Aro Bio’s New Drug Shows Promise in Treating Rare Pompe Disease

PHILADELPHIA, PA – February 05, 2026 – Aro Biotherapeutics has unveiled encouraging early results for its investigational drug, ABX1100, offering a potential new paradigm for treating Late-Onset Pompe Disease (LOPD), a rare and progressive neuromuscular disorder. Interim data from a Phase 1b clinical trial, presented at the 22nd annual WORLDSymposium in San Diego, demonstrated that the therapy was well-tolerated and successfully reduced the molecular machinery responsible for glycogen production in patients' muscles.

The findings represent a significant step forward for a patient community that has long dealt with burdensome treatments and persistent unmet medical needs. ABX1100, a first-of-its-kind substrate reduction therapy for Pompe, could offer a complementary or alternative approach to the current standard of care, potentially improving quality of life and clinical outcomes.

The Unmet Need in Pompe Disease

Late-Onset Pompe Disease is a genetic condition caused by a deficiency of the enzyme acid alpha-glucosidase (GAA). Without enough functional GAA, the body cannot properly break down glycogen, a complex sugar, leading to its toxic accumulation within the lysosomes of cells, especially in muscle tissue. This buildup causes progressive and irreversible muscle damage, leading to profound weakness, respiratory failure, and a significant loss of independence.

The current standard of care is enzyme replacement therapy (ERT), which involves regular intravenous infusions of a lab-made version of the missing GAA enzyme. While ERT has been a vital intervention since its introduction, its effectiveness is often limited. Many patients experience waning efficacy over time, and the therapy struggles to efficiently reach skeletal muscle, the primary site of damage in LOPD. Furthermore, the treatment regimen—requiring bi-weekly infusions that can last for hours—places a considerable burden on patients and their families, impacting their daily lives and leading to high rates of treatment discontinuation.

“Many patients with Pompe disease endure a significant loss of strength and independence, a burden compounded by the limited muscle-specific uptake of enzyme replacement therapy, the current standard of care,” noted Ozlem Goker-Alpan, M.D., president of the Lysosomal and Rare Disorders Research and Treatment Center, who presented the data.

A Novel Approach: Targeting the Source

Instead of replacing the deficient enzyme, ABX1100 employs a fundamentally different strategy: it reduces the production of glycogen at its source. The therapy is a sophisticated combination of two technologies: a short-interfering RNA (siRNA) and Aro’s proprietary Centyrin delivery platform.

The siRNA component is designed to specifically target and silence the GYS1 gene. This gene is responsible for producing glycogen synthase 1, the key enzyme that synthesizes glycogen in muscle tissue. By interfering with GYS1 messenger RNA (mRNA), ABX1100 effectively turns down the “faucet” of glycogen production, aiming to prevent its toxic accumulation before it can cause damage.

A major historical challenge for siRNA therapies has been delivering them to specific tissues beyond the liver. Aro’s Centyrin technology addresses this by acting as a molecular “GPS.” The Centyrin in ABX1100 is engineered to bind to the CD71 receptor, which is abundant on muscle cells. This ensures the siRNA payload is delivered precisely where it is needed most, leading to a targeted reduction of GYS1 in the affected muscle tissue.

Promising Early Signs from Clinical Trials

The interim Phase 1b data involved nine LOPD patients, all of whom were already receiving ERT. Patients received two infusions of ABX1100 over a 20-minute period, 28 days apart. The results provided a strong proof-of-principle for this novel approach.

Critically, the therapy was generally well-tolerated, with no serious adverse events, dose interruptions, or patient withdrawals reported. Safety is a paramount concern for any new therapy, and this early profile is a positive indicator.

Pharmacodynamic data from muscle biopsies showed that ABX1100 achieved a robust and sustained knockdown of GYS1 mRNA in the quadriceps muscle. This effect persisted for weeks after dosing, suggesting that the therapy could potentially be administered on a quarterly basis or even less frequently—a dramatic improvement over the current bi-weekly ERT schedule.

“The sustained knockdown of GYS1 mRNA in muscle, as demonstrated in this phase 1b trial in patients, and in the earlier phase 1 trial in healthy volunteers, provides proof of principle that GYS1 inhibition may be a viable therapeutic approach in patients with late-onset Pompe disease, and a source for hope for the Pompe community,” said Purnanand Sarma, Ph.D., chief executive officer of Aro Biotherapeutics.

Further analysis of exploratory biomarkers in the first four patients supported the drug's biological activity. Reductions were seen in creatine kinase (CK), a marker of muscle damage, and in Hex4, a biomarker specific to Pompe disease. These molecular signals suggest that by reducing glycogen synthesis, ABX1100 may be mitigating the underlying pathology of the disease.

Validating a Platform and Charting a Path Forward

The positive results for ABX1100 do more than just advance a single drug candidate; they provide crucial clinical validation for Aro’s entire Centyrin-siRNA platform. This success bolsters the company's strategy of developing targeted genetic medicines for a range of rare and immune-mediated diseases. The Philadelphia-based biotech, backed by significant venture capital including a recent $41.5 million Series B financing, has other programs in its pipeline targeting autoimmune and inflammatory conditions.

The study is the first to demonstrate the effect of a substrate reduction therapy in patients with LOPD. As Dr. Goker-Alpan stated, “The favorable safety profile, predictable pharmacokinetics, GYS1 mRNA knockdown, and biomarker reductions support further development of ABX1100 as an addition or alternative to ERT in patients with late-onset Pompe disease.”

Aro Biotherapeutics will continue to analyze data from the ongoing trial, with muscle biopsies taken at later time points to better understand the durability of the GYS1 knockdown. The insights gathered will be instrumental in designing future, larger-scale clinical studies to fully measure the clinical potential of this promising new therapy for patients in need of new therapeutic approaches to Pompe disease.