Biogen, Capsigen Create AAV Capsids to Deliver Gene Therapies

May 13, 2021 - Biogen and Capsigen recently entered into a collaboration to engineer novel adeno-associated virus (AAV) capsids to deliver gene therapies that address genetic causes of various central nervous system and neuromuscular disorders. 

Capsids are the protein coats that protect and facilitate delivery of a virus’ genetic payload into host cells, a Biogen spokesperson explained. 

The companies will utilize Capsigen’s proprietary TRADE platform and associated technologies with the intent to create and identify novel AAV capsids tailored to meet disease-specific transduction profiles.

Additionally, Capsigen’s capsid engineering expertise and Biogen’s discovery, development, manufacturing, and commercialization capabilities will help boost the goal to deliver gene therapies to patients most in need. 

“Through this collaboration, we aim to solve key technological challenges in the delivery of gene therapies to target tissues. One of our priorities for technology innovation is the discovery of AAV capsids with improved delivery profiles,” Alfred Sandrock, Jr., MD, PhD, head of research and development at Biogen, said in the announcement. 

“We are investing for the long-term by building platform capabilities and advanced manufacturing technologies with the goal of accelerating our efforts in gene therapy,” Sandrock continued. 

Capsigen will apply its vector engineering approaches to develop novel capsids designed to meet disease-specific transduction profiles, while Biogen will receive an exclusive license under Capsigen’s proprietary technology for a number of central nervous system and neuromuscular disease targets. 

Under the terms of agreement, Capsigen will receive a $15 million upfront payment and is eligible to receive nearly $42 million in potential research milestones. The company may also gain an additional $1.25 billion in potential development and commercial payments.

Additionally, Capsigen is eligible to receive royalties on future sales of products that include capsids resulting from the collaboration. 

“At Capsigen, we believe the next revolution in gene therapy will be driven by engineered AAV capsids designed to meet disease-specific transduction profiles,” said John Bial, chief executive officer of Capsigen. 

“Biogen is a leader in neuroscience, and we are excited for the opportunity to work with them to potentially bring new treatments to patients. This collaboration is consistent with our strategy to work with world-class companies to develop the next generation of gene therapies,” Bial continued. 

Many central nervous system disorders lack a cure due to the complexity of the system, the limited regenerative capacity of the tissue, and the difficulty in conveying conventional drugs to the organ due to the blood–brain barrier.

This creates a significant need for more specific and effective treatment options. Gene therapy has potential therapeutic molecules for these diseases and represents a notable option. This type of therapy can also allow a specific expression in target cells.

A 2020 PhRMA report stated that there are 362 investigational cell and gene therapies in clinical trials for various diseases. This includes two therapies using AAV vectors. 

The first gene therapy uses AAV factor VIII designed to stimulate the production of factor VIII for the treatment of hemophilia A. The second therapy uses AAV vector to deliver a high-activity Factor IX gene to the liver for the treatment of hemophilia B. 

AAV vectors are currently the leading platform for gene delivery for the treatment of a variety of central nervous system diseases, according to a 2019 Nature report. 

Recent advances in developing clinically desirable AAV capsids, optimizing genome designs, and revolutionary biotechnologies have contributed significantly to the growth of the gene therapy field.

Although hemophilia B gene therapy has achieved promising outcomes in human clinical trials, hemophilia A gene is further behind. But continued study of AAV biology and increased understanding of the challenges and limitations will build the foundation for future clinical success.