In the end of 2016, the Medical Product Agency (MPA) approved a clinical phase 1 trial, MASTIFF (MTH1, A phase) I, Study on Tumors Inhibition, First in human, First in class with EudraCT no: 2016-002624-80), investigating safety and tolerability of Karonudib in cancer patients with advanced solid malignancies. Thomas Helleday Foundation for Medical Research is the sponsor of the MASTIFF trial, but has appointed Oxcia AB to assist in the clinical development and commercialization.
Many cancers have a dysfunctional redox status and upregulated levels of MTH1, suggesting that MTH1 is necessary for the cancer cell to survive the high load of oxidative stress and oxidized nucleotides. MTH1 (NUDT1) is a sanitizing enzyme, hydrolysing oxidized nucleotides into their monophosphates, thereby hindering them to be incorporated into DNA and cause mutations (Nakabeppu et al., 2010). By knocking down MTH1, cancer cells can no longer survive, while normal cells still divide and live (Gad et al., Nature 2014; Rai et al., 2011, Ling et al., 2016 etc). In Professor Thomas Helleday laboratory at Karolinska Institute, small molecule inhibitors against MTH1 was identified and shown to kill a variety of cancer cells in vitro and reduce tumour growth in mice xenograft disease models (Gad et al., Nature 2014; Warpman Berglund et al., Annals of Oncology 2016).
Oxcia AB has been crucial for patent strategies and clinical development strategies for the MTH1 project. Oxcia AB has, been responsible for planning, preparing, initiating the clinical trial MASTIFF, and are now managing it according to GCP, GMP, GLP and applicable regulations.)