ProQR Presents Preclinical Proof of Concept for AX-0810 RNA Editing Targeting NTCP in Cholestatic Diseases

ProQR Therapeutics NV (Nasdaq: PRQR), a company focused on developing next-generation RNA therapies, has disclosed new preclinical data related to its innovative Axiomer™ RNA editing platform. This includes the first preclinical proof of concept for the AX-0810 program targeting cholestatic diseases. The findings were presented at the American Society of Gene & Cell Therapy (ASGCT) Annual Meeting in Baltimore.

Gerard Platenburg, ProQR's Chief Scientific Officer, expressed enthusiasm about the potential of their Axiomer ADAR RNA editing technology. For the first time in the field, the company has demonstrated proof of target engagement resulting in significant biomarker changes in non-human primates (NHPs). The AX-0810 program, which targets the NTCP transporter for cholestatic diseases, showed that Axiomer RNA editing oligonucleotides can effectively modulate serum bile acid levels. This is an important step as they advance toward clinical trials, expected to begin in late 2024 or early 2025.

AX-0810 focuses on the SLC10A1 RNA, utilizing the Axiomer technology to transiently and specifically reduce bile acid concentration in the liver. By targeting NTCP, the main transporter responsible for bile acid reuptake from the portal vein to the liver, AX-0810 aims to address cholestatic disorders. The program has shown promising results in preclinical models.

Key data from the ASGCT presentation highlighted that Axiomer editing oligonucleotides (EONs) can modulate NTCP protein function while maintaining protein expression. A significant correlation (R2 = 0.51) was found between NTCP editing levels and serum bile acids in NHPs. An early generation of EONs, named EON1, achieved up to 29% editing of NTCP in the liver of NHPs after a single dose, resulting in an eight-fold change in serum bile acids 72 hours post-treatment. Further optimizations have enhanced editing efficiency to 60% in vitro, and these findings were confirmed in NHPs, demonstrating consistency across models.

ProQR plans to advance AX-0810 into clinical development, aiming to initiate trials in late 2024 or early 2025. The company also expects to release translational data for AX-0810 in the second half of 2024, which will offer more details on the clinical trial design. Additionally, AX-1412, another Axiomer program targeting B4GALT1 for cardiovascular disease, will present preclinical proof of concept and translational data in the latter half of 2024, with plans to enter the clinic around the same period.

The company will host an investor webcast on May 9, 2024, to discuss the data presented at the ASGCT meeting. The webcast will be available on ProQR's website, where participants can also find poster presentations detailing the robust and durable RNA editing achieved in NHPs using Axiomer editing oligonucleotides.

ProQR's Axiomer technology represents a significant advancement in RNA therapy. By targeting specific single nucleotide changes in RNA through endogenous ADAR enzymes, Axiomer can potentially correct disease-causing mutations, modulate protein expression, or alter protein functions. This innovative approach has the potential to create a new class of medicines for a wide range of diseases.

ProQR Therapeutics continues its mission to transform lives with cutting-edge RNA therapies, and its Axiomer platform is a promising step toward addressing both rare and common diseases with significant unmet medical needs.