Figure 3.
Non-linear serum PK for M616 is captured reasonably well by a TMDD model, consisting of target binding parameters limited to the central compartment (see Methods). k12 and k21 first-order distribution rate constants, k21 = k12, kel first-order elimination rate constant, kint mAb-target internalization rate constant, kdeg first-order degradation rate constant for the target, V is the volume of distribution of the drug in the central compartment, Ro baseline target concentration. For the model, the second-order association rate (kon) was derived in the model using relation kon = First-order dissociation rate (koff)/Dissociation rate constant (KD).