Corporate Presentation SEPTEMBER 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
Our mission statement 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 S E P T E M B E R 2 0 1 9 | 3
Key corporate highlights • Demonstrated clinical proof of concept in Hemophilia B; achievement of planned 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 | 4
Our proprietary pipeline *Collaboration with Bristol-Myers Squibb 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
Key corporate goals • Topline data from HOPE-B pivotal study in 2020 Hemophilia B • BLA submission in 2021 • Initiate dosing in Phase I/II study before end of 2019 Huntington’s • Preliminary biomarker data on initial patients in 2020 Hemophilia A • Submit IND for AMT-180 in 2020 • Initiate IND-enabling study for SCA3 in 2019 Other Programs • Targeting one new IND-submission each year 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
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 | 7
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 | 8
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 | 9
Executing in Hemophilia B Target product profile • Increase FIX activity into normal range • Durable and predictable outcomes Hemophilia B • Low risk of immune responses AMT-061 • Greater patient eligibility due to AAV5 NAb profile • 10-15K patients in US/EU • Strong intellectual property • >$1.3B market in 2018 1 • Near-term goal: Complete • Potential to be first to market patient dosing in pivotal study 1 GlobalData report 2018 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
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 Main Safety Findings: 30 • 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 | 11
Etranacogene dezaparvovec (EtranaDez): HOPE-B Phase III pivotal study • Achieved planned enrollment of 56 patients with severe and moderately-severe H emophilia B • Expect to over-enroll up to six additional patients in September 2019 • 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 | 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 S E P T E M B E R 2 0 1 9 | 13
miQURE TM our unique gene silencing technology • One-time administration • Potential to degrade toxic gene products without toxic effects • Delivered with AAV and is active long term • Vector-generated miRNA in directly transduced brain cells can transfer horizontally and via the CSF to non-transduced cells to produce widespread effect in 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 S E P T E M B E R 2 0 1 9 | 14
miQURE™ vs. gene replacement Gene replacement Defect Deliver correct Correct gene gene gene function miQURE™ technology miQURE™ Reduce impact of Degrade toxic Toxic gene toxic gene gene 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 | 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 lowering of targeted mRNA in both the nucleus and the cytoplasm • Also prevents nuclear aggregates Bio- distribution • Spreads via extracellular vesicles (EV) in the CSF, protecting the whole & affected organ 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 S E P T E M B E R 2 0 1 9 | 16
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 | 17
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