Abstract: The present invention relates to polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which bind to P-selectin. The invention also relates to multimeric binding complexes of polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold that are binders of P-selectin. The invention also includes drug conjugates comprising said peptides and complexes, conjugated to one or more effector and/or functional groups, to pharmaceutical compositions comprising said peptide ligands, complexes and drug conjugates and the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by a cell adhesion molecule, such as P-selectin, including vaso-occlusive crisis and sickle cell disease-related conditions, cancer, or COVID-19.

Abstract: The present invention relates to polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of Nectin-4. The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and/or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by Nectin-4.

Abstract: The present invention relates to polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which bind to P-selectin. The invention also relates to multimeric binding complexes of polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold that are binders of P-selectin. The invention also includes drug conjugates comprising said peptides and complexes, conjugated to one or more effector and/or functional groups, to pharmaceutical compositions comprising said peptide ligands, complexes and drug conjugates and the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by a cell adhesion molecule, such as P-selectin, including vaso-occlusive crisis and sickle cell disease-related conditions, cancer, or COVID-19.

Abstract: The present invention relates to a heterotandem bicyclic peptide complex which comprises a first peptide ligand, which binds to Nectin-4, conjugated via a linker to two second peptide ligands, which bind to CD137. The invention also relates to the use of said heterotandem bicyclic peptide complex in preventing, suppressing or treating cancer.

Abstract: The present invention relates to heterotandem bicyclic peptide complexes which comprise a first peptide ligand, which binds to a component present on a cancer cell, conjugated via a linker to one or more second peptide ligands, which bind to one or more components present on a natural killer (NK) cell. The invention also relates to the use of said heterotandem bicyclic peptide complexes in preventing, suppressing or treating cancer.

Abstract: The present invention relates to drug conjugates comprising at least two polypeptides which are each covalently bound to non-aromatic molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. The invention also relates to pharmaceutical compositions comprising said drug conjugates and to the use of said drug conjugates in preventing, suppressing or treating diseases, such as those which may be alleviated by cell death, in particular diseases characterised by defective cell types, proliferative disorders such as cancer and autoimmune disorders such as rheumatoid arthritis.

Abstract: The present invention relates to a heterotandem bicyclic peptide complex which comprises a first peptide ligand, which binds to Nectin-4, conjugated via a linker to two second peptide ligands, which bind to CD137. The invention also relates to the use of said heterotandem bicyclic peptide complex in preventing, suppressing or treating cancer.

Abstract: The present invention relates to polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which bind to natural killer (NK) cells. The invention also includes multimeric binding complexes comprising at least two of said bicyclic peptide ligands. The invention also includes pharmaceutical compositions comprising said peptide ligands or said multimeric binding complexes and the use of said peptide ligands, multimeric binding complexes and pharmaceutical compositions in preventing, suppressing or treating a disease or disorder mediated by natural killer (NK) cells, such as inflammatory disorders, autoimmune disease and cancer.

Abstract: The present invention relates to multimers of polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. The invention also describes the multimerization of polypeptides through various chemical linkers and hinges of various lengths and rigidity using different sites of attachments within polypeptides. In particular, the invention describes multimers of peptides which are high affinity binders of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly the spike protein S1 of SARS-CoV-2. The invention also includes pharmaceutical compositions comprising said polypeptides and to the use of said polypeptides in suppressing or treating a disease or disorder mediated by infection of SARS-CoV-2 or for providing prophylaxis to a subject at risk of infection of SARS-CoV-2.

Abstract: The present invention relates to multimers of polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. The invention also describes the multimerization of polypeptides through various chemical linkers and hinges of various lengths and rigidity using different sites of attachments within polypeptides. In particular, the invention describes multimers of peptides which are high affinity binders of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly the spike protein S1 of SARS-CoV-2. The invention also includes pharmaceutical compositions comprising said polypeptides and to the use of said polypeptides in suppressing or treating a disease or disorder mediated by infection of SARS-CoV-2 or for providing prophylaxis to a subject at risk of infection of SARS-CoV-2.

Abstract: The present invention relates to polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of Nectin-4. The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and/or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by Nectin-4.

Abstract: The present invention relates to a method for determining an extent of cyclisation of a peptide ligand displayed on a genetic display system, wherein the peptide ligand comprises a polypeptide covalently linked to a molecular scaffold at two or more amino acid residues, comprising the steps of exposing the polypeptide displayed on the genetic display system to the molecular scaffold, wherein said polypeptide comprises two or more peptide reactive groups on said two or more amino acid residues which form covalent bonds with the molecular scaffold at two or more scaffold reactive groups, to give the peptide ligand; removing unreacted molecular scaffold from the genetic display system; exposing the peptide ligand displayed on the genetic display system to a first probe, wherein the first probe binds to a first unconjugated reactive group on the peptide ligand; and measuring the first unconjugated reactive group on the peptide ligand.

Abstract: A peptide ligand specific for EphA2 comprising a polypeptide comprising three residues selected from cysteine, L-2,3-diaminopropionic acid (Dap), N-beta-alkyl-L-2,3-diaminopropionic acid (N-AlkDap) and N-beta-haloalkyl-L-2,3-diaminopropionic acid (N-HAlkDap), with the proviso that at least one of said three residues is selected from Dap, N-AlkDap or N-HAlkDap, the said three residues being separated by at least two loop sequences, and a molecular scaffold, the peptide being linked to the scaffold by covalent alkylamino linkages with the Dap or N-AlkDap or N-HAlkDap residues of the polypeptide and by thioether linkages with the cysteine residues of the polypeptide when the said three residues include cysteine, such that two polypeptide loops are formed on the molecular scaffold.

Abstract: A peptide ligand specific for MT1-MMP comprising a polypeptide comprising two diaminopropionic acid (Dap) or N-alkyldiaminopropionic acid (N-AlkDap) residues, and a third residue selected from cysteine, Dap or N-AlkDap, separated by at least two loop sequences, and a molecular scaffold, the peptide being linked to the scaffold by covalent alkylamino linkages with the Dap or N-AlkDap residues of the polypeptide and by covalent thioether linkages with the cysteine when the third residue is cysteine, such that two polypeptide loops are formed on the molecular scaffold, wherein the peptide ligand comprises an amino acid sequence of formula (II): -A1-X1-U/O2-X3-X4-G5-A2-E6-D7-F8-Y9-X10-X11-A3- (SEQ ID NO: 1) (II) or a pharmaceutically acceptable salt thereof; wherein: A1, A2, and A3 are independently cysteine, L-2,3-diaminopropionic acid (Dap), N-beta-alkyl-L-2,3-diaminopropionic acid (N-AlkDap), or N-beta-haloalkyl-L-2,3-diaminopropionic acid (N-HAlkDap), provided that at least one of A1, A2, and A3 is Dap, N-Alk

Abstract: The present invention relates to polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of Nectin-4. The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and/or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by Nectin-4.

Abstract: A compound comprising at least one looped peptide structure attached via at least one alkylamino linkage to a scaffold. Preferably the looped peptide structure is a Bicycle structure comprising two peptide loops attached to the scaffold via two alkylamino linkages and one thioether linkage, one of the linkages being common to both loops.

Abstract: The present invention relates to multimers of polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. The invention also describes the multimerization of polypeptides through various chemical linkers and hinges of various lengths and rigidity using different sites of attachments within polypeptides. In particular, the invention describes multimers of peptides which are high affinity binders and activators of CD137. The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and/or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by CD137.

Abstract: The present invention relates to heterotandem bicyclic peptide complexes which comprise a first peptide ligand, which binds to a component present on a cancer cell, conjugated via a linker to two or more second peptide ligands, which bind to a component present on an immune cell. The invention also relates to the use of said heterotandem bicyclic peptide complexes in preventing, suppressing or treating cancer.

Abstract: The present invention relates to polypeptides which are covalently bound to molecular scaffolds such that two peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of IL-17. The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and/or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by IL-17.

Abstract: The present invention relates to polypeptides which are covalently bound to molecular scaffolds such that two peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of IL-17. The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and/or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by IL-17.