Corporate Presentation MAY 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 M A Y 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 M A Y 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 M A Y 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 M A Y 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 M A Y 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 M A Y 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 M A Y 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 M A Y 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 M A Y 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 M A Y 2 0 1 9 | 10
AMT-061: FIX activity at 26 weeks post-treatment Increases in FIX Activity up to 57% Main Efficacy Findings: Mean FIX activity at 26 weeks of 47.1% • 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 M A Y 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 M A Y 2 0 1 9 | 12
miQURE ™ Gene Silencing Technology 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 M A Y 2 0 1 9 | 13
miQURE TM our unique gene silencing technology • Degrades toxic genes without toxic effects • Delivered with AAV and is active long term • miRNA spreads in extracellular vesicles in the cerebrospinal fluid (CSF) to transduce the brain Shah R, et al. NEJM 2018;379:958-966. 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 M A Y 2 0 1 9 | 14
miQURE ™ vs. gene replacement Gene replacement Defect Deliver correct Correct gene gene gene function miQURE™ technology miQURE ™ treatment No toxicity Toxic Degrade toxic gene gene 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 M A Y 2 0 1 9 | 15
miQURE ™: important features • Expression from pol II promoter for tissue specificity and regulation • Specificity Liver- or brain-specific expression & • Scaffold for high processing precision and no off-target effects Regulation • No passenger strand • Expression comparable with cellular miRNAs ensures no saturation of the natural RNAi mechanism Safety • No direct toxicity • Induces cytoplasmic and nuclear gene lowering Bio- • Also prevents nuclear aggregates distribution • Spread via CSF and lymph with extracellular vesicles (EV) & Processing • Full protection of affected target organs 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 M A Y 2 0 1 9 | 16
miQURE ™ scaffold: high -processing precision with no off-target effects miQURE ™ conventional • High miQURE ™ processing miRNA precision (Dicer-independent) • Safer therapeutic. No Drosha Dicer Drosha miQURE ™ off -target effects (no passenger strand) Passenger strand (off-targets) • Proprietary IP/ FTO 2022 /license CSH Guide strand Guide strand (active) (active) No passenger 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 M A Y 2 0 1 9 | 17
miQURE ™: scaffold advantage - no off-target effects Processing fidelity superior to conventional miRNA iPS-derived neurons 200 iPS-derived astrocytes Relative expression (%) Relative to formulation buffer 150 100 50 0 1 L 1 1 2 2 6 1 1 N 6 2 2 2 C 3 1 P S B M A P F A 9 _ A L C P 2 P R F C 1 I B T R D 5 1 O 0 F 8 E R F T R A N G M C T B F C 2 C E R 1 P O G R P 3 N N R U E A H N F A N H G G A H L D C S N Z I R A D S Y P K A C A L I S K C A BLAST siSPOTR 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 M A Y 2 0 1 9 | 18
miQURE ™: cytoplasmic and nuclear gene lowering cytoplasm miQURE ™ spread of efficacy nucleus miQURE ™ • Conventional miRNA do not 1 result in nuclear silencing • miQURE ™ causes nuclear 2 3 silencing • Nuclear silencing is critical in HD and ALS-c9orf72 where Gene Degradation toxic mRNA and protein species cause the disease extracellular vesicles 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 M A Y 2 0 1 9 | 19
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