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A ProTide Transformation of Cordycepin

Potent Pre-Clinical Anti-Cancer Activity

The transformative properties of NUC-7738 allow us to exploit the unique mode of action of cordycepin

NUC-7738

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.

Animated acelarin Mode of Action (MOA)

NUC-7738 bypasses the key cancer resistance pathways of cordycepin

Discover NUC-7738 Key Facts

1
Overcomes Resistance Mechanisms
2
Unique
Mode of
Action
3
Initiate
Phase I study
in 2018

NUC-7738 Clinical Studies

We have completed the evaluation of NUC-7738 in preclinical toxicology studies.

NuCana Ongoing or Planned Clinical Studies

ACELARIN NUC-3373 NUC-7738
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 &
haematological malignancies
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