Avidity Reports Positive Results from Early-Stage DMD Study

Rare Daily Staff

Avidity Biosciences reported positive results from a phase 1/2 study of its experimental therapy AOC 1044 for the treatment of Duchenne muscular dystrophy mutations amenable to exon 44 skipping.

The study showed that AOC 1044 delivered concentrations of phosphorodiamidate morpholino oligomers (PMO) in skeletal muscle with up to 50-times greater concentrations of PMO in skeletal muscle following a single dose compared to peptide conjugated PMOs in healthy volunteers.

AOC 1044 was well tolerated, demonstrated statistically significant exon 44 skipping compared to placebo of up to 1.5 percent in healthy volunteers after a single dose of AOC 1044 and increased exon skipping in all participants. Avidity plans to provide a first look at AOC 1044 data in people living with Duchenne muscular dystrophy mutations amenable to exon 44 skipping in second half of 2024.

Duchenne muscular dystrophy (DMD) causes a lack of functional dystrophin that leads to stress and tears of muscle cell membranes, resulting in muscle cell death and the progressive loss of muscle function. The dystrophin protein maintains the integrity of muscle fibers and acts as a shock absorber through its role as the foundation of a group of proteins that connects the inner and outer elements of muscle cells. People living with DMD suffer from progressive muscle weakness that typically starts at a very young age. Over time, people with Duchenne will develop problems walking and breathing, and eventually, the heart and respiratory muscles will stop working. Those living with the condition often require special aid and assistance throughout their lives and have significantly shortened life expectancy. While there are treatments approved to treat people with DMD, there remains a very high unmet need.

AOC 1044 is designed to deliver phosphorodiamidate morpholino oligomers (PMOs) to skeletal muscle and heart tissue to specifically skip exon 44 of the dystrophin gene to enable dystrophin production in people living with Duchenne muscular dystrophy with mutations amenable to exon 44 skipping (DMD44). DMD is characterized by progressive muscle degeneration and weakness due to alterations of a protein called dystrophin that protects muscle cells from injury during contraction.

AOC 1044 consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a PMO targeting exon 44. In a preclinical model of DMD, a murine active AOC produced durable exon skipping and functional dystrophin protein in skeletal muscle and heart tissue following a single intravenous dose. AOC 1044 is currently in phase 1/2 development as part of the EXPLORE44 trial for the treatment of DMD mutations amenable to exon 44 skipping.

The EXPLORE44 trial is a randomized, placebo-controlled, double-blind, phase 1/2 clinical trial to evaluate AOC 1044 in healthy volunteers and participants with DMD mutations amenable to exon 44 skipping.

AOC 1044 delivered dose-dependent increases in PMO concentrations in skeletal muscle following a single dose of 5 mg/kg or 10 mg/kg, providing up to 50-times greater concentrations of PMO in skeletal muscle when compared to a single dose of peptide conjugated PMOs in healthy volunteers.

AOC 1044 produced statistically significant exon 44 skipping compared to placebo of up to 1.5 percent in healthy volunteers after a single dose of 10 mg/kg AOC 1044 at Day 29. AOC 1044 increased exon skipping in all participants.

AOC 1044 was well tolerated in healthy volunteers. All treatment-emergent adverse events in participants dosed with AOC 1044 were mild to moderate. There were no symptomatic hemoglobin changes, no hypomagnesemia and no renal events.

In addition to AOC 1044, Avidity is also advancing AOC 1001 in the MARINA open-label extension study for people living with myotonic dystrophy type 1 (DM1) and AOC 1020 in the phase 1/2 FORTITUDE trial for the treatment of facioscapulohumeral muscular dystrophy (FSHD).

“Data from our clinical programs continue to reinforce the broad and disruptive potential of our AOC platform for the treatment of high burden muscle diseases like DMD, DM1 and FSHD,” said Sarah Boyce, president and CEO.

Photo: Sarah Boyce, president and CEO