Our Approach

Overview

Our Technology and Scientific Approach

Antibody drug conjugates are an established therapeutic approach in oncology designed to specifically treat tumors while sparing healthy organs or tissue. ADCs consist of three key components: an antigen-specific antibody, a stable linker and a potent chemotherapeutic agent (also known as a warhead or toxin). The proteins predominantly found on the surface of cancer cells and to which the ADC binds are called cancer targets.

ADC Therapeutics’ proprietary ADCs are highly targeted drug constructs that combine monoclonal antibodies specific to surface tumor targets with the latest generation of a novel class of highly potent pyrrolobenzodiazepine (PBD) dimer toxins.

PBD dimers have a different mechanism of action than toxins such as maytansinoids and auristatins, which are commonly used in other ADCs such as those currently on the market. After binding of the antibody to a specific tumor cell surface antigen and internalization of the ADC, the cytotoxic PBD dimer is designed to be released inside the cells where it binds in the minor groove of DNA and forms potent cytotoxic DNA interstrand cross-links. The cross-links formed by the PBD dimer are designed to block cell division and kill the cancer cell. Importantly, PBD dimers are non-distorting of the DNA structure, making them invisible to repair mechanisms and therefore allow the cross-links to persist within the DNA. Together with the fact that PBDs are not a substrate for multidrug resistance proteins, this may result in long, durable responses, even in hard-to-treat tumors. ADC Therapeutics has access to the latest generation of PBD chemistry, which have been shown in preclinical studies to provide a superior therapeutic index compared to ADCs using earlier-generation PBD chemistry.

We believe the unique mechanism of action and “stealth-like” properties of PBD dimer toxins will result in ADC products with superior efficacy and a reduced drug resistance profile.

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