ProQR Therapeutics (PRQR) Investor update summary

Platform and pipeline

• Axiomer RNA-editing pipeline has multiple clinical readouts expected over the next 12 months; AX-0810 provided first human validation of NTCP target engagement.

• First participant dosed in AX-0811 Phase I; preclinical modeling projects up to 65% editing at lower doses than AX-0810, with a longer projected half-life and less frequent dosing.

• Initial AX-0811 target-engagement data from the first two cohorts are expected in early January 2027; AX-0422 and AX-2911 initial clinical data are expected in H1 2027.

Biliary atresia rationale

• Biliary atresia affects ~20,000 patients worldwide; 60%-80% ultimately require liver transplantation in early childhood despite Kasai surgery.

• NTCP modulation aims to reduce hepatic bile acid reuptake, redirecting bile acids toward plasma and urinary excretion to lessen intrahepatic cholestasis.

• In preclinical models, AX-0811 reduced hepatocyte bile acids by 67%; NTCP modulation reduced cholestasis scores by 67%.

• Disease can progress after Kasai; NTCP expression is upregulated, and continued hepatic bile acid retention is considered a contributor to liver injury and fibrosis.

AX-0810 clinical data

• Phase I Cohorts 1 and 2 tested four weekly subcutaneous doses at 3 and 6 mg/kg; assessments included TUDCA clearance, conjugated bile acids and total plasma bile acids.

• No serious adverse events, discontinuations or clinically significant liver enzyme changes were observed; no pruritus, hormone, vitamin D or bilirubin changes reported to date.

• Dose-dependent, durable, statistically significant target engagement across all three biomarkers included up to an eightfold increase in serum total bile acids; urinary excretion was directionally aligned with plasma increases.

• Pharmacokinetic data support an estimated half-life of 8 weeks; full data, including Cohort 3 and 12-week follow-up for all cohorts, planned for a conference later in 2026.