ProQR today announced AX-0810 for Cholestatic Diseases targeting NTCP and AX-1412 for Cardiovascular Disease targeting B4GALT1 as initial pipeline programs. These programs share several key characteristics including a deep rooting in human genetics, the potential to have a major impact in indications with high unmet medical need, the ability to leverage the existing proven delivery technology to the liver, the opportunity to monitor early biomarkers to establish target engagement in Phase I trials for human proof of concept, and the availability of well-defined clinical endpoints. Cholestatic disorders are caused by a buildup of bile acids in the liver. Without treatment, the damage progresses through various stages to ultimately liver failure.

Liver transplants are often necessary for primary sclerosing cholangitis (PSC) and biliary atresia (BA), two forms of cholestatic disease where currently there are no approved drugs. AX-0810 is designed to introduce a loss of function (LOF) variant that has been found in human genetics to prevent re-uptake of bile acids in liver. Based on its mechanism of action, AX-0810 has the potential to become a disease modifying treatment for a range of cholestatic diseases.

Cardiovascular diseases (CVDs) are a group of health conditions that affect the heart and blood vessels, such as atherosclerosis which can lead to severe problems like heart attacks, heart failure, and stroke. AX-1412 introduces a variant into B4GALT1 that is associated in human genetics with a significantly lower chance of developing cardiovascular disease. ProQR intends to advance AX-1412 targeting B4GALT1 to early clinical proof of concept stage, then would seek to partner this program.

At the R&D event, the Company also highlights platform proof of concept data, including consistent RNA editing reported in models in nervous system and liver: Up to 40% editing reported in the nervous system of mice in vivo leading to a 26-fold change in protein function recovery. Up to 50% editing reported in the liver of mice in vivo. Up to 50% editing reported in the nervous system of NHP in vivo Additionally, ProQR's Axiomer technology achieves increased editing efficiency and hepatocyte uptake in vivo demonstrating that GalNAc delivery technology does not interfere with A-to-I editing.

Beyond correction, the Axiomer RNA editing technology platform has broad applicability and proof of concept in multiple forms of protein modulation including by ability to modulate proteins by altering function, changing post-translational modifications, and modifying protein interactions, as shown in preclinical models.