Slide 1: Agenda
Agenda Welcome and introduction by Smital Shah Smital Shah Chief Financial Officer Phase 1/2 interim results and development of QR-110 by David Rodman, MD future David Rodman, MD Executive Vice President of Research & Development Next steps in Ophthalmology By Daniel de Boer Daniel A. de Boer Chief
Slide 2: Phase 1/2 interim results and development of QR-110
Phase 1/2 interim results development of QR-110 by David Rodman Executive Vice President of Research and Development and future P r o Q R – I n t e r i m R e s u l t s Q R - 1 1 0 P h a s e 1 / 2 T r i a l 4
Slide 3: QR-110 for LCA10
QR-110 for LCA10 LCA10 Lose sight in first years of life No therapy available ~2,000 patients with LCA10 in western world QR-110 Goal: Restore vision/ prevent vision loss in patients with LCA10 Locally adminis-tered in the eye. Routine intra-vitreal procedure Anticipated infrequent dosing of 4 times
Slide 4: Clinical study design – PQ-110-001
Clinical study design – PQ-110-001 Open label, multiple dose, dose escalation study, Phase 1/2 Adult Low dose Adult Mid dose Adult High dose Pediatric Low dose Pediatric Mid dose Pediatric High dose = DSMC review 1 loading dose & 3 maintenance doses over 1 year: • • 160 µg loading dose / 80 µg maint
Slide 5: Interim results summary
Interim results summary • The trial met its primary and secondary objectives Safe and well tolerated in >1500 subject treatment-days analyzed Mechanistic proof-of-concept confirmed by improvement in FST Clinical proof-of-concept confirmed by BCVA and supported by improvement in mobility course The f
Slide 6: Baseline Demographics
Baseline Demographics Pediatric and adult patients (8-44 age range), with severely impaired vision (µg) P r o Q R – I n t e r i m R e s u l t s Q R - 1 1 0 P h a s e 1 / 2 T r i a l 8 M 2nd CEP290 Allele Age / Group Baseline VA (logMAR) Treated Eye Dose c.2506_2507delGA 19 / A LP / LP RE 160/80 160/
Slide 7: Disposition and Safety Results
Disposition and Safety Results 10 subjects enrolled, no early terminations or SAEs Safety findings: • Generally well tolerated with occasional mild AEs related to injection, typical to IVT. • No SAEs. • No early discontinuations. • Independent DSMC agreed that there were no safety concerns. P r o Q
Slide 8: Top Line Efficacy Results
Top Line Efficacy Results Concordant improvement in all outcome measures = improved Nystagmus tracking (OCI) - Log10mm (n=7) -0.14 (0.08) -0.04 (0.06) P r o Q R – I n t e r i m R e s u l t s Q R - 1 1 0 P h a s e 1 / 2 T r i a l 10 Direction of improvement Responder threshold Change from baseline at
Slide 9: Best Corrected Visual Acuity (BCVA)
Best Corrected Visual Acuity (BCVA) Majority of subjects had clinically meaningful improvement Individual subject responses p=0.011 Clinically meaningful (-0.3 LogMAR) P r o Q R – I n t e r i m R e s u l t s Q R - 1 1 0 P h a s e 1 / 2 T r i a l 11 Improvement Change from baseline (LogMAR) EDTRS (Lo
Slide 10: BCVA effect was maintained for at least months
BCVA effect was maintained for at least 6 months Clinically meaningful (-0.3 LogMAR) Dose 1 Dose 2 Dose 3 P r o Q R – I n t e r i m R e s u l t s Q R - 1 1 0 P h a s e 1 / 2 T r i a l 12 Improvement
Slide 11: Mobility Course for LCA10
Mobility Course for LCA10 • Large dynamic range to accommodate lower visual acuity. Grading scores: • Measures functional visual performance using a series of courses at increasing difficulty and multiple light intensities. • > 2 levels considered meaningful. High-Contrast Visual Navigation Challeng
Slide 12: Video slide placeholder
Video slide placeholder P r o Q R – I n t e r i m R e s u l t s Q R - 1 1 0 P h a s e 1 / 2 T r i a l 14
Slide 13: Mobility Course Improved
Mobility Course Improved at month 3 and month 6 Mean change from baseline through month 6 3.0 Month 3 Mean (SEM) !:l 7 G 5 4 ."..;.. .:> ,.-... (!1 l,) ..., c: (IJ E I]) <·-l.J, ;Q::o:. Clinically Meaningful (21evels) > •J) = 2..0-================ I]) I]) c I]) V) n) CCI c 3=: (IJ 1.::> - > 3 n) 0
Slide 14: Change in BCVA tracks with change in Mobility
Change in BCVA tracks with change in Mobility Responder Non-responder P r o Q R – I n t e r i m R e s u l t s Q R - 1 1 0 P h a s e 1 / 2 T r i a l 16
Slide 15: Full Field Stimulus Test (FST)
FullField Stimulus Test (FST) Measured with blue and red light Month 3 Mean (SEM) Mean Change from Baseline through month 6 -150 -150 ('J c"J"' .E, .E, -o "D u u ·1.25 ·1 25 0' 0' ...., .._. ..., c: (IJ E 0 0 .c .c 1.00 1.00 u. 0 0.. 0 00 o.u 0 ·0./J 0 ......J..-<lJ L QJ (IJ ·0.75 ...J > 0 lo.. <l.J
Slide 16: Ocular instability (OCI)
Ocular instability (OCI) Measuring nystagmus (involuntary eye movement) Month 3 Mean (SEM) Mean change from baseline through month 6 -0.30 -0.5 -0.4 -0.25 E E E E ..., c: (IJ E 0 -03 gp -0.20 tl.O. 0 -0.2 (I) (I) c (I) lll c (IJ (I) -0.1 5 lll I1J > 0 lo.. -0.1 I1J ..0 Q. E -0.10 E 0 g 0.0 L '+--0.0
Slide 17: Example of restoration of anatomy detected by OCT
Example of restoration of anatomy detected by OCT Normal retina Restoration of EZ-line in subject Baseline EZ line in normal retina shows outer segments by EZ-line, as detected by OCT Month 1 LCA10 retina Month 2 EZ line in missing in LCA10 retina due to lack of of outer segments Month 3 P r o Q R –
Slide 18: Summary of Phase 1/2 interim analysis
Summary of Phase 1/2 interim analysis • QR-110 was safe and well tolerated. • Approximately 60% of subjects demonstrated improvement in BCVA and performance on mobility course. • Improvement was seen within two months of the first dose and has been maintained throughout ongoing dosing and monitoring
Slide 19: Preliminary design pivotal Phase 2/3 trial
Preliminary design pivotal Phase 2/3 trial 0 month 3 month 6 month 9 month 12 month Treatment group (dose level 1) Treatment group (dose level 2) Control group P r o Q R – I n t e r i m R e s u l t s Q R - 1 1 0 P h a s e 1 / 2 T r i a l 21 •Double-blind, controlled, 12-month, dose • Primary (regist
Slide 20: Next steps in Ophthalmology
Next steps in by Daniel A. de Boer Chief Executive Officer Ophthalmology P r o Q R – I n t e r i m R e s u l t s Q R - 1 1 0 P h a s e 1 / 2 T r i a l 22
Slide 21: ProQR inherited blindness platform
ProQR inherited blindness platform REGISTRATIONAL Ophthalmology Predictive optic cup model Intravitreal delivery is routine procedure Broad distribution allows to target central and peripheral diseases RNA oligos could potentially target >300 IRDs P r o Q R – I n t e r i m R e s u l t s Q R - 1 1 0
Slide 22: QR-110 interim data summary
QR-110 interim data summary • The Phase 1/2 trial met its primary and secondary objectives Safe and well tolerated in >1500 subject treatment-days analyzed Mechanistic proof-of-concept confirmed by improvement in FST Clinical proof-of-concept confirmed by visual acuity and supported by improvement i
Slide 23: Q&A
Q&A P r o Q R – I n t e r i m R e s u l t s Q R - 1 1 0 P h a s e 1 / 2 T r i a l 25
Slide 24: IT'S IN OUR RNA
IT’S IN OUR RNA P r o Q R – I n t e r i m R e s u l t s Q R - 1 1 0 P h a s e 1 / 2 T r i a l 26
Slide 25: ProQR
ProQR ProQR - Interim Results QR-110 Phase 1/2 Trial IT’S IN OUR RNA 26