Our second ProTide to enter clinical studies is a ProTide transformation of the widely used anti-cancer medicine, 5-FU. It is uniquely designed to overcome the key cancer resistance mechanisms that limit the efficacy of 5-FU, improve upon the safety profile and reduce the dosing administration burdens associated with 5-FU.
NUC-3373 generates the same active anti-cancer metabolite, FUDR-MP, as 5-FU, but at far higher concentrations. It shares the features common to all ProTides: the ability to enter cells without the need for membrane transporters; deliver the activated nucleotide analog; and avoid enzymatic degradation to potentially toxic compounds. Unlike 5-FU, NUC-3373 consists of the active anti-cancer metabolite, FUDR-MP, and a novel protective phosphoramidate moiety. This moiety allows NUC-3373 to enter the cell without the need for any membrane transporters. Once inside the cancer cell, the phosphoramidate moiety is optimally cleaved off, resulting in deprotection and the release of FUDR-MP. This bypasses the need for any activating enzymes, resulting in significantly higher levels of the active anti-cancer metabolite, which may lead to improved efficacy as compared to 5-FU. In addition, because NUC-3373 avoids breakdown by the enzyme DPD, certain toxic byproducts are not released. With these important features, we believe NUC-3373 has the potential for a significantly improved efficacy and tolerability profile compared to 5-FU.
With an improved pharmacokinetic and pharmacodynamic profile, and a significantly longer half-life, NUC-3373 may also have a more favorable dosing regimen relative to 5-FU.
NUC-3373 is currently in a Phase I study of patients with advanced solid tumours. Our initial focus is to develop NUC-3373 for patients with colorectal and breast cancers, but we also plan to target other cancers.
Phase I dose-escalation study in patients with advanced solid tumours.
Phase Ib study combining NUC-3373 with leucovorin, oxaliplatin and irinotecan in patients with recurrent metastatic colorectal cancer.
|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