Corporate Presentation APRIL 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 A P R I L 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 Annual Report on Form 10-K filed on February 28, 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 A P R I L 2 0 1 9 | 2
Our mission To deliver curative, one-time therapies that transform the lives of 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 A P R I L 2 0 1 9 | 3
Our strategic imperatives Develop a proprietary pipeline of gene therapy candidates focused on Pipeline liver-directed and CNS disorders Maintain leadership in commercial-scale manufacturing of AAV gene Manufacturing therapies Enabling Invest and leverage next-generation technologies that optimize and Technologies expand the applicability of gene therapy to patients Intellectual Expand and maintain our leading IP portfolio Property Commercialization Retain valuable commercial rights 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 A P R I L 2 0 1 9 | 4
Expanding 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 A P R I L 2 0 1 9 | 5
Near-term goals Complete enrollment in HOPE-B Phase III pivotal study of AMT-061 Hemophilia B Huntington’s Initiate dosing of Phase I/II study of AMT-130 Submit IND for AMT-180 Hemophilia A Initiate IND-enabling toxicology study for one additional program Other Programs 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 A P R I L 2 0 1 9 | 6
Leading the way in AAV manufacturing Large-scale AAV Manufacturing • Based in Lexington, MA, expanding to 80,000 ft 2 3 rd generation insect cell, baculovirus • • Demonstrated 500L stirred-tank production • Scalable up to 2 x 2,000L • Strong intellectual property position Benefits • Control and flexibility • Consistent process from preclinical to commercial • 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 A P R I L 2 0 1 9 | 7
Leveraging AAV5: a potentially best-in-class vector AAV5 – Clinically demonstrated tolerability and outcomes AAV5 Vector • Long-term follow-up data demonstrating safety and tolerability • 25 patients have received AAV5 across 4 clinical studies 1 • Demonstrated clinical outcomes in the liver and brain • Low avidity of pre-existing neutralizing antibodies • Favorable immunogenicity profile for systemic, intravenous delivery • No confirmed T-cell-mediated immune responses to capsid 1 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 A P R I L 2 0 1 9 | 8
Hemophilia B 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 A P R I L 2 0 1 9 | 9
Executing in Hemophilia B Target product profile • Potential for functionally-curative increases in FIX activity • Durable and predictable outcomes Hemophilia B AMT-061 • Low risk of immune responses • Greater patient eligibility due to low levels of NABs • 10-15K patients in US/EU • >$1B market in 2016 1 • Strong intellectual property • Near-term goal: Complete • Potential to be first to market enrollment in pivotal study 1 GlobalData report 2016 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 A P R I L 2 0 1 9 | 10
AMT-061: FIX activity up to 16 weeks post-treatment Increases in FIX Activity up to 51% Main Efficacy Findings: Mean FIX activity at 12 weeks of 38% Sustained increases in FIX activity No bleeding events post-infusion No infusions of replacement therapy No requirement of immunosuppression Main Safety Findings: Well-tolerated No serious adverse events No inhibitor development 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 A P R I L 2 0 1 9 | 11
AMT-061: HOPE-B Phase III pivotal study • Patient dosing underway • Open label, single-dose, multi-center, multi-national trial • Approximately 50 patients with severe and moderately-severe hemophilia B • Patients with AAV5 antibodies will not be excluded • Patients will 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 A P R I L 2 0 1 9 | 12
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 A P R I L 2 0 1 9 | 13
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 • Preclinically shown to be generally safe and well-tolerated • 3-7 per 100K people 1 • No treatments available • Targets full length HTT protein aggregates and highly toxic • Strong preclinical data HTT exon1 protein fragments • Near-term goal: Initiate clinical study in 2019 • Potential to be first to market 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 A P R I L 2 0 1 9 | 14
AMT-130: widespread distribution in brain Penetration throughout NHP brain Vector DNA distribution Vector genome copies g DNA per 1 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 A P R I L 2 0 1 9 | 15
AMT-130: strong reduction of mHTT Comparable mutant huntingtin protein Libechov transgenic (tgHD) minipigs: • Life-span: 12-20 years knockdown at 6 and 12 months • Body weight: 50-140 kg • Brain weight: 90-100 g • Highly developed immune system mutant HTT protein MRI-guided CED (% from naive) caudate putamen l M l e n a s s m a a t e l u n t r a / a u n S m m o o d d l o - p P l u a g a e o r m t a t y l b f a e a u C m e e h N=12 m P r r T P A T e o C S 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 A P R I L 2 0 1 9 | 16
AMT-130: Phase I/II dose escalation study Efficacy Endpoints IND Cleared – Phase I/II Study Overview Clinical Parameters (e.g. UHDRS) • Objectives: assess safety, tolerability and efficacy • Multicenter, randomized, double-blinded study Quantitative Motor Function • Controlled with imitation surgery Volumetric MRI and MRS • Two dose cohorts with a total of 25 patients Biomarkers (e.g. mHTT in CSF) • Early manifest patients with ≥ 44 CAG repeats Patient-reported outcomes • 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 A P R I L 2 0 1 9 | 17
Research Pipeline Expansion 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 A P R I L 2 0 1 9 | 18
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