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CREATING MEDICINESfor patientsin need
Date:November 2020
Nasdaq:PRQR
Forward looking statements
ProQR Therapeutics - Corporate Presentation 2
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 operations, future preclinical and clinical trial plans and related timing of trials and results, research and development, future financial position, future revenues, projected costs, prospects, therapeutic potential of our product candidates, plans and objectives of management, are forward-looking statements. The words “aim,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.
Forward-looking statements are based on management's beliefs and assumptions and on information available to management only as of the date of this presentation. Our actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, the risks, uncertainties and other factors in our filings made with the Securities and Exchange Commission, including certain sections of our annual report filed on Form 20-F. These risks and uncertainties include, among others, the cost, timing and results of
preclinical studies and clinical trials and other development activities by us and our collaborative partners whose operations and activities may be slowed or halted by the COVID-19 pandemic; the likelihood of our clinical programs being executed on timelines provided and reliance on our contract research organizations and predictability of timely enrollment of subjects and patients to advance our clinical trials and maintain their own operations; our reliance on contract manufacturers to supply materials for research and development and the risk of supply interruption from a contract manufacturer; the potential for future data to alter initial and preliminary results of early-stage clinical trials; the unpredictability of the duration and results of the regulatory review of applications or clearances that are necessary to initiate and continue to advance and progress our clinical programs; the ability to secure, maintain and realize the intended benefits of collaborations with partners; the possible impairment of, inability to obtain, and costs to obtain intellectual property rights; possible safety or efficacy concerns that could emerge as new data are generated in research and development; and general business, financial and accounting risks and litigation. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these forward-looking statements, even if new information becomes available in the future, except as required by law.
3ProQR Therapeutics - Corporate Presentation
>2,000,000 people living with Inherited retinal
disease
4ProQR Therapeutics - Corporate Presentation
>2,000,000 people living with Inherited retinal
disease
Very few have a
treatment
RNA therapies in pipeline for >100,000 IRD patients
5
QRX-461for Usher Syndrome
Sepofarsenfor LCA10
QR-411 for Usher Syndrome
QR-1123for P23H adRP
QR-421a for Usher Syndrome
Other programs for mutations causing
IRD’s
QR-1011 for Stargardt’s
Disease
QRX-136for LCA10
5,000
10,000
15,000
20,000
25,000
30,000
35,000
40,000
45,000
50,000
0
~10,000
~2,000
~1,000 ~2,000
~16,000
~7,000
~500
ProQR Therapeutics - Corporate Presentation
ProQR at a glance
ProQR Therapeutics - Corporate Presentation 6
Patient-focused RNA THERAPEUTICS platform company, developing drugs for RARE INHERITED RETINAL DISEASES
Platform for RNA therapies targeting inherited blindness
Sepofarsen (QR-110) for LCA10 with positive clinical data
• Phase 1/2 top-line results show rapid, significant and durable improvement in vision• Preliminary data from InSight extension study consistent with benefit seen in Phase
1/2 – additional data anticipated in H2 2021• Phase 2/3 Illuminate trial ongoing with enrollment expected to complete Q1 2021
QR-421a for Usher syndrome Exon 13
• Encouraging findings reported from interim analysis of first two cohorts of Phase 1/2 Stellar trial – dose expansion and dose escalation cohorts complete with next interim analysis expected H1 2021
QR-1123 for P23H adRP (in-licensed from Ionis)
• Phase 1/2 Aurora trial ongoing; Initial data expected in 2021
QR-504a for Fuchs Endothelial Corneal Dystrophy proof of mechanism study ready to start H1 2021, pending lifting of COVID-19 restrictions at study site
Deep pipeline in ophthalmology with targets for multiple additional programs
Cash runway expected to fund operations into 2023
RNA therapies for inherited retinal diseases
ProQR Therapeutics - Corporate Presentation 7
Reverse blindness with 1 - 2 routine injections per year
RNA TherapyIntravitreal administration
RNA Therapy characteristics
• Intravitreal injection under local anesthesia
• RNA molecules reach the entire retina, ability to treat peripheral retinal disease
• Robust improvements in vision observed in clinical trial
• Favorable benefit/risk profile observed in clinical trial
• Naked molecules, no vectors needed for delivery
• Medicines designed to repair a specific mutation• No changes have to be made to the DNA
Sepofarsen (QR-110) for LCA10
8
LCA10
Lose sight in first years of life
No approved therapy currently available
p.Cys998X mutation affects ~2,000 patients in the Western world
RNA therapy: sepofarsen
Goal: Restore vision/ prevent vision loss in patients with LCA10
Locally adminis-tered in the eye. Routine intra-vitreal procedure
Anticipated infrequent dosing of 2 times a year
√ Established modality in eye√ Strong preclinical proof of concept in
human retina in preclinical models√ Top-line Phase 1/2 clinical trial results
showed rapid, significant and durable activity and was well tolerated
√ Orphan drug designation & Rare pediatric disease designation
√ FDA Fast track designation and access to EMA PRIME program
• Phase 2/3 Illuminate trial ongoing with enrollment expected to complete Q1 2021
• Pediatric trial expected to start 2021
ProQR Therapeutics - Corporate Presentation
Sepofarsen clinical trials
ProQR Therapeutics - Corporate Presentation 9
LCA10
Phase 1/2 (completed)
Phase 1/2 extension(ongoing)
Phase 2/3 (ongoing)
Pediatric(planned)
Mobility(ongoing)
Phase 1/2 + extension trial design
10
Open label, extension trial, LCA10 patients with 1 or 2 copies of p.Cys998X
= DSMC review
Adult 320/160µg dose
Adult 160/80µg dose
Pediatric 160/80µg dose
Pediatric 320/160µg dose
12 months treatment in worse eyeScreeningbaseline
Analysis 3-month Data + 2nd eye
Extension trial 160/80µg dose
Phase 1/2 Study – 1st eye treatment only Extension Study
ProQR Therapeutics - Corporate Presentation
Target registration dose – key outcomesPhase 1/2: First eye treated, second eye untreated
11
Eye BCVA – LogMAR (n=6)
Red FST – log cd/m2 (n=6)
Blue FST – log cd/m2 (n=6)
Mobility course – composite score (n=6)
Treated 1st eye
-0.93 (0.43)p=0.13 vs. 2nd eye
-0.66 (0.14)p<0.05 vs. 2nd eye
-0.63 (0.31)p=0.09 vs. 2nd eye
4.0 (1.27)p=0.06 vs. 2nd eye
Untreated 2nd eye -0.22 (0.11) 0.05 (0.17) 0.12 (0.16) 2.7 (1.11)
-1.2
-1
-0.8
-0.6
-0.4
-0.2
0
0.2
Chan
ge in
BCV
A (L
ogM
AR)
BCVA
1st eye 2nd eye
ImprovedAcuity
ImpairedAcuity
-1
-0.8
-0.6
-0.4
-0.2
0
0.2
Chan
ge in
FST
(log
cd/
m2 )
FST
MoreSensitive
LessSensitive
-0.5
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
Chan
ge in
Mob
ility
(lev
els)
Mobility
1st eye 2nd eye
MoreImpairment
LessImpairment
ProQR Therapeutics - Corporate Presentation
1st eye red light 2nd eye red light
1st eye blue light 2nd eye blue light
Phase 1/2 extension study - change from baseline to 3 months post dosing
12
Subject P2 Subject P3 Subject P1Subject P11* (homozygous)
*= 6 month value of 2nd eye as 3 month visit was missed due to COVID-191st eye
-3
-2.5
-2
-1.5
-1
-0.5
0BCVA FST Red FST Blue
BCVA
(Log
MAR
) FST (Log cd/m2)
-3
-2.5
-2
-1.5
-1
-0.5
0BCVA FST Red FST Blue BCVA FST Red FST BlueBCVA FST Red FST Blue
X
ProQR Therapeutics - Corporate Presentation
Dir
ectio
n of
impr
ovem
ent
Preliminary data – July 2020
Phase 1/2 extension study - change from baseline to 3 months post dosing
13
Consistent treatment response in both eyes-3
-2.5
-2
-1.5
-1
-0.5
0BCVA FST Red FST Blue
BCVA
(Log
MAR
) FST (Log cd/m2)
*= 6 month value of 2nd eye as 3 month visit was missed due to COVID-19
X X
-3
-2.5
-2
-1.5
-1
-0.5
0BCVA FST Red FST Blue BCVA FST Red FST BlueBCVA FST Red FST Blue
Subject P2 Subject P3 Subject P1
1st eye 2nd eye
Subject P11* (homozygous)
ProQR Therapeutics - Corporate Presentation
Preliminary data – July 2020
Dir
ectio
n of
impr
ovem
ent
Phase 1/2 extension study - change from baseline to 3 months post dosing
14
Consistent treatment response in both eyes-3
-2.5
-2
-1.5
-1
-0.5
0BCVA FST Red FST Blue
BCVA
(Log
MAR
) FST (Log cd/m2)
*= 6 month value of 2nd eye as 3 month visit was missed due to COVID-19
X X
-3
-2.5
-2
-1.5
-1
-0.5
0BCVA FST Red FST Blue BCVA FST Red FST BlueBCVA FST Red FST Blue
Subject P2 Subject P3 Subject P1
1st eye 2nd eye
Subject P11* (homozygous)
ProQR Therapeutics - Corporate Presentation
Preliminary data – July 2020
Dir
ectio
n of
impr
ovem
ent
Subject P3: Illustration of BCVA improvement
• Baseline: 2.4 LogMAR (20/1000)
• 3 months: 1.12 LogMAR (20/125)
• Improvement: 1.28 LogMAR*
*From being worse than legally blind to navigating freely, watching tv and being able to see family faces.
ProQR Therapeutics - Corporate Presentation 15
Baseline (2.4 LogMAR) M3 (1.12 LogMAR) M9 (0.58 LogMAR)
Using “Thru My Eyes” App
Ph 1/2 informed Ph 2/3 enrichment strategyAll subjects with baseline of Hand Motion or better responded on BCVA
ProQR Therapeutics - Corporate Presentation 16
3 2 1 04LogMARscale
HM CF 20/200 20/20LP
Ph 1/2 informed Ph 2/3 enrichment strategyAll subjects with baseline of Hand Motion or better responded on BCVA
* = Homozygous subject
ProQR Therapeutics - Corporate Presentation 17
-2.66
-1
-0.8
-0.6
-0.4
-0.2
0
Chan
ge fr
om b
asel
ine
(Log
MAR
)
-2.5
P14.0
P24.0
Subject
Baseline
P24.0
P14.0
P104.0
P94.0
P64.0
3 2 1 04LogMARscale
HM CF 20/200 20/20LP
1st eye at 12 months 2nd eye at 3 months (P3 at 6 months)
Direction of im
provement
Ph 1/2 informed Ph 2/3 enrichment strategyAll subjects with baseline of Hand Motion or better responded on BCVA
* = Homozygous subject
ProQR Therapeutics - Corporate Presentation 18
Phase 3 population
-2.66
-1.7
-1
-0.8
-0.6
-0.4
-0.2
0
Chan
ge fr
om b
asel
ine
(Log
MAR
)
-2.5
P14.0
P24.0
P32.4
P52.1
P42.45
P71.05
Subject
Baseline
P11*0.63
P81.9
P24.0
P31.66
P14.0
P11*0.48
P104.0
P94.0
P64.0
3 2 1 04LogMARscale
HM CF 20/200 20/20LP
1st eye at 12 months 2nd eye at 3 months (P3 at 6 months)
Direction of im
provement
Mean change from baseline In Ph 3 population:
-0.53 LogMAR
FST responses: Subject with LP at baselineLP patients are responders on light sensitivity measure
ProQR Therapeutics - Corporate Presentation 19
-3.5
-3
-2.5
-2
-1.5
-1
-0.5
0
FST Red FST Blue FST Red FST Blue FST Red FST Blue FST Red FST Blue FST Red FST Blue
P1 P1 P6 P6 P9 P9 P10 P10 P2 P2
Change from Baseline in FST in LP Patients
1st eye at 12 months 2nd eye at 3 months
Direction of im
provement
Sepofarsen pivotal Phase 2/3 trial
ProQR Therapeutics - Corporate Presentation 20
Expected to complete enrollment Q1 2021
• Double-masked, randomized, controlled, 12-month, multiple dose study
• Could serve as the sole registration trial• Sites in North America, select EU
countries, and South America
• 30+ patients >8 years old• Multiple IVT injections in both eyes• First patient dosed in April 2019• Primary (registration) endpoint:
• Visual Acuity (ETDRS, BRVT)
• Key secondary endpoints • Mobility course• Full field stimulus testing (FST)• Ocular instability (OCI)• Optical coherence tomography (OCT)
0 month 3 month 6 month 9 month
12 month Primary Endpoint 15 month 18 month 21 month 24 month
sepofarsen: 80 µg loading dose, 40 µg maintenance dose (n=10) Safety
sepofarsen: 160 µg loading dose, 80 µg maintenance dose (n=10) Safety
Sham-procedure (n=10) Crossover
= Dose 1st eye = Dose 2nd eye
ILLUMINATE Study: rationale for success
• Clinically significant and durable BCVA improvement data at 12 months, a registrable endpoint
• Target patient population confirmed--all patients with Hand Motion or better in Ph 1/2 showed VA improvement
• Target registration dose (160/80ug) confirmed
• 6 months dosing interval confirmed
• Positive Benefit:Risk confirmed in Ph 1/2
• Consistent, supportive secondary endpoints data
• 2nd eye dosing confirms Benefit:Risk, responder profile and dose interval
ProQR Therapeutics - Corporate Presentation 21
Pivotal trial significantly de-risked—7 reasons to believe
QR-421a for Ush2a
ProQR Therapeutics - Corporate Presentation 22
Designed to treat genetic vision loss in Usher syndrome and non-syndromic RP
RNA therapy for Usher & nsRP
Develop hearing and vision loss in childhood and are completely blind by mid adulthood
USH2A exon 13 mutations affect ~16,000 patients in Western world.Approximately 15-25% has exon 13 mutations on both alleles
√ RNA is established modality in eye√ Strong preclinical proof of concept
in patient-derived retinal model√ Orphan drug designation &
Rare pediatric disease designation√ Fast track designation
Partnership
Awarded $7.5M financial support from FFB to conduct trial
For USH2A exon 13 no therapy available
Unmet need
• QR-421a is targeted to reverse vision loss or stop disease progression and eventually treat asymptomatic patients based on genetic diagnosis
• Dose escalation and expansion cohorts complete – next IA expected H1 2021
QR-421a Phase 1/2 trial in Usher & nsRP
ProQR Therapeutics - Corporate Presentation 23
~200 day half-life allows for informative single dose FIH trial design
Stellar Phase 1/2 trial• Randomized, single ascending dose, global
multicenter, longitudinal, 24-months study
• Goals include safety and efficacy
• Inclusion criteria: visual field of ≥10o
1 month24 months total
DSMC
DSMC
COHORT 150 µg
COHORT 2100 µg
0 month
1 month 3 months0 monthDSMC = Dose in one eye = DSMC review
• Visual Field (VF) and retinal sensitivity: Microperimetry, static perimetry, dark-adapted chromatic perimetry, full-field stimulus threshold test
COHORT 2B100 µg Homozygous
COHORT 3200 µg
Interim Analysis 1
24 month masked follow-up
to measure durability of effect and inform
dosing interval
Interim Analysis 2
3 months
Key endpoints include: • Visual acuity (VA): Best-Corrected VA
• Retinal structure: EZ-area on SD-OCT
• Patient Reported Outcomes
25% of treated subjects defined as responder
ProQR Therapeutics - Corporate Presentation 24
1 of 3 homozygous versus 1 of 5 heterozygous subjects demonstrated benefit in multiple outcome measures v. untreated eye
Pattern of Benefit
SubjectBaseline
visual impairment
Genetic background Dose Days OCT EZ
area DAC FST BCVA
Responder 1 Moderate Homozygous 50µg 270
Responder 2 Severe Heterozygous 100µg 120
Mild-moderate disease informative
Severe disease informative= Benefit = No change
QR-421a Interim Analysis summary
Objectives for Interim Analysis• Explore safety, tolerability and find examples
of responders to inform further development
Safety and tolerability• A total of more than 1,350 subject-treatment
days at time of Interim Analysis
• No serious ocular or non-ocular Adverse
Events
• No evidence of inflammation, cystoid macular
edema, retinal thinning, or treatment-
associated cataracts
Activity• 25% (2 of 8) of QR-421a-treated patients
demonstrated a benefit on 3 condordant
endpoints
• None of the patients in the sham control
group had such a response
Summary conclusion of Interim Analysis• Encouraging responder examples suggest
early signals of target engagement and clinical
activity of QR-421a and support continuing the
trial with expansion and dose escalation to
inform path to registration
ProQR Therapeutics - Corporate Presentation 25
Reported in March 2020 after 3 or more months of treatment
QR-1123 for P23H adRP
ProQR Therapeutics - Corporate Presentation 26
Gapmer targeting autosomal dominant RP due to the P23H mutation in RHO
P23H adRP
Progressive reduction in night & peripheral vision. Blindness is frequent in mid-adulthood
No therapy available
~2,500 patients with P23H adRP in United States
RNA therapy: QR-1123
Goal: Restore vision/prevent vision loss in patients with P23H adRP
Locally adminis-tered in the eye. Routine intra-vitreal procedure
Anticipated infrequent dosing of 4 times a year or less
√ Established modality in eye√ Strong preclinical proof of concept in vivo√ In-licensed from Ionis Pharmaceuticals√ 2-year Natural History Study is completed
and will be used to accelerate clinical development
√ Received IND clearance√ Orphan drug designation
Next steps • Phase 1/2 trial ongoing, first patient dosed• Initial data on track for 2021
Aurora Phase 1/2 trial • Double-masked, randomized, sham controlled
• Goals include safety, tolerability and efficacy
• Up to 35 adult patients
• Initial data expected in 2021
QR-1123 Phase 1/2 trial in adRP patients
ProQR Therapeutics - Corporate Presentation 27
1 month
DSMC
75 µg n=1
0 month
150 µg n=1
12-month follow up
300 µg n=3
QR-1123: n=6 Sham: n=2
Single dose
Multiple dose(every 3 months)
DSMC
DSMC
Potential to add additional single and multiple dose cohorts at different dose levels
Key endpoints include: • Visual acuity
• Visual field
• OCT
• Patient Reported Outcomes
= Dose in one eye through intravitreal administration
QR-504a for FECD3
ProQR Therapeutics - Corporate Presentation 28
Fuchs Endothelial Corneal Dystrophy
Front of the eye disease leading to blindness in 50+ years of age
>250,000 patients with Repeat expansion in TCF4in Western world
√ RNA is established modality in eye√ Rapid delivery to corneal cells√ Strong preclinical proof of concept
in human primary cell models
• Proof of mechanism study expected to start H1 2021, pending lifting of COVID-19 restrictions at study site
RNA therapy: QR-504a
For FECD3 repeat expansion in TCF4No therapy available
Strong preclinical PoC in human primary cell models. Development candidate selected
Strong PoC
Multiple upcoming program milestonesSepofarsen (QR-110) for LCA10• Positive top-line results Phase 1/2 announced
Q4 2019• Phase 2/3 Illuminate trial expected to complete
enrollment Q1 2021• Primary endpoint is mean change from
baseline in BCVA at 12 months• Next interim analysis for InSight extension study,
including data on second eye treatment H2 2021• Pediatric trial expected to start in 2021
QR-421a for Usher syndrome 2A exon 13• Stellar Phase 1/2 trial dose expansion and dose
escalation cohorts completed• Next interim analysis H1 2021
QR-1123 for P23H adRP• Aurora Phase 1/2 trial underway Q4 2019• Initial data on track for 2021
QR-504a for Fuchs endothelial corneal dystrophy• Proof of mechanism study expected to start
H1 2021, pending lifting of COVID-19 restrictions at study site
Ophthalmology Pipeline• Rapidly advancing several discovery
and nonclinical stage ophthalmology programs to mature into development and clinical trials
ProQR Therapeutics - Corporate Presentation 29
ProQR since 2012
• Based in Leiden, the Netherlands with an office in Cambridge, MA
• 160 employees (35 nationalities)
• 2014 IPO NASDAQ: PRQR
• FD Shares outstanding: ~64 million
• Cash position (Q3 2020) €88.8 million
• $7.5M grant funding awarded by Foundation Fighting Blindness
• €4.8M Innovation Credit from Dutch government for sepofarsen program
• Strategic convertible debt financing agreements with Pontifax and Kreos (Q3 2020)
• Projected cash runway into 2023
• Robust IP estate consisting of 30 fully owned patent families and 9 licenses
ProQR Therapeutics - Corporate Presentation 30
Facts and figures
Strong team with proven track record
ProQR Therapeutics - Corporate Presentation 31
Management team Supervisory board
Daniel de BoerChief Executive Officer
Honorary former board member
Gerard PlatenburgChief Innovation Officer
Smital ShahChief Business & Financial Officer
Naveed ShamsChief Scientific Officer
Antoine Papiernik
Henri Termeer
James Shannon
Alison Lawton
Dinko ValerioChairman
Tiffany BurtVP Commercial
Leadership team
Aniz GirachChief Medical Officer
Bart Filius
Theresa Heggie
Scientific Advisory Board
32ProQR Therapeutics - Corporate Presentation
Phillip D. ZamorePhD
Thaddeus DryjaMD
Art LevinPhD
James ShannonMD (Chair)
Donald S. FongMD
Mike CheethamPhD
J. Timothy StoutMD, PhD, MBA
Martin MaierPhD
IT’S INOUR RNA
Inherited blindness pipeline beyond LCA10 and Usher syndrome
ProQR Therapeutics - Corporate Presentation 34
DISCOVERY PRECLINICAL DEVELOPMENT PROOF OF CONCEPT TRIALS
LATE STAGE/REGISTRATIONAL
TRIALS
OphthalmologySepofarsen (QR-110) for LCA10 p.Cys998X
QR-421a for Usher syndrome 2A exon 13
QR-1123 for P23H adRP - discovered by Ionis
QR-504a for FECD3
QR-411 for Usher syndrome 2A PE40
QR-1011 for Stargardt’s disease c.5461-10T>C
QRX-461 for Usher syndrome undisclosed mutation
QRX-136 for LCA undisclosed mutation
Sepofarsen reference slides
ProQR Therapeutics - Corporate Presentation 35
Sepofarsen for LCA10
ProQR Therapeutics - Corporate Presentation 36
Splice correction for p.Cys998X CEP290 mRNA
In wild-type cellsCEP290 maintains cilium
structure and enables normal protein transport
In p.Cys998X-LCA10 cellsprotein transport
is hampered and the outer segment degenerates
Exclusion of the cryptic exon from the mutated
mRNA leads to wild-type CEP290 protein
Exon 27Exon 26 XExon 27Exon 26
Exon 26 Exon 27
Outersegment
Innersegment
Nucleus
Connectingcilium
pre-mRNA
DNA
mRNA
sepofarsen
mRNA
pre-mRNA Exon 26 Exon 27X
Exon 27Exon 26
sepofarsen
Exon 26 Exon 27X
Phase 1/2 – trial design
ProQR Therapeutics - Corporate Presentation 37
Open label, multiple dose, dose escalation study
• Enrolled 11 LCA10 patients (age range 8-44) with 1 or 2 copies of the p.Cys998X mutation
• Intravitreal injections in one eye
• Participating sites: major sites in EU (UGhent) and US (UPenn, UIowa)
Objectives:
• Base case: Safety/tolerability & Mechanistic proof-of-concept (full-field stimulation)
• Up-side: Clinical proof-of-concept (best corrected visual acuity), Identify target dose, Mobility course feasibility in LCA10
• Explore: Additional secondary outcome measures
Top-line data, reported in October 2019:
• Validated efficacy of sepofarsen with statistically significant increase in vision in target registration dose group,
• Established efficacious dose regimen with acceptable
benefit/risk and provides strong guidance for population enrichment for the pivotal trial.
• Eligible patients will be rolled over into an extension trial where they will be offered to also get their second eye treated
= DSMC review
Adult 320/160µg dose
Adult 160/80µg dose
Pediatric 160/80µg dose
Pediatric 320/160µg dose
12 months treatment in worse eyeScreeningbaseline
Roll-over to extension+ 2nd eye treatment
DSMC
DSMC
DSMC
DSMC
DSMC
Phase 1/2 – Baseline Demographics
ProQR Therapeutics - Corporate Presentation 38
160µg/80µg cohort, n=6; 2 LP only, 3 BRVT, 1 ETDRS320µg/160µg cohort, n=5; 3 LP only, 1 BRVT, 1 ETDRS
Gender 2nd CEP290 Allele Age/Group Baseline BCVA[LogMAR] Treated Eye Dose [µg]
M c.2503_2504delAC 19 / Adult LP / LP Right 160/80
M c.4723A>T 41 / Adult LP / LP Right 160/80
M c.5668G>T 44 / Adult 2.4 / 2.3 Left 160/80
F c.4438‐3delC 16 / Pediatric 2.5 / 2.5 Right 160/80
M c.6277delG 8 / Pediatric 1.9 / 2.1 Left 160/80
F c.2991+1655A>G 14 / Pediatric 0.6 / 0.6 Left 160/80
F c.3167_3168insA 21 / Adult LP / LP Right 320/160
F c.4723A>T 27 / Adult 1.1 / 0.7 Right 320/160
F c.4393C>T 24 / Adult LP / LP Right 320/160
M c.6277delG 10 / Pediatric 1.9 / 1.4 Right 320/160
F c.547_550delTACC 15 / Pediatric LP / LP Right 320/160
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 motion | 2.0 LogMAR = Finger counting | 1.0 LogMAR = 20/200 | 0.0 LogMAR 20/20
Top-line safety summary
ProQR Therapeutics - Corporate Presentation 39
Phase 1/2 (001) study: Positive benefit/risk in 160µg/80µg cohort with 50% incidence of lens opacity; Subclinical retinal findings in 320µg/160µg cohort
Cataracts Cystoid Macular Edema Retinal thinning
SAE/AE 6 SAE (surgery)/2 AE 0 SAE / 2 AE 0 SAE / 2 AE
Dose-dependent incidence Yes Yes Yes
Timing (160μg/80μg cohort) 8-12 months No cases No cases
Timing (320μg/160μg cohort) 3-9 months 3-4 months 3-10 months
Treatment-responsive Yes Yes Stabilized
Example of mobility course
ProQR Therapeutics - Corporate Presentation 40
Before and after treatment
Link:https://youtu.be/YqVN3A7I1_4
Phase 1/2 top-line efficacy resultsPrimary and key secondary outcome measures pooled analysis n=11
Objective Assessment Direction of improvement
Responder threshold
Mean change from baseline at month 12 (SEM)
Treated eye Untreated eye
Mechanistic proof-of-concept
Full field stimulus (FST) red – log cd/m2 (n=10)
↓= improved -0.5-0.92 (0.18)
p<0.01 vs. CE-0.16 (0.16)
Full field stimulus (FST) blue – log cd/m2 (n=10)
↓= improved -0.5-0.79 (0.23)
p<0.02 vs. CE0.02 (0.11)
Clinical proof-of-concept
Best corrected visual acuity (BCVA) – LogMAR (n=11)
↓= improved -0.3-0.55 (0.26)
p<0.05 vs. CE-0.11 (0.07)
Secondaryoutcome*
Mobility course – composite score (n=10)
↑ = improved 22.5 (0.99)
p=0.1 vs. CE1.75 (0.75)
*Additional exploratory outcome measures, including OCI, PLR, OCT, PROs being analyzed
ProQR Therapeutics - Corporate Presentation 41
BCVA stratified by dose cohortPrimary outcome measure – mean change in BCVABenefit maintained from month 3 to month 12
Mean ΔBCVALogMAR
Treated eye (SEM) Untreated eye (SEM)
month 3 month 12 month 3 month 12
Pooled analysis (n=11)
-0.50(0.24)
-0.55(0.26)
0.0(0.04)
-0.11(0.07)
160μg/80μg (n=6) -0.81(0.41)
-0.93(0.43)
0.01(0.08)
-0.22(0.11)
320μg/160μg (n=5) -0.13(0.1)
-0.11(0.07)
0.0 (0.0)
0.01(0.04)
Phase2/3 trialtargetdose
ProQR Therapeutics - Corporate Presentation 42
160µg/80µg cohortConsistent improvement with favorable benefit/risk
Responder (%)
Treated eye Untreated eye
US responder threshold
EU responder threshold
US responder threshold
EU responder threshold
160μg/80μg (n=6) 67% 83% 33% 33%
* = homozygous subject
Responder Rate
Safety Findings
-2.66
-1.7
-1
-0.9
-0.8
-0.7
-0.6
-0.5
-0.4
-0.3
-0.2
-0.1
0*
US
4.0 4.02.4 2.1 2.45 0.63
BCVA baseline (LogMAR)
Chan
ge fr
om b
asel
ine
(Log
MAR
)
EU
160μg/80μg (n=6)
Tolerability No issues
Systemic safety No issues
Lens opacity 3 findings
Cataract surgery outcome 2 surgeries. Complete recovery of pre-cataract benefit 2/2 subjects
Retinal findings No issues
Safety Findings
ProQR Therapeutics - Corporate Presentation 43
-1
-0.9
-0.8
-0.7
-0.6
-0.5
-0.4
-0.3
-0.2
-0.1
0
320µg/160µg cohortLess improvement with dose-limiting safety findings
BCVA baseline (LogMAR)
Chan
ge fr
om b
asel
ine
(Log
MAR
)
4.01.05 4.0
USEU
4.01.9
Responder (%)
Treated eye Untreated eye
US responder threshold
EU responder threshold
US responder threshold
EU responder threshold
320μg/160μg (n=5) 20% 20% 0% 0%
320µg/160µg (n=5)
Tolerability No issues
Systemic safety No issues
Lens opacity 5 findings
Cataract surgery outcome 4 surgeries. Complete recovery ofpre-cataract benefit 4/4 subjects
Retinal findings 4 findings in 3 individuals
Responder Rate
Safety Findings
CME treated topically with improvement. Retinal thinning stabilized 2-3 months
ProQR Therapeutics - Corporate Presentation 44
Phase 1/2 showed rapid and sustained benefitTreated Subjects (n=11) across 2 cohorts
45
Eye BCVA – LogMAR (n=11)
Red FST – log cd/m2 (n=10)
Blue FST – log cd/m2 (n=10)
Mobility course – composite score (n=10)
Treated (TE)
-0.55 (0.26) p<0.05 vs. CE
-0.91 (0.18)p<0.01 vs. CE
-0.79 (0.23)p<0.02 vs. CE
2.5 (0.99) p=0.1 vs. CE
Untreated (CE) -0.12 (0.07) -0.16 (0.16) 0.02 (0.11) 1.75 (0.75)
-0.8
-0.7
-0.6
-0.5
-0.4
-0.3
-0.2
-0.1
0
0.1
0.2
Chan
ge in
BCV
A (L
ogM
AR)
BCVA
1st eye 2nd eye
ImprovedAcuity
ImpairedAcuity
-1.2
-1
-0.8
-0.6
-0.4
-0.2
0
0.2
Chan
ge in
FST
(log
cd/
m2 )
FST
MoreSensitive
LessSensitive
-0.5
0
0.5
1
1.5
2
2.5
3
3.5
Chan
ge in
Mob
ility
(lev
els)
Mobility
MoreImpairment
LessImpairment
* Visual acuity and FST peaks associated with cataract occurrence. These subjects regained their pre-cataract visual acuity after surgery.
*
ProQR Therapeutics - Corporate Presentation
1st eye red light 2nd eye red light
1st eye blue light 2nd eye blue light
-3.5-3
-2.5-2
-1.5-1
-0.50
0.5
Subject P2
46
Baseline characteristics
• 41yrs, Male, Heterozygous
• Light Perception, both eyes
Treatment response
• First eye• Significant and sustained benefit
• Lost benefit after not being redosed in first eye for 15 months, as expected
• Scheduled to be redosed in first eye after COVID-19
• Second eye • Responded the same way as first eye
• Maximum treatment response -2.74 LogMAR
BCVAChange from baseline
FST redChange from baseline
FST blueChange from baseline
160 μg 80 μg 80 μg
-2.66
-2.5
IVT injection1st eye2nd eye
-1.5-1
-0.50
0.51
1.52
-2-1.5
-1-0.5
00.5
11.5
Onset of lens opacity
Lens replacement
BCVA
(Log
MAR
)
Dir
ectio
n of
impr
ovem
ent
Dir
ectio
n of
impr
ovem
ent
FST
(log
cd/m
2 )FS
T (lo
g cd
/m2 )
Dir
ectio
n of
impr
ovem
ent
ProQR Therapeutics - Corporate Presentation
80 μg 80 μg 80 μg
Subject P3
47
Baseline characteristics
• 44yrs, Male, Heterozygous
• 1st eye: 2.4 LogMAR(HM); 2nd eye: 1.66 LogMAR(CF)
Treatment response
• First eye• Significant and sustained benefit
• Developed a cataract in first eye at month 20 leading to reduction in BCVA
• Lens replacement completed, follow-up measurement pending COVID-19 measures to lift
• Second eye • Responded the same way as first eye
• Maximum treatment response -1.82 LogMAR
160 μg
IVT injection1st eye2nd eye
Onset of lens opacity
Lens replacement
-2
-1.5
-1
-0.5
0
0.5
-1.5
-1
-0.5
0
0.5
-2.5
-2
-1.5
-1
-0.5
0
0.5BCVAChange from baseline
FST redChange from baseline
FST blueChange from baseline
BCVA
(Log
MAR
)
Dir
ectio
n of
impr
ovem
ent
Dir
ectio
n of
impr
ovem
ent
FST
(log
cd/m
2 )FS
T (lo
g cd
/m2 )
Dir
ectio
n of
impr
ovem
ent
ProQR Therapeutics - Corporate Presentation
-1.28
-0.8
Subject P11
48
IVT injection1st eye2nd eye
-1
-0.8
-0.6
-0.4
-0.2
0
0.2
-1
-0.8
-0.6
-0.4
-0.2
0
0.2
-0.35-0.3
-0.25-0.2
-0.15-0.1
-0.050
0.05
-0.25
-0.06BCVAChange from baseline
FST redChange from baseline
FST blueChange from baseline
BCVA
(Log
MAR
)
Dir
ectio
n of
impr
ovem
ent
Dir
ectio
n of
impr
ovem
ent
FST
(log
cd/m
2 )FS
T (lo
g cd
/m2 )
Dir
ectio
n of
impr
ovem
ent
160 μg
Baseline characteristics
• 14yrs, Female, Homozygous
• 1st eye: 0.63 LogMAR(20/80); 2nd eye: 0.48 LogMAR(20/50)
Treatment response
• First eye• Benefit sustained for 15+ months, likely due to
homozygous genotype• Subject will likely get redosed in first eye
• Second eye • Responded the same way as first eye
ProQR Therapeutics - Corporate Presentation
-2.5
-2
-1.5
-1
-0.5
0
0.5
Subject P1
49
Baseline characteristics
• 19yrs, Male, Heterozygous
• Light Perception, both eyes
Treatment response
• First eye• No response on BCVA as started trial at
Light perception only• Meaningful response on FST• Subject perceives meaningful benefit
• Second eye • Responded the same way as first eye
160/80 μg 80 μg 80 μg
IVT injection1st eye2nd eye
Onset of lens opacity
-2.5
-2
-1.5
-1
-0.5
0
0.5
-3-2.5
-2-1.5
-1-0.5
00.5
80 μg 80 μg 80 μg
BCVAChange from baseline
FST redChange from baseline
FST blueChange from baseline
BCVA
(Log
MAR
)
Dir
ectio
n of
impr
ovem
ent
Dir
ectio
n of
impr
ovem
ent
FST
(log
cd/m
2 )FS
T (lo
g cd
/m2 )
Dir
ectio
n of
impr
ovem
ent
ProQR Therapeutics - Corporate Presentation
Mobility Course for LCA10
ProQR Therapeutics - Corporate Presentation 50
Optimized for Phase 2/3 study based on Phase 1/2 trial results
• Large dynamic range to accommodate lower visual acuity.
• Measures functional visual performance using a series of courses at increasing difficulty and multiple light intensities.
• > 2 levels considered meaningful.
• Validation study ongoing
Course Light level Score
Fail all courses
High contrast 400 lux 1
High contrast 250 lux 2
High contrast 125 lux 3
High contrast 50 lux 4
High contrast 10 lux 5
High contrast 4 lux 6
High contrast 1 lux 7
Low contrast 400 lux 8
Low contrast 250 lux 9
Low contrast 125 lux 10
Low contrast 50 lux 11
Low contrast 10 lux 12
Low contrast 4 lux 13
Low contrast 1 lux 14
Low-Contrast Visual Navigation Challenge at 1, 4, 10, 50, 125, 250, 400 lux (Ora, Inc. LCVNC™)
High-Contrast Visual Navigation Challenge at 1, 4, 10, 50, 125, 250, 400 lux (Ora, Inc. HCVNC™)
Grading scores:
QR-421a reference slides
ProQR Therapeutics - Corporate Presentation 51
Disease progression and endpoints
ProQR Therapeutics - Corporate Presentation 52
100° 20° 10° 0°
Visual Acuityin Snellen
Visual field in degrees vision
20/20 20/20 No Light Perception
OutcomeMeasures
Disease Progressionwith Patient Age Hearing
impairmentNight blindness(start rod degeneration)
Loss of visual field (rod degeneration)
Loss of central vision(cone degeneration)
Mild to Moderate disease Severe disease
600Complete blindness(rods and cones degenerated)
Dark-Adapted ChromaticPerimetry
Static Perimetry Micro-Perimetry
OCT – EZ area
Best Corrected Visual Acuity
Full-field Stimulation Test
Ranges are illustrative, not exact
20/32
Interim analysis - trial population baseline characteristics
Cohort Genotype PhenotypeVisual
impairment severity
Months of follow-up
50µg (n=4)
3 homozygous1 heterozygous
2 Usher2 nsRP
2 mild-moderate2 severe 6-11
100µg (n=4)
0 homozygous4 heterozygous
2 Usher2 nsRP
3 mild-moderate1 severe 3-4
Sham (n=6)
1 homozygous5 heterozygous
2 Usher4 nsRP
5 mild-moderate1 severe 3-9
ProQR Therapeutics - Corporate Presentation 53
Safety and tolerability
• No serious ocular or non-ocular Adverse Events.
• No evidence of inflammation.
• No treatment-associated cataracts.
• No cases of cystoid macular edema or retinal thinning.
ProQR Therapeutics - Corporate Presentation 54
A total of more than 1350 subject-treatment days at time of Interim Analysis
-1
0
1
2
3
4
5
6
-0.1
0
0.1
0.2
0.3
0.4
0.5
0.6
0 4 8 12 16 20 24 28 32 36-3
-2
-1
0
1
2
3
0 4 8 12 16 20 24 28 32 36-10
-5
0
5
10
15
20
0 4 8 12 16 20 24 28 32 36
Responder 1 Concordant benefit in FST, EZ area and DAC relative to untreated eye (change from baseline)
ProQR Therapeutics - Corporate Presentation 55
Waning response at later time points informs dosing interval
Direction ofImprovement
Direction ofImprovement
Direction ofImprovement
White FST, CFB (log cd/m2 left and dB right)
DAC Cyan HoV total V, CFB (dB.steradian)
EZ area, CFB (%)
Weeks Weeks Weeks
Baseline demographics• Age/Gender: 30 yo/Female• Genetic background: Homozygous• Visual impairment: Moderate
• Visual acuity (BCVA): • Left eye – 74 letters (Snellen 20/32)• Right eye (treated) – 70 letters (Snellen 20/40)
• Received a single 50µg dose
Untreated EyeTreated Eye50µg dose x 1
Responder 2Concordant improvement in FST, BCVA and DAC relative to untreated eye (change from baseline)
100µg dose x 1
ProQR Therapeutics - Corporate Presentation 56
-14
-12
-10
-8
-6
-4
-2
0
2
-1.4
-1.2
-1
-0.8
-0.6
-0.4
-0.2
0
0.2
0 4 8 12-3-2-1012345678
0 4 8 12 16 20-10
-5
0
5
10
15
0 4 8 12 16
Direction ofImprovement
Direction ofImprovement
BCVA, CFB (ETDRS letters)
Direction ofImprovement
Untreated EyeTreated Eye
White FST, CFB (log cd/m2 left and dB right)
DAC Cyan HoV total V, CFB (dB.steradian)
Baseline demographics• Age/Gender: 60 yo/Male• Genetic background: Heterozygous• Visual impairment: Severe
• Visual acuity (BCVA): • Left eye (treated) – 33 letters (Snellen 20/250)• Right eye – 35 letters (Snellen 20/200)
• Received a single 100µg dose
Weeks Weeks Weeks
Progress against trial goals√ Establish early safety and tolerability
• Thus far, generally well tolerated with no serious adverse events
√ Characterize early examples of functional target engagement and if present, duration of benefit to inform dosing interval• 2 of 8 QR-421a-treated subjects demonstrated treatment benefit• 0 of 6 sham-treated subjects met the responder definition
√ Assess utility of various outcome measures in moderate versus advanced disease
√ Inform further dose-ranging and the subject enrichment strategy for next steps in development• Enrichment for homozygous exon 13 mutation subjects in the 100µg dose cohort• Dose escalation to a 200µg dose cohort
Characterize the contributions of drug dose and gene dose
Follow treatment-responsive subjects to characterize the duration of response and estimate the dosing interval
57ProQR Therapeutics - Corporate Presentation
∆Exon13 Usherin protein is functional
ProQR Therapeutics - Corporate Presentation 58
Time (ms)
Wild-type range
Ampl
itude
Treated exon 13 mutant zebrafish
Exon 13 mutant zebrafish without treatment
Erwin van Wijk, Radboudumc, Nijmegen, the Netherlands
ERG with light stimulus in zebrafishUsherin protein (in red) in zebrafish retina
Treated with oligo
With usherinprotein
Without usherin protein
Visual fields:
ProQR Therapeutics - Corporate Presentation 59
Quantifying visual field defects
Usher syndrome Earlier stage disease
Later stage disease
Potentially viable photoreceptors as shown by OCT. Indicates potential area of visual functional restoration by QR-421a
Dark-adaptedchromatic (DAC)perimetry (Medmont)
Microperimetry (MAIA)
Automated perimetry (Octopus)
Visual field measurement
ProQR Therapeutics - Corporate Presentation 60
Sens
itivi
ty (d
B)
Isopter plot(Definition isopter: a line of equalretinal sensitivity in the visual field)
Positive outcome: Evidence of visual field expansion at few points of the isopter
Profile plot
Eccentricity (degrees of visual field)
Visual field measurement
ProQR Therapeutics - Corporate Presentation 61
Increased visual field
Sens
itivi
ty (d
B)
Profile plot
Isopter plot
Sens
itivi
ty (d
B)
Eccentricity (degrees of visual field)
Visual field measurement
ProQR Therapeutics - Corporate Presentation 62
Sens
itivi
ty (d
B)
Eccentricity (degrees of visual field)
Isopter plot
Profile plotIncreased visual field
Sens
itivi
ty (d
B)
Full Field Stimulus Test (FST)
• Test of most sensitive part of the retina
• White light for total retina
• Blue light for rods (mostly peripheral)
• Red light for cones (mostly central macula)
ProQR Therapeutics - Corporate Presentation 63
All study subjects
GoalDirectional improvement in treatment group
Visual Acuity
• Snellen VA chart used in Clinical Practice
Snellen Visual Acuity ETDRS/LogMAR Visual Acuity
• ETDRS Chart used as Gold Standard for assessing VA in Clinical Trials
• Alternative VA scales used for VA with low vision patients
Only applicable in severe patients
Goals (in severe patients only)
• In responder analysis an improvement of -0.2 LogMAR (2 lines, or 10-letters) is considered meaningful by EMA
• In responder analysis an improvement of -0.3 LogMAR (3 lines, or 15-letters) is considered meaningful by FDA
• Noise of assay is likely 0.1 LogMAR (1 line, or 5-letters)
ProQR Therapeutics - Corporate Presentation 64
Visual Field (VF)
• Dark Adapted Chromatic Perimetry (Medmont)
• Measure of visual field in peripheral vision
• Patients are dark adapted prior to measurement
• Measures visual field at different wavelengths (colors)
• Static visual field (Octopus)
• Measure of visual field in peripheral vision
• Gold standard in measuring VF
• Measures visual field with white light only
ProQR Therapeutics - Corporate Presentation 65
For moderate patients
Medmont device for DAC perimetry
Hill of Vision visualPerimetry data
GoalsImprovement above the noise of the assay and/or improvement in hill of vision analysis
Visual Field (VF)
• Micro perimetry (Maia)
• Measures visual field in the macula (0-20°visual field)
• Measures visual field with white light
ProQR Therapeutics - Corporate Presentation 66
For severe patients
GoalsImprovement above the noise of the assay and/or improvement in hill of vision analysis
OCT – EZ-line
• Imaging of the retina through high resolution OCT
• Visualizes anatomy of the central 6mm of the retina
• Degeneration of photoreceptor cells in the macula is visible at <20° visual field as depicted by EZ-line
ProQR Therapeutics - Corporate Presentation 67
Only applicable in severe patients
Severe Usher Syndrome
Normal OCT
GoalRestoration of the EZ line after treatment compared to baseline
Patient Reported Outcomes
• Patient Global Impression of Severity (PGI-S)Very brief questionnaire about the subject’s (eye) condition in the past week
• Patient Global Impression of Change (PGI-C)Very brief questionnaire about the change in the subject’s condition since he/she started in the study
• Veteran Administration Low Vision Visual Acuity Functioning Questionnaire (VFQ-20)20 questions rating how difficult a certain functional task is
ProQR Therapeutics - Corporate Presentation 68
A range of PRO’s applicable to all subjects in the trial
QR-1123 reference slides
ProQR Therapeutics - Corporate Presentation 69
QR-1123 for P23H adRP
• P23H mutation in the rhodopsin (RHO) gene causes autosomal dominant Retinitis Pigmentosa (adRP)• Rhodopsin is the light sensitive pigment in
rods in the retina• P23H mutant rhodopsin is misfolded and
toxic, causing progressive loss of rods (night and peripheral vision affected)
• Eventual loss of cones (central vision) causes patients to become legally blind by ~40-50 years of age
• P23H is the most prevalent mutation associated with adRP in the US, accounting for ~2,500 patients
• QR-1123 inhibits the formation of toxic mutant version of rhodopsin protein• QR-1123 selectively binds to the mutant
RHO mRNA• Gapmer structure causes RNase H
mediated cleavage of mutant mRNA without affecting the WT mRNA
• QR-1123 slows retinal degeneration in aggressive humanized mouse models of adRP
• Potential to reverse toxic effect and restore vision in P23H adRP patients
ProQR Therapeutics - Corporate Presentation 70
Disease Background & Clinical Phenotype
Rhodopsin Rhodopsin
QR-1123
Rhodopsin
MoA QR-1123QR-1123 blocks expression of toxic P23H mutant RHO protein
Healthy people inherit two wild type copies of the rhodopsin gene
P23H mutant rhodopsin is misfolded and toxic, causing progressive loss of rods
QR-1123 suppresses P23H mRNA with an allele specific mechanism
ProQR Therapeutics - Corporate Presentation 71
mRNA Rhodopsin
protein
Rhodopsin
Outersegment
Innersegment
Nucleus
Connectingcilium
RNA
DNA
DNA
Rhodopsin
QR-1123 is specific for P23H allele
ProQR Therapeutics - Corporate Presentation 72
Strong and specific suppression of P23H in cells QR-1123 is selective for P23H in vivo
QR-1123 preserves ONL and improves ERG in P23H rat model
ProQR Therapeutics - Corporate Presentation 73
Murray et al., 2015 IOVS 56: 6362
QR-1123 surrogate improves ERG in P23H Tg ratstrong correlation with ONL preservation
QR-1123 surrogate preserves ONLin P23H Tg rat
mRHO AS03 PBS QR-1123 surrogate Control oligo
Light level Light level
Ampl
itude
(µV)
Ampl
itude
(µV)
QR-1123 reduces retinal degeneration in humanized P23H mice
ProQR Therapeutics - Corporate Presentation 74
Optic Nerve Head (ONH)
Superior retina
Inferiorretina
Lens
Optic NerveHead
Superior Inferior
Additional Appendix
ProQR Therapeutics - Corporate Presentation 75
QR-411 for Usher syndrome
ProQR Therapeutics - Corporate Presentation 76
Designed to treat genetic eye disease in Usher syndrome
Usher
Develop hearing loss and blindness in childhood and turn completely blind by mid adulthood
PE40 mutation affects ~1,000 patients in Western world
√ RNA is established modality in eye√ Strong preclinical proof of concept
in patient retinal organoids
RNA therapy: QR-411
For Usher PE40no therapy available
Strong preclinical PoC in patient retinal model. Development candidate selected
Strong PoC
√ Orphan drug designation
QR-1011 for Stargardt’s disease
ProQR Therapeutics - Corporate Presentation 77
Stargardt’s disease
Develop blindness in childhood and turn completely blind by mid adulthood
~7,000 patients with c.5461-10T>C in ABCA4in Western world
√ RNA is established modality in eye√ Strong preclinical proof of concept
Next steps • Progression into patient retinal
organoid model
RNA therapy: QR-1011
For Stargardt’s c.5461-10T>C in ABCA4 no therapy available
Preclinical PoC and efficacy in human mini-gene models
Strong PoC
Potential broad applicability• >20,000 G-to-A mutations
described in literature• Proprietary Axiomer platform
technology can target G-to-A mutations
• Potentially broader applicability in protein modulation and stop-codon mutations
Strong IP protection• Invented in house at ProQR
laboratories• Protected with 8 patents families,
protecting Axiomer as a platform• Key collaborations with ADAR
experts in the world
Unique A-to-I RNA editing• A-to-I editing in RNA• Using endogenous ADAR• ADAR is recruited by a single
stranded Editing Oligonucleotide (EON)
• I is translated as a G, allowing to target G-to-A mutations
Axiomer® RNA editing platform
ProQR Therapeutics - Corporate Presentation 78
Editing Oligonucleotide (EON) mediated A-to-I editing
ProQR spun-off non-core activitiesWings Therapeutics
Clinical stage company focussed on development of life changing therapies for Dystrophic Epidermolysis Bullosa
• Spun out of ProQR in March 2019 with QR-313 for Exon 73 mutations and all other DEB activities
• Wings led by CEO Deborah Ramsdall, Executive Chairman Mark de Souza, PhD, and Chief Medical Officer Hal Landy, MD
• ProQR has a minority stake and will be eligible for milestone and royalty rights to commercial products
Amylon Therapeutics
Company focussed on the development of CNS products with initial focus on HCHWA-D
• ProQR incubated the activities of Amylon since 2015 and spun the company out in 2017
• The initial focus of Amylon is on its development program AT-010 for HCHWA-D, a brain disease caused by a mutation in beta-amyloid leading to stroke in mid-adulthood
• ProQR retained a majority stake in the company and will be eligible for milestone and royalty rights to commercial
ProQR Therapeutics - Corporate Presentation 79
Broad IP estate• ProQR built a broad IP estate consisting of:
• 30 fully owned patent families• 9 external licenses (Radboud University, Leiden University, INSERM, Ionis Pharmaceuticals,
University of Rochester, Vico Therapeutics)
• Patent terms (excluding potential extensions):• sepofarsen for LCA10 through 2036• QR-421a for Usher exon 13 through 2037• QR-1123 for adRetinitis Pigmentosa through 2036• QR-504a for Fuchs Endothelial Corneal Distrophy through 2036• QR-411 for Usher PE40 through 2037• QR-1011 for Stargardt disease through 2038• Axiomer® platform technology through 2041
ProQR Therapeutics - Corporate Presentation 80