uniQure N.V. · NASDAQ:QURE
uniQure — Investor Presentation (April 2019)
26 slides from uniQure's investor presentation, April 2019
Slide 1: Corporate Presentation April 2019
Corporate Presentation APRIL 2019 DELIVERING GENE THERAPY TO PATIENTS APRIL 2019 | 1
Slide 2: Forward-looking Statements
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
Slide 3: Our mission
Our mission To deliver curative, one-time therapies that transform the lives of patients. DELIVERING GENE THERAPY TO PATIENTS APRIL 2019 | 3
Slide 4: Our strategic imperatives
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 a
Slide 5: Expanding our proprietary pipeline
Expanding our proprietary pipeline DELIVERING GENE THERAPY TO PATIENTS APRIL 2019 | 5
Slide 6: Near-term goals
Near-term goals Hemophilia B Complete enrollment in HOPE-B Phase III pivotal study of AMT-061 Huntington’s Initiate dosing of Phase I/II study of AMT-130 Hemophilia A Submit IND for AMT-180 Other Programs Initiate IND-enabling toxicology study for one additional program DELIVERING GENE THERAPY TO PA
Slide 7: Leading the way in AAV manufacturing
Leading the way in AAV manufacturing Large-scale AAV Manufacturing • Based in Lexington, MA, expanding to 80,000 ft2 • 3rd generation insect cell, baculovirus • Demonstrated 500L stirred-tank production • Scalable up to 2 x 2,000L • Strong intellectual property position Benefits • Control and flexib
Slide 8: Leveraging AAV5: a potentially best-in-class vector
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 studies1 • Demonstrated clinical outcomes in the liver and brai
Slide 9: Hemophilia B AMT-061
Hemophilia B AMT-061 DELIVERING GENE THERAPY TO PATIENTS APRIL 2019 | 9
Slide 10: Executing in Hemophilia B
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 • 10-15K patients in US/EU • Greater patient eligibility due to low levels of NABs • >$1B market in
Slide 11: AMT-061: FIX activity up to 16 weeks post-treatment
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 Ma
Slide 12: AMT-061: HOPE-B Phase III pivotal study
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;
Slide 13: Huntington's Disease AMT-130
Huntington’s Disease AMT-130 DELIVERING GENE THERAPY TO PATIENTS A P R I L 2 0 1 9 | 13
Slide 14: Executing in Huntington's Disease
Executing in Huntington’s Disease Target product profile • One-time administration of disease-modifying therapy Huntington’s • Proprietary miQURETM silencing platform AMT-130 • Strong mHTT knockdown in both deep structures and cortex • 3-7 per 100K people1 • Preclinically shown to be generally safe
Slide 15: AMT-130: widespread distribution in brain
AMT-130: widespread distribution in brain Penetration throughout NHP brain Vector DNA distribution Vector genome copies per g DNA 1 1 Lower Limit of Detection Samaranch L. et al, Gene Ther. 2017 Apr;24(4):253-261. Figure 3 DELIVERING GENE THERAPY TO PATIENTS A P R I L 2 0 1 9 | 15
Slide 16: AMT-130: strong reduction of mHTT
AMT-130: strong reduction of mHTT Libechov transgenic (tgHD) minipigs: Comparable mutant huntingtin protein • Life-span: 12-20 years • Body weight: 50-140 kg knockdown at 6 and 12 months • Brain weight: 90-100 g • Highly developed immune system mutant HTT protein MRI-guided CED (% from naive) caudat
Slide 17: AMT-130: Phase I/II dose escalation study
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
Slide 18: Research Pipeline Expansion
Research Pipeline Expansion DELIVERING GENE THERAPY TO PATIENTS A P R I L 2 0 1 9 | 18
Slide 19: AMT-180: a novel approach to hemophilia A
AMT-180: a novel approach to hemophilia A Novel Approach • Product Construct – AAV5 including C7 Promoter and FIX-Super9 • Super9 is a proprietary modified FIX that, when activated through normal mechanisms, then activates FX independently of FVIII Long-term and Effective in all HemA Compatible with
Slide 20: AMT-180: expression levels in NHPs
AMT-180: expression levels in NHPs expected to translate to therapeutically relevant FVIII mimetic activity in humans male Cynomolgus hFIX protein (%) in NHPs macaque 250 n=2 vehicle IV, 9e13 gc/kg 200 AAV5-LP1-Super9 adapted delivery AAV5-P-IDAV 150 AAV5-P-Super9 1) AAV5-LP1-Super9 100 2) AAV5-P-ID
Slide 21: AMT-190: a new approach to Fabry disease
AMT-190: a new approach to Fabry disease Novel Approach • Product Construct – AAV5 including modified NAGA • Modified NAGA has therapeutic α-gal activity and gB3 reduction More effective than Patients with and without Non-immunogenic replacement therapy inhibitors • More stable in plasma • Many Fabr
Slide 22: Wild type Fabry vs Modified NAGA
Wild type Fabry Modified NAGA Fabrazyme Replagal Tajima Y et al. Am J Human Genetics 2009 DELIVERING GENE THERAPY TO PATIENTS A P R I L 2 0 1 9 | 22
Slide 23: AMT-150: a gene therapy for SCA3
AMT-150: a gene therapy for SCA3 Novel Approach • AAV5, SCA3 miRNA administered by intrathecal or cisterna magna injection • Leverages HD platform and experience, including miQURE gene silencing technology • Potential to be first to market Cause Damage Symptoms Unmet Need • CAG repeat expansion • Br
Slide 24: AMT-150: 65% ataxin-3 lowering in SCA3 mice
AMT-150: 65% ataxin-3 lowering in brainstem of SCA- concept3 mice after cisterna magna injection of miQURE SCA3 mouse model Up to 65% ataxin-3 lowering in SCA3 mice miQURETM SCA3 mouse brainstem Mutant ataxin-3 protein (%) 100 Relative to control 75 • N = 3 per group 50 * * • In-life 6 weeks 25 0 Co
Slide 25: Near-term goals
Near-term goals Hemophilia B Complete enrollment in HOPE-B Phase III pivotal study of AMT-061 Huntington’s Initiate dosing of Phase I/II study of AMT-130 Hemophilia A Submit IND for AMT-180 Other Programs Initiate IND-enabling toxicology study for one additional program DELIVERING GENE THERAPY TO PA
Slide 26: uniQure
uniQure