Example of HTV strategy (for GPR103 antagonist in obesity and weight management)

TimescaleProject Start6 mo12 mo18+ mo
HTV statusLow (level 9)Low (level 8)Medium (level 6)High (level 2)
Target present in correct tissueTarget/pathway is altered in healthy vs. diseased populationPathway-related effect in clinical challenge modelClinical tool is hitting the target
EvidencemRNA expression data demonstrated GPR103 expression in human brain, including the hypothalamus, and QRFP (endogenous ligand) expression and binding in human hypothalamic neurons
Key activitiesIs there evidence that the GPR103 pathway and/or its ligands are dysregulated in obese patients (in silico analysis of internal and external databases)?Is there evidence that the GPR103 receptor ligands QRFP26 and QRFP43 are present in either the circulation or cerebrospinal fluid at different levels in humans between fasting and fed states?Does an exploratory clinical tool GPR103 antagonist reduce food intake in humans?
  • QRFP, pyroglutamylated RFamide peptide.