AX-0810/AX-0811 targeting NTCP for the treatment of cholestatic diseases

At ProQR, we are dedicated to improving the lives of patients and families affected by rare and common disorders using Axiomer, our innovative RNA editing platform technology.

AX-0810 is an RNA editing oligonucleotide that is a potential therapy for cholestatic diseases such as biliary atresia and primary sclerosing cholangitis. AX-0810 is a first generation therapy, while AX-0811 is a next generation candidate. 

In cholestatic livers diseases, bile acids can’t flow properly from the liver to the gut. Excess bile acids accumulate in the liver, triggering inflammation, which can lead to scarring. The surrounding tissues, including the bile duct, can also become irritated and stop working as they should.  

As the disease progresses, the liver’s ability to function deteriorates. In severe cases, this can cause irreversible damage that leads to liver failure, which requires a liver transplant. These diseases can affect individuals of all ages, yet treatment options are limited. 

Both therapies are designed to target liver cells called hepatocytes. These are the main cells that do most of the liver’s work. In these cells, AX-0810 and AX-0811 make a small change to the instructions (RNA) used to make a protein called NTCP. NTCP is a transport channel that lets bile acids into your liver cells.  

This edit is intended to help the liver produce a slightly different version of the NTCP protein, called NTCP Q68R. This version still works well for the body, but it allows fewer bile acids into the liver. By reducing bile acid uptake to the liver, AX-0810 and AX-0811 may help reduce bile acid buildup, which could be beneficial for people with cholestatic liver diseases. 

Scientists have found that some people naturally have the NTCP Q68R version from birth. These individuals report no clinical symptoms related to bile acid level concentrations. 

Using this approach, we aim to limit the concentration of bile acids in the liver of patients with cholestatic diseases so that the liver can recover and function properly. 

We are conducting a Phase 1 clinical trial in healthy adult volunteers to evaluate the safety, tolerability, pharmacokinetics, and target engagement of AX-0810. In June 2026, we announced positive interim results from the evaluable cohorts (3 mg/kg and 6 mg/kg) demonstrating that AX-0810 has a favorable safety and tolerability profile. Additionally, administration of AX-0810 resulted in increased hepatotoxic conjugated bile acids in circulation, keeping them from accumulating in the liver, and promoting the elimination of toxic bile acids through the urine.  

For more detail, read the full press release or watch our video update, describing the data and outlining next steps for both AX-0810 and AX-0811, our next-generation RNA editing therapy targeting NTCP for cholestatic diseases. 

The company plans to present  full data from the Phase 1 study at a medical or scientific conference later this year.