LUYE PHARMA has announced that the first patient has been enrolled in the China Phase II clinical trial for its self-developed innovative drug, LY03020. LY03020 is the world's first dual-target agonist targeting Trace Amine-Associated Receptor 1 (TAAR1) and 5-Hydroxytryptamine 2C Receptor (5-HT2CR). It is intended for treating schizophrenia, psychotic disorders associated with Alzheimer's disease, and bipolar disorder. The Phase II trial being conducted in China is a multicenter, randomized, double-blind, parallel-group, placebo-controlled, fixed-dose study. It aims to evaluate the efficacy, safety, and pharmacokinetic profile of LY03020 in patients with acute schizophrenia and to explore its effective dosage range. Previously, LY03020 also received approval to commence clinical trials in the United States, marking it as another innovative drug in the central nervous system (CNS) therapeutic area being developed by the group simultaneously in China and overseas.

Schizophrenia is a chronic, highly relapsing, and disabling disease, affecting approximately 23 million patients globally and 8 million in China. Traditional first- and second-generation antipsychotic drugs are ineffective for about 30% of patients. They primarily improve positive symptoms but have limited efficacy on negative and cognitive symptoms. Furthermore, they are prone to causing adverse reactions such as extrapyramidal symptoms (EPS), weight gain, elevated prolactin levels, and glucose/lipid metabolism abnormalities. LY03020 is a new-generation antipsychotic drug developed based on the group's New Molecular Entity/New Therapeutic Entity technology platform. It functions through dual targeting of TAAR1 and 5-HT2CR, rather than the 5-Hydroxytryptamine 1A Receptor (5-HT1AR). It is well-known that 5-HT1AR becomes desensitized and loses effectiveness after 4-6 weeks of continuous agonism. TAAR1 is primarily expressed on presynaptic membranes; agonizing this receptor can reduce the release of monoamine neurotransmitters like dopamine (DA) and serotonin (5-HT) into the synaptic cleft, thereby improving the core symptoms of schizophrenia. Agonizing 5-HT2CR can further reduce the release of neurotransmitters such as 5-HT, enhancing the control of negative symptoms, and by regulating neuronal firing transmission, it increases the control of positive symptoms. Additionally, it can help control weight gain and reduce metabolic syndrome-related adverse reactions like glucose/lipid metabolism abnormalities.

LY03020 has already demonstrated positive efficacy and safety signals in early-stage studies. Preclinical research results indicate that LY03020 can significantly improve positive and negative symptoms as well as cognitive impairment in schizophrenia. Compared to representative marketed products and products under investigation, it has shown significant effectiveness characteristics, with no observed significant risks of EPS, weight gain, metabolic syndrome (such as glucose/lipid metabolism abnormalities), or gastrointestinal adverse reactions. Results from the China Phase I clinical study indicate that LY03020 was generally safe and well-tolerated. All treatment-emergent adverse events were mild to moderate, with no reports of EPS-related adverse events or serious adverse events.

The group will actively advance the clinical research of LY03020, committed to providing better treatment options for patients and continuously strengthening its competitive advantage in the CNS therapeutic area. The CNS therapeutic area is one of the core strategic focuses for the group. The group has established a series of products with differentiated advantages in this area, covering various conditions including depression, schizophrenia, bipolar disorder, and Alzheimer's disease. These products include Erzofri® (paliperidone palmitate extended-release suspension for injection) and Rykindo® (risperidone extended-release microsphere injection), which are approved in the US; rivastigmine transdermal patch (twice/week), approved in several European countries, Japan, and China; and Ruoxinlin® (hydrochloride torudivaline sustained-release tablets), approved in China. Furthermore, the group's innovative pipeline continues to expand. In addition to LY03020, several other new molecular entities are in clinical stages, including the VMAT2/Sigma-1R dual-target new drug LY03015, the 5-HT2AR/5-HT2CR dual-target new drug LY03017, and the GABAAR/NET/DAT triple-target new drug LY03021.