Developing Novel Anti-Leukaemic Drugs from Iodinin Analogues

Acute myeloid leukaemia (AML) is a cancer disease wherein immature blood cells, called myeloblasts, grow and divide in an uncontrolled manner in the bone marrow. Since AML cannot be surgically removed, all patients undergo heavy chemotherapy. The disease is a severe condition associated with mortality in more than half of the patients, not only due to the disease itself, but unfortunately also because of the heavy treatment. There is a high unmet medical need for new and innovative therapies for AML. During the mapping of extracts from marine bacteria, our scientists identified a new compound exhibiting a strong effect on leukaemia cells. The effect was close to that of todays standard therapy, however the compound demonstrated lower toxicity compared to standard therapy. The compound showed very low solubility. A number of analogues of the compound have therefore been made. Some of these analogues show good solubility and high effect. During a 3 year project period we aim at creating a documentation package sufficient to attract potential industrial partners or investors. We have a compound which we have tested in cancer cells from patients with promising results. The compound induces cell death in cancer cells without the toxicity toward healthy cells to the extent traditional chemotherapy does. The compound has been administered to mice, but we have not succeeded in proving efficacy at tolerated dose. The inventors will continue to optimize the concept in search for a novel treatment.

Vi lykkes ikke med å vise effekt av stoffet vårt i en AML-musemodell. Imidlertid er konseptet dels beskyttet av et innvilget patent og en patentsøknad. Forskerne vil arbeide videre for å utvikle konseptet i håp om å utvikle en behandling.

Acute myeloid leukaemia (AML) has an incidence of 3/100 000. The disease is a highly severe condition associated with high mortality, not only due to the disease itself, but also because of life-threatening toxic side-effects of the standard chemotherapy. Since AML cannot be surgically removed, all patients undergo heavy chemotherapy during their treatment course. These patients often suffer from systemic infections related to the reduced immune defence from the disease itself, but more importantly due to the bone marrow toxicity of the induction therapy. The present standard-of-care treatment has a failure rate in approximately 50% of patients, leading to death and otherwise major side effects. There is therefore a high, unmet medical need for new and innovative targeted therapies for AML. During the mapping of extracts from marine bacteria, our scientists identified the phenazine-class compound iodinin. The compound exhibited a strong effect on leukaemia cells; in particular, the compound demonstrated a cell death inducing efficacy close to that of the first-line anthracycline drug Daunorubicin (DNR). In addition, the compound demonstrated lower toxicity to cardiomyoblasts compared to DNR. During a 3 year project period we aim at creating a documentation package sufficient to attract potential industrial partners or investors. Novo Nordisk Pre-Seed Funds granted a no-strings-attached grant of 500 kDKK in May 2013. In addition, the University of Oslo granted 500 kNOK in innovation funding in April 2015. To be able to continue pre-clinical development of these promising drug candidates we now aim to secure funding from BIOTEK2021.