Our third product candidate, is a ProTide transformation of cordycepin, a novel nucleoside analog with a unique mode of action, that has shown potent anti-cancer activity in preclinical studies. Cordycepin was isolated from the fungus cordyceps militaris in 1950. Since that time, cordycepin has not been successfully developed or approved as a chemotherapy, but has shown potent anti-cancer activity in multiple preclinical studies conducted by us as well as by other companies and research institutions.
Similar to our other ProTides, NUC-7738 is designed to generate the active anti-cancer metabolite of cordycepin, 3’ dATP, directly inside cells, bypassing the resistance mechanisms of transport, activation and breakdown. There is no need for the activating enzyme, adenosine kinase, or AK, to act on it, a process that has been shown to be rate-limiting. There is also no breakdown by the enzyme adenosine deaminase, or ADA. This results in significantly higher intracellular levels of 3’ dATP.
We have examined the in vitro cytotoxic activity of NUC-7738 across a range of different human cancer cell lines, including leukemia, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, T-cell leukemia, multiple myeloma, pancreas, colon, liver and breast cancers, as compared with the parent nucleoside analog, cordycepin. In 16 of the 20 cell lines examined, NUC-7738 was found to be more potent, and in three leukemia cell lines, NUC-7738 had over 50-times greater potency than cordycepin.
We have completed the evaluation of NUC-7738 in preclinical toxicology studies.
|ABC-08 - Phase Ib Study
in biliary tract cancer
|NuTide:301 - Phase I Study
in advanced solid tumours
|NuTide:701 - Phase I Study
in advanced solid tumours &
|PRO-105 - Phase II Study
in platinum-resistant ovarian cancer
|NuTide:302 - Phase Ib Study
in colorectal cancer
|Acelerate - Phase III Study
in metastatic pancreatic carcinoma