Target engagement markers to take the right drug to the market – PET tracers

We were asked to investigate a dual receptor agonist on target engagement of both receptors. Due to somewhat overlapping pharmacological effects of receptor agonism, the ability to distinguish the individual receptor’s contribution was limited. Also, a better understanding of how to weigh the level of receptor agonism against each other was sought for.

First-in-class PET tracer for the glucagon receptor

We developed positron emission tomography (PET) tracers against both receptors in order to investigate receptor occupancy by using dynamic PET scan technology and modelling. Receptor occupancy would thus be an important target engagement biomarker for the therapeutic effect of the receptor binding candidate drug. Tracers were developed in collaboration with the pharmaceutical company from in vitro characterization, through small and large animal in vivo verification, safety and dosimetry to GMP qualification of tracers and a clinical trial in T2D patients. The development of tracers, for which one was novel and the first to be used in man, resulted in a successful clinical trial generating timely support to mile-stone transition decision for the pharmaceutical company. In addition, this work has contributed significantly to science in this field and has generated several published articles in peer-reviewed scientific journals.

(presented at EASD 2017 and EASD 2019)

EASD

“Direct assessment of in vivo target engagement assists decision-making throughout the clinical phases of drug development.”

Olof Eriksson

Director PET Imaging

Target engagement in type 2 diabetes

Type 2 diabetes affects over 400 million people worldwide (WHO 2019). Although significant advances have been made in diabetes medicine there remains substantial unmet medical need. For new candidate drugs, it is necessary to have tools to investigate novel mechanisms of actions, efficacy and tissue distribution in order to guide development programme strategies or to differentiate against competition. In addition, complexity is increasing with e.g. dual or trigonal agonists that bind several targets with different but also overlapping biological effects. Therefore, sophisticated solutions are required for studying target engagement in clinical trials.

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