AL0804 is a highly brain penetrant GCS inhibitor being developed for the treatment of neuronopathic glycolipid storage diseases including Gaucher disease (Type II and III), GM2 gangliosidosis (Tay-Sachs and Sandhoff disease), GM1 gangliosidosis, and certain genetic forms of Parkinson’s disease.  AL0804 has superior potency and brain penetration compared to other brain penetrant GCS inhibitors currently in development for neuronopathic diseases.  In a head-to-head comparison of disease benefit in a mouse model of type 3 Gaucher disease, AL0804 showed significantly superior efficacy compared to the GCS inhibitor Venglustat. 

Preclinical IND enabling studies have been completed for AL0804, which support the further clinical development of AL0804.  A Phase 1/2 clinical trial of AL0804 is planned to start in 2024.

Publications and presentations:

Michael Babcock, Ying Feng, Benjamin Liou, Venette Fannin, Yi Lin, Jerry Shen, Ying Sun. Development of AL00804, a novel brain penetrant glucosylceramide synthase inhibitor, to treat Gaucher disease and other neuronopathic glycosphingolipid storage diseases. World Symposium Feb 22-26 2023, Orlando, Florida