Proqr Therapeutics N.v. · NASDAQ:PRQR
Proqr Therapeutics — Investor Day (November 2025)
31 slides from Proqr Therapeutics's investor day presentation, Nov 3, 2025
Slide 1: Entering the Clinic with AX-0810
ENTERING THE CLINIC WITH AX-0810 November 3, 2025 Establishing safety, PK, and the biomarker roadmap for proof of target engagement
Slide 2: Agenda and Speakers
ProQR Therapeutics – Investor & Analyst Event 2 Agenda Prof. dr. H.J. Henkjan Verkade, MD, PhD Professor of Pediatrics, Pediatric Gastroenterology and Hepatology, Beatrix Children's Hospital - University Medical Center Groningen Welcome & Agenda Sarah Kiely Strategic Overview Daniel A. de Boer AX-08
Slide 3: Forward-looking statements
Forward-looking statements This presentation contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as “continue,” "anticipate," "believe," "could," "estimate," "expect," "goal," "intend," "
Slide 4: Strategic Overview
Presenter: Daniel A. de Boer Strategic Overview ProQR Therapeutics – Investor & Analyst Event 4
Slide 5: Axiomer RNA editing journey: from invention to the clinic
ProQR Therapeutics – Investor & Analyst Event 5 Axiomer RNA editing journey From invention to the clinic 2014 2022 ProQR invents oligo mediated RNA Editing recruiting endogenous ADAR ProQR pivots to solely focus on ADAR editing ProQR and Eli Lilly enter into first 5 target partnership worth $1.25B 2
Slide 6: How Axiomer edits RNA
ProQR Therapeutics – Investor & Analyst Event 6 How Axiomer edits RNA Modify protein function Introduce protective variants MODULATE CORRECT PROTECT Correct disease-causing mutations NATURAL ADAR EDITING EDITING OLIGONUCLEOTIDE (EON)-directed EDITING ADAR A (Adenosine) I (Inosine) EON ADAR A (Adenos
Slide 7: Advancing RNA editing through pipeline and partnerships
PIPELINE ProQR Therapeutics – Investor & Analyst Event 7 Advancing RNA editing through pipeline and partnerships Axiomer AX-0810 for cholestatic diseases AX-2402 for Rett syndrome AX-1412 for cardiovascular diseases AX-2911 for MASH PARTNERSHIPS
Slide 8: Axiomer advancing to value inflection
Axiomer advancing to value inflection ProQR Therapeutics – Investor & Analyst Event 8 € EON-GUIDED ADAR RNA EDITING, INVENTED BY PROQR Now translating Axiomer in clinic Foundational IP estate securing long-term leadership in the field DIFFERENTIATED PIPELINE FOR RANGE OF HIGH UNMET NEEDS AX-0810 CTA
Slide 9: Pipeline horizons: near term, next, and beyond
Axiomer entering first-in-human (FIH) trial with AX-0810 targeting NTCP in cholestatic disease; CTA authorized – Phase 1 trial beginning to establish safety, PK, and target engagement Leading RNA editing CNS capability and first neuro pipeline program, AX-2402 for Rett syndrome, advancing rapidly –
Slide 10: Targeting NTCP to address unmet need in cholestatic diseases
Targeting NTCP to address unmet medical need in cholestatic diseases at the root cause AX-0810 ProQR Therapeutics – Investor & Analyst Event 10 Cristina Lopez Lopez, MD, PhD, Chief Medical Officer Prof. dr. H.J. Henkjan Verkade, MD, PhD, Professor of Pediatrics, Pediatric Gastroenterology and Hepato
Slide 11: Addressing unmet need in cholestatic diseases through NTCP modulation
Cholestatic diseases have high unmet medical need, especially Primary Sclerosing Cholangitis affecting adults (~80,000 patients) and Congenital Biliary Atresia affecting pediatrics early in life (~20,000 patients). Both conditions have no approved therapies and may require liver transplantation.1,2
Slide 12: Toxic accumulation of bile acids in the liver
ProQR Therapeutics – Investor & Analyst Event 12 Cholestatic diseases are characterized by toxic accumulation of bile acids in the liver NTCP, sodium taurocholate co-transporting polypeptide References: Zeng J, Fan J, Zhou H. Cell Biosci. 2023 Apr 29;13(1):77; Trauner M, Fuchs CD. Gut 2022;71:194–20
Slide 13: AX-0810: first-in-class RNA editing therapy targeting NTCP
ProQR Therapeutics – Investor & Analyst Event 13 AX-0810: first-in-class RNA editing therapy targeting NTCP for cholestatic diseases ADAR, Adenosine Deaminase Acting on RNA; BA, Biliary atresia; EON, Editing Oligonucleotide; NTCP, sodium taurocholate co-transporting polypeptide; PSC, Primary Scleros
Slide 14: AX-0810 grounded in human genetics with strong therapeutic rationale
ProQR Therapeutics – Investor & Analyst Event 14 AX-0810 grounded in human genetics with strong therapeutic rationale in cholestatic diseases STRONG BIOLOGICAL RATIONALE With evidence demonstrating the importance of NTCP in the disease TARGET VALIDATED IN HUMAN GENETICS Derisking the AX-0810 program
Slide 15: Addressing unmet need in cholestatic diseases through NTCP modulation
ProQR Therapeutics – Investor & Analyst Event 15 Addressing unmet need in cholestatic diseases through NTCP modulation Cholestatic diseases have high unmet medical need, especially Primary Sclerosing Cholangitis affecting adults (~80,000 patients) and Congenital Biliary Atresia affecting pediatrics
Slide 16: Prof. dr. H.J. Henkjan Verkade, MD, PhD
ProQR Therapeutics – Investor & Analyst Event 16 Prof. dr. H.J. Henkjan Verkade, MD, PhD Professor of Pediatrics, Pediatric Gastroenterology and Hepatology, Beatrix Children's Hospital - University Medical Center Groningen • Medical education and PhD at Erasmus University Rotterdam and the Universit
Slide 17: Phase 1 multiple ascending dose trial design
Multiple ascending dose (MAD) N=33 (24 on treatment, 9 on placebo) Cohort 1 (3mg/kg) (n=11) Cohort 2 (6mg/kg) (n=11) Cohort 3 (9mg/kg TBC) (n=11) ProQR Therapeutics – Investor & Analyst Event 33 CTA approved for first-in-human (FIH) trial Safety, tolerability, PK, and biomarker-based target engageme
Slide 18: Assessing AX-0810 safety, tolerability, and PK
Primary objective: to assess of safety, tolerability, and PK of AX-0810 Optimized dosing regimen in the FIH: • Concentrations relevant for chronic administration in cholestatic patients • MAD with weekly SC injection allows appropriate liver exposure • Assessment at doses expected to be pharmacologi
Slide 19: Clinically relevant biomarker strategy
ProQR Therapeutics – Investor & Analyst Event 35 Clinically relevant biomarker strategy to inform future development From target engagement to pharmacodynamics biomarkers TARGET ENGAGEMENT DISEASE RELEVANCE MECHANISTIC PHARMACODYNAMIC Total bile acids (TBAs) levels Assess effect on bile acids transp
Slide 20: Assessing total bile acids (TBA) levels
Control Axiomer 0 2 4 6 8 Con Axiomer trol Axiomer 0 2 4 6 8 Change from Baseline (Fold Change) 36 Assessing total bile acids (TBA) levels Demonstrating AX-0810 EON effect on liver bile uptake function ProQR Therapeutics – Investor & Analyst Event • NTCP transporter is responsible for >90% of total
Slide 21: Confirming AX-0810 specificity for NTCP
ProQR Therapeutics – Investor & Analyst Event 37 Confirming AX-0810 specificity for NTCP By assessing changes in bile acids profile Baseline Axiomer 0 50 100 Bile acids % Conjugated Bile Acids Unconjugated Bile Acids Plasma total bile acids profile * Axiomer * Expected direction of change in plasma
Slide 22: Safely and transiently mimic disease conditions with a TUDCA challenge
Safely and transiently mimic disease conditions with a TUDCA challenge ProQR Therapeutics – Investor & Analyst Event 38 Control EON treated 0.04 0.06 0.08 0.10 kel (min-1) TUDCA clearance from plasma with Axiomer * Axiomer * Expected direction of change in TUDCA clearance NTCP, sodium taurocholate c
Slide 23: Regular assessments scheduled to capture impact on biomarkers
ProQR Therapeutics – Investor & Analyst Event 39 Regular assessments scheduled to capture impact on biomarkers TUDCA challenge Elimination rate of orally administered TUDCA treatment vs placebo Bile acids measurement at baseline and few timepoints over the treatment and follow up period Measurement
Slide 24: Biomarker selection driving target engagement and translational readouts
Biomarker selection driving strong target engagement and translational readouts ProQR Therapeutics – Investor & Analyst Event 40 Objectives Preclinical data Target engagement Disease related biomarker Mechanistic pharmacodynamic Bile acids levels ✓ ✓ ✓ Increase in plasma bile acids Bile acids profil
Slide 25: Learnings from the FIH translating into the disease population
ProQR Therapeutics – Investor & Analyst Event Learnings from the FIH translating into the disease population Disease population Plasma TBA From ↑ in cholestasis to ↑↑↑ with AX-0810 Plasma conjugated bile acids from normal to ↑ with AX-0810 TUDCA challenge from ↓ clearance to ↓↓ with AX-0810 Disease
Slide 26: AX-0810 trial and next development steps
ProQR Therapeutics – Investor & Analyst Event 42 AX-0810 trial and next development steps Safety, tolerability, and PK data expected toward end of 2025 Safety, tolerability, PK, and target engagement data anticipated in H1 2026 Plan to include a patient cohort following completion of healthy volunte
Slide 27: Corporate Outlook
Presenter: Dennis Hom Corporate Outlook ProQR Therapeutics – Investor & Analyst Event 43
Slide 28: Axiomer advancing to value inflection
Axiomer advancing to value inflection ProQR Therapeutics – Investor & Analyst Event 44 € EON-GUIDED ADAR RNA EDITING, INVENTED BY PROQR Now translating Axiomer in clinic Foundational IP estate securing long-term leadership in the field DIFFERENTIATED PIPELINE FOR RANGE OF HIGH UNMET NEEDS AX-0810 CT
Slide 29: Q&A
Q&A
Slide 30: Q&A
Q&A Daniel A. de Boer Founder and Chief Executive Officer Gerard Platenburg Chief Scientific Officer Cristina Lopez Lopez, MD, PhD Chief Medical Officer Dennis Hom Chief Financial Officer
Slide 31: \ITSIN |
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