Audentes Therapeutics signed a licensing agreement and collaboration deal with Nationwide Children’s Hospital for vectorized antisense treatments for Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1). This collaboration will expand the scientific platform and pipeline to advance vectorized antisense treatments. This approach combines the delivery power of AAV with the precision tools of antisense oligonucleotides, or ASOs, to develop potential best-in-class therapeutic candidates for these neuromuscular diseases.
Under the terms of the deal, Audentes and Nationwide Children’s are collaborating to develop AT702, an AAV-antisense candidate designed to induce exon 2 skipping for DMD with duplications of exon 2 and mutations in exons 1-5 of the dystrophin gene. In preclinical studies of mice with exon 2 duplications, AT702 demonstrated robust proof-of-concept with dose-dependent increases in production of wild type or near-wild type length dystrophin protein and improvements in muscle function. Audentes is currently conducting additional preclinical work and expects to commence a Phase 1/2 study at Nationwide Children’s in the fourth quarter of 2019.
In addition, Audentes and Nationwide Children’s are evaluating vectorized RNA knockdown and vectorized exon skipping for DM1. Both approaches are designed to prevent the accumulation of toxic dystrophia myotonica-protein kinase (DMPK) RNA in affected cells, thereby restoring normal cellular function. RNA knockdown and exon skipping have both been clinically validated in studies with ASOs. As with DMD, combining these approaches with AAV delivery is expected to overcome the biodistribution limitations of ASO-based therapies. Preclinical studies are underway, and Audentes expects an IND for the selected product candidate, AT466, to be filed in 2020.
About Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is the most common type of muscular dystrophy in children, affecting approximately 1 in 3,500 to 5,000 male births, with more than 300,000 patients living with the disease worldwide. DMD is caused by mutations in the dystrophin gene, which encodes the protein dystrophin, a structural protein involved in maintaining muscle cell integrity. Patients with DMD typically develop muscle weakness in the early years of life and become wheelchair-bound in their early teens. As the disease progresses, patients typically develop respiratory, orthopedic, and cardiac complications. Cardiomyopathy and breathing difficulties usually begin by the age of 20, and few individuals with DMD live beyond their thirties. There is no cure for DMD.
About Myotonic Dystrophy Type 1
Myotonic dystrophy type 1 (DM1), is a rare, neuromuscular disease that affects multiple organ systems, and is characterized primarily by myotonia and progressive muscle wasting and weakness. DM1 has several forms which range in age of presentation and severity, including congenital, infantile, juvenile, and adult (classic). There are more than 100,000 patients living with DM1 across the United States, Europe, and Japan. The disease is inherited in an autosomal dominant pattern and is caused by a mutation called a CTG trinucleotide repeat in the dystrophia myotonica-protein kinase (DMPK) gene. Patients with DM1 experience reduced quality of life and shortened life expectancy. There are no disease modifying therapies approved for DM1.