FDA Clears IND for Aro Biotherapeutics' ABX1100 in LOPD Treatment

In a significant advancement for the treatment of Pompe disease, Aro Biotherapeutics, a clinical-stage biotech firm, has announced that its Investigational New Drug Application (IND) for ABX1100 has been approved by the U.S. Food and Drug Administration (FDA). This novel therapy is currently undergoing phase 1 clinical trials in patients with late-onset Pompe disease (LOPD), a rare genetic disorder.

The announcement coincides with a presentation at the 2025 WORLD Symposium™ in San Diego, California, where Aro Biotherapeutics showcased promising data from an initial phase 1 study involving normal healthy volunteers. In this study, ABX1100 demonstrated a significant knockdown of glycogen synthase 1 (GYS1) mRNA and protein in muscle tissue. The therapy was well-received by participants, showing a favorable safety profile and predictable pharmacokinetics in these early trials.

Susan Dillon, Ph.D., the co-founder, president, and CEO of Aro Biotherapeutics, expressed enthusiasm about the FDA’s clearance and the positive results from their phase 1 trial with healthy volunteers. She noted these developments as critical milestones that enhance confidence in continuing patient enrollment for ongoing studies targeting LOPD.

Pompe disease is characterized by a deficiency in an enzyme responsible for breaking down muscle glycogen, causing excessive glycogen accumulation and subsequent muscular dysfunction. ABX1100 utilizes Aro’s Centyrin technology to deliver a short-interfering RNA (siRNA) therapeutic payload directly to muscle tissue. This approach aims to inhibit the production of GYS1, a key enzyme in glycogen synthesis, thereby reducing glycogen levels and offering a potential new treatment option for patients.

The completed phase 1 study on normal healthy volunteers showed that ABX1100 could achieve up to 70% reduction in GYS1 mRNA and protein levels in muscle biopsy samples, ten weeks after administration. This reduction was noted following two doses administered at day one and day 29 of the trial, indicating that the therapy could maintain therapeutic GYS1 reduction levels. Pharmacokinetic analysis revealed rapid plasma clearance but sustained muscle presence, supporting the concept of quarterly maintenance dosing after initial loading doses.

Aro Biotherapeutics’ Chief Scientific Officer, Karyn O’Neil, Ph.D., highlighted the significance of these results, emphasizing that they demonstrate consistent, dose-dependent delivery to muscle tissue, allowing for prolonged knockdown of GYS1. This marks a crucial transition from preclinical to clinical stages for their Centyrin-siRNA platform.

Throughout the study, ABX1100 was well-tolerated across all administered doses, with no serious adverse events reported. The majority of side effects were mild and temporary, with no early discontinuations owing to adverse effects and no instances of anemia.

ABX1100, specifically developed for Pompe disease, comprises a CD71 receptor-binding Centyrin conjugated to siRNA, which targets GYS1 mRNA in muscle tissues. This investigational treatment aims to reduce the enzyme's levels and activity, which are critical for glycogen synthesis. Currently, ABX1100 is in early clinical development for Pompe disease and has received both Orphan Drug Designation and Rare Pediatric Disease status from the FDA.

Late-onset Pompe disease, a subtype of Pompe disease, typically manifests during adolescence or adulthood. The current treatment standard involves enzyme replacement therapy, which seeks to rectify the enzyme deficiency responsible for muscle glycogen breakdown. However, this approach has shown limited effectiveness and involves a burdensome regimen of frequent intravenous infusions.

Aro Biotherapeutics is pioneering the development of potent, tissue-targeted genetic therapies using its proprietary Centyrin technology, aiming to address a variety of diseases through its innovative pipeline.