On October 3, 2022, Avidity Biosciences, Inc. announced its planned FORTITUDE trial of AOC 1020 in adult participants with facioscapulohumeral muscular dystrophy. The FORTITUDE trial is a randomized, placebo-controlled, double-blind, Phase 1/2 clinical trial designed to evaluate single and multiple doses of AOC 1020 in 68 adult participants with FSHD. FORTITUDE will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AOC 1020 administered intravenously, with the primary objective being the safety and tolerability of AOC 1020 in FSHD patients.

Activity of AOC 1020 will be assessed using key biomarkers, including magnetic resonance imaging (ôMRIö) measures of muscle volume and composition. Though the Phase 1/2 trial is not statistically powered to assess functional benefit, it will explore the clinical activity of AOC 1020 including measures of mobility and muscle strength as well as patient reported outcomes and quality of life measures. Participants will have the option to enroll in an open-label extension study at the end of the treatment period in the FORTITUDE study.

In the first half of 2024, the Company plans to conduct a preliminary assessment in approximately half of the study participants in the FORTITUDE trial. In preclinical studies, a single intravenous dose with the murine version of AOC 1020 prevented development of muscle weakness demonstrated by three functional assays: i) treadmill running, ii) in vivo force and iii) compound muscle action potential. Additionally, data from a preclinical study conducted to assess pharmacology in the mouse model of FSHD showed robust dose-dependent down regulation of DUX4 genes in skeletal muscle for eight weeks following a single intravenous dose of the murine version of AOC 1020.

In addition to the preclinical studies described above, Avidity completed an IND-enabling good laboratory practice toxicology study of AOC 1020 in non-human primate. Results from the IND-enabling study showed that AOC 1020 was generally well tolerated and supported advancement into the clinic, with no dose limiting toxicity observed in NHP at the highest 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 highest dose tested in both NHP and murine models was the maximum feasible dose and was the no-observed adverse effect level.