ProQR Therapeutics (PRQR) investor relations material

Advances in ADAR RNA editing and clinical translation

• Clinical data now show successful RNA editing in patients, with alpha-1 antitrypsin deficiency (AATD) as a lead indication, demonstrating conversion from Z to M protein and durable, physiologically relevant protein levels after dosing.

• Editing approaches using GalNAc-conjugated oligos enable subcutaneous delivery, rapid onset, and sustained effects, with ongoing studies to optimize dose and durability, including higher dose cohorts and less frequent dosing intervals.

• Preclinical and early clinical data support the ability to mount acute phase responses and achieve MZ-like phenotypes, with plans to further engage regulatory agencies and expand to additional targets.

• AIRNA and others are leveraging advances in chemistry and oligo design to engage multiple ADAR isoforms, with preclinical data showing high protein levels and long durability in animal models, and clinical entry planned by year-end.

• ProQR’s lead, AX-0810, targets NTCP for cholestatic diseases, with phase 1 clearance and a focus on modulating protein function, not just correction, and CNS programs showing broad distribution and high editing efficiency.

Platform evolution, target selection, and field outlook

• Companies are using learnings from AATD to de-risk and expand pipelines, with new targets like PNPLA3 for liver disease and precision edits for protein-protein interactions, focusing on liver indications with clear biomarkers.

• The field is rapidly approaching the platform maturity seen in siRNA, with improved understanding of enzyme behavior, translation from animal to human, and the importance of target selection and biomarker association.

• Endogenous ADAR’s precision and catalytic activity in humans is now well validated, enabling transient, reversible edits and reducing concerns about off-target effects or immune responses.

• Investor focus is shifting from enzyme function to indication selection and proof of concept, with ongoing debate about editing efficiency versus DNA editing and the breadth of potential applications.

• The chemical toolbox and delivery strategies are well established, supporting faster clinical translation and the expectation that RNA editing will reach broad applicability more quickly than previous modalities.

Industry collaboration and future directions

• Partnerships with pharma and research organizations are accelerating CNS and liver programs, with confidential targets and ongoing collaborations to expand the reach of RNA editing.

• Panelists agree that the next wave of clinical data and target expansion will further validate the technology, with the first drugs likely to be followed by improved generations as the field matures.

• The focus is on translating clinical learnings back to preclinical models to refine platform capabilities and accelerate the path from target identification to human trials.

• There is consensus that RNA editing is poised for rapid growth, with the potential to address a wide range of genetic and protein-modulation diseases beyond current knockdown approaches.

• The session concluded with optimism about the pace of progress and the shift from theoretical enzyme discussions to practical therapeutic development.