Abstract: The present invention provides a computer-implemented method for estimating the cancer cell fraction (CCF) of at least one tumour-specific mutation in a subject. Also provided are related methods for monitoring the clonal dynamics of a tumour, monitoring a treatment of the tumour and methods for treating a subject having a cancer, as well as systems for implementing the methods of the invention.

Abstract: The present invention relates to compounds of formula I that function as inhibitors of PARG (Poly ADP-ribose glycohydrolase) enzyme activity: wherein R1a, R1b, R1c, R1d, W, X1, X2, X3, X4, X5, X6, X7, c are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which PARG activity is implicated.

Abstract: Disclosed herein are dietary compositions that are substantially devoid of at least cysteine or a salt thereof for use in treating a cancer. The dietary compositions and methods of the disclosure can be used to treat cancers that are MTAP-deficient, alone or in combination with a cancer therapy.

Abstract: The present invention relates to compounds of Formula I that function as inhibitors of BCL6 (B-cell lymphoma 6) activity: wherein X1, X2, R1, R2 and R3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which BCL6 activity is implicated.

Abstract: The invention relates to processes for preparing isoindolin-1-one derivatives, and in particular processes for preparing (2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoic acid. The invention also relates to crystalline forms of the compound (2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoic acid and its salts.

Abstract: The invention provides a compound of formula (I): or tautomer or a solvate or a pharmaceutically acceptable salt thereof, wherein the various substituents are as defined in the claims. Also provided are pharmaceutical compositions containing the compounds of formula (I), processes for making the compounds and the medical uses of the compounds.

Abstract: The present invention relates to a dietary product comprising a plurality of amino acids, wherein the dietary product comprises all the essential amino acids and wherein the dietary product is substantially devoid of at least two non-essential amino acids; methods and uses thereof in the treatment of cancer; stratification methods and biomarkers for such applications.

Abstract: The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain aldehyde dehydrogenase inhibitor compounds (also referred to herein as “ALDHI compounds”), that, inter alia, inhibit aldehyde dehydrogenase enzyme ALDH1A3. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit ALDH1A3 enzyme; to treat disorder (e.g., diseases) that are ameliorated by the inhibition of ALDHIA3 enzyme; to treat a proliferative disorder, cancer, obesity, diabetes, a cardiovascular disorder, etc.

Abstract: The present invention relates to compounds of formula I that function as inhibitors of RET (rearranged during transfection) kinase enzyme activity: wherein HET, bonds a, b, c and d, X1, X2, X3, X4, R2, and R3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which RET kinase activity is implicated.

Abstract: The present invention relates to compounds of formula I that function as inhibitors of RET (rearranged during transfection) kinase enzyme activity: wherein HET, X1, X2, X3, X4, integer a and R3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which RET kinase activity is implicated.

Abstract: The invention provides a method of inhibiting angiogenesis in an individual, the method comprising administering to the individual an agent that inhibits the interaction between CLEC14A and MMRN2. The inhibitor may be an antibody, a polypeptide, a peptide, a polynucleotide, a peptidomimetic, a natural product, a carbohydrate, an aptamer or a small molecule.

Abstract: The present disclosure provides antibody sequences found in antibodies that bind to human CD25. In particular, the present disclosure provides sequences of anti-human CD25 antibodies, which do not block the binding of CD25 to IL-2 or IL-2 signalling. Antibodies and antigen-binding portions thereof including such sequences can be used in 5 pharmaceutical compositions and methods of treatment, in particular for treating cancer.

Abstract: The present invention provides methods for predicting the treatment response of a cancer patient, using a tumour copy number profile for the patient. The method comprise analysing the copy number profile to assess whether the characteristics of at least one copy number feature are indicative of the presence of focal amplifications in the tumour genome, wherein the at least one copy number feature is selected from: copy number change-point, segment size and segment copy number. The patient is predicted as being likely to be resistant to treatment with an agent that induces the formation of micronuclei (e.g. doxorubicin) if the characteristics of the at least one copy number features are indicative of the presence of focal amplifications in the tumour genome. Also provided a related methods and systems.

Abstract: The present invention provides a method for predicting whether a human subject having breast cancer will be resistant to, or sensitive to, therapy with a cyclin-dependent kinase (CDK) inhibitor, the method comprising: a) measuring the gene expression in a sample obtained from the breast tumour of the patient to obtain a sample gene expression profile of at least the following modules: (i) a luminal vs.

Abstract: The present invention relates to compounds of formula I wherein R1, R4, Ar, W, X and Z are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1—also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.

Abstract: The specification generally relates to compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, where R, A1, A2 and A3 have any of the meanings defined herein. The specification also relates to the use of such compounds and salts thereof to treat or prevent DNA-PK mediated disease, including cancer. The specification further relates to pharmaceutical compositions comprising such compounds and salts; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; intermediates useful in the manufacture of such compounds and salts; and to methods of treating DNA-PK mediated disease, including cancer, using such compounds and salts.

Abstract: The present disclosure relates to use of an anti-CD25 antibody, not inhibiting IL-2-CD25 interaction, with enhanced binding to activating Fc gamma Rs that lead to effective depletion of tumor-infiltrating Treg cells and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies further improves tumor rejection.

Abstract: The present disclosure provides antibody sequences found in antibodies that bind to human CD25, in particular an anti CD25-a-674 antibody which do not block the binding of CD25 to IL-2 or IL-2 signalling. The claimed antibody binds to the epitopes: YQCVQGYRALHRGP (150 to 163) or SVCKMTHGKTRWTQP (166 to 180) on CD25 Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical compositions and methods of treatment, in particular for treating cancer.

Abstract: The present disclosure provides antibody sequences found in antibodies that bind to human CD25. In particular, the present disclosure provides sequences of anti-human CD25 antibodies, which do not block the binding of CD25 to IL-2 or IL-2 signalling. Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical compositions and methods of treatment, in particular for treating cancer.

Abstract: The present disclosure provides antibody sequences found in antibodies that bind to human CD25, in particular an anti CD25-a-672 antibody which do not block the binding of CD25 to IL-2 or IL-2 signalling. The claimed antibody binds to the epitopes: PHATFKAMA YKEGTM (42-56) and YQCVQGYRALH (150-160) on CD25. Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical compositions and methods of treatment, in particular for treating cancer.