(BUSINESS WIRE)–AceLink Therapeutics, Inc., a clinical stage biopharmaceutical company developing the next generation of oral substrate reduction therapies (SRTs) to address significant unmet medical needs and improve the quality of life of patients with inherited disorders of glycosphingolipid metabolism, today announced that it has received clearance from the U.S. Food and Drug Administration (FDA) to initiate a Phase 2 clinical trial of its lead program, AL1211.

“FDA clearance for AL1211 marks an important clinical milestone for AceLink,” said Jerry Shen, Ph.D., Chief Executive Officer and Founder of AceLink Therapeutics. “We are committed to providing a differentiated oral therapy for patients with Fabry Disease and Type 1 Gaucher Disease, who are desperately in need of a more convenient alternative to enzyme replacement therapy, and ultimately a better quality of life.”

AL1211 is an oral glucosylceramide synthase (GCS) inhibitor that is optimized to treat certain glycosphingolipid storage diseases, including Fabry Disease and Type 1 Gaucher Disease. Phase 1 clinical trials evaluated both single ascending dosing and multiple ascending dosing. AL1211 was orally administered to healthy volunteers as a single dose up to 60 mg or multiple doses of up to 30 mg once daily for 14 days. AL1211 was found to be safe and generally well tolerated. A dose-dependent increase in plasma levels of AL1211 correlated with reduction in plasma glucosylceramide, the pharmacodynamic marker of GCS inhibition, with the 30 mg dose levels reducing glucosylceramide by 78%. Globotriasosylceramide (Gb3), the disease-causing lipid of Fabry Disease, was also significantly reduced.

“This decision from the FDA is a critical achievement for our team. Given the encouraging results from our Phase 1 study, we look forward to further investigating AL1211 in our Phase 2 program as we strive to bring a novel treatment option to those patients who need it most,” said Pedro Huertas, M.D., Ph.D., Chief Medical Officer of AceLink. “Our clinical team has diligently prepared for this moment and we are eager to enroll patients as rapidly as possible.”

Phase 2 Trial Design

The Phase 2 trial for AL1211 is a randomized, dose-blinded, active-controlled, dose-ranging study of the safety and pharmacological activity of AL1211 in male patients with classic Fabry disease who are willing to switch from enzyme replacement therapy (ERT) to substrate reduction therapy.

About AL1211

AL1211 is a non-brain penetrating oral inhibitor of GCS, or glucosylceramide synthase, which is an enzyme that facilitates the first step in the production of glycosphingolipids, a diverse group of biologically active fatty molecules. Fabry disease is caused by genetic mutations that result in an abnormal intracellular buildup of the glycosphingolipids globotriaosylceramide (Gb3) and its metabolite lyso-Gb3.

By blocking the activity of GCS, AL1211 is designed to reduce this toxic buildup, decrease inflammation, and improve organ function, ultimately slowing disease progression. According to AceLink, the investigational therapy has high potency against GCS and other pharmacological properties which will allow once-daily oral dosing. Of note, the therapy is unable to cross the blood-brain barrier, meaning it will not get into the brain, therefore reducing the potential for adverse effects on the central nervous system.

About GCS inhibitor

GCS (glucosylceramide synthase) catalyzes the first step in the synthesis of glycosphingolipids, a group of bioactive molecules that play important roles in various cellular processes and diseases. GCS inhibitors reduce the production of glycosphingolipids, thereby exerting beneficial effects to diseases such as Fabry disease and Gaucher disease, which are caused by the accumulation of these lipids.

About Fabry Disease

Fabry Disease is a rare inherited disorder of glycosphingolipid (fat) metabolism resulting from the absent or markedly deficient activity of the lysosomal enzyme, α-galactosidase A (α-Gal A). This disorder belongs to a group of diseases known as lysosomal storage disorders. This enzymatic deficiency is caused by alterations (mutations) in the α-galactosidase A (GLA) gene that instructs cells to make the α-galactosidase A (α-Gal A) enzyme. Lysosomes function as the primary digestive tract of cells. Enzymes within lysosomes break down or digest particular compounds and intracellular structures. α-Gal A functions to break down complex sugar-lipid molecules called glycolipids, specifically, globotriaosylceramide (GL-3 or Gb3), its deacylated form Lyso-GL-3/Gb3 and related glycolipids, by removing the terminal galactose sugar from the end of these glycolipid molecules. The enzyme deficiency causes a continuous build-up of GL-3/Gb3 and related glycolipids in the body’s cells, resulting in the cell abnormalities and organ dysfunction that particularly affect small blood vessels, the heart, and kidneys (Desnick 2001, Germain 2010).

About AceLink Therapeutics, Inc.

Founded in 2018, AceLink Therapeutics is a clinical stage pharmaceutical company developing the next generation of oral substrate reduction therapies (SRTs) to address significant unmet medical needs and improve the quality of life of patients with inherited disorders of glycosphingolipid metabolism. The company is developing a pipeline of breakthrough therapeutics including a Phase II program for Fabry Disease and Type 1 Gaucher Disease. For more information, please visit www.acelinktherapeutics.com.