PPCA-03

PPCA-03 is an investigational RNA editing oligonucleotide developed by ProQR Therapeutics for the treatment of Alpha-1 antitrypsin deficiency (AATD). It utilizes the proprietary Axiomer technology platform, which employs synthetic Editing Oligonucleotides (EONs) to recruit endogenous Adenosine Deaminase Acting on RNA (ADAR) enzymes to a specific target mRNA sequence. PPCA-03 is specifically designed to correct the PiZ mutation (a G-to-A transition resulting in a Glu342Lys substitution) in the SERPINA1 mRNA. By facilitating site-specific A-to-I (adenosine-to-inosine) editing, the drug restores the wild-type protein sequence, potentially allowing for the production and secretion of functional alpha-1 antitrypsin protein. This approach aims to address both the liver disease caused by protein aggregation and the lung disease resulting from protein deficiency. While PPCA-03 served as a lead candidate in early development and proof-of-concept studies, ProQR has since advanced subsequent candidates such as AX-0810 (formerly QR-810) into clinical development.