LUYE PHARMA (02186) the innovative drug of antidepressant category 1 completed the first phase of clinical trial and the first subject has been enrolled.

On August 3rd, LUYE PHARMA (02186) announced that the Phase 1 clinical trial of its self-developed innovative drug LY03021 in China has completed the enrollment of the first subject. LY03021 is a norepinephrine transporter (NET)/dopamine transporter (DAT) inhibitor and a -aminobutyric acid A receptor positive allosteric modulator (GABAAR PAM), intended for the treatment of depression. LY03021 is developed based on LUYE PHARMA's new molecular entity/new therapeutic entity technology platform (NCE/NTE), as a novel antidepressant with a triple-target mechanism. LY03021 acts on the norepinephrine transporter (NET), dopamine transporter (DAT), and -aminobutyric acid A receptor (GABAAR). On one hand, LY03021 precisely targets the synaptic GABAA receptor subtypes 122 and the extrasynaptic GABAA receptor subtypes 43, with a more reasonable ratio of action intensity between 122 and 43 subtypes, enhancing GABA activation on GABAA receptors, regulating the glutamate-GABA balance in the brain, inhibiting overactivation of the hypothalamic-pituitary-adrenal (HPA) axis, and quickly exerting antidepressant effects. On the other hand, LY03021 increases levels of norepinephrine and dopamine by inhibiting NET and DAT, improving core symptoms, anhedonia, and sexual dysfunction in patients with depression. It can also lower sedation, drowsiness, and loss of consciousness due to GABA receptor activation through the "wake-up mechanism" of NE and DA. Non-clinical studies have shown that LY03021 significantly improves depressive symptoms in animal models 24 hours after administration, and its efficacy remains stable after continuous administration for 21 days, demonstrating both rapid onset of action and long-lasting efficacy. Additionally, the product has good safety, with a NOAEL (no observed adverse effect level) more than 50 times the effective dose. The Phase 1 clinical trial in China is a single-center, randomized, double-blind, placebo-controlled, dose-escalation study aimed at evaluating the safety, tolerability, and pharmacokinetic characteristics of LY03021 in healthy subjects.