Abstract: The present invention relates to a kit-of-parts comprising and a composition comprising a polyplex comprising a double stranded RNA (dsRNA) and a polymeric conjugate comprising a polyethyleneimine (PEI), one or more polyethylene glycol (PEG) moieties and one or more targeting moieties, and wherein each of said one or more targeting moieties is capable of 5 binding to PSMA; and at least one least one immune checkpoint modulator, wherein said at least one least one immune checkpoint modulator is capable of modulating an immune checkpoint protein. Further the invention relates to this composition or kit-of-parts for use in the treatment of cancer.

Abstract: The present invention relates to a polyplex for use in the treatment of castration resistant prostate cancer (CRPC) comprising a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEl), one or more polyethylene glycol (PEG) moieties, one or more linkers and one or more targeting moieties, wherein said LPEl is covalently bound to one or more PEG moieties and each of said one or more PEG moieties is conjugated via one of the one or more linkers to one of the one or more targeting moieties, wherein each of said one or more targeting moieties is capable of binding to a cancer antigen, and wherein said cancer antigen is prostate surface membrane antigen (PSMA). Further, the invention relates to a pharmaceutical composition for use in the treatment of CRPC.

Abstract: The present invention relates to a kit-of-parts comprising and a composition comprising a polyplex comprising a double stranded RNA (dsRNA) and a polymeric conjugate comprising a polyethyleneimine (PEI), one or more polyethylene glycol (PEG) moieties and one or more targeting moieties, and wherein each of said one or more targeting moieties is capable of binding to a cancer antigen; and at least one antibody, wherein said at least one antibody is capable of modulating an immune checkpoint protein. Further the invention relates to this composition or kit-of-parts for use in the treatment of cancer.

Abstract: The present invention relates to dual-site BACE1 inhibitors, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.

Abstract: The present invention relates to a polyplex for use in the treatment of castration resistant prostate cancer (CRPC) comprising a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEl), one or more polyethylene glycol (PEG) moieties, one or more linkers and one or more targeting moieties, wherein said LPEl is covalently bound to one or more PEG moieties and each of said one or more PEG moieties is conjugated via one of the one or more linkers to one of the one or more targeting moieties, wherein each of said one or more targeting moieties is capable of binding to a cancer antigen, and wherein said cancer antigen is prostate surface membrane antigen (PSMA). Further, the invention relates to a pharmaceutical composition for use in the treatment of CRPC.

Abstract: Provided herein are peptides having dual-site BACE1 inhibitory activity, useful for the treatment of, for example Alzheimer's disease and diabetes. One such peptide is a dual-site BACE1 inhibitor, or a pharmaceutically acceptable salt thereof, binding to both an enzymatic active site and an catalytic domain of the BACE enzyme, and an exosite inhibitory part is connected to an active-site inhibitory part of the dual site BACE1 inhibitor by a linker.

Abstract: The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8 and R9 are as described herein, compositions including the compounds and methods of using the compounds.

Abstract: The present invention relates to dual-site BACE1 inhibitors, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.

Abstract: Herein is reported a fusion polypeptide comprising i) one, two, three or four incretin receptor ligand polypeptides, and ii) one human immunoglobulin Fc-region, wherein at least one of the incretin receptor ligand polypeptides comprises an amino acid that is covalently conjugated to a lipid, and wherein each of the one, two, three or four incretin receptor ligand polypeptides is covalently conjugated by a peptide bond to a terminus of the human immunoglobulin Fc-region, whereby to each terminus of the human immunoglobulin Fc-region only a single incretin receptor ligand polypeptide is conjugated.

Abstract: The present invention relates to dual-site BACE1 inhibitors, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.

Abstract: The present invention relates to dual-site BACE1 inhibitors, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.

Abstract: The invention provides novel compounds and conjugates of these compounds useful for the delivery of biologically active substances. Further novel design criteria for chemically stabilized siRNA particular useful when covalently attached to a delivery polymer to achieve in vivo mRNA knock down are disclosed therein.

Abstract: Provided herein are glucagon analogs which exhibit potent activity at the GIP receptor, and, as such are contemplated for use in treating diabetes and obesity. In exemplary embodiments, the glucagon analog of the present disclosures exhibit an EC50 at the GIP receptor which is within the nanomolar or picomolar range.

Abstract: The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8 and R9 are as described herein, compositions including the compounds and methods of using the compounds.

Abstract: Provided herein are glucagon analogs which exhibit potent activity at the GIP receptor, and, as such are contemplated for use in treating diabetes and obesity. In exemplary embodiments, the glucagon analog of the present disclosures exhibit an EC50 at the GIP receptor which is within the nanomolar or picomolar range.

Abstract: The present invention relates to dual-site BACE1 inhibitors, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.

Abstract: The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to cell in vivo. The pharmacokinetic modulator improve in vivo targeting compared to the targeting ligand alone. Targeting ligand-pharmacokinetic modulator targeting moiety targeted RNAi polynucleotides can be administered in vivo alone or together with co-targeted delivery polymers.

Abstract: The invention provides novel compounds and conjugates of these compounds useful for the delivery of biologically active substances. Further novel design criteria for chemically stabilized siRNA particular useful when covalently attached to a delivery polymer to achieve in vivo mRNA knock down are disclosed therein.

Abstract: Herein is reported a fusion polypeptide comprising i) one, two, three or four incretin receptor ligand polypeptides, and ii) one human immunoglobulin Fc-region, wherein at least one of the incretin receptor ligand polypeptides comprises an amino acid that is covalently conjugated to a lipid, and wherein each of the one, two, three or four incretin receptor ligand polypeptides is covalently conjugated by a peptide bond to a terminus of the human immunoglobulin Fc-region, whereby to each terminus of the human immunoglobulin Fc-region only a single incretin receptor ligand polypeptide is conjugated.

Abstract: The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to cell in vivo. The pharmacokinetic modulator improve in vivo targeting compared to the targeting ligand alone. Targeting ligand-pharmacokinetic modulator targeting moiety targeted RNAi polynucleotides can be administered in vivo alone or together with co-targeted delivery polymers.