Aro Biotherapeutics Starts Phase 1b Trial Enrollment for ABX1100 in Late-Onset Pompe Disease

Aro Biotherapeutics, a clinical-stage biotechnology company, has announced the start of the Phase 1b portion of its clinical trial for ABX1100, aimed at treating late-onset Pompe disease (LOPD). ABX1100 uses siRNA therapy to target muscle tissue by utilizing a known receptor, CD71. This therapy works by inhibiting the production of the GYS1 enzyme, which is responsible for synthesizing glycogen. The Phase 1b study aims to enroll adults with LOPD to assess the safety and bioactivity of ABX1100.

Dr. Aneal Khan, the principal investigator of the trial and a pediatrician and medical geneticist at the Metabolic and Genetic in Calgary (MAGIC) Clinic in Alberta, Canada, highlighted the limitations of current enzyme replacement therapies (ERTs) for Pompe disease, emphasizing the need for new treatments with novel mechanisms of action. He expressed optimism about beginning the trial in the underserved Pompe disease population.

Pompe disease is a rare neuromuscular disorder caused by the harmful accumulation of glycogen in muscle tissue. This buildup results in muscle function loss, weakness, and disability, potentially leading to death from respiratory failure. Existing ERTs for Pompe disease have shown limited long-term effectiveness. Preclinical studies indicate that inhibiting GYS1 production might be a valuable addition or alternative to ERT.

Susan Dillon, Ph.D., co-founder, president, and CEO of Aro, acknowledged the encouraging preclinical and clinical evidence supporting ABX1100. She stated that ABX1100 could become the first new treatment for Pompe disease beyond ERT, with plans to dose the first patient in the Phase 1b study before the end of 2024. Dr. Dillon also mentioned that ABX1100 was well tolerated in a recently completed Phase 1a trial with normal healthy volunteers, demonstrating durable GYS1 mRNA knockdown in muscle biopsies, with effects lasting at least 10 weeks following a single dose. The Phase 1a study successfully identified a safe and effective starting dose for LOPD patient studies.

ABX1100 is an investigational treatment for Pompe disease. It consists of a CD71 receptor-binding Centyrin conjugated to a small interfering RNA (siRNA) that specifically interferes with the expression of GYS1 messenger RNA (mRNA). This reduces levels and overall activity of the GYS1 enzyme in muscle tissues. ABX1100 has demonstrated a favorable safety profile in toxicology studies, with durable reductions in GYS1 mRNA in muscles, supporting the potential for quarterly dosing. The treatment has received Orphan Drug Designation and Rare Pediatric Disease status from the United States Food and Drug Administration (FDA).

Aro Biotherapeutics is committed to developing potent and versatile tissue-targeted genetic medicines. The company has a platform based on proprietary protein technology called Centyrins. Aro is developing a pipeline of Centyrin-based therapeutic candidates for tissue-specific targeting of therapeutics for various diseases.