ProQR Therapeutics (PRQR) investor relations material

Strategic pipeline and clinical progress

• Multiple RNA editing programs are advancing, with AX-0810 and AX-0811 targeting NTCP for cholestatic diseases, including biliary atresia as the lead indication.

• AX-0810 demonstrated the first clinical validation of the Axiomer platform, showing dose-dependent NTCP target engagement and favorable safety in humans.

• AX-0811, a next-generation AI-discovered NTCP program, shows greater potency and longer half-life than AX-0810, with projected editing rates up to 65% in human liver at lower doses and less frequent dosing.

• Initial phase I data for AX-0811 from the first two cohorts are expected in early January 2027, with Phase 2 trials planned for mid-2027.

• Additional pipeline assets include AX-0422 for Hurler syndrome and AX-2911 for MASH, with initial human data expected in the first half of 2027.

Clinical rationale and data for NTCP modulation

• Biliary atresia is a severe pediatric cholestatic disease with rapid progression to cirrhosis and high rates of liver transplantation; no approved pharmacological treatments exist.

• NTCP is the main transporter for hepatic bile acid uptake; modulating NTCP reduces toxic bile acid accumulation and intrahepatic cholestasis, redirecting bile acids for renal clearance.

• Preclinical models show AX-0811 reduces hepatocyte/intrahepatic bile acid levels by 67% and improves histological cholestasis scores.

• NTCP modulation is highly selective, preserving hormone and drug transport functions, enabling safer long-term therapy.

• Clinical data confirm elimination of toxic conjugated bile acids and support translation to improved liver health outcomes.

Biomarker and clinical strategy

• Key biomarkers for target engagement include TUDCA, conjugated bile acids, and total bile acids, with clear increases observed in treated cohorts.

• AX-0810 and AX-0811 increase renal clearance of conjugated bile acids, reducing liver exposure and supporting the mechanism of action.

• Biomarker strategy is designed to translate target engagement into measurable improvements in liver injury enzymes, function, fibrosis, and clinical outcomes.

• IIT and Phase 2 trials in biliary atresia patients will focus on native liver survival and reduction in liver-related clinical events.

• AX-0811 is expected to outperform AX-0810 across all biomarkers in equivalent cohorts.