uniQure N.V. · NASDAQ:QURE
uniQure — Investor Presentation (July 2018)
43 slides from uniQure's investor presentation, July 2018
Slide 1: Corporate Presentation July 2018
Corporate Presentation JULY 2018
Slide 2: 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,” “poten
Slide 3: Our mission
Our mission: DELIVERING GENE THERAPY TO PATIENTS JULY 2018 | 3
Slide 4: Leon Buys is our mission personified
LEON BUYS is our mission personified. DELIVERING GENE THERAPY TO PATIENTS JULY 2018 | 4
Slide 5: Diagnosed with hemophilia B as a toddler
Diagnosed with HEMOPHILIA B when he was a toddler. Told he would need replacement therapy for the rest of his life. DELIVERING GENE THERAPY TO PATIENTS JULY 2018 | 5
Slide 6: Treated with uniQure investigational gene therapy
Treated with uniQure investigational gene therapy. Discontinued replacement therapy and enjoying an active life with his daughter Jersey. DELIVERING GENE THERAPY TO PATIENTS JULY 2018 | 6
Slide 7: Developing life-changing gene therapies
uniQure is developing potential life-changing gene therapies for people like Leon. DELIVERING GENE THERAPY TO PATIENTS JULY 2018 | 7
Slide 8: Three key areas, each with proof-of-concept
We are focused on three key areas, each with proof-of-concept Hemophilia B Huntington’s Cardiovascular Disease Disease AMT-061 AMT-130 AMT-126 AAV5 with Demonstrated strong, Bristol-Myers Squibb FIX-Padua transgene widespread lowering research collaboration of mHTT DELIVERING GENE THERAPY TO PATIENT
Slide 9: DELIVERING GENE THERAPY TO PATIENTS JULY 2018 | 9
DELIVERING GENE THERAPY TO PATIENTS JULY 2018 | 9
Slide 10: Several milestones across key programs
Several milestones across key programs • Initiate enrollment of AMT-061 pivotal trial Hemophilia B • Treat ∼3 patients to confirm dose of 2 x e13 gc/kg (AMT-061) • Announce clinical data (FIX activity) from initial ∼3 patients • Complete IND-enabling GLP safety study Huntington’s disease • Submit IN
Slide 11: Lexington and Amsterdam facilities
Lexington Amsterdam State-of-the-Art Manufacturing Research and Technology Center DELIVERING GENE THERAPY TO PATIENTS J U L Y 2 0 1 8 | 11
Slide 12: Large-scale AAV manufacturing capability
Large-scale AAV Manufacturing Capability • Based in Lexington, MA • 3rd generation insect cell, baculovirus • Scalable up to 2 x 2000L • Ready for commercial scale-up Benefits • Control process through commercialization • Highly scalable, cost-effective • High-volume capacity • Consistent, stable, h
Slide 13: Scalable, safe, cost effective manufacturing
Scaleable • Linear scaleability without complex transfection required for mammalian cells • No centrifugation step required Safe • No risk of replication competent viruses • There are no mammalian cell promoters used in the manufacturing • No serum used in process • Mammalian cells require serum whi
Slide 14: DELIVERING GENE THERAPY TO PATIENTS J U L Y 2 0 1 8 |
DELIVERING GENE THERAPY TO PATIENTS J U L Y 2 0 1 8 | 14
Slide 15: AAV5 clinically demonstrated tolerability and outcomes
AAV5 – Clinically demonstrated tolerability and outcomes AAV5 Vector • Data from 22 patients in 3 clinical studies1 • Demonstrated clinical outcomes in the liver and brain • Lowest prevalence of pre-existing neutralizing antibodies2 • Favorable immunogenicity profile for systemic, intravenous delive
Slide 16: AAV5: potential for broader patient access
AAV5: potential for broader patient access Boutin et al* Phylogenetic tree of AAV uniQure Number of Number of individuals individuals screened Positive (%) Assay 98 2 (2%) development Phase 1/2 AAV5 has the least conserved capsid sequence 10 0 (0%) screening (Only 50-67% homology with other serotype
Slide 17: Hemophilia B AMT-061
Hemophilia B AMT-061 DELIVERING GENE THERAPY TO PATIENTS J U L Y 2 0 1 8 | 17
Slide 18: Current market opportunity
Current market opportunity • Estimated ~10,000 patients with hemophilia B in U.S.1 and EU2 • Up to 60% of hemophiliacs have a severe or moderately-severe phenotype (< 2% of normal FIX) • Standard of care for severe hemophiliacs is a chronic, prophylactic FIX replacement therapy3 • Estimated annual c
Slide 19: Breakthrough Therapy and PRIME designations
January 2017 April 2017 Breakthrough Therapy Designation PRIME Designation U.S. Food & Drug Administration (FDA) European Medicines Agency (EMA) DELIVERING GENE THERAPY TO PATIENTS J U L Y 2 0 1 8 | 19
Slide 20: Padua FIX variant
Padua: expresses a protein with a single amino acid substitution that has been shown to have a ~6 to 7-fold increase in FIX activity compared to the wild-type FIX protein Goal of hemophilia B Gene Therapy R338L • Long-term safety, including favorable immunogenicity profile • Predictable, sustained a
Slide 21: Transduction in hepatocarcinoma cells
Transduction in Hepatocarcinoma cells In v it r o h F IX p r o t e in v s h F IX a c t iv it y 1 .5 1 .5 1x 6x h F IX p r o t e in ( u g /m l) h F IX a c t iv it y (IU /m l) 1 .0 1 .0 0 .5 0 .5 0 .0 0 .0 y y in in it it te te v v ti ti ro ro c c p p a a IX IX IX IX F F F F 1 0 0 1 6 6 6 6 0 * Equal
Slide 22: hFIX protein levels and FIX clotting activity
hFIX protein levels % FIX clotting activity h F IX p r o t e i n c F IX a c t iv it y a v e ra g e p o s t d o s e (d a y 4 - w k 2 5 ) B a s e l in e c o r r e c t e d a v e r a g e w k s 4 - 1 3 20 1000 % F IX c lo t tin g a c t iv ity (% o f n o rm a l h u m a n ) (% o f n o rm a l h u m a n ) %
Slide 23: Expected FIX activity over time
Peak(1) ∼6 to 8 Weeks FIX activity at 6 to 8 weeks after gene transfer expected to be ∼65% to 70% of peak ESTIMATED PATIENT VARIABILITY ∼30-50% ∼20-35% // (1) Based on computer simulations using AMT-061 animal data and AMT-060 Phase I/II clinical data (at one year follow-up) and animal data. DELIVER
Slide 24: Pivotal trial design
• 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: • Increa
Slide 25: Dose-confirmation study
• Patient recruitment underway at U.S. sites • Approximately three patients to receive a single dose of AMT-061 at 2 x e13 gc/kg • Approximately six to eight weeks of follow-up to observe FIX activity and confirm dose • Top line FIX data expected in 4Q ’18 • To be conducted in parallel with 6-month
Slide 26: AMT-061 timeline
2018 2019 Q1 Q2 Q3 Q4 Q1 Complete Comparability Protocol Chemistry, Manufacturing & Release Material for DC Study Controls Production of Material for Pivotal Regulatory Affairs & Submit IND Amendments Clinical Operations IRB/IBC Approvals & Site Contracting/Prep Initiate Patient Recruitment Patient
Slide 27: Padua patent family acquired
• Acquired a patent family covering the FIX-Padua or the “Padua mutant” • Factor IX with a leucine at the R338 position of the protein sequence • New U.S. and Canadian patents have issued in the family • Claims include methods of treating bleeding disorders with FIX-Padua in AAV gene therapy • Provi
Slide 28: Progress across regulatory, clinical, manufacturing and IP
Regulatory Clinical Manufacturing Intellectual Property • Submitted IND • Initiated enrollment • Successfully • Acquired patent amendments for in pivotal trial completed family — exclusive dose-confirmation comparability use of Padua-FIX in and pivotal studies • Recruiting patients protocol gene the
Slide 29: Huntington's Disease AMT-130
Huntington’s Disease AMT-130
Slide 30: Huntington's disease: a devastating disorder
Huntington’s disease: A devastating disorder • A rare, inherited neurodegenerative disease that leads to: • Loss of muscle coordination • Behavioral abnormalities • Cognitive decline • Results in complete physical and mental deterioration over time • Disease caused by expansion of CAG trinucleotide
Slide 31: Huntington's disease: a large, high-unmet medical need
Huntington’s disease: A large, high-unmet medical need • Estimated ~28,000 Huntington’s disease patients in the U.S.1 • Estimated ~35,000 Huntington’s disease patients in EU51 • Of these, 80% are in early to mid stages of disease • Typical diagnosis between 30 and 50 years old2 • No treatments avail
Slide 32: Orphan drug designations
September 2017 January 2018 Orphan Drug Designation Orphan Medicinal Product Designation U.S. Food & Drug Administration (FDA) European Medicines Agency (EMA) DELIVERING GENE THERAPY TO PATIENTS J U L Y 2 0 1 8 | 32
Slide 33: Disease progression and AMT-130 slowdown
Motor diagnosis Premanifest Manifest 100 function (% of normal) AMT-130 slowdown disease progression 1 2 3 4 5 0 presymptomatic prodromal early moderate advanced 25 45 65 Age Adapted from Ross et al., Nat. Rev. Neurol. 10, 204-2016 (2014) DELIVERING GENE THERAPY TO PATIENTS J U L Y 2 0 1 8 | 33
Slide 34: AMT-130 gene therapy for Huntington's disease
AMT-130 AMT-130 gene therapy for Huntington’s disease (HD) Putamen Caudate nucleus • Non-selective knockdown of huntingtin protein (HTT) in the brain • Utilizes proprietary miRNA that binds to and degrades HTT mRNA • One-time injection in the striatum, the primary affected structure in HD • AAV5 has
Slide 35: Therapeutic targeting of Huntington's disease pathway
Therapeutic Targeting Huntington’s Disease Pathway • mHTT primarily leads to damage in the striatum, and in later Degenerated stage disease, in parts of the cortex regions • Therapeutic targeting of the areas involved in the disease: • Striatum (caudate nucleus and putamen) Preserved • Globus pallid
Slide 36: Vector DNA distribution in NHP brain
Penetration throughout NHP brain Vector DNA distribution 8 10 V e c t o r g e n o m e c o p ie s 7 10 p er µ g D N A 6 10 5 10 1 4 LLO D 10 3 10 P u ta m e n C a u d a t e T h a la m u s C o rte x 13 1x10 g c A A V 5 - m iH T T 13 3x10 g c A A V 5 - m iH T T Samaranch L. et al, Gene Ther. 2017 Apr;2
Slide 37: Mutant huntingtin protein knockdown at 6 months
Libechov transgenic (tgHD) minipigs: Mutant huntingtin protein • Life-span: 12-20 years 200 knockdown at 6 months • Body weight: 50-140 kg h u m a n m u t a n t h u n t in g t in p r o t e in ( % ) • Brain weight: 90-100 g • Highly developed immune system 150 ( r e la t iv e t o n a iv e ) 47.0% 67.
Slide 38: Current status and next steps
Current Status Next Steps • Established pre-clinical proof of concept • Submit IND for AMT-130 in 2H 2018 • Ongoing nonclinical safety toxicology studies • Begin first-in-human clinical study • Granted Orphan Drug Designation by FDA • Granted Orphan Medicinal Drug Designation by EMA DELIVERING GENE
Slide 39: DELIVERING GENE THERAPY TO PATIENTS J U L Y 2 0 1 8 |
DELIVERING GENE THERAPY TO PATIENTS J U L Y 2 0 1 8 | 39
Slide 40: Bristol-Myers Squibb collaboration overview
Overview • Up to 10-targets focused on CV disease Landmark gene therapy • 4 of 10 targets designated thus far deal leveraging uniQure’s • +$140 million received to date technology platform • $2.3 billion in potential milestones • Up to double-digit royalties • All R&D paid by BMS • QURE is exclusive
Slide 41: Targeting S100A1: master regulator of heart function
Targeting S100A1: a master regulator of heart function CHF Market Current Status Next Steps • 5.7 million patients in US1 • Demonstrated DNA delivery and dose expression of • Data on heart function S100A1 expression in large animal model study in 2H 2018 • 50% die within 5 years1 • Validated clinica
Slide 42: Several milestones across key programs
Several milestones across key programs • Initiate enrollment of AMT-061 pivotal trial Hemophilia B • Treat ∼3 patients to confirm dose of 2 x e13 gc/kg (AMT-061) • Announce clinical data (FIX activity) from initial ∼3 patients • Complete IND-enabling GLP safety study Huntington’s disease • Submit IN
Slide 43: uniQure
uniQure