Despite its promising therapeutic efficacy in patients with narcolepsy type 1, the previously reported orally available orexin OX2 receptor (OX2R) agonist TAK-994 has also demonstrated off-target liver toxicity. Now, researchers from Takeda Pharmaceutical Co. Ltd. have reported the discovery and early evaluation of a new OX2R agonist, TAK-861, being developed for the treatment of narcolepsy and other hypersomnia disorders.