ProQR Therapeutics (PRQR) Status update summary

Pipeline and Clinical Development Updates

• Lead program AX-0810 for cholestatic diseases is advancing, with target engagement data in healthy volunteers expected this quarter and phase II development focused on biliary atresia, a severe pediatric disease with high unmet need.

• AX-0811, a next-generation NTCP-targeting oligonucleotide, demonstrates approximately threefold higher editing efficiency in preclinical models, with CTA submission expected mid-year and initial clinical data by year-end 2026.

• AX-0422 for Hurler syndrome (MPS I) is being developed as a wholly owned asset, with CTA filing expected in early 2027 and initial clinical biomarker data in the first half of 2027; the program aims to address both liver and CNS manifestations.

• AX-2911 targets PNPLA3 for MASH, showing superior reduction in liver fat compared to knockdown approaches, with an investigator-initiated trial in China and first-in-human trial planned for H1 2027.

• The pipeline is supported by AI-driven discovery, high-throughput screening, and strategic partnerships, with a financial runway into mid-2027 and multiple clinical catalysts anticipated.

Strategic and Platform Advances

• AI-enabled discovery and the Ginkgo Bioworks partnership have reduced candidate development timelines by up to 90% and improved editing efficiency up to sixfold, accelerating innovation across programs.

• Strategic partnership with Ginkgo Bioworks enables roboticized high-throughput data generation and includes a strategic equity investment.

• The platform is expanding into CNS indications, with Hurler syndrome serving as a bridge to future CNS programs such as Rett syndrome.

• Collaboration with Eli Lilly continues to progress, focusing on multiple RNA editing targets, while the Hurler program returns to internal development.

• The company is building an NTCP franchise by developing multiple generations of oligonucleotides in parallel, aiming for optimized dosing, scalability, and physician awareness.

Clinical and Regulatory Strategy

• AX-0810’s phase I study uses three biomarker readouts to assess NTCP modulation, with a twofold increase in serum bile acids as a key indicator and no safety signals observed.

• Biliary atresia was selected for phase II due to its severity, clear biological rationale, and established regulatory pathways, with PSC remaining a follow-on opportunity.

• AX-0422’s staged clinical approach starts with liver-directed editing, followed by CNS targeting via intrathecal administration, aiming for broad disease modification.

• Investigator-initiated trials in China for AX-2911 allow for efficient early data generation and optimization of clinical development in MASH.

• Regulatory strategies leverage established biomarkers and endpoints for accelerated approval, with long-term outcomes and post-market commitments planned.