ProQR Therapeutics (PRQR) The Citizens JMP Life Sciences Conference 2025 summary

Platform technology and differentiation

• Developing an RNA editing platform leveraging ADAR to modify specific mRNA bases, enabling precise correction of genetic defects without altering DNA.

• Technology uses chemically synthesized oligonucleotides to recruit endogenous ADAR, offering a de-risked approach due to established safety and manufacturing knowledge.

• Delivery is via naked oligonucleotides, with GalNAc conjugation for liver targeting and intrathecal administration for CNS, both leveraging proven delivery routes.

• Dosing is anticipated quarterly for liver and every six to nine months for CNS indications.

• Holds foundational IP in ADAR editing, with differentiation mainly in target selection and strategy rather than core technology.

Pipeline and clinical development

• Lead program AX-0810 targets cholestatic diseases (PSC and biliary atresia) by introducing a protective NTCP variant, aiming for disease modification in ~100,000 patients in the US and Europe.

• Proof of concept shown in human cells, mice, and primates; clinical trial application (CTA) submission planned this quarter, with initial human data expected by year-end and more complete data next year.

• First clinical study will enroll healthy volunteers in the Netherlands, measuring serum bile acid levels and other biomarkers to assess target engagement.

• Study design includes five doses over four weeks, followed by 12 weeks of monitoring to inform future dosing frequency.

• Indication selection between PSC and biliary atresia is ongoing, with the goal to develop for both.

Additional programs and strategic focus

• Second program targets B4GALT1 for cardiovascular disease prevention, with in vivo proof of concept and further updates expected in summer.

• Third program addresses Rett syndrome in CNS, supported by a $9 million grant from the Rett Syndrome Research Trust, leveraging RNA editing's ability to restore normal protein function without overexpression.

• Fourth program targets PNPLA3 mutation in MASH, aiming to restore wild-type protein function in a large patient population.

• Platform is designed for scalability, with learnings from one target applicable to others, similar to the siRNA model pioneered by Alnylam.

• Strategy is to independently commercialize rare disease products and seek partners for larger indications.