Aro Biotherapeutics Reports Positive Phase 1b Topline Results for ABX1100, a Muscle-targeted GYS1 siRNA, in Patients with Late-Onset Pompe Disease (LOPD)

ABX1100 demonstrated robust target knockdown, compelling functional improvement with associated biomarker reductions, and excellent safety and tolerability

Phase 1b data to inform continued development of ABX1100 as a potential therapeutic in LOPD

PHILADELPHIA--(BUSINESS WIRE)--Aro Biotherapeutics, a clinical-stage biotechnology company developing potent and tissue-targeted short-interfering RNA (siRNA) medicines in areas of high unmet need in rare muscle diseases, immunology, and oncology, today announced positive topline results from the Phase 1b portion of its study evaluating ABX1100, a novel investigational therapy for the treatment of late-onset Pompe disease (LOPD). In the study, ABX1100 achieved a robust and sustained knockdown of glycogen synthase 1 (GYS1) messenger RNA (mRNA), the enzyme responsible for glycogen production in muscle.

The topline Phase 1b data also showed positive effects on lung function and exploratory biomarkers in LOPD, findings that suggest functional improvement. ABX1100 was well tolerated among the nine patients with LOPD in the Phase 1b portion of the trial, consistent with previously reported Phase 1a results in 29 normal healthy volunteers. Full results will be presented at a future scientific conference.

“The totality of these data show compelling clinical evidence that ABX1100 may offer a substantial benefit to people with late-onset Pompe disease,” said Purnanand Sarma, Ph.D., chief executive officer of Aro Biotherapeutics.

In the Phase 1b portion of the trial, conducted at four sites in the United States and Canada, ABX1100 was administered without any pre-medication over <25-minute infusions on Days 1 and 29 (a loading dose regimen), as an add-on to enzyme replacement therapy (ERT). The nine patients, whose mean age was 54 years at study initiation, were followed for 20 weeks. Participants had been receiving ERT for a mean of 7.4 years (range 1-15 years). As per the study protocol, investigators collected muscle biopsies at baseline, Week 6, and Week 10 for the first four patients, and at baseline, Week 10, and Week 16 for the next five patients to investigate persistence of GYS1 mRNA knockdown.

ABX1100 demonstrated robust and sustained GYS1 mRNA knockdown at a target level of approximately 62% in the quadriceps muscle in all evaluable patients through Week 10. At Week 16, observed levels in muscle Gys1 short-interfering RNA (siRNA) and GYS1 mRNA support quarterly or less frequent dosing beyond the administered loading dose regimen.

The Phase 1b study monitored changes in patients’ lung function via Forced Vital Capacity Percent Predicted (FVC %pred), a measure that has been shown to continue to decline in LOPD patients on long-term ERT.¹ After only a two-dose loading regimen in seven patients (two patients were enrolled prior to implementation of FVC monitoring), investigators observed an overall mean improvement in FVC of approximately 2.5% at 5 months as compared to baseline. Additionally, patients with moderate and severe LOPD exhibited a more substantial improvement in FVC, suggesting a rapid functional response.

In addition to FVC, the study assessed the drug’s effect on exploratory biomarkers creatine kinase (CK, a biomarker for muscle damage) and urinary Hex4 (glucose tetrasaccharide, or Glc4, a measure of overall glycogen load) at Week 10. In a majority of patients, these biomarkers showed a reduction versus baseline at Week 10, consistent with the GYS1 mRNA knockdown and potential functional benefits.

ABX1100 was well tolerated in the patients with LOPD, who experienced no infusion reactions, no serious adverse events, no treatment discontinuations, and no clinically meaningful laboratory abnormalities, including anemia, throughout the study.

“This study provides clinical proof of concept for the use of RNA-based substrate reduction therapy to treat late-onset Pompe disease, representing the first time an siRNA therapy has been clinically evaluated in a lysosomal storage disorder," commented lead investigator Ozlem Goker-Alpan, M.D., president of the Lysosomal and Rare Disorders Research and Treatment Center in Fairfax, Va. "The impressive GYS1 mRNA knockdown data, along with the favorable safety profile and encouraging biomarker reductions, help us further characterize ABX1100 as a potentially promising addition or alternative to ERT in patients with LOPD. The early signals observed in forced vital capacity, while preliminary and based on a limited follow-up period, are also noteworthy and warrant confirmation in a larger, longer-duration study."

“The robust GYS1 mRNA knockdown is quite striking, as is the efficacy on lung function and LOPD biomarkers observed after the administration of just a two-dose loading regimen,” added Dr. Sarma. “In particular, the improvement in forced vital capacity – an approved endpoint in other LOPD registrational trials – will guide our discussions with regulatory authorities as we explore how to rapidly move this first-in-class therapy into registrational development.”

More information about the Phase 1b portion of the ABX1100 clinical trial is available at ClinicalTrials.gov, using the ID no. NCT06109948.

About ABX1100
ABX1100, an investigational treatment for Pompe disease, is comprised of a CD71 receptor-binding Centyrin conjugated to a short-interfering RNA (siRNA) that specifically interferes with expression of GYS1 messenger RNA (mRNA), thereby reducing levels and overall activity of GYS1, the enzyme responsible for glycogen production, in muscle tissues. ABX1100 has received Orphan Drug Designation and Rare Pediatric Disease status from the United States Food and Drug Administration.

About Pompe Disease
Pompe disease is a rare neuromuscular disorder caused by a genetic deficiency of the enzyme acid alpha-glucosidase (GAA), which leads to a toxic buildup of glycogen in the muscle. This buildup leads to progressive loss of muscle function, weakness, and disability that can eventually progress to death from respiratory failure.² Late-onset Pompe disease (LOPD) is a subtype of Pompe that has onset after the first year of life. The current standard of care for LOPD is enzyme replacement therapy (ERT), which aims to restore genetically deficient enzymes. Despite the availability of ERT, significant unmet need remains due to limited ERT efficacy and burden of care. ERT requires intravenous infusions that can last as long as 6 hours, multiple times a month.

About Aro Biotherapeutics
Aro Biotherapeutics is a biotechnology company working to develop potent and versatile tissue-targeted short-interfering RNA (siRNA) medicines for the treatment of immune-mediated diseases and diseases with high unmet medical need. The company is developing a wholly owned pipeline of therapeutic candidates for a diverse set of diseases, employing a proprietary protein technology called Centyrins, which are small proteins engineered for exceptional efficiency, versatility, and safety. For more information, visit https://www.AroBiotx.com/.

Reference

1. Berger KI, Chien YH, Dubrovsky A, et al. Changes in forced vital capacity over ≤13 years among patients with late-onset Pompe disease treated with alglucosidase alfa: new modeling of real-world data from the Pompe Registry. J Neurol. 2024; 271(8): 5433-5446.
2. Pompe disease. MedlinePlus. U.S. Department of Health and Human Services, National Institutes of Health, National Library of Medicine; 2016. https://medlineplus.gov/genetics/condition/pompe-disease/. Accessed January 29, 2026.

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