Griffin Discoveries aims to develop novel H4R antagonist with a differentiated profile compared to reference ligands and competitor clincical candidates. The antagonist JNJ7777120 is a very potent compound in a variety of in vivo models despite its relatively short pharmacokinetic half-life. We have studied the residence time of this compound and found a dissociative half-life for the histamine H4 receptor of approximately 60 minutes. This relatively long dissociative half-life may explain the exceptional potency of this well known reference antagonist.

Studying target residence time is a concept that is proving to be increasingly important in late stage lead optimization. Not only can it confer improved efficacy to drug candidates, but it also contributes to an improved safety profile because of the lower doses that are needed for pharmacodynamic efficacy.

Griffin Discoveries has recently identified a development candidate that combines an excellent PK profile in rodents with a long dissociative half-life, and thus increased H4 receptor residence time.