Ligand Technology

  • Ligands

    TDCs can employ a variety of ligands. These include small molecule ligands, peptides and peptidomimetics, and antibody fragments (including our DVD-Fab technology described below). This enables the intact TDCs to be cleared from the body within 24-36 hours after dosing which minimizes systemic exposure and can both reduce off-target systemic toxicity as well as allow the mitigation of adverse effects by managing dose and scheduling. Furthermore, the smaller size of TDCs containing small molecule or antibody fragment ligands is expected to improve tumor penetration, further improving activity.

    TDCs can also employ antibody ligands when required by selecting and using SiLinkers with prolonged stability at physiological pH. When coupled to our payload cassettes this enables us to uniformly and stoichiometrically attach a discrete number of payloads to the antibody ligand. Using this approach we believe we can routinely generate SiLinker ADCs with a Drug-to-Antibody Ratio (DAR) of six or more. We believe this attribute of our technology may be best explored in collaboration with ADC companies looking to explore higher DARs in their ADC programs.

  • DVD-Fab Ligand Technology

    Our Dual Variable Domain (DVD) ligand targeting technology, DVD-Fabs, contain the Fab variable regions present in all antibodies that function as “recognition motifs” allowing specific binding of antibodies to receptors or other cell surface proteins. DVD-Fabs are antibody fragments that do not contain the large Fc component of full antibody molecules. They are modular in that targeting regions can be adapted to essentially any receptor an antibody can be raised against. Our DVD-Fabs contain a reactive chemical group allowing us to seamlessly connect them with our payloads and payload cassettes.

  • DVD-Fab Ligand

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