TDCs can employ a variety of ligands. These include small molecule ligands, peptides and peptidomimetics, and antibody fragments. 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.