SAN DIEGO, CA — Avidity Biosciences, Inc. (Nasdaq: RNA), a biopharmaceutical company committed to delivering a new class of RNA therapeutics called Antibody Oligonucleotide Conjugates (AOCs™), today announced positive AOC 1044 data in healthy volunteers from the Phase 1/2 EXPLORE44™ clinical trial for the treatment of Duchenne muscular dystrophy mutations amenable to exon 44 skipping (DMD44). AOC 1044 delivered unprecedented 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% in healthy volunteers after a single dose of 10 mg/kg AOC 1044 and increased exon skipping in all participants. Avidity plans to provide a first look at AOC 1044 data in people living with DMD44 in 2H 2024.
AOC 1044 is designed to deliver PMO to skeletal muscle and heart tissue to specifically skip exon 44 of the dystrophin gene to enable dystrophin production. AOC 1044 has been granted Orphan Designation by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), and Fast Track Designation by the FDA. AOC 1044 is the first of multiple AOCs the company is developing for DMD.
“We are excited with the early data set of AOC 1044 demonstrating unprecedented delivery of therapeutic oligonucleotide in skeletal muscle and consistent exon skipping in healthy volunteers,” said Sarah Boyce, president and chief executive officer. “We are rapidly advancing AOC 1044 and look forward to sharing data in people living with DMD44 in 2024. 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.”
Phase 1/2 EXPLORE44 Healthy Volunteer Data
- AOC 1044 delivered unprecedented, 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% 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 (MARINA-OLE™) 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).
The EXPLORE44™ Phase 1/2 Trial of AOC 1044
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 (DMD44). EXPLORE44 will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of single and multiple ascending doses of AOC 1044 administered intravenously. EXPLORE44 is expected to enroll approximately 40 healthy volunteers and 24 participants with DMD44, ages seven to 27 years old. The EXPLORE44 trial will assess exon skipping and dystrophin protein levels in participants with DMD44. Participants with DMD44 will have the option to enroll into an extension study. For more information about the EXPLORE44 trial, visit the EXPLORE44 study website or visit http://www.clinicaltrials.gov and search for NCT05670730.
About Duchenne muscular dystrophy (DMD)
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. DMD is a monogenic, X-linked, recessive disease that primarily affects males, with one in 3,500 to 5,000 boys born worldwide having Duchenne.
About AOC 1044
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.
About Avidity
Avidity Biosciences, Inc.’s mission is to profoundly improve people’s lives by delivering a new class of RNA therapeutics – Antibody Oligonucleotide Conjugates (AOCs™). Avidity is revolutionizing the field of RNA with its proprietary AOCs, which are designed to combine the specificity of monoclonal antibodies with the precision of oligonucleotide therapies to address targets and diseases previously unreachable with existing RNA therapies. Utilizing its proprietary AOC platform, Avidity demonstrated the first-ever successful targeted delivery of RNA into muscle and is leading the field with clinical development programs for three rare muscle diseases: myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD). Avidity is broadening the reach of AOCs with its advancing and expanding pipeline including programs in cardiology and immunology through internal discovery efforts and key partnerships. Avidity is headquartered in San Diego, CA.
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