ProQR Therapeutics N.V. (Nasdaq: PRQR) announced that the Central Committee on Research Involving Human Subjects (CCMO) has authorized the company's Clinical Trial Application (CTA) for a Phase 1 study of AX-0810 in healthy volunteers, following review under the new European Medicines Agency (EMA) centralized review process. AX-0810 is the company's lead investigational editing oligonucleotide (EON) targeting NTCP, being developed for the treatment of cholestatic diseases including primary sclerosing cholangitis and biliary atresia.
First-in-Class RNA Editing Approach
AX-0810 represents a first-in-class investigational RNA editing oligonucleotide that harnesses the body's endogenous ADAR enzymes to selectively modulate NTCP function. Through this novel mechanism, AX-0810 aims to reduce toxic bile acid accumulation in the liver and improve outcomes in cholestatic diseases, which are characterized by inflammation, fibrosis, and progressive liver failure. By targeting a key pathogenic process that drives disease progression, AX-0810 has the potential to be disease-modifying.
The therapy is the first program from ProQR's Axiomer RNA editing pipeline to enter clinical development and marks a significant milestone for the company's next-generation RNA base editing technology platform.
Phase 1 Trial Design and Objectives
With the CTA approval, ProQR is authorized to begin dosing in its Phase 1 study, which will be conducted in the Netherlands. The Phase 1 study will evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) via biomarkers to establish proof of target engagement. The trial is focused on healthy volunteers and is designed to inform future studies in patients.
According to the company's forward-looking statements, initial Phase 1 clinical data for AX-0810 is anticipated in Q4 2025, with clinical updates across multiple programs expected throughout 2025.
Axiomer Technology Platform
ProQR is pioneering the Axiomer technology, which uses a cell's own editing machinery called ADAR to make specific single nucleotide edits in RNA. Axiomer "Editing Oligonucleotides" (EONs) mediate single nucleotide changes to RNA in a highly specific and targeted way using molecular machinery present in human cells called ADAR (Adenosine Deaminase Acting on RNA).
The Axiomer EONs are designed to recruit and direct endogenously expressed ADARs to change an Adenosine (A) to an Inosine (I) in the RNA – an Inosine is translated as a Guanosine (G) – correcting an RNA with a disease-causing mutation back to a normal (wild type) RNA, modulating protein expression, or altering a protein so that it will have a new function that helps prevent or treat disease.
Expert Involvement and Industry Event
In connection with this milestone, ProQR will host a virtual Investor and Analyst Event on November 3, 2025, beginning at 10 am ET. The event, entitled "Entering the Clinic with AX-0810: Establishing Safety, PK, and the Biomarker Roadmap for Proof of Target Engagement," will feature presentations by ProQR Management and Key Opinion Leader Professor Henkjan J. Verkade, MD, PhD.
Professor Verkade is a pediatric gastro/hepatologist at the Beatrix Children's Hospital of the University Medical Center Groningen, The Netherlands. His main research interests include bile acid transport, metabolism, and signaling in health and pediatric liver disease; mechanisms and treatment of pediatric cholestatic liver diseases; and development of biomarkers and novel therapies for rare inherited liver disorders. He has authored more than 300 peer-reviewed publications and more than 15 book chapters.
