Aro Biotherapeutics has announced FDA clearance of its Investigational New Drug (IND) application for ABX1100, a novel therapy for late-onset Pompe disease (LOPD). This clearance allows Aro to proceed with clinical trials of ABX1100 in LOPD patients, building on encouraging Phase 1 data in healthy volunteers. The company is presenting data at the 2025 WORLDSymposium™ in San Diego, CA.
Targeting Glycogen Synthase 1 in Pompe Disease
LOPD results from a genetic deficiency in alpha-glucosidase, leading to glycogen accumulation in muscle tissue. ABX1100 leverages Aro’s Centyrin technology to deliver a short-interfering RNA (siRNA) payload directly to muscle tissue. This siRNA inhibits the production of glycogen synthase 1 (GYS1), a key enzyme in glycogen synthesis. By reducing GYS1 activity, ABX1100 aims to decrease glycogen levels and alleviate disease symptoms.
Phase 1 Trial Results in Healthy Volunteers
Data from a Phase 1 study in normal healthy volunteers (NHVs) demonstrated that ABX1100 achieved durable knockdown of GYS1 messenger RNA (mRNA) and protein in muscle tissue. Specifically, the investigators observed approximately 70% knockdown of GYS1 mRNA and protein at 10 weeks following two doses of ABX1100. The drug was well-tolerated, exhibiting predictable pharmacokinetics (PK) with rapid clearance from plasma but durable persistence in muscle.
Clinical Development and Next Steps
The FDA's IND clearance, combined with the Phase 1 healthy volunteer trial data, provides strong momentum for the ABX1100 clinical development program. Aro Biotherapeutics has already dosed the first patient in an open-label Phase 1 clinical trial of ABX1100 in patients with LOPD in Canada (NCT06109948). This trial will assess the safety and tolerability of ABX1100 in LOPD patients currently receiving enzyme replacement therapy (ERT). Patients receive one dose of ABX1100 on day one and a booster dose on day 29 and are followed for 16 weeks to assess response.
Management Commentary
"FDA clearance of our IND application, combined with the encouraging data from our phase 1 healthy volunteer trial, provide tremendous momentum for the ABX1100 clinical development program," said Susan Dillon, Ph.D., co-founder, president and chief executive officer of Aro. Karyn O’Neil, Ph.D., co-founder and chief scientific officer of Aro, commented, "The phase 1 results demonstrate consistent and dose-dependent delivery to the muscle, allowing ABX1100 to knock down GYS1 with a long duration of effect."
About Late-Onset Pompe Disease
Late-onset Pompe disease (LOPD) is a subtype of Pompe disease typically diagnosed during adolescence or adulthood. It is characterized by a deficiency in alpha-glucosidase, leading to glycogen accumulation in muscle tissue, resulting in progressive muscle weakness and respiratory failure. Current standard of care involves enzyme replacement therapy (ERT), which has limitations and significant treatment burden. ABX1100 offers a novel approach by targeting GYS1 to reduce glycogen production directly in muscle tissue.
