NUCLEASES – MERK KGAA

In December 2020, Artios entered into an exciting research collaboration and license agreement with Merck KGaA , Pharmaceutical company in Darmstadt, Germany, a leading team of specialists in Healthcare and Life Sciences (https://www.merckgroup.com/en/company.html) for the identification of novel DDR nuclease inhibitors in the oncology field.

What are Nucleases?

Nucleases are the molecular scissors that are responsible for cutting DNA to facilitate its processing by other enzymes. Specifically, nucleases employ divalent metal cations to catalyse the cleavage of the phosphdiester backbone between the sugar and phosphate groups of DNA. As an integral part in the DNA metabolic machinery, nucleases are required for virtually all types of DNA repair, as well as DNA replication, transcription and DNA homeostasis e.g., telomere maintenance. Acting in concert with a variety of other DNA repair enzymes, nucleases are critical in resolving damage caused by exogenous environmental factors such as reactive oxygen species, ionising radiation, UV light or alkylating agents, as well as that resulting from intrinsic errors in replication or recombination.

Misregulation of nucleases has been implicated in a wide variety of diseases, including cancer. In addition, several clinically relevant synthetic lethalities have been reported, e.g. HRD and ALT among others, making nucleases attractive therapeutic targets. To-date, DNA repair nucleases are a completely undrugged enzyme class and the full potential of targeting nucleases as a therapeutic strategy remains unexplored.

Artios has built a unique technology platform for prosecuting nucleases. Leveraging our expertise in DDR drug discovery and our bespoke DDR Platform, we have developed a portfolio of multiple nuclease programmes, each of which has the potential to deliver a first-in-class therapy in this novel target class.

Artios has granted Merck KGaA a sole license to certain intellectual property rights to research and develop compounds.