AL1211 is a glucosylceramide synthase (GCS) inhibitor with unique and superior properties to other GCS inhibitors currently approved or in development. AL1211 is more potent and has a better off-target activity profile than other GCS inhibitors.  AL1211 also has excellent penetration into the tissues that are affected in Fabry disease like heart and kidney.  Importantly, AL1211 has low brain penetration, which maximizes the treatment of peripheral organs without concern for negative effects in the brain.

AL1211 provides a more convenient and more effective treatment compared to enzyme replacement therapy (ERT), which requires burdensome intravenous infusions and the benefits can be limited due to poor tissue penetration.

We have conducted IND enabling studies that support the clinical development of AL1211.  We have completed Phase 1 clinical trials of AL1211 in both Australia and China and these studies have shown consistent and robust pharmacokinetic and pharmacodynamic responses with increasing AL1211 exposure corelating with greater reduction in plasma GL1 and GL3 levels.  Importantly, both studies showed that AL1211 was safe and well tolerated, with no observed serious adverse effects at any dose levels tested.  We have received regulatory clearance in both China (NMPA) and US (FDA) to start Phase 2 clinical trials in Fabry patients, which are currently underway. 

AL1211 is also being developed for type I Gaucher disease (non-neuronopathic). Earlier generation GCS inhibitors have shown that they work well to treat type I Gaucher disease.  However, these inhibitors have lower potency, rapid and variable metabolism, and can cause adverse gastrointestinal effects. With superior drug properties including a better safety profile, AL1211 will be a better option for treating this form of Gaucher disease.

Publications and presentations:
Michael Babcock, Jianhong Zheng, Li Li, Marvin Garovoy, Yuqiao Shen. Development of AL01211, a novel Glucosylceramide Synthase Inhibitor, to treat Fabry disease. 7th International Update on Fabry Disease, 29–31 May 2022, Würzburg, Germany
Michael Babcock, Jianhong Zheng, Li Li, Jessica Gail Shurr, Marvin Garovoy, Jerry Shen. Development of AL01211, an oral, non-brain penetrant glucosylceramide synthase inhibitor (GCSi), to treat Fabry disease. World Symposium Feb 22-26 2023, Orlando, Florida
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