ProQR ANALYST & INVESTOR EVENT NACFC 2016, Orlando, Florida Date: Presenters: October 27th, 2016 Daniel de Boer, Noreen Henig and JP Clancy Agenda Overview and introduction by Daniel de Boer The relevance of the Nasal Po

ProQR ANALYST & INVESTOR EVENT NACFC 2016, Orlando, Florida Date: Presenters: October 27th, 2016

Daniel de Boer, Noreen Henig and JP Clancy

Agenda Overview and introduction by Daniel de Boer The relevance of the Nasal Potential Difference test in CF

by JP Clancy, M.D. Results of the QR-010 NPD study by Noreen Henig, M.D. Pipeline and path ahead by Daniel de Boer Q&A session with JP Clancy, M.D., Noreen Henig, M.D., Smital Shah and Daniel de Boer ProQR Therapeutics 2

Forward looking statements This presentation contains forward-looking statements that involve substantial risks

and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including but not limited to, statements regarding our strategy, future operations, future pre-clinical 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 products, 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 represent our management s beliefs and assumptions only as of the date of this presentation. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and

you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. The forward-looking statements

contained in this presentation reflect our current views with respect to future events, and we assume no obligation to update any forward-looking statements except as required by applicable law. These forward-looking statements are subject to a

number of risks, uncertainties and assumptions, including those that may be described in greater detail in the annual report filed on Form 20-F for the year ended December 31, 2015 that we have filed with the U.S. Securities and Exchange Commission

(the SEC ) and any subsequent filings we have made with the SEC. We have included important factors in the cautionary statements included in that annual report, particularly in the Risk Factors section, and subsequent filings with the SEC

that we believe could cause actual results or events to differ materially from the forward-looking statements that we make. ProQR Therapeutics 3

ProQR s CF journey From an idea to clinical proof of concept in 4 years Leiden, The Netherlands & Palo

Alto, CA 2012 2013 2014 2015 2016 Founding of ProQR around an idea to impact CF using RNA repair Saliva secretion assay in homozygous F508 mouse model showed near wild type functional restoration

Delivery further de-risked through compelling in vitro and in vivo data in CF like mucus Strong functional NPD data in homozygous F508 mouse model up to 80% restoration Start of two global

clinical studies of QR-010 in 80 CF patients Positive clinical proof of concept for QR-010 with strong NPD response in homozygous F508 patients ProQR Therapeutics 4

CFTR is hydrating mucus in normal lung cell CFTR Chloride RNA DNA CFTR in normal lung cell: In healthy

people CFTR protein is formed CFTR protein acts as a chloride channel Due to chloride transport the extracellular mucus is hydrated ProQR Therapeutics 5

Absence of CFTR is leading to dehydration of mucus CFTR Chloride RNA DNA CFTR in CF lung cell: In CF

patients no functional CFTR protein is formed In absence of CFTR chloride can not flow out of the cell Due to the lack of chloride transport the extracellular mucus dehydrates ProQR Therapeutics 6

CFTR and ENaC channels in normal lung cell ENaC CFTR Down regulator Sodium Chloride In healthy people:

CFTR and ENaC cooperate to regulate Chloride and Sodium balance CFTR is a down regulator of ENaC channel activity ProQR Therapeutics 7

CFTR and ENaC channels in CF lung cell ENaC CFTR Down regulator Sodium Chloride In CF patients: In

absence of CFTR protein ENaC is unregulated and thus hyperactive This contributes to the CF phenotype ProQR Therapeutics 8

ENaC CFTR Down regulator Confirmation: Downregulation of ENaC (Max Basal PD) CFTR mediated total chloride

transport (mv) normalized at 0 Cl timepoint 20 10 0 -10 -20 -30 -40 ringer s amiloride zero chloride isoproterenol units = time in minutes CF patient WT NPD is the only direct in vivo measurement of CFTR activity: Restoration of

CFTR activity is the primary measurement CFTR activity is measured on the right Downregulation of ENaC is indirect effect of CFTR ENaC activity as measured by sodium transport is measured on the left (Max Basal PD) Primary: Improvement in

chloride transport ProQR Therapeutics 9

CFTR restoration confirmed by ENaC normalization

Change from baseline

CFTR activity is confirmed by normalization of ENaC activity

Total Chloride Transport (CFTR)

change from baseline -4.1mV

CFTR mediated total chloride transport

normalized at 0 Cl timepoint

20 10 0 -10 -20 -30 -40

ringer s amiloride zero chloride isoproterenol

units = time in minutes

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Putting QR-010 NPD results in perspective

Total Chloride Transport

TDN Center of CFTR detection

Sermet-Gaudelus et al,

Accurso et al NEJM, 2010

Rowe et al, Methods Mol biol, 2011

Classical CF with severe

Rowe et al, Methods Mol biol, 2011

+ Lumacaftor (200mg)

Interpretations are adapted from publications

Clancy et al, Thorax 2012

Treatment period for all mention therapies is 28 days

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The relevance of the Nasal Potential

Difference test in CF

Professor of Pediatrics, Research Director Pulmonary Medicine

Cincinnati Children s

ProQR Therapeutics 12

NPD is the only direct measurement of CFTR function

NPD is only direct measurement of both sodium and chloride channel function

downregulation of ENaC is well understood

A response on both chloride transport and change in basal PD provides validation of a functioning CFTR

Nasal epithelium well represents (in histology and ion transport) the lung epithelium

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NPD methods and interpretation is standardized

NIH-PA Author Manuscript NIH-

NATIONAL INSTITUTES OF HEALTH

Methods Mol Biol. Author manuscript; available in PMC 2013 September 03.

Methods Mol Biol. 2011 ; 741: 69-86. doi:10.1007/978-1-61779-117-8_6.

Nasal Potential Difference Measurements to Assess CFTR Ion Channel Activity

Departments of Medicine, Pediatrics, and Physiology and Biophysics MCLM, University of Alabama, 35294-0006, Birmingham, AL, USA

Jean-Paul Clancy, and

Departments of Medicine, Pediatrics, and Physiology and Biophysics MCLM,

University of Alabama, 35294-0006, Birmingham, AL, USA

Respiratory Medicine and Cystic Fibrosis Center, Shaare Zedek Medical Center, 91031, Jerusalem, Israel

Steven M. Rowe: smrowe@uab.edu; Jean-Paul Clancy: john.clancy@cchmc.org

available online PLOS ONE

Optimizing Nasal Potential Difference Analysis for CFTR Modulator Development: Assessment of Ivacaftor in CF Subjects with the G551D-CFTR

Steven M. Rowe1, Bo Liu1, Aubrey Hill1, Heather Hathorne1, Morty Cohen2a, John R. Beamer2b,

Frank J. Accurso3, Qunming Dong4, Claudia L. Ordonez4c, Anne J. Stone4, Eric R. Olson4,

P. Clancy5*, for the VX06-770-101 Study Group

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Relevance of NPD for the lower airway

Detection of Cystic Fibrosis Transmembrane Conductance Regulator Activity in Early-Phase Clinical Trials

Steven M. Rowe1,2,3,4, Frank Accurso5, and John P. Clancy3,4

1Department of Medicine,

2Department of Physiology and Biophysics, 3Department of Pediatrics, and 4Cystic Fibrosis Research Center,

University of Alabama at Birmingham, Birmingham,

Alabama; and 5Department of Pediatrics, University of Colorado, Denver, Colorado

The nasal epithelium is a faithful representation of the histologic and ion

transport features of the pulmonary epithelium, supporting its use as a biomarker for the lower airway.

Rowe, Accurso, Clancy. PATS 2007

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Bronchial Current (A/cm2 )

Nasal Current (A/cm2 )

Good correlation between bronchial current and Nasal current

CHARACTERIZATION OF BRUSHED HUMAN UPPER AND LOWER AECS TO DETECT AND

QUANTIFY CFTR FUNCTION