EHMTI-0315. AMG 334, the first potent and selective human monoclonal antibody antagonist against the CGRP receptor

Results AMG 334 is a potent inhibitor of [125I]-CGRP binding to the human CGRP receptor with a Ki of 0.02 nM. It exhibited full inhibition of CGRP-stimulated cAMP production with an IC50 of 2.3 nM in cell-based functional assays. Potency of AMG 334 at the cyno CGRP receptor is similar to that at the human receptor, but with significant reduced potency at dog, rabbit and rat receptors. AMG 334 also demonstrates > 5000-fold selectivity over other closely related receptors in the family. The receptor kinetics studies using [125I]-AMG 334 reveals a dissociation t1/2 off of 67 min. In the cyno study, AMG 334 produces a significant and sustained inhibitory effect on capsaicin-induced increase in dermal blood flow.