First Patient Enrolled in China for Phase Ⅱ Clinical Trial of Luye Pharma’s Class 1 Innovative Drug Targeting VMAT2/Sigma-1

Shanghai, January 15, 2025 - Luye Pharma Group today announced the enrollment of the first patient in China for a Phase Ⅱ clinical trial of LY03015, a VMAT2 (vesicular monoamine transporter 2) inhibitor and a Sigma-1 receptor agonist. Filed under China’s Class 1 pathway, LY03015 is intended for the treatment of tardive dyskinesia (TD) and Huntington's disease (HD). It is being developed in both China and the U.S., which will further reinforce the company’s central nervous system (CNS) portfolio.

TD is an abnormal, involuntary movement disorder associated with the long-term use of dopamine receptor blockers such as antipsychotics. It is characterized by involuntary, rhythmic, repetitive and stereotyped movements. In 67% to 89% of TD patients, involuntary movements persist permanently, leading to a high rate of disability. The average prevalence of TD among patients taking antipsychotics is 25.3%¹. HD is an autosomal dominant neurodegenerative disorder, with typical symptoms including choreiform involuntary movements, cognitive impairment, and psychiatric or behavioral abnormalities².

VMAT2 inhibitors are currently the only drugs with proven clinical efficacy and safety in the treatment of TD and HD. However, there are still varying degrees of clinical challenges to the currently marketed VMAT2 inhibitors, such as insufficient efficacy due to serious adverse reactions caused by off-target effects, drug metabolism problems, the black box warnings for the increased risk of depression and suicidal thoughts and behaviors, or warnings for the increased cardiovascular risk.

LY03015 is a next-generation VMAT2 inhibitor developed by Luye Pharma on its New Chemical Entity/New Therapeutic Entity (NCE/NTE) platform. It works by inhibiting the transport function of VMAT2, reducing the release of dopamine (DA) from presynaptic neurons, thereby decreasing the DA-induced stimulation of hypersensitive D2 receptors without blocking D2 receptors on the postsynaptic membrane, to help alleviate the symptoms of TD and HD. Meanwhile, LY03015 is potent in agonizing Sigma-1 receptors. The activation of Sigma-1 receptor pathways reduces oxidative stress, provides neuroprotection, and improves cognitive function. This helps to treat TD and HD through multiple mechanisms, leading to better outcomes.

Preclinical studies show that LY03015 is superior to the marketed VMAT2 inhibitors in terms of pharmacologic and pharmacokinetic properties both in vitro and in vivo, having no off-target effects, and better cardiac safety. A Phase Ⅰ clinical trial shows that LY03015 is safe and well-tolerated in general with a relatively long half-life, which can be administered orally once a day. Compared with the marketed VMAT2 inhibitors, LY03015 is not metabolized by CYP2D6, thereby reducing the risk of drug interactions mediated by this enzyme.

The Phase Ⅱ clinical trial of LY03015 to be conducted in China is a multicenter, randomized, double-blind, and placebo-controlled study in TD patients.

Data from IQVIA shows that the three originator drugs based on VMAT2 inhibitors approved for marketing by the U.S. FDA generated approximately USD 3.069 billion in combined worldwide sales in 2023, growing 42% from 2022. In the first half of 2024, their combined worldwide sales were approximately USD 1.812 billion, growing 28% year-on-year.

“Antipsychotics are widely used in clinical practice, but they often lead to movement disorders like TD, a common problem in treating mental illness that seriously compromises patients' quality of life," said Dr. Tian Jingwei, Executive Vice President of Luye Institute for Innovative Research. "There are limited treatments available for TD and HD. Through further clinical trials, LY03015 will have the potential to address the limitations of the currently marketed VMAT2 inhibitors with respect to activity, efficacy, and safety."

There is a huge demand for CNS drugs, including those for treating TD and HD. However, new drug development in this therapeutic area has been relatively slow. Luye Pharma has developed a range of internationally competitive innovative drugs and formulations, and has become a leader among Chinese pharmaceutical companies in this therapeutic area. Here are some examples: Erzofri^® (paliperidone palmitate) extended-release injectable suspension and Rykindo^® (risperidone) for extended-release injectable suspension, both have been approved for marketing in the U.S.; and Ruoxinlin^® (Toludesvenlafaxine Hydrochloride Extended-Release Tablets) and Jinyouping^® (Rotigotine Microspheres for Injection), both have been launched in China. In addition, the company is also conducting clinical studies for several drugs filed under China’s Class 1 pathway, such as LY03020, a dual TAAR1/5-HT_2CR agonist, and LY03021, which targets NET/DAT/GABA_AR.