Proqr Therapeutics N.v. · NASDAQ:PRQR
Proqr Therapeutics — Technical Presentation (March 2021)
41 slides from Proqr Therapeutics's technical presentation, Mar 24, 2021
Slide 1: QR-421A STELLAR Trial results
Exhibit 99.1 QR-421A STELLAR Trial results March 24, 2021
Slide 2: Forward looking statements
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 regarding our strategy, future operat
Slide 3: Agenda
Agenda 1. Introduction Daniel de Boer Next steps Daniel de Boer 2. Results of Stellar Phase 1/2 Aniz Girach, MD Q&A Daniel de Boer, Aniz Girach and Smital Shah Daniel de Boer Founder and Chief Executive Officer Aniz Girach, MD Chief Medical Officer Smital Shah Chief Business & Financial Officer
Slide 4: >2,000,000 people living with inherited retinal disease
>2,000,000 people living with inherited retinal disease
Slide 5: The impact of USH2A mediated vision loss
The impact of USH2A mediated vision loss This video is not available in the pdf. Please register to watch the full presentation.
Slide 6: Results of Stellar Phase 1/2 Trial
Results of Stellar Phase 1/2 Trial By Aniz Girach, MD, Chief Medical Officer
Slide 7: QR-421a for Usher syndrome and non-syndromic retinitis pigmentosa (nsRP)
QR-421a for Usher syndrome and non-syndromic retinitis pigmentosa (nsRP) Potential first-in-class RNA therapy QR-421a targets Exon 13 mutations in Ush2a ( >16,000 patients) QR-421a aims to prevent patients from going blind $7.5M co-funding from Foundation Fighting Blindness
Slide 8: Usher syndrome / nsRP are slow progressing
Usher syndrome / non-syndromic retinitis pigmentosa (nsRP) are slow progressing QR-421a targets early-moderate and advanced disease Early-moderate disease Losing visual field from the outside-inward Advanced disease Losing visual acuity (VA) Progression rate varies from patient to patient; best cont
Slide 9: Patient baseline disease stage informs endpoints
Patient baseline disease stage informs endpoints VA of less than 70 letters (20/40) at baseline is advanced disease Early-moderate disease Visual Field As measured by Static Perimetry Advanced disease Visual Acuity As measured by BCVA (Best Corrected Visual Acuity) 0 (20/20) 70 letters 1 (20/200) 2
Slide 10: QR-421a Phase 1/2 trial in Usher & nsRP
QR-421a Phase 1/2 trial in Usher & nsRP Enrollment completed; 2nd and final Interim Analysis conducted Final Interim Analysis Interim Analysis 1 nth 1 month COHORT 2 100 µg (n=4) 3 months COHORT 2B 100 µg Homozygous (n=3) COHORT 3 200 µg Homozygous (n=3) COHORT 1 50 µg (n=4) DS MC 0 month 1 month3 m
Slide 11: Enrolled population and treated patients
Treated: n=14 Enrolled Population: n=20 Advanced: n=6 n=6 n=5 n=5 n=4 Sham: n=6 n=6 Early-moderate disease: baseline VA ≥ 70 letters (20/40)
Slide 12: Summary of trial results
Summary of trial results Trial met its key objectives Well tolerated with no serious adverse events Clinical proof of concept established Best Corrected Visual Acuity (BCVA) in advanced patients Static Perimetry in early-moderate patients Concordant improvements in multiple other endpoints Identifie
Slide 13: QR-421a was well tolerated
QR-421a was well tolerated QR-421a was well tolerated in >3,700 subject follow up days No SAEs, no inflammation Cataracts occur in >30% patients in natural history of disease 1 patient had worsening of pre-existing cataracts in both the treated and untreated eye with cataract extractions in both eye
Slide 14: Advanced population efficacy results
Advanced population efficacy results Population with progressed visual acuity loss
Slide 15: BCVA stabilization in treated eye
BCVA stabilization in treated eye Mean 6 letter benefit at week 48 Mean change from baseline in BCVA All QR-421a treated patients (n=14) 6 letter benefit Single dose Stabilization of vision observed in treated eye vs decline in untreated eye in all patients 6 letter benefit at week 48, after single
Slide 16: BCVA stabilization driven by advanced population
BCVA stabilization driven by advanced population Mean 9.3 letter benefit at week 48 BCVA response is driven by advanced disease population Stabilization of vision in treated eye after single dose Deterioration of untreated eye in line with expected natural history of disease Mean 9.3 letter benefit
Slide 17: Benefit in BCVA in advanced population
Benefit in BCVA in advanced population Mean BCVA benefit between treated and untreated eyes Advanced population (n=6) Single dose Difference between treated and untreated eyes demonstrate BCVA benefit in advanced patients Response is consistent with disease state 9.3 letter benefit at week 48 in the
Slide 18: Stabilization of retinal structure in treated eyes
Stabilization of retinal structure in treated eyes Measured by OCT based Ellipsoid Zone (EZ) in the central macular area Ellipsoid zone area: % mean change from baseline All QR-421a treated subjects Single dose Stabilization in the treated eyes out to 48 weeks, after single dose Deterioration in unt
Slide 19: Stabilization of microperimetry in treated eyes
Stabilization of microperimetry in treated eyes Measuring retinal sensitivity in central visual field 0.5 Mean change from baseline in microperimetry seeing zones All QR-421a treated subjects Single dose Stabilization in the treated eyes out to week 24, after single dose Durability of response in li
Slide 20: BCVA selected as primary endpoint for advanced population
BCVA selected as primary endpoint for advanced population Patient population identified 100% of the advanced patients were responders No difference between homozygous and heterozygous genotype No difference between Usher and nsRP Dose for next trial identified No difference between different dose le
Slide 21: Early-moderate population efficacy results
Early-moderate population efficacy results Population with visual field loss, but minimal visual acuity loss
Slide 22: Visual field: Benefit on retinal sensitivity
Visual field: Benefit on retinal sensitivity Improvement measured by static perimetry after single dose Mean total retinal sensitivity improvement using static perimetry All QR-421a-treated patients (n=14) Single dose Analysis: total retinal sensitivity improvement difference between treated and unt
Slide 23: Improvement in treated eyes on static perimetry
Improvement in treated eyes on static perimetry Measuring retinal sensitivity in peripheral visual field Mean number of retinal loci with ≥7dB improvement in static perimetry All QR-421a treated patients Single dose Benefit observed in treated eyes vs untreated eyes Benefit sustained for 9+ months a
Slide 24: Static perimetry improvement driven by early-moderate population
Static perimetry improvement driven by early-moderate population Mean number of retinal loci with ≥7dB improvement in static perimetry Early-moderate population (n=8) Single dose Benefit observed in treated eyes vs untreated eyes after single dose Magnitude greater in early-moderate population Stati
Slide 25: Static perimetry selected as primary endpoint for early-moderate population
Static perimetry selected as primary endpoint for early-moderate population Benefit in mean total retinal sensitivity improvement observed in all treated eyes 7dB analysis in all treated group crossed threshold for regulatory approval with a more pronounced benefit in early-moderate patients Effect
Slide 26: Benefit in vision in treated group, not sham group
Benefit in vision in treated group, not sham group Observed in advanced population Mean change from baseline in BCVA Advanced population (n=6) Single dose 4 Change in BCVA (ETDRS letters) 0 -2 -4 -6 -8 QR-421a Treated eyes Untreated eyes
Slide 27: Benefit in vision in treated group, not sham group
Benefit in vision in treated group, not sham group Observed in advanced population Mean change from baseline in BCVA Advanced population (n=6) Single dose 4 Change in BCVA (ETDRS letters) 0 -2 -4 -6 -8 QR-421a Treated eyes Untreated eyes Sham Treated eyes
Slide 28: Benefit in vision in treated group, not sham group
Benefit in vision in treated group, not sham group Observed in advanced population Mean change from baseline in BCVA Advanced population (n=6) Single dose Mean BCVA benefit between treated and untreated eyes Advanced population (n=6) Single dose 12.3 letter difference 48 Change in BCVA (ETDRS letter
Slide 29: Sham in line with untreated eye and natural history
Sham in line with untreated eye and natural history Ellipsoid zone area: % mean change from baseline All QR-421a treated subjects Single dose 15 10 5 EZ area (%) Mean Change from Baseline in BCVA Advanced Population Single dose Change in BCVA (ETDRS letters) 2 0 Mean Number of retinal loci with ≥7dB
Slide 30: Dosing interval identified at 6 months
Dosing interval identified at 6 months Ellipsoid zone area: % mean change from baseline All QR-421a treated subjects Single dose 15 10 5 EZ area (%) Mean Change from Baseline in BCVA Advanced Population Single dose Change in BCVA (ETDRS letters) 2 0 Mean Number of retinal loci with ≥7dB improvement
Slide 31: Summary of Phase 1/2 results
Summary of Phase 1/2 results QR-421a was well tolerated Clinical proof of concept established, consistent with baseline disease, after single dose Advanced disease: 100% of patients had a BCVA benefit, 0% in sham group Early-moderate population: Improvement on Static Perimetry Supported by key secon
Slide 32: QR-421a planned Phase 2/3 for Advanced Patients
QR-421a planned Phase 2/3 for Advanced Patients Preliminary design, to be agreed with regulators 0 month3 month6 month9 month 12 month 15 month18 month21 month24 month Month 18 Primary endpoint Potential Month 12 Interim Analysis Month 18 Primary Endpoint QR-421a: dose 1 QR-421a: dose 2 Sham-procedu
Slide 33: QR-421a planned Phase 2/3 for Early-Moderate patients
QR-421a planned Phase 2/3 for Early-Moderate patients Preliminary design, to be agreed with regulators 0 month3 month6 month9 month 12 month 15 month18 month21 month24 month Potential Month 12 Interim Analysis Month 18 Primary Endpoint QR-421a: dose 1 QR-421a: dose 2 Sham-procedure = Dose Double-mas
Slide 34: Next steps
Next steps By Daniel A. de Boer, Chief Executive Officer
Slide 35: >2,000,000 people living with inherited retinal disease
>2,000,000 people living with inherited retinal disease
Slide 36: Investigational RNA therapies in pipeline for >100,000 IRD patients
Investigational RNA therapies in pipeline for >100,000 IRD patients 50,000 45,000 40,000 ~10,000 ~500 35,000 30,000 ~7,000 25,000 20,000 ~16,000 ~2,000 ~1,000 15,000 10,000 5,000 ~2,000 0 Sepofarsen for LCA10 QR-421a for Usher Syndrome QR-1123 for P23H adRP QR-411 for Usher Syndrome QR-1011 for Star
Slide 37: Deep pipeline in ophthalmology with multiple near-term catalysts
Deep pipeline in ophthalmology With multiple near-term catalysts Pediatric study DISCOVERY PRECLINICAL PHASE 1/2 PHASE 2/3 NEXT MILESTONE Sepofarsen (QR-110) for LCA10 p.Cys998X Completed pivotal enrollment in Q1 2021, Insight data update in H2 2021 QR-421a for Usher syndrome 2A exon 13 Phase 2/3 st
Slide 38: Synergistic commercial infrastructure
Synergistic commercial infrastructure ~35 specialist sites across EU and US see >80% of the patients Specialized sites see patients with all different IRDs Allowing for cross-portfolio synergies IVT administration provides access advantage Integrated clinical development Deep network in IRD speciali
Slide 39: Full catalyst calendar
Full catalyst calendar 20212022 Q1 Q2 Q3 Q4 Q1 Q2 Sepofarsen LCA10 Complete enrollmentStart pediatric Illuminate in Q1study in 2021 InSight open label extension study data update in H2 Illuminate readout H1 2022 QR-421a USH2A Usher syndrome & RP Start Phase 2/3 Celeste and Sirius trials QR-1123 RHO
Slide 40: Q&A
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Slide 41: \ IT’S IN
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