Uniqure N.v. · NASDAQ:QURE

Uniqure — ASGCT 2018

18 slides from Uniqure's conference presentation, May 19, 2018

  1. Slide 1: Therapeutic FIX Activity After Single Treatment With AMT-060 (AAV5-FIX) In Hemophilia B

    Therapeutic Factor IX (FIX) Activity After Single Treatment With AMT-060 (AAV5-FIX) In Hemophilia B Patients With Pre-existing Anti-AAV5 Humoral Immunity Anna Majowicz, Bart Nijmeijer, Margit Lampen, Lisa Spronck, Martin de Haan, Harald Petry, Sander van Deventer, Christian Meyer, Marco Tangelder, V

  2. 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

  3. Slide 3: Pre-existing neutralizing antibodies impact AAV gene therapy efficacy

    ▪ 1:5 anti-AAV8 NAB titer totally blocks in vivo liver transduction in Non- human Primates (NHP) with AAV8-hFIX (Jiang et al., Blood 2006) ▪ 1:17 titer of pre-existing anti-AAV2 NAB is described to “modulate linear dose response” in humans to AAV2-hFIX treatment: 1:17 mean hFIX activity of 3% 1:2 me

  4. Slide 4: AAV5

    AAV5 ASGCT 2018 19 May 2018 | 4

  5. Slide 5: Patient FIX activity and pre-existing anti-AAV5 status

    Patient # FIX activity (basal) Pre-existing anti-AAV5 Total pre-existing anti-AAV5 NAB titer, GFP-based (ELISA) assay Low dose cohort (5e12 gc/kg) 1 < 1% Negative Negative 2 < 1% Negative Negative 3 < 1% Negative Positive (87) 4 1.5% Negative Positive (256) 5 < 1% Negative Negative High dose cohort

  6. Slide 6: Anti-AAV5 NAB titer in healthy donors by assay

    n= 50 healthy donors GFP-based assay LUC-based assay Total anti-AAV5 (ELISA) and anti-AAV5 NAB measured 1/50 tested positive 32/50 tested positive with a LUC-based assay show strong correlation 40 10 4 r=0.85 (p<0.0001) In h ib itio n o f tr a n s d u c tio n 10 4 **** (% re la tiv e to c o n tr o l

  7. Slide 7: FIX activity post treatment by patient and anti-AAV5 titer

    Patient # * FIX activity * Median FIX acivity post * Pre-existing Pre-existing * Total pre-existing anti-AAV5 (ELISA) (basal) treatment (min-max) anti-AAV5 NAB anti-AAV5 titer, GFP- NAB titer, based assay LUC-based assay Low dose cohort (5e12 gc/kg) 1 < 1% 6.6% (5.2-8.8) Negative <4 Negative 2 < 1%

  8. Slide 8: Anti-AAV5 antibody levels over time in patients

    Ig G Ig M Patient 5 1 .2  1 0 5 Patient 1 1 .2  1 0 5 Patient 4 1 .2  1 0 5 Patient 3 1 .2  1 0 5 110 5 110 5 110 5 110 5 T o t a l a n t i-A A V 5 a b T o t a l a n t i-A A V 5 a b T o t a l a n t i-A A V 5 a b T o t a l a n t i-A A V 5 a b 810 4 810 4 810 4 810 4 610 4 610 4 610 4 6

  9. Slide 9: Anti-AAV5 NAB titer as high as 340 did not impair efficacy

    ▪ Anti-AAV5 NAB titer as high as 340 did not impair the efficacy of AAV5-FIX (AMT-060) therapy in human. ▪ The patient with the highest anti-AAV5 NAB titer had the highest FIX activity in his dose cohort. ASGCT 2018 19 May 2018 | 9 9

  10. Slide 10: NHP study design: IV injection of AAV5-FIX dose groups

    GROUPS IV injection of AAV5-FIX [gc/kg] 1. n=3 5 e11 2. n=5 5 e12 3. n=3 2.5 e13 4.n=3 9 e13 ASGCT 2018 19 May 2018 | 10

  11. Slide 11: No inhibition of liver transduction in NHP with pre-existing anti-AAV5 NAB

    % of hFIX in the plasma No inhibition of liver transduction by AAV5 in NHP with pre-existing anti-AAV5 NAB up to titer of 1030 ASGCT 2018 19 May 2018 | 11

  12. Slide 12: Anti-AAV5 NAB titers did not impair efficacy in humans or NHP

    ▪ Anti-AAV5 NAB titer as high as 340 did not impair the efficacy of AAV5-FIX (AMT-060) therapy in human. ▪ Anti-AAV5 NAB titer as high as 1030 did not impair the efficacy of AAV5-FIX (AMT-060) liver transduction in NHP. ASGCT 2018 19 May 2018 | 12 12

  13. Slide 13: Anti-AAV NAB prevalence in humans

    uniQure ii % ‘ Anti-AAV NAB prevalence in humans ASGCT 2018 19 May 2018 | 13

  14. Slide 14: Anti-AAV5 NAB titers in healthy donor sera and eligibility

    97% n=100 53 donors (53%) <2 anti-AAV5 NAB >2 anti-AAV5 NAB 340 cut-off anti-AAV5 NAB 1030 cut-off 47%, median titer = 27 92% eligible 97% eligible 4 1 0 a n t i- A A V 5 ( 1 6 0 ) N A B t ite r a n tNAB anti-AAV5 i- A A titer V 5 ( 1in 6 0healthy ) N A B tdonor ite r sera 100 92% n = 100 100 97% n

  15. Slide 15: Prevalence of anti-AAV5, AAV8 and AAV2 NAB

    anti-AAV5 titer anti-AAV8 titer anti-AAV2 titer NAB >2: 47% NAB >2: 37% NAB >2: 49% median titer = 27 median titer = 87 median titer = 97 mean titer= 453.9 mean titer= 805.6 mean titer= 4504 ASGCT 2018 19 May 2018 | 15

  16. Slide 16: Prevalence of anti-AAV5, AAV8 and AAV2 NAB with references

    ** * anti-AAV5 titer anti-AAV8 titer anti-AAV2 titer NAB >2: 47% NAB >2: 37% NAB >2: 49% median titer = 27 median titer = 87 median titer = 97 *Jiang et al., Blood 2006 mean titer= 453.9 mean titer= 805.6 mean titer= 4504 ** Manno et al., Nature Medicine 2006 ASGCT 2018 19 May 2018 | 16

  17. Slide 17: 97% of individuals can benefit from AAV5-based gene therapy

    ▪ 97% of all individuals can benefit from AAV5-based gene therapy ▪ 37% of individuals would be excluded from AAV8-based studies; 91.9% of these can still benefit from AAV5-based gene therapy ▪ 49% of individuals would be excluded from AAV2-based studies; 93.9% of these can still benefit from AAV5-b

  18. Slide 18: Questions

    uniQure Questions ASGCT 2018 19 May 2018 | 18

uniQure — ASGCT 2018 on 6ix