LUYE PHARMA (02186): Innovative drug LY03015 (VMAT2 inhibitor/Sigma-1R agonist) successfully completed bridging clinical trials in the United States.

LUYE PHARMA (02186) has announced that its independently developed new molecular entity LY03015 has successfully completed bridging clinical trials in the United States, supporting the upcoming efficacy clinical trials in the U.S. The trial also found that the Caucasian population demonstrated better safety tolerance compared to the Chinese population. LY03015 is the world's first vesicular monoamine transporter 2 (VMAT2) inhibitor and Sigma-1R agonist, targeting indications for the treatment of tardive dyskinesia (TD) and Huntington's disease (HD) related chorea. Previously, the group completed a multi-center, randomized, double-blind, placebo-controlled Phase II clinical trial in China, enrolling a total of 121 moderate to severe TD patients. The results showed that after six weeks of continuous administration, all three dosage groups of LY03015 exhibited excellent efficacy, significantly improving TD symptoms swiftly, with a clear dose-response relationship. Among these, the AIMS efficacy rate (the percentage of patients with 50% improvement in the Abnormal Involuntary Movement Scale AIMS 1-7) in the 20 mg dosage group reached 76.5%, surpassing historical treatment levels and nearly doubling compared to the historical data from double-blind controlled registration clinical trials of currently reported first-line treatment drugs. The bridging clinical study being conducted in the United States is an open-label, single-dose, parallel study aimed at evaluating the pharmacokinetics, safety, and tolerance of a single oral administration of LY03015 in the 20 mg dosage group among healthy subjects from China and the Caucasian population. The study included 12 healthy subjects from both Chinese and Caucasian groups, and the results showed that there were no racial differences in pharmacokinetics between the Caucasian and Chinese populations; the overall safety and tolerance were good, with adverse events (TEAEs) being mild during the treatment period, and no serious adverse events (SAEs) occurred; the safety tolerance in Caucasian subjects was significantly better than that in Chinese subjects, with TEAE occurrence rates of 33.3% and 83.3%, respectively. This study confirmed that LY03015 exhibits consistent pharmacokinetics in Caucasian and Chinese populations, with better safety tolerance observed in the Caucasian population. Combining the previous Phase II clinical results from China, the group plans to adopt a simplified administration method for the upcoming efficacy clinical trials in U.S. patients, which is expected to create differentiated market value in terms of efficacy, onset speed, and ease of administration compared to the currently commonly used titration treatment approaches. In addition, the group has long been committed to the central nervous system (CNS) therapeutic field, and LY03015 is another innovative CNS drug being developed simultaneously in China and the United States. The group has now established a portfolio of multiple differentiated first-class innovative CNS small molecules, covering various diseases such as schizophrenia, depression, and Alzheimer's disease; besides LY03015, LY03017 is a new generation 5-hydroxytryptamine 2A receptor (5-HT2AR) inverse agonist and 5-hydroxytryptamine 2C receptor (5-HT2CR) antagonist, with proposed indications including Alzheimers disease with psychotic disorders, Parkinson's disease with psychotic disorders, negative symptoms of schizophrenia, depression, and bipolar disorder; LY03020, as a new generation antipsychotic, is the worlds first trace amine-associated receptor 1 (TAAR1) and 5-hydroxytryptamine 2C receptor (5-HT2CR) dual-target agonist, intended for the treatment of schizophrenia, Alzheimers disease with psychotic disorders, and bipolar disorder. These two innovative molecules have advanced to Phase II clinical trials in China. Additionally, LY03021 is a pioneering three-target antidepressant innovative molecule, acting as a positive allosteric modulator (PAM) of the gamma-aminobutyric acid A receptor (GABAAR), a norepinephrine transporter (NET) inhibitor, and a dopamine transporter (DAT) inhibitor, and it has also progressed to Phase I clinical trials in China.