AceLink Therapeutics’ AL01211 shows promising results in Phase 2 Fabry disease trial

AceLink Therapeutics, Inc., a clinical-stage biotechnology company focused on next-generation therapies, has released promising interim data from its Phase 2 clinical trial evaluating AL01211 in treatment-naïve, classic male Fabry disease patients. The findings, presented during a late-breaking oral session at the 2025 WORLD Symposium in San Diego, California, underscore the potential of AL01211 as an effective oral substrate reduction therapy (SRT) for Fabry disease, offering hope for improved patient outcomes.

AL01211, a proprietary glucosylceramide synthase (GCS) inhibitor, is designed to provide an oral alternative to enzyme replacement therapy (ERT), which has long been the standard treatment for Fabry disease. The investigational drug demonstrates high potency with single-digit nanomolar IC50, strong selectivity, and pharmacological properties that support once-daily oral administration. This innovation could eliminate the need for frequent intravenous infusions, which often pose a burden for patients managing this rare, inherited disorder.

What is AL01211 and how does it target Fabry disease?

Fabry disease is a rare genetic disorder caused by mutations in the GLA gene, leading to deficient activity of the enzyme alpha-galactosidase A. This deficiency results in the accumulation of harmful substances known as glycosphingolipids, particularly globotriaosylceramide (GL3), in various tissues. This buildup can cause severe complications, including kidney failure, heart disease, and stroke.

AL01211 is a non-brain-penetrant GCS inhibitor that works by reducing the synthesis of glycosphingolipids, effectively addressing the root cause of Fabry disease. By inhibiting GCS, AL01211 disrupts the production of GL3, thus preventing its harmful accumulation. This approach represents a shift from traditional therapies like ERT, which primarily focus on replacing the deficient enzyme but do not fully halt the production of glycosphingolipids.

According to interim data from the ongoing Phase 2 study, AL01211 has shown promising results in reducing GL3 levels, stabilizing key clinical markers, and improving the overall health of Fabry disease patients.

What are the key findings from AceLink Therapeutics’ Phase 2 clinical trial?

The Phase 2 open-label trial is designed to assess the safety, pharmacokinetics, pharmacodynamics, and therapeutic efficacy of AL01211 in classic male Fabry disease patients who have not previously received approved treatments. AceLink Therapeutics successfully enrolled 18 patients across six clinical sites in China, with patient enrollment completed in December 2024. Topline results from this trial are anticipated in the third quarter of 2025.

Interim results reveal that AL01211 is generally safe and well tolerated. Patients receiving a 30 mg daily dose of AL01211 experienced a 50% reduction in GL3 substrate levels, while those on a higher dose of 60 mg exhibited even more rapid and substantial decreases. This dose-dependent response suggests that AL01211 effectively reduces glycosphingolipid accumulation, a key therapeutic target in Fabry disease management.

In addition to biochemical improvements, preliminary clinical data indicate that AL01211 helps stabilise disease progression. Patients showed improvements in kidney function markers, such as estimated glomerular filtration rate (eGFR) and proteinuria levels. Moreover, positive trends were observed in pain reduction, quality of life assessments, and overall symptom management. These findings highlight the potential of AL01211 to offer comprehensive benefits beyond biomarker changes, addressing both the physical and emotional burdens of Fabry disease.

What do experts say about the potential of AL01211?

Dr. Yan Ouyang, a leading investigator from Professor Nan Chen’s team at Ruijing Hospital, presented the interim findings at the WORLD Symposium. According to Dr. Chen, the results demonstrate encouraging safety and efficacy trends for AL01211, underscoring its potential to fill critical gaps in current Fabry disease treatment options. Dr. Chen expressed optimism about the ongoing research, noting that further data will help validate the drug’s role in the broader Fabry disease treatment landscape.

Michael Babcock, Head of Research and Development at AceLink Therapeutics, highlighted the company’s commitment to advancing therapies for rare diseases. He stated that AL01211 represents a significant step forward in the development of oral substrate reduction therapies, which could transform the lives of patients with glycosphingolipid-related disorders. Babcock also acknowledged the invaluable support from the patient community and clinical investigators, whose participation is crucial in driving rare disease research forward.

How does AL01211 fit into the future of Fabry disease treatment?

Founded in 2018, AceLink Therapeutics is dedicated to addressing unmet medical needs through the development of innovative therapies for inherited metabolic disorders. The company’s pipeline includes programs targeting both Fabry disease and Type 1 Gaucher disease, reflecting its focus on conditions linked to glycosphingolipid metabolism.

AL01211’s potential as an oral therapy offers significant advantages over traditional ERT, including improved patient convenience, reduced treatment burden, and the possibility of greater long-term disease control. As the biotech industry increasingly shifts toward patient-centric treatments, AL01211 stands out as a promising candidate poised to reshape the Fabry disease treatment paradigm.

With final Phase 2 results expected later in 2025, the medical community will be watching closely to see whether AL01211 can deliver on its early promise. If successful, it could pave the way for new standards in rare disease management, offering hope to patients who face limited therapeutic options.