CREATING MEDICINES for patients in need - Nasdaq: Date

 
CREATING MEDICINES for patients in need - Nasdaq: Date
CREATING
MEDICINES
for patients
in need
Nasdaq:   Date:
PRQR      March 2020
CREATING MEDICINES for patients in need - Nasdaq: Date
Forward looking statements
This presentation contains forward-looking statements that               disclosed in our forward-looking statements, and you should not
involve substantial risks and uncertainties. All statements, other       place undue reliance on our forward-looking statements. Actual
than statements of historical facts, contained in this                   results or events could differ materially from the plans,
presentation, including but not limited to, statements regarding         intentions and expectations disclosed in the forward-looking
our strategy, future operations, future preclinical and clinical trial   statements we make. The forward-looking statements contained
plans and related timing of trials and results, research and             in this presentation reflect our current views with respect to
development, future financial position, future revenues,                 future events, and we assume no obligation to update any
projected costs, prospects, therapeutic potential of our product         forward-looking statements except as required by applicable law.
candidates, plans and objectives of management, are forward-             These forward-looking statements are subject to a number of
looking statements. The words “aim,” “anticipate,” “believe,”            risks, uncertainties and assumptions, including those that may
“estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,”     be described in greater detail in the annual report filed on Form
“target,” “potential,” “will,” “would,” “could,” “should,” “continue,”   20-F for the year ended December 31, 2018 that we have filed
and similar expressions are intended to identify forward-looking         with the U.S. Securities and Exchange Commission (the “SEC”)
statements, although not all forward-looking statements contain          and any subsequent filings we have made with the SEC. We have
these identifying words.                                                 included important factors in the cautionary statements
                                                                         included in that annual report, particularly in the Risk Factors
Forward-looking statements represent our management’s beliefs            section, and subsequent filings with the SEC that we believe
and assumptions only as of the date of this presentation. We             could cause actual results or events to differ materially from the
may not actually achieve the plans, intentions or expectations           forward-looking statements that we make.

ProQR Therapeutics – Corporate Presentation                                                                                               2
CREATING MEDICINES for patients in need - Nasdaq: Date
ProQR at a glance
                                              Platform for RNA therapies targeting                                      Broad RNA platform
  Patient-centric RNA                         inherited blindness                                                       in other therapeutic
                                                                                                                        areas
  THERAPEUTICS                                Sepofarsen (QR-110) for LCA10 with positive
                                              clinical data                                                                 Fully owned and in
  platform company,                                                                                                     •

                                              •   Phase 1/2 top-line results show rapid, significant and durable            house developed
  developing drugs for                            improvement in vision                                                     Axiomer® RNA editing
  RARE DISEASES                               •   Pivotal Phase 2/3 Illuminate trial ongoing;                               platform with very
                                                                                                                            broad applicability
  with well understood                            data expected H1 2021

                                              QR-421a for Usher syndrome Exon 13                                        •   Majority ownership in
  causality                                                                                                                 CNS spin-out company
                                              •   First patient dosed in single dose Phase 1/2 Stellar trial;
                                                                                                                            Amylon
                                                  data expected late Q1 2020
                                                                                                                        •   Minority stake in DEB
                                              QR-1123 for P23H adRP (in-licensed from Ionis)
                                                                                                                            spin-out company
                                              •   Preclinical activities and natural history study completed by Ionis       Wings Therapeutics
                                              •   Phase 1/2 Aurora trial ongoing; Initial data expected in 2021

                                              Pursuing deep pipeline in ophthalmology with many targets that
                                              can progress into clinical development rapidly

ProQR Therapeutics – Corporate Presentation                                                                                                         3
CREATING MEDICINES for patients in need - Nasdaq: Date
RNA therapies for genetic disease
Taking away the underlying cause of disease in the RNA
                 Normal cell                               Diseased cell                         Treated cell
                   (retina)                                   (retina)                              (retina)

                                                                                                                   RNA Therapy

                                          RNA

Nucleus                                   DNA

                                                In genetic disease a mistake in a     An RNA therapy repairs the RNA,
     In healthy cells parts of the DNA,
                                                gene, called a mutation, is copied   without changing the patient’s DNA.
    called genes, are copied into RNAs
                                                  into the RNA thereby causing          The cell can now perform its
   so the cell can perform its function
                                                             disease                     function like a normal cell

ProQR Therapeutics – Corporate Presentation                                                                                4
CREATING MEDICINES for patients in need - Nasdaq: Date
RNA therapies for inherited retinal diseases
Reverse blindness with 1 - 2 routine injections per year

RNA Therapy characteristics                                      RNA Therapy
                                                                 Intravitreal administration
• Personalized medicine designed to repair a specific mutation

• No changes made to the DNA

• Robust improvements in vision observed in clinical trial

• Favorable benefit/risk profile observed in clinical trial

• Naked molecules, no vectors needed for delivery

• Intravitreal injection under local anesthesia

• RNA molecules reach the entire retina, ability to treat
  peripheral retinal disease

ProQR Therapeutics – Corporate Presentation                                                    5
CREATING MEDICINES for patients in need - Nasdaq: Date
ProQR RNA therapy development pipeline
                                                                                                            LATE STAGE/
                                                                                           PROOF OF
                                                   DISCOVERY   PRECLINICAL DEVELOPMENT                    REGISTRATIONAL
                                                                                         CONCEPT TRIALS
                                                                                                               TRIALS

Ophthalmology
 Sepofarsen (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

ProQR Therapeutics – Corporate Presentation                                                                                6
CREATING MEDICINES for patients in need - Nasdaq: Date
ProQR’s VISION2023
  A FULLY INTEGRATED INHERITED RETINAL DISEASE COMPANY BY 2023

   2         APPROVED
             PRODUCTS                         3   LATE STAGE
                                                  PROGRAMS     7   EARLY STAGE
                                                                   PROGRAMS

ProQR Therapeutics – Corporate Presentation                                      7
CREATING MEDICINES for patients in need - Nasdaq: Date
2019 Accomplishments
•   Initiated the sepofarsen pivotal trial Illuminate for LCA10,
    ProQR’s first pivotal trial

•   Advanced two new molecules into clinical trials:
    •   QR-421a for Usher syndrome 2A exon 13
    •   QR-1123 for autosomal dominant retinitis pigmentosa (adRP)

•   Received PRIME and rare pediatric disease designations
    for sepofarsen

•   Raised capital to extend runway into 2022

•   Strengthened the Board with Bart Filius, COO & CFO Galapagos and
    Theresa Heggie, head of commercial Alnylam ex-US

•   Added Aniz Girach, Chief Medical Officer and Tiffany Burt, Head of
    commercial to our leadership team

•   Expanded pipeline with addition of several new programs for IRDs

ProQR Therapeutics – Corporate Presentation                              8
CREATING MEDICINES for patients in need - Nasdaq: Date
2020: Generating significant momentum
•   Sepofarsen for LCA10
    • Phase 2/3 pivotal Illuminate trial enrolling
    • Update for inSight extension study H2 2020, including data
       from contralateral eye treatment
    • Prepare for submission of NDA and MAA after Illuminate
       readout in H1 2021
    • Gear up commercial preparations for potential launch of
       sepofarsen in 2022
•   QR-421a for Usher syndrome type 2
    • On track to report 3 month interim data from Stellar trial in
      late Q1 2020 to inform next steps in development
•   QR-1123 for adRP
    • Report when Aurora trial is fully enrolled; on track for clinical
      data read-out in 2021
•   QR-504a in Fuchs’ endothelial corneal dystrophy (FECD3)
    • Advance into clinical development in 2020
•   Axiomer® technology: Advance our unique RNA editing platform
    to support development and strategic collaborations

ProQR Therapeutics – Corporate Presentation                               9
CREATING MEDICINES for patients in need - Nasdaq: Date
Eyes on the RNA Opportunity
                                              The opportunity:
                                              >100 tangible targets
                                              remain after further filtering
                                              for disease state and
                                              population size

                                              ProQR projects its RNA
Foundation of common                          technology can address
characteristics, irrespective                 about 25% of the mutations
of the target                                 at a molecular level
•   Intravitreal administration is
    routine procedure                         >300 genes causing
•   Acceptable safety profile                 Inherited Retinal Diseases,
•   Broad distribution throughout             described with
    the entire retina                         >50 pathogenic mutations
•   Long half life allowing for               per gene, leading to
    infrequent dosing                         >15,000 targets.

ProQR Therapeutics – Corporate Presentation                                 10
Sepofarsen (QR-110) for LCA10
LCA10

          Lose sight in first                   No therapy                        p.Cys998X
          years of life                         available                         mutation affects
                                                                                  ~2,000 patients in
                                                                                  the Western world

RNA therapy: sepofarsen

          Goal: Restore                         Locally adminis-                  Anticipated
          vision/ prevent                       tered in the eye.                 infrequent dosing
          vision loss in                        Routine intra-                    of 2 times a year
          patients with                         vitreal procedure
          LCA10

  √ Established modality in eye                      √ Orphan drug designation & Rare pediatric
  √ Strong preclinical proof of concept in             disease designation
    human retina in preclinical models               √ FDA Fast track designation and access to
  √ Top-line Phase 1/2 clinical trial results          EMA PRIME program
    showed rapid, significant and durable            • Pivotal Phase 2/3 Illuminate trial initiated;
    efficacy and favorable benefit/risk                data expected H1 2021

ProQR Therapeutics – Corporate Presentation                                                            11
Phase 1/2 – trial design
Open label, multiple dose, dose escalation study
Screening                                                  Roll-over to extension
 baseline         12 months treatment in worse eye          + 2nd eye treatment         •   Enrolled 11 LCA10 patients (age range 8-44) with
                                                                                            1 or 2 copies of the p.Cys998X mutation

        DS
                                                                                        •   Intravitreal injections in one eye
        MC            Adult 160/80µg dose
                                                                                        •   Participating sites: major sites in EU (UGhent) and
                                                                                            US (UPenn, UIowa)
                      DS
                      MC       Adult 320/160µg dose
                                                                                        Objectives:
                                                                                        •   Base case: Safety/tolerability & Mechanistic
                                                                                            proof-of-concept (full-field stimulation)
                      DS
                      MC      Pediatric 160/80µg dose                                   •   Up-side: Clinical proof-of-concept (best corrected
                                                                                            visual acuity), Identify target dose, Mobility course
                              DS
                                       Pediatric 320/160µg dose                             feasibility in LCA10
                              MC
                                                                                        •   Explore: Additional secondary outcome measures
DS
MC    = DSMC review

  Top-line data, reported in October 2019:                                   benefit/risk and provides strong guidance for population
  •    Validated efficacy of sepofarsen with statistically significant       enrichment for the pivotal trial.
       increase in vision in target registration dose group,             •   Eligible patients will be rolled over into an extension trial
  •    Established efficacious dose regimen with acceptable                  where they will be offered to also get their second eye treated

ProQR Therapeutics – Corporate Presentation                                                                                                         12
Top-line efficacy results
Primary and key secondary outcome measures pooled analysis n=11

                                                                                              Mean change from
                                                    Direction of        Responder         baseline at month 12 (SEM)
 Objective                  Assessment
                                                   improvement          threshold
                                                                                         Treated (TE)    Untreated (CE)

                 Full field stimulus (FST)                                                -0.92 (0.18)
Mechanistic                                         ↓= improved             -0.5                           -0.16 (0.16)
                 red – log cd/m2 (n=10)                                                  p
Example of mobility course
Before and after treatment

                                              Link:
                                              https://youtu.be/
                                              YqVN3A7I1_4

ProQR Therapeutics – Corporate Presentation                   14
BCVA stratified by dose cohort
Primary outcome measure – mean change in BCVA
Benefit maintained from month 3 to month 12

                                         Treated eye (SEM)     Contralateral eye (SEM)
Mean ΔBCVA
LogMAR
                                   month 3         month 12    month 3      month 12

Pooled analysis                       -0.50           -0.55      0.0           -0.11
(n=11)                                 (0.24)         (0.26)     (0.04)        (0.07)
                                                                                         Phase
                                      -0.81           -0.93     0.01           -0.22     2/3 trial
160μg/80μg (n=6)                                                                         target
                                       (0.41)         (0.43)     (0.08)        (0.11)
                                                                                         dose
320μg/160μg (n=5)                     -0.13           -0.11      0.0           0.01
                                        (0.1)         (0.07)     (0.0)         (0.04)

ProQR Therapeutics – Corporate Presentation                                                    15
160µg/80µg cohort
  Consistent improvement with favorable benefit/risk
                                               BCVA baseline (LogMAR)                                            Responder Rate
                                        4.0    2.4    2.1   2.45    0.63 *   4.0                                      Treated eye           Contralateral eye
                                  0
                                -0.1                                                         Responder (%)        US            EU            US          EU
Change from baseline (LogMAR)

                                                                                                              responder     responder     responder   responder
                                -0.2                                                  EU                      threshold     threshold     threshold   threshold

                                -0.3                                                  US
                                                                                           160μg/80μg (n=6)     67%            83%          33%          33%
                                -0.4
                                -0.5
                                                                                                                 Safety Findings
                                -0.6
                                -0.7                                                                                                  160μg/80μg (n=6)

                                -0.8                                                       Tolerability                      No issues
                                -0.9                                                       Systemic safety                   No issues
                                 -1                                                        Lens opacity                      3 findings
                                                             * = homozygous subject                                          2 surgeries. Complete recovery of
                                                                                           Cataract surgery outcome
                                                                                                                             pre-cataract benefit 2/2 subjects
                                               -1.7                                        Retinal findings                  No issues
                                       -2.66

  ProQR Therapeutics – Corporate Presentation                                                                                                                   16
Key outcome measures change month 12
Target registration dose level: 160µg/80µg (n=6)
Every six-month dosing interval-maintained benefit
                                                    BCVA                                                        FST                                                                               Mobility
Impaired 0.2                                                                 Less    0.2                                                          Less    4.5
 Acuity                                                                    Sensitive                                                           Impairment
                                                                                                                                                                                      4
                                 0
                                                                                                           0
                                                                                                                                                                                    3.5
     Change in BCVA (LogMAR)

                                                                                                                                                      Change in Mobility (levels)
                               -0.2                                                                                                                                                   3

                                                                                 Change in FST (cd/m2)
                                                                                                         -0.2
                                                                                                                                                                                    2.5
                               -0.4
                                                                                                         -0.4                                                                         2
                               -0.6
                                                                                                                                                                                    1.5
                                                                                                         -0.6
                               -0.8                                                                                                                                                   1

                                                                                                                                                                                    0.5
                                                                                                         -0.8
                                -1
                                                                                                                                                                                      0

                               -1.2                                                                       -1                                                                        -0.5
Improved                                                                     More                                                                 More
 Acuity                                                                    Sensitive                                                           Impairment

                                                                               Treated eye blue light           Contralateral eye blue light
                                      Treated Eye      Contralateral Eye                                                                                                                   Treated Eye   Contralateral Eye
                                                                               Treated eye red light            Contralateral eye red light

ProQR Therapeutics – Corporate Presentation                                                                                                                                                                            17
Summary of Phase 1/2 top-line data
• The Phase 1/2 trial met all primary and upside objectives
    • Target dose identified
    • Positive benefit/risk for safety
    • Identified primary endpoint for Phase 2/3

• Final data validate Phase 2/3 assumptions
    • Strong, significant and durable response in target dose out to one year
      (primary endpoint in Phase 2/3)
    • Target population performed better than excluded population
    • Mobility performance supported BCVA and is being validated as a key secondary
      outcome measure for the registration trial
    • Six-month dosing frequency feasible

ProQR Therapeutics – Corporate Presentation                                           18
Sepofarsen Pivotal Phase 2/3 trial
Design agreed on with FDA
                                                                             12 month
                                                                         Primary Endpoint
0 month                 3 month          6 month           9 month                              15 month           18 month           21 month          24 month

           sepofarsen: 160 µg loading dose, 80 µg maintenance dose
                                                                                                                    Safety
                                    (n=10)

            sepofarsen: 80 µg loading dose, 40 µg maintenance dose
                                                                                                                    Safety
                                     (n=10)

                                  Sham-procedure (n=10)                                                            Crossover

     = Dose first eye              = Dose second eye

 •   Double-masked, randomized, controlled,            •    30+ patients >8 years old                      •   Key secondary endpoints
     12-month, multiple dose study                     •    Multiple IVT injections in both eyes               •    Mobility course
 •   Could serve as the sole registration trial        •    First patient dosed in April 2019                  •    Full field stimulus testing (FST)
 •   Sites in North America and select EU              •    Primary (registration) endpoint:                   •    Ocular instability (OCI)
     countries                                              •   Visual Acuity (ETDRS, BRVT)                    •    Optical coherence tomography (OCT)

ProQR Therapeutics – Corporate Presentation                                                                                                                19
Ophthalmology pipeline
Building on success of sepofarsen
                                                                                                                               LATE STAGE/
                                                                                                            PROOF OF
                                                        DISCOVERY              PRECLINICAL DEVELOPMENT                       REGISTRATIONAL
                                                                                                          CONCEPT TRIALS
                                                                                                                                  TRIALS

Ophthalmology
    Sepofarsen (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

•      Acceptable benefit/risk safety profile (sepofarsen)          •   Optic cup accurately predicted:
•      Durable response with infrequent dosing                          •   Clinically efficacious intravitreal dose level
•      Intravitreal administration delivers to the retina               •   Response to treatment
•      Clinically meaningful vision improvement in a majority of        •   Time to onset of response
       low vision patients
                                                                    •   To be further validated in future trials of sepofarsen and
                                                                        other IRD programs

ProQR Therapeutics – Corporate Presentation                                                                                               20
QR-421a for Usher syndrome
Designed to treat genetic vision loss in Usher and non-syndromic RP
RNA therapy for Usher

          Develop hearing and vision                USH2A exon 13 mutations affect
          loss in childhood and are                 ~16,000 patients in Western world
          completely blind by mid
          adulthood

Partnership                               Unmet need

          Awarded $7.5M                             For USH2A exon 13 no
          financial support from                    therapy available
          FFB to conduct trial

  √ RNA is established modality in eye        Stellar Phase 1/2 trial
  √ Strong preclinical proof of concept       • 3-month interim analysis on first and
    in patient retinal model                     second cohort expected late Q1
  √ Orphan drug designation & Rare               2020, including top-line safety and
    pediatric disease designation                efficacy data
  √ Fast track designation
  √ First patient dosed

ProQR Therapeutics – Corporate Presentation                                             21
“Read-through” from LCA10 to Ush2a
   •    CEP290 and Usherin are co-localized in
                                                                                      Outer segment (OS)
        the connecting cilium of photoreceptors
                                                                CEP290
   •    Sepofarsen and QR-421a have similar                                           Usherin

        concentration-response curves in retinal                                                                Connecting
                                                                                                                Cilium (CC)
        organoids
                                                                                      Inner segment (IS)
   •    QR-421a has additional preclinical
        translational PoC in animal model

                                                               Active in retinal   Active in               Active in
       Candidate            Cellular MoA         Target cell
                                                                  organoid         animals                 humans

                          Restore cilium      Photoreceptor          Yes
 sepofarsen                                                                        Unknown                   Yes
                          and OS              Cones                 ≤1µM
                          Restore cilium      Photoreceptor          Yes
 QR-421a                                                                             Yes                     TBD
                          and OS              Rods                  ≤1µM

ProQR Therapeutics – Corporate Presentation                                                                              22
The study population and endpoints
Visual field
in degrees         100°                                                            20°                      10°                           0°
vision

                                              STELLAR participants baseline:
                                              • ≥10° Visual Field

                                              Mild to Moderate disease                   Severe disease

                                              • >20° visual field (more than             •
QR-421a Phase 1/2 trial in Usher 2a patients
~200 day half-life allows for informative FIH trial design
                                                                         Interim                                  3 Month Interim Analysis
                                                                         Analysis             24 months total
            0 month        1 month                                                                                expected in late Q1 2020

                             DS                                                                                   • Data reported from 8 treated
COHORT 1                     MC
50 µG                                                                                                               subjects on low and mid
4 active                                                                                                            dose and 4 patients on sham
2 sham                                       DS                                                                     treatment
                                                                                           24 month masked
                                             MC
                                                                                                 follow-up        • Data will include all safety
                                                                                          to measure durability
                                                                                                                    and efficacy endpoints 3 or
                                                                                           of effect and inform
                                                  DS                                                                more months of treatment
                            COHORT 2              MC                                          dosing interval
                            100 µG                                                                                • Option to escalate up to a
                            4 active                                                                                cohort of 200 µg or expand
                            2 sham                               DS                                                 first 2 cohorts
                                                                 MC

  = Dose in one eye   DS     = DSMC review        0 month      1 month   3 months
                      MC

   Stellar Phase 1/2 trial                                               Key endpoints include:
   • Single dose, double-masked, randomized, controlled                  visual acuity, visual field (DAC
                                                                         perimetry (Medmont), automated
   • Goals include safety and efficacy PoC and dose interval
                                                                         perimetry (Octopus), microperimetry
   • Up to 18 adult patients with moderate to severe eye disease         (MAIA)), FST, OCT and Patient
   • Inclusion criteria: visual field of ≥10o                            Reported Outcomes

ProQR Therapeutics – Corporate Presentation                                                                                                        24
Most sensitive endpoints by subgroup
Patients with moderate disease                                  Patients with severe disease
• Full field stimulus                                           • Full field stimulus
  (blue, red and white light)                                     (blue, red and white light)
• Static Perimetry                                              • Micro perimetry by Maia device
  (white light) by Octopus device
                                                                • Visual Acuity
• Dark Adapted Chromatic Perimetry
                                                                • OCT(EZ)
  (color light) by Medmont device
                                                                • Patient Reported Outcomes
• Patient Reported Outcomes

  Detailed explanation of each endpoint can be found in the reference slides at the end of this presentation

ProQR Therapeutics – Corporate Presentation                                                                    25
Objectives in STELLAR trial
                                                                                        Other endpoints
    Primary Endpoint: Safety                              Pharmacodynamic signal        •   Visual function
     Acceptable safety profile                           E.g. FST, DAC perimetry           • Visual acuity
                                                                                            • DAC perimetry
                                                                                            • Static Perimetry
                                                                                            • Microperimetry
                                                                                        •   Structural
                                                                                            • OCT: (EZ)

                                         Go Signal                                      •   Other end points
                                                                                            • Mobility Course
                                      to next phase of trial
                                                                                            • PROs

  Positive outcome for the interim analysis would look similar to other early trials:
  Identify active dose levels based on an improvement in a pharmacodynamic
  signal and some examples of improvement in visual function

ProQR Therapeutics – Corporate Presentation                                                                      26
QR-1123 for P23H adRP
Gapmer targeting autosomal dominant RP due to the P23H mutation in RHO

P23H adRP

           Progressive reduction              No therapy                      ~2,500 patients with
           in night & peripheral              available                       P23H adRP in United
           vision. Blindness is                                               States
           frequent in mid-
           adulthood

RNA therapy: QR-1123

           Goal: Restore                      Locally adminis-                Anticipated
           vision/prevent                     tered in the eye.               infrequent dosing
           vision loss in                     Routine intra-                  of 4 times a year
           patients with                      vitreal procedure               or less
           P23H adRP

   √   Established modality in eye                      √ Received IND clearance
   √   Strong preclinical proof of concept in vivo      √ Orphan drug designation
   √   In-licensed from Ionis Pharmaceuticals
   √   2-year Natural History Study is completed        Next steps
       and will be used to accelerate clinical          • Phase 1/2 trial ongoing, first patient dosed
       development                                      • Clinical development similar to QR-421a

ProQR Therapeutics – Corporate Presentation                                                              27
QR-1123 for P23H adRP
Disease Background & Clinical Phenotype
• P23H mutation in the rhodopsin (RHO) gene           • QR-1123 inhibits the formation of toxic
  causes autosomal dominant Retinitis                   mutant version of rhodopsin protein
  Pigmentosa (adRP)                                     • QR-1123 selectively binds to the mutant
  • Rhodopsin is the light sensitive pigment in           RHO mRNA
     rods in the retina                                 • Gapmer structure causes RNase H
  • P23H mutant rhodopsin is misfolded and                mediated cleavage of mutant mRNA
     toxic, causing progressive loss of rods (night       without affecting the WT mRNA
     and peripheral vision affected)                    • QR-1123 slows retinal degeneration in
  • Eventual loss of cones (central vision)               aggressive humanized mouse models
     causes patients to become legally blind by           of adRP
     ~40-50 years of age                                • Potential to reverse toxic effect and restore
                                                          vision in P23H adRP patients
• P23H is the most prevalent mutation
  associated with adRP in the US, accounting
  for ~2,500 patients

ProQR Therapeutics – Corporate Presentation                                                           28
MoA QR-1123
QR-1123 blocks expression of toxic P23H mutant RHO protein

           Outer
           segment

           Connecting
           cilium

           Inner                                     RNA
           segment

                                                     DNA
           Nucleus
                                                     DNA

protein

                                                                                                                     QR-1123

mRNA                    Rhodopsin    Rhodopsin                   Rhodopsin          Rhodopsin            Rhodopsin          Rhodopsin

              Healthy people inherit two wild type         P23H mutant rhodopsin is misfolded and     QR-1123 suppresses P23H mRNA
                 copies of the rhodopsin gene               toxic, causing progressive loss of rods   with an allele specific mechanism

ProQR Therapeutics – Corporate Presentation                                                                                               29
QR-1123 Phase 1/2 trial in adRP patients
                          0 month    1 month                     12-month follow up

             75 µg                     DS
             n=1                       MC

Single       150 µg                                       DS
dose         n=1                                          MC

             300 µg                                                       DS
                                                                          MC
             n=3

                      Multiple dose               QR-1123: n=6
                      (every 3 months)            Sham: n=2

  = Dose in one eye through intravitreal administration                                   Potential to add additional single and multiple dose cohorts at different dose levels

  Aurora Phase 1/2 trial                                                       Key endpoints include:
  • Double-masked, randomized, sham controlled                                 • Visual acuity
  • Goals include safety, tolerability and efficacy                            • Visual field
  • Up to 35 adult patients                                                    • OCT
  • Initial data expected in 2021                                              • Patient Reported Outcomes

ProQR Therapeutics – Corporate Presentation                                                                                                                                       30
QR-504a for FECD3
Fuchs Endothelial Corneal Dystrophy

          Front of the eye disease                 >250,000 patients with Repeat
          leading to blindness in 50+              expansion in TCF4
          years of age                             in Western world

RNA therapy: QR-504a                      Strong PoC

          For FECD3 repeat                         Strong preclinical PoC in
          expansion in TCF4                        human primary cell
          No therapy available                     models. Development
                                                   candidate selected

  √ RNA is established modality in eye        Next steps
  √ Rapid delivery to corneal cells           • Progression into development
  √ Strong preclinical proof of concept
    in human primary cell models

ProQR Therapeutics – Corporate Presentation                                        31
Inherited blindness pipeline beyond
LCA10 and Usher syndrome
                                                                                                                       LATE STAGE/
                                                                                                      PROOF OF
                                                      DISCOVERY           PRECLINICAL DEVELOPMENT                    REGISTRATIONAL
                                                                                                    CONCEPT TRIALS
                                                                                                                          TRIALS

Ophthalmology
    Sepofarsen (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 Phase 1/2 trial completed                       •   QR-1123 Phase 1/2 trial ongoing, first data expected
•      First patient dosed in Phase 2/3 pivotal Illuminate            2021
       trial; Data expected H1 2021                               •   Rapidly advancing several undisclosed discovery
•      QR-421a Stellar Phase 1/2 trial is expected to readout         stage ophthalmology programs into development
       Interim Analysis in late Q1 2020                               and clinical trials

ProQR Therapeutics – Corporate Presentation                                                                                           32
Axiomer®                             RNA editing platform
Editing Oligonucleotide (EON) mediated A-to-I editing

  Unique A-to-I RNA editing                   Strong IP protection                   Potential broad applicability
  • A-to-I editing in RNA                     • Invented in house at ProQR           • >20,000 G-to-A mutations
  • Using endogenous ADAR                       laboratories                           described in literature
  • ADAR is recruited by a single             • Protected with 8 patents families,   • Proprietary Axiomer platform
    stranded Editing Oligonucleotide            protecting Axiomer as a platform       technology can target G-to-A
    (EON)                                     • Key collaborations with ADAR           mutations
  • I is translated as a G, allowing to         experts in the world                 • Potentially broader applicability
    target G-to-A mutations                                                            in protein modulation and stop-
                                                                                       codon mutations

ProQR Therapeutics – Corporate Presentation                                                                                33
Strong team with proven track record
Management team                                  Supervisory board
                                                       Dinko Valerio
            Daniel de Boer                             Chairman
            Chief Executive Officer

                                                       James Shannon
            Smital Shah
            Chief Business & Financial Officer

                                                       Alison Lawton
            David Rodman
            Executive Vice President of
            Research & Development
                                                       Antoine Papiernik
            Gerard Platenburg
            Chief Innovation Officer
                                                       Bart Filius

Leadership team                                        Theresa Heggie

            Aniz Girach
            Chief Medical Officer
                                                 Honorary former board member
            Tiffany Burt                               Henri Termeer
            VP Commercial

ProQR Therapeutics – Corporate Presentation                                     34
World-class Scientific Advisory Committee

            Art Levin                                       Annemieke Aartsma Rus
            PhD                                             PhD

            Phillip D. Zamore                               Peter A. Beal
            PhD                                             PhD

            Cy Stein                                        Yi-Tao Yu
            MD                                              PhD
                                NUCLEIC ACID THERAPEUTICS

            Thaddeus Dryja                                  Peter Adamson
            MD                                              PhD

ProQR Therapeutics – Corporate Presentation                                         35
Broad IP estate
• ProQR built a broad IP estate consisting of:
  • 27 fully owned patent families
  • 7 external licenses (MGH, INSERM, Radboud University, Ionis Pharmaceuticals, Rochester
    and Leiden University)

• Patent terms (excluding possible extension):
  • Eluforsen for F508del through 2033
  • 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 2039

ProQR Therapeutics – Corporate Presentation                                                  36
Several upcoming milestones
Sepofarsen (QR-110) for LCA10                      QR-1123 for P23H adRP
√ Positive top-line results Phase 1/2              √ Aurora Phase 1/2 trial underway Q4 2019
    announced Q419                                 • Initial data expected 2021
√ Phase 2/3 Illuminate trial initiated
    • Enrollment ongoing                           QR-504a for Fuchs’ Endothelial Corneal
• Update on INSIGHT extension study                Dystrophy
    expected in H2 2020, including data on         • Advance into clinical development in 2020
    contralateral eye treatment
                                                   Ophthalmology Pipeline
QR-421a for Usher syndrome 2A exon 13              • Rapidly advancing several discovery
• Stellar Phase 1/2 trial to report interim          and nonclinical stage ophthalmology
    data in late Q1 2020 to inform next steps in     programs to mature into development
    development                                      and clinical trials

ProQR Therapeutics – Corporate Presentation                                                      37
ProQR since 2012
Facts and figures

• Based in Leiden, the Netherlands
• 160 employees (35 nationalities)
• 2014 IPO NASDAQ: PRQR
• FD Shares outstanding: ~57 million (post October 2019 financing)
• Cash position (Q4 2019) €112.0 million; no debt
    • Includes net proceeds from October 2019 of €48.6 million
    • $7.5M grant funding awarded by Foundation Fighting Blindness in February 2018
    • €4.7M Innovation Credit from Dutch government for sepofarsen program
• Projected cash runway into 2022

ProQR Therapeutics – Corporate Presentation                                           38
IT’S IN
OUR RNA
Sepofarsen reference slides

ProQR Therapeutics – Corporate Presentation   40
Sepofarsen for LCA10
Splice correction for p.Cys998X CEP290 mRNA

Outer
segment

Connecting
cilium                                                                                                             sepofarsen
Inner                                     mRNA
segment

                                          pre-mRNA

Nucleus
                                          DNA

    mRNA          Exon 26   Exon 27                   Exon 26   X     Exon 27         Exon 26       Exon 27

                                                                                  sepofarsen

pre-mRNA        Exon 26       Exon 27                 Exon 26   X     Exon 27    Exon 26        X        Exon 27

                 In wild-type cells                   In p.Cys998X-LCA10 cells    Exclusion of the cryptic
             CEP290 maintains cilium                      protein transport       exon from the mutated
              structure and enables                     is hampered and the            mRNA leads to
             normal protein transport                outer segment degenerates   wild-type CEP290 protein

ProQR Therapeutics – Corporate Presentation                                                                           41
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
                                                                          Baseline BCVA
      Gender                2nd CEP290 Allele         Age/Group                                    Treated Eye            Dose [µg]
                                                                            [LogMAR]
          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

ProQR Therapeutics – Corporate Presentation                                                                                            42
Disposition
>4000 subject treatment-days at two dose levels

                                               6 treated
                                                            6 completed
                                              160µg/80µg
                                                                          roll-over to
  12 screened                   11 enrolled
                                                                           extension
                                               5 treated
                                                            5 completed
                                              320µg/160µg

  1 screen fail

ProQR Therapeutics – Corporate Presentation                                          43
Top-line safety summary
Positive benefit/risk in 160µg/80µg cohort with 50% incidence of lens opacity
Subclinical retinal findings in 320µg/160µg cohort

                                                                     Cystoid Macular
                                                  Cataracts                            Retinal thinning
                                                                         Edema

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

ProQR Therapeutics – Corporate Presentation                                                               44
320µg/160µg cohort
  Less improvement with dose-limiting safety findings
                                             BCVA baseline (LogMAR)                                         Responder Rate
                                       1.9    1.05     4.0     4.0    4.0                                      Treated eye              Contralateral eye
                                  0
                                -0.1                                                Responder (%)            US            EU            US            EU
Change from baseline (LogMAR)

                                                                                                         responder     responder     responder     responder
                                -0.2                                        EU                           threshold     threshold     threshold     threshold

                                -0.3                                        US
                                                                                 320μg/160μg (n=5)          20%           20%            0%            0%
                                -0.4
                                -0.5
                                                                                                             Safety Findings
                                -0.6
                                -0.7                                                                                             320µg/160µg (n=5)

                                -0.8                                             Tolerability                           No issues
                                -0.9                                             Systemic safety                        No issues
                                 -1                                              Lens opacity                           5 findings
                                                                                                                        4 surgeries. Complete recovery of
                                                                                 Cataract surgery outcome
                                                                                                                        pre-cataract benefit 4/4 subjects
                                                                                 Retinal findings                       4 findings in 3 individuals

                                                                                 CME treated topically with improvement. Retinal thinning stabilized 2-3 months

  ProQR Therapeutics – Corporate Presentation                                                                                                               45
Sustained improvement in BCVA for at least 1 year
All responses (7/7) were maintained for a minimum of 6 months
after a maintenance dose
                                                          All treated (n=11)          160μg/80μg Cohort (n=6)
Impaired                                           0.2                         0.2
 Acuity
           Change from baseline in BCVA (logMAR)

                                                     0                           0

                                                   -0.2                        -0.2                                            Minimal Clinically
                                                                                                                               Important Difference
                                                   -0.4                        -0.4                                            (MCID) (-0.3 LogMAR)

                                                   -0.6                        -0.6

                                                   -0.8                        -0.8

                                                    -1                          -1

Improved
                                                   -1.2                        -1.2
 Acuity

                                                                                             Treated eye   Contralateral
                                                                                                                TE       eye
                                                                                                                         CE

ProQR Therapeutics – Corporate Presentation                                                                                                  46
Example of a 160µg/80µg responder
7/7 trial subjects with BCVA improvement sustained that benefit
during ≥6-month dosing interval
                        BCVA (LogMAR)                                         FST (cd/m2)                                     Mobility (Levels)
Impaired    3                                           Less         0                                         Less    20
 Acuity                                               Sensitive                                             Impairment
                                                                   -0.2                                                  18
           2.5                                                     -0.4
                                                                                                                         16
                                                                   -0.6
                                                                                                                         14
            2                                                      -0.8
                                                                    -1                                                   12

           1.5                                                     -1.2                                                  10
                                                                   -1.4                                                  8
            1                                                      -1.6
                                                                                                                         6
                                                                   -1.8
                                                                                                                         4
           0.5                                                      -2
                                                                   -2.2                                                  2

            0                                                      -2.4                                                  0
Improved                                                 More                                                  More
 Acuity                                                Sensitive                                            Impairment
                 Dose    Dose              Dose
                                                                            TE blue light    TE red light                                   TE
                                6m interval*

*7/7 trial subjects with BCVA improvement sustained that benefit during ≥6-month dosing interval

ProQR Therapeutics – Corporate Presentation                                                                                                       47
Example of homozygous subject
13-letter improvement in BCVA with robust improvement in
mobility and FST
                         BCVA (LogMAR)                            FST (cd/m2)                                     Mobility (Levels)
Impaired    0.7                                 Less        0                                      Less    20
 Acuity                                       Sensitive                                         Impairment
                                                          -0.2                                               18
           0.65
                                                          -0.4
                                                                                                             16
            0.6                                           -0.6
                                                                                                             14
                                                          -0.8
           0.55
                                                           -1                                                12

            0.5                                           -1.2                                               10
                                                          -1.4                                               8
           0.45
                                                          -1.6
                                                                                                             6
            0.4                                           -1.8
                                                                                                             4
                                                           -2
           0.35
                                                          -2.2                                               2

            0.3                                           -2.4                                               0
Improved                                        More                                               More
 Acuity                                       Sensitive                                         Impairment
                  Dose
                                                                 TE blue light   TE red light
                            12m interval

ProQR Therapeutics – Corporate Presentation                                                                                           48
Top-line efficacy data
Target registration dose level: 160µg/80µg (n=6)

Group mean                                           Treated eye          Contralateral eye

BCVA (LogMAR)                                               -0.93                -0.22
                                                    P
Mobility Course for LCA10
• Large dynamic range to accommodate lower visual acuity.                                                             Grading scores:

                                                                                                                   Course      Light level   Score
• Measures functional visual performance using a series of                                                         Fail all courses           0

  courses at increasing difficulty and multiple light intensities.                                                 BRE        100% LED        1
                                                                                                                   BRE        10% LED         2
                                                                                                                   HCRE       400 lux         3

• > 2 levels considered meaningful.                                                                                HCRE       50 lux          4
                                                                                                                   HCRE       1 lux           5
                                                                                                                   HCVNC      400 lux         6
                                                                                                                   HCVNC      250 lux         7
                                                                                                                   HCVNC      125 lux         8
                                                                                                                   HCVNC      50 lux          9
                                                                                                                   HCVNC      10 lux          10
                                                                                                                   HCVNC      4 lux           11
                                                                                                                   HCVNC      1 lux           12
                                                                                                                   LCVNC      400 lux         13
                                                                                                                   LCVNC      250 lux         14
                                                                                                                   LCVNC      125 lux         15
                                                                                                                   LCVNC      50 lux          16
Backlit Room Exit at 10%     High-Contrast Room Exit   High-Contrast Visual          Low-Contrast Visual
                                                                                                                   LCVNC      10 lux          17
and 100% backlighting        at 1, 50, 400 lux         Navigation Challenge at       Navigation Challenge at
intensity (Ora, Inc. BRE™)   (Ora, Inc. HCRE™)         1, 4, 10, 50, 125, 250, 400   1, 4, 10, 50, 125, 250, 400   LCVNC      4 lux           18

                                                       lux (Ora, Inc. HCVNC™)        lux (Ora, Inc. LCVNC™)        LCVNC      1 lux           19

ProQR Therapeutics – Corporate Presentation                                                                                                          50
QR-421a reference slides

ProQR Therapeutics – Corporate Presentation   51
∆Exon13 Usherin protein is functional
                                                                                ERG with light stimulus in zebrafish
        Usherin protein (in red) in zebrafish retina

     With usherin         Without usherin     Treated
        protein                                                                                             Wild-type range
                              protein         with oligo

                                                           Amplitude
                                                                                                    Time (ms)

                                                                            Exon 13 mutant zebrafish without treatment
                                                                            Treated exon 13 mutant zebrafish

                                                                       Erwin van Wijk, Radboudumc, Nijmegen, the Netherlands

ProQR Therapeutics – Corporate Presentation                                                                                    52
Visual fields:
Quantifying visual field defects

                                                         Usher syndrome   Earlier stage disease
                      Microperimetry
                      (MAIA)                                              Later stage disease

                                                                          Potentially viable
                                                                          photoreceptors
                                                                          as shown by OCT.
                                                                          Indicates potential
                                                                          area of visual
                                                                          functional
                        Automated                                         restoration by
                        perimetry                                         QR-421a
                        (Octopus)

                                       Dark-adapted
                                       chromatic (DAC)
                                       perimetry
                                       (Medmont)

ProQR Therapeutics – Corporate Presentation                                                       53
Visual field measurement
  Sensitivity (dB)

                                                              Profile plot
                                                                                                        Positive outcome:
                                                                                                        Evidence of visual field
                                                                                                        expansion at few points of
                                                                                                        the isopter
                     Eccentricity (degrees of visual field)

                                                                      Isopter plot
                                                                      (Definition isopter: a line of equal
                                                                      retinal sensitivity in the visual field)

ProQR Therapeutics – Corporate Presentation                                                                                          54
Visual field measurement
                                                                                                        Increased visual field

                                                                                     Sensitivity (dB)
  Sensitivity (dB)

                                                              Profile plot

                     Eccentricity (degrees of visual field)

                                                                      Isopter plot

ProQR Therapeutics – Corporate Presentation                                                                                  55
Visual field measurement
                                                                                                        Increased visual field

                                                                                     Sensitivity (dB)
  Sensitivity (dB)

                                                              Profile plot

                     Eccentricity (degrees of visual field)

                                                                      Isopter plot

ProQR Therapeutics – Corporate Presentation                                                                                  56
Full Field Stimulus Test (FST)
All study subjects

• 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)

  Goal
  Directional improvement in treatment group

ProQR Therapeutics – Corporate Presentation         57
Visual Acuity
Only applicable in severe patients
Snellen Visual Acuity                         ETDRS/LogMAR Visual Acuity                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
•   Snellen VA chart used in                  •   ETDRS Chart used as Gold Standard
    Clinical Practice                             for assessing VA in Clinical Trials   •   Noise of assay is likely 0.1
                                                                                            LogMAR (1 line, or
                                              •   Alternative VA scales used for VA         5-letters)
                                                  with low vision patients

ProQR Therapeutics – Corporate Presentation                                                                                58
Visual Field (VF)
For moderate patients

• 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)
                                                                       Medmont device for DAC perimetry
    • Measure of visual field in peripheral vision
    • Gold standard in measuring VF
    • Measures visual field with white light only

  Goals
  Improvement above the noise of the assay and/or
  improvement in hill of vision analysis                        Perimetry data               Hill of Vision visual

ProQR Therapeutics – Corporate Presentation                                                                          59
Visual Field (VF)
For severe patients

• Micro perimetry (Maia)
    • Measures visual field in the macula (0-20°
      visual field)
    • Measures visual field with white light

  Goals
  Improvement above the noise of the assay
  and/or improvement in hill of vision analysis

ProQR Therapeutics – Corporate Presentation        60
OCT – EZ-line
Only applicable in severe patients

• Imaging of the retina through high                    Normal OCT
  resolution OCT
    • Visualizes anatomy of the central 6mm
      of the retina
                                                   Severe Usher Syndrome
    • Degeneration of photoreceptor cells in
      the macula is visible at
Patient Reported Outcomes
A range of PRO’s applicable to all subjects in the trial

• 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                        62
QR-1123 reference slides

ProQR Therapeutics – Corporate Presentation   63
QR-1123 is specific for P23H allele
           Strong and specific
        suppression of P23H in cells          QR-1123 is selective for P23H in vivo

ProQR Therapeutics – Corporate Presentation                                           64
QR-1123 preserves ONL and improves ERG in
P23H rat model

            QR-1123 surrogate preserves ONL                          QR-1123 surrogate improves ERG in P23H Tg rat
                     in P23H Tg rat                                    strong correlation with ONL preservation
          mRHO AS03                           PBS                      QR-1123 surrogate                    Control oligo

                                                    Amplitude (µV)

                                                                                           Amplitude (µV)
                                                                             Light level                       Light level

Murray et al., 2015 IOVS 56: 6362

ProQR Therapeutics – Corporate Presentation                                                                                  65
QR-1123 reduces retinal degeneration
in humanized P23H mice

                                                                        Superior
                                                                        retina

                                                                 Lens   Optic Nerve
                                                                        Head (ONH)

                                                                        Inferior
                                                                        retina

                                              Optic
                   Superior                   Nerve   Inferior
                                              Head

ProQR Therapeutics – Corporate Presentation                                        66
Additional Appendix

ProQR Therapeutics – Corporate Presentation   67
QR-411 for Usher syndrome
Designed to treat genetic eye disease in Usher syndrome
Usher

          Develop hearing loss and                  PE40 mutation affects ~1,000
          blindness in childhood and                patients in Western world
          turn completely blind by
          mid adulthood

RNA therapy: QR-411                       Strong PoC

          For Usher PE40                            Strong preclinical PoC in
          no therapy available                      patient retinal model.
                                                    Development candidate
                                                    selected

  √ RNA is established modality in eye        Next steps
  √ Strong preclinical proof of concept       • IND-enabling studies expected to start
    in patient retinal organoids                in 2020
  √ Orphan drug designation                   • Clinical development similar to QR-421a

ProQR Therapeutics – Corporate Presentation                                               68
QR-1011 for Stargardt’s disease
Stargardt’s disease

          Develop blindness in                      ~7,000 patients with
          childhood and turn                        c.5461-10T>C in ABCA4
          completely blind by mid                   in Western world
          adulthood

RNA therapy: QR-1011                      Strong PoC

          For Stargardt’s c.5461-                   Preclinical PoC and
          10T>C in ABCA4 no                         efficacy in human mini-
          therapy available                         gene models

  √ RNA is established modality in eye        Next steps
  √ Strong preclinical proof of concept       • Progression into patient retinal
                                                organoid model

ProQR Therapeutics – Corporate Presentation                                        69
ProQR spun-off non-core activities
Wings Therapeutics                                         Amylon Therapeutics

                         Clinical stage company focussed                        Company focussed on the
                         on development of life changing                        development of CNS products with
                         therapies for Dystrophic                               initial focus on HCHWA-D
                         Epidermolysis Bullosa

•   Spun out of ProQR in March 2019 with QR-313 for        •   ProQR incubated the activities of Amylon since 2015
    Exon 73 mutations and all other DEB activities             and spun the company out in 2017

•   Wings will be led by interim CEO Mark de Souza,        •   The initial focus of Amylon is on its development
    former CEO of Lotus Tissue Repair and Hal Landy,           program AT-010 for HCHWA-D, a brain disease
    former medical advisor to Lotus Tissue Repair and          caused by a mutation in beta-amyloid leading to
    CMO of Enobia                                              stroke in mid-adulthood

•   ProQR has a minority stake and will be eligible for    •   ProQR retained a majority stake in the company and
    milestone and royalty rights to commercial products        will be eligible for milestone and royalty rights to
                                                               commercial

ProQR Therapeutics – Corporate Presentation                                                                        70
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