Astellas, Audentes Merger May Lead to New Exon-skipping Treatments for MD

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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Astellas Pharma recently agreed to acquire Audentes Therapeutics, a move it expects will result in faster development of potentially best-in-class therapies for rare neuromuscular diseases, including muscular dystrophy (MD).

Audentes’ vectorized exon-skipping technology — which uses a modified adeno-associated virus (AAV) vector to allow cells to skip over specific sections of genes — will complement Astellas’ own work,  Kenji Yasukawa, president and CEO of Astellas, said in a press release.

“Recent scientific and technological advances in genetic medicine have advanced the potential to deliver unprecedented and sustained value to patients, and even to curing diseases with a single intervention,” Yasukawa said.

“Audentes has developed a robust pipeline of promising product candidates which are complementary to our existing pipeline, including its lead program AT132,” he added. “By joining together with Audentes’ talented team, we are establishing a leading position in the field of gene therapy with the goal of addressing the unmet needs of patients living with serious, rare diseases.”

The technology uses the modified AAV vector to deliver small molecules — antisense oligonucleotides — complementary to the RNA sequence of a gene of interest, which allow cells to skip over specific exons while they are producing proteins.

Exons are the coding regions of genes that provide instructions to make proteins.

Audentes had started developing several therapies for Duchenne muscular dystrophy (DMD) based on its exon-skipping technology. These include AT702, AT751 and AT753.

All three treatment candidates use the same AAV delivery vector. However, as they target different DMD gene exons, the potential therapies are intended for distinct subgroups of patients. AT702 is designed to skip exon 2 and is meant for those who either have duplications in exon 2 or mutations in exons 1-5. AT751 is designed for those with mutations amenable to exon 51 skipping, and AT753 for people with alterations amenable to exon 53 skipping.

Audentes had also started developing and testing AT466, an experimental treatment for myotonic dystrophy type 1.

The acquisition also gives Astellas direct access to AT132, Audentes’ lead gene therapy candidate for the treatment of X-linked myotubular myopathy.

AT132 uses an AAV8 viral vector to deliver a functional copy of the MTM1 gene to muscle cells. This enables the production of myotubularin, an important enzyme for the development and maintenance of muscle cells. 

Matthew R. Patterson, chairman and CEO of Audentes, said his company is “very pleased” with the agreement. “With its focus on innovative science and a global network of research, development and commercialization resources, we believe that operating as part of the Astellas organization optimally positions us to advance our pipeline programs and serve our patients,” he said.

Under the terms of the agreement, Audentes will become an independent subsidiary of Astellas and will have access to scientific resources to accelerate the development and manufacturing of the combined product pipeline. The transaction, worth $3 billion, is expected to take place early this year.