Abstract: An amatoxin-linker construct contains an amatoxin according to formula (I) wherein R1 and R2 are each —OH, R3 is NH2, or a linker which carries a reactive group Y for linking said amatoxin to a target-binding moiety, R4 is H or a linker which carries a reactive group Y for linking said amatoxin to a target-binding moiety, R5 is absent or ?O, and wherein R3 and R4 cannot be the same. The amatoxin-linker construct is used in the manufacture of a binding moiety-toxin conjugate for the treatment of a solid tumor, and a respective binding moiety-toxin conjugate can be used for the treatment of a solid tumor.

Abstract: Amatoxins, as well as antibody-drug conjugates (ADCs) comprising an amatoxin are provided, as well as compositions and methods of using the same. The compositions and methods provided herein can be used for cancer therapy. They can also be used to prepare a patient for hematopoietic stem cell transplant therapy and to improve the engraftment of hematopoietic stem cell transplants by selectively depleting endogenous hematopoietic stem cells prior to the transplant procedure. Methods and compositions for the treatment of various hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, as well as prevention of graft-versus-host-disease (GVHD), are provided.

Abstract: Amatoxins, as well as antibody-drug conjugates (ADCs) and compositions have amatoxin and can be used for cancer therapy, to prepare a patient for hematopoietic stem cell transplant therapy and to improve the engraftment of hematopoietic stem cell transplants by selectively depleting endogenous hematopoietic stem cells prior to the transplant procedure. Methods and compositions treat various hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases and prevent graft-versus-host disease (GVHD).

Abstract: The present invention relates to prodrugs comprising a linker comprising five- or six-membered cyclic acetals and an adjacent specific cleavage site, and to precursor compounds for the synthesis of said prodrugs. In one aspect the present invention relates to antibody-targeted amatoxin conjugates comprising said linkers, to methods for their synthesis, and to the use of said antibody-targeted amatoxin conjugates. In a further aspect, the invention relates to pharmaceutical compositions comprising said conjugates, and to the use of said conjugates or compositions for therapeutic purposes, in particular for tumor therapy and oncology.

Abstract: The present invention relates to an amatoxin-linker construct comprising an amatoxin according to formula (I) wherein: R1 and R2 are each —OH, R3 is NH2, or a linker which carries a reactive group Y for linking said amatoxin to a target-binding moiety, R4 is H or a linker which carries a reactive group Y for linking said amatoxin to a target-binding moiety, R5 is absent or ?O, wherein R3 and R4 cannot be the same, for use in the manufacture of a binding moiety-toxin conjugate for the treatment of a solid tumor, and a respective binding moiety-toxin conjugate for the treatment of a solid tumor.

Abstract: A conjugate contains an amatoxin, a target-binding moiety wherein the target is CD37, i.e., a CD37-binding moiety, and optionally a linker linking the amatoxin and said CD37-binding moiety, and the conjugate is prepared in a synthesis method. A pharmaceutical composition contains the conjugate for use in the treatment of immune cell-, particularly B-cell and/or lymphoma associated diseases and/or malignancies.

Abstract: The present application relates to conjugates comprising an amatoxin a target-binding moiety wherein the target is CD37, i.e., a CD37-binding moiety, and optionally a linker linking said amatoxin and said CD37-binding moiety. The invention further relates to the synthesis of said conjugates. In addition, the invention relates to a pharmaceutical composition comprising such conjugate for use in the treatment of immune cell-, particularly B-cell and/or lymphoma associated diseases and/or malignancies.

Abstract: The present application relates to a conjugate comprising an amatoxin, a target-binding moiety wherein the target is CD20, i.e., a CD20-binding moiety, and optionally a linker linking said amatoxin and said CD20-binding moiety. The invention further relates to the synthesis of said conjugate. In addition, the invention relates to a pharmaceutical composition comprising such conjugate, particularly for use in the treatment of B-cell and/or lymphoma associated diseases and/or malignancies.

Abstract: The present disclosure relates to new antibody-drug-conjugates (ADCs) comprising a favorable modular linker linking the pharmaceutically active drug substance with the antibody. The present disclosure further relates to methods of producing the antibody-drug conjugate as well as to uses thereof and pharmaceutical compositions comprising the same. Embodiments of the present disclosure have been particularly developed as antibody-drug conjugates for use in the treatment of Guanylate Cyclase 2C (GUCY2C)-positive gastrointestinal cancers and will be described hereinafter with reference to this application. However, it will be appreciated that the present disclosure is not limited to this particular field of use.

Abstract: The present disclosure relates to modular linker compounds for target-binding drug conjugates (TBDCs) and in particular to modular linker compounds for antibody-drug-conjugates (ADCs). The present disclosure further relates to methods of synthesizing the modular linker compound, to target-binding drug conjugates comprising the modular linker compound of the present disclosure as well as to pharmaceutical compositions comprising target-binding drug conjugates compound of the present disclosure. Embodiments of the present disclosure have been particularly developed as target-binding drug conjugates for use in the treatment of cancer and will be described hereinafter with reference to this application. However, it will be appreciated that the present disclosure is not limited to this particular field of use.

Abstract: The present disclosure pertains to the provision of NAMPT inhibitors, a method of synthesizing the same as well as their use in antibody-drug-conjugates. The present disclosure further pertains to pharmaceutical compositions comprising the NAMPT inhibitors of the disclosure and their use in cancer treatment. In a further aspect, the present disclosure pertains to a method of treatment using the NAMPT inhibitors of the disclosure.

Abstract: The present application relates to conjugates comprising an amatoxin, a target-binding moiety wherein the target is CD37, i.e., a CD37-binding moiety, and optionally a linker linking said amatoxin and said CD37-binding moiety. The invention further relates to the synthesis of said conjugates. In addition, the invention relates to a pharmaceutical composition comprising such conjugate for use in the treatment of immune cell-, particularly B-cell and/or lymphoma associated diseases and/or malignancies.

Abstract: The present application relates to conjugates comprising an amatoxin, a target-binding moiety wherein the target is CD37, i.e., a CD37-binding moiety, and optionally a linker linking said amatoxin and said CD37-binding moiety. The invention further relates to the synthesis of said conjugates. In addition, the invention relates to a pharmaceutical composition comprising such conjugate for use in the treatment of immune cell, particularly B-cell and/or lymphoma associated diseases and/or malignancies (FIG. 1).

Abstract: The invention relates to a conjugate comprising (a) an amatoxin comprising (i) an amino acid 4 with a 6?-deoxy position; and (ii) an amino acid 8 with an S-deoxy position; (b) a target-binding moiety; and (c) optionally a linker linking said amatoxin and said target-binding moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate.

Abstract: The present application relates to a composition comprising (a) at least one immune checkpoint inhibitor and (b) at least one conjugate, wherein said conjugate is comprising (i) a target binding moiety, (ii) at least one amatoxin, and (iii) optionally at least one linker connecting said target binding moiety with said at least one amatoxin. The present application further relates to said composition for use in treating a patient having a cancer, and to a pharmaceutical formulation comprising said composition and additional excipients, as well as to methods of producing and using said composition (FIG. 1).

Abstract: The present application pertains to pharmaceutical compositions for use in the treatment of cancer, whereby said pharmaceutical compositions are administered subcutaneously and wherein the pharmaceutical compositions of the invention comprise at least one conjugate that comprises an antibody which specifically binds to a cell surface antigen on a cancer cell and at least one amatoxin-linker payload. The present invention further pertains to methods of treating a patient afflicted with cancer using the pharmaceutical compositions of the invention.

Abstract: In a first aspect the present application pertains to an anti-GUCY2C antibody, corresponding antibody-drug conjugates comprising amatoxin for use in the treatment of gastrointestinal cancers, such as colorectal cancer, and pancreatic cancer. In a second aspect the present invention pertains to pharmaceutical compositions comprising the antibody-drug conjugates of the invention for use in the treatment of gastrointestinal cancer. The present invention also pertains to methods of treatment of gastrointestinal cancer using the antibody-drug conjugates of the invention.

Abstract: The present application relates to humanized and/or deimmunized antibodies, antibody fragments or antibody derivatives that bind to Prostate Specific Membrane Antigen (PSMA) and methods for using said antibodies, antibody fragments or antibody derivatives in the treatment of prostate cancer and other neoplastic as well as neurological diseases.

Abstract: This application relates to amatoxin analogs in which the trans-4-substituent on the proline residue of the amatoxin is an R group other than a hydroxy, constructs comprising such amatoxin analogs coupled to a linker and conjugates comprising such amatoxin analog-linker constructs conjugated to a target moiety. The application also relates to uses of such amatoxin analogs, for example, in treatment of cancer.

Abstract: The invention relates to methods for synthesizing amanitin derivatives having an amino group attached to position 6? of the central tryptophan moiety. The invention furthermore relates to an amanitin derivative having an amino group attached to position 6? of the central tryptophan moiety, conjugates of such amanitin derivative, and pharmaceutical compositions comprising such conjugates.