Our AF Drug Candidates
Xention has identified two potent, selective antagonists of Kv1.5. The first of these, XEN-D0101, has been assessed in a Phase 1 study that utilised extensive cardiovascular safety monitoring to establish the safety of modulating the Kv1.5 target. This compound is currently being assessed in a proof-of-mechanism electrophysiology Phase 1 study at multiple European sites.
XEN-D0103 is more potent and more selective than XEN-D0101 and has recently completed pre-clinical development. XEN-D0103 demonstrates a very high degree of selectivity over non-atrial ion channels such as hERG, Nav1.5 and the L-type cardiac calcium channel. XEN-D0103 causes a significant extension of the action potential duration in human atrial tissue, but has no effect on the action potential duration in human ventricular tissue.
XEN-D0103 demonstrates efficacy in a canine model of AF in the clinical setting. Administration of XEN-D0103 reduced AF duration, AF inducibility and increased the atrial effective refractory period and AF cycle length in a dose-dependent fashion, without significant effects on ventricular action potential or QTc.
Our IKACh programme is undergoing lead optimisation, and potent, selective compounds have already been identified. Evaluation of compounds in pre-clinical AF models indicates that these compounds reduce AF duration and extend atrial refractory period thus demonstrating good in vivo efficacy.