Platform

Avidity - AOC

Pioneering a New Class of Oligonucleotide Therapies called AOCs

AOC therapeutics combine the tissue selectivity of monoclonal antibodies (mAbs) and the precision of oligonucleotide therapies.

Our AOC platform was developed out of our deep experience with oligonucleotide therapeutics, modulation of RNA processes, antibody engineering and conjugation, and drug delivery techniques. Based on the data-driven hypothesis that the delivery of oligonucleotides can be greatly enhanced by using antibodies as conjugates, our scientists have established a framework for screening potential cell surface protein-mAb pairs to determine which pairs we believe are well suited to deliver active oligonucleotides to specific cell types. We have identified multiple cell surface protein-mAb pairs that can deliver oligonucleotides into various tissue and cell types to induce pharmacologic changes. For example, we have employed AOCs built on a scaffold of a mAb or mAb fragment that binds with high selectivity and affinity to transferrin receptor 1 (TfR1) to deliver oligonucleotides to cell types outside of the liver, in particular to muscle.

Our AOC platform also affords us the option to deploy various types of oligonucleotides, including siRNAs and PMOs, whose specific mechanisms of action modify RNA function in different ways. This flexibility allows us to use oligonucleotides that are tailored to modulate a given disease process. Mechanisms of these oligonucleotides can range from reducing the expression of a disease-related RNA with siRNAs, to correction of aberrant processing of RNAs with splice modifying oligonucleotides. In preclinical studies, our AOCs have demonstrated pharmacologic responses as measured by mRNA reduction in liver, skeletal muscle, cardiac muscle, B- and T-cells and lymphocyte subsets, as well as macrophages.

Percent Reduction Of Target Gene Expression

Advantages of Our AOCs

Potential Advantages of Our AOCs

We believe that the product candidates derived from our AOC platform will have the potential to offer the following distinct advantages:

Advantages of Our AOCs

Avidity is initially focused on developing a pipeline of AOCs in muscle diseases including myotonic dystrophy type 1 (DM1), muscle atrophy, Duchenne Muscular Dystrophy (DMD), Facioscapulohumeral Muscular Dystrophy (FSHD) and Pompe disease.

Avidity - Pipeline

In addition to our wholly-owned programs for muscle diseases, we also have development efforts focused on immune cells and other cell types.

As one of the first applications of our technology, Avidity is advancing a pipeline of therapeutic candidates for the treatment of serious muscle diseases including myotonic dystrophy ("DM1"), muscle atrophy, Duchenne Muscular Dystrophy ("DMD"), facioscapulohumeral muscular dystrophy (“FSHD”) and Pompe disease.

In addition to our wholly-owned programs for muscle diseases, we also have development efforts focused on immune cells and other cell types.

Myostatin mRNA levels over time after a single dose of myostatin siRNA. Expression of myostatin mRNA is significantly reduced in mice after a single intravenous dose of 3 mg/kg siRNA against myostatin conjugated to a monoclonal antibody against the transferrin receptor. Controls groups consisting of an inactive siRNA or intravenously injected saline had little or no change in myostatin mRNA.