Proqr Therapeutics N.v. · NASDAQ:PRQR
Proqr Therapeutics — Corporate Update (April 2022)
36 slides from Proqr Therapeutics's corporate update, Apr 13, 2022
Slide 1: Strategy Update
STRATEGY UPDATE Nasdaq: PRQR Date: April 13, 2022
Slide 2: Agenda
ProQR Therapeutics - Strategy Update 2 Agenda Intro Sarah Kiely Vice President Investor Relations and Corporate Communications Presentation Daniel A. de Boer Founder & CEO Q&A Daniel A. de Boer Founder & CEO Smital Shah Chief Business and Financial Officer Aniz Girach, MD Chief Medical Officer Gerar
Slide 3: Forward looking statements
ProQR Therapeutics - Strategy Update Forward looking statements This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including but not limited to, statements
Slide 4: Two strategic pillars underpin our approach
Two strategic pillars underpin our approach Operating at the intersection of RNA therapy and genetic eye diseases ProQR Therapeutics - Strategy Update Axiomer® RNA editing technology 4 Very few have a treatment Genetic eye diseases A-to-I editing
Slide 5: Overview
Overview • Illuminate missed primary endpoint • No critical trial conduct issues identified • Post-hoc Illuminate analysis completed • Sepofarsen demonstrates efficacy signal consistent with earlier trials when comparing the active treatment and sham eyes to their corresponding contralateral eyes (C
Slide 6: RNA therapy for Leber congenital amaurosis: Sepofarsen
RNA therapy for Leber congenital amaurosis 10 Sepofarsen ProQR Therapeutics - Strategy Update 6
Slide 7: CEP290-mediated LCA10
ProQR Therapeutics - Strategy Update CEP290-mediated LCA10 CEP290-mediated LCA10 is an ultra orphan disease Disease biology well-understood for genetic approaches One of the most aggressive forms of inherited retinal blindness Preclinical and early clinical data demonstrates potential for sepofarsen
Slide 8: Illuminate trial operational review
Illuminate trial operational review • All operational elements of Illuminate were reviewed • Included review of site-to-site variations, patient inclusion criteria, CMC aspects, clinical data analysis, among others • Removal of 1 patient in the post-hoc analyses (patient was at light perception at b
Slide 9: Primary analysis
ProQR Therapeutics - Strategy Update Primary analysis Primary analysis of treated group vs parallel sham group showed no effect 9 -0,16 -0,11 -0,25 -0,20 -0,15 -0,10 -0,05 0,00 0,05 0,10 Pooled sepofarsen n=23 Sham n=12 Change in BCVA (logMAR) BCVA - CFB at Month 12 ANCOVA Direction of improvement -
Slide 10: Sepofarsen treated patients self-report an improvement in vision on 2 separate PROs
ProQR Therapeutics - Strategy Update Sepofarsen treated patients self-report an improvement in vision on 2 separate PROs Single question PGI-C • 14/23 (61%) patients on sepofarsen self reported an improvement in their vision • 3/12 (25%) of patients in sham reported an improvement in vision VFQ-25 c
Slide 11: Is sham the right control for small sample size trials?
Is sham the right control for small sample size trials? ProQR Therapeutics - Strategy Update 11 • Significant visit-to-visit variability makes sham very noisy as a control in small sample size trials • Variability observed in sham eyes moves in parallel with each other in both eyes • Using the diffe
Slide 12: Comparing to contralateral eye corrects for variability
ProQR Therapeutics - Strategy Update 12 Comparing to contralateral eye corrects for variability The “treated eye (TE) minus untreated eye (CE) analysis” BCVA – CFB at Month 12 -0,11 -0,07 -0,03 -0,25 -0,20 -0,15 -0,10 -0,05 0,00 0,05 0,10 Sham TE Sham CE Sham TE-CE Change in BCVA (logMAR) Delta trea
Slide 13: BCVA post-hoc analysis
ProQR Therapeutics - Strategy Update BCVA at Month 12 post-hoc analysis No change in sham when TE is compared to sham CE 13 -0,16 -0,11 -0,25 -0,20 -0,15 -0,10 -0,05 0,00 0,05 0,10 Pooled sepofarsen n=23 Sham n=12 Change in BCVA (logMAR) Direction of improvement Sepofarsen vs sham BCVA - CFB at Mont
Slide 14: FST - Comparing sham and contralateral eye as control
-0,20 -0,48 -1,20 -1,00 -0,80 -0,60 -0,40 -0,20 0,00 0,20 Pooled sepofarsen n=22 Sham - n=12 Change in FST (log cd/m 2 ) -0,44 -0,70 -1,20 -1,00 -0,80 -0,60 -0,40 -0,20 0,00 0,20 Pooled sepofarsen n=23 Sham n=12 Change in FST (log cd/m 2 ) FST - Comparing sham and contralateral eye as control ProQR
Slide 15: Meta analysis - Combining Ph1/2 and Ph2/3 data
Meta analysis - Combining Ph1/2 and Ph2/3 data BCVA TE-CE shows consistent and significant benefit compared to sham TE-CE ProQR Therapeutics - Strategy Update 15 -0,40 -0,30 -0,20 -0,10 0,00 0,10 0,20 Baseline 1 3 6 9 12 Change in BCVA (logMAR) Time in Months Pooled sepofarsen n=29 Sham n=12 Sepofar
Slide 16: Sepofarsen next steps
Sepofarsen next steps • Illuminate results to be discussed with EMA and FDA in Q3 • Evaluate next steps for program after regulatory feedback • Any further investment post Q3 (standalone or with a partner) subject to clear guidance from regulators • Continuing the Illuminate and Brighten trials as r
Slide 17: Learnings for IRD pipeline
Learnings for IRD pipeline Scientific rationale for IRD platform remains sound • Evidence of benefit in post-hoc analysis of Illuminate is consistent with preclinical and early clinical data • Dose levels predicted by preclinical data appear to demonstrate clinical activity • Safety profile manageab
Slide 18: RNA therapy for retinitis pigmentosa and Usher syndrome: Ultevursen
RNA therapy for retinitis pigmentosa and Usher syndrome Ultevursen ProQR Therapeutics - Strategy Update 18
Slide 19: Ultevursen (QR-421a) for USH2A-mediated RP
Ultevursen (QR-421a) for USH2A-mediated RP Designed to treat genetic vision loss in Usher syndrome & retinitis pigmentosa ProQR Therapeutics - Strategy Update RNA therapy for Usher & nsRP Develop hearing and vision loss in childhood and are completely blind by mid adulthood USH2A exon 13 mutations a
Slide 20: Ultevursen Phase 1/2 Stellar trial results
Ultevursen Phase 1/2 Stellar trial results Concordant benefit in multiple endpoints ProQR Therapeutics - Strategy Update Ultevursen treated eye Contralateral eye BL 4 12 24 36 48 -2 0 2 4 6 8 10 12 14 BL 1 4 8 12 16 24 36 48 -10 -8 -6 -4 -2 0 2 4 6 Weeks Weeks Change in BCVA (ETDRS letters) # of loc
Slide 21: BCVA stabilization driven by advanced population
BCVA stabilization driven by advanced population Mean change from baseline in BCVA after single injection ProQR Therapeutics - Strategy Update • BCVA response is driven by advanced disease population • Stabilization of vision in treated eye after single dose • Mean 9.3 letter benefit at week 48 • Me
Slide 22: Ultevursen summary and next steps
Ultevursen summary and next steps • Ultevursen data continue to be robust; however clinical development can be optimized based on sepofarsen learnings • Single dose resulted in benefit for up to 72 weeks • Dose predicted preclinically observed to be active • Concordant response across multiple endpo
Slide 23: Company Strategy Update
Company Strategy Update ProQR Therapeutics - Strategy Update 23
Slide 24: Portfolio prioritization and restructuring initiatives
ProQR Therapeutics - Strategy Update Portfolio prioritization and restructuring initiatives Suspend further investment QR-1123 for P23H adRP QR-504a for FECD3 IRD research 24 Sepofarsen for CEP290 mediated LCA10 Workforce Reduce workforce by 30%, expected to be effective in Q2 Axiomer® Prioritize an
Slide 25: RNA base-editing platform technology Axiomer
RNA base-editing platform technology Axiomer® ProQR Therapeutics - Strategy Update 25
Slide 26: Axiomer RNA base-editing platform technology
ProQR Therapeutics - Strategy Update Axiomer® RNA base-editing platform technology Axiomer® A-to-I editing • Exploiting endogenous ADAR • Recruited by synthetic Editing Oligonucleotide (EON) • I is translated as a G, allowing to target G-to-A mutations • Specific, potent, and stable by design • >20,
Slide 27: Axiomer has the potential to target broad range of diseases
Repairing G-to-A Mutations Axiomer® has the potential to target broad range of diseases ProQR Therapeutics - Strategy Update Ophthalmology >1,100 targets • Leber Congenital Amaurosis 4 • Usher syndrome • Fuchs Endothelial Corneal Dystrophy • Retinitis Pigmentosa type 3 • Stargardt Disease • Primary
Slide 28: Axiomer - beyond mutation repair
Axiomer® - beyond mutation repair Site-specific protein engineering & Post-translational modifications ProQR Therapeutics - Strategy Update Alter phosphorylation sites Targeting of phosphorylation sites (activity switches) to regulate protein activity Potential to edit more than 400 different types
Slide 29: Targets in liver and nervous system licensed exclusively to Lilly
Up to 5 targets in liver and nervous system are licensed exclusively to Lilly ProQR will maintain all global exclusive rights to the >1,100 genetic eye disease targets of Axiomer® • ProQR will develop selected targets in ophthalmology • The initial batch of genetic eye disease targets that ProQR wil
Slide 30: Axiomer therapeutic applications
Axiomer® therapeutic applications IRD, liver, CNS and beyond ProQR Therapeutics - Strategy Update 30
Slide 31: Substantial A-to-I editing in multiple models
Substantial A-to-I editing in multiple models Potential to go after retina, liver and CNS targets ProQR Therapeutics - Strategy Update Editing of ACTB in WT human retinal organoids Editing of CEP290 in LCA human retinal organoids Retina • Over 40% editing in patient derived retinal organoids and ove
Slide 32: Axiomer patent protection beyond 2040
Axiomer® patent protection beyond 2040 Docket Priority Feature Status 0004 17 Dec 2014 Targeted RNA Editing using endogenous ADARs Granted EP US JP RU ZA 0013 22 Jun 2016 ‘Single stranded’ EONs Granted US on 27APR21 0014 01 Sep 2016 Chemically modified EONs Granted EP US 0016 19 Jan 2017 EONs + prot
Slide 33: Next steps Axiomer platform
Next steps Axiomer® platform In house strategy • Expand investments in Axiomer® platform and pipeline development and target selection activities • Expect to present further non-clinical data updates throughout 2022 • Planning to announce internal development targets in H2 2022 • Develop in vivo PoC
Slide 34: Summary
Summary ProQR Therapeutics - Strategy Update 34
Slide 35: Strategic priorities and milestones
ProQR Therapeutics - Strategy Update 35 Strategic priorities and milestones Strategic priorities • Genetic eye disease Explore regulatory path for ophthalmology based on comparing active treatment and sham eyes versus their corresponding contralateral eye with EMA and FDA; subject to regulatory feed
Slide 36: It's in our RNA
\ IT’S IN ProQR) ouR RNA