LEIDEN, Netherlands & CAMBRIDGE, Mass., June 25, 2026 (GLOBE NEWSWIRE) — ProQR Therapeutics N.V. (Nasdaq: PRQR) (ProQR or the Company), a clinical-stage biotechnology company dedicated to changing lives through transformative RNA therapies based on its proprietary Axiomer™ RNA editing technology platform, today announced positive target engagement data from its ongoing Phase 1 clinical study evaluating AX-0810, the Company’s first investigational Axiomer RNA editing oligonucleotide (EON), in healthy volunteers.
AX-0810 is a GalNAc-conjugated, subcutaneously administered Axiomer RNA EON designed to selectively modulate NTCP, a key transporter responsible for bile acid uptake from the bloodstream into the liver. Through this novel mechanism, AX-0810 aims to reduce toxic bile acid accumulation in the liver, the underlying driver of cholestatic liver diseases including biliary atresia, and has the potential to be disease modifying.
AX-0810 Phase 1 Study Overview
The ongoing multiple ascending dose (MAD) Phase 1 study enrolled 33 healthy volunteers, including 24 participants receiving AX-0810 and nine participants receiving placebo across the 3 mg/kg, 6 mg/kg, and 9 mg/kg cohorts. The data reported today include findings from 22 participants in cohorts 1 and 2, receiving 3 mg/kg and 6 mg/kg doses, respectively. Data from the 9 mg/kg cohort are not yet available.
NTCP Target Engagement Confirmed Across All Three Predefined Biomarker Measures
The data demonstrated clear evidence of NTCP target engagement consistent with the biological rationale and preclinical findings. Across the evaluable 3 mg/kg and 6 mg/kg cohorts, administration of AX-0810 resulted in dose-dependent increases in total bile acids in serum of up to 8-fold, exceeding the Company’s predefined target engagement threshold of 2-fold as a meaningful indication of NTCP modulation. Concordant dose-dependent changes in conjugated bile acids and circulating TUDCA levels further support specificity of NTCP modulation.
Administration of AX-0810 resulted in increased hepatotoxic conjugated bile acids in circulation, keeping them from accumulating in the liver, supporting the specificity of NTCP modulation and the expected pharmacologic profile. Increased circulating TUDCA (i.e., decreased clearance through NTCP) following challenge further confirms NTCP target engagement. Together, the Company believes the consistent dose-response observed across these independent biomarker measures provides convergent evidence of NTCP modulation in humans following administration of AX-0810.
Increased levels of conjugated bile acids in serum circulation led to dose-dependent and statistically significantly increased urinary excretion of conjugated bile acids, indicating that NTCP modulation may allow the body to lower concentration of toxic bile acids.
AX-0810 is designed to specifically edit the bile acid binding pocket of the NTCP protein, while preserving the other functions of the protein such as hormonal transport. The Phase 1 data to date confirmed there were no changes in hormone levels in circulation, supporting the intended mechanism of action of AX-0810. The Company anticipates that preservation of the other NTCP functions and the expected infrequent dosing frequency could be key differentiators of ProQR’s RNA editing approach in modulating NTCP for cholestatic disease.
Favorable Safety and Pharmacokinetic Profile
AX-0810 demonstrated a favorable safety and tolerability profile in cohorts 1 and 2, with no serious adverse events or pruritus reported across the evaluated cohorts to date. Pharmacokinetic findings were consistent with the expected profile, including half-life of eight weeks based on available data, supportive of sustained target engagement.
“The concordant responses across all three predefined biomarkers provide compelling clinical target engagement evidence that AX-0810 is modulating NTCP biology in humans as intended,” said Cristina Lopez Lopez, MD, PhD, Chief Medical Officer of ProQR. “We observed dose-dependent increases in total bile acids of up to 8-fold, together with a selective shift toward protecting the liver from toxic conjugated bile acid uptake, and increased circulating TUDCA levels following a challenge in which TUDCA was orally administered. These findings support the expected pharmacology of NTCP modulation and were accompanied by a favorable safety and tolerability profile and pharmacokinetics consistent with sustained target engagement. The biomarker responses observed in healthy volunteers were consistent with the biology predicted from our preclinical studies, supporting our confidence in the translational potential of NTCP modulation for patients with biliary atresia, a disease with significant unmet medical need.”
Participants in the Phase 1 study of AX-0810 continue to be followed through the planned 12-week follow-up period across all cohorts. ProQR plans to present full data from the Phase 1 study at a medical or scientific conference later this year.
AX-0811 Next Generation NTCP EON Demonstrates Cholestasis Reduction in Animal Model
The biomarker findings established in the AX-0810 Phase 1 study support continued advancement of ProQR’s NTCP franchise, including AX-0811, a next-generation NTCP-targeting RNA editing oligonucleotide generated using the Company’s AI-enabled discovery engine. AX-0811 demonstrated robust cholestasis reduction in a preclinical cholestasis animal model and in humans is projected based on modeling to support at least 4-fold higher editing at lower dose levels, with a projected half-life greater than three months. ProQR expects to submit a Clinical Trial Application (CTA) in mid-2026 for AX-0811 and anticipates initial human clinical data in healthy volunteers by year-end 2026.
Next Development Steps for NTCP Franchise and Beyond
The Company has selected biliary atresia (BA) as the initial indication for Phase 2 development of AX-0810 or AX-0811, based on strong biological rationale and high unmet medical need. To inform the design of the Phase 2 program, ProQR plans to conduct an investigator-initiated trial (IIT) in pediatric participants with BA in China. The Company expects to report initial clinical data from the IIT in the first half of 2027.
“The AX-0810 data represent an important milestone both for the NTCP program and for the Axiomer RNA editing platform,” said Daniel A. de Boer, Founder and Chief Executive Officer of ProQR. “The human target engagement data generated with AX-0810, together with the promising preclinical profile of AX-0811, strengthen our confidence in the potential of the NTCP franchise to address significant unmet need in biliary atresia and further reinforce the broad potential of our Axiomer RNA editing platform”.
Upcoming anticipated milestones:
NTCP franchise
- AX-0810 data from the 9 mg/kg cohort and 12-week follow up from the ongoing Phase 1 study expected by year-end 2026
- AX-0811 CTA filing in mid-2026, with initial data in healthy volunteers expected by year-end 2026
- IIT in pediatric biliary atresia in China, with initial data targeted for first half of 2027
- Potentially registration-enabling Phase 2 program, subject to regulatory interactions, expected to start in mid-2027 with first interim analysis data expected by mid-2028
Other pipeline candidates
- AX-0422 for MPS1 / Hurler Syndrome (IDUA) CTA filing for a first-in-patient study anticipated in early 2027 and initial data expected in the first half of 2027
- AX-2911(PNPLA3) FIH IIT in China expected in the first half of 2027
