Luye Pharma Group Ltd. has announced that LY03015—the industry’s first vesicular monoamine transporter 2 (VMAT2) inhibitor and sigma-1 receptor (Sigma-1R) agonist to reach clinical trials—met its primary endpoint in a multicentre, randomised, double-blind, placebo-controlled Phase 2 trial for tardive dyskinesia (TD) in China.

Key trial metrics • Design: 121 patients with moderate-to-severe TD randomised 1:1:1:1 to receive LY03015 (5 mg, 10 mg or 20 mg) or placebo once daily for six weeks, followed by two-week wash-out. • Efficacy: AIMS item 1–7 response rates showed a dose-response of 25.9 % (5 mg), 52.0 % (10 mg) and 76.5 % (20 mg) versus placebo (p<0.01 for 10 mg and 20 mg). The 20 mg arm nearly doubled historical response rates (~40 %) of current first-line VMAT2 inhibitors. • Symptom improvement: Least-squares mean reductions in AIMS total score exceeded 4.0 points across all dose groups at week 6 (p<0.05 vs. placebo) with ≈3-point improvements sustained two weeks post-treatment, indicating limited rebound. • Safety: No treatment-related serious adverse events; common adverse events were somnolence, akathisia and dizziness, predominantly mild to moderate. No treatment-related QT prolongation observed.

Market and clinical context Tardive dyskinesia affects an estimated 25.30 % of patients on long-term antipsychotics, underpinning a global TD therapeutics market of roughly USD 5.00 billion. Current VMAT2 inhibitors leave about 60 % of patients without clinically meaningful improvement, and carry safety concerns related to off-target metabolites or CYP2D6-dependent metabolism.

Differentiation of LY03015 Developed via Luye Pharma’s AI-enabled drug-design platform, LY03015 combines VMAT2 inhibition with Sigma-1R activation to deliver both symptomatic control (dopamine modulation) and potential disease modification (BDNF-mediated synaptic repair).

Next steps Following completion of the successful China Phase 2 study and last-subject-out of a U.S. pharmacokinetic bridging trial, Luye Pharma intends to initiate parallel Phase 3 trials in China and the United States.

Pipeline overview Leveraging its AI-driven discovery platform, Luye Pharma is advancing a differentiated CNS portfolio, including LY03017 (5-HT2A/2C modulator, Phase 2) and LY03020 (TAAR1/5-HT2C agonist, Phase 2) for psychiatric indications, and LY03021 (GABAAR PAM/NET/DAT inhibitor, Phase 1) for major depressive disorder.