Luye Pharma’s Dual TAAR1/5-HT2CR Agonist LY03020 Approved for Clinical Trials in China

Shanghai, August 5, 2024 - Luye Pharma Group today announced that the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) has approved its Investigational New Drug (IND) application for LY03020 filed under the Class 1 pathway for investigational drugs. LY03020, a dual TAAR1/5-HT_2CR agonist, is intended to treat schizophrenia and Alzheimer's disease psychosis (ADP).

Developed on Luye Pharma's New Chemical Entity/New Therapeutic Entity (NCE/NTE) platform, LY03020 is a next-generation antipsychotic and the first agonist against both the trace amine-associated receptor 1 (TAAR1) and the 5-HT_2C receptor (5-HT_2CR) in the world.

"Unlike the existing antipsychotics that typically antagonize D2 and 5-HT2A receptors on the postsynaptic membrane, the next-generation antipsychotics agonize those receptors on the presynaptic membrane. Compared with the existing antipsychotics, LY03020 targets both TAAR1 and 5-HT_2CR, and thus is able to reduce adverse reactions such as extrapyramidal symptoms (EPS) and metabolic syndromes while significantly improving the negative symptoms and cognitive impairments associated with schizophrenia. It is expected to address the unmet treatment needs of patients." said Dr. Tian Jingwei, Executive Vice President of Luye Institute for Innovative Research. "In the Central Nervous System (CNS) therapeutic area, we have successfully built a differentiated portfolio of innovative products, and we are also actively exploring and developing the next-generation drugs with new mechanisms of action, to meet the treatment needs of more and more patients, and to maintain our leading edge in this therapeutic area."

Schizophrenia is a severe mental disorder affecting approximately 8 million people in China.¹ About 30% of the treatment-resistant schizophrenia patients do not respond well to the first- and second-generation antipsychotics.² Additionally, 9.83 million people in China suffer from Alzheimer's disease, and this number is still growing.³ Approximately 30% of those patients would experience ADP, typically manifested by aggressive behaviors, agitations, hallucinations, or delusions,⁴ imposing a significant burden to their caregivers and the entire society physically or financially.

LY03020 targets both TAAR1 and 5-HT_2CR. TAAR1 is primarily expressed on the presynaptic membrane, and its activation reduces the release of monoamine neurotransmitters such as dopamine (DA) and serotonin (5-HT) into the synaptic cleft. 5-HT_2CR is expressed on both pre- and post-synaptic membranes. The activation of presynaptic HT_2CR further lowers the release of neurotransmitters like 5-HT and enhances the inhibition of negative symptoms. The activation of postsynaptic HT_2CR helps to reduce metabolic syndromes such as weight gain and abnormal glucose/lipid levels.

Preclinical studies have demonstrated that LY03020 significantly improves the positive and negative symptoms as well as cognitive impairments associated with schizophrenia, and also significantly improves the positive and negative symptoms of ADP, without noticeable risks for EPS as well as metabolic syndromes like weight gain and abnormal glucose/lipid levels.

There is a huge demand for treatments in the CNS therapeutic area, which includes schizophrenia and Alzheimer's disease. However, new drug development in this area has been relatively slow. Luye Pharma has been working in this area for a long time, and has developed a range of internationally competitive innovative drugs and formulations, making it a Chinese leader in this 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 developing several investigational drugs simultaneously in China and abroad, such as LY03015, which targets VMAT2 and Sigma1.

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About Luye Pharma Group

Luye Pharma Group is an international pharmaceutical company dedicated to the R&D, manufacturing and sale of innovative medications. The company has established R&D centers in China, the U.S. and Europe, with a robust pipeline of over 30 drug candidates in China and more than 10 drug candidates in other international markets. Luye Pharma maintains high-level international standards in novel drug delivery technologies including microspheres, liposomes, and transdermal drug delivery systems. The company has achieved multiple innovations in new chemical entities and antibodies, and is also actively making strategic developments in the fields of cell therapies and gene therapies.

Luye Pharma is developing a global supply chain of 8 manufacturing sites built up around the world, with GMP quality management and control systems established in line with international standards. With more than 30 products covering the central nervous system, oncology, cardiovascular, metabolism and other therapeutic areas, business is conducted in over 80 countries and regions around the world, including the largest pharmaceutical markets -- China, the U.S., Europe and Japan, as well as in fast growing emerging markets.

References：

1. Huang Y, et al. Lancet Psychiatry. 2019;6(3):211-224.
2. Disease Analysis: Schizophrenia. www.datamonitorhealthcare.com.
3. Rujing Ren.et al. The China Alzheimer Report 2022. General Psychiatry. 2022; 35(1): e100751.
4. Cummings J. et al. Criteria for Psychosis in Major and Mild Neurocognitive Disorders: International Psychogeriatric Associations (IPA) Consensus Clinical and Research Definition. Am J of Geriatric Psychiatry. 2020; 28 (12); 1256-1269.