Proqr Therapeutics N.v. · NASDAQ:PRQR
Proqr Therapeutics — Investor Presentation (September 2021)
29 slides from Proqr Therapeutics's investor presentation, Sep 9, 2021
Slide 1: The Axiomer opportunity
CREATING MEDICINES The Axiomer opportunity Nasdaq: PRQR Date: September 9, 2021
Slide 2: Forward looking statements
Forward looking statements THis presentation conti fowardlskng statment that moe Precincts dna ils andthe elope cies by os substantial risks and: ‘other than Fare ficeerraecrtasycaeini ed rg arncl nasi, statements regarding our strategy future operations, futur preclinical and Clinical trial plans a
Slide 3: Agenda
Agenda dn a a Welcome & Introduction Daniel de Boer, Chief Executive Officer Axiomer® RNA Editing Technology Gerard Platenburg, Chief Innovation Officer Axiomer® Intellectual Property Bart Klein, Sr. VP Innovation
Slide 4: Two strategic pillars underpin our approach
Two strategic pillars underpin our approach Genetic eye diseases RNA editing technologies Mae cana TET YT Hee any a * HA Axiomer® Trident® qe ih 1H iv aii fa a i Atto-| editing U-to- editing initia yh havea Mint Hi wi 4 Ht Ha treatment HE RY Hn ‘ fl ii A On. nih uth th ! (t wn i iH aan Means anit hi
Slide 5: ProQR pipeline
ProQR pipeline aecucat ase v2 nse Sepofarsen (QR-10)for cto em oo. a) (98-1123 or 23H adn? maa) nse for 03 — iy RAI frUshersdrome cn EDN Qnrott orstrgactasese == EEN ercsst forushersncrome EY ie) = = (QRK-136 for LCA Up to 5 undisclosed targets using Axiomer? Undisclosed non-ophtha target FULLY OWNE
Slide 6: RNA editing licensing and research collaboration with Lilly
Axiomer® RNA editing licensing and research collaboration with Lilly Litt, Announced global licensing and research collaboration with Lilly on up to five targets using our proprietary Axiomer platform Focused on the discovery, development, and commercialization of potential new medicines for genetic
Slide 7: Axiomer technology
Axiomer® technology Therapeutic oligonucleotides for directing site-specific A-to-I editing in RNA by endogenous ADAR enzymes
Slide 8: A brief history of targeted RNA modulation
A brief history of targeted RNA modulation 1980s 1990s 2014 e e e hag > RNA knockdown Exon skipping Axiomer® technology ogy ogy invented at ProQR Crude technique to degrade RNA A technique to remove an exon Ability to edit a single base in strands that harbor a disease- harboring a disease-causing R
Slide 9: ADAR is the body's own system to edit RNA
ADAR is the body’s own system to edit RNA ADAR deaminase domain ADAR = Adenosine Deaminase Acting on RNA ADARis an RNA editing system that is present in all human cells In the human body, ADAR is responsible for editing RNA to, for example, Target adenosine create different isoforms of proteins chan
Slide 10: EONs designed to recruit endogenous ADAR
EONs designed to recruit endogenous ADAR ADAR deaminates target A in EON-target RNA complex Endogenous editing
Slide 11: EONs designed to recruit endogenous ADAR
EONs designed to recruit endogenous ADAR ADAR deaminates target A in EON-target RNA complex Endogenous editing OAR dsR80s
Slide 12: EONs designed to recruit endogenous ADAR
EONs designed to recruit endogenous ADAR ADAR deaminates target A in EON-target RNA complex Endogenous editing EON-directed therapeutic editing RNA OAR dsR80s
Slide 13: EONs designed to recruit endogenous ADAR
EONs designed to recruit endogenous ADAR ADAR deaminates target A in EON-target RNA complex Endogenous editing EON-directed therapeutic editing RNA OAR dsR80s ~ RNA s25 RNA wa, eee
Slide 14: RNA editing platform
Axiomer® RNA editing platform Editing Oligonucleotide (EON) mediated A-to-/ editing al Unique A-to-I RNA editing + Actos editing in RNA + Using endogenous ADAR + ADARis recruited by a single stranded Editing OligoNucleotide (on) + Lis translated as aG, allowing to target G-to-A mutations and make de
Slide 15: Leveraging four decades of oligonucleotide modality science
Leveraging four decades of oligonucleotide modality science Axiomer® platform on of ide ADAR + Significant experience with the modality of + The mechanism is present in all cells, Axiomer® oligonucleotide therapies that is directly applicable EONS can guide the endogenous ADAR to edit a to Axiomer®,
Slide 16: Applicable for monogenic diseases and beyond
Axiomer® applicable for monogenic diseases and beyond >20,000 genetic diseases Correct genetic mutations that cause disease Restore wild-type protein Correct stop codons Non-genetic diseases + Alter protein functionality + Modify signaling pathways + (Pre}mRNA + IncRNA + Pri} miRNA RNA + (Pre-mRNA +
Slide 17: Axiomer is uniquely positioned in genetic medicines
Axiomer® is uniquely positioned in genetic medicines + Axiomer® edits RNA using the body's + RNAwill only be edited in cells where it own machinery - no external enzymes is expressed have to be inserted into the cells : * Reduced complexity due to non-viral Edits in RNA are reversible by stopping de
Slide 18: Axiomer is broadly validated across multiple genes
Axiomer® is broadly validated across multiple genes NT EON Reverse G-to-A mutation rp 85% Atco c AtpBjcc Reverse G-to-A mutation midua 60% (None; WT target) mUshza 80% Reverse G:to-A mutation USHA 50% | Inactivate protease site app 50% {| Inactivate kinase site hePHES 60% \ Ky Inactivate kinase site
Slide 19: Axiomer has the potential to target broad range of diseases
Axiomer® has the potential to target broad range of diseases 20,000 G>A D ovmimaimotogy — @ ews sioos en Gi Sees earaivawtaar = Leber Cage “ Sptewetmarscmeyn sytem Nearest opens Ooere Pais + Gers « teegans ose aad * ® oem + RencrPeneom oped tune OF ver i @ “ Bimntongen —| Seee Athan Axiomer' Gocome
Slide 20: Axiomer partnership with Lilly
Axiomer® partnership with Lilly Axiomer® vv La, Up to 5 targets in liver and nervous system are licensed exclusively to Lilly
Slide 21: ProQR to develop Axiomer applications in genetic eye disease
ProQR to develop Axiomer® applications in genetic eye disease . “4. OOS cee errs ropa i «The tslboc feet ee Axiomer® disease targets that ProQR will svc ns epee Seen ees - Lt, Up to 5 targets in li nervous system are licensed exclusively to Lilly and
Slide 22: ProQR to develop Axiomer applications in genetic eye disease
ProQR to develop Axiomer® applications in genetic eye disease Yo) Prog will intain all global ae Remainder of he>20,00 * ONE eee targets remain unencumbered . in ophthalmology with strong potential for Axiomer® Ge eerie nee & Tecatentiaersp advance into the pipeline willbe additional partnerships, &
Slide 23: Patent estate protects key features of EON design and ADAR recruitment
Axiomer® patent estate protects key features of EON design and ADAR recruitment Portfolio of 11 patent families ‘Any guide with structures that ‘Chemically modified guides recruit endogenous editors recruiting A tol editors Any editor Protection of different designs of ADAR recruiting editing oligon
Slide 24: Patents broadly cover EON chemistry & chirality
Patents broadly cover EON chemistry & chirality @a @c EON e G 3 ? =o a es a Ce O Base Target RNA Mismatches and analogs Improved PD I Ribose modification ADARstructure 2-H; 2-OMe; MOE; 2-F; 2NH2, LNA.TNA Improved PK and PD = Linkage ADAR structure PO; PS; PN; MeP; UNA; PAc Improved PK and PD
Slide 25: Patent protection beyond 2040
Axiomer® patent protection beyond 2040 Ee SS 17DEC2014 Targeted RNA Editing using endogenous ADARS (Granted CEE Iie RUUS ZA 0013 © -22JUN2016 ‘Single stranded’ EONs Granted US 0014 O1SEP2016 Chemically modified EONS. Granted EP US ZA 0016 ——19JAN2017__ EONS + protecting SONs Published 0020 14FEB2018
Slide 26: Key collaborations with RNA experts
Key collaborations with RNA experts Scientific Advisory Board Research collaborations Peter A Beal Pho Te mitagen 4x lONIS Pro FS Hoven bhmijssc: 7 YitTao ve voyager sD Alnylam ee |S | Pia Anionis ZAlnylam
Slide 27: RNA editing platform
Axiomer® RNA editing platform + EON mediated ADAR editing discovered at the ProQR labs in 2014 + Foundational IP estate of 11 patent families that protect the platform beyond 2040 * Applicable in >20,000 disease targets throughout several organs + ProQR to focus on development of eye targets + Annou
Slide 28: Q&A
Q&A be bebe Daniel de Boer Chief Executive Officer Gerard Platenburg Chief Innovation Officer Smital Shah Chief Business and Financial Officer
Slide 29: \ IT’S IN
\ IT’S IN ProQR) ouR RNA
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