AskBio Inc., a gene therapy subsidiary of Bayer AG, announced encouraging interim safety results from its Phase 1/2 LION-CS101 clinical trial evaluating AB-1003 gene therapy in patients with limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9). The data, presented at the 30th Annual International Congress of the World Muscle Society in Vienna, Austria, showed no dose-limiting toxicities or serious adverse events up to 52 weeks post-treatment in the first cohort of five participants.
Trial Design and Safety Profile
The LION-CS101 trial is a double-blind, randomized, placebo-controlled, dose-escalation study evaluating AB-1003 in adult participants aged 18-65 years with genetic confirmation of LGMD2I/R9. Participants in the first cohort received a single intravenous infusion of AB-1003 or placebo and were followed for 52 weeks during the main trial before entering a planned four-year long-term follow-up period.
Safety assessments included comprehensive monitoring through adverse event tracking, laboratory testing, physical examinations, vital signs, electrocardiograms, and echocardiograms. The most commonly reported treatment-emergent adverse events affecting more than two participants were mild-to-moderate in severity and included headaches, falls, and nausea.
Three participants experienced asymptomatic transient transaminase elevations without changes in bilirubin levels, which returned to baseline after adjusting corticosteroid treatment. Based on these safety data, the Data Safety Monitoring Board recommended advancing to the second cohort, which was announced earlier in 2025.
Gene Therapy Mechanism and Development
AB-1003 is an investigational recombinant adeno-associated virus (AAV)-based gene therapy designed to restore fukutin-related protein (FKRP) enzyme activity primarily inside muscle cells. The therapy is administered as a one-time intravenous infusion and has not been approved by any regulatory authority.
"These initial safety data are encouraging and suggest an acceptable safety profile for AB-1003," said Canwen Jiang, MD, PhD, Chief Development Officer and Chief Medical Officer at AskBio. "We believe AAV-mediated gene therapy has the potential to restore FKRP function and stabilize disease progression, and we are excited to continue our clinical research efforts with the goal of developing an effective treatment for limb-girdle muscular dystrophy."
Disease Background and Unmet Need
LGMD2I/R9 is a rare form of limb-girdle muscular dystrophy caused by mutations in the FKRP gene and is associated with weakness and wasting of arm and leg muscles. Symptoms may start appearing from childhood to adulthood, with affected individuals experiencing difficulty running and walking. The condition gradually worsens over time, and patients generally rely on wheelchairs for mobility and may experience impaired heart and lung function.
The disease is estimated to affect fewer than 5,000 people in the United States. Currently, there is no approved treatment, and management is based on addressing the signs and symptoms present in each individual patient.
Trial Progress and Future Plans
The LION-CS101 trial was initiated in 2023 and will include up to 14 participants across six sites throughout the United States. All five participants enrolled in the first cohort are actively participating and are expected to remain in the trial until completion. Enrollment in the second cohort is currently ongoing.
The trial includes two sequential, dose-level cohorts, with adult participants diagnosed with LGMD2I/R9 receiving a single intravenous infusion of AB-1003 or placebo. The presentation of interim data represents blinded Cohort 1 safety results, with the data presented by Chris Passalacqua, MD, Vice President of Neuromuscular Medical Affairs at AskBio.
