Target Mediated Drug Disposition (TMDD)

TMDD occurs when the binding to the target has an effect on drug pharmacokinetics. For most cell surface targets TMDD has to be expected and an appropriate PK/PD strategy has to be put in place. Why? Because in a bad scenario drug can be cleared at a rate making an acceptable dose and dosing schedule for many indications impossible.

For Antibody-Drug Conjugates the situation is different. Effective toxin delivery critically depends on efficient internalisation by the target receptor. Thus, TMDD can be a sign of toxin getting delivered.

What is the solution to TMDD?
An early quantitative assessment of risk with the right experimental strategy – before discovering rapid clearance in first in human studies.