MABTOX

Generation and Evaluation of “Next-generation” Antibody-Toxin-Conjugates for Cancer Therapy

Therapeutic antibodies have transformed cancer therapy during the last decade, due to their high selectivity of targeting cancer cells in comparison to standard small molecule chemotherapy. Most recently, the coupling of cellular toxins to therapeutic antibodies has demonstrated even greater efficacy in the therapy of cancer and the first, highly potent antibody-drug conjugate (ADC), Adcetris®, was FDA approved in August 2011.
All ADCs currently in clinical development are generated by chemical conjugation of small molecule toxins to antibodies. This is an inefficient process, as site and ratio of toxin coupling cannot be controlled. In addition, the chemical conjugation involves chemical modification of potentially functional parts of the antibody. This can have negative effects on stability, specificity, CMC properties and the overall structure of the antibody. All this renders ADC manufacturing highly challenging, complicates regulatory procedures, and adds to development time and costs.
The SME consortium has complementary proprietary technologies and proposes to leverage this complementary expertise and know-how for defining novel processes of enzymatically conjugating small molecule toxins to antibodies that allow full control about toxin coupling site and ratio. Due to the high selectivity of enzymatic conjugation and physiologic conjugation conditions, it is expected that more homogeneous ADCs are generated with better CMC properties, higher potency, and at lower cost-of-goods in manufacturing. The consortium members believe that this represents a disruptive technology that will be highly competitive to traditional chemical conjugation, currently dominated by U.S.-based ADC technology companies Seattle Genetics and Immunogen. In addition to novel composition-of-matter IP, important novel know-how for ADC development will be created. Most importantly, better quality and potency of these “next-generation” ADCs will eventually benefit cancer patients.

• ZIP Solutions S.L., ES
• Tube Pharmaceuticals GmbH, AT
• evitria AG, CH
• Protagen Protein Services GmbH, DE
• Oncotest GmbH Prof. Dr. H. H. Fiebig, DE
• JPT Peptide Technologies GmbH, DE
• Biomedal SL, ES
• TBD-Biodiscovery OU, EE
• InnoTune BVBA, BE