Antibody-Drug Conjugates (ADC)

The present Competitive Intelligence Report about Antibody-Drug Conjugates (ADC) / Immunoconjugates provides a competitor evaluation in the field of tumor targeting antibodies conjugated with a drug payload for treatment of cancer as of June 2009.

The newer generations of antibodies are characterized by having increased effector functions. This can be achieved either by engineering the antibody itself to optimize Fc effector functions such as ADCC and CDC, or adding payload functions to the antibody by incorporating a second targeting specificity to recruit immune effector cells or fusing it with toxins or cytokines. A more mature and advanced technology is conjugating the antibody with a cytotoxic drug moiety. The basic principle of antibody-drug conjugates is to use the antibody moiety for targeting the tumor and for tumor-specific delivery of a cytotoxic agent. One such antibody-drug conjugate (ADC) is already commercially available while other earlier projects were hampered by a small therapeutic window, mainly due to systemic toxicity caused by the premature release of the cytotoxic drug from an instable linker between antibody and drug.

The most advanced technologies today offer stable linker technology and cytotoxic prodrugs which only become effective once the conjugate has entered the tumor cell by endocytosis and the drug cleared by proteolytic digestion from the conjugate inside the cell. A high tumor specific expression of the target is a prerequisite for lowering the systemic side effects of the ADC. The therapeutic window further can be improved if the cytotoxic agent is a prodrug only activated by intracellular enzymes. Further advances have been made by selecting cytotoxic drugs without drug resistance, by using peptide linkers instead of chemical moieties and by

At present, two further antibody-drug conjugates are in pivotal clinical studies and at least four different ADC molecules in phase II clinical evaluation. The early stage clinical pipeline consists of at least seven different phase I ADCs and further six in IND enabling studies. The preclinical pipeline is rather full by more than 9 ADCs in advanced preclinical phase and many more in earlier stages.

The report includes a compilation of current active projects in research and development of antibody-drug conjugates and other immunoconjugates in oncology. In addition, the report lists company-specific R&D pipelines of antibody-drug conjugates. Competitor projects are listed in a tabular format providing information on:

• Drug Codes,
• Target / Mechanism of Action,
• Class of Compound,
• Company,
• Product Category,
• Indication,
• R&D Stage and
• additional comments with a hyperlink leading to the source of information.