II U.S. Clinical Trial
Slide 37: AMT-130: summary and conclusions
AMT-130: summary and conclusions Promising data show early trends of a positive impact on disease progression and support continued development of AMT-130 • AMT-130 was generally well-tolerated with a manageable safety profile • Patients treated with both doses of AMT-130 show early evidence of pres
Slide 38: AMT-130 Clinical Program Next Steps
AMT-130 Clinical Program Next Steps
Slide 39: AMT-130: next steps in clinical development
AMT-130: next steps in clinical development • Q3 2023: Completion of enrollment in Phase I/II trial in EU/UK • 2H 2023: Initiation of Cohort 3 in Phase I/II trial in the U.S. to investigate the effects of immunosuppression on perioperative safety • Q4 2023: Clinical update on Phase I/II trial includ
Slide 40: Key Opinion Leader Perspective
Key Opinion Leader Perspective Sarah Tabrizi, M.D., FRCP, P.h.D., FMedSci University College London
Slide 41: Research Analyst Questions
uniQure ee ss Research Analyst . Questions i aaaaas e ® i & ry 5.
Slide 42: Closing Remarks
uniQure Closing Remarks
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