Slide 1: 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 2: Agenda
Agenda Welcome and by Smital Shah introduction Smital Shah Chief Business & Financial Officer Top-line results of Phase 1/2 by David Rodman, MD trial David Rodman, MD Executive Vice President Research & Development Inherited retinal by Daniel de Boer disease pipeline Daniel A. de Boer Chief Executiv
Slide 3: Sepofarsen Phase 1/2 trial topline results
Sepofarsen Phase 1/2 trial topline results David Rodman, MD - Executive Vice Research & Development President P r o Q R T h e r a p e u t i c s O c t o b e r 1 0 , 2 0 1 9 4
Slide 4: Phase 1/2 data presentation agenda
Phase 1/2 data presentation agenda • • Trial design and top-line summary Best corrected visual acuity • Secondary outcome measures P r o Q R T h e r a p e u t i c s O c t o b e r 1 0 , 2 0 1 9 5
Slide 5: Trial design and top-line summary
Trialdesign and top-line summary Protocol, baseline demographics, subject disposition and top-line efficacy data P r o Q R T h e r a p e u t i c s O c t o b e r 1 0 , 2 0 1 9 6
Slide 6: Phase 1/2 – Trial design
Phase 1/2 – Trial design Open label, multiple dose, dose escalation study, 11 LCA10 patients with 1 or 2 copies of p.Cys998X, age 8-44, 3 sites (2 US, 1 EU) Screening baseline Roll-over to extension + 2nd eye treatment 12 months treatment in worse eye Adult 160/80µg dose Adult 320/160µg dose Pediatr
Slide 7: Phase 1/2 – Baseline Demographics
Phase 1/2 – Baseline Demographics 160µg/80µg cohort, n=6; 2 LP only, 3 BRVT, 1 ETDRS 320µg/160µg cohort, n=5; 3 LP only, 1 BRVT, 1 ETDRS BRVT = Berkley Rudimentary Vision Test (1.7-4.0 LogMAR) | ETDRS = Standard Eye Chart (0.0-1.6 LogMAR) 4.0 LogMAR = Light perception (LP) only | 3.0 LogMAR = Hand m
Slide 8: Disposition
Disposition >4000 subject treatment-days at two dose levels 6 treated 160µg/80µg 6 completed roll-over to extension 12 screened 11 enrolled 5 treated 320µg/160µg 5 completed 1 screen fail P r o Q R T h e r a p e u t i c s O c t o b e r 1 0 , 2 0 1 9 9
Slide 9: Top-line efficacy results
Top-lineefficacy results Primary and key secondary outcome measures pooled analysis n=11 Mechanistic proof-of-concept p<0.02 vs. CE = improved 2 1.75 (0.75) outcome* score (n=10) p=0.1 vs. CE *Additional exploratory outcome measures, including OCI, PLR, OCT, PROs being analyzed P r o Q R T h e r a p
Slide 10: Example of mobility course responder (video)
Example of mobility course responder (video) Before and after treatment P r o Q R T h e r a p e u t i c s O c t o b e r 1 0 , 2 0 1 9 11
Slide 11: Top-line safety summary
Top-line safety summary Positive benefit/risk in 160µg/80µg cohort with 50% incidence of lens opacity Subclinical retinal findings in 320µg/160µg cohort Edema SAE/AE P r o Q R T h e r a p e u t i c s O c t o b e r 1 0 , 2 0 1 9 12 Cataracts Retinal thinning Cystoid Macular 6 SAE (surgery)/2 AE 0 SAE
Slide 12: Phase 1/2 – Progress against Objectives
Phase 1/2 – Progress against Objectives Base-case and upside objectives achieved Regulatory agreement and global Ph2/3 adaptive pivotal trial underway manageable with surgery identified and agreed with FDA and EMA P r o Q R T h e r a p e u t i c s O c t o b e r 1 0 , 2 0 1 9 13 Objectives Outcome Sa
Slide 13: Best corrected visual acuity
Best corrected visual acuity Primary outcome measure: best corrected visual acuity (BCVA), month 12 vs. baseline P r o Q R T h e r a p e u t i c s O c t o b e r 1 0 , 2 0 1 9 14
Slide 14: BCVA stratified by dose cohort
BCVA stratified by dose cohort Primary outcome measure – mean change in BCVA Benefit maintained from month 3 to month 12 Phase 2/3 trial target dose (0.0) P r o Q R T h e r a p e u t i c s O c t o b e r 1 0 , 2 0 1 9 15 Mean BCVA LogMAR Treated eye (SEM) Contralateral eye (SEM) month 3 month 12 mont
Slide 15: 160µg/80µg cohort
160µg/80µg cohort Consistent improvement with favorable benefit/risk Responder Rate BCVA baseline (LogMAR) 0.63 * 2.4 2.1 2.45 4.0 4.0 0 -0.1 -0.2 -0.3 -0.4 -0.5 -0.6 -0.7 -0.8 -0.9 -1 EU US 160μg/80μg (n=6) 67% 83% 33% 33% Safety Findings * = homozygous subject pre-cataract benefit 2/2 subjects -1.
Slide 16: 320µg/160µg cohort
320µg/160µg cohort Less improvement with dose-limiting safety findings Responder Rate BCVA baseline (LogMAR) 4.0 1.05 4.0 4.0 1.9 0 -0.1 -0.2 -0.3 -0.4 -0.5 -0.6 -0.7 -0.8 -0.9 -1 EU US 320μg/160μg (n=5) 20% 20% 0% 0% Safety Findings pre-cataract benefit 4/4 subjects CME treated topically with impro
Slide 17: Sustained improvement in BCVA for at least one year
Sustained improvement in BCVA for at least 1 year All responses maintenance (7/7) were maintained for dose All treated (n=11) a minimum of 6 months after a 160μg/80μg Cohort (n=6) 0.2 0.2 Impaired Acuity 0 0 -0.2 -0.2 Minimal Clinically Important Difference (MCID) (-0.3 LogMAR) -0.4 -0.4 -0.6 -0.6 -
Slide 18: Secondary outcome measures
Secondary outcome measures Mobility testing and full field stimulation P r o Q R T h e r a p e u t i c s O c t o b e r 1 0 , 2 0 1 9 19
Slide 19: Key outcome measures change month 12
Key outcome measures change month Target registration dose level: 160µg/80µg (n=6) 12 Every six-month dosing interval-maintained benefit BCVA (LogMAR) FST (cd/m2) Mobility (Levels) 0.2 0.2 4.5 Impaired Acuity Less Sensitive Less Impairment 4 0 0 3.5 -0.2 3 -0.2 2.5 -0.4 -0.4 2 -0.6 1.5 -0.6 1 -0.8 0
Slide 20: Example of a 160µg/80µg responder
Example of a 160µg/80µg responder >6-month dosing interval 7/7 trial subjects with BCVA improvement sustained that benefit during BCVA (LogMAR) FST (cd/m2) Mobility (Levels) 3 0 -0.2 -0.4 -0.6 -0.8 -1 -1.2 -1.4 -1.6 -1.8 -2 -2.2 -2.4 20 Impaired Acuity Less Sensitive Less Impairment 18 2.5 16 14 2 1
Slide 21: Example of homozygous subject
Example of homozygous subject 13-letter improvement in BCVA with robust improvement in mobility and FST BCVA (LogMAR) FST (cd/m2) Mobility (Levels) 0.7 0 -0.2 -0.4 -0.6 -0.8 -1 -1.2 -1.4 -1.6 -1.8 -2 -2.2 -2.4 20 Impaired Acuity Less Sensitive Less Impairment 18 0.65 16 0.6 14 0.55 12 0.5 10 8 0.45
Slide 22: Top-line efficacy data
Top-lineefficacy data Target registration dose level: 160µg/80µg (n=6) P<0.01 vs. baseline P<0.01 vs. baseline P<0.01 vs. baseline P<0.01 vs. baseline Significance assessed by mixed effects repeated measures model P r o Q R T h e r a p e u t i c s O c t o b e r 1 0 , 2 0 1 9 23 Group mean Contralate
Slide 23: Pivotal phase 2/3 trial
Pivotal phase 2/3 trial Design agreed Adaptive repowering on with FDA and EMA 12-month primary endpoint 0 month 3 month 6 month 9 month 15 month 18 month 21 month 24 month sepofarsen: 160µg loading dose, 80µg maintenance dose (n=10) Safety sepofarsen: 80µg loading dose, 40µg maintenance dose (n=10)
Slide 24: Inherited retinal disease pipeline
Inherited retinal diseasepipeline Daniel A. de Boer - Chief Executive Officer P r o Q R T h e r a p e u t i c s O c t o b e r 1 0 , 2 0 1 9 25
Slide 25: ProQR's VISION 2023
ProQR’s VISION2023 2 3 7 LATE STAGE EARLY STAGE PROGRAMS COMMERCIAL PRODUCTS PROGRAMS P r o Q R T h e r a p e u t i c s O c t o b e r 1 0 , 2 0 1 9 26 A FULLY INTEGRATED INHERITED RETINAL DISEASE COMPANY BY 2023
Slide 26: Inherited retinal disease pipeline
Inherited retinal disease pipeline REGISTRATIONAL Ophthalmology P r o Q R T h e r a p e u t i c s O c t o b e r 1 0 , 2 0 1 9 27 Sepofarsen (QR-110) for LCA10 p.Cys998X QR-421a for Usher syndrome 2A exon 13 QR-1123 for P23H adRP - discovered by Ionis QR-504 for FECD3 QR-411 for Usher syndrome 2A PE4
Slide 27: ProQR's VISION 2023: the 3 pillars
ProQR’s VISION2023 majority of IRD patients P r o Q R T h e r a p e u t i c s O c t o b e r 1 0 , 2 0 1 9 28 Commercial •Establish IRD specialized commercial infrastructure in North America and Europe •Focused on ~approx. 30 specialist centers that treat •Leverage commercial infrastructure for multi
Slide 28: Summary
Summary • Sepofarsen for LCA10 • Phase 1/2 Illuminate Phase 2/3 top line data confirms all assumptions for the pivotal trial on track to deliver data in H1 2021 Phase 2/3 • • QR-421a for Usher syndrome • On track to deliver 12 patient interim data in Q1 2020 • QR-1123 for adRP • Recently opened IND
Slide 29: Summary
Summary Sepofarsen for LCA10 * Phase 1/2 top line data confirms all assumptions for the Phase 2/3 Illuminate pivotal trial * Phase 2/3 on track to deliver data in H1 2021 QR-421a for Usher syndrome * Ontrack to deliver 12 patient interim data in Q1 2020 QR-1123 for adRP * Recently opened IND and exp
Slide 30: It's in our RNA
IT’S IN OURRNA
Slide 31: It's in our RNA
e\ IT’S IN OUR RNA