First Person Dosed with an Antibody Oligonucleotide Conjugate (AOC™) for the treatment of ...

First Person Dosed with an Antibody Oligonucleotide Conjugate (AOC™) for the treatment of myotonic dystrophy type 1 (DM1)

First Person Dosed with an Antibody Oligonucleotide Conjugate (AOC™)
for the treatment of myotonic dystrophy type 1 (DM1)

Avidity Bioscience, a californian biotech company committed to delivering a new class of RNA therapeutics, announced that the first participants in the Phase 1/2 MARINA trial have been dosed with its lead Antibody Oligonucleotide Conjugate (AOC™),  AOC 1001, marking the first time a person has been dosed with an AOC. AOCs are designed to combine the proven technology of monoclonal antibodies with the precision and potency of oligonucleotide therapies to access previously untreatable tissue and cell types. AOC 1001 consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a small interfering RNA (siRNA). It is designed to address the root cause of DM1 by targeting DMPK, the disease-related mRNA. The FDA and EMA have granted Orphan Designation for AOC 1001. Last October, the FDA has granted Fast Track Designation to AOC 1001, for the treatment of this inherited muscular dystrophy. “The AOC platform was developed entirely in-house at Avidity. Our team has created this new technology through years of engineering and following the data to optimize each component of our AOCs,” said Art Levin, Ph.D., Avidity’s CSO. “This is a turning point for Avidity and the RNA field as AOCs target other cells and tissues that were previously unreachable.  Avidity’s AOCs are designed to expand the reach of oligonucleotide therapeutics to treat a broader range of diseases.”

A preliminary assessment in H2 2022
The AOC 1001 Phase 1/2 MARINA (NCT05027269) trial is enrolling adults with DM1. This randomized, double-blind, placebo-controlled, Phase 1/2 clinical trial is expected to enroll approximately 44 adults with DM1.The first doses in the MARINA trial were administered to patients at Virginia Commonwealth University and University of Rochester Medical Center (NY). The primary objective of this study is to evaluate the safety and tolerability of single and multiple ascending doses of AOC 1001 administered intravenously. The MARINA trial will begin to assess the activity of AOC 1001 across key biomarkers, including spliceopathy, an important biomarker for DM1, and knockdown of DMPK mRNA. In the second half of 2022, Avidity plans to conduct a preliminary assessment of safety, tolerability and key biomarkers in approximately half of the study participants.
In preclinical studies, AOC 1001 successfully delivered siRNAs targeting DMPK mRNA to muscle cells, resulting in durable, dose-dependent reductions of DMPK RNA across a broad range of muscles including skeletal, cardiac, and smooth muscles. has commenced clinical testing with the ongoing Phase 1/2 MARINATM trial in adults with DM1.
Avidity Biosciences’ pipeline also includes programs in facioscapulohumeral muscular dystrophy (FSHD), Duchenne Muscular Dystrophy (DMD), muscle atrophy and Pompe disease. The company is planning for AOC 1044, the lead of three programs for the treatment of DMD, and its AOC FSHD program to enter the clinic in 2022.