Shanghai, April 20th, 2026 — Luye Pharma Group today announced that the first subject has been enrolled in a U.S. pharmacokinetic (PK) bridging clinical trial of its new molecular entity LY03015. This is the world’s first investigational drug designed to inhibit vesicular monoamine transporter 2 (VMAT2) and activate sigma-1 receptor (Sigma-1R). It is intended for the treatment of tardive dyskinesia (TD) and Huntington’s disease (HD).
By targeting VMAT2 and Sigma-1R, LY03015 is designed to control the symptoms of both TD and HD and potentially modify their pathologies. On the one hand, it reduces the release of presynaptic neuronal dopamine (DA) by inhibiting the function of VMAT2, thereby reducing the stimulation of supersensitive D2 receptors by DA without blocking postsynaptic D2 receptors, which may help alleviate symptoms. On the other hand, by activating Sigma-1R, it may also stimulate the release of brain-derived neurotrophic factor (BDNF) and promote synaptic remodeling to help restore the impaired corticostriatal synaptic connectivity, with the potential to provide a sustained symptom relief and reduce recurrence following treatment discontinuation.
The clinical trial being conducted in the U.S. is an open-label, single-dose, and parallel-group bridging study designed to evaluate the safety, tolerability, and pharmacokinetic profile of LY03015 in healthy Chinese and Caucasian adults, providing key evidence to support dose selection for subsequent U.S. Phase Ⅱ and Phase Ⅲ clinical trials. Luye Pharma has a long-established presence in the central nervous system (CNS) therapeutic area. Being another investigational CNS drug under development in both China and the U.S., LY03015 is expected to complete a Phase Ⅱ clinical trial in China soon.
TD is a movement disorder characterized by abnormal involuntary movements associated with the long-term use of dopamine receptor-blocking agents, including antipsychotic medications. Approximately 67% to 89% of the patients with TD experience permanent involuntary movements, resulting in a high rate of disability1. Among patients receiving antipsychotic medications, the average prevalence of TD is approximately 25.3%2. HD is an autosomal dominant neurodegenerative disorder, with typical symptoms including choreiform involuntary movements, cognitive impairment, and psychiatric or behavioral abnormalities3.
VMAT2 inhibitors have been the only class of drugs approved by the U.S. Food and Drug Administration (FDA) for the treatment of TD and HD to date. There is a substantial unmet need in treating the two diseases. Luye Pharma will accelerate the clinical development of LY03015 in both China and the U.S. to further validate its therapeutic potential and enhance the company’s competitive edge in this field.
The CNS therapeutic area is a strategic focus for Luye Pharma. The company has built a differentiated product portfolio targeting multiple conditions such as major depressive disorder, schizophrenia, bipolar disorder, and Alzheimer’s disease. This portfolio includes two extended-release injectable suspensions -- Erzofri® (paliperidone palmitate) and Rykindo® (risperidone), both approved for marketing in the U.S.; the Rivastigmine Twice Weekly Transdermal Patch, which has been approved for marketing in Japan, China, and several European countries; and Ruoxinlin® (Toludesvenlafaxine Hydrochloride Sustained-Release Tablets), which has been approved for marketing in China. Luye Pharma is also conducting clinical trials for several other investigational drugs, including LY03017, which targets 5-HT2AR/5-HT2CR, LY03020, which targets TAAR1/5-HT2CR, and LY03021, which targets GABAAR/NET/DAT.
References:
1. Wang Xixi, Wan Xinhua. Clinical Diagnosis and Treatment of Tardive Dyskinesia [J]. Medical Journal of Peking Union Medical College Hospital, 2022,13(4): 644-651, DOI: 10.12290/xhyxzz.2021-0717.
2. Liang Q, Wang D, Zhou H, et al. Tardive dyskinesia in Chinese patients with schizophrenia: Prevalence, clinical correlates and relationship with cognitive impairment. Journal of Psychiatric Research. 2022;151:181–187.
3. Chinese Society of Neurogenetics. Chinese guidelines for diagnosis and treatment of Huntington’s disease 2023 [J]. Chinese Neurosurgical Journal, 2023, 56(8): 848-855. DOI: 10.3760/cma.j.cn113694-20221226-00968.
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