Shanghai, China, June 19, 2024 – Shanghai Henlius Biotech, Inc. (2696. HK) announced that the results from the preclinical study of HLX99, an innovative small molecule drug independently developed by the company, was released as a poster presentation at the ENCALS (European Network to Cure ALS) meeting 2024, which was hosted in Stockholm, Sweden.

HLX99 is the first innovative product of Henlius in the treatment field of neurodegenerative diseases. Neurodegenerative diseases, such as Amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD), etc. are accompanied with dysfunction of multiple systems including the dysregulation of gut microbiota. The causal relationships are still not well established due to the lack of longitudinal data, drug intervention data, etc. However, accumulated data suggest a critical role of gut microbiota in these diseases and therapeutics targeting gut microbiota dysbiosis induced host metabolism dysregulation may hold a great promise for the treatment of neurodegenerative diseases.

HLX99, with multiple pharmacological activities, such as microbiota regulation, immune regulation and oxidative stress inhibition, is a potential treatment strategy for neurodegenerative diseases. In vitro, HLX99 protected H₂O₂ induced neuronal death and abnormal T cell proliferation. In vivo, in the SOD1^G93A ALS transgenic mouse model, HLX99 prolonged the survival of ALS transgenic mice, delayed the symptom onset, decreased the disease severity and improved the muscle stress. Importantly, neurofilament light chain (NFL), a well-accepted ALS biomarker, was significantly decreased after the treatment. Furthermore, in the MPTP induced PD model, HLX99 ameliorated MPTP-induced grip strength decrease and loss of dopamine neuron. In another 6-OHDA induced PD model, HLX99 improved the fault step rate as well. Mechanistically, 16s RNA sequencing of microbiota showed that HLX99 recondition the gut microbiota composition to a relative healthy state. And subsequently, the blood metabolites were also regulated by HLX99. 

In conclusion, these data showed that HLX99 exhibits anti-neurodegenerative activities in multiple models. HLX99 has therapeutic effects on multiple pathogenic factors in the management of neurodegenerative diseases. Plus its excellent preclinical safety profile, HLX99 may represent an attractive therapeutic strategy for the treatment of neurodegenerative diseases. Our data warrant further development of HLX99 into the clinical setting.