The next-generation Kv7 opener XEN1101 demonstrated significant seizure reduction in a Phase IIb randomized controlled trial for adult focal epilepsy and is being evaluated in Phase III (44, 115); (3) Second messenger fine-tuning—The neuromodulator-cAMP axis can induce a positive shift in HCN (particularly HCN2/4) gating. This evidence concerns the gene MALAT1 and focal epilepsy.