Heidelberg Pharma Research Gmbh

Heidelberg Pharma Gmbh

Michael Kulke

Torsten Hechler

Werner Simon

Christian Lutz

Christoph Müller

Susanne Werner-Simon

Andreas Pahl

Jan Anderl

Christoph Mueller

Erwin Boehm

Eggert Stockfleth

Anikó Pálfi

Francesca Gallo

Barbara Korsak

Christoph MÜLLER

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.

B-lymphocyte specific amatoxin antibody conjugates

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.

Amanitin conjugates

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.

Method of treating cancer using amanitin derivatives

The invention relates to novel methods for synthesizing amanitin derivatives having a hydroxy group attached to the central tryptophan moiety. The invention furthermore relates to novel amanitin derivatives having a hydroxy group attached to position 4', 5&#x2032; or 7&#x2032; of the central tryptophan moiety, novel conjugates of such amanitin derivatives, and pharmaceutical compositions comprising such conjugates.

Method for synthesizing amanitins

The invention relates to a PSMA-targeting conjugate comprising (a) an amatoxin; (b) a small molecule PSMA-targeting moiety; and (c) optionally a linker linking said amatoxin and said small molecule PSMA-targeting moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate.

PSMA-targeting amanitin conjugates

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 BCMA-binding moiety comprising (i) the variable domains of humanized antibody J22.9-ISY, and (ii) a heavy chain constant region comprising a D265C mutation; and (c) a protease-cleavable linker linking said amatoxin and said target-binding moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate, particularly for use in the treatment of multiple myeloma.

Amanitin antibody conjugates

The invention relates to novel methods for synthesizing amanitin derivatives having an amino group attached to position 6' of the central tryptophan moiety. The invention furthermore relates to a novel amanitin derivative having an amino group attached to position 6&#x2032; of the central tryptophan moiety, novel conjugates of such amanitin derivative, and pharmaceutical compositions comprising such conjugates.

The present invention is directed to the systemic administration of Fosfluridine Tidoxil, (5-fluorouridine)-5'-phosphoric acid (3-dodecylmercapto-2-decyloxy)propylester or a salt thereof, for the treatment of intraepithelial proliferative diseases such as actinic keratosis. The Fosfluridine Tidoxil can be systemically administered alone or in combination with topical treatment agents.

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Ladenburg, Germany

Michael Kulke