Cantor Global Healthcare Conference October 2, 2019 D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S S E P T E M B E R 2 0 1 9 | 1
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 to,” “may,” “plan,” “potential,” “predict,” “project,” “should,” "will,” “would” and similar expressions. Forward-looking statements are based on management's beliefs and assumptions and on information available to management only as of the date of this presentation. These forward-looking statements include, but are not limited to, statements regarding the development of our gene therapies, the success of our collaborations, and the risk of cessation, delay or lack of success of any of our ongoing or planned clinical studies and/or development of our product candidates. Our actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, risks associated with collaboration arrangements, our and our collaborators’ clinical development activities, regulatory oversight, development of product candidates, product commercialization and intellectual property claims, as well as the risks, uncertainties and other factors described under the heading "Risk Factors" in uniQure’s Quarterly Report on Form 10-Q filed on July 29, 2019. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these forward-looking statements, even if new information becomes available in the future. D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S S E P T E M B E R 2 0 1 9 | 2
Key corporate achievements and capabilities • Demonstrated clinical proof of concept in Hemophilia B; achievement of patient 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 Phase I/II study this year • Strong pipeline of additional product candidates approaching the clinic including in Hemophilia A, Fabry disease, and SCA3 • Global commercial rights retained for all core programs • Leadership in large-scale, cGMP manufacturing of AAV gene therapies • Portfolio of enabling technologies and IP, including miQURE ™ gene silencing, FIX -Padua variant, re-administration, manufacturing processes and AAV5 and other novel vectors and promoters D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S S E P T E M B E R 2 0 1 9 | 3
Our proprietary pipeline D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S S E P T E M B E R 2 0 1 9 | 4 *Collaboration with Bristol-Myers Squibb
Leading the way in AAV manufacturing Large-scale AAV Manufacturing • Based in Lexington, MA, expanded to 80,000 ft 2 Proprietary 3 rd generation insect cell, baculovirus • • Demonstrated 500L stirred-tank production • Scalable up to 2 x 2,000L • Strong intellectual property position Potential Benefits • Control and flexibility • Consistent process from small-scale to large-scale • Highly scalable, cost-effective • High-volume capacity • Consistent, stable, high-quality product D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S S E P T E M B E R 2 0 1 9 | 5
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 studies 1 • Observed clinical effects in the liver and brain • Low avidity of pre-existing neutralizing antibodies (NAbs) • Favorable immunogenicity profile for systemic, intravenous delivery • No confirmed T-cell-mediated immune responses to capsid 1 uniQure clinical trials in Hemophilia B, Sanfilippo B and Acute Intermittent Porphyria D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S S E P T E M B E R 2 0 1 9 | 6
Hemophilia B Etranacogene dezaparvovec (AMT-061) D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S S E P T E M B E R 2 0 1 9 | 7
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-treatment 70 Participant 2 FIX activity one-stage aPTT • No infusions of replacement therapy for bleeds Participant 3 60 54,1 • No requirement of immunosuppression (% of normal) 50 • No exclusion of patients with pre-existing NAbs 50,9 40 30,1 30 Main Safety Findings: • Well-tolerated 20 • No serious adverse events related to treatment 10 • No inhibitor development 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 Week D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S S E P T E M B E R 2 0 1 9 | 8
Etranacogene dezaparvovec (EtranaDez): HOPE-B Phase III pivotal study • Achieved enrollment of 62 patients with severe and moderately-severe Hemophilia B • Open label, single-dose, multi-center, multi-national trial • Patients with AAV5 neutralizing antibodies not excluded • Patients serve as their own control; 6-month lead-in to establish baseline • Study objectives: • Increase FIX activity • Reduce frequency of bleeding episodes • Decrease use of FIX replacement therapy • Assess efficacy and safety D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S S E P T E M B E R 2 0 1 9 | 9
Huntington’s Disease AMT-130 D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S S E P T E M B E R 2 0 1 9 | 10
Executing in Huntington’s Disease Target product profile • One-time administration of disease-modifying therapy Proprietary miQURE TM silencing platform • Huntington’s AMT-130 • Strong mHTT knockdown in both deep structures and cortex • Targets full length HTT protein aggregates and highly toxic HTT • 3-7 per 100K people 1 exon1 protein fragments • No treatments available • Strong preclinical data • Potential to be first to market • Near-term goal: Initiate dosing of Phase I/II 1 Rawlins, MD. Neuroepidemiology 2016;46:144-153 D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S S E P T E M B E R 2 0 1 9 | 11
Huntington’s disease: expected progression of brain pathology Somatomotor • The striatum is the primary site of cortex Frontal Somatosensory lobe pathology cortex 2 Parietal 3 • Premanifest stage: atrophy 3 lobe spreads and cortical thinning occurs 1 Occipital lobe • Motor symptoms manifest as atrophy increases The shading and arrows indicate the progression of pathology. Darker shading represents earlier onset. 1. McColgan P, Tabrizi SJ. Eur J Neurol. 2018;25(1):24-34; 2.Tabrizi SJ, et al. Lancet Neurol 2009;8(9):791-801; Figure adapted from Brundin P, et al. Nat Rev Mol Cell Biol 2010;11:301-7. 3. Nopoulos PC, et al. Neurobiol Dis 2010;40(3):544-54 D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S S E P T E M B E R 2 0 1 9 | 12
AMT-130: goal of clinical treatment to slow or halt disease progression from an early stage Penetration throughout NHP brain Vector DNA distribution 8 1 0 V e c t o r g e n o m e c o p i e s 7 1 0 p e r g D N A 6 1 0 5 1 0 1 4 L L O D 1 0 3 1 0 P u t a m e n C a u d a t e T h a la m u s C o r t e x 1 3 g c A A V 5 - m iH T T 1 x 1 0 1 3 g c A A V 5 - m iH T T 3 x 1 0 1 Lower Limit of Detection Samaranch L. et al, Gene Ther. 2017 Apr;24(4):253-261. Figure 3 D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S S E P T E M B E R 2 0 1 9 | 13
AMT-130: strong reduction of mHTT Comparable mutant huntingtin protein Libechov transgenic (tgHD) minipigs: knockdown at 6 and 12 months • Life-span: 12-20 years • Body weight: 50-140 kg • Brain weight: 90-100 g Cortex Striatum • Highly developed immune system 125 6 months mutant HTT protein 12 months MRI-guided CED 100 (% from naive) 75 30% 50 50% caudate 70% 25 putamen 0 Prefrontal Somato-S/M Temporal Caudate Putamen Amygdala Thalamus Pons Cerebellum N=12 Bars represent average ± SEM of n=3-4 animals/group D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S S E P T E M B E R 2 0 1 9 | 14
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 follow-up (5 years for treated patients) D E L I V E R I N G G E N E T H E R A P Y T O P A T I E N T S S E P T E M B E R 2 0 1 9 | 15
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