Our pipeline programs share several key characteristics including a deep rooting in human genetics, the potential to have a major impact in a high unmet medical need, the ability to leverage the existing proven delivery technology for delivery to hepatocytes in liver, the opportunity to monitor early biomarkers to establish target engagement in Phase I trials for human proof of concept and availability of well-defined clinical endpoints.
Pipeline Overview ProQR pipeline
ProQR is pioneering a next-generation RNA technology called Axiomer™, which uses a cell’s own editing machinery called ADAR to make specific single nucleotide edits in RNA to reverse a mutation or modulate protein expression and could potentially yield a new class of medicines for both rare and prevalent diseases with unmet need. Our initial discovery programs aim to explore the potential of our platform across diseases that originate in the liver and nervous system.
ProQR programs
Click the '+' icon for more information, including estimated population.
AX-0810
- Disease
- Cholestatic Diseases targeting NTCP
Program AX-0810 for Cholestatic Diseases targeting NTCP is now in the clinical, start phase
Estimated population: ~100.000
Cholestatic disorders are caused by a buildup of bile acids in the liver which can lead to inflammation. Without treatment, the damage can worsen over time and ultimately lead to liver failure. Liver transplants are often necessary for primary sclerosing cholangitis (PSC, ~80,000 patients in the US and EU) and biliary atresia (BA, ~20,000 patients worldwide), two forms of cholestatic disease where currently there are no approved drugs.
Biliary atresia is a severe pediatric cholestatic disease that affects newborns and young children. In BA, the bile ducts are blocked or absent, leading to obstructed bile flow. Despite early surgical intervention, most patients still progress.
AX-0810 and AX-0811 are designed to introduce a loss of function (LOF) variant that has been found in human genetics to prevent reuptake of bile acids in the liver. Based on this mechanism of action, AX-0810 and AX-0811 have the potential to become disease modifying treatments for a range of cholestatic diseases, including biliary atresia as primary indication.
AX-0811
- Disease
- Cholestatic Diseases targeting NTCP
Program AX-0811 for Cholestatic Diseases targeting NTCP is now in the non-clinical, finished phase
Estimated population: ~100.000
Cholestatic disorders are caused by a buildup of bile acids in the liver which can lead to inflammation. Without treatment, the damage can worsen over time and ultimately lead to liver failure. Liver transplants are often necessary for primary sclerosing cholangitis (PSC, ~80,000 patients in the US and EU) and biliary atresia (BA, ~20,000 patients worldwide), two forms of cholestatic disease where currently there are no approved drugs.
Biliary atresia is a severe pediatric cholestatic disease that affects newborns and young children. In BA, the bile ducts are blocked or absent, leading to obstructed bile flow. Despite early surgical intervention, most patients still progress.
AX-0810 and AX-0811 are designed to introduce a loss of function (LOF) variant that has been found in human genetics to prevent reuptake of bile acids in the liver. Based on this mechanism of action, AX-0810 and AX-0811 have the potential to become disease modifying treatments for a range of cholestatic diseases, including biliary atresia as primary indication.
AX-0422
- Disease
- Hurler syndrome targeting IDUA W402X
Program AX-0422 for Hurler syndrome targeting IDUA W402X is now in the non-clinical phase
Estimated population: ~500-1000
Hurler syndrome is the most severe form of a group of rare diseases called Mucopolysaccharidosis type I (or MPS I). It is caused by genetic mutations in the alpha-L-iduronidase (IDUA), resulting in accumulation of harmful substances (known as glycosaminoglycans, or GAGs). This buildup damages the cells and drives the disease. Hurler syndrome affects multiple organs, including the brain, heart, lung, liver, and bones. Symptoms begin early in life and lead to significant health problems and, ultimately, early mortality.
AX-0422 is designed to directly correct the most common mutation reported in the severe form helping to restore normal function and reduce the buildup of excess GAGs. Current treatment options do not fully address all disease manifestations and present some limitations. AX-0422 has the potential to address both peripheral and neurological manifestations of Hurler syndrome.
AX-2911
- Disease
- MASH targeting PNPLA3
Program AX-2911 for MASH targeting PNPLA3 is now in the non-clinical, start phase
Metabolic dysfunction-associated steatohepatitis (or MASH) is a common liver disease that is increasing worldwide. People with MASH have a high unmet medical need, as the disease progressively damages the liver function and increases the risk of liver cancer, and liver-related mortality. About half of the individuals with MASH carry a variant in a gene called Patatin-like phospholipase domain-containing 3 (or PNPLA3), which is the strongest known genetic risk factor for disease progression. The variant causes fat accumulation in the liver cells, ultimately negatively impacting the liver function.
AX-2911 is designed to restore PNPLA3 enzyme function and as such address the root cause of MASH.
AX-2402
- Disease
- Rett syndrome targeting MECP2 R270X
Program AX-2402 for Rett syndrome targeting MECP2 R270X is now in the non-clinical, start phase
Estimated population: ~5000
Rett syndrome is a progressive neurodevelopmental disorder caused by genetic mutations in the Methyl CpG binding protein 2 (MECP2) and diagnosed primarily in females. It is characterized by apparently normal psychomotor development during the first six to 18 months after birth, followed by a period of developmental stagnation, then a regression in language and motor skills, followed by long-term relative stability. During the phase of regression, affected patients develop repetitive, stereotypic hand movements that replace purposeful hand use. Additional symptoms include gait ataxia and apraxia, seizures, tremors, episodic apnea and/or hyperpnea, gastrointestinal issues, scoliosis and musculoskeletal problems, anxiety and sleep issues and bruxism.
In December 2024, the Rett Syndrome Research Trust and ProQR expanded their RNA editing partnership in Rett Syndrome. Axiomer™ has the potential to restore the precise level of MECP2 protein regulatory function, which is lacking in Rett Syndrome, and become a disease modifying therapy.
Partnered pipeline
Eli Lilly and Company
Since 2021 ProQR has had a global licensing and research collaboration with Eli Lilly and Company. The partnership focuses on the discovery, development, and commercialization of potential new medicines for genetic disorders.
The ongoing collaboration uses ProQR’s proprietary Axiomer™ RNA editing platform to progress multiple RNA editing drug targets toward clinical development and commercialization.
