Abstract: The invention provides NUC-7738 (3?-deoxyadenosine-5?-O-[phenyl(benzyloxy-L-alaninyl)] phosphate), a phosphoramidate derivative of 3?-deoxyadenosine, for use in the treatment of a proliferative disease, such as cancer, by reducing the amount of extra-cellular PD-L1 protein (e.g. soluble PD-L1 or exosomal PD L1) and/or increasing the amount of OX40-L. The invention also relates to the use of NUC-7738 in combination with an immune oncology agent such as an immune checkpoint inhibitor.

Abstract: The invention relates to 5-fluoro-2?-deoxyuridine-5?-O-[1-naphthyl (benzoxy-L-alaninyl)] phosphate (NUC-3373), or a pharmaceutically acceptable salt thereof, for use in the treatment of cancer, in particular by intravenous infusion for a continuous period of up to 10 hours. The invention also relates to methods of treating cancer by administration of NUC-3373 to particular sub-groups of cancer patient. The invention further relates to methods for selecting a patient for treatment with NUC-3373.

Abstract: The present invention relates to chemical compounds, the compounds for use in a method of treatment, particularly in a method of prophylaxis or treatment for cancer, a process for preparation of the compounds and pharmaceutical compositions comprising the compounds. The compounds may, in particular, be useful in the treatment of leukaemia, lymphoma and/or solid tumours in Homo sapiens. The compounds are derivatives of cordycepin (3?-deoxyadenosine).

Abstract: The present invention is a process for the preparation of certain 5?-phosphoramidate nucleotide diastereoisomers. The phosphoramidates include those useful in the treatment of cancer such as NUC-3373 (5-fluoro-2?-deoxyuridine-5?-O-[1-naphthyl(benzyloxy-L-alaninyl)]phosphate].

Abstract: This invention relates to pharmaceutical formulations and formulation strategies of protides (phosphoramidate derivatives of nucleosides) and, in particular, protides useful in the treatment of cancer such as NUC-3373 (5-fluoro-2?-deoxyuridine-5?-O-[1-naphthyl (benzoxy-L-alaninyl)] phosphate) and NUC-7738 (3?-deoxyadenosine-5?-O-[phenyl(benzyloxy-L-alaninyl)] phosphate). In particular, the invention relates to formulations which comprise a polar aprotic solvent, for example dimethyl acetamide (DMA).

Abstract: Phosphoramidate derivatives of 5-fluoro-2?-deoxyuridine are disclosed for use in the treatment of cancer, especially in the treatment of cancer where the patient shows resistance, for example, in a patient with cells with a lowered level of nucleoside transporter proteins and/or with nucleoside kinase-deficient cells and/or with mycoplasma-infected cells and/or with cells with a raised level of thymidylate synthase.

Abstract: The present invention generally relates to a novel process for the preparation of 3?-deoxyadenosine derivatives, and particularly NUC-7738 (3?-deoxyadenosine-5?-O-[phenyl(benzyloxy-L-alaninyl)] phosphate) an anticancer ProTide of deoxyadenosine.

Abstract: This invention relates to pharmaceutical formulations and formulation strategies of protides (phosphoramidate derivatives of nucleosides) and, in particular, protides useful in the treatment of cancer such as NUC-3373 (5-fluoro-2?-deoxyuridine-5?-O-[1-naphthyl (benzoxy-L-alaninyl)] phosphate) and NUC-7738 (3?-deoxyadenosine-5?-O-[phenyl(benzyloxy-L-alaninyl)] phosphate). In particular, the invention relates to formulations which comprise a polar aprotic solvent, for example dimethyl acetamide (DMA).

Abstract: This invention relates to pharmaceutical formulations of gemcitabine-[phenyl-benzoxy-L-alaninyl)]-phosphate, a monophosphate derivative of the well-known oncology drug gemcitabine. In particular, the invention relates to formulations which comprise a polar aprotic solvent, preferably dimethyl acetamide (DMA). Formulations comprising these solvent provide therapeutically effective treatments of gemcitabine-[phenyl-benzoxy-L-alaninyl)]-phosphate. The invention also relates to methods of using said formulations and kits comprising said formulations.

Abstract: Disclosed is NUC-1031 (gemcitabine-[phenyl-benzoxy-L-alaninyl)]-phosphate), a ProTide derivative of gemcitabine, for use in targeting cancer stem cells. This targeting of cancer stem cells may be employed in the prevention or treatment of cancer. NUC-1031 may be used in treatment of relapsed or refractory cancer in a human patient. Without wishing to be bound by any hypothesis, it is believed that the ability of NUC-1031 to target cancer stem cells contributes to its utility in the treatment of relapsed or refractory cancers.

Abstract: Provided are medical uses and methods for targeting cancer stem cells employing ProTide compounds, particularly in the prevention or treatment of cancer. The ProTide may be other than one selected from the group consisting of: NUC-1031; a ProTide derived from cordycepin; and a ProTide derived from 8-chloroadenosine. The medical uses and methods for targeting cancer stem cells are particularly useful in the treatment of relapsed or refractory cancer in human patients. Also provided are methods of selecting patients who will benefit from prevention or treatment of cancer through the medical uses or methods of treatment of the invention.

Abstract: The present invention relates to compounds comprising a salt of a diphosphate phosphoramidate of a nucleoside drug, e.g., clofarabine. The compounds are useful in the treatment of cancer, e.g., leukemia.

Abstract: Phosphoramidate derivatives of 5-fluoro-2?-deoxyuridine are disclosed for use in the treatment of cancer, especially in the treatment of cancer where the patient shows resistance, for example, in a patient with cells with a lowered level of nucleoside transporter proteins and/or with nucleoside kinase-deficient cells and/or with mycoplasma-infected cells and/or with cells with a raised level of thymidylate synthase.

Abstract: This invention relates to a combination of gemcitabine-[phenyl-benzoxy-L-alaninyl)]-phosphate (chemical name: 2?-Deoxy-2?,2?-difluoro-D-cytidine-5?—O-[phenyl (benzoxy-L-alaninyl)] phosphate) (NUC-1031) and a platinum-based anticancer agent selected from cisplatin, picoplatin, lipoplatin and triplatin. The combinations are useful in the treatment of cancer and particularly biliary tract and bladder cancer.

Abstract: This invention relates to a prodrug of the monophosphate nucleotide of the well-known oncology drug gemcitabine. Specifically, it relates to gemcitabine-[phenyl-benzoxy-L-alaninyl)]-phosphate when present as a single phosphate diastereoisomer and, in particular, it relates to the (S)-phosphate diastereoisomer which offers a remarkable and unexpected increase in solubility relative to the (R)-diastereoisomer. The (S)-phosphate epimer is also preferentially taken up into cyclodextrin solutions over the (R)-diastereoisomer.

Abstract: The present invention provides a method for the preparation of intermediates useful in the synthesis of gemcitabine-[phenyl-benzoxy-L-alaninyl)]-phosphate. It also provides a method of preparing gemcitabine-[phenyl-benzoxy-L-alaninyl)]-phosphate.

Abstract: The present invention relates to compounds comprising a salt of a diphosphate phosphoramidate of a nucleoside drug, e.g. clofarabine. The compounds are useful in the treatment of cancer, e.g. leukemia.

Abstract: Phosphoramidate derivatives of 5-fluoro-2?-deoxyuridine are disclosed for use in the treatment of cancer, especially in the treatment of cancer where the patient shows resistance, for example, in a patient with cells with a lowered level of nucleoside transporter proteins and/or with nucleoside kinase-deficient cells and/or with Mycoplasma-infected cells and/or with cells with a raised level of thymidylate synthase.

Abstract: The present invention is a process for the preparation of certain 5?-phosphoramidate nucleotide diastereoisomers. The phosphoramidates include those useful in the treatment of cancer such as NUC-3373 (5-fluoro-2?-deoxyuridine-5?-O-[1-naphthyl(benzyloxy-L-alaninyl)]phosphate].

Abstract: This invention relates to a combination of gemcitabine-[phenyl-benzoxy-L-alaninyl)]-phosphate (chemical name: 2?-Deoxy-2?,2?-difluoro-D-cytidine-5?-O-[phenyl (benzoxy-L-alaninyl)]phosphate)(NUC-1031) and a platinum-based anticancer agent selected from carboplatin, oxaliplatin, satraplatin and nedaplatin. The combinations are useful in the treatment of cancer and particularly ovarian cancer.