On October 13, 2022, Avidity Biosciences, Inc. announced its planned EXPLORE44 trial of AOC 1044 in healthy volunteers and participants with Duchenne muscular dystrophy. The EXPLORE44 trial is a randomized, placebo-controlled, double-blind, Phase 1/2 clinical trial to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of single and multiple ascending doses of AOC 1044 administered intravenously, with the primary objective being the safety and tolerability of AOC 1044 in adult healthy volunteers and pediatric and adult participants with DMD mutations amenable to exon 44 skipping. The EXPLORE44 trial will assess exon skipping and dystrophin protein levels in participants with DMD44 and will also explore measures of muscle function, patient-reported outcomes and quality of life.
DMD44 is ultra rare, constituting approximately 7% of DMD patients, approximately 900 of which are in the United States. Participants with DMD44 will have the option to enroll in an extension study at the end of the treatment period in the EXPLORE44 trial. The overall development program for AOC 1044, which includes the EXPLORE44 trial and the extension study is designed to potentially support accelerated approval in the United States.
In the second half of 2023, the Company plans to present results from the healthy volunteer portion of the EXPLORE44 trial. Preclinical studies showed that an antibody oligonucleotide conjugate approach targeting exon 23 in a murine model of DMD demonstrated exon skipping, dystrophin restoration and improved muscle function and serum biomarkers of muscle damage. Additionally, data from a preclinical study of AOC 1044 in patient-derived myotubes showed dose-dependent dystrophin restoration, and a preclinical study in non-human primate (NHP) observed dose-dependent exon skipping in skeletal and heart muscle with AOC 1044.
In addition to the preclinical studies described above, Avidity completed an IND-enabling good laboratory practice (GLP) toxicology study of AOC 1044 in NHP. Results from the IND-enabling study showed that AOC 1044 was generally well tolerated and supported advancement into the clinic, with no dose limiting toxicity observed in NHP at the high dose tested. The study did not observe any treatment-related histopathologic toxicity, platelet or renal toxicity or any changes in safety pharmacology parameters (cardiac, respiratory and neurological).
The high dose tested in both NHP and murine models was the maximum feasible dose and was the no-observed adverse effect level (NOAEL). Results of a nine-month chronic toxicology study of AOC 1044 in NHPs was consistent with the results of the IND-enabling study.