S2: Compound's target occupancy profile

How to best optimize your compound's target occupancy profile, also considering long residence times?
Maarten Huisman, PhD

Maarten Huisman, PhD


Janssen Pharmaceutical Companies
of Johnson & Johnson


Maarten Huisman, PhD


Long residence times gained interest in the pharmaceutical industry with two main drivers. Firstly, to overcome a poor PK profile.

Secondly, to keep exposures as low as possible to improve the safety profile of the IND/NME. Target occupancy is the result of a complex interplay between PK, affinity, binding kinetics and the biology of the target.

Depending the required target occupancy profile (e.g. 50±10% or always >90%), the properties to optimize for may be very different.

To improve drug design we developed, and applied, extremely early an in silico PK/PD model, using only the available data at that stage (mouse PK, binding kinetic parameters, and target turnover rate).

During the presentation the concept of long residence times and binding kinetics will be explained as well as the above mentioned complex interplay. The presentation will focus on what properties to optimize for to steer towards the desired target occupancy profile.